bluuebunny/crossref_metadata_2025 huggingface dataset:
Collagen Anomalies as Clues for Diagnosis: Part 2
Authors: Santos-Alarcón Sergio , López-López Omar Francisco , Flores-Terry Miguel Ángel , Villamil-Cerda Dante , Allemant-Ortiz Luis Jesús , Ríos-Martín Juan José , Alegría Victoria , Requena Luis
Published: June 2017

Background:

Collagen is the most abundant protein in the body and the main structural component of the skin.

Objective:

To provide a review of the histopathology of collagen alterations and to propose a classification with the most important types of collagen anomalies in dermatopathology. The authors describe some of the main morphological clues of collagen anomalies for specific diagnosis of some cutaneous inflammatory and neoplastic conditions.

Methods:

The authors review histopathologic collagen anomalies, concerning both morphology and disposition in some inflammatory and neoplastic cutaneous conditions, and they review previous terminology and proposed a classification of the most important types of collagen anomalies that can be seen in dermatopathological practice.

Results:

Collagen anomalies in skin can be classified into lamellar fibrosis, sclerosis, and “balls” and “rings” of collagen. Lamellar fibrosis presents as long and thin collagen bundles forming a delicate network, which can be disposed in a parallel pattern, onion-bulb-like pattern, and storiform pattern. Sclerosis is characterized by large, thick, and eosinophilic bundles of collagen, which may present as a homogenous-diffuse pattern or as individual thick bundles of collagen with few or abundant number of fibroblasts between them. Finally, the authors propose the terms “balls” and “rings” of collagen. The term “balls” of collagen stands for thick, homogenous, eosinophilic, globular collagen bundles, with no distinguishable individual composing fibers, which include the floating sign and the free-floating sign. The term “rings” of collagen is characterized by sclerotic collagen arranged in a homogenous rimming pattern around vessels without independent fibers in its composition.

Conclusions:

Collagen anomalies may be important clues to establish specific clues for specific diagnoses in dermatopathology.
Fluoxetine induces paradoxical effects in C57BL6/J mice: comparison with BALB/c mice
Authors: Gosselin Thomas , Le Guisquet Anne-Marie , Brizard Bruno , Hommet Caroline , Minier Frédéric , Belzung Catherine
Published: June 2017

The C57BL6/J mouse is the most commonly used strain in genetic investigations and behavioural tests. However, only a few studies have used C57BL6/J mice to assess the effects of antidepressant compounds. We carried out a study to compare the behavioural effects of fluoxetine (FLX) in a model of depression in two mice strains: C57BL6/J and BALB/c. We used an 8-week unpredictable chronic mild stress (UCMS) protocol during which FLX was administered (15 mg/kg, oral) from the third week to the end of the protocol. We found that UCMS induced degradation of the coat state in the two strains. Moreover, as expected, we observed that FLX elicited antidepressant-like effects in the BALB/c mice by reducing the coat state deterioration and the latency of grooming in splash test. However, in the C57BL6/J mice, it did not induce this action, but instead triggered an opposite effect: an increased sniffing latency in the novelty suppression of feeding test. We conclude that FLX exerts a paradoxical effect in the C57Bl6/J strain. This observation is consistent with some clinical features of hyper-reactivity to FLX observed in humans. Therefore, the UCMS protocol used in C57Bl6/J mice could be a good model to study the mechanisms of the paradoxical effects caused by selective serotonin reuptake inhibitors.
Association between menopause and lumbar disc degeneration: an MRI study of 1,566 women and 1,382 men
Authors: Lou Chao , Chen Hongliang , Mei Liangwei , Yu Weiyang , Zhu Kejun , Liu Feijun , Chen Zhenzhong , Xiang Guangheng , Chen Minjiang , Weng Qiaoyou , He Dengwei
Published: June 2017

Objective:

The aim of this study was to revisit and further investigate the association between menopause and disc degeneration in the lumbar spine using a magnetic resonance imaging-based eight-level grading system.

Methods:

This study cohort comprised of 1,566 women and 1,382 age-matched men who were admitted for low back pain from June 2013 to October 2016. Data on age, weight, height, body mass index, age at natural menopause, and years since menopause (YSM) were obtained. Lumbar disc degeneration was assessed using a magnetic resonance imaging-based eight-level grading system.

Results:

After adjustment for the confounding factors of age, height, and weight, young age-matched men were more susceptible to disc degeneration than premenopausal women (P < 0.05). However, after menopause, postmenopausal women had a significant tendency to develop more severe disc degeneration than their age-matched men (P < 0.05), and also compared with premenopausal and perimenopausal women (P < 0.01). Postmenopausal women were divided into nine subgroups by every 5 YSM. When YSM was less than 15 years, a positive trend was observed between YSM and severity of disc degeneration, respectively, at L1/L2 (r = 0.241), L2/L3 (r = 0.193), L3/L4 (r = 0.191), L4/L5 (r = 0.165), L5/S1 (r = 0.153), and all lumbar discs (r = 0.237) (P < 0.05 or 0.01). The analysis of covariance indicated a significant difference in each disc level (P < 0.05 or 0.01) between every two groups. When YSM was more than 15 years, the significant difference, however, disappeared in each disc level (P > 0.05).

Conclusions:

Menopause is associated with lumbar disc degeneration. The association occurred in the first 15 YSM, suggesting estrogen deficiency might be a risk factor of disc degeneration of the lumbar spine. Further studies need to be carried out for deciding whether age or menopause plays a more important role in the progression of disc degeneration in the lumbar spine.
Androgens in postmenopausal women: a review
Authors: Shifren Jan L. , Davis Susan R.
Published: June 2017

There is significant interest in the use of androgen therapy for postmenopausal women. This review provides background on endogenous androgens in women, describes factors that affect circulating androgen concentrations, and examines the relationship between low levels of androgens and sexual problems. Possible effects of androgens in postmenopausal women beyond sexual function also are discussed. Clinical trials of androgen therapy for the treatment of hypoactive sexual desire disorder are reviewed, with a discussion of potential risks. A practical approach to using androgens to treat low sexual desire with associated distress is presented, accompanied by an illustrative case.
Time to first occurrence of breast pain and vaginal bleeding in phase 3 trials of CE/BZA
Authors: Pinkerton JoAnn V. , Bushmakin Andrew G. , Bobula Joel , Lavenberg Joanne , Komm Barry S. , Abraham Lucy
Published: June 2017

Objective:

In studies of the menopausal therapy, conjugated estrogens/bazedoxifene, breast pain and vaginal bleeding rates were comparable to placebo and lower than conjugated estrogens/medroxyprogesterone acetate (MPA). This post hoc analysis determined median time to occurrence of these events.

Methods:

Participants in phase 3 conjugated estrogens/bazedoxifene trials recorded breast pain and vaginal bleeding in daily diaries. Median time to first incident was determined in women taking conjugated estrogens 0.45 mg/bazedoxifene 20 mg, conjugated estrogens 0.625 mg/bazedoxifene 20 mg, placebo, and conjugated estrogens 0.45 mg/MPA 1.5 mg (active control in Selective estrogens, Menopause, And Response to Therapy [SMART]-5 trial). We included on-treatment data (12 weeks-2 years) in healthy postmenopausal women (SMART-1), those seeking treatment for menopausal symptoms (SMART-5), and those with moderate/severe vasomotor symptoms (SMART-2). Analyses were performed using SAS Proc Lifetest.

Results:

With conjugated estrogens/MPA as comparator, median time to breast pain was 299 days for conjugated estrogens/MPA, 353 for placebo, and more than 365 (median not reached) for conjugated estrogens 0.45 mg/bazedoxifene 20 mg and conjugated estrogens 0.625 mg/bazedoxifene 20 mg. Median time to vaginal bleeding was 314, 341, 357, and 362 days, respectively. Breast pain and vaginal bleeding survival curves were not significantly different for conjugated estrogens/bazedoxifene and placebo in any study, but were (P < 0.0001) when conjugated estrogens/MPA was added to the sample in SMART-5.

Conclusions:

The time course of breast pain and vaginal bleeding with conjugated estrogens/bazedoxifene was similar to that of placebo during treatment for up to 2 years. Events occurred significantly earlier with conjugated estrogens/MPA versus conjugated estrogens/bazedoxifene or placebo.
Placebo effects of a sham opioid solution: a randomized controlled study in patients with chronic low back pain
Authors: Klinger Regine , Kothe Ralph , Schmitz Julia , Kamping Sandra , Flor Herta
Published: June 2017

This study tested the experimental placebo effect in a group of chronic pain patients. Forty-eight patients having chronic back pain participated in a randomized clinical trial that tested the efficacy of a sham opioid solution (NaCl) compared with an alleged neutral, completely inactive solution (NaCl). We shaped the placebo effect by 2 interventions: verbal instruction and conditioning. The patients were either told that the “solution reduces pain and improves physical capacity” or the “solution is neutral, a placebo.” Half of each group was additionally conditioned (coupling solution with reduced experimental pain), yielding 4 subgroups with 12 participants each. Outcome measures were as follows: the patients' clinical back pain ratings and acute pain ratings (both examined by numerical rating scale 0-10) and self-rated functional capacity (0%-100%; time required for the exercise). Expected pain relief before and after solution intake was also assessed. The inactive solution (NaCl), when presented as an effective treatment (sham “opioid” solution), induced placebo analgesia as evident in lower ratings of the patients' clinical back pain (F(3.12,144.21) = 25.05, P < 0.001), acute pain ratings (F(1.99,87.40) = 18.12, P < 0.01), and time needed to complete a series of daily activities exercises (F(1,44) = 8.51, P < 0.01) as well as increased functional capacity (F(1,44.00) = 19.42, P < 0.001). The 2 manipulations (instruction and conditioning) changed pain expectations, and they were maintained in both sham opioid groups. The results suggest that it may be clinically useful to explicitly integrate placebo analgesia responses into pain management.
The Affordable Care Act Reduces Hypertension Treatment Disparities for Mexican-heritage Latinos
Authors: McKenna Ryan M. , Alcalá Héctor E. , Lê-Scherban Félice , Roby Dylan H. , Ortega Alexander N.
Published: June 2017

Objectives:

Mexican-heritage Latinos have lower prevalence of hypertension, but have worse patterns of treatment and control compared with non-Latino whites. This study examined the impact of the Affordable Care Act (ACA) insurance expansion on reducing disparities in treatment and medication use among Mexican-heritage Latinos with hypertension.

Research Design:

Using the 2009–2014 waves of the California Health Interview Survey, we examine health care access, utilization, and medication use among Mexican-heritage Latinos and non-Latino whites with hypertension. Multivariable logistic regression analyses were performed to adjust for socioeconomic and demographic factors. Interactions between race/ethnicity and year variables were conducted to capture the effects of the passage of the ACA.

Results:

Among those with hypertension, the full implementation of the ACA (year 2014) is associated with a greater likelihood of being insured, but the race/ethnicity interaction indicates that this gain is less substantial for Mexican-heritage Latinos. The odds of having a usual source of care other than the emergency department increased after the passage of the ACA, and interaction effects indicate that this gain was more substantial for Mexican-heritage Latinos. The odds of having any physician visit and taking blood pressure mediations decreased among non-Latino whites but increased among Mexican-heritage Latinos.

Conclusions:

The implementation of the ACA in California has helped reduce some of the disparities in health care access, utilization, and medication use between non-Latino whites and Mexican-heritage Latinos with hypertension. However, sustained progress is threatened by looming repeals of ACA provisions.
Surround Propinquity and Tonic Accommodation
Authors: Nguyen Tammy , Stark Lawrence R.
Published: June 2017

Purpose

Previous studies of dark focus have found evidence of a propinquity response, in which subjects accommodate to the perceived distance of their surroundings despite being in absolute darkness. Their distance perception in a lighted room allows a spatial representation to persist within the darkened room. This study sought to establish the significance and magnitude of the propinquity response in a large sample of young adults, and to determine whether the propinquity response can be predicted by a subject’s initial dark focus in an unknown dark room.

Methods

Dark focus was measured with a dynamic infrared optometer (Plusoptix PowerRef 3) in 30 young adult subjects, 26 of whom were naive to the testing room and its dimensions. Dark focus was then measured at varying dioptric wall distances of 0.25–4D. The subject viewed the lighted room before each measurement. For each individual, the dark focus was plotted as a function of dioptric wall distance. The slope of this function was used as a measure of the propinquity response.

Results

The mean initial dark focus value was 1.05D (SD 1.04D) for the 26 naive subjects. The mean slope of the plot of dark focus as a function of dioptric wall distance was small (+0.097), yet highly statistically significant (P = .0002). The propinquity response function showed no statistically significant quadratic or cubic trends, and so may be considered linear. No statistically significant correlation was found between naive dark focus and propinquity response (r = +0.246, P = .226).

Conclusions

Propinquity seems to be a small but statistically significant factor in dark focus measurements. Though it is unlikely to contaminate tonic accommodation measurements in large samples under normal laboratory conditions, a minority of individuals exhibit large propinquity responses equal to that of proximal accommodation in lighted conditions.
Visually Evoked Potential Markers of Concussion History in Patients with Convergence Insufficiency
Authors: Poltavski Dmitri , Lederer Paul , Cox Laurie Kopko
Published: June 2017

Purpose

We investigated whether differences in the pattern visual evoked potentials exist between patients with convergence insufficiency and those with convergence insufficiency and a history of concussion using stimuli designed to differentiate between magnocellular (transient) and parvocellular (sustained) neural pathways.

Methods

Sustained stimuli included 2-rev/s, 85% contrast checkerboard patterns of 1- and 2-degree check sizes, whereas transient stimuli comprised 4-rev/s, 10% contrast vertical sinusoidal gratings with column width of 0.25 and 0.50 cycles/degree. We tested two models: an a priori clinical model based on an assumption of at least a minimal (beyond instrumentation’s margin of error) 2-millisecond lag of transient response latencies behind sustained response latencies in concussed patients and a statistical model derived from the sample data.

Results

Both models discriminated between concussed and nonconcussed groups significantly above chance (with 76% and 86% accuracy, respectively). In the statistical model, patients with mean vertical sinusoidal grating response latencies greater than 119 milliseconds to 0.25-cycle/degree stimuli (or mean vertical sinusoidal latencies >113 milliseconds to 0.50-cycle/degree stimuli) and mean vertical sinusoidal grating amplitudes of less than 14.75 mV to 0.50-cycle/degree stimuli were classified as having had a history of concussion. The resultant receiver operating characteristic curve for this model had excellent discrimination between the concussed and nonconcussed (area under the curve = 0.857; P < .01) groups with sensitivity of 0.92 and specificity of 0.80.

Conclusions

The results suggest a promising electrophysiological approach to identifying individuals with convergence insufficiency and a history of concussion.
Retinal Macroaneurysm Associated with Congenital Anomalous Retinal Artery
Authors: Kumar Vinod , Agarwal Rinky , Chandra Parijat
Published: June 2017

Purpose

Retinal arteriolar macroaneurysms are a common cause of vision loss in elderly patients with hypertension and cardiovascular disease. Their occurrence in the young, however, is not well known. The purpose of this article is to describe an unusual cause of retinal arteriolar macroaneurysm in a healthy young man.

Case report

A 30-year-old man presented with preretinal hemorrhage and macular exudation due to ruptured retinal artery macroaneurysm. The patient was treated with intravitreal bevacizumab and laser photocoagulation to the macroaneurysm. The exudation and preretinal hemorrhage resolved over several months. Fluorescein angiogram at this stage revealed a congenital anomalous retinal artery.

Conclusions

Congenital anomalous retinal artery may be associated with retinal artery macroaneurysm even in the young age in the absence of any other predisposing factors. The presentation and treatment of such retinal artery macroaneurysm, however, may remain the same to those that occur in older patients.
Feedback Simulation for Acupressure Training and Skill Assessment
Authors: Noll Eric , Romeiser Jamie , Shodhan Shivam , Madariaga Maria Cecilia , Guo Xiaojun , Rizwan Sabeen , Al-Bizri Ehab , Bennett-Guerrero Elliott
Published: June 2017

Introduction

Previous acupressure studies have yielded varying results. This could be due to differences in the amount of pressure applied to the acupressure point (acupoint) by study personnel within a study as well as between studies. Standardizing the level of pressure applied at an acupoint could improve clinical care and future research.

Methods

As part of an ongoing randomized clinical trial of postoperative acupressure, five trainees were asked to perform 2 minutes of acupressure and light touch sessions on a simulator. The applied weight was recorded every minute. Individual skill assessment was performed using cumulative sum analysis. Six pretraining and 20 posttraining measurements in each acupressure and light touch group were compared with an expert's simulation values.

Results

Before training (baseline), there was significant difference in applied weight (grams) between the expert [5705 (636)] and five trainees [2998 (798),P= 0.004]. Four of the five trainees crossed the lower decision limit assessing proficiency in the acupressure group, and all five trainees were successful in the light touch group. The trainees' average number of measurements needed to cross the lower decision limit (H0), that is, defining that an individual failure rate does not statistically differ from the acceptable failure rate, was 21.3 measurements for acupressure. After this feedback simulation, trainees' scores showed no significant difference (P> 0.05) when assessed against the expert.

Conclusions

Feedback simulation for acupressure training and skill assessment, evaluated by cumulative sum analysis, may help in improving the standardization of acupressure therapy performed during clinical practice or research.
The Role of Extracorporeal Membrane Oxygenation Simulation Training at Extracorporeal Life Support Organization Centers in the United States
Authors: Weems Mark F. , Friedlich Philippe S. , Nelson Lara P. , Rake Alyssa J. , Klee Laura , Stein James E. , Stavroudis Theodora A.
Published: June 2017

Introduction

Extracorporeal membrane oxygenation (ECMO) requires a multidisciplinary healthcare team. The Extracorporeal Life Support Organization publishes training guidelines but leaves specific requirements up to each institution. Simulation training has shown promise, but it is unclear how many institutions have incorporated simulation techniques into ECMO training to date.

Methods

We sent an electronic survey to ECMO coordinators at Extracorporeal Life Support Organization sites in the United States. Participants were asked about training practices and the use of simulation for ECMO training. Descriptive results were reported as the percentage of total responses for each question. Logistic regression was used to identify characteristics associated with simulation use.

Results

Of 94 responses (62% response rate), 46% had an ECMO simulation program, whereas 26% report a program is in development. Most (61%) have been in operation for 2 to 5 years. Sixty-three percent use simulation for summative assessment, and 76% have multidisciplinary training. Access to a simulation center [odds ratio (OR) = 4.7, 95% confidence interval (CI) = 1.7–12.5], annual ECMO caseload of greater than 20 (OR = 2.5, 95% CI = 1.5–5.8), and having a pediatric cardiothoracic intensive care unit (OR = 2.8, 95% CI = 1.2–6.7) are each associated with increased likelihood of mannequin-based ECMO simulation. Common scenarios include pump failure (93%), oxygenator failure (90%), and circuit rupture (76%).

Discussion

Extracorporeal membrane oxygenation simulation is growing but remains in its infancy. Centers with access to a simulation center, higher caseloads, and pediatric cardiothoracic intensive care units are more likely to have ECMO simulation programs. Extracorporeal membrane oxygenation simulation is felt to be beneficial, and further work is needed to delineate best training practices for ECMO providers.
Glove Port Transanal Excision of Rectal Tumors an Alternative Method for Rectal Tumor Excision: Single Center Experience
Authors: Dharamavaram Sridhar , Sapre Dimple , Mohammed Ahmed M.A. , Badrinath Krishnamurthy
Published: June 2017

Aim:

Transanal minimal invasive surgery has been practiced for several years for excision of rectal tumors however there is no standard consensus about its applications. This minimally invasive approach helps in avoiding major rectal resections and its associated risk of mortality and morbidity.

The aim of this study is to describe a single center experience with transanal glove port excision of rectal tumors which are not amenable to colonoscopic excision.

Materials and Methods:

Between the years 2011 and 2014, 9 patients underwent glove port excision of rectal tumors located within 15 cm from the anal verge. Glove port was constructed using circular anal dilator, standard surgical glove and a wound protector retractor; regular laparoscopic instruments were used. The median follow-up period was for 18 months (range, 9 to 27 mo) and all patients had flexible sigmoidoscopy for follow-up to look for any recurrence of the tumors.

Results:

All patients underwent transanal excision of rectal tumors successfully using glove port device and laparoscopic instruments. Full thickness excision of the tumor was performed in all patients and there was no significant postoperative morbidity. The final histology of 6 patients was benign and the remaining 3 patients had malignancy reported in the specimen. During the follow-up period between 12 and 18 months 3 patients had a recurrence of the polyp which was removed endoscopically without the need for any further surgical intervention.

Conclusions:

Glove port excision of rectal tumors is a feasible alternative to conventional surgical treatment for large benign rectal tumors.

What does this paper add to the literature?

This article demonstrates that performing local excision of rectal tumors can be achieved safely at a lower cost using simple platforms that are constructed locally like the glove ports. It also highlights the benefits of using the available laparoscopic kits to perform the procedure while making use of the previously acquired skills
The Role Safety Steps in Success and Complication Rate of Endoscopic Retrograde Cholangiopancreatography
Authors: Sevinç Bariş , Karahan Ömer
Published: June 2017

Background:

Endoscopic retrograde cholangiopancreatography (ERCP) is widely used for treatment of biliary disorders. There are several studies to increase the success rate and decrease the complication rate of ERCP. In this study we aimed to evaluate the affect of safety steps in success and complication rate of ERCP.

Materials and Methods:

In this cohort study patients were evaluated under 2 groups divided as before the introduction of safety steps and after. Successful cannulation rate, difficult cannulations, and complications of the procedure were recorded.

Result:

Failed ampullary cannulation rates were 8.2% in group 1 and 4% in group 2. In terms of postprocedural complications; in group 2 complication rates significantly decreased from 10.7% to 4.3%. Moreover, post-ERCP pancreatitis rate decreased from 9.1% in group 1 to 4% in group 2.

Conclusions:

Introduction of safety steps, significantly increase the cannulation rate and decrease both overall complication rate and pancreatitis risk.
Minimally Invasive Cholecystolithotomy to Treat Cholecystolithiasis in Children: A Single-center Experience With 23 Cases
Authors: Lin Xiaokun , Cai Jingli , Wang Jisheng , Chen Congde , He Guorong , Han Yijiang
Published: June 2017

Objective:

Minimally invasive cholecystolithotomy is recently popularized treatment that may offer advantages over laparoscopic cholecystectomy, especially in China. However, there are few reports concerning the use of this technique in the pediatric population. This report describes our initial experience with minimally invasive cholecystolithotomy using laparoscopy combined with choledochoscopy to treat cholecystolithiasis in children.

Materials and Methods:

A retrospective review of 23 pediatric patients with cholecystolithiasis who underwent minimally invasive cholecystolithotomy using laparoscopy combined with choledochoscopy from January 2009 to December 2015 was performed.

Results:

The operations were successful in all 23 cases. None required conversion to conventional laparoscopic cholecystectomy. The average operative time was 68 minutes (range, 45 to 97 min). The average bleeding volume during surgery was 30 mL (range, 10 to 55 mL). The average length of hospital stay was 5.2 days (range, 3 to 7 d). There were no perioperative complications. All patients were followed for 9 to 12 months without any obvious gastrointestinal symptoms. None had a recurrence of stones in the gall bladder.

Conclusions:

Minimally invasive cholecystolithotomy using laparoscopy combined with choledochoscopy is a safe and viable technique that may be used successfully in pediatric surgery.
Reexamining the Association of Body Mass Index With Overall Survival Outcomes After Liver Transplantation
Authors: Chang Su-Hsin , Liu Xiaoyan , Carlsson Nils P. , Park Yikyung , Colditz Graham A. , Garonzik-Wang Jacqueline M. , Chapman William C. , Wellen Jason R. , Doyle Maria B. , Alhamad Tarek
Published: June 2017

Background

Several studies have shown that obese patients undergoing liver transplantation (LT) have an increased risk of mortality regardless of Model of End Stage Liver Disease (MELD) scores. The purpose of this study is to identify the range of body mass index (BMI) at LT associated with the lowest risks of posttransplant mortality by MELD category.

Methods

A retrospective cohort of patients aged 18 years or older from the Organ Procurement and Transplantation Network database undergoing LT between February 27, 2002, and December 31, 2013, was identified and followed up through March 14, 2014. Patients' MELD score at the time of transplantation was categorized into 10 or lower (MELD1), 11 to 18 (MELD2), 19 to 24 (MELD3), and 25 or higher (MELD4). Multivariable adjusted Cox proportional hazard analyses were conducted.

Results

Among 48 226 patients in the analytic cohort (14.8% were in MELD1, 33.7% were in MELD2, 19.6% were in MELD3, and 32.0% were in MELD4), 25% died with mean follow-up of 1371 days. For MELD1, patient BMI ranging from 30 to 33 was associated with a better survival outcome than BMI less than 30 or 33 or greater; for MELD2, BMI ranging from 28 to 37 had a better survival outcome than BMI less than 28 or 37 or greater; for MELD3, the survival outcome improved with an increasing BMI; for MELD4, the survival outcome was not associated with patient BMI.

Conclusions

This study provides evidence that obesity in LT patients is not necessarily associated with higher posttransplantation mortality and highlights the importance of the interaction between BMI and MELD category to determine their survival likelihood.
A review of cohesive zone modelling as an approach for numerically assessing hydrogen embrittlement of steel structures
Authors: Jemblie L. , Olden V. , Akselsen O. M.
Published: June 2017

Simulation of hydrogen embrittlement (HE) requires a coupled approach; on one side, the models describing hydrogen transport must account for local mechanical fields, while, on the other side, the effect of hydrogen on the accelerated material damage must be implemented into the model describing crack initiation and growth. This study presents a review of coupled diffusion and cohesive zone modelling as a method for numerically assessing HE of a steel structure. While the model is able to reproduce single experimental results by appropriate fitting of the cohesive parameters, there appears to be limitations in transferring these results to other hydrogen systems. Agreement may be improved by appropriately identifying the required input parameters for the particular system under study.

This article is part of the themed issue ‘The challenges of hydrogen and metals’.
Convergence of Wnt, Growth Factor and Trimeric G protein signals on Daple
Authors: Aznar Nicolas , Dunkel Ying , Sun Nina , Satterfield Kendall , He Fang , Lopez-Sanchez Inmaculada , Ghassemian Majid , Sahoo Debashis , Kufareva Irina , Ghosh Pradipta
Published: June 2017

Cellular proliferation, differentiation, and morphogenesis are shaped by multiple signaling cascades; their concurrent dysregulation plays an integral role in cancer progression and is a common feature of many malignancies. Three such cascades that contribute to the oncogenic potential are the Wnt/Frizzled(FZD), growth factor-receptor tyrosine kinases (RTKs), and G-proteins/GPCRs. Here we identify Daple, a modulator of trimeric G-proteins and a Dishevelled (Dvl)-binding protein as an unexpected point of convergence for all three cascades. Daple-dependent activation of Gαi and enhancement of non-canonical Wnt signals is not just triggered by Wnt5a/FZD to suppress tumorigenesis, but also hijacked by growth factor-RTKs to stoke tumor progression. Phosphorylation of Daple by both RTKs and non-RTKs triggers Gαi activation and potentiates non-canonical Wnt signals that trigger epithelial-mesenchymal transition. In patients with colorectal cancers, concurrent upregulation of Daple and the prototype RTK, EGFR, carried poor prognosis. Thus, this work defines a novel growth factor↔G-protein↔Wnt crosstalk paradigm in cancer biology.
An elective course for medical students on innovation and entrepreneurship
Authors: Reinertsen Erik , Mohan Arun , Fusaro Angela
Published: June 2017

Here we describe “Innovation and Entrepreneurship in Medicine” (IEMed), a short elective course that exposed medical students to innovation and entrepreneurship. We assess students’ self-rated familiarity with various learning objectives after the course and report survey outcomes. Students were most interested in further educational offerings focused on startups and innovation. However, students self-reported relatively lower levels of understanding in regulatory, reimbursement, and legal aspects of health tech. Most participants reported a desire to collaborate with or consult for industry partners, rather than to found or work at a startup. We conclude with a broader discussion of the need to expose medical students to opportunities in the technology industry.
Comprehensive genome and transcriptome analysis reveals genetic basis for gene fusions in cancer
Authors: Fonseca Nuno A. , He Yao , Greger Liliana ,   PCAWG3, Brazma Alvis , Zhang Zemin
Published: June 2017

Gene fusions are an important class of cancer-driving events with therapeutic and diagnostic values, yet their underlying genetic mechanisms have not been systematically characterized. Here by combining RNA and whole genome DNA sequencing data from 1188 donors across 27 cancer types we obtained a list of 3297 high-confidence tumour-specific gene fusions, 82% of which had structural variant (SV) support and 2372 of which were novel. Such a large collection of RNA and DNA alterations provides the first opportunity to systematically classify the gene fusions at a mechanistic level. While many could be explained by single SVs, numerous fusions involved series of structural rearrangements and thus are composite fusions. We discovered 75 fusions of a novel class of inter-chromosomal composite fusions, termedbridged fusions, in which a third genomic location bridged two different genes. In addition, we identified 522 fusions involving non-coding genes and 157 ORF-retaining fusions, in which the complete open reading frame of one gene was fused to the UTR region of another. Although only a small proportion (5%) of the discovered fusions were recurrent, we found a set of highly recurrent fusion partner genes, which exhibited strong 5’ or 3’ bias and were significantly enriched for cancer genes. Our findings broaden the view of the gene fusion landscape and reveal the general properties of genetic alterations underlying gene fusions for the first time.
Effects of Prenatal Stress on Structural Brain Development and Aging in Humans
Authors: Franke Katja , Bergh Bea van den , de Rooij Susanne R. , Roseboom Tessa J. , Nathanielsz Peter W. , Witte Otto W. , Schwab Matthias
Published: June 2017

Healthy brain aging is a major determinant of quality of life, allowing integration into society at all ages. Human epidemiological and animal studies indicate that in addition to lifestyle and genetic factors, environmental influences in prenatal life have a major impact on brain aging and age-associated brain disorders. The aim of this review is to summarize the existing literature on the consequences of maternal anxiety, stress, and malnutrition for structural brain aging and predisposition for age-associated brain diseases, focusing on studies with human samples. In conclusion, the results underscore the importance of a healthy mother-child relationship, starting in pregnancy, and the need for early interventions if this relationship is compromised.
Investigation of polymorphisms in theP. falciparumartemisinin resistance markerkelch13in asymptomatic infections in a rural area of Cameroon
Authors: Safeukui Innocent , Fru-Cho Jerome , Mbengue Alassane , Suresh Niraja , Njimoh Dieudonne L. , Bumah Violet V , Nkuo-Akenji Theresa , Titanji Vincent PK , Haldar Kasturi
Published: June 2017

Background

The genetic variability of the artemisinin resistance (AR) molecular markerkelch13 (k13)has been extensively investigated inPlasmodium falciparummalaria parasites from symptomatic infections in South East (SE) Asia where AR is highly prevalent, as well as in Africa where evidence of AR has emerged only recently. However, molecular surveillance and risk of transmission of AR also require monitoring asymptomatic infection. Here, molecular analyses were used to investigate polymorphisms ink13and their potential for transmission in asymptomatic adults in Bolifamba, Cameroon in Central Africa.

Methods

Using polymerase chain reaction (PCR), we amplified and sequenced the full length ofk13fromP. falciparuminfections detected in the blood of 33 asymptomatic adults (age: 18-55 years-old) collected in a cross-sectional study from July 2008 to October 2009. Risk of increased transmission was assessed by quantifying gametocytes by qPCR. Quantitative ELISA was used to detect plasma levels of PfHRP2 to establish total parasite burdens associated with asymptomatic infection.

Results

Out of 33 isolates tested, 14 (42.4%) presented at least one single nucleotide polymorphism (SNP) ink13.Five non-synonymous SNPs were detected (K189T/N, N217H, R393K and E433K). None were located in the ß-propeller domain, where AR mutations have been detected in both SE Asian and, more recently, African parasites. K189T/N and N217H have been previously reported in African strains, but R393K and E433K are new polymorphisms. Gametocytes were detected in 24.2% of infections, without significant association with detectedk13polymorphisms. Notably, polymorphisms outside of the ß-propeller domain detected ink13were associated with a significant increase of PfHRP2 plasma levels but not circulating parasite levels detected by qPCR.

Conclusions

This study provides the baseline prevalence ofk13polymorphisms in asymptomatic infection for molecular surveillance in tracking AR. Unexpectedly, it also suggests association ofk13polymorphisms outside of the ß-propeller domain with totalP. falciparumburden in asymptomatic infection, that needs to be validated in future studies.
Mitochondrial DNA SNPs associated with Schizophrenia exhibit Highly Variable Inter-allelic Haplogroup Affiliation and Nuclear Genogeographic Affinity: Bi-Genomic Linkage Disequilibrium raises Major Concerns for Link to Disease
Authors: Hagen Christian M , Gonçalves Vanessa F , Hedley Paula L , Bybjerg-Grauholm Jonas , Bækvad-Hansen Marie , Hansen Christine S , Kanters Jørgen K , Nielsen Jimmi , Mors Ole , Demur Alfonso B , Als Thomas D , Nordentoft Merete , Børglum Anders , Mortensen Preben Bo , Kennedy James , Werge Thomas M , Hougaard David M , Christiansen Michael
Published: June 2017

Mitochondria play a significant role in human diseases. However, disease associations with mitochondrial DNA (mtDNA) SNPs have proven difficult to replicate. A reanalysis of eight schizophrenia-associated mtDNA SNPs, in 23,743 normal Danes and 2,538 schizophrenia patients, revealed marked inter-allelic differences in haplogroup affiliation and nuclear ancestry, genogeophraphic affinity (GGA). This bi-genomic linkage disequilibrium (2GLD) could entail population stratification. Only two mitochondrial SNPs, m. 15043A and m. 15218G, were significantly associated with schizophrenia. However, these associations disappeared when corrected for haplogroup affiliation. The extensive 2GLD documented is a major concern when interpreting historic as well as designing future mtDNA association studies.
Neurodynamics and connectivity during facial fear perception: The role of threat exposure and signal congruity
Authors: Cushing Cody , Im Hee Yeon , Adams Reginald B. , Ward Noreen , Albohn Daniel N. , Steiner Troy G. , Kveraga Kestutis
Published: June 2017

Fearful faces convey threat cues whose meaning is contextualized by eye gaze: While averted gaze is congruent with facial fear (both signal avoidance), direct gaze is incongruent with it, as direct gaze signals approach. We have previously shown using fMRI that the amygdala is engaged more strongly by fear with averted gaze, which has been found to be processed more efficiently, during brief exposures. However, the amygdala also responds more to fear with direct gaze during longer exposures. Here we examined previously unexplored brain oscillatory responses to characterize the neurodynamics and connectivity during brief (∼250 ms) and longer (∼883 ms) exposures of fearful faces with direct or averted eye gaze. We replicated the exposure time by gaze direction interaction in fMRI (N=23), and observed greater early phase locking to averted-gaze fear (congruent threat signal) with MEG (N=60) in a network of face processing regions, with both brief and longer exposures. Phase locking to direct-gaze fear (incongruent threat signal) then increased significantly for brief exposures at ∼350 ms, and at ∼700 ms for longer exposures. Our results characterize the stages of congruent and incongruent facial threat signal processing and show that stimulus exposure strongly affects the onset and duration of these stages.
Coevolution of virulence and immunosuppression in multiple infections
Authors: Kamiya Tsukushi , Mideo Nicole , Alizon Samuel
Published: June 2017

This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (http://dx.doi.org/10.24072/pci.evolbiol.100043). Many components of host-parasite interactions have been shown to affect the way virulence (i.e., parasite-induced harm to the host) evolves. However, coevolution of multiple parasite traits is often neglected. We explore how an immunosuppressive mechanism of parasites affects and coevolves with virulence through multiple infections. Applying the adaptive dynamics framework to epidemiological models with coinfection, we show that immunosuppression is a double-edged-sword for the evolution of virulence. On one hand, it amplifies the adaptive benefit of virulence by increasing the abundance of coinfections through epidemiological feedbacks. On the other hand, immunosuppression hinders host recovery, prolonging the duration of infection and elevating the cost of killing the host. The balance between the cost and benefit of immunosuppression varies across different background mortality rates of hosts. In addition, we find that immunosuppression evolution is influenced considerably by the precise trade-off shape determining the effect of immunosuppression on host recovery and susceptibility to further infection. These results demonstrate that the evolution of virulence is shaped by immunosuppression while highlighting that the evolution of immune evasion mechanisms deserves further research attention.
p53 is essential for DNA methylation homeostasis in naïve embryonic stem cells, and its loss promotes clonal heterogeneity
Authors: Tovy Ayala , Spiro Adam , McCarthy Ryan , Shipony Zohar , Aylon Yael , Allton Kendra , Ainbinder Elena , Furth Noa , Tanay Amos , Barton Michelle , Oren Moshe
Published: June 2017

DNA methylation is a key regulator of embryonic stem cell (ESC) biology, dynamically changing between naïve, primed, and differentiated states. The p53 tumor suppressor is a pivotal guardian of genomic stability, but its contributions to epigenetic regulation and stem cell biology are less explored. We report that, in naïve mouse ESCs (mESCs), p53 restricts the expression of the de novo DNA methyltransferases Dnmt3a and Dnmt3b while up-regulating Tet1 and Tet2, which promote DNA demethylation. The DNA methylation imbalance in p53-deficient (p53−/−) mESCs is the result of augmented overall DNA methylation as well as increased methylation landscape heterogeneity. In differentiating p53−/− mESCs, elevated methylation persists, albeit more mildly. Importantly, concomitant with DNA methylation heterogeneity, p53−/− mESCs display increased cellular heterogeneity both in the “naïve” state and upon induced differentiation. This impact of p53 loss on 5-methylcytosine (5mC) heterogeneity was also evident in human ESCs and mouse embryos in vivo. Hence, p53 helps maintain DNA methylation homeostasis and clonal homogeneity, a function that may contribute to its tumor suppressor activity.
Nigeria’s construction industry: barriers to effective communication
Authors: Ejohwomu Obuks Augustine , Oshodi Olalekan Shamsideen , Lam Ka Chi
Published: June 2017

Purpose

Communication plays an important role in the quality of the relationship, trust and collaboration among construction project teams. Literature suggests that effective communication is vital for achieving improved project performance. The purpose of this paper is to identify and assess the barriers to effective communication in the Nigerian construction industry, using attribution theory paradigm.

Design/methodology/approach

Questionnaires detailing 15 barriers to effective communication were administered to consultants and contractors engaged in the Nigerian construction sector. In total, 100 valid responses were analysed using mean score, factor analysis and factor score.

Findings

Unclear project objectives, ineffective reporting systems and poor leadership were ranked as the most significant barriers to effective communication. Factor analysis uncovered that the principal reasons responsible for ineffective communication include: managerial and technical barriers and credibility and background barriers.

Practical implications

The results provide information on barriers which needs to be addressed in order to improve communication in construction projects in Nigeria. There is a need to conduct post-completion reviews of construction projects so that project team members can learn and share knowledge on past experiences. Although the present study was conducted in the Nigerian context, it is envisaged that the research outcome will be widely applicable to other developing countries.

Originality/value

The study provides insights on the perceived barriers to effective communication in Nigerian construction projects. The paper presents the direction for further research aimed at improving communication in construction projects in Nigeria.
BIM-enabled sustainability assessment of material supply decisions
Authors: Ahmadian F.F. Alireza , Rashidi Taha H. , Akbarnezhad Ali , Waller S. Travis
Published: June 2017

Purpose

Enhancing sustainability of the supply process of construction materials is challenging and requires accounting for a variety of environmental and social impacts on top of the traditional, mostly economic, impacts associated with a particular decision involved in the management of the supply chain. The economic, environmental, and social impacts associated with various components of a typical supply chain are highly sensitive to project and market specific conditions. The purpose of this paper is to provide decision makers with a methodology to account for the systematic trade-offs between economic, environmental, and social impacts of supply decisions.

Design/methodology/approach

This paper proposes a novel framework for sustainability assessment of construction material supply chain decisions by taking advantage of the information made available by customized building information models (BIM) and a number of different databases required for assessment of life cycle impacts.

Findings

The framework addresses the hierarchy of decisions in the material supply process, which consists of four levels including material type, source of supply, supply chain structure, and mode of transport. The application is illustrated using a case study.

Practical implications

The proposed framework provides users with a decision-making method to select the most sustainable material alternative available for a building component and, thus, may be of great value to different parties involved in design and construction of a building. The multi-dimensional approach in selection process based on various economic, environmental, and social indicators as well as the life cycle perspective implemented through the proposed methodology advocates the life cycle thinking and the triple bottom line approach in sustainability. The familiarity of the new generation of engineers, architects, and contractors with this approach and its applications is essential to achieve sustainability in construction.

Originality/value

A decision-making model for supply of materials is proposed by integrating the BIM-enabled life cycle assessment into supply chain and project constraints management. The integration is achieved through addition of a series of attributes to typical BIM. The framework is supplemented by a multi-attribute decision-making module based on the technique for order preference by similarity to ideal solution to account for the trade-offs between different economic and environmental impacts associated with the supply decisions.