bluuebunny/crossref_metadata_2025 huggingface dataset:
δ-COP contains a helix C-terminal to its longin domain key to COPI dynamics and function
Authors: Arakel Eric C. , Richter Kora P. , Clancy Anne , Schwappach Blanche
Published: June 2016

Significance

We systematically dissect the structural elements of the δ subunit of the coat protein I (COPI) vesicle coat. We demonstrate that the µ-homology domain is dispensable for essential COPI functions. We map a key helix, positionally analogous to a helix observed in clathrin adaptor (AP) structures but without assigned function in AP, let alone COPI. This helix shows all features of an amphipathic helix that can enable interactions of a protein with the membrane. Indeed, the residues on its hydrophobic surface were specifically required for its function. Both findings substantially refine current models of coat formation and restrict the mechanisms of how the coat polymer is constructed or how HDEL cargo is recognized by COPI.
Brain white matter structure and
COMT
gene are linked to second-language learning in adults
Authors: Mamiya Ping C. , Richards Todd L. , Coe Bradley P. , Eichler Evan E. , Kuhl Patricia K.
Published: June 2016

Significance

Second-language learning in adulthood is a topic of wide interest given globalization, and levels of proficiency are highly variable among individuals. Here we demonstrate a significant correlation between individuals’ white matter fiber-tract properties in language areas and participation in an English language immersion program. Moreover, we found that this relationship was influenced by genetic variation (catechol-O-methyltransferase gene). Individuals with the Methionine (Met)/Valine (Val) or Val/Val genotype, but not the Met/Met genotype, showed higher fractional anisotropy and lower radial diffusivity during immersion. Values of brain measurements reversed after the immersion ended. These results suggest that second-language learning is influenced by an interaction between brain white matter structure and genetic factors.
Phosphorylation of CMG helicase and Tof1 is required for programmed fork arrest
Authors: Bastia Deepak , Srivastava Pankaj , Zaman Shamsu , Choudhury Malay , Mohanty Bidyut K. , Bacal Julien , Langston Lance D. , Pasero Philippe , O’Donnell Michael E.
Published: June 2016

Significance

Programmed replication fork arrest (PFA) at specific terminator sites and the proteins that bind to these sites functionally interconnect replication, transcription, and recombination. PFA prevents collision between replication and transcription that can cause genome instability, promotes intrachromatid recombination at ribosomal (r)DNA that controls replicative life span, and maintains rDNA homeostasis. This work reveals the mechanism of PFA by showing that the Tof1 protein of budding yeast remains associated with the replication fork only when it is phosphorylated, and uses the CMG helicase that drives the replication fork as a landing pad. Tof1–Csm3 promotes PFA by preventing the terminator protein Fob1 from getting displaced by other factors such as the Rrm3 helicase by counteracting the latter. This important mechanism appears to be evolutionarily conserved.
A time-varying group sparse additive model for genome-wide association studies of dynamic complex traits
Authors: Marchetti-Bowick Micol , Yin Junming , Howrylak Judie A. , Xing Eric P.
Published: June 2016

Motivation: Despite the widespread popularity of genome-wide association studies (GWAS) for genetic mapping of complex traits, most existing GWAS methodologies are still limited to the use of static phenotypes measured at a single time point. In this work, we propose a new method for association mapping that considers dynamic phenotypes measured at a sequence of time points. Our approach relies on the use of Time-Varying Group Sparse Additive Models (TV-GroupSpAM) for high-dimensional, functional regression.

Results: This new model detects a sparse set of genomic loci that are associated with trait dynamics, and demonstrates increased statistical power over existing methods. We evaluate our method via experiments on synthetic data and perform a proof-of-concept analysis for detecting single nucleotide polymorphisms associated with two phenotypes used to assess asthma severity: forced vital capacity, a sensitive measure of airway obstruction and bronchodilator response, which measures lung response to bronchodilator drugs.

Availability and Implementation: Source code for TV-GroupSpAM freely available for download at http://www.cs.cmu.edu/~mmarchet/projects/tv_group_spam, implemented in MATLAB.

Contact:  epxing@cs.cmu.edu

Supplementary Information:  Supplementary data are available at Bioinformatics online.
GSA-Lightning: ultra-fast permutation-based gene set analysis
Authors: Chang Billy Heung Wing , Tian Weidong
Published: June 2016

Summary: The computational speed of many gene set analysis methods can be slow due to the computationally demanding permutation step. This article introduces GSA-Lightning, a fast implementation of permutation-based gene set analysis. GSA-Lightning achieves significant speedup compared with existing methods, particularly when the number of gene sets and permutations are large.

Availability and implementation: The GSA-Lightning R package is available on Github at https://github.com/billyhw/GSALightning and on R Bioconductor. The package also contains a comprehensive user's guide with a step-by-step tutorial vignette.

Contact:  weidong.tian@fudan.edu.cn

Supplementary information:  Supplementary data are available at Bioinformatics online.
Gender Differences in Alzheimer Disease: Brain Atrophy, Histopathology Burden, and Cognition
Authors: Filon Jessica R. , Intorcia Anthony J. , Sue Lucia I. , Vazquez Arreola Elsa , Wilson Jeffrey , Davis Kathryn J. , Sabbagh Marwan N. , Belden Christine M. , Caselli Richard J. , Adler Charles H. , Woodruff Bryan K. , Rapscak Steven Z. , Ahern Geoffrey L. , Burke Anna D. , Jacobson Sandra , Shill Holly A. , Driver-Dunckley Erika , Chen Kewei , Reiman Eric M. , Beach Thomas G. , Serrano Geidy E.
Published: June 2016

Multiple studies suggest that females are affected by Alzheimer disease (AD) more severely and more frequently than males. Other studies have failed to confirm this and the issue remains controversial. Difficulties include differences in study methods and male versus female life expectancy. Another element of uncertainty is that the majority of studies have lacked neuropathological confirmation of the AD diagnosis. We compared clinical and pathological AD severity in 1028 deceased subjects with full neuropathological examinations. The age of dementia onset did not differ by gender but females were more likely to proceed to very severe clinical and pathological disease, with significantly higher proportions having a Mini-Mental State Examination score of 5 or less and Braak stage VI neurofibrillary degeneration. Median neuritic plaque densities were similar in females and males with AD but females had significantly greater tangle density scores. In addition, we found that AD-control brain weight differences were significantly greater for females, even after adjustment for age, disease duration, and comorbid conditions. These findings suggest that when they are affected by AD, females progress more often to severe cognitive dysfunction, due to more severe neurofibrillary degeneration, and greater loss of brain parenchyma.
Impact of pretreatment whole-tumor perfusion computed tomography and 18F-fluorodeoxyglucose positron emission tomography/computed tomography measurements on local control of non–small cell lung cancer treated with stereotactic body radiotherapy
Authors: Aoki Masahiko , Akimoto Hiroyoshi , Sato Mariko , Hirose Katsumi , Kawaguchi Hideo , Hatayama Yoshiomi , Seino Hiroko , Kakehata Shinya , Tsushima Fumiyasu , Fujita Hiromasa , Fujita Tamaki , Fujioka Ichitaro , Tanaka Mitsuki , Miura Hiroyuki , Ono Shuichi , Takai Yoshihiro
Published: June 2016

This study aimed to investigate the correlation between the average iodine density (AID) detected by dual-energy computed tomography (DE-CT) and the maximum standardized uptake value (SUVmax) yielded by [18F] fluorodeoxyglucose positron emission tomography (18F-FDG PET) for non–small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). Seventy-four patients with medically inoperable NSCLC who underwent both DE-CT and 18F-FDG PET/CT before SBRT (50‒60 Gy in 5‒6 fractions) were followed up after a median interval of 24.5 months. Kaplan–Meier analysis was used to determine associations between local control (LC) and variables, including AID, SUVmax, tumor size, histology, and prescribed dose. The median AID and SUVmax were 18.64 (range, 1.18–45.31) (100 µg/cm3) and 3.2 (range, 0.7–17.6), respectively. No correlation was observed between AID and SUVmax. Two-year LC rates were 96.2% vs 75.0% (P = 0.039) and 72.0% vs 96.2% (P = 0.002) for patients classified according to high vs low AID or SUVmax, respectively. Two-year LC rates for patients with adenocarcinoma vs squamous cell carcinoma vs unknown cancer were 96.4% vs 67.1% vs 92.9% (P = 0.008), respectively. Multivariate analysis identified SUVmax as a significant predictor of LC. The 2-year LC rate was only 48.5% in the subgroup of lower AID and higher SUVmax vs >90% (range, 94.4–100%) in other subgroups (P = 0.000). Despite the short follow-up period, a reduction in AID and subsequent increase in SUVmax correlated significantly with local failure in SBRT-treated NSCLC patients. Further studies involving larger populations and longer follow-up periods are needed to confirm these results.
Statin Effects to Reduce Hepatosteatosis as Measured by Computed Tomography in Patients With Human Immunodeficiency Virus
Authors: Lo Janet , Lu Michael T. , Kim Elli A. , Nou Eric , Hallett Travis R. , Park Jakob , Hoffmann Udo , Grinspoon Steven K.
Published: June 2016

Hepatosteatosis is highly prevalent among patients living with human immunodeficiency virus. In a 1-year, randomized, double-blind trial of atorvastatin or placebo, atorvastatin increased liver/spleen ratio among patients with nonalcoholic fatty liver disease, indicating a reduction in hepatosteatosis. This reduction in hepatosteatosis is associated with reduction in low-density lipoprotein cholesterol with statin therapy.
Morbidity and Mortality Among Community-Based People Who Inject Drugs With a High Hepatitis C and Human Immunodeficiency Virus Burden in Chennai, India
Authors: Mehta Shruti H. , McFall Allison M. , Srikrishnan Aylur K. , Kumar M. Suresh , Nandagopal Paneerselvam , Cepeda Javier , Thomas David L. , Sulkowski Mark S. , Solomon Sunil S.
Published: June 2016

Background.  There are limited data on clinical outcomes of hepatitis C virus (HCV) infection from low- and middle-income countries. We characterize mortality and liver disease progression in a cohort of people who inject drugs (PWID) with high HCV burden.

Methods.  In a cohort of PWID in Chennai, India, 851 persons were observed semiannually. Information on death was obtained through verbal autopsy and liver disease progression, which was defined as an incident liver stiffness measurement of ≥12.3 kPa if it was <12.3 at baseline. Poisson and Cox regression were used to identify factors associated with mortality and disease progression, respectively.

Results.  At baseline, 36.9% of cases were infected with HCV, 16.7% were infected with human immunodeficiency virus (HIV), 71.6% had no or mild stiffness, 14.9% had moderate stiffness, and 13.5% had severe stiffness or cirrhosis. Mortality was significantly higher among those with moderate (mortality rate ratio [MRR] = 2.31) and severe stiffness (MRR = 4.86) at baseline, those with ongoing substance use, those who were HIV monoinfected and not on antiretroviral therapy (ART) (MRR = 6.59), and those who were HIV/HCV coinfected regardless of ART status (MRR for no ART = 5.34; MRR for ART = 4.51). Of those with no or mild stiffness, 25.9% and 6.4% had evidence of progression to moderate and severe stiffness or cirrhosis, respectively; 38.3% of those with moderate stiffness had evidence of progression to severe stiffness or cirrhosis. Factors associated with progression included age, alcohol use, body mass index, and chronic HCV infection.

Conclusions.  We observed significant morbidity and mortality primarily driven by untreated HIV, HIV/HCV coinfection, and alcohol use. Even with improved access to HIV treatment, in the absence of HCV treatment, outcomes are unlikely to improve for HIV/HCV-coinfected persons.
The Effects of a 4-Layer Compression Bandaging System on Skin Perfusion Pressure in Healthy Adults
Authors: Chimera Nicole J. , Brass Corstiaan , Terryberry Karl , Matthews Lynn , Boggs Ryan G. , Denz William , Brogan Michael
Published: June 2016

OBJECTIVE:

Current practice precludes compression in patients with wounds and reduced arterial flow; however, this treatment may reduce edema and vascular resistance, thus improving distal circulation. The objective of this study was to determine the effects of compression on skin perfusion pressure (SPP), edema, and ankle range of motion.

DESIGN:

This was a quasi-experimental time series.

SETTING:

The study was conducted at The Center for Skin Integrity in Cheektowaga, New York.

PARTICIPANTS:

The study participants were 20 healthy adults, 10 in a younger age bracket (22.10 [SD, 2.77] years, 23.14 [SD, 5.03] kg/m2) and 10 in an older age bracket (55.90 [SD, 4.48] years, 28.84 [SD, 4.83] kg/m2).

INTERVENTIONS:

Sixty minutes of Profore Multi-layer Compression was performed.

MAIN OUTCOME MEASURES:

Precompression and postcompression measurements: SPP, Ankle Brachial Index, calf circumference (15 cm proximal to lateral malleolus), and static and dynamic ankle dorsiflexion range of motion (DF ROM) compared between young and older adults.

MAIN RESULTS:

There was a significant main effect for time for SPP (P = .049) and static (P = .02) and dynamic (P = .03) DF ROM. Skin perfusion pressure significantly increased at 40, 50, and 60 minutes of compression compared with precompression. Static and dynamic DF ROM significantly increased from precompression to postcompression. Although not statistically significant, calf circumference decreased by 6 cm in the older-adult group postcompression.

CONCLUSION:

A 4-layer compression dressing system improved SPP; this may be secondary to the decongestion of a proximal confined space. The 4-layer compression dressing also improves DF ROM postcompression and may reduce lower-extremity edema. Seeing these results in healthy participants suggests the need for future research in a patient population to determine if compression can be used to offload arterial structures and thus promote wound healing in patients.
The Effect of Ozonated Olive Oil on Neovascularizatıon in an Experimental Skin Flap Model
Authors: Kırkıl Cüneyt , Yiğit Mehmet Volkan , Özercan İbrahim Hanifi , Aygen Erhan , Gültürk Barış , Artaş Gökhan
Published: June 2016

OBJECTIVE:

Angiogenesis is an important factor for flap viability. It has been reported that ozonated oil contributed to improved neovascularization in an acute cutaneous wound healing model. This study was undertaken to evaluate the effect of ozonated olive oil on vascular endothelial growth factor (VEGF)–mediated neovascularization of skin flaps in rats.

STUDY DESIGN:

A skin flap model was established in 21 rats and evaluated within 3 groups. No treatment was given to the rats in group 1. Olive oil and ozonated olive oil were topically applied (twice daily) to the flap surface for 7 days in groups 2 and 3, respectively. Immunohistochemical staining was performed to analyze the expressions of VEGF and CD34.

RESULTS:

The mean numbers of VEGF- and CD34-positive staining microvascular structures were 8.86 (SD, 1.35) and 10.29 (SD, 1.80) in group 1, 15.00 (SD, 1.41) and 15.57 (SD, 1.72) in group 2, and 25.14 (SD, 2.41) and 25.00 (SD, 2.16) in group 3. The VEGF and CD34 expressions in group 3 were significantly higher than those in group 2 (P < .001). Their expressions in group 2 were significantly higher than those in group 1 (P < .001).

CONCLUSIONS:

Both ozonated olive oil and olive oil improved neovascularization when they were topically applied on skin flaps. The effect of ozone was more prominent.
The Impact of Venous Leg Ulcers on Body Image and Self-esteem
Authors: Salomé Geraldo Magela , de Almeida Sergio Aguinaldo , de Jesus Pereira Maria Teresa , Massahud Marcelo Renato , de Oliveira Moreira Carmelita Naira , de Brito Maria José Azevedo , Ferreira Lydia Masako
Published: June 2016

OBJECTIVE:

To evaluate self-esteem and body image in patients with venous leg ulcers (VLUs).

DESIGN:

A multicenter, prospective, descriptive, analytical, clinical study.

SETTINGS:

A nursing care and education center of a university hospital, a health center, and an outpatient wound care clinic in Brazil.

PATIENTS:

Fifty-nine consecutive adult patients with VLUs and Doppler ankle-brachial index ranging from 0.8 to 1.0 were recruited for the study. Exclusion criteria were mixed ulcers, arterial ulcers, and diabetic foot ulcers.

MAIN OUTCOME MEASURES:

A questionnaire assessing sociodemographic and clinical characteristics of patients, the Brazilian version of the Body Investment Scale, and the Rosenberg Self-esteem (RSE)/UNIFESP-EPM (São Paulo da Universidade Federal de São Paulo–Escola Paulista de Medicina) scale were administered to all patients.

MAIN RESULTS:

Most participants were women, aged between 60 and 70 years, and smokers; 33 (56%) were divorced, widowed, or single, and 26 (44%) were married. The patients had the ulcer for a mean of 5.42 years. Exudate and foul odor were present in most cases. Twenty-one ulcers (36%) measured 29 cm2 or less in surface area, and 17 (29%) ulcers measured between 30 and 49 cm2 (mean, 3.39 cm2). The mean RSE score was 22.66, indicating low self-esteem. The mean Body Investment Scale total score was 27.49, and the scores on the body image and body touch subscales were also low, indicating negative feelings about the body.

CONCLUSION:

Patients with VLUs had low self-esteem and negative feelings about their bodies.
Dynamic Lower Extremity Deformity in Children With Pseudoachondroplasia
Authors: Gaebe Glen , Kruse Richard , Rogers Kenneth , Mackenzie William G. , Holmes Laurens
Published: June 2016

Background:

Pseudoachondroplasia is a diverse group of skeletal dysplasias with a common pathway of altered cartilage oligomeric matrix protein (COMP) production. This rhizomelic dwarfism is commonly associated with deformities of the lower extremities, accelerated osteoarthritis, and ligamentous laxity. One of the most common alignment problems is coronal knee angulation which combined with tibial torsion, results in a complex deformity. The outcome of surgical correction of these deformities is variable.

Methods:

This study used 3-dimensional gait analysis to describe the kinematic deformities in 12 children (aged 3 to 15 y) and compared them to the static deformities measured on standing anteroposterior radiograph.

Results:

Both gait analysis and radiographs showed large variability in the coronal deformities but strong correlation to each other. Gait analysis showed mean varus alignment of the knee to be 13.5±13.1 degrees; that mean is not statistically different from radiographs, which showed a mean varus of 16.2±17.1 degrees. The correlation coefficient between radiographic and kinematic measurement was 0.70. The kinematic internal tibial torsion measured an average 15±19 degrees, which was moderately correlated to knee varus (r=0.45, P<0.01).

Conclusions:

Measurements of varus-valgus alignment correlated well between gait analysis and radiographs. Tibial torsion correlated with varus. In the absence of gait analysis, anteroposterior standing leg length radiographs with the patella facing foreward can be used to assess deformity. As this study does not correlate these measurements to postoperative results, an appropriately powered prospective study and further investigation of biological effects of altered cartilage oligomeric matrix protein production are needed to explain the variable surgical outcomes.

Level of Evidence:

Level IV—case series without control group).
A Novel Classification System Based on Dissemination of Musculoskeletal Infection is Predictive of Hospital Outcomes
Authors: Mignemi Megan E. , Benvenuti Michael A. , An Thomas J. , Martus Jeffrey E. , Mencio Gregory A. , Lovejoy Stephen A. , Copley Lawson A. , Williams Derek J. , Thomsen Isaac P. , Schoenecker Jonathan G.
Published: June 2016

Background:

Musculoskeletal infections (MSKIs) are a common cause of pediatric hospitalization. Children affected by MSKI have highly variable hospital courses, which seem to depend on infection severity. Early stratification of infection severity would therefore help to maximize resource utilization and improve patient care. Currently, MSKIs are classified according to primary diagnoses such as osteomyelitis, pyomyositis, etc. These diagnoses, however, do not often occur in isolation and may differ widely in severity. On the basis of this, the authors propose a severity classification system that differentiates patients based on total infection burden and degree of dissemination.

Methods:

The authors developed a classification system with operational definitions for MSKI severity based on the degree of dissemination. The operational definitions were applied retrospectively to a cohort of 202 pediatric patients with MSKI from a tertiary care children’s hospital over a 5-year period (2008 to 2013). Hospital outcomes data [length of stay (LOS), number of surgeries, positive blood cultures, duration of antibiotics, intensive care unit LOS, number of days with fever, and number of imaging studies] were collected from the electronic medical record and compared between groups.

Results:

Patients with greater infection dissemination were more likely to have worse hospital outcomes for LOS, number of surgeries performed, number of positive blood cultures, duration of antibiotics, intensive care unit LOS, number of days with fever, and number of imaging studies performed. Peak C-reactive protein, erythrocyte sedimentation rate, white blood cell count, and temperature were also higher in patients with more disseminated infection.

Conclusions:

The severity classification system for pediatric MSKI defined in this study correlates with hospital outcomes and markers of inflammatory response. The advantage of this classification system is that it is applicable to different types of MSKI and represents a potentially complementary system to the previous practice of differentiating MSKI based on primary diagnosis. Early identification of disease severity in children with MSKI has the potential to enhance hospital outcomes through more efficient resource utilization and improved patient care.

Level of Evidence:

Level II—prognostic study.
ACR Appropriateness Criteria® Hodgkin Lymphoma—Unfavorable Clinical Stage I and II
Authors: Roberts Kenneth B. , Younes Anas , Hodgson David C. , Advani Ranjana , Dabaja Bouthaina S. , Dhakal Sughosh , Flowers Christopher R. , Ha Chul S. , Hoppe Bradford S. , Mendenhall Nancy P. , Metzger Monika L. , Plastaras John P. , Shapiro Ronald , Smith Sonali M. , Terezakis Stephanie A. , Winkfield Karen M. , Constine Louis S.
Published: June 2016

These guidelines review the historical evolution of treatment for early-stage Hodgkin lymphoma (HL) with current standards that rely on prognostic factors to risk stratify and direct current treatment schemes that includes differentiation of favorable and unfavorable presentations. The major clinical trials for unfavorable early-stage HL are reviewed. Patients in this heterogenous subgroup of classic HL are best managed with sequential chemotherapy and radiotherapy. The role of imaging response assessment as a means to modify therapy is a strategy under investigation. Tailoring the radiation treatment volume and radiation dose prescription along with selective use of modern conformal techniques is expected to help reduce long-term toxicities. Many patients are well served receiving involved-site radiotherapy to 30 Gy after appropriate systemic therapy intensity; but, there are nuances for which some variations in the chemotherapy and radiotherapy specifics are appropriately individualized. Following a discussion of the current evidence-based treatment algorithms, several different example cases are reviewed to help physicians make appropriate treatment decisions. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
Symptoms and effects of physical factors in Japanese middle-aged women
Authors: Yokota Megumi , Makita Kazuya , Hirasawa Akira , Iwata Takashi , Aoki Daisuke
Published: June 2016

Objective:

The aim of the study was to clarify the prevalence and severity rates of symptoms and investigate whether symptoms varied in relation to body mass index (BMI).

Methods:

The study group composed of 1,969 women, aged 40 to 60 years, who presented at our department from 1993 through 2014. The participation rate was 98%. The presence or absence of symptoms was evaluated by having the participants complete the Keio Questionnaire, a self-administered questionnaire. To allow the results to be compared according to ovarian function, serum levels of follicle-stimulating hormone and estradiol were measured. Participants were classified into three groups according to BMI: underweight, normal weight, and overweight. Symptoms were also compared among these subgroups.

Results:

The most common symptom was general fatigue. Vasomotor symptoms differed significantly between pre- and postmenopause status. When symptoms were analyzed according to BMI, the severity rates of the following symptoms were significantly higher in the overweight group than in the normal weight and underweight groups: hot flushes, sweats, joint pain, numbness, and incontinence. On the contrary, the underweight group had significantly higher severities of cold constitution, nervousness, and wrinkled skin than did the other groups. In addition, an increase in BMI was associated with an increased severity of vasomotor symptoms.

Conclusions:

The prevalence and severities of shoulder stiffness, considered a characteristic symptom in Japanese women, were high. Increased BMI was shown to be associated with a higher severity of vasomotor symptoms, joint pain, nervousness, and urinary symptoms.
Longtime napping is associated with cardiovascular risk estimation according to Framingham risk score in postmenopausal women
Authors: Li Feng , Sun Kan , Lin Diaozhu , Qi Yiqin , Li Yan , Yan Li , Ren Meng
Published: June 2016

Objective:

Menopause can affect the physiological timing system, which could result in circadian rhythm changes and development of napping habits. Whether longtime napping in postmenopausal women is associated with cardiovascular disease is, however, still debated. The present study aims to investigate this association.

Methods:

We conducted a population-based study in 4,616 postmenopausal Chinese women. Information on sleep duration was self-reported. The Framingham General Cardiovascular Risk Score was calculated and used to identify participants at high risk of coronary heart disease (CHD).

Results:

Increased daytime napping hours were positively associated with cardiovascular disease risk factors in postmenopausal women, such as age, waist circumference, systolic blood pressure, triglycerides, fasting glucose, postload glucose, and hemoglobin A1C (all P for trend <0.05). The prevalence of high risk of CHD increased with daytime napping hours, and was 3.7%, 4.3%, and 6.9% in the no daytime napping group, the 0.1 to 1 hour group, and the more than 1 hour group, respectively (P for trend = 0.005). Compared with the no daytime napping group, postmenopausal women with daytime napping more than 1 hour had higher risk of CHD in both univariate (odds ratio 1.94, 95% CI, 1.29-2.95) and multivariate (odds ratio 1.61, 95% CI, 1.03-2.52) logistic regression analyses. No statistically significant association was detected between night sleeping hours and high risk of CHD in postmenopausal participants.

Conclusions:

Daytime napping is positively associated with estimated 10-year CHD risk in postmenopausal Chinese women.
Media and education of the consumer
Authors: Shapiro Marla
Published: June 2016

The landscape has changed in how consumers get their health information. A shift to the Internet and social media are now the way many consumers obtain their health and medical information. In addition, the highly complex information in medicine and science separates health journalism from other forms of journalism. In this article, the question of the role of media in educating consumers is examined. It is clear that knowledge translation is complex and begs the cooperation of scientists and journalists alike.
An Inexpensive Bismuth-Petrolatum Dressing for Treatment of Burns
Authors: Chattopadhyay Arhana , Chang Kathleen , Nguyen Khoa , Galvez Michael G. , Legrand Anais , Davis Christopher , McGoldrick Rory , Long Chao , Pham Hung , Chang James
Published: June 2016

Background:

Xeroform remains the current standard for treating superficial partial-thickness burns but can be prohibitively expensive in developing countries with prevalent burn injuries. This study (1) describes the production of an alternative low-cost dressing and (2) compares the alternative dressing and Xeroform using the metrics of cost-effectiveness, antimicrobial activity, and biocompatibility in vitro, and wound healing in vivo.

Methods:

To produce the alternative dressing, 3% bismuth tribromophenate powder was combined with petroleum jelly by hand and applied to Kerlix gauze. To assess cost-effectiveness, the unit costs of Xeroform and components of the alternative dressing were compared. To assess antimicrobial properties, the dressings were placed on agar plated with Escherichia coli and the Kirby-Bauer assay performed. To assess biocompatibility, the dressings were incubated with human dermal fibroblasts and cells stained with methylene blue. To assess in vivo wound healing, dressings were applied to excisional wounds on rats and the rate of re-epithelialization calculated.

Results:

The alternative dressing costs 34% of the least expensive brand of Xeroform. Antimicrobial assays showed that both dressings had similar bacteriostatic effects. Biocompatibility assays showed that there was no statistical difference (P < 0.05) in the cytotoxicity of Xeroform, alternative dressing, and Kerlix gauze. Finally, the in vivo healing model showed no statistical difference (P < 0.05) in mean re-epithelialization time between Xeroform (13.0 ± 1.6 days) and alternative dressing (13.5 ± 1.0 days).

Conclusions:

Xeroform is biocompatible, reduces infection, and enhances healing of burn wounds by preventing desiccation and mechanical trauma. Handmade petrolatum gauze may be a low-cost replacement for Xeroform. Future studies will focus on clinical trials in burn units.
Awareness of Glaucoma and Eye Health Services Among Faith-based Communities in Kumasi, Ghana
Authors: Murdoch Calum , Opoku Kennedy , Murdoch Ian
Published: June 2016

Purpose:

To determine awareness of glaucoma, “hinta anifraye” and available eye health services among urban communities in Kumasi, Ghana. “Hinta anifraye” is a recently developed term for glaucoma in the local Twi language.

Materials and Methods:

Convenience sampling was used to survey the communities of 4 churches and 2 mosques in Kumasi, recruiting participants as they arrived to attend religious services. Ten interviewers collected data by quantitative, interviewer-administered questionnaires. An awareness grading system was devised to categorize participant knowledge from level 0 to 4.

Results:

Of a total 484 respondents, 269 (56%; 95% confidence interval, 52%-60%) had heard of glaucoma, and 284 (60%; 95% confidence interval, 56%-64%) had heard of either glaucoma or hinta anifraye. Only 142 (29%) had disease-specific knowledge of symptoms or causes. TV and radio were the main reported sources of information. Education, religious community, English language, male sex, and older age were all found to be significant indicators of awareness, with education shown to be a key confounding factor. Overall 436 (90%) mentioned either a hospital or doctor as a place they knew they could seek help for an eye problem.

Conclusions:

Awareness of glaucoma is higher than previously suggested from similar studies, but still very low from a global perspective. The findings suggest that media is a useful tool in disseminating health messages. Awareness of professional care was found to be remarkably high. Eye health promotion is recommended to raise awareness of glaucoma among this population.
Reduced thermal sensitivity and increased opioidergic tone in the TASTPM mouse model of Alzheimer's disease
Authors: Aman Yahyah , Pitcher Thomas , Simeoli Raffaele , Ballard Clive , Malcangio Marzia
Published: June 2016

Individuals with Alzheimer's disease (AD) are in susceptible patient groups in which pain is an important clinical issue that is often underdiagnosed. However, it is unclear whether decreased pain complaints in patients with AD result from elevated pain tolerance or an impaired ability to communicate sensations. Here, we explored if AD-related pathology is present in key regions of the pain pathway and assessed whether nociceptive thresholds to acute noxious stimulation are altered in the double-mutant APPswe × PS1.M146V (TASTPM) transgenic mouse model of AD. TASTPM mice exhibited an age-dependant cognitive deficit at the age of 6 months, but not at 4 months, a deficit that was accompanied by amyloid plaques in the cortex, hippocampus, and thalamus. In the spinal cord, β-amyloid (APP/Aβ) immunoreactivity was observed in dorsal and ventral horn neurons, and the expression of vesicular glutamate transporter 2 (VGLUT2) was significantly reduced, while the expression of the inhibitory peptides enkephalins was increased in TASTPM dorsal horn, consistent with an increased inhibitory tone. TASTPM mice displayed reduced sensitivity to acute noxious heat, which was reversed by naloxone, an opioid antagonist. This study suggests that increased inhibition and decreased excitation in the spinal cord may be responsible for the reduced thermal sensitivity associated with AD-related pathology.
Medical Device Labeling
Authors: Brown Cedric , Marion Jill , Kaushiva Anchal
Published: June 2016

The US Food and Drug Administration’s (FDA’s) mission, through its Center for Devices and Radiological Health, is to protect and promote public health. One part of protecting patients when reviewing new medical devices is to ensure that the associated device labeling can be effectively used by the device operator—or can effectively complement training on the use of the device. This article outlines some examples of how clinical engineers and clinicians can work together to help device manufacturers and the FDA ensure that device labeling effectively communicates key information about the medical device and shares some examples of reports that the FDA has received related to problems with device labeling.
Quality Assurance of Noninvasive Blood Pressure Monitors Using a Simulator
Authors: Newell Sara Rose , Hoffman-Petersen Nikolai , Brantlov Steven
Published: June 2016

Blood pressure (BP) measurement is the most common measurement that is made in clinical domains, and it is fundamental in diagnosing, managing, and treating hypertension. The purpose of this study is to examine if external manufacturer supplied cuffs and an internal simulator cuff could be used interchangeably, such that noninvasive BP (NIBP) monitors could be tested using solely the internal simulator cuff, hereby promoting quality assurance standardization and reproducibility. Most Omron 705IT monitors were excluded from tachycardia and obese simulations because of an excess of error readings from these monitors during these simulations. Results for Omron 705IT showed that differences between the measured value using the external cuff and the measured value using the internal cuff ranged from −1 to 2.91 mm Hg. Results for A&D UA-767Plus showed that differences between the measured value using the external cuff and the measured value using the internal cuff ranged from −1 to 3 mm Hg. This study showed that it was not possible to use external and internal cuffs interchangeably for both Omron 705IT and A&D UA767PlusBT. A variety of factors may have had an influence on measurements obtained using external and internal cuffs. These may include, but are not limited to, differing external and internal cuff hose lengths and simulator employment of proprietary and manufacturer specific algorithms. These results suggest that it is not possible to use solely the internal simulator cuff when testing NIBP monitors from these 2 manufacturers. Although research shows great promise with regard to using simulators for quality assuring NIBP monitors, there is still a lack of clarity regarding the extent to which the internal simulator cuff can be employed.
A Pharmacokinetic Study Examining Acetazolamide as a Novel Adherence Marker for Clinical Trials
Authors: Hampson Aidan J. , Babalonis Shanna , Lofwall Michelle R. , Nuzzo Paul A. , Krieter Phillip , Walsh Sharon L.
Published: June 2016

Rationale

Accurate assessment of medication adherence is critical for determination of medication efficacy in clinical trials, but most current methods have significant limitations. This study tests a subtherapeutic (microdose) of acetazolamide as a medication ingestion marker because acetazolamide is rapidly absorbed and excreted without metabolism in urine and can be noninvasively sampled.

Methods

In a double-blind, placebo-controlled, residential study, 10 volunteers received 15 mg oral acetazolamide for 4 consecutive days. Acetazolamide pharmacokinetics were assessed on day 3, and its pharmacokinetic and pharmacodynamic interactions with a model medication (30 mg oxycodone) were examined on day 4. The rate of acetazolamide elimination into urine was followed for several days after dosing cessation.

Results

Erythrocyte sequestration (half-life = 50.2 ± 18.5 h, mean ± SD, n = 6), resulted in the acetazolamide microdose exhibiting a substantially longer plasma half-life (24.5 ± 5.6 hours, n = 10) than previously reported for therapeutic doses (3-6 hours). After cessation of dosing, the rate of urinary elimination decreased significantly (F
3,23 = 247: P < 0.05, n = 6) in a predictable manner with low intersubject variability and a half-life of 16.1 ± 3.8 h (n = 10). For each of 4 consecutive mornings after dosing cessation, the rates of urinary acetazolamide elimination remained quantifiable.

There was no overall effect of acetazolamide on the pharmacodynamics, Cmax, Tmax, or elimination half-life of the model medication tested. Acetazolamide may have modestly increased overall oxycodone exposure (20%, P < 0.05) compared with one of the 2 days when oxycodone was given alone, but there were no observed effects of acetazolamide on oxycodone pharmacodynamic responses.

Conclusions

Coformulation of a once-daily trial medication with an acetazolamide microdose may allow estimation of the last time of medication consumption for up to 96 hours postdose. Inclusion of acetazolamide may therefore provide an inexpensive new method to improve estimates of medication adherence in clinical trials.
Measuring Mortality Performance
Authors: Jiang H. Joanna , Reiter Kristin L. , Wang Jia
Published: June 2016

Background:

Safety-net hospitals (SNHs) tend to be weaker in financial condition than other hospitals, leading to a concern about how the quality of care at these hospitals would compare to other hospitals.

Objectives:

To assess mortality performance of SNHs using all-payer databases and measures for a broad range of conditions and procedures.

Design:

Longitudinal analysis of hospitals from 2006 through 2011 with data from the Healthcare Cost and Utilization Project State Inpatient Databases, the American Hospital Association Annual Survey, and the Area Health Resources File.

Subjects:

A total of 1891 urban, nonfederal, general acute hospitals from 31 states.

Methods:

SNHs were identified by the percentage of Medicaid and uninsured patients. Hospital mortality performance was measured by 2 composites covering 6 common medical conditions and 4 surgical procedures with risk adjustment for patient characteristics. Differences in each composite between SNHs and non-SNHs were estimated through generalized estimating equations to control for hospital factors and community resources.

Results:

Inpatient mortality rates declined over time for all hospitals. Small differences in risk-adjusted mortality rates between SNHs and non-SNHs were found only among teaching hospitals. After controlling for hospital factors, these differences were substantially reduced and remained significant only for surgical mortality rates. The small gap in surgical mortality rates diminished in later years.

Conclusions:

SNHs appeared to perform equally well as other hospitals in medical and surgical mortality measures. Policymakers should continue to monitor the quality of care at SNHs and ensure that it would not decline under the current value-based purchasing program.
Percutaneous Transhepatic Cholangioplasty to Treat Multiple Intrahepatic Biliary Strictures After Hepatoportoenterostomy
Authors: Weidner Melissa , Mitchell Sally , Schwarz Kathleen
Published: June 2016

In children with biliary atresia, hepatoportoenterostomy (HP) is recommended to improve bile flow. Biliary strictures are known potential complications after HP, which can again impair bile flow often leading to biliary cirrhosis and liver transplantation. In patients who are status post HP and have biliary strictures, nonsurgical therapeutic options such as endoscopic dilation can pose technical difficulties due to altered anatomy. Percutaneous transhepatic cholangiography with cholangioplasty is a valuable tool for obstructive cholangiopathies, but to our knowledge this has not been previously demonstrated to be successful in patients with multiple intrahepatic biliary strictures status post HP. Herein, we present 3 patients status post HP who presented with multiple intrahepatic biliary strictures and underwent successful percutaneous transhepatic cholangiography with cholangioplasty.
A Pilot Study of Intensified PEG-Asparaginase in High-risk Acute Lymphoblastic Leukemia: Children’s Oncology Group Study AALL08P1
Authors: Rodriguez Vilmarie , Kairalla John , Salzer Wanda L. , Raetz Elizabeth A. , Loh Mignon LC , Carroll Andrew J. , Heerema Nyla A. , Wood Brent L. , Borowitz Michael J. , Burke Michael J. , Asselin Barbara L. , Devidas Meenakshi , Winick Naomi J. , Carroll William L. , Hunger Stephen P. , Dreyer ZoAnn E.
Published: June 2016

AALL08P1 was designed to determine whether biweekly intensified pegaspargase (I-PEG) was feasible and safe in pediatric patients with newly diagnosed high-risk B-precursor lymphoblastic leukemia when given with Children’s Oncology Group hemiaugmented BFM therapy. High-risk average (HR-Avg) patients received standard pegaspargase dosing (6 doses), whereas high-risk high (HR-High) patients received I-PEG biweekly from the start of Consolidation until day 1 of Maintenance. Feasibility and safety were defined in advance as ≥65% of patients tolerating at least 8 doses of I-PEG and 90% requiring ≤49 weeks from day 1 of Consolidation to the initiation of Maintenance. Targeted toxicities included allergic reactions, anaphylaxis, pancreatitis, thrombosis, bleeding, central nervous system events, and sepsis. AALL08P1 enrolled 104 patients; 54 were classified as HR-Avg and 30 as HR-High after completion of induction therapy. Only 53% (16/30) of the HR-High patients received ≥8 total doses of I-PEG and 50% (15/30) took ≤49 weeks from start of Consolidation to the initiation of Maintenance. I-PEG did not significantly increase grade 2 to 5 targeted toxicities. I-PEG was not feasible or safe as defined in AALL08P1. Complete assessment of this regimen was limited due to removal of patients from I-PEG regimen and early closure of the study.
Aggressive Metastatic Inflammatory Myofibroblastic Tumor After Allogeneic Stem Cell Transplant With Fatal Pulmonary Toxicity From Crizotinib
Authors: Shash Hwazen , Stefanovici Camelia , Phillips Susan , Cuvelier Geoffrey D.E.
Published: June 2016

Inflammatory myofibroblastic tumors (IMTs) are rare tumors with an intermediate spectrum of biological behavior. IMTs are uncommon secondary malignancies after hematopoietic stem cell transplant. The presence of anaplastic lymphoma kinase rearrangements in 50% of IMTs has led to therapeutic trials with crizotinib, although limited experience remains with crizotinib use in children. We describe the first reported case of a highly aggressive and metastatic IMT (secondary malignancy) in an 8-year-old girl following umbilical cord blood transplant. Although tumor response was demonstrated with anaplastic lymphoma kinase inhibition, she later developed fatal pulmonary toxicity from diffuse alveolar damage, a feature felt most likely to be due to crizotinib.
Harris Platelet Syndrome in Patients of Non-Indian Origin
Authors: Aslan Deniz
Published: June 2016

Inherited giant platelet disorders are a subgroup of congenital thrombocytopenias characterized by decreased platelet counts along with macroplatelets and variable bleeding symptoms. Harris platelet syndrome, a newly described rare entity, is a subtype of inherited giant platelet disorders and is characterized by mild-to-severe thrombocytopenia, macroplatelets, and no bleeding manifestations. This entity was observed incidentally in healthy blood donors from India in the early 2000s, and the reported cases to date have without exception originated from the same region of the Indian subcontinent. We herein report the occurrence of Harris platelet syndrome in patients from a different ethnogeographic origin.
GSTM1 and GSTP1 Genetic Polymorphisms and Their Associations With Acute Lymphoblastic Leukemia Susceptibility in a Jordanian Population
Authors: AL-Eitan Laith N. , Rababa'h Doaa M. , Alkhatib Rami Q. , Khasawneh Rame H. , ALjarrah Omaiema A.
Published: June 2016

The genetic variations between different individuals in the xenobiotic detoxifying enzyme activity were shown to change susceptibility to acute lymphoblastic leukemia (ALL). The current study aimed to assess the association of GSTM1 and GSTP1 genetic polymorphisms with the susceptibility of ALL. This case-control study (N=264) involved 88 Jordanian ALL children and 176 healthy controls from an ethnically homogenous Jordanian children population. The polymerase chain reaction assay was used to genotype GSTM1 (null/present) and the polymerase chain reaction–restriction fragment length polymorphism technique was also applied to detect the genetic polymorphisms of GSTP1 (Ile105Val) at the rs1695 position. The biallelic analysis revealed that there was no association between GSTM1 double-null genotype and ALL (P=0.57). However, there was a strong association between GSTP1 (Ile105Val) polymorphism genotypes and alleles within GSTP1 gene and ALL (P=0.00049 and 0.000044, respectively). A combination between GSTM1 double-null genotype and rs1695 also showed an association with ALL (P=0.042). This study showed that the rs1695 single nucleotide polymorphism within the GSTP1 gene is strongly implicated in ALL among Jordanian children with ALL. These results indicate that genetic variants of GSTP1 gene influence the risk of developing ALL in the Jordanian children of Arab ancestry.