bluuebunny/crossref_metadata_2025 huggingface dataset:
Socioeconomic, religious, spiritual and health factors associated with symptoms of common mental disorders: a cross-sectional secondary analysis of data from Bhutan’s Gross National Happiness Study, 2015
Authors: Sithey Gyambo , Li Mu , Wen Li Ming , Kelly Patrick J , Clarke Kelly
Published: February 2018

Objective

Common mental disorders (CMDs) are a major cause of the global burden of disease. Bhutan was the first country in the world to focus on happiness as a state policy; however, little is known about the prevalence and risk factors of CMDs in this setting. We aim to identify socioeconomic, religious, spiritual and health factors associated with symptoms of CMDs.

Design and setting

We used data from Bhutan’s 2015 Gross National Happiness (GNH) Survey, a multistage, cross-sectional nationwide household survey. Data were analysed using a hierarchical analytical framework and generalised estimating equations.

Participants

The GNH Survey included 7041 male and female respondents aged 15 years and above.

Measures

The 12-item General Health Questionnaire was used to measure symptoms of CMDs. We estimated the prevalence of CMDs using a threshold score of ≥12.

Results

The prevalence of CMDs was 29.3% (95% CI 26.8% to 31.8%). Factors associated with symptoms of CMDs were: older age (65+) (β=1.29, 95% CI 0.57 to 2.00), being female (β=0.70, 95% CI 0.45 to 0.95), being divorced or widowed (β=1.55, 95% CI 1.08 to 2.02), illiteracy (β=0.48, 95% CI 0.21 to 0.74), low income (β=0.37, 95% CI 0.15 to 0.59), being moderately spiritual (β=0.61, 95% CI 0.34 to 0.88) or somewhat or not spiritual (β=0.76, 95% CI 0.28 to 1.23), occasionally considering karma in daily life (β=0.53, 95% CI 0.29 to 0.77) or never considering karma (β=0.80, 95% CI 0.26 to 1.34), having poor self-reported health (β=2.59, 95% CI 2.13 to 3.06) and having a disability (β=1.01, 95% CI 0.63 to 1.40).

Conclusions

CMDs affect a substantial proportion of the Bhutanese population. Our findings confirm the importance of established socioeconomic risk factors for CMDs, and suggest a potential link between spiritualism and mental health in this setting.
Understanding the characteristics of recurrent visits to the emergency department by paediatric patients: a retrospective observational study conducted at three tertiary hospitals in Korea
Authors: Kim Byung-Soo , Kim Jung-Youn , Choi Sung-Hyuk , Yoon Young-Hoon
Published: February 2018

Objectives

The number of paediatric patients visiting the emergency department (ED) continues to rise. In South Korea, approximately 25% of the patients who visit the ED are paediatric patients. In the USA, about 20% of the paediatric population were found to have visited the ED in the past year. A recent study demonstrated that 4.5%–8% of patients account for 25% of all ED visits. Therefore, the aim of this study was to identify the characteristics of recurrent visits.

Methods

Design: retrospective observational study. Setting: this study examined and analysed medical record data involving three tertiary EDs. Participants: a total of 46 237 ED visits by patients <16 years during 1-year period. Main outcome measures: data collected included the number of recurrent ED patients, frequency of recurrent visits, age, sex, insurance status, period until recurrent visit (days), main diagnosis and ED discharge results.

Results

Excluding patients with multiple visits, the total number of paediatric patients who fit the study criteria was 33 765. Among these patients, 23 384 (69.2%) had no recurrent ED visits in the subsequent year after their first visit. A total of 15 849 (46.8%) patients were toddlers (between age 1 and 4 years). In the patient group without a recurrent visit, fever was the most common diagnosis.

Conclusions

Our study reviewed medical records to inspect the characteristics of patients who return to care. Higher recurrent visit frequency was associated with using the 119 rescue centre service, having a medical condition, with younger age and a higher rate of hospitalisation. Analysis of the factors associated with frequent ED visits will help to improve care for paediatric patients who visit the ED.
What factors mediate the inter-relationship between frailty and pain in cognitively and functionally sound older adults? A prospective longitudinal ageing cohort study in Taiwan
Authors: Chiou Jing-Hui , Liu Li-Kuo , Lee Wei-Ju , Peng Li-Ning , Chen Liang-Kung
Published: February 2018

Objectives

The main aim was to investigate the complex inter-relationship between frailty and pain, and the mediating roles of cognitive function, morbidity and mood in this nexus.

Design

A cross-sectional analysis.

Setting

A prospective community-dwelling population-based cohort.

Participants

1682 adults age ≥50 years without evident cognitive or functional impairment, or history of cancer.

Primary and secondary outcome measures

The mediating effect of depression, cognitive function and comorbidity on the nexus between pain and frailty among older and middle-aged adults.

Results

The pain score among older subjects (≥65 years), increased with the degree of frailty (robust=0.96±0.82; pre-frail=1.13±0.86; frail=1.63±1.02; P<0.001); multivariate analysis gave the same result, while moderate pain was associated with frailty in older subjects (OR=3.00, 95% CI 1.30 to 6.60). Conversely, pain and frailty among middle-aged subjects (aged 50–64 years) did not appear to be significantly related; in mediation analysis, pain exerted an indirect effect on frailty via depression (indirect effect=0.03, 95% CI 0.01 to 0.07), while neither cognitive function nor comorbidity had any significant effect in mediating the relationship between pain and frailty.

Conclusion

In cognitively and functionally sound community-dwelling adults aged ≥50 years, moderate pain was related to frailty in those older than 65 years, but not younger ones. Besides the direct influence of pain on frailty, depression partially mediated the pain–frailty nexus. The mechanism by which depression influences pain and frailty requires further investigation.
Urban green spaces and cancer: a protocol for a scoping review
Authors: Porcherie Marion , Lejeune Mathilde , Gaudel Marion , Pommier Jeanine , Faure Emmanuelle , Heritage Zoé , Rican Stéphane , Simos Jean , Cantoreggi Nicola Luca , Roué Le Gall Anne , Cambon Linda , Regnaux Jean-Philippe
Published: February 2018

Introduction

Green space in the built environment is an important topic on the health agenda today. Studies have shown that access to green spaces is associated with better mental and physical health, yet green spaces can also be detrimental to health if they are not managed appropriately. Despite the increasing interest in urban green spaces, little research has so far been conducted into the links between green spaces and cancer.

Objective

The purpose of this scoping review is therefore to map the literature available on the types of relationship between urban green spaces and cancer.

Method and analysis

We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 guideline to report the protocol. To conduct this scoping review, we will use a structured search strategy based on controlled vocabulary and relevant key terms related to green space, urban space and cancer. We will search MEDLINE (PubMed), GreenFILE (EBSCOhost), Cumulative Index to Nursing and Allied Health Literature (EBSCOhost) and ScienceDirect as electronic database as well as hand-search publications for grey literature. This review will therefore provide evidence on this current topic, one which could have practical implications for policy-makers involved in choices which are more conducive to healthy living.

Ethics and dissemination

No primary data will be collected since all data that will be presented in this review are based on published articles and publicly available documents, and therefore ethics committee approval is not a requirement. The findings of this review will be presented at workshops and conferences, and will be submitted for publication in a peer-reviewed journal.
Role of the family doctor in the management of adults with obesity: a scoping review
Authors: Sturgiss Elizabeth A , Elmitt Nicholas , Haelser Emily , van Weel Chris , Douglas Kirsty A
Published: February 2018

Objectives

Obesity management is an important issue for the international primary care community. This scoping review examines the literature describing the role of the family doctor in managing adults with obesity. The methods were prospectively published and followed Joanna Briggs Institute methodology.

Setting

Primary care. Adult patients.

Included papers

Peer-reviewed and grey literature with the keywords obesity, primary care and family doctors. All literature published up to September 2015. 3294 non-duplicate papers were identified and 225 articles included after full-text review.

Primary and secondary outcome measures

Data were extracted on the family doctors’ involvement in different aspects of management, and whether whole person and person-centred care were explicitly mentioned.

Results

110 papers described interventions in primary care and family doctors were always involved in diagnosing obesity and often in recruitment of participants. A clear description of the provider involved in an intervention was often lacking. It was difficult to determine if interventions took account of whole person and person-centredness. Most opinion papers and clinical overviews described an extensive role for the family doctor in management; in contrast, research on current practices depicted obesity as undermanaged by family doctors. International guidelines varied in their description of the role of the family doctor with a more extensive role suggested by guidelines from family medicine organisations.

Conclusions

There is a disconnect between how family doctors are involved in primary care interventions, the message in clinical overviews and opinion papers, and observed current practice of family doctors. The role of family doctors in international guidelines for obesity may reflect the strength of primary care in the originating health system. Reporting of primary care interventions could be improved by enhanced descriptions of the providers involved and explanation of how the pillars of primary care are used in intervention development.
Protocol investigating the clinical utility of an objective measure of attention, impulsivity and activity (QbTest) for optimising medication management in children and young people with ADHD ‘QbTest Utility for Optimising Treatment in ADHD’ (QUOTA): a feasibility randomised controlled trial
Authors: Hall Charlotte L , James Marilyn , Brown Sue , Martin Jennifer L , Brown Nikki , Selby Kim , Clarke Julie , Vijayan Hena , Guo Boliang , Sayal Kapil , Hollis Chris , Groom Madeleine J
Published: February 2018

Introduction

Attention-deficit hyperactivity disorder (ADHD) is characterised by symptoms of inattention, hyperactivity and impulsivity. To improve outcomes, the National Institute for Health and Care Excellence ADHD guidelines recommend regular monitoring of symptoms when children commence medication. However, research suggests that routine monitoring rarely happens, and clinicians often rely on subjective information such as reports from parents and teachers to ascertain improvement. These sources can be unreliable and difficult to obtain. The addition of an objective test of attention and activity (QbTest) may improve the objectivity, reliability and speed of clinical decision-making and so reduce the time to identify the optimal medication dose. This study aims to assess the feasibility and acceptability of a QbTest medication management protocol delivered in routine healthcare services for children with ADHD.

Method and analysis

This multisite feasibility randomised controlled trial (RCT) will recruit 60 young people (aged 6–17 years old), diagnosed with ADHD, and starting stimulant medication who are seen by Child and Adolescent Mental Health Services or Community Paediatric services. Participants will be randomised into one of two arms. In the experimental arm (QbTest protocol), the participant will complete a QbTest at baseline (prior to medication initiation), and two follow-up QbTests on medication (2–4 weeks and 8–10 weeks later). In the control arm, participants will receive treatment as usual, with at least two follow-up consultations. Measures of parent-, teacher- and clinician-rated symptoms and global functioning will be completed at each time point. Health economic measures will be completed. Clinicians will record treatment decision-making. Acceptability and feasibility of the protocol will be assessed alongside outcome measure completion rates. Qualitative interviews will be conducted.

Ethics and dissemination

The findings will be used to inform the development of a fully powered RCT. The results will be submitted for publication in peer-reviewed journals. The study has ethical approval.

Trial registration number

NCT03368573; Pre-results.
Management, characteristics and outcomes of patients with acute coronary syndrome in Sri Lanka
Authors: Galappatthy Priyadarshani , Bataduwaarachchi Vipula R , Ranasinghe Priyanga , Galappatthy Gamini K S , Wijayabandara Maheshi , Warapitiya Dinuka S , Sivapathasundaram Mythily , Wickramarathna Thilini , Senarath Upul , Sridharan Sathasivam , Wijeyaratne Chandrika N , Ekanayaka Ruvan
Published: February 2018

Background

Ischaemic heart disease is the leading cause of in-hospital mortality in Sri Lanka. Acute Coronary Syndrome Sri Lanka Audit Project (ACSSLAP) is the first national clinical-audit project that evaluated patient characteristics, clinical outcomes and care provided by state-sector hospitals.

Methods

ACSSLAP prospectively evaluated acute care, in-hospital care and discharge plans provided by all state-sector hospitals managing patients with ACS. Data were collected from 30 consecutive patients from each hospital during 2–4 weeks window. Local and international recommendations were used as audit standards.

Results

Data from 87/98 (88.7%) hospitals recruited 2177 patients, with 2116 confirmed as having ACS. Mean age was 61.4±11.8 years (range 20–95) and 58.7% (n=1242) were males. There were 813 (38.4%) patients with unstable angina, 695 (32.8%) with non-ST-elevation myocardial infarction (NSTEMI) and 608 (28.7%) with ST-elevation myocardial infarction (STEMI). Both STEMI (69.9%) and NSTEMI (61.4%) were more in males (P<0.001). Aspirin, clopidogrel and statins were given to over 90% in acute setting and on discharge. In STEMI, 407 (66.9%) were reperfused; 384 (63.2%) were given fibrinolytics and only 23 (3.8%) underwent primary percutaneous coronary intervention (PCI). Only 42.3 % had thrombolysis in <30 min and 62.5% had PCI in <90 min. On discharge, beta-blockers and ACE inhibitors/angiotensin II receptor blockers were given to only 50.7% and 69.2%, respectively and only 17.6% had coronary interventions planned.

Conclusions

In patients with ACS, aspirin, clopidogrel and statin use met audit standards in acute setting and on discharge. Vast majority of patients with STEMI underwent fibrinolyisis than PCI, due to limited resources. Primary PCI, planned coronary interventions and timely thrombolysis need improvement in Sri Lanka.
Interphysician agreement on subclassification of myocardial infarction
Authors: Gard Anton , Lindahl Bertil , Batra Gorav , Hadziosmanovic Nermin , Hjort Marcus , Szummer Karolina Elisabeth , Baron Tomasz
Published: February 2018

Objective

The universal definition of myocardial infarction (MI) differentiates MI due to oxygen supply/demand mismatch (type 2) from MI due to plaque rupture (type 1) as well as from myocardial injuries of non-ischaemic or multifactorial nature. The purpose of this study was to investigate how often physicians agree in this classification and what factors lead to agreement or disagreement.

Methods

A total of 1328 patients diagnosed with MI at eight different Swedish hospitals 2011 were included. All patients were retrospectively reclassified into different MI or myocardial injury subtypes by two independent specially trained physicians, strictly adhering to the third universal definition of MI.

Results

Overall, there was a moderate interobserver agreement with a kappa coefficient (κ) of 0.55 in this classification. There was substantial agreement when distinguishing type 1 MI (κ: 0.61), compared with moderate agreement when distinguishing type 2 MI (κ: 0.54). In multivariate logistic regression analyses, ST elevation MI (P<0.001), performed coronary angiography (P<0.001) and larger changes in troponin levels (P=0.023) independently made the physicians agree significantly more often, while they disagreed more often with symptoms of dyspnoea (P<0.001), higher systolic blood pressure (P=0.001) and higher C reactive protein levels on admission (P=0.016).

Conclusion

Distinguishing MI types is challenging also for trained adjudicators. Although strictly adhering to the third universal definition of MI, differentiation between type 1 MI, type 2 MI and myocardial injury only gave a moderate rate of interobserver agreement. More precise and clinically applicable criteria for the current classification, particularly for type 2 MI diagnosis, are urgently needed.
Identification of novel fusion transcripts in multiple myeloma
Authors: Lin Mingxuan , Lee Peak Ling , Chiu Lily , Chua Constance , Ban Kenneth H K , Lin Adeline H F , Chan Zit Liang , Chung Tae-Hoon , Yan Benedict , Chng Wee-Joo
Published: February 2018

Aims

Multiple myeloma (MM) is a heterogeneous disease characterised by genetically complex abnormalities. The classical mutational spectrum includes recurrent chromosomal aberrations and gene-level mutations. Recurrent translocations involving theIGHgene such as t(11;14), t(4;14) and t(14;16) are well known. However, the presence of complex genetic abnormalities raises the possibility that fusions other than the recurrentIGHtranslocations exist. We therefore employed a targeted RNA-sequencing panel to identify novel putative fusions in a local cohort of MM.

Methods

Targeted RNA-sequencing was performed on 21 patient samples using the Illumina TruSight RNA Pan-Cancer Panel (comprising 1385 genes). Fusion calls were generated from the Illumina RNA-Sequencing Alignment software (V.1.0.0). These samples had conventional cytogenetic and fluorescence in situ hybridisation data for the common recurrent chromosomal abnormalities (t(11;14), t(4;14), t(14;16) and 17p13 deletion). The MMRF CoMMpass dataset was analysed using the TopHat-fusion pipeline.

Results

A total of 10 novel fusions were identified by the TruSight RNA Pan-Cancer Panel. Two of these fusions,HGF/CACNA2D1andSMC3/MXI1, were validated by reverse transcription PCR and Sanger sequencing as they involve genes that may have biological relevance in MM genesis. Four of these (MAP2K4/MAP2K4P1) are likely to be spurious secondary to misalignment of reads to a pseudogene. One record of theHGF/CACNA2D1fusion was identified from the MMRF CoMMpass dataset.

Conclusions

The identification of novel fusions offers insights into the biology of MM and might have clinical relevance. Further functional studies are required to determine the biological and clinical relevance of these novel fusions.
Exogenous ketone salts do not improve cognitive responses after a high-intensity exercise protocol in healthy college-aged males
Authors: Waldman Hunter S. , Basham Steven A. , Price Ffi G. , Smith JohnEric W. , Chander Harish , Knight Adam C. , Krings Ben M. , McAllister Matthew J.
Published: February 2018

This study examined the effects of a dl-β-hydroxybutyrate (βHB) containing beverage on cognitive and performance measures during a bout of repeated Wingates. Fifteen healthy, college-aged males (mean ± SD; age: 23.1 ± 2.4 years, height: 165.4 ± 2.0 cm, mass: 81.4 ± 9.2 kg) volunteered for the present study. Trial 1 consisted of baseline measures and familiarization for the protocol. During trials 2 and 3, subjects reported to the laboratory, after a 10-h fast, and ingested 11.38 g of βHB or a placebo (PLA) beverage 30 min before exercise. Participants then completed a cognitive challenge (CC), consisting of a 5-min FitLight response task while cycling. At the cessation of the test, participants then completed four 15-s repeated Wingates with 4 min of rest between, followed by another 5-min CC response task. Blood ketones, glucose, and lactate were measured pre-CC and post-Wingates. βHB levels were significantly higher compared with PLA (0.53 vs. 0.21 mmol/L), respectively. A significant order effect was observed across trials 2 and 3 for total FitLight misses and hits, regardless of treatment. Further, there were no significant differences among Wingate power output between treatments, although fatigue index was higher in the βHB group compared with PLA (32.3 vs. 29.4 W/s), respectively. In conclusion, βHB did not improve high-intensity cycling or cognitive performance measures; however, these findings might be partially explained by the absolute dosing protocol used for βHB in the present study as opposed to a relative (g/kg) dosing protocol used in previous research.
Breaking into emergency shuttle service: Aspects and impacts of retracting buses from existing scheduled bus services
Authors: Diab Ehab , Feng Guangnan , Shalaby Amer
Published: February 2018

High-quality transit service is a vital aspect of any modern city. When unexpected interruptions to the transit service occur, they reduce the quality of service provided to the public. One of the main strategies that is employed to deal with rail service interruptions is “bus bridging,” whereby buses from scheduled services are deployed to offer shuttle services. Very few efforts are found in the literature that have investigated this policy’s effectiveness. Therefore, this study aims at exploring the different aspects and impacts of retracting buses from scheduled services in response to subway and streetcar service interruptions in Toronto. It explores the size of the deployment, as well as the system response and recovery times using detailed subway and streetcar shuttle service reports collected in 2015. The paper shows remarkable fluctuations not only in the utilized number of shuttle service buses over time, but also on the service response and recovery times.
Determinants of home range size and space use patterns in a protected wolf (Canis lupus) population in the central Apennines, Italy
Authors: Mancinelli S. , Boitani L. , Ciucci P.
Published: February 2018

Large carnivores are amongst the most susceptible species to human activities, and human-modified environments pose a threat to carnivore conservation. Wolves (Canis lupus Linnaeus, 1758) in the central Apennines, Italy, have coexisted with humans since historic times and represent a good case study to assess their spatiotemporal response to anthropogenic factors. From 2008 to 2010, we investigated the spatial behavior of wolves (seven wolves in five packs and six floaters) in the Abruzzo Lazio and Molise National Park. Orographically corrected annual home ranges of resident wolf packs, estimated through the Brownian bridge movement model, averaged 104 ± 24 km2 (mean ± SD), whereas floaters used two- to fourfold larger areas (293.8–408.7 km2). We did not detect any seasonal effect on home range size, but home ranges were larger during the night and in areas of greater road density, especially during summer. By estimating core areas through an individual-based approach, we also revealed a habitat-mediated response to human presence and activity, as resident wolves preferentially established core areas at greater elevation and in the more forested and inaccessible portions of the home range.
Aggression and plasma testosterone in male golden hamsters (Mesocricetus auratus) in response to encounters with receptive vs. nonreceptive females
Authors: Zhao Xin , Liu Dingzhen
Published: February 2018

Exposure to sexual stimuli can lead to increased aggression in male mammals, but it is unclear whether the aggression is related to the receptiveness of the females. Interactions with receptive females elicit testosterone (T) pulses that are important for sexual behaviors. We investigated the effects of male–female interactions on subsequent aggressive behaviors and T responses in the golden hamster (Mesocricetus auratus (Waterhouse, 1839)). Three groups (n = 18, 17, and 18) of males were exposed to receptive females, nonreceptive females, and blank (control), respectively. Then, we randomly chose eight animals from each group and measured their aggression toward an unfamiliar male conspecific; the remaining 29 males were used for a T assay (to avoid effects of aggression on T levels). The results show that interactions with females led to significantly higher male aggression and T levels than were found in control males. The increased aggression was not related to the receptiveness of the females, but receptive females elicited higher levels of T in males than nonreceptive females. Our findings suggest that the elevated aggression following the sexual encounter may serve to defend the female, by enhancing the ability of males to exclude other males from the vicinity of females, whereas the post-encounter T release may serve to assist mating behaviors and reproductive success.
Viable Cell Culture Banking for Biodiversity Characterization and Conservation
Authors: Ryder Oliver A. , Onuma Manabu
Published: February 2018

Because living cells can be saved for indefinite periods, unprecedented opportunities for characterizing, cataloging, and conserving biological diversity have emerged as advanced cellular and genetic technologies portend new options for preventing species extinction. Crucial to realizing the potential impacts of stem cells and assisted reproductive technologies on biodiversity conservation is the cryobanking of viable cell cultures from diverse species, especially those identified as vulnerable to extinction in the near future. The advent of in vitro cell culture and cryobanking is reviewed here in the context of biodiversity collections of viable cell cultures that represent the progress and limitations of current efforts. The prospects for incorporating collections of frozen viable cell cultures into efforts to characterize the genetic changes that have produced the diversity of species on Earth and contribute to new initiatives in conservation argue strongly for a global network of facilities for establishing and cryobanking collections of viable cells.
Protection from chronic stress- and depressive symptom-induced vascular endothelial dysfunction in female rats is abolished by preexisting metabolic disease
Authors: Brooks Steven D. , Hileman Stanley M. , Chantler Paul D. , Milde Samantha A. , Lemaster Kent A. , Frisbee Stephanie J. , Shoemaker J. Kevin , Jackson Dwayne N. , Frisbee Jefferson C.
Published: February 2018

While it is known that chronic stress and clinical depression are powerful predictors of poor cardiovascular outcomes, recent clinical evidence has identified correlations between the development of metabolic disease and depressive symptoms, creating a combined condition of severely elevated cardiovascular disease risk. In this study, we used the obese Zucker rat (OZRs) and the unpredictable chronic mild stress (UCMS) model to determine the impact of preexisting metabolic disease on the relationship between chronic stress/depressive symptoms and vascular function. Additionally, we determined the impact of metabolic syndrome on sex-based protection from chronic stress/depressive effects on vascular function in female lean Zucker rats (LZRs). In general, vasodilator reactivity was attenuated under control conditions in OZRs compared with LZRs. Although still impaired, conduit arterial and resistance arteriolar dilator reactivity under control conditions in female OZRs was superior to that in male or ovariectomized (OVX) female OZRs, largely because of better maintenance of vascular nitric oxide and prostacyclin levels. However, imposition of metabolic syndrome in combination with UCMS in OZRs further impaired dilator reactivity in both vessel subtypes to a similarly severe extent and abolished any protective effect in female rats compared with male or OVX female rats. The loss of vascular protection in female OZRs with UCMS was reflected in vasodilator metabolite levels, which closely matched those in male and OVX female OZRs subjected to UCMS. These results suggest that presentation of metabolic disease in combination with depressive symptoms can overwhelm the vasoprotection identified in female rats and, thereby, may reflect a severe impairment to normal endothelial function.

NEW & NOTEWORTHY This study addresses the protection from chronic stress- and depression-induced vascular dysfunction identified in female compared with male or ovariectomized female rats. We determined the impact of preexisting metabolic disease, a frequent comorbidity of clinical depression in humans, on that vascular protection. With preexisting metabolic syndrome, female rats lost all protection from chronic stress/depressive symptoms and became phenotypically similar to male and ovariectomized female rats, with comparably poor vasoactive dilator metabolite profiles.
The HCM-linked W792R mutation in cardiac myosin-binding protein C reduces C6 FnIII domain stability
Authors: Smelter Dan F. , de Lange Willem J. , Cai Wenxuan , Ge Ying , Ralphe J. Carter
Published: February 2018

Cardiac myosin-binding protein C (cMyBP-C) is a functional sarcomeric protein that regulates contractility in response to contractile demand, and many mutations in cMyBP-C lead to hypertrophic cardiomyopathy (HCM). To gain insight into the effects of disease-causing cMyBP-C missense mutations on contractile function, we expressed the pathogenic W792R mutation (substitution of a highly conserved tryptophan residue by an arginine residue at position 792) in mouse cardiomyocytes lacking endogenous cMyBP-C and studied the functional effects using three-dimensional engineered cardiac tissue constructs (mECTs). Based on complete conservation of tryptophan at this location in fibronectin type II (FnIII) domains, we hypothesized that the W792R mutation affects folding of the C6 FnIII domain, destabilizing the mutant protein. Adenoviral transduction of wild-type (WT) and W792R cDNA achieved equivalent mRNA transcript abundance, but not equivalent protein levels, with W792R compared with WT controls. mECTs expressing W792R demonstrated abnormal contractile kinetics compared with WT mECTs that were nearly identical to cMyBP-C-deficient mECTs. We studied whether common pathways of protein degradation were responsible for the rapid degradation of W792R cMyBP-C. Inhibition of both ubiquitin-proteasome and lysosomal degradation pathways failed to increase full-length mutant protein abundance to WT equivalence, suggesting rapid cytosolic degradation. Bacterial expression of WT and W792R protein fragments demonstrated decreased mutant stability with altered thermal denaturation and increased susceptibility to trypsin digestion. These data suggest that the W792R mutation destabilizes the C6 FnIII domain of cMyBP-C, resulting in decreased full-length protein expression. This study highlights the vulnerability of FnIII-like domains to mutations that alter domain stability and further indicates that missense mutations in cMyBP-C can cause disease through a mechanism of haploinsufficiency.

NEW & NOTEWORTHY This study is one of the first to describe a disease mechanism for a missense mutation in cardiac myosin-binding protein C linked to hypertrophic cardiomyopathy. The mutation decreases stability of the fibronectin type III domain and results in substantially reduced mutant protein expression dissonant to transcript abundance.
Cognitive Function Declines Significantly during Haemodialysis in a Majority of Patients: A Call for Further Research
Authors: Dasgupta Indranil , Patel Mitesh , Mohammed Nuredin , Baharani Jyoti , Subramanian Thejasvi , Thomas G. Neil , Tadros George
Published: February 2018

Introduction: Cognitive impairment (CI) is very common condition that occurs in haemodialysis patients and it is associated with reduced functional capacity and mortality. We assessed the change in cognitive function during haemodialysis and associated risk factors. Methods: All patients ≥50 years, on haemodialysis for ≥3 months, no dementia from 2 dialysis centres were selected. Cognition was assessed before and after a haemodialysis session using parallel versions of the Montreal Cognitive Assessment (MOCA) tool. Multiple regression was used to examine potential confounders. Results: Eight-two patients completed both tests – median age 73 (52–91) years, 59% male, dialysis vintage 41 (3–88) months. Sixty-two (76%) had CI at baseline. Cognition declined over dialysis (MOCA 21 ± 4.8 to 19.1 ± 4.1, p < 0.001) and domains affected were attention, language, abstraction and delayed recall. Age and dialysis vintage were independently associated with decline. Conclusion: Cognitive function declines over a haemodialysis session and this has significant clinical implications over health literacy, self-management and tasks like driving. More research is needed to find the cause for this decline in cognition.
A Case of Neurotrophic Keratopathy Associated with Nasopharyngeal Carcinoma
Authors: Sato Tomoko , Sugioka Koji , Kodama-Takahashi Aya , Fukuda Masahiko , Mishima Hiroshi , Shimomura Yoshikazu
Published: February 2018

Purpose: To report a case of neurotrophic keratopathy associated with nasopharyngeal carcinoma. Case Report: A 59-year-old man who had been diagnosed with a nasopharyngeal carcinoma was referred to the authors because of visual disturbance and pain in his right eye. Slit-lamp examination revealed a corneal epithelial defect and corneal stromal edema surrounding the epithelial defect area in his right eye. Magnetic resonance imaging showed a mass in his cavernous sinus, which was identified as nasopharyngeal carcinoma (NPC). We diagnosed neurotrophic keratopathy associated with NPC and initiated treatment with preservative-free artificial tears, antibiotic eye drops, fibronectin, a therapeutic contact lens, and amniotic membrane transplantation. However, the persistent corneal epithelial defect was unresponsive to these treatments. Conclusion: Neurotrophic keratopathy secondary to NPC is thought to be rare. We presented a case of neurotrophic keratopathy associated with cavernous sinus metastasis of an NPC. The development of new and more effective treatments for this refractory disease is anticipated.
rhIGF-1 Treatment Increases Bone Mineral Density and Trabecular Bone Structure in Children with PAPP-A2 Deficiency
Authors: Hawkins-Carranza Federico G. , Muñoz-Calvo María T. , Martos-Moreno Gabriel Á. , Allo-Miguel Gonzalo , Del Río Luis , Pozo Jesús , Chowen Julie A. , Pérez-Jurado Luis A. , Argente Jesús
Published: February 2018

Aim: Our objective was to determine changes in bone mineral density (BMD), trabecular bone score (TBS), and body composition after 2 years of therapy with recombinant human insulin-like growth factor-1 (rhIGF-1) in 2 prepubertal children with a complete lack of circulating PAPP-A2 due to a homozygous mutation in PAPP-A2 (p.D643fs25*) resulting in a premature stop codon. Methods: Body composition, BMD, and bone structure were determined by dual-energy X-ray absorptiometry at baseline and after 1 and 2 years of rhIGF-1 treatment. Results: Height increased from 132 to 145.5 cm (patient 1) and from 111.5 to 124.5 cm (patient 2). Bone mineral content increased from 933.40 to 1,057.97 and 1,152.77 g in patient 1, and from 696.12 to 773.26 and 911.51 g in patient 2, after 1 and 2 years, respectively. Whole-body BMD also increased after 2 years of rhIGF-1 from baseline 0.788 to 0.869 g/cm2 in patient 1 and from 0.763 to 0.829 g/cm2 in patient 2. After 2 years of treatment, both children had an improvement in TBS. During therapy, a slight increase in body fat mass was seen, with a concomitant increase in lean mass. No adverse effects were reported. Conclusion: Two years of rhIGF-1 improved growth, with a tendency to improve bone mass and bone microstructure and to modulate body composition.
Absence of Nicotinamide Nucleotide Transhydrogenase in C57BL/6J Mice Exacerbates Experimental Atherosclerosis
Authors: Vozenilek Aimee E. , Vetkoetter Matthew , Green Jonette M. , Shen Xinggui , Traylor James G. , Klein Ronald L. , Orr A. Wayne , Woolard Matthew D. , Krzywanski David M.
Published: February 2018

Background: Mitochondrial reactive oxygen species (ROS) contribute to inflammation and vascular remodeling during atherosclerotic plaque formation. C57BL/6N (6N) and C57BL/6J (6J) mice display distinct mitochondrial redox balance due to the absence of nicotinamide nucleotide transhydrogenase (NNT) in 6J mice. We hypothesize that differential NNT expression between these animals alters plaque development. Methods: 6N and 6J mice were treated with AAV8-PCSK9 (adeno-associated virus serotype 8/proprotein convertase subtilisin/kexin type 9) virus leading to hypercholesterolemia, increased low-density lipoprotein, and atherosclerosis in mice fed a high-fat diet (HFD). Mice were co-treated with the mitochondria-targeted superoxide dismutase mimetic MitoTEMPO to assess the contribution of mitochondrial ROS to atherosclerosis. Results: Baseline and HFD-induced vascular superoxide is increased in 6J compared to 6N mice. MitoTEMPO diminished superoxide in both groups demonstrating differential production of mitochondrial ROS among these strains. PCSK9 treatment and HFD led to similar increases in plasma lipids in both 6N and 6J mice. However, 6J animals displayed significantly higher levels of plaque formation. MitoTEMPO reduced plasma lipids but did not affect plaque formation in 6N mice. In contrast, MitoTEMPO surprisingly increased plaque formation in 6J mice. Conclusion: These data indicate that loss of NNT increases vascular ROS production and exacerbates atherosclerotic plaque development.
What We Do and Do Not Know about Women and Kidney Diseases; Questions Unanswered and Answers Unquestioned: Reflection on World Kidney Day and International Women’s Day
Authors: Piccoli Giorgina B. , Alrukhaimi Mona , Liu Zhi-Hong , Zakharova Elena , Levin Adeera ,   on behalf of the World Kidney Day Steering Committee
Published: February 2018

Chronic kidney disease affects approximately 10% of the world’s adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women’s Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women’s health and specifically their kidney health, on the community and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world’s population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to have an impact on women, with profound consequences for child bearing, and on the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.
Low Skeletal Muscle Density Is Associated with Early Death in Patients with Perihilar Cholangiocarcinoma Regardless of Subsequent Treatment
Authors: van Vugt Jeroen L.A. , Gaspersz Marcia P. , Vugts Jaynee , Buettner Stefan , Levolger Stef , de Bruin Ron W.F. , Polak Wojciech G. , de Jonge Jeroen , Willemssen François E.J.A. , Groot Koerkamp Bas , IJzermans Jan N.M.
Published: February 2018

Background: Low skeletal muscle mass is associated with increased postoperative morbidity and worse survival following resection for perihilar cholangiocarcinoma (PHC). We investigated the predictive value of skeletal muscle mass and density for overall survival (OS) of all patients with suspected PHC, regardless of treatment. Methods: Baseline characteristics and parameters regarding disease and treatment were collected from all patients with PHC from 2002 to 2014. Skeletal muscle mass and density were measured at the level of the third lumbar vertebra on CT. The association between skeletal muscle mass and density with OS was investigated using the Kaplan-Meier method and Cox survival. Results: Median OS in 233 included patients did not differ between those with and without low skeletal muscle mass (p = 0.203), whereas a significantly different median OS (months) was observed between patients with low (HR 7.0, 95% CI 4.7–9.3) and high (HR 12.1, 95% CI 8.1–16.1) skeletal muscle density (p = 0.004). Low skeletal muscle density was independently associated with decreased OS (HR 1.78, 95% CI 1.03–3.07, p = 0.040) within the first 6 months but not after 6 months (HR 0.68, 95% CI 0.44–1.07, p = 0.093), after adjusting for age, tumour size and suspected peritoneal or other distant metastases on imaging. Conclusion: A time-dependent effect of skeletal muscle density on OS was found in patients with PHC, regardless of subsequent treatment. Low skeletal muscle density may identify patients at risk for early death.
Malformações congênitas em regiões de monocultivo no estado de Minas Gerais, Brasil
Authors: Dutra Lidiane Silva , Ferreira Aldo Pacheco
Published: February 2018

Objective: to analyze the association between the use of agrochemicals and congenital malformations in municipalities with greater exposure, as well as to evaluate the nature of the correlation between the trend observed and the volume of agrochemicals considered as endocrine disruptors in the state of Minas Gerais, Brazil, between 1994 and 2014. Model Study: Cross-sectional study, exploratory, descriptive and quantitative character. Method: Rates of malformations for the periods 1994-2003 and 2004-2014 were calculated from the information on live births available at SINASC/Ministry of Health. Odds Ratio tested the association between types of malformations and variables for each variable separately. The significance was set at p<0.05. Results: there was an increasing trend in the rates of congenital malformation in the state of Minas Gerais, especially at Triângulo Mineiro/Alto Paraíba and Vale do Mucuri/Jequitinhonha regions. It was found that the rates for congenital malformations were higher for the years of greatest exposure (2004-2014) and had a statistically significant association for all congenital malformations in the state of Minas Gerais. Conclusion: Maternal exposure to pesticides was related with higher incidence of congenital malformations.
CD4+ T lymphocytopenia associated with sideropenia: case report
Authors: De Vito Fernanda Bernadelli , Ribeiro Juliana Lima , Silva Ane Rose Lopes , Souza Helio Moraes de
Published: February 2018

Importance of the issue: Idiopathic CD4 T lymphocytopenia is an unusual immune defect in which there is an unexplained deficit of CD4 T cells. This case presents a 39-year-old female patient, with CD4+ T lymphocytopenia, who was not infected with immunosuppressive viruses neither was she subjected to immunosuppressive therapies. Comments: While monitoring the patient, she was found to have very low serum ferritin and, after parenteral iron therapy, there were changes in CD4+ cell levels, indicating that, in this case, lymphocytopenia was secondary to sideropenia. The patient is being kept under strict control of serum iron and periodic immunological evaluation, and she has not showed any clinical and/or laboratory adverse events so far. It is known that iron deficiency is an important factor in the genesis of immunological changes that occur in patients with iron deficiency anemia. It is important to understand the effects of iron deficiency on the immune system due to its high prevalence worldwide. Moreover, it could also help to clarify several cases of idiopathic CD4 lymphocytopenia.
Chylous ascites secondary to Hodgkin’s lymphoma in a HIV/aids patient: case report and literature review
Authors: Silva Júnior Mário Luciano de Mélo , Leonídio Hildenice Ferreira Bernardes , Lira Mariana Montenegro de Melo , Arraes Luciana Cardoso Martins , Padilha Carlos Eduardo Guimarães , Araújo Paulo Sérgio Ramos de
Published: February 2018

Study design: case report. Case report: Man, 42 years old, diagnosed with aids two years ago, had developed enlarging in abdominal volume six months from admission. Computed tomography imaging showed free liquid in peritoneal cavity and increased retroperitoneal and mesenteric lymph nodes, besides splenomegaly. Ascitic fluid had milky appearance and high triglycerides levels. Hodgkin's lymphoma (mixed cellularity) was confirmed by histopathological analysis of a video-laparoscopic lymph node biopsy, Ann Arbor IIIS staging. Chemotherapy and continuation of highly active antiretroviral therapy resulted in weight gain and reduction of abdominal volume. Chylous ascites is a rare condition, which has a vast differential diagnosis. Discussion: In our review, the majority (15/18, 83%) of chylous ascites in HIV/aids-patients are due to infectious causes (mainly Mycobacterium avium complex and tuberculosis infection), in highly immunocompromised patients (mean TCD4=87cell/mL). To the best of our knowledge, this is the first case of chylous ascites secondary to Hodgkin’s lymphoma in a patient with aids.
Gardner Syndrome: case report and brief review of the literature
Authors: Cruz Isabela Azevedo Nicodemos da , Vergílio Fernanda Sasaki , Silva Lorena Luryann Cartaxo da , Cruz Gabriela Azevedo Nicodemos da
Published: February 2018

Type of study: Case report. Relevance and comments: Gardner Syndrome is a variant of Familial Adenomatous Polyposis (FAP), with the association of gastrointestinal polyps, soft tissue tumors and bone tumors. It is a rare disorder and early diagnosis is crucial to reduce its morbimortality. The present report illustrates a case of Gardner Syndrome with its clinical and radiologic features, as well as a brief review of the literature.