bluuebunny/crossref_metadata_2025_split huggingface dataset:
BHBA treatment improves cognitive function by targeting pleiotropic mechanisms in transgenic mouse model of Alzheimer's disease
Authors: Wu Yancheng , Gong Yuhong , Luan Yongxin , Li Yang , Liu Juxiong , Yue Zitong , Yuan Boyu , Sun Jingxuan , Xie Changxin , Li Lijuan , Zhen Junli , Jin Xinxin , Zheng Yan , Wang Xiaomin , Xie Liwei , Wang Wei 
Published: December 2019

AbstractAccumulation of amyloid β (Aβ) peptide, inflammation, and oxidative stress contribute to Alzheimer's disease (AD) and trigger complex pathogenesis. The ketone body β‐hydroxybutyrate (BHBA) is an endogenous metabolic intermediate that protects against stroke and neurodegenerative diseases, but the underlying mechanisms are unclear. The present study aims to elucidate the protective effects of BHBA in the early stage of AD model and investigate the underlying molecular mechanisms. Three‐and‐half‐month‐old double‐transgenic mice (5XFAD) overexpressing β‐amyloid precursor protein (APP) and presenilin‐1 (PS1) were used as the AD model. The 5XFAD mice received 1.5 mmol/kg/d BHBA subcutaneously for 28 days. Morris water maze test, nest construction, and passive avoidance experiments were performed to assess the therapeutic effects on AD prevention in vivo, and brain pathology of 5XFAD mice including amyloid plaque deposition and microglia activation were assessed. Gene expression profiles in the cortexes of 5XFAD‐ and BHBA‐treated 5XFAD mice were performed with high‐throughput sequencing and bioinformatic analysis. Mouse HT22 cells were treated with 2 mM BHBA to explore its in vitro protective effects of BHBA on hippocampal neurons against Aβ oligomer toxicity, ATP production, ROS generation, and mitochondrial aerobic respiratory function. APP, BACE1, and neprilysin (NEP) expression levels were evaluated in HT22 cells following treatment with BHBA by measuring the presence or absence of G protein‐coupled receptor 109A (GPR109A). BHBA improved cognitive function of 5XFAD mice in Morris water maze test, nesting construction and passive avoidance experiments, and attenuated Aβ accumulation and microglia overactivation in the brain. BHBA also enhanced mitochondrial respiratory function of hippocampal neurons and protected it from Aβ toxicity. The enzymes, APP and NEP were regulated by BHBA via G‐protein‐coupled receptor 109A (GPR109A). Furthermore, RNA sequencing revealed that BHBA‐regulated genes mainly annotated in aging, immune system, nervous system, and neurodegenerative diseases. Our data suggested that BHBA confers protection against the AD‐like pathological events in the AD mouse model by targeting multiple aspects of AD and it may become a promising candidate for the prevention and treatment of AD.
14 Years Later: A Follow-Up Case-Study Analysis of 8 Health Professions Education Scholarship Units
Authors: Humphrey-Murto Susan , O’Brien Bridget , Irby David M. , van der Vleuten Cees , ten Cate Olle , Durning Steven , Gruppen Larry , Hamstra Stanley J. , Hu Wendy , Varpio Lara 
Published: December 2019

Purpose
Internationally, health professions education scholarship units (HPESUs) are often developed to promote engagement in educational scholarship, yet little is known about how HPESUs change over time or what factors support their longevity. In hopes of helping HPESUs thrive, this study explored factors that shaped the evolution of 8 HPESUs over the past 14 years.

Method
This study involved retrospective case-study analysis of the 8 American, Canadian, and Dutch HPESUs profiled in a 2004 publication. First, the research team summarized key elements of HPESUs from the 2004 articles, then conducted semistructured interviews with the current unit directors. In the first set of questions, directors were asked to reflect on how the unit had changed over time, what successes the unit enjoyed, what enabled these successes, what challenges the unit encountered, and how these challenges were managed. In the second set of questions, questions were tailored to each unit, following up on unique elements from the original article. The team used Braun and Clarke’s 6-phase approach to thematic analysis to identify, analyze, and report themes.

Results
The histories of the units varied widely—some had grown by following their original mandates, some had significant mission shifts, and others had nearly disappeared. Current HPESU directors identified 3 key factors that shaped their HPESU’s longitudinal development: the people working within and overseeing the HPESU (the need for a critical mass of scholars, a pipeline for developing scholars, and effective leadership), institutional structures (issues of centralization, unit priorities, and clear messaging), and funding (the need for multiple funding sources).

Conclusions
Study findings offer insights that may help current HPESU directors to strategically plan for their unit’s continued development. Tactically harnessing the factors identified could help directors ensure their HPESU’s growth and contend with the challenges that threaten the unit’s success.
Sleep Moderating the Relationship Between Pain and Health Care Use in Youth With Sickle Cell Disease
Authors: Valrie Cecelia R. , Alston Kristen , Fuh Beng , Redding-Lallinger Rupa , Sisler India 
Published: December 2019

Objectives:
The purpose of the current study was to investigate the influence of sleep on the relationship between pain and health care use (HCU) in youth with sickle cell disease (SCD). It was hypothesized that poor sleep would be related to higher HCU and would strengthen the relationship between high pain frequency and more HCU among youth with SCD.

Materials and Methods:
Ninety-six youth with SCD (aged 8 to 17 y) and their guardians were recruited from 3 regional pediatric SCD clinics. Guardians reported on the youth’s pain frequency and HCU using the Structured Pain Interview for parents, and youth wore a sleep actigraph for up to 2 weeks to assess sleep duration and sleep efficiency. A series of regression models were calculated with the following outcomes: emergency department visits, hospitalizations, and health care provider contacts.

Results:
Inconsistent with hypotheses, poor sleep was not directly related to HCU. Also, higher sleep duration appeared to strengthen the relationship between high pain frequency and more emergency department visits.

Conclusions:
Findings suggest that good sleep may serve as a protective factor for better matching pain to HCU. Results should be interpreted in the context of study limitations. Research is needed to investigate possible mechanisms linking sleep duration to HCU in response to pain and to ascertain if sleep patterns influence the relationship between pain and other functional outcomes in youth with SCD. Clinically, these findings support the need to acknowledge and address the role that sleep plays in responding to SCD pain in pediatric populations.
Cosyntropin for the Treatment of Refractory Postdural Puncture Headache in Pediatric Patients
Authors: Zapapas Michelle K. , Gralla Jane , Tong Suhong , Eisdorfer Seth 
Published: December 2019

Objectives:
Postdural puncture headache is a challenging complication of diagnostic, therapeutic, and unintentional lumbar puncture. Literature evidence supports cosyntropin as a viable noninvasive therapy for adults who have failed conservative management, but pediatric data are limited. The purpose of this retrospective chart review was to describe the use of intravenous cosyntropin for refractory pediatric postdural puncture headache at a single free-standing tertiary care pediatric hospital.

Methods:
Patients who had received cosyntropin were identified. Charts were retrospectively reviewed for indication, dosing information, efficacy, and side effects. The response was defined as a 50% reduction in pain score, with a secondary efficacy measure of time to discharge after the first dose.

Results:
Over a 5-year period, 26 patients received 37 doses of cosyntropin. Dosing ranged from 5 to 15 mcg/kg (median, 10.4 mcg/kg). There was a significant reduction in pain scores after the first dose of cosyntropin (P=0.008). Eighty-one percent of patients (n=21) achieved either a 50% reduction in pain or were discharged within 24 hours after the first dose. The median time to 50% pain reduction in 13 patients who achieved it before or discharge was 5 hours (range, 1 to 30 h). The median time to discharge after the first dose was 20 hours (range, 2 to 72 h). Ten patients received >1 dose of cosyntropin. Three patients required an epidural blood patch. No adverse effects related to treatment were identified.

Discussion:
This study suggests that while further research is warranted, cosyntropin is a potential alternative to epidural blood patch for pediatric patients with postdural puncture headache who fail conservative management.
Cannabis Use Disorder and Perioperative Outcomes in Major Elective Surgeries
Authors: Goel Akash , McGuinness Brandon , Jivraj Naheed K. , Wijeysundera Duminda N. , Mittleman Murray A. , Bateman Brian T. , Clarke Hance , Kotra Lakshmi P. , Ladha Karim S. 
Published: December 2019

Abstract

Background
Although cannabis is known to have cardiovascular and psychoactive effects, the implications of its use before surgery are currently unknown. The objective of the present study was to determine whether patients with an active cannabis use disorder have an elevated risk of postoperative complications.

Methods
The authors conducted a retrospective population-based cohort study of patients undergoing elective surgery in the United States using the Nationwide Inpatient Sample from 2006 to 2015. A sample of 4,186,622 inpatients 18 to 65 yr of age presenting for 1 of 11 elective surgeries including total knee replacement, total hip replacement, coronary artery bypass graft, caesarian section, cholecystectomy, colectomy, hysterectomy, breast surgery, hernia repair, laminectomy, and other spine surgeries was selected. The principal exposure was an active cannabis use disorder, as defined by International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) diagnostic codes for cannabis dependence and cannabis abuse. The primary outcome was a composite endpoint of in-hospital postoperative myocardial infarction, stroke, sepsis, deep vein thrombosis, pulmonary embolus, acute kidney injury requiring dialysis, respiratory failure, and in-hospital mortality. Secondary outcomes included hospital length of stay, total hospital costs, and the individual components of the composite endpoint.

Results
The propensity-score matched-pairs cohort consisted of 27,206 patients. There was no statistically significant difference between patients with (400 of 13,603; 2.9%) and without (415 of 13,603; 3.1%) a reported active cannabis use disorder with regard to the composite perioperative outcome (unadjusted odds ratio = 1.29; 95% CI, 1.17 to 1.42; P < 0.001; Adjusted odds ratio = 0.97; 95% CI, 0.84 to 1.11; P = 0.63). However, the adjusted odds of postoperative myocardial infarction was 1.88 (95% CI, 1.31 to 2.69; P < 0.001) times higher for patients with a reported active cannabis use disorder (89 of 13,603; 0.7%) compared with those without (46 of 13,603; 0.3%) an active cannabis use disorder (unadjusted odds ratio = 2.88; 95% CI, 2.34 to 3.55; P < 0.001).

Conclusions
An active cannabis use disorder is associated with an increased perioperative risk of myocardial infarction.

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Mitochondria and ageing with HIV
Authors: Hunt Matthew , Payne Brendan A.I. 
Published: December 2019

Purpose of review
Some older people living with HIV (PLWH) exhibit features of unsuccessful ageing, such as frailty. Mitochondrial dysfunction is one of the best characterized ageing mechanisms. There has been recent interest in whether some people ageing with HIV may have an excess of mitochondrial dysfunction. This review aims to address this question through: analogy with ageing and chronic disease; discussion of the key unknowns; suggested ways that measures of mitochondrial dysfunction might be incorporated into HIV research studies.

Recent findings
Recent data suggest that mitochondrial dysfunction in PLWH may not be wholly a legacy effect of historical nucleoside analog reverse transcriptase inhibitor exposures. Research in the non-HIV setting has altered our understanding of the important mediators of mitochondrial dysfunction in ageing.

Summary
Mitochondrial dysfunction is a very plausible driver of adverse ageing phenotypes in some older PLWH. As such it may be a target for therapeutic interventions. Currently, however, there remain considerable uncertainties around the extent of this phenomenon, and its relative importance. Current studies are likely to clarify these questions over the next few years.
Metabolic syndrome, clustering of cardiovascular risk factors and high carotid intima–media thickness in children and adolescents
Authors: Zhao Min , Caserta Carmelo A. , Medeiros Carla C.M. , López-Bermejo Abel , Kollias Anastasios , Zhang Qian , Pacifico Lucia , Reinehr Thomas , Litwin Mieczysław , Bassols Judit , Romeo Elisabetta L. , Ramos Thacira D.A. , Stergiou George S. , Yang Lili , Xargay-Torrent Silvia , Amante Angela , Estrela Tatianne M. , Grammatikos Evangelos , Zhang Yuanyuan , Prats-Puig Anna , Franklin de Carvalho Danielle , Yang Liu , Carreras-Badosa Gemma , de Oliveira Simões Mônica , Hou Yaping , Lizarraga-Mollinedo Esther , Shui Wang , Guo Teng , Wang Mingming , Zhang Yanqing , Bovet Pascal , Xi Bo 
Published: December 2019

Objective:
The clinical utility of screening for pediatric metabolic syndrome (MetS) in children and adolescents is still controversial. We examined the performance of pediatric MetS vs. clustering of cardiovascular risk factors (which are the components of MetS) for predicting high carotid intima–media thickness (cIMT) in children and adolescents.

Methods:
Participants included 2427 children and adolescents aged 6–17 years from population-based studies in three countries (Brazil, China and Italy). Pediatric MetS was defined using either the modified National Cholesterol Education Program Adult Treatment Panel III criteria or the modified International Diabetes Federation criteria. Clustering of cardiovascular risk factors was calculated as the sum of five components of MetS (i.e. central obesity, elevated blood pressure, elevated triglycerides, reduced HDL-cholesterol and elevated fasting blood glucose). High cIMT was defined as cIMT at least 95th percentile values for sex and age developed from European children.

Results:
Presence of one, two or at least three cardiovascular risk factors (using the National Cholesterol Education Program Adult Treatment Panel III criteria), as compared with none, was associated with gradually increasing odds of high cIMT [odds ratios (95% confidence intervals): 1.60 (1.29–1.99), 2.89 (2.21–3.78) and 4.24 (2.81–6.39), respectively]. High cIMT was also associated with presence (vs. absence) of MetS (odds ratio = 2.88, 95% confidence interval = 1.95–4.26). However, clustering of cardiovascular risk factors predicted high cIMT markedly better than MetS (area under the curve of 0.66 vs. 0.54, respectively). Findings were similar using the International Diabetes Federation criteria for pediatric MetS.

Conclusion:
In children and adolescents, a graded score based on five cardiovascular risk factors (used to define MetS) predicted high cIMT markedly better than MetS. These findings do not support the clinical utility of MetS for screening youth at increased cardiovascular risk, as expressed in this study by high cIMT.
Urinary sodium-to-potassium ratio and plasma renin and aldosterone concentrations in normotensive children: implications for the interpretation of results
Authors: Martinez-Aguayo Alejandro G. , Campino Carmen , Rodriguez-Fernandez Maria , Poggi Helena , D’apremont Ivonne , Moore Rosario , Garcia Hernan , Solari Sandra , Allende Fidel , Peredo Soledad , Trincado Claudia , Carvajal Cristian , Arancibia Monica , Ossa Jose Tomas , Sifaqui Sofia , Fardella Carlos E. , Baudrand Rene 
Published: December 2019

Objectives:
To identify associations among the plasma renin concentration (PRC), plasma aldosterone and urinary sodium (Na)/potassium (K) ratio, and to integrate these variables into a nomogram with the aim of estimating the expected versus observed aldosterone concentration.

Methods:
We studied 40 healthy normotensive children (5–8 years old, 57.5% girls) who were born at term and were adequate for their gestational age. Following overnight fasting, the PRC and plasma aldosterone in blood samples were measured, and the Na/K ratio was calculated from a simultaneously obtained urinary spot sample. A mathematical function was defined with these three variables, and a nomogram was built that would return the expected aldosterone concentration from the obtained plasma renin and urinary Na/K ratio values.

Results:
The PRC (B =  5.9, P < 0.001) and urinary Na/K ratio (B = −98.1, P = 0.003) were significant independent predictors of plasma aldosterone. The correlation between the observed plasma aldosterone and the expected plasma aldosterone, as obtained from the nomogram, was r = 0.88, P < 0.001. The average difference between the observed and expected plasma aldosterone was −0.89, with a standard deviation of ±30%.

Conclusion:
The strong correlation between the urinary Na/K ratio, from urine samples taken at the same as the blood samples, and plasma renin and aldosterone concentrations allowed us to build a nomogram to predict aldosterone levels. This approach may be useful for evaluating the renin–angiotensin–aldosterone system (RAAS) in pediatric patients with hypertension and RAAS dysfunction.
Deposition of Fluorescently Tagged Lysozyme on Contact Lenses in a Physiological Blink Model
Authors: Phan Chau-Minh , Qiao Han , Yee Alan , Jones Lyndon 
Published: December 2019

Purpose:
To visualize the deposition of fluorescein isothiocyanate (FITC) lysozyme on daily disposable contact lenses (CLs) using a novel blink model.

Methods:
Three daily disposable conventional hydrogel CLs (etafilcon A, omafilcon A, and nelfilcon A) and three silicone hydrogel CLs (delefilcon A, senofilcon A, and somofilcon A) were evaluated in the study. The CLs were mounted onto a novel blink model and exposed to an artificial tear solution containing FITC lysozyme for 2 and 10 hr. The flow rate and blink speed were set to 1 μL/min and 6 blinks/min, respectively. After the incubation period, a 5-mm-diameter disc was punched out from the center of the lens and mounted on a microscope slide. The slides were imaged using the Zeiss 510 Meta confocal laser scanning microscope, which scanned the lens from the front to the back surface at 5-μm increments.

Results:
There was an increase in deposition of FITC lysozyme for all lens types with increasing incubation time (P<0.05), with the exception of somofilcon A, which did not show statistical significance between 2 and 10 hr (P>0.05). The conventional hydrogel CLs deposited higher amounts of FITC lysozyme than the silicone hydrogel CLs (P<0.001), with etafilcon A depositing the highest at all time points (P<0.05). Interestingly, at the 2-hr incubation time, most CLs showed a higher amount of deposition at the front surface than the back surface of the lens. In particular, etafilcon A showed preferred deposition at the front surface at all time points.

Conclusion:
The results suggest that there is differential deposition at the front surface of the CL, which is exposed to the prelens tear film, compared with the back surface of the CL, which is exposed to the postlens tear film. Therefore, it may be beneficial to design CL materials with differing surface properties for the front and back surfaces of the CL to enhance interactions with the tear film and ocular surface.
Is Arthroscopic Hip Labral Repair/Reconstruction Surgery Effective for Treating Femoroacetabular Impingement in the Presence of Osteoarthritis?
Authors: Nakashima Hirotaka , Utsunomiya Hajime , Kanezaki Shiho , Suzuki Hitoshi , Nakamura Eiichiro , Larson Christopher M. , Sakai Akinori , Uchida Soshi 
Published: December 2019

Objective:
To investigate clinical outcomes after arthroscopic labral preservation surgery for femoroacetabular impingement (FAI) in the presence of osteoarthritis (OA) compared with FAI without significant OA.

Design:
Retrospective case–control study.

Setting:
Department of Orthopaedic Surgery and Sports Medicine, Hospital of Academic Institute.

Patients:
Femoroacetabular impingement patients (n = 97; ≥35 years) undergoing arthroscopic FAI correction with labral preservation surgery from March 2009 to April 2014 were enrolled in this study.

Interventions:
Patients were divided into 2 groups: FAI group (79 patients), with Tonnis grade 0 or 1, and FAI + OA group (18 patients), with Tonnis grade 2 or 3.

Main Outcome Measures:
We examined the clinical outcomes using the Modified Harris Hip Score (MHHS), Nonarthritic Hip Score (NAHS), and the conversion rate to total hip arthroplasty (THA).

Results:
No significant differences existed between the 2 groups with respect to age, sex, follow-up period, or preoperative MHHS or NAHS. The mean MHHS and NAHS at the final follow-up were significantly lower in the FAI + OA group than in the FAI group. There was a significant difference in the rate of conversion to THA and failure between the 2 groups (THA 5% vs 50%) (failure 15% vs 67%).

Conclusion:
Patients with FAI in the presence of OA did not improve after arthroscopic labral preservation surgery and had a high conversion rate to THA.

Level of Evidence:
Level III.
Feasibility of a Novel Strategy for Cardiovascular Screening During the Preparticipation Physical Examination
Authors: Dennison Roberta , Kerkhof Deanna L. , Honda Trenton , Calatroni Renato , Corrado Gianmichel D. 
Published: December 2019

Objective:
To determine the feasibility of simultaneously conducting history and physical (H&P), limb-lead electrocardiogram (ECG), and preparticipation echocardiography by frontline providers (PEFP) at one screening station.

Methods:
This cross-sectional study compares limb-lead versus 12-lead ECG as part of a preparticipation physical examination (PPE) including H&P and PEFP conducted in year 1 and year 2 on 2 cohorts (n = 36, n = 53, respectively) of college athletes at one institution. Year 1 screening was conducted at 3 stations, one station per screening component. Time to complete each station was recorded, and total time for screening was the summation of times for each station. Year 2 screening was conducted at one station; timing began when the patient entered the room and ended when all 3 components of screening were complete. An unpaired t test was used to compare the mean time difference between years 1 and 2 screening stations.

Results:
Year 1 screening time was significantly longer than time to complete cardiac screening using the year 2 protocol (10.51 ± 1.98 vs 3.96 ± 1.43 minutes, respectively; P < 0.001). Five athletes in year 1 and 3 athletes in year 2 were referred to cardiology for further evaluation; all athletes were ultimately cleared to participate.

Conclusions:
A comprehensive PPE can be completed in a timely fashion using a single screening station and limb-lead ECG to improve efficiency, while still allowing providers to gather information on history, physical examination, heart rhythm, and heart structure. This strategy may serve as a potential solution in the longstanding debate over best practices for PPEs.