bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of the Global SARS-CoV-2 (COVID-19) Pandemic on Neuroanesthesiology Fellowship Programs Worldwide and the Potential Future Role for ICPNT Accreditation
Authors: Rajan Shobana , Bebawy John , Avitsian Rafi , Lee Chanhung Z. , Rath Girija , Luoma Astri , Bilotta Federico , Pierce John T. , Kofke William A.
Published: October 2020

Background:

The COVID-19 pandemic is an international crisis placing tremendous strain on medical systems around the world. Like other specialties, neuroanesthesiology has been adversely affected and training programs have had to quickly adapt to the constantly changing environment.

Methods:

An email-based survey was used to evaluate the effects of the pandemic on clinical workflow, clinical training, education, and trainee well-being. The impact of the International Council on Perioperative Neuroscience Training (ICPNT) accreditation was also assessed.

Results:

Responses were received from 14 program directors (88% response rate) in 10 countries and from 36 fellows in these programs. Clinical training was adversely affected because of the cancellation of elective neurosurgery and other changes in case workflow, the introduction of modified airway and other protocols, and redeployment of trainees to other sites. To address educational demands, most programs utilized online platforms to organize clinical discussions, journal clubs, and provide safety training modules. Several initiatives were introduced to support trainee well-being during the pandemic. Feelings of isolation and despair among trainees varied from 2 to 8 (on a scale of 1 to 10). Fellows all reported concerns that their clinical training had been adversely affected by the coronavirus disease 2019 (COVID-19) pandemic because of decreased exposure to elective subspecialty cases and limited opportunities to complete workplace-based assessments and training portfolio requirements. Cancellation of examination preparation courses and delayed examinations were cited as common sources of stress. Programs accredited by the ICPNT reported that international networking and collaboration was beneficial to reduce feelings of isolation during the pandemic.

Conclusion:

Neuroanesthesia fellowship training program directors introduced innovative ways to maintain clinical training, educational activity and trainee well-being during the COVID-19 pandemic.
Long non-coding RNA plasmacytoma variant translocation 1 linked to hypoxia-induced cardiomyocyte injury of H9c2 cells by targeting miR-135a-5p/forkhead box O1 axis
Authors: Xu Jin-Juan , Zheng Wei-Hong , Wang Jun , Chen Yuan-Yuan
Published: October 2020

Background

Myocardial infarction occurs due to insufficient (ischemia) blood supply to heart for long time; plasmacytoma variant translocation 1 (PVT1) is a long non-coding RNAs (lncRNAs) involved in the pathogenesis of various diseases, including heart disease; However, few studies have explored its role. The present study evaluated the effects of lncRNA PVT1 on hypoxic rat H9c2 cells.

Methods

Hypoxic injury was examined by measuring cell viability and apoptosis by using cell counting kit-8 activity and flow cytometry assays. Gene expressions after hypoxia were estimated by quantitative real time polymerase chain reaction and the signaling pathway were explored by Western blot analysis. RNA immunoprecipitation and luciferase reporter assays were applied to examine the interactions among genes. Data were analyzed using t-test with one-way or two-way analysis of variance.

Results

The lncRNA PVT1 is up-regulated in hypoxia-stressed H9c2 cells and knockdown of PVT1 mitigates hypoxia-induced injury in H9c2 cells. PVT1 acts as a sponge for miR-135a-5p and knockdown of PVT1 attenuated the increased hypoxia-induced injury by up-regulating miR-135a-5p. Forkhead box O1 (FOXO1) was identified as a target of miR-135a-5p, and the expression was negatively regulated by miR-135a-5p. The exploration of the underlying mechanism demonstrated that knockdown of FOXO1 reversed PVT1/miR-135a-5p mediated hypoxia-induced injury in H9c2 cells.

Conclusions

PVT1 plays a crucial role in hypoxia-injured H9c2 cells through sponging miR-135a-5p and then positively regulating FOXO1.
Current U.S. Guideline-Based Management Strategies for Special Clinical Situations Involving Hypertensive Crises
Authors: Satheeshkumar Anudeeksha , Pena Camilo , Nugent Kenneth
Published: October 2020

Hypertensive crises, although somewhat rare in hypertensive patients, might become an increasingly relevant issue in the future as the number of adults living with hypertension in the United States increases. Many of the current U.S. clinical guidelines for the treatment and management of a variety of medical conditions do not factor hypertensive crises into their recommendations or only consider them in a limited fashion in the context of other medical conditions. This review article summarizes the definitions of hypertensive crises/urgent hypertension/emergent hypertension, the epidemiological profile and outcomes of patients, current U.S. clinical guidelines’ recommendations for the general treatment of hypertensive crises, and current U.S. clinical guidelines’ recommendations for the treatment of acute kidney injuries, acute ischemic stroke, aortic dissection, and acute heart failure in relation to hypertensive crises. All physicians who manage hypertensive patients, but particularly physicians who work in intensive care units, emergency departments and in U.S. hospitals, should review hypertensive crises guidelines and relevant treatments, and understand current recommendations.
Network-Specific Corticothalamic Dysconnection in Attention-Deficit Hyperactivity Disorder
Authors: Hua Mao-Hsiu , Chen Yen-Ling , Chen Mu-Hong , Huang Kai-Lin , Hsu Ju-Wei , Bai Ya-Mei , Tsai Shih-Jen , Wu Yu-Te
Published: October 2020

Background:

Functional connectivity (FC) is believed to be abnormal in attention-deficit hyperactivity disorder (ADHD). Most studies have focused on frontostriatal systems, and the role of the thalamic network in ADHD remains unclear. The current study used FC magnetic resonance imaging (fcMRI) to explore corticothalamic network properties and correlated network dysconnection with ADHD symptom severity.

Methods:

Eighteen adolescents with ADHD and 16 healthy controls aged 12 to 17 years underwent resting functional MRI scans, clinical evaluations, and 2 parent rating scales, namely the Swanson, Nolan, and Pelham IV scale and the Child Behavior Checklist. Six a priori cortical regions of interest were used to derive 6 networks: the dorsal default mode network, frontoparietal network, cingulo-opercular network (CON), primary sensorimotor network (SM1), primary auditory network, and primary visual network (V1). The corticothalamic connectivity for each network was calculated for each participant and then compared between the groups. We also compared the 2 scales with the network connectivity.

Results:

The corticothalamic connectivity within the CON was significantly reduced (p < 0.05) among adolescents with ADHD compared with the controls. The corticothalamic dysconnection within the CON, SM1, and V1 networks negatively correlated with ADHD symptom severity.

Conclusion:

This network analysis indicates that corticothalamic dysconnection in ADHD involves the CON, SM1, and V1 networks and relates to symptom severity. The findings provide evidence of dysfunctional thalamus-related networks in ADHD.
At-risk-measure Sampling in Case–Control Studies with Aggregated Data
Authors: Garber Michael D. , McCullough Lauren E. , Mooney Stephen J. , Kramer Michael R. , Watkins Kari E. , Lobelo R.L. Felipe , Flanders W. Dana
Published: October 2020

Transient exposures are difficult to measure in epidemiologic studies, especially when both the status of being at risk for an outcome and the exposure change over time and space, as when measuring built-environment risk on transportation injury. Contemporary “big data” generated by mobile sensors can improve measurement of transient exposures. Exposure information generated by these devices typically only samples the experience of the target cohort, so a case-control framework may be useful. However, for anonymity, the data may not be available by individual, precluding a case–crossover approach. We present a method called at-risk-measure sampling. Its goal is to estimate the denominator of an incidence rate ratio (exposed to unexposed measure of the at-risk experience) given an aggregated summary of the at-risk measure from a cohort. Rather than sampling individuals or locations, the method samples the measure of the at-risk experience. Specifically, the method as presented samples person–distance and person–events summarized by location. It is illustrated with data from a mobile app used to record bicycling. The method extends an established case–control sampling principle: sample the at-risk experience of a cohort study such that the sampled exposure distribution approximates that of the cohort. It is distinct from density sampling in that the sample remains in the form of the at-risk measure, which may be continuous, such as person–time or person–distance. This aspect may be both logistically and statistically efficient if such a sample is already available, for example from big-data sources like aggregated mobile-sensor data.
Residential proximity to green space and preeclampsia in California
Authors: Weber Kari A. , Lyons Evan , Yang Wei , Stevenson Charlotte , Stevenson David K. , Shaw Gary M.
Published: October 2020

Background:

We investigated whether residing near more green space might reduce the risk of preeclampsia.

Methods:

Participants were women who delivered a live, singleton birth between 1998 and 2011 in eight counties of the San Joaquin Valley in California. There were 7276 cases of preeclampsia divided into mild, severe, or superimposed on preexisting hypertension. Controls were 197,345 women who did not have a hypertensive disorder and delivered between 37 and 41 weeks. Green space was estimated from satellite data using Normalized Difference Vegetation Index (NDVI), an index calculated from surface reflectance at the visible and near-infrared wavelengths. Values closer to 1 denote a higher density of green vegetation. Average NDVI was calculated within a 50 m, 100 m, and 500 m buffer around each woman’s residence. Odds ratios and 95% confidence intervals were estimated comparing the lowest and highest quartiles of mean NDVI to the interquartile range comparing each preeclampsia phenotype, divided into early (20–31 weeks) and late (32–36 weeks) preterm birth, to full-term controls.

Results:

We observed an inverse association in the 500 m buffer for women in the top quartile of NDVI and a positive association for women in the lowest quartile of NDVI for women with superimposed preeclampsia. There were no associations in the 50 and 100 m buffers.

Conclusion:

Within a 500 m buffer, more green space was inversely associated with superimposed preeclampsia. Future work should explore the mechanism by which green space may protect against preeclampsia.
Evaluation and Diagnostic Testing
Authors: PURISCH STEPHANIE E. , ALGODI MOHAMMED , TAUB CYNTHIA , GOFFMAN DENA
Published: October 2020

The evaluation of cardiovascular disease in pregnancy is challenging due to overlaps between cardiac and normal pregnancy symptomatology, as well as concerns about the potential impact, if any, of imaging studies on fetal development. We discuss here an approach to the evaluation of the pregnant cardiac patient and review the safety and utility of available diagnostic tests, including labs, electrocardiogram, echocardiography, stress testing, computed tomography, magnetic resonance imaging, and cardiac catheterization. Importantly, the majority of standard imaging studies can be safely performed in pregnancy, and a high index of suspicion must be maintained when evaluating pregnant patients, especially those with preexisting cardiovascular disease.
LONGITUDINAL CHANGES IN QUANTITATIVE AUTOFLUORESCENCE DURING PROGRESSION FROM INTERMEDIATE TO LATE AGE-RELATED MACULAR DEGENERATION
Authors: Reiter Gregor S. , Hacker Valentin , Told Reinhard , Schranz Markus , Krotka Pavla , Schlanitz Ferdinand G. , Sacu Stefan , Pollreisz Andreas , Schmidt-Erfurth Ursula
Published: October 2020

Purpose:

To prospectively investigate the development of quantitative autofluorescence (qAF) during progression from intermediate to late age-related macular degeneration (AMD).

Methods:

Quantitative autofluorescence images from patients with intermediate AMD were acquired every three months with a Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany) using a built-in autofluorescence reference. The association between changes in longitudinal qAF and progression toward late AMD was assessed using Cox regression models with time-dependent covariates.

Results:

One hundred and twenty-one eyes of 71 patients were included, and 653 qAF images were acquired. Twenty-one eyes of 17 patients converted to late AMD (median follow-up: 21 months; 12 eyes: atrophic AMD; nine eyes: neovascular AMD). The converting patients' mean age was 74.6 ± 4.4 years. Eleven eyes in the converting group (52.4%) were pseudophakic. The presence of an intraocular lens did not affect the qAF regression slopes (P > 0.05). The median change for atrophic AMD was −2.34 qAF units/3 months and 0.78 qAF units/3 months for neovascular AMD. A stronger decline in qAF was significantly associated with an increased risk of developing atrophic AMD (hazard ratio = 1.022, P < 0.001). This association, however, was not present in the group progressing toward neovascular AMD (hazard ratio = 1.001, P = 0.875).

Conclusion:

The qAF signal declines with progression to atrophy, contrary to developing neovascularization. Quantitative autofluorescence may allow identification of patients at risk of progressing to late AMD and benefits individualized patient care in intermediate AMD.
NONPERFUSION AREA QUANTIFICATION IN BRANCH RETINAL VEIN OCCLUSION
Authors: Kadomoto Shin , Muraoka Yuki , Uji Akihito , Tamiya Ryosuke , Oritani Yasuyuki , Kawai Kentaro , Ooto Sotaro , Murakami Tomoaki , Iida-Miwa Yuko , Tsujikawa Akitaka
Published: October 2020

Purpose:

To precisely quantify retinal nonperfusion areas (NPAs) in branch retinal vein occlusion using widefield optical coherence tomography angiography (OCTA) and examine their association with neovascular complications.

Methods:

We enrolled 26 patients with treatment-naïve branch retinal vein occlusion and prospectively examined them for 12 months. After 3 monthly ranibizumab injections to treat macular edema, each patient underwent ultra-widefield (UWF) fluorescein angiography (FA) and OCTA. Ultra-widefield FA was additionally performed at Month 12. For UWF FA, the retinal NPA was measured using the equipment's built-in software. For OCTA, we used panoramic image montaged from 5 single 12 × 12 mm2 images and quantified the retinal NPA using a Gullstrand eye with a grid scale at each patient. Measurements were expressed in terms of actual values and disc area units.

Results:

The retinal NPAs as measured using single OCTA and panoramic OCTA were significantly associated with that measured using UWF FA (P < 0.001 for both). Retinal neovascularization lesions were observed in 4 (15.4%) of 26 eyes. For patients with accompanying neovascularization, the retinal NPA measured using UWF FA, single OCTA, and panoramic OCTA were 187.9 ± 39.5 mm2 (109.9 ± 21.4 disc area), 34.3 ± 13.7 mm2 (19.9 ± 7.7 disc area), and 106.6 ± 24.5 mm2 (62.4 ± 13.6 disc area), respectively, which were larger than for those without neovascularization (P < 0.001, 0.014, and <0.001, respectively).

Conclusion:

Using widefield OCTA, we could quantify the retinal NPA of eyes with branch retinal vein occlusion. These could serve as valid references to assess the risk of neovascular complications.
Evolution of doctor shopping for oxycodone in the 67 million inhabitants in France as a proxy for potential misuse or abuse
Authors: Soeiro Thomas , Pradel Vincent , Lapeyre-Mestre Maryse , Micallef Joëlle
Published: October 2020

This nationwide study aimed to compare use of oxycodone and doctor shopping for oxycodone in 2010 and 2016, and to quantify doctor shopping for oxycodone by sex, age, formulation, and dosage in 2010 and 2016. This study is a cross-sectional comparative analysis of doctor shopping based on all dispensings of oxycodone in France, in 2010 and 2016. Dispensings of oxycodone were extracted from the Système national des données de santé, which covers the 67 million inhabitants in France. Quantification of doctor shopping relies on an algorithm accounting for overlapping prescriptions, which is a proxy for potential misuse or abuse. The number of subjects who received oxycodone increased by 214% from 67,838 subjects in 2010 to 212,753 subjects in 2016, and the number of subjects with doctor-shopping behavior increased by 197%, from 1066 subjects in 2010 to 3163 subjects in 2016. For 30- to 44-year-old men, the total quantity of oxycodone obtained by doctor shopping increased by 391%, from 4582 defined daily doses in 2010 to 22,517 defined daily doses in 2016. By formulation and dosage, the total quantity of oxycodone obtained by doctor shopping increased with the dosage for both immediate-release and extended-release tablets in 2010 and 2016. The widespread extent of doctor shopping and its 3-fold increase in line with population exposure is a strong signal in the French context. These results are another argument to avoid trivializing oxycodone to prevent misuse, potential abuse, and potential oxycodone-related deaths, but it requires caution to prevent compromising effective treatment of pain.
Safety and efficacy of an equimolar mixture of oxygen and nitrous oxide: a randomized controlled trial in patients with peripheral neuropathic pain
Authors: Bouhassira Didier , Perrot Serge , Riant Thibault , Martiné-Fabre Gaelle , Pickering Gisèle , Maindet Caroline , Attal Nadine , Ranque Garnier Stéphanie , Nguyen Jean-Paul , Kuhn Emmanuelle , Viel Eric , Kieffert Patrick , Tölle Thomas , Delorme Claire , Deleens Rodrigue , Giniès Patrick , Corand-Dousset Virginie , Dal-Col Clémence , Serrie Alain , Chevrillon Emmanuel , Gov Christian , Ramirez-Gil Juan Fernando , Delval Cécile , Schaller Manuella , Bessière Baptiste , Houéto Patrick , Sommer Claudia ,   the ProtoTOP group
Published: October 2020

Nitrous oxide (N2O) is an odorless and colorless gas routinely used as an adjuvant of anesthesia and for short-duration analgesia in various clinical settings mostly in the form of an N2O/O2 50%-50% equimolar mixture (EMONO). Experimental studies have suggested that EMONO could also induce long-lasting analgesic effects related to the blockade of N-methyl-D-aspartate receptors. We designed the first international multicenter proof of concept randomized, placebo-controlled study to assess the efficacy and safety of a 1-hour administration of EMONO or placebo (medical air) on 3 consecutive days up to 1 month after the last administration in patients with chronic peripheral neuropathic pain. A total of 240 patients were recruited in 22 centers in France and Germany and randomly assigned to 1 study group (120 per group). Average pain intensity (primary outcome), neuropathic pain characteristics (Neuropathic Pain Symptom Inventory), Patient Global Impression of Change, anxiety, depression, and quality of life were systematically assessed before and after treatment. The changes in average pain intensity between baseline and 7 days after the last administration were not significantly different between the 2 groups. However, evoked pain intensity (predefined secondary endpoint) and Patient Global Impression of Change (exploratory endpoint) were significantly improved in the EMONO group, and these effects were maintained up to 4 weeks after the last treatment administration. Mostly transient side effects were reported during the treatment administration. These encouraging results provide a basis for further investigation of the long-term analgesic effects of EMONO in patients with neuropathic pain.
Transient activation of spinal trigeminal neurons in a rat model of hypoxia-induced headache
Authors: Waldmann Dennis , Messlinger Karl
Published: October 2020

The mechanisms underlying headaches attributed to hypoxia are poorly known. The activation of spinal trigeminal neurons with meningeal afferent input is believed to be responsible for the generation of headaches. In the caudal spinal trigeminal nucleus of anaesthetized and ventilated rats, the spontaneous firing of neurons with input from the exposed parietal dura mater and the activity evoked by mechanical stimuli to the dura and the adjacent periosteum were recorded, whereas the O2 fraction of the ventilation gas was stepwise reduced by omitting O2 and adding nitrogen. The expiratory CO2 level, the arterial pressure, the pulse rate, and the peripheral O2 saturation (SpO2) were registered. The meningeal blood flow was recorded using laser Doppler flowmetry; video imaging was used to measure the diameter of dural and medullary arteries. Lowering O2 in the ventilation gas from hyperoxic to normoxic and finally hypoxic conditions was followed by an increase in spontaneous activity up to 300% of the initial activity in most neurons, whereas the activity in a minor fraction of neurons ceased. The mechanical threshold was reduced under hypoxia. Arterial pressure, pulse rate, and SpO2 fell during stepwise lowering of the O2 concentration, whereas the arteries of the dura mater and the medulla dilated. Increased neuronal activity in the spinal trigeminal nucleus following lowering of the inhaled O2 goes along with variations in cardiovascular parameters. The experiments may partly model the conditions of high altitudes and other hypoxic states as risk factors for headache generation.
Donor-specific antibodies in lung transplantation
Authors: Hachem Ramsey R.
Published: October 2020

Purpose of review

The development of donor-specific antibodies (DSA) after lung transplantation has been recognized as an important risk factor for poor outcomes over the past 20 years. Recently, this has been a focus of intense research, and the purpose of this review is to summarize our current understanding of humoral responses and important recent findings as well as to identify areas of future research.

Recent findings

Recent studies have identified donor-derived cell-free DNA (ddcfDNA) as an important biomarker associated with antibody-mediated rejection (AMR). Importantly, ddcfDNA levels are noted to be elevated approximately 3 months before the onset of clinical allograft dysfunction, making ddcfDNA a particularly appealing biomarker to predict the onset of AMR. Additional notable recent findings include the identification of an independent association between the isolation of Pseudomonas aeruginosa from respiratory specimens and the development of DSA. This finding provides potential insights into crosstalk between innate and alloimmune responses and identifies a potential therapeutic target to prevent the development of DSA.

Progress in the field of humoral responses after lung transplantation has been slow, but ongoing and future research in this area are critically necessary to improve patient outcomes in the future.
Differences in Posttraumatic and Psychosocial Outcomes Among Refugees, Asylum Seekers, and Internally Displaced Persons
Authors: Dolezal Michael L. , Alsubaie Mohammed K. , Sheikh Ifrah , Rosencrans Peter , Walker Rosemary S. , Zoellner Lori A. , Bentley Jacob A.
Published: October 2020

Refugees, asylum seekers, and internally displaced persons differ in their experiences, potentially affecting posttraumatic outcomes such as posttraumatic stress disorder (PTSD) symptoms, posttraumatic cognitions, and posttraumatic growth (PTG), as well as psychosocial outcomes such as social connection, discrimination, and well-being. We explored these differences in a sample of N = 112 Muslim displaced persons. Results from planned contrasts indicated that refugees reported more PTSD symptoms (t[46.63] = 3.04, p = 0.004, d = 0.77) and more PTG (t[94] = 2.71, p = 0.008, d = 0.61) than asylum seekers. Higher posttraumatic cognitions predicted less social connections across displacement immigration category. The strength of this relationship was more pronounced for asylum seekers than refugees (b = −0.43, p = 0.014). Refugees may focus more on direct threats from others, resulting in more PTSD symptoms, whereas asylum seekers' uncertainty may pose a greater threat, exacerbating posttraumatic beliefs that drive social disconnection.
Sustaining Exemplary Practice
Authors: Lyman Bret , Parchment Joy
Published: October 2020

Nurse leaders must be proficient at fostering organizational learning within their teams and throughout their companies. Organizational learning can be achieved by creating a culture conducive to learning, integrating learning practices into the team's routines, and leveraging the impact of learning by cultivating a strong, vibrant institutional memory. Authors describe the concept of organizational learning, provide strategies for fostering a culture where organizational learning thrives, and underscore the nurse leaders' role in leading organizations to achieve and sustain exemplary practice.
A Contemporary Model for Undergraduate Nursing Education
Authors: Aller Loretta
Published: October 2020

Background

Health care trends including advanced technology, higher patient acuity, and shorter employment orientation have impacted the environment in which new-graduate nurses are entering the workforce. These issues are contributing to new nurses leaving the workforce prematurely. Theoretical foundations for nursing education need to be updated to better prepare graduates for entry into this burdened environment.

Purpose

The purpose of this study was to explore, from the student perspective, the process of educational development into professional licensure-ready graduates.

Method

Grounded theory was used to explore the developmental process of undergraduate nursing education.

Results

Two simultaneous developmental processes emerged: decision-making and self-doubt/self-efficacy. Early in the nursing program, students made very few patient care decisions and were plagued with self-doubt. As knowledge and experience were gained, decisions became based on patient conditions, self-doubt decreased, self-efficacy emerged, and students relayed increased comfort, confidence, and competence.

Conclusion

A contemporary nursing education framework has been developed for testing.
Increasing age is associated with elevated circulating interleukin-6 and enhanced temporal summation of mechanical pain in people living with HIV and chronic pain
Authors: Slawek Deepika E. , Merlin Jessica S. , Owens Michael A. , Long Dustin M. , Gonzalez Cesar E. , White Dyan M. , Lopez Salvador A. , Heath Sonya L. , Goodin Burel R.
Published: October 2020

Introduction:

In the current antiretroviral treatment era, people living with HIV (PLWH) can achieve a near-normal life expectancy. However, as PLWH grow older, they are increasingly prone to developing chronic health conditions including pain. One possible explanation for increased pain in older populations with HIV is that aging is associated with inflammation and altered pain modulatory processes (ie, increased facilitation and decreased inhibition).

Objectives:

Our study aimed to examine how age affects endogenous pain modulatory processes in PLWH with chronic pain and to examine how age affects serum inflammatory cytokines.

Methods:

A total of 80 PLWH (median CD4+ = 646; 24% detectable viral load >50; 99% on antiretroviral therapy) with chronic pain provided demographic information (age, sex, and race) and completed standardized questionnaires to assess mood and clinical pain severity. Blood assays were completed to determine circulating levels of interleukin-6 (IL-6) and tumor necrosis factor-α, as well as CD4+ and HIV viral load. Temporal summation of mechanical pain and conditioned pain modulation assessed pain facilitation and inhibition, respectively.

Results:

Mean age was 48.9 (8.2) years; range: 26 to 67, with 45% >50 years. In adjusted multiple regression models, increasing age was associated with elevated levels of circulating IL-6 (P < 0.01), but not tumor necrosis factor-α. Increasing age was also associated with enhanced temporal summation of mechanical pain (P < 0.01), but not conditioned pain modulation. Greater circulating levels of IL-6 were correlated with enhanced temporal summation of mechanical pain (r = 0.304, P < 0.01), but the association was no longer significant after adjustment for covariates.

Conclusion:

Findings suggest that high levels of some circulating proinflammatory cytokines as well as enhanced pain facilitatory processes together may contribute to the chronic pain experienced by older adults with HIV.
Epigenetic Mechanisms Underlying HIV-Infection Induced Susceptibility of CD4+ T Cells to Enhanced Activation-Induced FasL Expression and Cell Death
Authors: Ghare Smita S. , Chilton Paula M. , Rao Aakarsha V. , Joshi-Barve Swati , Peyrani Paula , Reyes Vega Andrea , McClain Craig J. , Bryant Kendall , Cook Robert L. , Freiberg Mathew , Barve Shirish
Published: October 2020

Background:

Chronic immune activation and CD4+ T cell depletion are significant pathogenic features of HIV infection. Expression of Fas ligand (FasL), a key mediator of activation-induced cell death in T cells, is elevated in people living with HIV-1 infection (PLWH). However, the epigenetic mechanisms underlying the enhanced induction of FasL expression in CD4+ T lymphocytes in PLWH are not completely elucidated. Hence, the current work examined the effect of HIV infection on FasL promoter-associated histone modifications and transcriptional regulation in CD4+ T lymphocytes in PLWH.

Method:

Flow cytometric analysis was performed to examine the Fas-FasL expression on total CD4+ T cells and naïve/memory CD4+ T cell subsets. Epigenetic FasL promoter histone modifications were investigated by chromatin immunoprecipitation-quantitative real-time polymerase chain reaction analysis using freshly isolated total CD4+ T lymphocytes from HIV-1 infected and noninfected individuals.

Results:

All naïve/memory CD4+ T cell subsets from PLWH showed markedly greater frequency of FasL expression. Notably, examination of functional outcome of FasL/Fas co-expression demonstrated the preferential susceptibility of Tcm and Tem subsets to activation-induced apoptosis. Importantly, these CD4+ T cells collectively demonstrated a distinct FasL promoter histone profile involving a coordinated cross-talk between histone H3 modifications leading to enhanced FasL gene expression. Specifically, levels of transcriptionally permissive histone H3K4-trimethylation (H3K4Me3) and histone H3K9-acetylation (H3K9Ac) were increased, with a concomitant decrease in the repressive H3K9-trimethylation (H3K9Me3).

Conclusion:

The present work demonstrates that epigenetic mechanisms involving promoter-histone modifications regulate transcriptional competence and FasL expression in CD4+ T cells from PLWH and render them susceptible to activation-induced cell death.
Clinical, Immunological, and Virological Outcomes Among Youths With Perinatal HIV After Transition to Adult Units in Spain From 1997 to 2016
Authors: Aguilera-Alonso David , Sainz Talía , Jimenez de Ory Santiago , Bernardino Ignacio , Díez Cristina , Torres Berta , Merino Dolores , Iribarren José A. , Portilla Irene , Ríos María José , Ibarra Sofía , Sanz José , Bellón José María , Carrasco Itziar , Muñoz-Fernández María Ángeles , Ramos José Tomás , Navarro María Luisa ,   CoRISpe Cohort Working Group and CoRISpe-FARO Cohort Working Group
Published: October 2020

Background:

Children living with HIV are reaching adulthood and transitioning to adult clinics. This study aimed to describe clinical and immunovirological status after transition in patients with perinatal HIV.

Methods:

Patients participating in the Spanish multicenter pediatric HIV cohort (CoRISpe) transferred to adult care (FARO cohort) from 1997 to 2016 were included. Clinical and immunovirological data were collected from 12 years old to the last follow-up moment after transition (up to December 2017). We used mixed-effect models to analyze changes in CD4 counts or viral suppression and multivariate analysis for risk factors for virological failure (VF) and immune status after transition. Transition years were classified into 5-year periods.

Results:

Three hundred thirty-two youths were included. The median age at transition was 18 years (interquartile range: 16.3–18.9) and 58.1% women. The median follow-up time after transition was 6.6 years (interquartile range: 4.6–9.8), and 11 patients (3.3%) died. The immunovirological status at transition improved over the last periods. Globally, VF decreased from 27.7% at transition to 14.4% at 3 years post-transition (P < 0.001), but no changes were observed in the last 2 transition periods. There were no significant differences in CD4 over the transition period. Risk factors for VF after transition were female sex, being born abroad and VF at transition, and for lower CD4 after transition were Romani heritage, younger age at transition, lower CD4 nadir, and CD4 at transition.

Conclusions:

After transition, virological suppression improved in the early transition periods, and immunological status remained stable. Nevertheless, some patients had higher risk of worse outcomes. Identifying these patients may aid during transition.
Brief Report: Drug Overdose Deaths Among People With HIV in New York City, 2007–2017
Authors: Braunstein Sarah L. , Robbins Rebekkah S. , Ramaswamy Chitra , Daskalakis Demetre C.
Published: October 2020

Background:

Preventable deaths, including those because of drug overdose (OD), are a significant public health concern in New York City (NYC). Trends in drug OD death among people with HIV (PWH) in NYC have not been described.

Methods:

We selected PWH from the NYC HIV Registry who died during 2007–2017, resided in NYC at death, and died because of drug OD. We characterized PWH who died of drug OD and analyzed CD4 and viral load tests from surveillance to evaluate retention in care and viral suppression (viral load < 200 cc/mL) in the 12 months before death as markers of care-seeking.

Results:

From 2007 to 2017, 870 NYC PWH died of drug OD. Of the total OD deaths, 821 (94.4%) were classified as accidental and 49 (5.6%) as intentional. Although the rate of OD deaths among PWH declined during the full period, from 58.5 per 100,000 in 2007 to 47.9 per 100,000 in 2017, it increased from 2014 (30.9/100,000) to 2016 (53.3/100,000) and stayed high through 2017 (47.9/100,000). Decedents during 2007–2017 were predominantly men (70.8%), Black (38.0%) or Latino/Hispanic (38.7%), aged 40–59 years (73.2%), and had a history of injection drug use (43.0%). Over 3-quarters (80.1%) of decedents were retained in HIV care in the 12 months preceding death; 45.4% were viral suppression.

Conclusions:

A sizeable number of PWH died of OD during 2007–2017, and OD death rates in recent years increased. Predeath care patterns reveal frequent interaction with the health care system, underscoring missed opportunities for harm-reduction and suicide prevention interventions for PWH.
How sperm competition shapes the evolution of testes and sperm: a meta-analysis
Authors: Lüpold Stefan , de Boer Raïssa A. , Evans Jonathan P. , Tomkins Joseph L. , Fitzpatrick John L.
Published: October 2020

Females of many species mate with multiple males, thereby inciting competition among ejaculates from rival males for fertilization. In response to increasing sperm competition, males are predicted to enhance their investment in sperm production. This prediction is so widespread that testes size (correcting for body size) is commonly used as a proxy of sperm competition, even in the absence of any other information about a species' reproductive behaviour. By contrast, a debate about whether sperm competition selects for smaller or larger sperm has persisted for nearly three decades, with empirical studies demonstrating every possible response. Here, we synthesize nearly 40 years of sperm competition research in a meta-analytical framework to determine how the evolution of sperm number (i.e. testes size) and sperm size (i.e. sperm head, midpiece, flagellum and total length) is influenced by varying levels of sperm competition across species. Our findings support the long-held assumption that higher levels of sperm competition are associated with relatively larger testes. We also find clear evidence that sperm competition is associated with increases in all components of sperm length. We discuss these results in the context of different theoretical predictions and general patterns in the breeding biology and selective environment of sperm.

This article is part of the theme issue ‘Fifty years of sperm competition’.
Imminent risk of predation reduces the relative strength of postcopulatory sexual selection in the guppy
Authors: Glavaschi Alexandra , Cattelan Silvia , Grapputo Alessandro , Pilastro Andrea
Published: October 2020

Fifty years of research on sperm competition has led to a very good understanding of the interspecific variation in sperm production traits. The reasons why this variation is often very large within populations have been less investigated. We suggest that the interaction between fluctuating environmental conditions and polyandry is a key phenomenon explaining such variation. We focus here on imminent predation risk (IPR). IPR impacts significantly several aspects of prey behaviour and reproduction, and it is expected to influence the operation of sexual selection before and after mating. We estimated the effect of IPR on the male opportunity for pre- and postcopulatory sexual selection in guppies (Poecilia reticulata), a livebearing fish where females prefer colourful males and mate multiply. We used a repeated-measures design, in which males were allowed to mate with different females either under IPR or in a predator-free condition. We found that IPR increased the total opportunity for sexual selection and reduced the relative contribution of postcopulatory sexual selection to male reproductive success. IPR is inherently variable and our results suggest that interspecific reproductive interference by predators may contribute towards maintaining the variation in sperm production within populations.

This article is part of the theme issue ‘Fifty years of sperm competition'.
Three decades of sperm competition in birds
Authors: Birkhead Tim R. , Montgomerie Robert
Published: October 2020

In the three decades, since Birkhead and Møller published
Sperm competition in birds
(1992, Academic Press) more than 1000 papers have been published on this topic, about half of these being empirical studies focused on extrapair paternity. Both technological innovations and theory have moved the field forward by facilitating the study of both the mechanisms underlying sperm competition in both sexes, and the ensuing behavioural and morphological adaptations. The proliferation of studies has been driven partly by the diversity of both behaviours and morphologies in birds that have been influenced by sperm competition, but also by the richness of the theory developed by Geoff Parker over the past 50 years.

This article is part of the theme issue ‘Fifty years of sperm competition’.
Matrix metalloproteinase-14 regulates collagen degradation and migration of mononuclear cells during infection with genotype VII Newcastle disease virus
Authors: Hu Zenglei , Gu Han , Ni Jie , Hu Shunlin , Hu Jiao , Wang Xiaoquan , Liu Xiaowen , Liu Xiufan
Published: October 2020

Upregulation of matrix metalloproteinase (MMP)−14, a major driven force of extracellular-matrix (ECM) remodelling and cell migration, correlates with ECM breakdown and pathologic manifestation of genotype VII Newcastle disease virus (NDV) in chickens. However, the functional relevance between MMP-14 and pathogenesis of genotype VII NDV remains to be investigated. In this study, expression, biofunction and regulation of MMP-14 induced by genotype VII NDV were analysed in chicken peripheral blood mononuclear cells (PBMCs). The results showed that JS5/05 significantly increased expression and membrane accumulation of MMP-14 in PBMCs, correlating to enhanced collagen degradation and cell migration. Specific MMP-14 inhibition significantly impaired collagen degradation and migration of JS5/05-infected cells, suggesting dependence of these features on MMP-14. In addition, MMP-14 upregulation correlated with activation of the extracellular signal-regulated kinase (ERK) pathway upon JS5/05 infection, and blockage of the ERK signalling significantly suppressed MMP-14-mediated collagen degradation and migration of JS5/05-infected cells. Using a panel of chimeric NDVs derived from gene exchange between genotype VII and IV NDV, the fusion and haemagglutinin-neuraminidase genes were identified as the major viral determinants for MMP-14 expression and activity. In conclusion, MMP-14 was defined as a critical regulator of collagen degradation and cell migration of chicken PBMCs infected with genotype VII NDV, which may contribute to pathology of the virus. Our findings add novel information to the body of knowledge regarding virus–host biology and NDV pathogenesis.
NHS Hospital ‘Learning from Deaths’ reports: A qualitative and quantitative analysis of the first year of a countrywide patient safety programme
Authors: Brummell Zoe , Vindrola-Padros Cecilia , Braun Dorit , Moonesinghe S. Ramani
Published: October 2020

Introduction

Potentially preventable deaths occur worldwide within healthcare organisations. Organisational learning from incidents is essential to improve quality of care. In England, inconsistencies in how NHS secondary care trusts reviewed, investigated and shared learning from deaths, resulted in the introduction of national guidance on ‘Learning from Deaths’ (LfDs) in 2017. This guidance provides a ‘framework for identifying, reporting, investigating and learning from deaths’. Amendments to NHS Quality Account regulations, legally require NHS trusts in England to report quantitative and qualitative information relating to patient deaths annually. The programme intended trusts would share this learning and take measurable action to prevent future deaths.

Method

We undertook qualitative and quantitative secondary data analysis of all NHS secondary care trust LfDs reports within their 2017/18 Quality Accounts, to review how organisations are using the LfDs programme to learn from and prevent, potentially preventable deaths.

Results

All statutory elements of LfDs reporting were reported by 98 out of 222 (44%) trusts. The percentage of deaths judged more likely than not due to problems in healthcare was between 0% and 13%. The majority of trusts (89%) reported lessons learnt; the most common learning theme was poor communication. 106 out of 222 trusts (48%) have shared or plan to share the learning within their own organisation. The majority of trusts (86%) reported actions taken and 47% discussed or had a plan for assessment of impact. 37 out of 222 trusts (17%) mentioned involvement of bereaved families.

Conclusions

The wide variation in reporting demonstrates that some trusts have engaged fully with LfDs, while other trusts appear to have disengaged with the programme. This may reveal a disparity in organisational learning and patient safety culture which could result in inequity for bereaved families. Many themes identified from the LfD reports have previously been identified in national and international reports and inquiries. Further work is needed to strengthen the LfDs programme.
Role of Professionalism in the Policy Response to COVID-19: Does a Public Health or Medical Background Help?
Authors: Li X. , Lai W. , Wan Q. , Chen X.
Published: October 2020

Less than 5 percent of Chinese cities had top-ranked officials with public health or medical backgrounds (PHMBGs). Does professionalism improve their response to a public crisis like the COVID-19 pandemic? Collecting résumés of government and Party officials in almost all prefectural Chinese cities, and matching with other data sources, including weather conditions, city characteristics, COVID-19-related policies, and health outcomes, we demonstrate that cities whose top officials had PHMBGs witnessed significantly lower infection rates, and often lower death rates, than cities whose top officials lacked such backgrounds. Mechanism testing suggests that the effects were at least partially explained by more rapid lockdown or community closure. Our findings offer insights into better preparation for future epidemics via improving leadership team composition, particularly recruiting major officials with PHMBGs.

One Sentence Summary

Cities whose top officials had PHMBGs saw lower infection and death rates, attributable to more rapid decision to lock down and close communities.
CpelTdm.jl: a Julia package for targeted differential DNA methylation analysis
Authors: Abante Jordi , Goutsias John
Published: October 2020

Motivation

Identifying regions of the genome that demonstrate significant differences in DNA methylation between groups of samples is an important problem in computational epigenetics. Available methods assume that methylation occurs in a statistically independent manner at individual cytosine-phosphate-guanine (CpG) sites or perform analysis using empirically estimated joint probability distributions of methylation patterns at no more than 4 contiguous CpG sites. These approaches can lead to poor detection performance and loss of reliability and reproducibility due to reduced specificity and sensitivity in the presence of insufficient data.

Results

To accommodate data obtained with different bisulfite sequencing technologies, such as RRBS, ERRBS, and WGBS, and improve statistical power, we developed CpelTdm.jl, a Julia package for targeted differential analysis of DNA methylation stochasticity between groups of unmatched or matched samples. This package performs rigorous statistical analysis of methylation patterns within regions of the genome specified by the user that takes into account correlations in methylation and results in robust detection of genomic regions exhibiting statistically significant differences in methylation stochasticity. CpelTdm.jl does not only detect mean methylation differences, as it is commonly done by previous methods, but also differences in methylation entropy and, more generally, between probability distributions of methylation.

Availability and Implementation

This Julia package is supported for Windows, MacOS, and Linux, and can be freely downloaded from GitHub:https://github.com/jordiabante/CpelTdm.jl.

Contacts

jabante1@jhu.eduorgoutsias@jhu.edu.
Genome-wide identification and transcriptional analyses of the R2R3-MYB gene family in wheat
Authors: Xiao Chunsheng , Jia Yong , Watt Calum , Chen Wenshuai , Zhang Yujuan , Li Chengdao
Published: October 2020

MYB transcription factors (TFs) represents one of the largest TF families in plants. In this study, we performed genome-wide MYB-domain screening and identified a total of 997 MYBs in wheat(Triticum aestivum),among which 445 were 2-domain MYBs (R2R3-MYBs) that were clustered into 15 subgroups with varied conservation profiles. Homologous genes were highly conserved across the three subgenomes, with minor variations contributed by segmental duplications. Tandem and proximal gene duplications have contributed significantly to the expansion of the wheatMybgene family. Furthermore, comprehensive transcriptome profiling ofR2R3-Mybgenes in 61 different tissue and time point samples revealed a clear pattern of temporal and spatial variations within six expression groups. The comprehensive genomic and transcriptional analyses provided valuable insights into the evolution and biological functions ofR2R3-Mybgenes in wheat. They would serve as a useful guide to further investigate the potential agronomic traits controlled by this large TF family.