bluuebunny/crossref_metadata_2025 huggingface dataset:
Behavioral and Personal Characteristics Associated With Risk of SARS-CoV-2 Infection in a Spanish University Cohort
Authors: Amer Fares , Gil-Conesa Mario , Carlos Silvia , Ariño Arturo H , Carmona-Torre Francisco , Martínez-González Miguel A , Fernandez-Montero Alejandro
Published: April 2023

The aim of this study was to analyze the life habits and personal factors associated with increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) risk in a university environment with in-person lectures during the coronavirus disease 2019 (COVID-19) pandemic. To our knowledge, there are no previous longitudinal studies that have analyzed associations of behavioral and personal factors with the risk of SARS-CoV-2 infection on an entire university population. A cohort study was conducted in the 3 campuses of the University of Navarra between August 24, 2020, and May 30, 2021, including 14,496 students and employees; the final sample included 10,959. Descriptive and multivariate-adjusted models were fitted using Cox regression. A total of 1,032 (9.4%) participants were diagnosed with COVID-19 (879 students and 153 employees), almost 50% living with their families. COVID-19 was associated with living in college or residence (hazard ratio (HR) = 1.96, 95% CI: 1.45, 2.64), motor transportation (HR = 1.35, 95% CI: 1.14, 1.61), South American origin (HR = 1.43, 95% CI: 1.20, 1.72), and belonging to Madrid’s campus (HR = 3.11, 95% CI: 2.47, 3.92). International students, especially from Latin America, mostly lived in university apartments or shared flats and cohabited with 4–11 people. Living in a big city (Madrid), was a significant risk factor.
Stimulation of non-motor subthalamic nucleus impairs selective response inhibition via prefrontal connectivity
Authors: Waldthaler Josefine , Sperlich Alexander , Stüssel Charlotte , Steidel Kenan , Timmermann Lars , Pedrosa David J
Published: April 2023

Given the inconsistent results in the past, there is an ongoing debate whether and how deep brain stimulation in the subthalamic nucleus modifies cognitive control processes like response inhibition in persons with Parkinson’s disease. In this study, we examined how the location of the stimulation volume within the subthalamic nucleus affects the performance in an antisaccade task but also how its structural connectivity is related to response inhibition. Antisaccade error rates and latencies were collected in 14 participants on and off deep brain stimulation in a randomized order. Stimulation volumes were computed based on patient-specific lead localizations using preoperative MRI and postoperative CT scans. Structural connectivity of the stimulation volumes with pre-defined cortical oculomotor control regions as well as whole-brain connectivity was estimated using a normative connectome. We showed that the detrimental effect of deep brain stimulation on response inhibition, measured as antisaccade error rate, depended upon the magnitude of the intersection of volumes of activated tissue with the non-motor subregion of the subthalamic nucleus and on its structural connectivity with regions of the prefrontal oculomotor network including bilateral frontal eye fields and right anterior cingulate cortex. Our results corroborate previous recommendations for avoidance of stimulation in the ventromedial non-motor subregion of the subthalamic nucleus which connects to the prefrontal cortex to prevent stimulation-induced impulsivity. Furthermore, antisaccades were initiated faster with deep brain stimulation when the stimulation volume was connected to fibres passing the subthalamic nucleus laterally and projecting onto the prefrontal cortex, indicating that improvement of voluntary saccade generation with deep brain stimulation may be an off-target effect driven by stimulation of corticotectal fibres directly projecting from the frontal and supplementary eye fields onto brainstem gaze control areas. Taken together, these findings could help implement individualized circuit-based deep brain stimulation strategies that avoid impulsive side effects while improving voluntary oculomotor control.
Prognostic echocardiographic findings in patients supported with venoarterial extracorporeal membrane oxygenation for cardiogenic shock
Authors: Siriwardena Maithri , Brahmbhatt Darshan H , Douflé Ghislaine , Fan Eddy , Billia Filio
Published: April 2023

Aims

Echocardiography is critical in the management of patients supported with veno-arterial extracorporeal membrane oxygenation (V-A ECMO). This study aimed to identify the incidence of critical echocardiographic findings and determine their prognostic significance.

Methods and results

All available echocardiograms, hemodynamic variables and outcomes of patients with CS supported with V-A in the period of 2011-2018 at the Toronto General Hospital were retrospectively reviewed. Critical echocardiographic findings were defined as minimal to no left ventricular (LV) ejection, the presence of intra-cardiac clot, significant pericardial effusion and malpositioning of ECMO cannulae. 130 patients were included in this study with in-hospital mortality of 58.5%. Critical findings were most often seen in the first echocardiogram (42/121; 35%). The incidence of critical findings in the first echocardiogram was minimal to no LV ejection in 28 patients (23%), intracardiac thromboses in 8 patients (6.6%), tamponade in 5 patients (4%) and malpositioned cannulae in 1 patient (0.8%). Presence of a critical finding in the first study was associated with an odds ratio for in-hospital mortality of 2.32 (95% CI 1.01-5.06, P = 0.011).

Conclusion

The initial echocardiogram was most likely to demonstrate a critical finding of which the most common was minimal to no LV ejection. Critical echocardiographic findings carried prognostic significance for in-hospital mortality.
Using Immersive Virtual Reality to Enhance Social Interaction Among Older Adults: A Cross-Site Investigation
Authors: Kalantari Saleh , Xu Tong Bill , Mostafavi Armin , Kim Benjamin , Dilanchian Andrew , Lee Angella , Boot Walter R , Czaja Sara J
Published: April 2023

Background and Objectives

Virtual reality (VR) applications are increasingly being targeted toward older adults as a means to maintain physical and cognitive skills and to connect with others, especially during the coronavirus disease 2019 era. Our knowledge about how older adults interact with VR is limited, however, since this is an emerging area and the related research literature is still rather slim. The current study focused specifically on older adults’ reactions to a social-VR environment, examining participant’s views about the possibility of meaningful interactions in this format, the impacts of social-VR immersion on mood and attitude, and features of the VR environment that affected these outcomes.

Research Design and Methods

The researchers designed a novel social-VR environment with features intended to prompt conversation and collaborative problem-solving among older adults. Participants were recruited from 3 diverse geographic locations (Tallahassee, FL; Ithaca, NY; and New York City, NY), and were randomly assigned to a partner from one of the other sites for social-VR interaction. The sample consisted of 36 individuals aged 60 and older.

Results

Reactions to the social VR were quite positive. Older adults reported high levels of engagement in the environment and perceived the social VR to be enjoyable and usable. Perceived spatial presence was found to be a central driver of positive outcomes. A majority of the participants indicated a willingness to reconnect with their VR partner in the future. The data also identified important areas for improvement that were of concern to older adults, such as the use of more realistic avatars, larger controllers more suited to aging hands, and more time for training/familiarization.

Discussion and Implications

Overall, these findings suggest that VR can be an effective format for social engagement among older adults.
441 Understanding the unintended consequences of new healthcare technologies aimed at supporting patient safety: a qualitative study
Authors: Abdelaziz S , Garfield S , McLeod M , Norton J , Lloyd J , Wheeler C , Neves A L , van Dael J , Franklin B D
Published: April 2023

Introduction

Technologies such as electronic prescribing, clinical decision support systems, and electronic medication dispensers, are increasingly being introduced into healthcare. Existing toolkits focus on the implementation of such technologies, rather than identifying and mitigating any unintended consequences technologies may have on patient safety. They also focus on high-level organisational issues instead of those faced by end-users: frontline staff, patients and carers.

Aim

To identify and classify types of unintended consequences that may be encountered by technologies’ end-users, in order to inform development of a tool for identifying and preventing technology-related risks on patient safety.

Methods

Five focus group discussions with healthcare professionals, patients and carers were conducted through video-conferencing. Healthcare professionals with experience of using/implementing healthcare technologies and known to the research team via professional networks were invited to participate. Patient/carer participants were recruited using convenience sampling via an external research-participant organisation. Participants were asked to identify patient safety risks associated with the use of healthcare technologies, drawn from their own experiences and through consideration of hypothetical risks. Discussions were audio-recorded and transcribed verbatim. Transcripts were analysed by two researchers (NVivo R1.6) and two public partners (manually), using iterative inductive thematic analysis.

Results

Eleven healthcare professionals and 29 patients and carers participated in focus groups. Three focus groups comprised patients, carers, and healthcare professionals. Two involved solely patients and carers. Analysis revealed five areas of unintended consequences (Table 1). Most unintended consequences identified by patients and carers were similar to those described by healthcare professionals. Healthcare professionals also described additional unintended consequences associated with technologies designed specifically for their use.

Conclusion

A limitation of the study is that many of the unintended consequences identified related to virtual health technologies used during the COVID-19 pandemic, which may affect generalisability. A strength is that unintended consequences that have been overlooked in existing literature, such as the build-up of patients’ psychological dependence on technologies, were identified. Developing a tool based on these will allow implementers and users of healthcare technologies to consider such issues and address the potential risks they may have on patient safety before healthcare technologies are fully implemented in practice.
A pressure-robust HHO method for the solution of the incompressible Navier–Stokes equations on general meshes
Authors: Castanon Quiroz Daniel , Di Pietro Daniele A
Published: April 2023

In a recent work (Castanon Quiroz & Di Pietro (2020) A hybrid high-order method for the incompressible Navier–Stokes problem robust for large irrotational body forces. Comput. Math. Appl., 79, 2655–2677), we have introduced a pressure-robust hybrid high-order method for the numerical solution of the incompressible Navier–Stokes equations on matching simplicial meshes. Pressure-robust methods are characterized by error estimates for the velocity that are fully independent of the pressure. A crucial question was left open in that work, namely whether the proposed construction could be extended to general polytopal meshes. In this paper, we provide a positive answer to this question. Specifically, we introduce a novel divergence-preserving velocity reconstruction that hinges on the solution inside each element of a mixed problem on a subtriangulation, then use it to design discretizations of the body force and convective terms that lead to pressure robustness. An in-depth theoretical study of the properties of this velocity reconstruction, and their reverberation on the scheme, is carried out for arbitrary polynomial degrees $k\geq 0$ and meshes composed of general polytopes. The theoretical convergence estimates and the pressure robustness of the method are confirmed by an extensive panel of numerical examples.
Burnout Among Breast Radiologists: How Can We Restore Fulfillment?
Authors: Dwan Dennis , Dialani Vandana
Published: April 2023

Physician burnout is increasing in prevalence and has negative implications for the quality of patient care and the health and wellbeing of physicians. Surveys before the COVID-19 pandemic showed high rates of burnout among breast radiologists, and the COVID-19 pandemic has further increased stress. This article summarizes strategies to combat burnout, including improving individual resilience by increasing mindfulness about handling stress, making goals, and noting personal accomplishments. However, more effective change is likely to occur when there is change at both a personal and an organizational level, which includes identifying the stakeholders in a workplace and determining what changes must occur to increase joy and decrease rates of burnout. Despite the increasing rates of burnout, breast radiologists report high rates of personal career satisfaction. Self-reflection and positive steps to increase joy at work are important in maintaining career fulfillment in these challenging times.
Diversity and dynamics of endosymbionts in a single population of sweet potato weevil,Cylas formicarius(Coleoptera: Brentidae): a preliminary study
Authors: Xu Jin , Tan Jian-Bin , Li Yi-Dan , Xu Yuan-Hao , Tang An , Zhou Hong-Kai , Shi Pei-Qiong
Published: April 2023

Endosymbionts live symbiotically with insect hosts and play important roles in the evolution, growth, development, reproduction, and environmental fitness of hosts. Weevils are one of the most abundant insect groups that can be infected by various endosymbionts, such as Sodalis, Nardonella, and Wolbachia. The sweet potato weevil, Cylas formicarius (Coleoptera: Brentidae), is a notorious pest in sweet potato (Ipomoea batatas L.) cultivation. Currently, little is known about the presence of endosymbionts in C. formicarius. Herein, we assessed the endosymbiont load of a single geographic population of C. formicarius. The results showed that Nardonella and Rickettsia could infect C. formicarius at different rates, which also varied according to the developmental stages of C. formicarius. The relative titer of Nardonella was significantly related to C. formicarius developmental stages. The Nardonella-infecting sweet potato weevils were most closely related to the Nardonella in Sphenophorus levis (Coleoptera, Curculionidae). The Rickettsia be identified in bellii group. These results preliminarily revealed the endosymbionts in C. formicarius and helped to explore the diversity of endosymbionts in weevils and uncover the physiological roles of endosymbionts in weevils.
Lessons from Canada’s notice of compliance with conditions policy for the life-cycle regulation of drugs
Authors: McPhail Melanie , Zhang Howard , Bhimani Zohra , Bubela Tania
Published: April 2023

Innovative health technologies are not well regulated under current pathways, leading regulators to adopt contextual, life-cycle regulatory models, which authorize drugs based on earlier clinical evidence subject to the conduct of post-market trials that confirm clinical benefit and safety. In this paper, we evaluate all drugs authorized in Canada under the Notice of Compliance with conditions (NOC/c) policy from 1998 to 2021 to analyze its function, identify challenges and areas for improvement, and make recommendations to inform Health Canada’s regulatory reforms. We analyzed a sample of 148 drugs authorized between 1998 and 2021, including characteristics about the pre- and post-market clinical trials, finding that most NOC/c authorizations are based on one, single-arm clinical trial using a surrogate endpoint. Post-market trials are more likely to be randomized, Phase III trials but mostly use surrogate endpoints. Based on our findings, we recommend increasing decision-making transparency throughout the regulatory process, developing comprehensive eligibility criteria for selecting appropriate health technologies, modernizing pre-market evidence requirements, adopting a more active role in designing post-market trials, and utilizing automatic expiry, stronger penalties, and ongoing disclosure of the status of post-market trials to promote compliance.
Effectiveness of Booster Doses of Monovalent mRNA COVID-19 Vaccine Against Symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children, Adolescents, and Adults During Omicron Subvariant BA.2/BA.2.12.1 and BA.4/BA.5 Predominant Periods
Authors: Ciesla Allison Avrich , Wiegand Ryan E , Smith Zachary R , Britton Amadea , Fleming-Dutra Katherine E , Miller Joseph , Accorsi Emma K , Verani Jennifer R , Shang Nong , Derado Gordana , Pilishvili Tamara , Link-Gelles Ruth
Published: April 2023

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.2/BA.2.12.1 and BA.4/BA.5 subvariants have mutations associated with increased capacity to evade immunity when compared with prior variants. We evaluated mRNA monovalent booster dose effectiveness among persons ≥5 years old during BA.2/BA.2.12.1 and BA.4/BA.5 predominance.

Methods

A test-negative, case-control analysis included data from 12 148 pharmacy SARS-CoV-2 testing sites nationwide for persons aged ≥5 years with ≥1 coronavirus disease-2019 (COVID-19)-like symptoms and a SARS-CoV-2 nucleic acid amplification test from April 2 to August 31, 2022. Relative vaccine effectiveness (rVE) was estimated comparing 3 doses of COVID-19 mRNA monovalent vaccine to 2 doses; for tests among persons ≥50 years, rVE estimates also compared 4 doses to 3 doses (≥4 months since third dose).

Results

A total of 760 986 test-positive cases and 817 876 test-negative controls were included. Among individuals ≥12 years, rVE of 3 versus 2 doses ranged by age group from 45% to 74% at 1-month post vaccination and waned to 0% by 5–7 months post vaccination during the BA.4/BA.5 period.

Adults aged ≥50 years (fourth dose eligible) who received 4 doses were less likely to have symptomatic SARS-CoV-2 infection compared with those with 3 doses; this rVE remained >0% through at least 3 months since last dose. For those aged ≥65 years, rVE of 4 versus 3 doses 1-month post vaccination was higher during BA.2/BA.2.12.1 (rVE = 49%; 95% confidence interval [CI], 43%–53%) than BA.4/BA.5 (rVE = 40%; 95% CI, 36%–44%). In 50- to 64-year-olds, rVE estimates were similar.

Conclusions

Monovalent mRNA booster doses provided additional protection against symptomatic SARS-CoV-2 infection during BA.2/BA.2.12.1 and BA.4/BA.5 subvariant circulation, but protection waned over time.
Cis mutagenesis in vivo reveals extensive noncanonical functions of Dscam1 isoforms in neuronal wiring
Authors: Zhang Shixin , Yang Xi , Dong Haiyang , Xu Bingbing , Wu Lili , Zhang Jian , Li Guo , Guo Pengjuan , Li Lei , Fu Ying , Du Yiwen , Zhu Yanda , Shi Jilong , Shi Feng , Huang Jianhua , He Haihuai , Jin Yongfeng
Published: April 2023

Drosophila Down syndrome cell adhesion molecule 1 (Dscam1) encodes tens of thousands of cell recognition molecules via alternative splicing, which are required for neural function. A canonical self-avoidance model seems to provide a central mechanistic basis for Dscam1 functions in neuronal wiring. Here, we reveal extensive noncanonical functions of Dscam1 isoforms in neuronal wiring. We generated a series of allelic cis mutations in Dscam1, encoding a normal number of isoforms, but with an altered isoform composition. Despite normal dendritic self-avoidance and self-/nonself-discrimination in dendritic arborization (da) neurons, which is consistent with the canonical self-avoidance model, these mutants exhibited strikingly distinct spectra of phenotypic defects in the three types of neurons: up to ∼60% defects in mushroom bodies, a significant increase in branching and growth in da neurons, and mild axonal branching defects in mechanosensory neurons. Remarkably, the altered isoform composition resulted in increased dendrite growth yet inhibited axon growth. Moreover, reducing Dscam1 dosage exacerbated axonal defects in mushroom bodies and mechanosensory neurons but reverted dendritic branching and growth defects in da neurons. This splicing-tuned regulation strategy suggests that axon and dendrite growth in diverse neurons cell-autonomously require Dscam1 isoform composition. These findings provide important insights into the functions of Dscam1 isoforms in neuronal wiring.
Is symptom duration before DMARD therapy a determinant of direct and indirect costs in DMARD-naïve RA patients? A systematic review
Authors: Sahbudin Ilfita , Singh Ruchir , Trickey Jeanette , Baranskaya Aliaksandra , Tracy Alexander , Raza Karim , Filer Andrew , Jowett Sue , Boonen Annelies
Published: April 2023

Objective

Early treatment of RA improves clinical outcomes; however, the impact on health economic outcomes is unclear. This review sought to investigate the relationship between symptom/disease duration and resource utilization/costs and the responsiveness of costs following RA diagnosis.

Methods

A systematic search was performed on Pubmed, EMBASE, CINAHL and Medline. Studies were eligible if patients were DMARD-naïve and fulfilled 1987 ACR or 2010 ACR/EULAR RA classification criteria. Studies had to report symptom/disease duration and resource utilization or direct/indirect costs as health economic outcomes. The relationships between symptom/disease duration and costs were explored.

Results

Three hundred and fifty-seven records were identified in a systematic search; nine were eligible for analysis. The mean/median of symptom/disease duration in studies ranged between 25 days and 6 years. Annual direct costs of RA following diagnosis showed a U-shaped distribution in two studies. Longer symptom duration before starting a DMARD (>180 days) was associated with lower health-care utilization in the first year of RA diagnosis in one study. Annual direct and indirect costs 6 months before RA diagnosis were higher in patients with shorter symptom duration (<6 months) in one study. Given the clinical and methodological heterogeneities, the association between symptom/disease duration and costs after diagnosis was not computed.

Conclusion

The association between symptom/disease duration at the time of DMARD initiation and resource utilization/cost in patients with RA remains unclear. Health economic modelling with clearly defined symptom duration, resource utilization and long-term productivity is vital to address this evidence gap.
Sodium oxybate in treatment-resistant rapid-eye-movement sleep behavior disorder
Authors: During Emmanuel H , Hernandez Beatriz , Miglis Mitchell G , Sum-Ping Oliver , Hekmat Anahid , Cahuas Ana , Ekelmans Adrian , Yoshino Fuyumi , Mignot Emmanuel , Kushida Clete A
Published: April 2023

Study Objectives

Symptomatic therapies for rapid-eye-movement (REM) sleep behavior disorder (RBD) are limited. Sodium oxybate (SXB), a gamma-aminobutyric acid (GABA)-B agonist, could be effective but has not been evaluated against placebo.

Methods

This double-blind, parallel-group, randomized, placebo-controlled trial in 24 participants was conducted at the Stanford Sleep Center. Patients were adults with definite iRBD or Parkinson’s disease and probable RBD (PD-RBD), and persistence of ≥ 2 weekly episodes despite standard therapy. Patients were randomized 1:1 to receive SXB during a 4-week titration followed by a 4-week stable dosing period. Primary outcome was number of monthly RBD episodes according to a diary filled by patients and partners. Secondary outcomes were severity, number of severe RBD episodes, and objective RBD activity on video polysomnography.

Results

Twelve iRBD and 12 PD-RBD participated (mean 65.8 years), and 22 (n = 10 SXB, 12 placebo) completed the study. Although no significant between-group difference was found, SXB showed reduction of monthly RBD episodes by 23.1 (95% CI −36.0, −10.2; p = 0.001) versus 10.5 with placebo (95% CI, −22.6, 1.6; p = 0.087). Improvement from baseline was similarly observed for RBD overall severity burden (each episode weighted for severity), number of severe episodes, and objective RBD activity per video-polysomnography. Two participants receiving SXB withdrew due to anxiety and dizziness. The majority of adverse events are otherwise resolved with dose adjustment.

Conclusion

SXB could reduce RBD symptoms; however, response was inconsistent and a large placebo effect was observed across patient-reported outcomes. Larger studies using objective endpoints are needed.

Clinical Trial

Treatment of REM Sleep Behavior Disorder (RBD) With Sodium Oxybate

https://clinicaltrials.gov/ct2/show/NCT04006925 ClinicalTrials.gov identifier: NCT04006925
The pandemic, telemedicine, and andrology: what have we learned?
Authors: Moukhtar Hammad Muhammed A , El-Achkar Adnan , Nguyen Tuan , Barham David W , Tran Joshua , Jenkins Lawrence , Yafi Faysal A
Published: April 2023

Background

Telemedicine gained wide acceptance during the COVID-19 pandemic, as it was deemed critical for patient care when lockdowns were implemented worldwide. While there is evidence to suggest that urology patients were receptive to telemedicine, no systematic review has been done to date on andrology patients and their perception of telemedicine.

Methods

Three electronic databases, PubMed, Scopus, and Web of Science, were searched from their inception until June 2022 for relevant articles. Two independent teams reviewed abstracts and extracted data from the selected manuscripts. A meta-analysis was completed in line with PRISMA 2020 and AMSTAR Guidelines. For our study, we limited telemedicine to communication through videoconferencing or telephone encounters between patients and medical professionals. Positive response to telemedicine was defined as patients “wishing for telemedicine consultation”, “preferring telemedicine over in person”, “accepting the current telemedicine arrangement”, “having needs addressed with teleconsultation”, or “willingness to do a teleconsultation”.

Results

Of the 1128 retrieved abstracts, 56 underwent full-text review and 12 were included in the final analysis, comprising a total cohort of >4021 cases. Video visits were evaluated in 5 studies, telephone encounters were analyzed in 2 studies, and both methods were examined in 1 randomized control study. Three studies showed that andrology and sexual medicine are compatible with telemedicine, with few 30- and 90-day in-person revisit rates. Telemedicine was shown to save an average cost of US$149-$252 per patient, and 8 studies that directly assessed andrology patient perceptions of telemedicine showed that most patients had a “positive perception.”

Pooled analyses of the positive responses to telemedicine were 68.7% (95% CI, 49.4%-83.1%, P = 0.057), and those of patients who recommended telemedicine were 65.1% (95% CI, 18.4%-93.9%, P = 0.577). While the percentage of patients recommending telemedicine was high among studies using videoconferencing, the percentage dropped in studies using telephone visits only. The difference between recommending video and telephone practices was statistically significant, with 84.6% pooled proportion for recommending video practice compared to 38.9% pooled proportion for recommending telephone practice, P = 0.035. In the telephone-only encounters, up to 27.1% of patients preferred in-person visits, as security and privacy of any mode of telecommunication were of concern.

Conclusions

Most patients have a positive perception of telemedicine, particularly with videoconferencing and less so with telephone visits. These results suggest that telemedicine will likely continue to play a pivotal role in andrology and sexual medicine practices.
The role of Gel‐Ppy‐modified nerve conduit on the repair of sciatic nerve defect in rat model
Authors: Jiang Liangfu , Ouyang Xingyu , Zhang Dupiao , Wang Gang , Zhang Zhe , Wang Wei , Yan Hede
Published: April 2023

The serious clinical challenge of peripheral nerve injury (PNI) is nerve regeneration. Nerve conduit represents a promising strategy to contribute to nerve regeneration by bridging injured nerve gaps. However, due to a unique microenvironment of nerve tissue, autologous nerves have not been substituted by nerve conduit. Nerve regeneration after nerve conduit implantation depends on many factors, such as conductivity and biocompatibility. Therefore, Gelatin (Gel) with biocompatibility and polypyrrole (Ppy) with conductivity is highly concerned. In this paper, Gel‐Ppy modified nerve conduit was fabricated with great biocompatibility and conductivity to evaluate its properties of enhancing nerve regeneration in vivo and in vitro. The proliferation of Schwann cells on Gel‐Ppy modified nerve conduit was remarkably increased. Consistent with in vitro results, the Gel‐Ppy nerve conduit could contribute to the regeneration of Schwann cell in vivo. The axon diameters and myelin sheath thickness were also enhanced, resulting in the amelioration of muscle atrophy, nerve conduction, and motor function recovery. To explain this interesting phenomenon, western blot results indicated that the Gel‐Ppy conduit facilitated nerve regeneration via upregulating the Rap1 pathway to induce neurite outgrowth. Therefore, the above results demonstrated that Gel‐Ppy modified nerve conduit could provide an acceptable microenvironment for nerve regeneration and be popularized as a novel therapeutic strategy of PNI.
Effectiveness of Cultural Sensitivity Training on Undergraduate Students’ Knowledge, Self-Efficacy, and Ethnocultural Empathy
Authors: Butte Katie J. , Hristova Lena
Published: April 2023

Institutional racism and systemic bias must be addressed in health care education with embedded cultural sensitivity training. We report the results of remote training on culturally sensitive care to increase knowledge, self-efficacy, and empathy in undergraduate nursing students (n = 16). The training included four weekly remote sessions (~90 minutes). A pre-post survey indicated knowledge and self-efficacy increased (p < .01); empathy increased but not significantly, likely because of ceiling effects (p > .11). Compliance (94%) and satisfaction were excellent. This pilot study demonstrates a flexible, effective training model for nurse educators to implement within or alongside undergraduate nursing curricula.
The Translated Proximal Humerus Fracture: A Comparison of Operative and Nonoperative Management
Authors: Cosic Filip , Kirzner Nathan , Edwards Elton , Page Richard , Kimmel Lara , Gabbe Belinda
Published: April 2023

Objectives:

To report on the long-term outcomes of the management of translated proximal humerus fractures.

Design:

A prospective cohort study was conducted from January 2010 to December 2018.

Setting:

Academic Level 1 trauma center.

Participants/Patients:

A total of 108 patients with a proximal humerus fracture with ≥100% translation, defined as no cortical bony contact between the shaft and humeral head fragments, were included.

Intervention:

Patients were managed nonoperatively with sling immobilization or with operative management as determined by the treating surgeon.

Main Outcome Measures:

Outcome measures were the Oxford Shoulder Score, EQ-5D-5L, return to work, and radiological outcomes. Complications recorded included further surgery, loss of position/fixation, nonunion/malunion, and avascular necrosis.

Results:

Of the 108 patients, 76 underwent operative intervention and 32 were managed nonoperatively. The mean (SD) age in the operative group was 54.3 (±20.2) years and in the nonoperative group was 73.3 (±15.3) years (P < 0.001). There was no association between Oxford Shoulder Score and management options (mean 38.5 [±9.5] operative versus mean 41.3 [±8.5] nonoperative, P = 0.48). Operative management was associated with improved health status outcomes; EQ-5D utility score adjusted mean difference was 0.16 (95% CI, 0.04–0.27; P = 0.008); EQ-5D VAS adjusted mean difference was 19.2 (95% CI, 5.2–33.2; P = 0.008). Operative management was associated with a lower odds of nonunion (adjusted OR 0.30; 95% CI, 0.09–0.97; P = 0.04), malunion (adjusted OR 0.14; 95% CI, 0.04–0.51; P = 0.003), and complications (adjusted OR 0.07; 95% CI, 0.02–0.32; P = 0.001).

Conclusion:

Translated proximal humerus fractures with ≥100% displacement demonstrate improved health status and radiological outcomes after surgical fixation.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Dynamic Changes in Lumbar Spine Kinematics During Gait May Explain Improvement in Back Pain and Disability in Patients With Hip-Spine Syndrome
Authors: Chen Stephen R. , LeVasseur Clarissa M. , Como Christopher J. , Couch Brandon K. , Talentino Spencer E. , Klatt Brian A. , O’Malley Michael J. , Donaldson William F. , Lee Joon Y. , Shaw Jeremy D. , Anderst William J.
Published: April 2023

Study Design.

Prospective cohort.

Objective.

Determine if total hip arthroplasty (THA) changes lumbar spine kinematics during gait in a manner that explains the improvements in back pain seen in patients with hip-spine syndrome.

Summary of Background Data.

For patients with hip-spine syndrome, improvements in both hip and back pain have been demonstrated after THA; however, the exact mechanism of improvement in back pain remains unknown, as no corresponding changes in lumbar spine static radiographic parameters have been identified.

Methods.

Thirteen patients with severe, unilateral hip osteoarthritis scheduled to undergo THA with concomitant back pain and disability were tested at baseline and 6 months after THA. Harris Hip Score (HHS) and Oswestry Disability Index questionnaires were completed; the static orientation of the spine and pelvis were measured on standing radiographs, and lumbar spine kinematics were measured during treadmill walking using a validated measurement system that matched subject-specific bone models created from CT scans to dynamic biplane radiographs.

Results.

After THA, both the Oswestry Disability Index (36.3–11.3, P<0.001) and Harris Hip Score (55.7–77.9, P<0.001) improved; however, there were no changes in static intervertebral or pelvis orientation. During gait after THA, the overall lumbar spine (L1 to L5) was less lordotic from heel strike to contralateral toe off (P<0.001), the L4 and L5 vertebra were less anteriorly tilted by 3.9° (P=0.038) from midstance to contralateral heel strike and by 3.9° (P=0.001) during stance, respectively.

Conclusion:

The decreased anterior tilt of the 2 lowest lumbar vertebrae and the corresponding loss of lumbar lordosis may reduce facet loading during the stance phase of gait after THA. This change in lumbar spine kinematics during gait is a potential mechanism to explain the observed improvements in back pain and disability after THA.

Level of Evidence.

4.
Individualized red-cell transfusion strategy for non-cardiac surgery in adults: a randomized controlled trial
Authors: Liao Ren , Liu Jin , Zhang Wei , Zheng Hong , Zhu Zhaoqiong , Sun Haorui , Yu Zhangsheng , Jia Huiqun , Sun Yanyuan , Qin Li , Yu Wenli , Luo Zhen , Chen Yanqing , Zhang Kexian , Ma Lulu , Yang Hui , Wu Hong , Liu Limin , Yuan Fang , Xu Hongwei , Zhang Jianwen , Zhang Lei , Liu Dexing , Huang Han
Published: April 2023

Background:

Red-cell transfusion is critical for surgery during the peri-operative period; however, the transfusion threshold remains controversial mainly owing to the diversity among patients. The patient's medical status should be evaluated before making a transfusion decision. Herein, we developed an individualized transfusion strategy using the West-China-Liu's Score based on the physiology of oxygen delivery/consumption balance and designed an open-label, multicenter, randomized clinical trial to verify whether it reduced red cell requirement as compared with that associated with restrictive and liberal strategies safely and effectively, providing valid evidence for peri-operative transfusion.

Methods:

Patients aged >14 years undergoing elective non-cardiac surgery with estimated blood loss > 1000 mL or 20% blood volume and hemoglobin concentration <10 g/dL were randomly assigned to an individualized strategy, a restrictive strategy following China's guideline or a liberal strategy with a transfusion threshold of hemoglobin concentration <9.5 g/dL. We evaluated two primary outcomes: the proportion of patients who received red blood cells (superiority test) and a composite of in-hospital complications and all-cause mortality by day 30 (non-inferiority test).

Results:

We enrolled 1182 patients: 379, 419, and 384 received individualized, restrictive, and liberal strategies, respectively. Approximately 30.6% (116/379) of patients in the individualized strategy received a red-cell transfusion, less than 62.5% (262/419) in the restrictive strategy (absolute risk difference, 31.92%; 97.5% confidence interval [CI]: 24.42–39.42%; odds ratio, 3.78%; 97.5% CI: 2.70–5.30%; P<0.001), and 89.8% (345/384) in the liberal strategy (absolute risk difference, 59.24%; 97.5% CI: 52.91–65.57%; odds ratio, 20.06; 97.5% CI: 12.74–31.57; P<0.001). No statistical differences were found in the composite of in-hospital complications and mortality by day 30 among the three strategies.

Conclusion:

The individualized red-cell transfusion strategy using the West-China-Liu's Score reduced red-cell transfusion without increasing in-hospital complications and mortality by day 30 when compared with restrictive and liberal strategies in elective non-cardiac surgeries.

Trial registration:

ClinicalTrials.gov, NCT01597232.
SHED-derived exosomes ameliorate hyposalivation caused by Sjögren's syndrome via Akt/GSK-3β/Slug-mediated ZO-1 expression
Authors: Du Zhihao , Wei Pan , Jiang Nan , Wu Liling , Ding Chong , Yu Guangyan
Published: April 2023

Background:

Sjögren's syndrome (SS) is an autoimmune disorder characterized by sicca syndrome and/or systemic manifestations. The treatment is still challenging. This study aimed to explore the therapeutic role and mechanism of exosomes obtained from the supernatant of stem cells derived from human exfoliated deciduous teeth (SHED-exos) in sialadenitis caused by SS.

Methods:

SHED-exos were administered to the submandibular glands (SMGs) of 14-week-old non-obese diabetic (NOD) mice, an animal model of the clinical phase of SS, by local injection or intraductal infusion. The saliva flow rate was measured after pilocarpine intraperitoneal injection in 21-week-old NOD mice. Protein expression was examined by western blot analysis. Exosomal microRNA (miRNAs) were identified by microarray analysis. Paracellular permeability was evaluated by transepithelial electrical resistance measurement.

Results:

SHED-exos were injected into the SMG of NOD mice and increased saliva secretion. The injected SHED-exos were taken up by glandular epithelial cells, and further increased paracellular permeability mediated by zonula occluden-1 (ZO-1). A total of 180 exosomal miRNAs were identified from SHED-exos, and Kyoto Encyclopedia of Genes and Genomes analysis suggested that the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) pathway might play an important role. SHED-exos treatment down-regulated phospho-Akt (p-Akt)/Akt, phospho-glycogen synthase kinase 3β (p-GSK-3β)/GSK-3β, and Slug expressions and up-regulated ZO-1 expression in SMGs and SMG-C6 cells. Both the increased ZO-1 expression and paracellular permeability induced by SHED-exos were abolished by insulin-like growth factor 1, a PI3K agonist. Slug bound to the ZO-1 promoter and suppressed its expression. For safer and more effective clinical application, SHED-exos were intraductally infused into the SMGs of NOD mice, and saliva secretion was increased and accompanied by decreased levels of p-Akt/Akt, p-GSK-3β/GSK-3β, and Slug and increased ZO-1 expression.

Conclusion:

Local application of SHED-exos in SMGs can ameliorate Sjögren syndrome-induced hyposalivation by increasing the paracellular permeability of glandular epithelial cells through Akt/GSK-3β/Slug pathway-mediated ZO-1 expression.
Right ventricular-arterial uncoupling as an independent prognostic factor in acute heart failure with preserved ejection fraction accompanied with coronary artery disease
Authors: Jia Hongdan , Liu Li , Bi Xile , Li Ximing , Cong Hongliang
Published: April 2023

Background:

Right ventricular (RV)-arterial uncoupling is a powerful independent predictor of prognosis in heart failure with preserved ejection fraction (HFpEF). Coronary artery disease (CAD) can contribute to the pathophysiological characteristics of HFpEF. This study aimed to evaluate the prognostic value of RV-arterial uncoupling in acute HFpEF patients with CAD.

Methods:

This prospective study included 250 consecutive acute HFpEF patients with CAD. Patients were divided into RV-arterial uncoupling and coupling groups by the optimal cutoff value, based on a receiver operating characteristic curve of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP). The primary endpoint was a composite of all-cause death, recurrent ischemic events, and HF hospitalizations.

Results:

TAPSE/PASP ≤0.43 provided good accuracy in identifying patients with RV-arterial uncoupling (area under the curve, 0.731; sensitivity, 61.4%; and specificity, 76.6%). Of the 250 patients, 150 and 100 patients could be grouped into the RV-arterial coupling (TAPSE/PASP >0.43) and uncoupling (TAPSE/PASP ≤0.43) groups, respectively. Revascularization strategies were slightly different between groups; the RV-arterial uncoupling group had a lower rate of complete revascularization (37.0% [37/100] vs. 52.7% [79/150], P <0.001) and a higher rate of no revascularization (18.0% [18/100] vs. 4.7% [7/150], P <0.001) compared to the RV-arterial coupling group. The cohort with TAPSE/PASP ≤0.43 had a significantly worse prognosis than the cohort with TAPSE/PASP >0.43. Multivariate Cox analysis showed TAPSE/PASP ≤0.43 as an independent associated factor for the primary endpoint, all-cause death, and recurrent HF hospitalization (hazard ratios [HR]: 2.21, 95% confidence interval [CI]: 1.44–3.39, P <0.001; HR: 3.32, 95% CI: 1.30–8.47, P = 0.012; and HR: 1.93, 95% CI: 1.10–3.37, P = 0.021, respectively), but not for recurrent ischemic events (HR: 1.48, 95% CI: 0.75–2.90, P = 0.257).

Conclusion:

RV-arterial uncoupling, based on TAPSE/PASP, is independently associated with adverse outcomes in acute HFpEF patients with CAD.
Alveolar target ventilation and dead space in children under anaesthesia
Authors: Gardon Aurelien , De Queiroz Siqueira Mathilde , Cerceuil Eloise , Bouhamri Noureddine , Chassard Dominique , Baudin Florent
Published: April 2023

INTRODUCTION

Ventilator settings in children under anaesthesia remain difficult because of the changes in the physiology and the high dead space.

OBJECTIVE

To determine the alveolar minute-volume to sustain normocapnia in children under mechanical ventilation.

DESIGN

A prospective observational study.

SETTINGS

This study was performed between May and October 2019 in a tertiary care children's hospital.

PATIENTS

Children between 2 months and 12 years, weighing between 5 and 40 kg, admitted for general anaesthesia.

INTERVENTION

Volumetric capnography was used to estimate the alveolar and dead space volume (Vd).

MAIN OUTCOME MEASURES

Total and alveolar minute ventilation in (ml kg-1 min−1) over 100 breaths.

RESULTS

Sixty patients were included comprising 20 per group: 5 to 10 kg (group 1), 10 to 20 kg (group 2), 20 to 40 kg (group 3). Seven patients were excluded for aberrant capnographic curves. After normalisation to weight, the median [IQR] tidal volume per kilogram was similar between the three groups: 6.5 ml kg−1 [6.0 to 7.5 ml kg−1], 6.4  ml kg−1 [5.7 to 7.3  ml kg−1], 6.4  ml kg−1 [5.3 to 6.8  ml kg−1]; P = 0.3. Total Vd (in ml kg−1) was negatively correlated to weight (r = -0.62, 95% confidence interval -0.41 to -0.76, P < 0.001). The total normalised minute ventilation (ml kg−1 min−1) to obtain normocapnia was higher in group 1 than in group 2 and in group 3; 203  ml kg−1 min−1 [175 to 219 ml kg−1 min−1], 150  ml kg−1 min−1 [139 to 181  ml kg−1 min−1] and 128  ml kg−1 min−1 [107 to 157  ml kg−1 min−1]; P < 0.001 (mean ± SD), but (mean ± SD) alveolar minute ventilation was similar between the three groups; 68 ± 21  ml kg−1 min−1.

CONCLUSION

Total dead space volume (including apparatus dead space) represents a major component of tidal volume in children less than 30 kg, when using large heat and moisture exchanger filters. The total minute ventilation necessary to achieve normocapnia decreased with increasing weight, while the alveolar minute ventilation remained constant.

TRIAL REGISTRATION

ClinicalTrials.gov, identifier: NCT03901599
Microbiologic Epidemiology of Early-onset Sepsis in Neonates Born at ≥35 0/7 Weeks’ Gestation in Korea During 2009–2018
Authors: Yoon Yoonsun , So Hyejin , Lee Joon Kee , Kim Dongsub , Jo Kyo Jin , Kim Hyun Ho , Kim Yoo-Jin , Lee Jina , Jo Dae Sun , Kim Yun-Kyung , Park Su Eun , Chang Yun Sil , Kim Yae-Jean
Published: April 2023

Background:

Sepsis within the first 3 days of life remains a leading cause of neonatal mortality and morbidity. However, few studies have addressed the epidemiology of sepsis in late preterm and term neonates, particularly in Asia. We aimed to estimate the epidemiology of early-onset sepsis (EOS) in neonates born at ≥35 0/7 weeks’ gestation in Korea.

Methods:

A retrospective study was conducted in neonates with proven EOS born at ≥35 0/7 weeks’ gestation from 2009 to 2018 at seven university hospitals. EOS was defined as identifying bacteria from a blood culture within 72 hours after birth.

Results:

A total of 51 neonates (0.36/1,000 live births) with EOS were identified. The median duration from birth to the first positive blood culture collection was 17 hours (range, 0.2–63.9). Among the 51 neonates, 32 (63%) patients were born by vaginal delivery. The median Apgar score was 8 (range, 2–9) at 1 minute and 9 (range, 4–10) at 5 minutes. The most common pathogen was group B Streptococcus (n = 21; 41.2%), followed by coagulase-negative staphylococci (n = 7; 13.7%) and Staphylococcus aureus (n = 5, 9.8%). Forty-six (90.2%) neonates were treated with antibiotics on the first day of symptom onset, and 34 (73.9%) neonates received susceptible antibiotics. The overall 14-day case-fatality rate was 11.8%.

Conclusion:

This is the first multicenter study on the epidemiology of proven EOS in neonates born at ≥35 0/7 weeks’ gestation and found that group B Streptococcus was the most common pathogen in Korea.
Regulation of granulocyte colony-stimulating factor-induced hematopoietic stem cell mobilization by the sympathetic nervous system
Authors: Suzuki Tomohide , Ishii Shinichi , Katayama Yoshio
Published: April 2023

Purpose of review

Granulocyte colony-stimulating factor (G-CSF) is now a standard agent to mobilize hematopoietic stem cells (HSCs) from the bone marrow to circulation. This review introduced mechanistic insights from the aspect of the sympathetic nervous system (SNS).

Recent findings

Mobilization efficiency is determined by the balance between promotion and suppression pathways critically regulated by the SNS. G-CSF-induced high catecholaminergic tone promotes mobilization by (1) the strong suppression of osteolineage cells as a hematopoietic microenvironment and (2) fibroblast growth factor 23 production from erythroblasts, which inhibits CXCR4 function in HSCs. Simultaneously, SNS signals inhibit mobilization by (1) prostaglandin E2 production from mature neutrophils to induce osteopontin in osteoblasts to anchor HSCs and (2) angiopoietin-like protein 4 production from immature neutrophils via peroxisome proliferator-activated receptor δ to inhibit BM vascular permeability.

We now know not only the regulatory mechanisms of G-CSF-induced mobilization but also the leads about unfavorable clinical phenomena, such as low-grade fever, bone pain, and poor mobilizers. Recent understanding of the mechanism will assist clinicians in the treatment for mobilization and researchers in the studies of the hidden potential of BM.