Provider Experience with Teleneurology in an Academic Neurology Department.

Introduction: Teleneurology has become widely adopted during severe acute respiratory syndrome coronavirus 2 pandemic. However, provider impressions about the teleneurology experience are not well described. Methods: A novel questionnaire was developed to collect provider impressions about video teleneurology encounters. All providers in the University of Pennsylvania Health System (UPHS) Neurology Department (N = 162) were asked to complete a questionnaire after each video teleneurology patient encounter between April and August 2020. Individual patient and encounter-level data were extracted from the electronic medical record. Results: One thousand six hundred three surveys were completed by 55 providers (response rate of 10.12%). The history obtained and the ability to connect with the patient were considered the same or better than an in-person visit in almost all encounters. The quality of the physician-patient relationship was good or excellent in 93%, while the overall experience was the same as an in-person visit in 73% of visits and better in 12%. Sixty-eight percent of respondents reported that none of the elements of the neurological examination if performed in person would have changed the assessment and plan. Assessment of the visit as the same or better increased from 83% in April to 89% in July and 95% in August. Headache (91%), multiple sclerosis and neuroimmunology (96%), and movement disorder (89%) providers had the highest proportion of ratings of same or better overall experience and neuromuscular providers the lowest (60%). Conclusions: Provider impressions about the teleneurology history, examination, and provider-patient relationship are favorable in the majority of responses. Important differences emerge between provider specialty and visit characteristics groups.

Neurotoxicities in the treatment of HIV between dolutegravir, rilpivirine and dolutegravir/rilpivirine: a meta-analysis.

OBJECTIVE: To assess the risk of neuropsychiatric adverse effects (ie, depression, anxiety, insomnia, dizziness, suicidal behaviour) among patients treated with rilpivirine, dolutegravir and dolutegravir/rilpivirine. DESIGN: This is a systematic review and meta-analysis of randomised controlled trials. Quality of evidence was assessed using Jadad scoring system. DATA SOURCES: Three electronic databases were searched for available publications up to 1 May 2020. Searches included relevant studies, trial registers, conference proceeding abstracts and grey literature. INCLUSION CRITERIA: Randomised controlled trials with data focused on adult participants (ie, 18 years of age or older) receiving dolutegravir 50 mg, rilpivirine 25 mg or combination of dolutegravir 50 mg/rilpivirine 25 mg once daily. RESULTS: Twenty studies with a minimum duration of 48 weeks and average Jadad score of 4 were included (n=10 998). Primary objective demonstrated a relative risk (RR) synergistic effect on depressive symptoms for dolutegravir/rilpivirine (RR=2.82; 95% CI (1.12 to 7.10)) when compared with dolutegravir (RR=1.10; 95% CI (0.88 to 1.38)) and rilpivirine (RR=1.08; 95% CI (0.80 to 1.48)). Secondary objectives showed no difference between dolutegravir, rilpivirine and dolutegravir/rilpivirine to efavirenz. Additionally, excluding efavirenz studies, dolutegravir and dolutegravir/rilpivirine yielded increased depression (RR=1.34; 95% CI (1.04 to 1.74)). CONCLUSION: The combination of dolutegravir/rilpivirine appears to increase the risk of depressive symptoms. Despite the increase, the clinical significance is unknown and needs further study. Additionally, neurotoxicity risk appears similar between dolutegravir, rilpivirine and dolutegravir/rilpivirine antiretroviral therapy when compared with efavirenz-based antiretroviral therapy.

Establishment of a murine hepatocellular carcinoma model by hydrodynamic injection and characterization of the immune tumor microenvironment.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant neoplasms. Current treatments for HCC, such as tyrosine kinase inhibitors, have limited efficacy, highlighting the urgent need for better therapies. Immunotherapies, including anti-programmed death receptor 1 (PD-1) and anti-Cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and more recently, the combination of anti-PD-L1 and anti-vascular endothelial growth factor (VEGF) monoclonal antibodies, have shown efficacy against HCC, resulting in Food and Drug Administration (FDA) approval. However, these immunotherapies only show efficiency in a small proportion of patients, meaning there is a great need to improve and optimize treatments against HCC. Accurate animal models that mimic human HCC are necessary to help better understand the nature of these tumors, which in turn will allow the development and testing of new treatments. Existing pre-clinical HCC models can be divided into non-genetic and genetic models. Non-genetic models involve implanting human or murine HCC cell lines or inducing tumors using chemical compounds or dietary modifications. These models have limitations, including slow tumor development and a lack of resemblance to human HCC. Genetic models, on the other hand, manipulate gene expression to induce HCC in mice and provide a better understanding of the effects of specific genes on tumor development. One method commonly used to generate HCC is hydrodynamic tail vein injection (HTVI), which consists of the delivery of oncogenes directly to the liver, resulting in expression and subsequent hepatocyte transformation. Usually, Sleeping Beauty transposase-containing plasmids are used to achieve stable and long-term gene expression. Once the HCC tumor is generated, and a proper tumor microenvironment (TME) is established, it is important to study the immune compartment of the TME, which plays a crucial role in HCC development and response to treatment. Techniques like flow cytometry can be used to analyze the immune cell populations in HCC tumors and assess their impact on tumor development and survival in mice. In this article, we thoroughly describe an example of the methodology to successfully generate HCC murine models via HTVI, and we propose a way to characterize the immune TME by flow cytometry.

The Genetic Variant TNFA (rs361525) Is Associated with Increased Susceptibility to Developing Dengue Symptoms.

Dengue virus (DENV) is the causal agent of dengue fever. The symptoms and signs of dengue vary from febrile illness to hemorrhagic syndrome. IFITM3 and TNFA are genes of the innate immune system. Variants IFITM3 (rs12252 T>C) and TNFA (rs1800629 G > A and rs361525 G>A) might alter gene expression and change the course of the disease. Our first objective was to determine whether these variants were associated with the susceptibility and severity of dengue. The second was to assess the association of these variants with each symptom. We studied 272 cases with suspected dengue infection, of which 102 were confirmed dengue cases (DENV+) and 170 were dengue-like cases without DENV infection (DENV-). Samples of 201 individuals from the general population of Mexico were included as a reference. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism technique. Odds ratios and confidence intervals were calculated using Pearson's chi-square test and later adjusted for age and sex with a binary logistic regression model. Haldane correction is applied when necessary. We found a significantly higher frequency of the A allele of TNFA rs361525 in both the DENV+ and DENV- groups compared with the general population. Focusing on DENV+ and DENV-, the frequency of the A allele of TNFA rs361525 was higher in the DENV+ group. A broad spectrum of symptoms was related to the A allele of both TNFA variants. We conclude that TNFA rs361525 increases the susceptibility to symptomatic dengue but can also be associated with susceptibility to other dengue-like symptoms from unknown causes.

Brevundimonas brasiliensis sp. nov.: a New Multidrug-Resistant Species Isolated from a Patient in Brazil.

To increase knowledge on Brevundimonas pathogens, we conducted in-depth genomic and phenotypic characterization of a Brevundimonas strain isolated from the cerebrospinal fluid of a patient admitted in a neonatal intensive care unit. The strain was identified as a member of the genus Brevundimonas based on Vitek 2 system results and 16S rRNA gene sequencing and presented a multidrug resistance profile (MDR). Several molecular and biochemical tests were used to characterize and identify the species for in-depth results. The draft genome assembly of the isolate has a total length of 3,261,074 bp and a G+C of 66.86%, similar to other species of the genus. Multilocus sequence analysis, Type (Strain) Genome Server, digital DNA-DNA hybridization, and average nucleotide identity confirmed that the Brevundimonas sp. studied represents a distinct species, for which we propose the name Brevundimonas brasiliensis sp. nov. In silico analysis detected antimicrobial resistance genes (AMRGs) mediating resistance to ß-lactams (penP, blaTEM-16, and blaBKC-1) and aminoglycosides [strA, strB, aac(6')-Ib, and aac(6')-Il]. We also found AMRGs encoding the AcrAB efflux pump that confers resistance to a broad spectrum of antibiotics. Colistin and quinolone resistance can be attributed to mutation in qseC and/or phoP and GyrA/GyrB, respectively. The Brevundimonas brasiliensis sp. nov. genome contained copies of type IV secretion system (T4SS)-type integrative and conjugative elements (ICEs); integrative mobilizable elements (IME); and Tn3-type and IS3, IS6, IS5, and IS1380 families, suggesting an important role in the development and dissemination of antibiotic resistance. The isolate presented a range of virulence-associated genes related to biofilm formation, adhesion, and invasion that can be relevant for its pathogenicity. Our findings provide a wealth of data to hinder the transmission of MDR Brevundimonas and highlight the need for monitoring and identifying new bacterial species in hospital environments. IMPORTANCE Brevundimonas species is considered an opportunistic human pathogen that can cause multiple types of invasive and severe infections in patients with underlying pathologies. Treatment of these pathogens has become a major challenge because many isolates are resistant to most antibiotics used in clinical practice. Furthermore, there are no consistent therapeutic results demonstrating the efficacy of antibacterial agents. Although considered a rare pathogen, recent studies have provided evidence of the emergence of Brevundimonas in clinical settings. Hence, we identified a novel pathogenic bacterium, Brevundimonas brasiliensis sp. nov., that presented a multidrug resistance (MDR) profile and carried diverse genes related to drug resistance, virulence, and mobile genetic elements. Such data can serve as a baseline for understanding the genomic diversity, adaptation, evolution, and pathogenicity of MDR Brevundimonas.

Mindfulness and Balanced Time Perspective: Predictive Model of Psychological Well-Being and Gender Differences in College Students.

BACKGROUND: The aims of the study were to establish an adjustment model to analyze the relationship among mindfulness, balanced time perspective (BTP) and psychological well-being (PWB) in college students and to explore gender differences among the variables. METHOD: The sample consisted of 380 college students, 220 women and 160 men, uniformly distributed according to the university's faculties. RESULTS: The results indicate that the synergy between mindfulness and BTP predicts the variance of PWB by 55%. Regarding gender differences, it was found that women have a greater tendency towards Past Positive than men and men a higher tendency towards Present Hedonistic than women. In addition, in the group of women, a stronger relationship was found among the variables and, consequently, a greater predictive value for PWB (58%), displaying an enhanced disposition to high PWB compared to men. CONCLUSIONS: Together, mindfulness and BTP promote optimal psychological functioning and alleviate or reduce discomfort. Thus, their promotion and training in universities is especially important given the high prevalence of anxiety and depressive symptoms in college students.

Identification of a New Endo-ß-1,4-xylanase Prospected from the Microbiota of the Termite Heterotermes tenuis.

Xylanases are hemicellulases that break down xylan to soluble pentoses. They are used for industrial purposes, such as paper whitening, beverage clarification, and biofuel production. The second-generation bioethanol production is hindered by the enzymatic hydrolysis step of the lignocellulosic biomass, due to the complex arrangement established among its constituents. Xylanases can potentially increase the production yield by improving the action of the cellulolytic enzyme complex. We prospected endo-ß-1,4-xylanases from meta-transcriptomes of the termite Heterotermes tenuis. In silico structural characterization and functional analysis of an endo-ß-1,4-xylanase from a symbiotic protist of H. tenuis indicate two active sites and a substrate-binding groove needed for the catalytic activity. No N-glycosylation sites were found. This endo-ß-1,4-xylanase was recombinantly expressed in Pichia pastoris and Escherichia coli cells, presenting a molecular mass of approximately 20 kDa. Enzymatic activity assay using recombinant endo-ß-1,4-xylanase was also performed on 1% xylan agar stained with Congo red at 30 °C and 40 °C. The enzyme expressed in both systems was able to hydrolyze the substrate xylan, becoming a promising candidate for further analysis aiming to determine its potential for application in industrial xylan degradation processes.

Coping, resilience, and emotional well-being in pharmacy students during the COVID-19 pandemic.

INTRODUCTION: The purpose of this study was to investigate the significant contributions of coping, resilience, personal characteristics, and health behaviors on the emotional well-being of pharmacy students during the COVID-19 pandemic. COVID-19 was identified in December 2019 and declared a pandemic by the World Health Organization in March 2020. Pharmacy students may experience greater stress during this outbreak because of interruptions in classes or rotations, concerns regarding personal or family health, and social isolation from peers. These changes may result in behavior shifts, difficulty concentrating, and increased use of negative coping strategies. The extent to which these factors affect overall student well-being during a pandemic is largely unknown. METHODS: A cross-sectional study of 3 colleges of pharmacy was completed during May to July 2020 via an online, anonymous 64-item questionnaire using REDCap software. Linear regression and descriptive statistical analyses were conducted using SPSS version 26. RESULTS: Using the enter method, levels of coping strategies, personal resilience, and Hispanic ethnic identity explain 29% of the variance in emotional well-being scores in pharmacy students during the first months of the COVID-19 pandemic (F (2,76) = 11.785, P < .000, R2 = 0.317, R2 adjusted = 0.291). For this sample (N = 104), higher levels of resilience, greater use of coping strategies, and identifying as Hispanic were significant predictors of emotional well-being. DISCUSSION: Student mental health continues to be important, especially during crises and pandemics. Therefore, pharmacy programs should cultivate an environment that supports the emotional well-being of their students. Campus-based initiatives may be needed to encourage healthy coping behaviors and bolster students' personal resilience to better prepare them for providing front-line patient care in the future.

Meta-Analysis of Speech Recognition Outcomes in Younger and Older Adults With Cochlear Implants.

Purpose Meta-analyses were conducted to compare pre- to postoperative speech recognition improvements and postoperative scores after cochlear implantation in younger (< 60 years) and older (> 60 years) adults. Method Studies were identified with electronic databases and through manual search of the literature. In the primary analyses, effect sizes between pre- and postoperative scores for each age group were calculated using a formula appropriate for repeated-measures designs. Using the effect sizes, two separate meta-analyses using a random-effects restricted maximum likelihood model were conducted for experiments using word and sentence recognition stimuli in quiet. Secondary meta-analyses were conducted to examine average postimplant, percent correct word recognition, sentence recognition, and speech recognition in noise in studies that included both older and younger age groups. Traditional Hedges's g effect sizes were calculated between the two groups. Results For the primary analyses, experiments using word and sentence recognition stimuli yielded significant, large effect sizes for the younger and older adult cochlear implant recipients with no significant differences between the older and younger age groups. However, the secondary meta-analyses of postoperative scores suggested significant differences between age groups for stimuli in quiet and noise. Conclusions Although older and younger adults with implants achieve the same magnitude of pre- to postimplant speech recognition benefit in quiet, the overall postoperative speech recognition outcomes in quiet and noise are superior in younger over older adults. Strategies to mitigate these group differences are critical for ensuring optimal outcomes in elderly individuals who are candidates for cochlear implants.

Evaluation of Inhibitory Activity In Silico of In-House Thiomorpholine Compounds between the ACE2 Receptor and S1 Subunit of SARS-CoV-2 Spike.

At the end of 2019, the world was struck by the COVID-19 pandemic, which resulted in dire repercussions of unimaginable proportions. From the beginning, the international scientific community employed several strategies to tackle the spread of this disease. Most notably, these consisted of the development of a COVID-19 vaccine and the discovery of antiviral agents through the repositioning of already known drugs with methods such as de novo design. Previously, methylthiomorphic compounds, designed by our group as antihypertensive agents, have been shown to display an affinity with the ACE2 (angiotensin converting enzyme) receptor, a key mechanism required for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) entry into target cells. Therefore, the objective of this work consists of evaluating, in silico, the inhibitory activity of these compounds between the ACE2 receptor and the S1 subunit of the SARS-CoV-2 spike protein. Supported by the advances of different research groups on the structure of the coronavirus spike and the interaction of the latter with its receptor, ACE2, we carried out a computational study that examined the effect of in-house designed compounds on the inhibition of said interaction. Our results indicate that the polyphenol LQM322 is one of the candidates that should be considered as a possible anti-COVID-19 agent.

Comprehension of Top 200 Prescribed Drugs in the US as a Resource for Pharmacy Teaching, Training and Practice.

Pharmacists have access to a plethora of information related to drugs. Online compendia concerning top 200 prescribed drugs are readily-accessible, comparatively-easy to search. While these resources provide some information about the commonly prescribed drugs, they lack in furnishing in-depth knowledge to pharmacy students, pharmacists and other healthcare professionals. The aim of this paper is to present the relevant details of top 200 most prescribed drugs in the United States. The names and therapeutic classes of top 200 prescribed drugs were compiled from online resources. The pharmacological actions of drugs, any reported adverse reactions and black box warnings are collected from drug bank resources, such as AccessPharmacy and Lexicomp. The paper provides comprehensive information about top 200 prescribed drugs, which includes generic names, pharmacological action, route of administration and adverse reaction profile including black box warning when applicable. Overall, the drug list may serve as an easy access of ideas for pharmacists, researchers and other healthcare professionals interested in developing new strategies for treating patients with various ailments.