Search

Anxiety disorders are the most prevalent psychiatric disorders, exhibiting strong female bias. Clinical studies implicate declining estradiol levels in the exacerbation of anxiety symptoms in the premenstrual phase of the menstrual cycle. This study aimed to simulate estradiol fluctuation-linked anxiety behavior in larval zebrafish, using an estradiol treatment withdrawal model. Contrary to model aims, estradiol treatment withdrawal decreased both basal activity and anxiety-like hyperlocomotion (ANOVA main effect of dose, P  < 0.0001 and P  < 0.01, respectively) in the light/dark transition test. The accuracy of the estradiol washout model was not improved by longer durations of treatment or withdrawal. Basal activity was slightly altered by supraphysiological concentrations of WAY-200070 in the absence of added estradiol. Estrogen receptor (ER) β expression was not upregulated in larvae exposed to physiologically relevant, low concentrations of estradiol. Longer exposure to low concentrations of estradiol increased antioxidant capacity ( P  < 0.01). In addition, acute exposure to low concentrations of estradiol increased basal activity. Data suggest that in the current models, estradiol-associated altered activity levels were linked to more favorable redox status, rather than reflecting altered anxiety levels. As such, it is recommended that zebrafish larval behavioral analysis be conducted in parallel with mechanistic studies such as redox indicators, for investigations focused on ER signaling., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Objectives: To determine the impact of telementoring on caregiver performance during a high-fidelity medical simulation model (HFMSM) of a critically ill patient in a resource-limited setting., Design: A two-center, randomized, controlled study using a HFMSM of a patient with community-acquired pneumonia complicated by acute respiratory distress syndrome., Setting: A notional clinic in a remote location staffed by a single clinician and nonmedical assistant., Participants: Clinicians with limited experience managing critically ill patients., Interventions: Telemedicine (TM) support., Measurements: The primary outcome was clinical performance as measured by accuracy, reliability, and efficiency of care. Secondary outcomes were patient survival, procedural quality, subjective assessment of the HFMSM, and perceived workload., Main Results: TM participants ( N = 11) performed better than non-TM (NTM, N = 12) in providing expected care (accuracy), delivering care more consistently (reliability), and without consistent differences in efficiency (timeliness of care). Accuracy: TM completed 91% and NTM 42% of expected tasks and procedures. Efficiency: groups did not differ in the mean (± sd) minutes it took to obtain an advanced airway successfully (TM 15.2 ± 10.5 vs. NTM 22.8 ± 8.4, p = 0.10) or decompress a tension pneumothorax with a needle (TM 0.7 ± 0.5 vs. NTM 0.6 ± 0.9, p = 0.65). TM was slower than NTM in completing thoracostomy (22.3 ± 10.2 vs. 12.3 ± 4.8, p = 0.03). Reliability: TM performed 13 of 17 (76%) tasks with more consistent timing than NTM. TM completed 68% and NTM 29% of procedural quality metrics. Eighty-two percent of the TM participants versus 17% of the NTM participants simulated patients survived ( p = 0.003). The groups similarly perceived the HFMSM as realistic, managed their patients with personal ownership, and experienced comparable workload and stress., Conclusions: Remote expertise provided with TM to caregivers in resource-limited settings improves caregiver performance, quality of care, and potentially real patient survival. HFMSM can be used to study interventions in ways not possible with real patients.

Background: Disparities in physical and mental health among Black, Indigenous, and People of Color (BIPOC) are well-documented and mirrored in the Veteran population. Chronic stress due to racism and discrimination is one possible mechanism driving these negative health outcomes. The Race-Based Stress and Trauma Empowerment (RBSTE) group is a novel, manualized, health promotion intervention designed to address the direct and indirect impacts of racism among Veterans of Color. This paper describes the protocol of the first pilot randomized controlled trial (RCT) of RBSTE. This study will examine the feasibility, acceptability, and appropriateness of RBSTE compared to an active control (an adaptation of Present-Centered Therapy; PCT) in a Veterans Affairs (VA) healthcare setting. A secondary aim is to identify and optimize strategies for holistic evaluation., Methods: Veterans of Color (N = 48) endorsing perceived discrimination and stress will be randomized to RBSTE or PCT; both groups will be delivered in 8 weekly, 90-min virtual group sessions. Outcomes will include measures of psychological distress, discrimination and ethnoracial identity, holistic wellness, and allostatic load. Measures will be administered at baseline and post-intervention., Conclusion: This study will inform future interventions targeting identity-based stressors and represents an important step in advancing equity for BIPOC in medicine and research., Clinical Trial Registration Number: NCT05422638., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Emtricitabine/tenofovir disoproxil fumarate [FTC-TDF] is a daily oral medication taken by HIV-negative individuals for pre-exposure prophylaxis (PrEP) to prevent human immunodeficiency virus (HIV) infection. A higher incidence of sexually transmitted infections (STIs) among PrEP users has been reported compared to STI incidence before PrEP use. Asymptomatic incident STI rates were investigated among 78 patients presenting for PrEP in Honolulu, Hawai'i, from April 2018 to May 2019. Testing for oropharyngeal gonorrhea, urethral gonorrhea and chlamydia, rectal gonorrhea and chlamydia, and syphilis was performed. Incident STI percentages were calculated at each follow-up visit. Ninety-seven percent of patients were men who have sex with men (MSM). Forty-seven percent of patients had follow-up data 6 months after initiation and 28% after 1 year. Thirty-two percent of patients self-reported an STI before initiating PrEP. More than half reported anonymous partners. There were 35 positive STI tests during the study period, and 25% of patients had one or more positive tests during this time. At initiation, 17% of patients were found to have an STI, followed by 16% at 3 months, 14% at 6 months, 8% at 9 months, and 5% at 12 months. At all visits, chlamydia was the most common STI detected; at 6 months, 18% of all rectal tests were positive for chlamydia. There were inconsistent condom use and high STI rates from screening during PrEP initiation and follow-up, offering an opportunity to identify asymptomatic STIs in this population. This study is the first report in Hawai'i of STI rates among PrEP users., (©Copyright 2021 by University Health Partners of Hawai‘i (UHP Hawai‘i).)

Considering that the phenomenon of accelerated ageing contributes to early onset of various chronic diseases, modelling of the relevant dysregulated systems or responses is vital for research aimed at identification of potential therapeutic targets. Here, we aimed to establish a model capable of simulating the redox and inflammatory changes of accelerated ageing-specifically, the aim was early phase accelerated ageing, which would allow therapeutic intervention in a preventative approach prior to clinical disease manifestation. A secondary aim was to evaluate the sensitivity of the model to reflect preventative treatment efficacy. Daily D-galactose injections (250 mg/kg body mass/day) for 8 weeks in 9-week-old male Wistar rats induced a model of early accelerated ageing (decreased plasma FRAP; P < 0.05 and altered inflammatory signalling) and an aged profile in lymph node ultrastructure, but did not yet result in telomere shortening. Preventative daily oral antioxidant administration (grape seed-derived polyphenol, 100 mg/kg body mass) prevented tissue ageing, beneficially modulated the inflammatory response, including neutrophil chemokinetic capacity, and tended to increase absolute telomere length. Data suggests that using a mild model of D-galactose administration than those employed to induce neurodegeneration, simulated the point where oxidative stress starts to overwhelm the endogenous antioxidant response and where a pro-inflammatory phenotype switch manifests. Furthermore, despite the expected small effect size, the model was sufficiently sensitive to reflect benefits of preventative antioxidant treatment in the context of ageing. This model presents a practical model for use in drug discovery, particularly in the context of preventative medicine aimed at limiting oxidative stress-associated ageing. Since this starting point of accelerated ageing as illustrated by current data, is not expected to reflect major ageing-associated changes yet, we recommend that future preventative drug discovery studies employ a longitudinal study design in order to clearly demonstrate the delay of this starting point by preventative strategies.

Rheumatoid arthritis is prevalent in more than 1% of the global population, with the highest occurrence between ages 35 and 50, which places a huge burden on the economy. Drug discovery for the prevention of this chronic disease is; therefore, a priority. It is known that subclinical progression of many chronic non-communicable diseases is exacerbated via accelerated ageing, a pro-inflammatory phenotype shift. However, rheumatoid arthritis additionally has significant humoral immune activation, inflammatory signalling-and thus the accelerated ageing profile-may differ from other chronic inflammatory diseases. The current study simulated inflammatory arthritis onset in a collagen-induced arthritis (CIA) rodent model, to characterise the redox and inflammatory profile at the onset of clinical symptoms, in different tissues, in the presence and absence of preventative antioxidant treatment. The data illustrate that an increased free radical level are evident already very early on in RA disease progression. Furthermore, oxidative stress seems to somewhat precede a significant pro-inflammatory state, perhaps due to humoral immune activation. Our data across different compartments further suggest that the compensatory increase in endogenous antioxidant activity is gradually exhausted at a different pace, with the liver showing the first signs of oxidant damage, even before significant evidence exist in circulation. The current data further suggest that preventative antioxidant intervention may have a sparing effect on endogenous antioxidant mechanisms and preserve telomere length to delay disease progression-or at least the accelerated ageing known to exacerbate RA symptoms-although it did not seem to have a significant direct effect on the autoimmune activity.