Hereditary angioedema (HAE) is a rare disorder linked to kallikrein-kinin system dysregulation, which leads to uncontrolled activation of plasma prekallikrein. Donidalorsen is an antisense oligonucleotide designed to selectively degrade prekallikrein messenger RNA and thereby reduce prekallikrein production. We aimed to develop population pharmacokinetic and pharmacokinetic/pharmacodynamic models of donidalorsen and evaluate the impact of potential intrinsic/extrinsic covariates on exposure and prekallikrein response. Plasma donidalorsen and prekallikrein data were obtained from phase 1 to 3 studies in healthy volunteers (NCT03263507, 721744-CS9) and adult and adolescent patients with HAE (NCT04030598, NCT05139810). The evaluated doses were 20, 40, 60, and 80 mg every 4 weeks (Q4W) and 80 mg every 8 weeks (Q8W), administered subcutaneously over 13-21 weeks. Donidalorsen pharmacokinetics were well described by a linear 2-compartment model with first-order absorption. The population terminal elimination half-life was 31.4 days. Prekallikrein was well described by an indirect response model with inhibition of prekallikrein production by donidalorsen. Covariate analysis identified body weight as the main factor affecting pharmacokinetic exposure; however, this effect was not considered clinically significant. The developed population pharmacokinetic/pharmacodynamic model well characterized the donidalorsen exposure-prekallikrein response relationship. Modeling analyses support that no dose adjustment is needed with respect to intrinsic/extrinsic factors in adults and adolescents with HAE. The nearly identical simulated pharmacokinetic or prekallikrein time courses for Q4W versus monthly dosing and for Q8W versus every-2-month dosing regimens support switching to more convenient regimens for patients.

Resistance training plays a crucial role in cardiovascular health by promoting epigenetic adaptations that beneficially modulate gene expression. These modifications include DNA methylation, histone alterations, and regulation by non-coding RNAs, which directly affect cardiac muscle and the vascular system. Such epigenetic changes lead to improved cardiac function, reduced inflammation, optimized metabolism, and protection against cardiovascular diseases. Resistance training induces the release of signaling molecules that mediate favorable systemic adaptations. Studies demonstrate that resistance training, especially when combined with aerobic training, improves cardiovascular risk factors such as blood pressure and lipid profile. Epigenetic regulation is fundamental to the plasticity of the cardiovascular system and the reversibility of exercise-induced adaptations. Although extreme exercise may pose risks, regular and moderate resistance training is safe and effective in the prevention and management of cardiovascular diseases through these molecular mechanisms. Further investigation into these epigenetic modifications may unveil novel exercise-based therapeutic strategies to enhance cardiovascular health.

A captive senile talapoin monkey (Miopithecus talapoin) developed sudden neurological signs and died within 24 h. Necropsy revealed an extensive infarct in the right hemisphere, from occipital to frontal lobe. Microscopy showed a thrombus, neuronal edema, and necrosis, and arteriosclerosis, characterizing an ischemic stroke.

Individuals with attention-deficit/hyperactivity disorder, their families and clinicians may report worsening symptoms despite compliant use of medication, suggesting potential tolerance, but evidence remains conflicting. Some studies have also suggested tachyphylaxis, or acute tolerance, though research is limited. We conducted the first systematic review of empirical studies focussing on tolerance/tachyphylaxis to attention-deficit/hyperactivity disorder medication to clarify their potential clinical relevance.

As registered on PROSPERO (CRD42024594759), we searched PubMed, OVID (including PsychInfo and MEDLINE) and Web of Knowledge up to 1 September, 2024, and assessed the risk of bias using National Institutes of Health quality assessment tools.

The identified 17 studies were either interventional or observational, and varied greatly in design and duration. Four investigated tachyphylaxis, nine tolerance to the subjective and behavioural effects, and four tolerance to cardiovascular effects. We found preliminary evidence of tachyphylaxis to the affective or behavioural effects of stimulants, as well as tolerance to the subjective effects of d-amphetamine, such as drug liking and excitation, in neurotypical volunteers in the short term. Conversely, there was little or no evidence for tolerance to the therapeutic or cardiovascular effects of attention-deficit/hyperactivity disorder medication in clinical settings in the longer term. Quality was rated as low in most studies because of small sample sizes and methodological limitations.

Overall, these results do not support the hypothesis that tolerance commonly develops to the therapeutic effects of attention-deficit/hyperactivity disorder medication, although robustly designed longitudinal studies are needed to provide more conclusive evidence. Clinicians may consider other potential explanations for reduced therapeutic effects over time, including natural fluctuations of symptoms, limited compliance, life events and co-occurrent mental health conditions.

Medical students have high needs for mental health care. Traditional models of campus-based health care have limitations in meeting medical students' unique needs, including hours of accessibility, diversity of practitioners, and geographic limitations in a distributed educational model. Internal surveys performed before and after a Liaison Committee on Medical Education accreditation survey showed that students had low rates of satisfaction with access to mental health services.

A working group was formed at the Drexel University College of Medicine in fall 2022 to analyze student feedback on access to mental health care 2 years before (2020 and 2022) and 1 year after (2024) 1 telehealth intervention. On the basis of the student feedback desiring after-hours care and diverse practitioners and within the context of a distributive medical education model, telehealth was considered a promising way to meet students' needs. On the basis of student priorities, a telehealth company with multiple service offerings (scheduled counseling, on-demand therapy available 24/7, psychiatry visits, and health coaching) was vetted and ultimately chosen to begin in the 2023 to 2024 academic year.

Students readily adopted the use of telehealth services for their mental health needs. Approximately 15 months after implementation, nearly half of medical students in this study are registered for the telehealth service. Internal surveys after widespread use of the mobile app for 8 months showed improvements in students' satisfaction with available mental health resources.

Telehealth mental health services can augment traditional, institutionally based practitioners. Moreover, students readily use telehealth services to meet their needs and perceive benefits from doing so. Next steps include evaluating whether students' engagement and satisfaction with telehealth services are sustained throughout medical school and reassessing the current fiscal model to ensure the service's long-term sustainability.

A fundamental pillar of science is the estimation of the effect size of associations. However, this task is sometimes difficult and error-prone. To facilitate this process, the R package metaConvert automatically calculates and flexibly converts multiple effect size measures. It applies more than 120 formulas to convert any relevant input data into Cohen's d, Hedges' g, mean difference, odds ratio, risk ratio, incidence rate ratio, correlation coefficient, Fisher's r-to-z transformed correlation coefficient, variability ratio, coefficient of variation ratio, or number needed to treat. Researchers unfamiliar with R can use this software through a browser-based graphical interface (https://metaconvert.org/). We hope this suite will help researchers in the life sciences and other disciplines estimate and convert effect sizes more easily and accurately.

Vesicular monoamine transporter 2 inhibitors (VMAT2-Is), valbenazine and deutetrabenazine, are the only FDA-approved medications for tardive dyskinesia (TD); tetrabenazine is used off-label. TD diagnosis and VMAT2-I use data remain limited. This study characterizes trends in TD diagnosis and VMAT2-I use among adults (aged 18 to 65 years) with mental health diagnoses receiving antipsychotics.

We analyzed 2017-2022 MarketScan data. TD and mental health diagnoses were identified using ICD-10 codes, and VMAT2-I use from prescription claims. Mental health diagnoses were hierarchically categorized as schizophrenia, bipolar disorder (BPD), major depressive disorder (MDD), or other. Descriptive analyses summarized trends, and multivariable logistic regression assessed predictors of VMAT2-I use.

Among a cohort of 729,262 adults, TD diagnosis increased from 0.45% (N=849) in 2017 to 0.57% (N=1194) in 2022. VMAT2-I use increased from 0.05% (N=100) to 0.22% (N=454). Predictors of VMAT2-I use included first-generation antipsychotic use versus second-generation use only [adjusted odds ratio (aOR): 2.06, 95% CI: 1.59-2.67], schizophrenia (aOR: 8.40, 95% CI: 6.57-10.74) or BPD (aOR: 3.18, 95% CI: 2.62-3.86), versus other mental health diagnoses, female versus male sex (aOR: 1.32, 95% CI: 1.14-1.51), age 51 to 65 versus age 18 to 34 years (aOR: 5.57, 95% CI: 4.63-6.71), and calendar year (aOR: 1.42 95% CI: 1.36-1.48). Among patients with TD, schizophrenia (aOR: 1.80; 95% CI: 1.26-2.57), BPD (aOR: 1.85; 95% CI: 1.39-2.46), and age [aOR: 3.55; 95% CI: 2.70-3.84 (51 to 65 vs. 18 to 34 y)] were predictors of VMAT2-I use.

TD remains underdiagnosed, with treatment rates low, highlighting the need for improved TD recognition and VMAT2-I access.

Bipolar disorder is a severe mental disorder affecting millions worldwide, necessitating comprehensive policies and interventions.

To provide assessment of global inequalities in the burden of bipolar disorder and their projected trajectories to 2050.

Global Burden of Disease 2021 data from 204 countries and territories were analyzed, stratified by age, gender, and Socio-demographic Index (SDI) quintiles. Age-standardized prevalence (ASPR), incidence (ASIR), and years lived with disability (ASR YLD) per 100,000 population were calculated. Inequalities were assessed using the slope index of inequality (SII) and concentration index (CI), and ARIMA models were applied to project trends to 2050.

From 1990 to 2021, global incidence of BD increased, while prevalence and years lived with disability (YLDs) remained relatively stable (ASPR: 453.7 [95% UI: 381.6-540.8] to 454.6 [95% UI: 377.9-545.8]). Females consistently had higher prevalence than males (474.2 vs. 435.0 per 100,000 in 2021). High-SDI regions reported the highest rates, with Australasia reaching 1110.8 (95% UI: 940.3-1305.9). The SII for incidence rose slightly (10.87-11.38), while the CI declined (0.096-0.012), indicating increasing absolute but decreasing relative inequalities. Projections suggest a rising global burden, with female prevalence remaining higher and incidence rates converging between genders (global ASIR: 33.8 per 100,000).

Global inequalities in bipolar disorder persist, disproportionately affecting females and high-SDI regions. Projected trends indicate an increasing burden with a narrowing gender gap in incidence, emphasizing the need for targeted interventions and further research on long-term impacts, including the effects of COVID-19.

While interest in the therapeutic and recreational use of hallucinogens has increased, national surveillance often reports use in aggregate, potentially masking shifting trends among pharmacologically distinct substances. This study assessed trends in specific hallucinogens from 2021 to 2023 and identified correlates of use, with particular attention to subgroup patterns in populations commonly prioritized for prevention and access-focused interventions.

Using nationally representative NSDUH data (2021-2023; ages ≥12), we estimated annual past-year prevalence of LSD, PCP, ecstasy (MDMA), ketamine, Salvia divinorum, and tryptamines (including DMT). We fit survey-weighted logistic regression models with year (continuous) to assess trends and pooled multivariable models to examine demographic correlates.

Although overall past-year hallucinogen use was stable (2.83 % [95 % CI: 2.52-3.14] in 2021; 2.82 % [2.52-3.12] in 2023), substance-specific trends diverged. LSD declined (aOR per year=0.83, 95 % CI: 0.75-0.93), from 0.88 % (0.72-1.04) in 2021-0.58 % (0.47-0.68) in 2023. Ketamine increased (aOR=1.11, 95 % CI: 1.02-1.21), from 1.61 % (1.42-1.80) to 1.91 % (1.67-2.16). Ecstasy/MDMA and tryptamines were stable, and PCP and Salvia remained rare. Use concentrated among young adults and males; adjusted models indicated higher odds among uninsured respondents and those below the federal poverty level.

Despite stable overall hallucinogen prevalence, significant increases were observed for ketamine alongside declines for LSD, suggesting a shifting landscape of hallucinogen use. Substance-specific monitoring may better inform screening, prevention, and harm-reduction efforts than aggregate hallucinogen indicators, especially as ketamine's medical availability expands and disparities in access to mental health treatment persist.

Sexually transmitted infections (STIs) are a major global health concern, with millions of new cases occurring annually, particularly among young adults. These infections can lead to serious health complications, including infertility and increased risk of HIV, and are compounded by social stigma and mental health challenges. There have been significant global increases in STI diagnoses in recent years. The objective of this systematic review is to synthesise evidence on the predictors of trends in gonorrhoea, chlamydia, syphilis, and HIV over the last ten years. We aim to provide insight into the multifaceted drivers of the recent increasing STI diagnosis rates.

We have developed a comprehensive search strategy that includes searching for relevant published literature and grey literature. We will include studies that contain evidence of longitudinal associations between changes in the incidence of diagnoses of four targeted STIs (i.e., gonorrhoea, chlamydia, syphilis, and HIV) during the last ten years. In addition, we will explore changes in sociodemographic and behavioural variables during the same time among representative samples of national populations. We will conduct a narrative analysis of the included studies.

The proposed synthesis plan is part of a larger research project that has been designed in response to the priorities of sexual health policymakers in Ireland. It will provide useful information regarding recent international trends in diagnoses of gonorrhoea, chlamydia, syphilis, and HIV, which will inform further efforts to understand the recent increases in STI diagnoses in Ireland. We acknowledge that it will be limited by publication bias, the biases affecting the included studies, a potential lack of data on important sub-populations, and restrictions related to testing availability across countries. Ultimately, trends in STI diagnoses are best understood through the design of comprehensive behavioural surveillance systems, which this review may usefully inform.