Stress is associated with the onset of various neurological disorders, such as depression, post-traumatic stress disorder, and anxiety. Although extensively studied, the metabolic changes triggered in response to stress remain unclear. We conducted a descriptive observational study on acute stress responses in university students, combining psychometric, biochemical, and untargeted metabolomic analyses, along with machine learning predictions. In this study, forty participants underwent both relaxation and stress induction through a modified Trier Social Stress Test. Validated psychometric tests confirmed proper induction of both states. Although most biomarkers show significant changes under acute stress state, the machine learning predictive model identified salivary α-amylase and the State-Trait Anxiety Inventory-state (STAI-s) as potential stress markers. Additionally, several metabolic pathways, including steroid hormone biosynthesis, glycerophospholipid metabolism, linoleic acid metabolism, tyrosine metabolism, and aminoacyl-tRNA biosynthesis, presented alterations under acute mental stress. Our findings highlight the impact of acute mental stress on multiple metabolic pathways directly implicated in stress-related disorders. These findings advance the understanding of the adverse effects systematically associated with stress and provide evidence supporting the potential role of salivary α-amylase and STAI-s as stress markers. Yet, they should be regarded as important hypothesis generators. However, further studies are needed for final validation.

Genome wide association studies of schizophrenia reveal a complex polygenic risk architecture comprised of hundreds of risk variants; most are common in the population, non-coding, and act by genetically regulating the expression of one or more gene targets ("eGenes"). It remains unclear how the myriad genetic variants that are predicted to confer individually small effects combine to yield substantial clinical impacts in aggregate. Here, we demonstrate that convergence (i.e., the shared downstream transcriptomic changes with a common direction of effect), resulting from one-at-a-time perturbation of schizophrenia eGenes, influences the outcome when eGenes are manipulated in combination. In total, we apply pooled and arrayed CRISPR approaches to target 21 schizophrenia eGenes in human induced pluripotent stem cell-derived glutamatergic neurons, finding that functionally similar eGenes yield stronger and more specific convergent effects. Points of convergence constrain additive relationships between polygenic risk loci: consistent with a liability threshold model, combinatorial perturbations of these same schizophrenia eGenes reveal that pathway-level convergence predicts when observed effects will fail to sum to levels predicted by an additive model. Targeting points of convergence as novel therapeutic targets may prove more efficacious than individually reversing the effects of multiple risk loci.

Accumulating evidence suggests that oxidative stress (OS) contributes to the onset and progression of schizophrenia (SCZ). However, the pattern of OS alterations in first-episode, drug-naïve patients and their associations with clinical and cognitive features remain unclear. In this study, 98 first-episode SCZ patients and 96 matched healthy controls were recruited. Plasma levels of total antioxidant capacity (TAC), malondialdehyde (MDA), lipid peroxidation (LPO), NADPH oxidase (NOX), glutathione S-transferase (GST), and glutathione reductase (GR) were measured. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), and cognitive performance was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Compared with controls, patients exhibited significantly higher TAC, MDA, and LPO levels but lower NOX levels, while GST and GR showed no significant differences. RBANS total and subscale scores were markedly reduced in patients, indicating generalized cognitive impairment. Correlation analyses revealed that GST was positively correlated with total PANSS scores, GR with negative symptoms, and LPO with overall cognition, attention, and delayed recall. These findings indicate that first-episode SCZ patients display an imbalance between oxidative and antioxidant systems, and specific OS markers are linked to symptom severity and cognitive dysfunction. OS alterations may serve as potential early biomarkers and therapeutic targets for schizophrenia.

As critical care medical education advances within a competency-based framework, effective assessment strategies are essential to ensure trainees acquire the necessary skills for high-stakes situations. Despite growing interest, assessment practices remain inconsistent, with significant variations in their application, although conceptual and technological innovations support this process. This scoping review aimed to map the literature on innovation in assessment within graduate and fellowship critical care medical education.

Following the Joanna Briggs Institute framework and PRISMA-ScR, a search of four databases (PubMed, Scopus, Web of Science, and LILACS) was conducted for articles published from January 2014 to June 2025.

Sixty-eight peer-reviewed articles were analyzed across four domains: assessment methods and tools, competency frameworks, innovation and technology, and ethics in assessment. Assessment in critical care is shifting toward a structured, multimodal, formative, and longitudinal model. Commonly used tools include workplace-based assessments and simulations. Milestones and entrustable professional activities are increasingly used to support entrustment decisions and track progress. Technology-enhanced strategies, including high-fidelity simulations, mobile apps, and artificial intelligence, improve feedback quality and real-time assessment. Ethical challenges, especially rater bias, underassessment of professionalism, and inequities, remain persistent concerns, highlighting the importance of fairness and transparency in evaluation.

Graduate critical care assessment is advancing towards a programmatic, multidimensional model that integrates clinical and professional competencies. Emerging frameworks and digital platforms support more equitable, formative, and trustworthy evaluations. Future efforts should focus on standardization, bias, and ethical practices throughout the assessment continuum.

Sickle cell disease (SCD) is a devastating genetic hematologic disorder affecting approximately 80,000 African Americans. Beyond the well-characterized vaso-occlusive pain crises, patients experience significant psychological morbidity, including kinesiophobia (fear of movement) and depression, which profoundly impact quality of life and functional outcomes. This comprehensive review synthesizes current evidence on the relationship between kinesiophobia and depression in SCD patients, with particular attention to gender differences, underlying pathophysiological mechanisms, and clinical implications for multidisciplinary care. We conducted a systematic examination of the literature on kinesiophobia, depression, and psychosocial factors in SCD, incorporating data from multiple cohort studies totaling 247 adult African American patients. Assessment instruments included the Tampa Scale for Kinesiophobia (TSK), Beck Depression Inventory (BDI), and Center for Epidemiologic Studies Depression Scale-Revised (CESD-r). Kinesiophobia prevalence in SCD patients (mean TSK score = 30.48) was comparable to patients with chronic back pain and fibromyalgia. Significant gender differences emerged, with women demonstrating strong positive correlations between kinesiophobia and depression (BDI r = 0.31, p = 0.045; CESD-r = 0.54, p = 0.009), while no significant relationships were observed in men (BDI r = 0.24, p > 0.05; CESD-r = 0.13, p > 0.05). The relationship appears mediated by psychomotor retardation, somatization, and pain catastrophizing behaviors. Fear of movement represents a clinically significant but underrecognized contributor to depressive symptomatology in women with SCD. These findings highlight the need for gender-specific psychological interventions and integrated care approaches that address both physical and mental health components of this complex genetic disorder.

Vascular inflammation is a key aspect of plaque vulnerability. Cross-sectional studies suggest that increased carotid perivascular adipose tissue (PVAT) attenuation on CTA, which is thought to reflect vascular inflammation, is associated with stroke.

We investigated the predictive value of carotid PVAT attenuation for ischemic stroke and TIA in a longitudinal study of symptomatic patients with carotid plaque.

We included patients with recent TIA or stroke and a ≥2 ​mm carotid plaque with <70 ​% stenosis who underwent CTA and MRI and were clinically followed-up for 5 years. Mean PVAT attenuation (-190 to -30 Hounsfield Units (HU)) was quantified within a radial distance from the outer vessel wall equal to the vessel diameter on the CTA slice containing the thickest plaque. Cox proportional hazards models assessed associations with ipsilateral stroke and TIA risk. Predictive value was compared with intraplaque hemorrhage (IPH) and the European Carotid Surgery Trial (ECST) score using the C-index.

Among 159 patients (74 ​% men; 69 (63-73) years), 11 ischemic strokes and 10 TIAs occurred over 5.1 (3.1-5.6) years. Increased PVAT attenuation was independently associated with ischemic stroke or TIA (HR: 3.21 per 10 HU increase, 95%CI:1.70-6.05) and ischemic stroke alone (HR: 5.60, 95%CI:1.93-16.31). PVAT attenuation alone predicted ischemic stroke or TIA (C-index: 0.71, 95%CI:0.70-0.73) and ischemic stroke alone (C-index: 0.78, 95%CI:0.63-0.93). Adding PVAT attenuation improved prediction beyond IPH (C-index: 0.66-0.68 to 0.81-0.84) and the ECST score (0.64-0.75 to 0.75-0.86, respectively).

In symptomatic patients, PVAT attenuation is an independent marker for ischemic stroke and TIA risk.

This systematic review and meta-analysis examine the association between environmental air pollution and the risk of depression and anxiety. We systematically searched studies published up to March 2025 and included 81 eligible studies focusing on particulate matter (PM_2.5, PM₁₀), nitrogen dioxide (NO₂), and black carbon (BC). Random-effects meta-analyses were performed to calculate pooled relative risks for short-term (<30 days) and long-term (≥30 days) exposures. We assessed study heterogeneity, publication bias, risk of bias, and evidence quality. Findings reveal consistent associations between long- and short-term exposure to air pollution and increased depression and anxiety risk. Long-term exposure to all pollutants was positively associated with both outcomes, with PM_2.5 showing the most consistent association with anxiety and PM_2.5 and BC yielding the largest risks for depression. Short-term exposure to PM_2.5, PM₁₀ and NO₂ also showed small but significant associations. Although high heterogeneity, publication bias, and risk of bias reduced evidence certainty-particularly for BC-overall patterns were robust across pollutants and analytical approaches. These findings indicate that air pollution is a potentially modifiable environmental risk factor for common mental health disorders, warranting further high-quality longitudinal research.

Thiamine (vitamin B1) status might play a role in cognition and mental health. Recent research suggests that there are ethnic differences in thiamine status. We aimed to test the hypothesis that black individuals have a higher risk of thiamine deficiency than white individuals, based on the erythrocyte transketolase activity coefficient (ETKAC), and assess differences in thiamine intake, using nutritional survey data METHODS: We used the published data of the UK's National Diet and Nutrition Survey Rolling programme (2008-2019) and examined differences in the ETKAC between ethnicities and risk of thiamine deficiency (ETKAC > 1.25). We also used dietary data to determine differences in thiamine intake between ethnic groups.

Within the NDNS 2008-2019 ETKAC measurements were available for 5657 participants (5170 white, 92 black, 228 Asian, 93 mixed and 74 other ethnic groups). The median ETKAC of black participants was higher (1.15 (0.08) median (IQR)) than white (1.10 (0.07)) or Asian (1.12 (0.08)), indicating poorer thiamine status among black participants. The prevalence of thiamine deficiency was 5% among black participants, being greater than among white (0.5%) and Asian participants (1.3%). This was independent of age, sex, body composition and socio-economic status. Dietary assessment data suggested that thiamine intake was on average lower for black participants compared to white or Asian participants Including dietary intake into the model was not sufficient to correct for the ethnic difference in thiamine status.

This study suggests that there are ethnic differences in thiamine status that cannot be readily explained by intake alone.

Although researchers have called for participatory, equitable, and decolonial global implementation research to be conducted, practical examples on how to do so are scarce, particularly in partnership with historically marginalised groups. In this Viewpoint, we share four recommendations on how to instil systems thinking principles into global implementation research to make it more participatory and equitable. Our recommendations centre around co-learning with community partners to gain a deep understanding of their preferences and the system, to then co-creating interventions and implementation strategies that consider structural drivers of health and centre around Indigenous knowledges and practices. For each recommendation, we contrast the traditional implementation science approach with our participatory systems thinking approach. We also suggest eight phases inspired by systems thinking principles and tools that researchers can follow to align with our recommendations. We share practical examples emerging from our experiences collaborating with policy makers and Maya Indigenous community partners with lived mental health experience in co-creating mental health interventions in rural Guatemala. Drawing from our team's discussions, we reflect on the ways in which our participatory systems thinking approach has brought us closer to conducting equitable implementation research. We also reflect on how historical and structural determinants of social inequities permeate our efforts to ensure research relevance, participation, and trust among partners.

Lassa virus (LASV) is a persistent threat to public health in west Africa and beyond. LASV is endemic in west Africa and each year it is responsible for an estimated 2·7 million infections, 23 700 hospitalisations, and 5000 deaths. With over 32 reported cases of Lassa fever imported into non-endemic countries-one-third of which were fatal-the importance of enhanced detection and management of Lassa fever extends beyond west Africa.

The prevalence, pathogenesis, and persistence (PREPARE) study was a prospective cohort study among patients admitted to two hospitals in a hyperendemic area of Liberia. Any patients aged 5 years or older with a febrile illness were eligible to enrol and be tested for Lassa fever. The study aimed to measure the prevalence of LASV infection and assess the signs and symptoms, LASV viral replication kinetics, and LASV-specific IgM and IgG responses longitudinally among adults and children with laboratory-confirmed Lassa fever.

From July 10, 2018, to Aug 12, 2024, a total of 435 participants were enrolled, including 362 admitted with a febrile illness and 73 who were directly admitted with clinical suspicion for Lassa fever. Lassa fever was diagnosed by plasma LASV RT-PCR in 41 (11%) of 362 febrile participants and 47 (64%) of 73 participants directly admitted with suspected Lassa fever, resulting in a total of 88 cases of confirmed Lassa fever. At entry, anorexia (71 [81%] of 88 vs 178 [51%] of 347), severe fatigue or weakness (63 [72%] vs 178 [51%]), and nausea or vomiting (39 [44%] vs 95 [27%]) were more likely to be reported by participants with Lassa fever than by participants who tested LASV RNA negative. Among the participants with Lassa fever, 11 (13%) of 88 died after admission. Mental status changes, seizures, acute kidney failure, hyperkalaemia, and metabolic acidosis were more frequent in patients with Lassa fever who died than in patients who survived. Median cycle threshold values at study entry for glycoprotein complex gene (GPC) or polymerase gene (L) were lower in those who died (GPC cycle threshold 22·4 [IQR 20·0-27·9]; L cycle threshold 21·7 [19·0-27·7]) than in those who survived (GPC cycle threshold 31·5 [28·0-33·9]; L cycle threshold 32·3 [28·0-33·9]). Among the 70 participants with Lassa fever who consented to longitudinal follow-up through their hospitalisation, seven died and these participants tended to have lower cycle threshold values and lower IgM and IgG LASV responses compared with survivors.

In a region of Liberia where it is endemic, Lassa fever is a prevalent cause of morbidity and mortality. Several symptoms were more likely in those with Lassa fever but overlap with those caused by other common infectious diseases. Compared with survivors, those who died during hospitalisation for Lassa fever tended to have evidence of organ dysfunction along with higher viral loads at study entry and during follow-up and lower antibody levels during their illness, suggesting a muted humoral immune response might be a factor in the development of severe Lassa fever.

US National Institute of Allergy and Infectious Diseases and National Institutes of Health.