Biofluid proteins are promising transdiagnostic markers for delineating disease heterogeneity in psychosis. This study examined proteomic profiles in a transdiagnostic early psychosis sample to test the hypothesis that psychosis is associated with proteomic signatures of premature aging. We analyzed proteomic data from 85 individuals with early psychosis and 35 healthy controls from the Human Connectome Project for Early Psychosis (HCP-EP), using the Olink platform across four validated panels (Cardiometabolic, Inflammation, Cardiovascular II, and III). Our dual analytic strategy included: (1) calculating an index based on senescence-associated secretory phenotype (SASP) proteins to assess cellular aging, and (2) analyzing all 374 proteins using Gene Set Enrichment Analysis to identify whether predefined biological pathways are collectively enriched. We compared the SASP index and enriched pathways between groups and examined associations with sociodemographic, physical health, cognitive, psychological well-being, psychosocial functioning, symptom, and medication data. The SASP index was significantly elevated in the psychosis group. Pathway analyses revealed enrichment of two inflammation-related pathways in psychosis after multiple comparison correction: Cellular Response to Tumor Necrosis Factor and Monocyte Chemotaxis. The higher SASP index and the enriched inflammatory pathways were associated with increased body mass index (BMI) and reduced psychological well-being. Our findings are consistent with prior research linking psychosis to premature aging and an increased inflammation response. They also underscore the value of examining multiple biomarkers and biological pathways simultaneously and highlight the importance of conceptualizing psychosis as a whole-body condition. However, given the sample size, results should be considered preliminary. Larger, longitudinal studies are needed to track proteomic changes over time and assess the predictive value of these biomarkers for identifying vulnerable individuals and clinical outcomes.

First-episode psychosis (FEP) may result from a variety of secondary etiologies, making lumbar puncture (LP) for cerebrospinal fluid (CSF) investigations an important diagnostic consideration in this context. However, the lack of high-quality evidence on the prevalence of clinically-relevant CSF abnormalities hampers clinical consensus on when to pursue LP in FEP.

Determine a meta-analytic estimate of the prevalence of clinically-available CSF abnormalities in FEP.

Electronic databases Ovid MEDLINE, Embase, PsycINFO, and Web of Science were searched from inception to October 2024. References of included articles were also screened.

We included studies that performed LP on a cohort of FEP and reported results of clinically-available CSF analysis, enabling prevalence-estimates of abnormalities.

Data was extracted following PRISMA and MOOSE guidelines. Pooled prevalences were calculated by random-effects models. Moderators were tested using meta-regression analysis, and heterogeneity assessed by I² index.

Prevalence of clinically-available CSF abnormalities, focusing on clinically-relevant markers and number needed to assess (NNA).

Thirty-seven papers comprising 3,330 FEP patients who underwent LP were included, allowing calculation of prevalence estimates for 14 clinically-available CSF abnormalities. Of clinically-relevant abnormalities, the prevalence of CSF-restricted oligoclonal bands (OCB2) was 7.1% (95% CI 3.3-12.0, NNA 14), pleocytosis was 3.2% (95% CI 2.1-4.4, NNA 31) and anti-NMDAR antibodies was 2.3% (95% CI 0.1-6.4, NNA 43). Subgroup analysis showed that anti-NMDAR antibodies were mainly detected in studies that selected patients with high suspicion of secondary causes and were low in studies which excluded patients with a high index of suspicion of a secondary cause, based on clinical and ancillary testing. OCB2 was detected at appreciable prevalence in both the high-suspicion and low-suspicion subgroups; a high-suspicion subgroup estimate could not be derived for pleocytosis.

The most common clinically-relevant CSF abnormality, CSF-restricted oligoclonal bands, had a pooled prevalence of 7.1%, similar to the reported prevalence of a clinically-relevant abnormality on brain MRI. The probability of detecting an abnormality was higher among patients with a high index of suspicion for a secondary cause, and this was most marked for anti-NMDAR antibodies. However, few included studies reported healthy controls, and none explicitly tested whether presence of these abnormalities alter treatment response or outcomes, so the specificity and treatment implications of these findings for psychosis will benefit from future research.

Impulsivity is frequently examined in relation to adolescent non-suicidal self-injury (NSSI), yet the strength of this association remains unclear because findings vary across studies. This study quantified the association and examined potential sources of heterogeneity.

A three-level random-effects meta-analysis of 37 studies (N = 69,572) accounted for hierarchical dependencies among effect sizes. Potential moderators included assessment modality (self-report scale, semi-structured interview, or neurocognitive task), specific measurement instrument, impulsivity domain, sample source, and psychiatric comorbidity.

Impulsivity was significantly associated with NSSI severity (d = 0.46) and was higher among adolescents with NSSI than controls (d = 0.37). Effect sizes varied significantly across specific impulsivity measurement instruments after FDR correction. In contrast, the omnibus test of broader assessment modalities was nonsignificant. Separately, self-report scales yielded a significant pooled estimate (d = 0.48), whereas neurocognitive tasks yielded a small and nonsignificant estimate (d = 0.11); these subgroup estimates do not establish modality differences. Neither sample source nor psychiatric comorbidity significantly moderated the association. Trait and symptom-level impulsivity yielded significant pooled estimates (d = 0.48 and 0.40, respectively). Negative urgency showed a relatively large pooled estimate (d = 0.60) based on only four effect sizes.

Several moderator estimates were based on few effect sizes, limiting their precision.

Impulsivity is an important but nonspecific correlate of adolescent NSSI. Heterogeneity was more consistently associated with specific measurement instruments, highlighting measurement specificity when interpreting the impulsivity-NSSI literature. Self-report and neurocognitive measures may capture partly different aspects of impulsivity, warranting further multimethod research.

Transcranial alternating current stimulation (tACS) provides promising evidence as a technology to modulate brain oscillations. Individualized brain oscillation measures from magnetoencephalography (MEG) or electroencephalography (EEG) (M/EEG) can optimize frequency, location (montage), and timing of tACS. This systematic review aims to comprehensively characterize the parameter space and outcomes of M/EEG-informed personalized tACS interventions.

We conducted a systematic review of the literature up to January 2024, per PRISMA guidelines. The pre-registered search strategy combined terms related to M/EEG and tACS. Any study that utilized M/EEG-informed individualized tACS intervention was included, and relevant variables were extracted.

Seventy-eight publications comprising 143 distinct experiments were identified, including 128 EEG-informed and 15 MEG-informed studies. Frequency-based individualization was predominant (93%), followed by timing-based (4.2%; stimulation onset or phase) and montage-based (2.8%) methods. The most frequently individualized frequency band was alpha (69.2%), followed by theta (15.4%), gamma (5.6%), beta (4.9%), delta (2.1%), and dual-frequency protocols (2.8%). Outcome measures most commonly assessed physiological changes (28.7%) and cognitive functions, particularly perception (18.9%) and memory and learning (17.5%). 77.9% of sham-controlled experiments reported significant positive outcomes, compared to 56.2% of those with active control.

Over the past decade, personalized M/EEG informed tACS trials provide growing evidence for effectiveness of this technology in engaging brain oscillations. This systematic review highlights key methodological parameter space in this technology and its outcomes. It also provides a roadmap for future trials with rigorous active control arms to optimize engaging brain oscillations and impacting cognitive functions and clinical outcomes.

Work-related stress is a growing concern among healthcare professionals, with potential adverse effects on psychological well-being and quality of care. Midwifery practice, characterised by high emotional demands and frequent exposure to critical events, may increase vulnerability to occupational stress and psychological distress. This study aimed to evaluate perceived stress and psychological well-being among italian midwives and to compare hospital-based and community-based settings. We conducted a cross-sectional multicentric observational study on 175 midwives (140 hospital-based; 35 community-based). Perceived stress was assessed using the 10-item Perceived Stress Scale (PSS-10), and psychological well-being was evaluated with the Psychological General Well-Being Index (PGWBI). Hospital-based midwives reported significantly higher perceived stress than community-based midwives. A significant negative correlation between perceived stress and psychological well-being was found in both groups, with a stronger association observed in the hospital setting. The work setting significantly influences midwives' mental health, with hospital practice associated with higher stress and lower psychological well-being. These findings emphasize the urgent need for tailored organizational support, structural interventions, and policy initiatives to safeguard midwives' psychological health and enhance workforce retention.

Dietary inflammatory load, quantified using the Dietary Inflammatory Index (DII), reflects pro-inflammatory dietary patterns that may contribute to impaired bone health. However, population-based evidence regarding the association between dietary inflammatory potential and bone mineral density (BMD) among adults with type 2 diabetes (T2D) remains limited, particularly regarding potential sex-specific differences. This cross-sectional study assessed the association between the DII and low BMD (osteopenia or osteoporosis) in adults with T2D. Data from the 2007 to 2010, 2013 to 2014, and 2017 to 2018 cycles of the National Health and Nutrition Examination Survey were analyzed. DII scores were computed from 22 dietary components; participants lacking BMD or DII data were excluded. Low BMD was defined from femoral neck and lumbar spine BMD, with osteoporosis and osteopenia both classified into a single category ("low BMD"). Weighted logistic regression was used to examine the relationship between DII score and low BMD overall and according to sex, adjusted for age, race/ethnicity, body mass index, socioeconomic variables, and clinical confounders. Subgroup analyses, interaction tests, and sex-stratified correlation analyses were performed for consistency. Data from 1768 adults with T2D, of whom 798 had low BMD, were included. Higher DII scores were significantly associated with an increased risk for low BMD in women (femoral neck: odds ratio = 2.575, 95% confidence interval = 1.484-4.468, P = .001; lumbar spine: odds ratio = 1.864, 95% confidence interval = 1.111-3.129, P = .018), with no significant association observed in men. A significant interaction according to sex was detected (P for interaction = .02); however, no interactions were found for age or body mass index. Findings suggested that an elevated DII is independently associated with low BMD in women with T2D. Clinically, sex-specific, anti-inflammatory dietary strategies may help mitigate the risk for low BMD in this population.

The relationship between different autoimmune diseases (ADs) and pancreatitis has been reported in epidemiological studies. This study systematically investigated the causal effects of ADs factors on pancreatitis using Mendelian randomization (MR). We selected 17 common ADs as exposures from the largest genome-wide association study dataset in Europe. The outcome variables included acute pancreatitis (AP), chronic pancreatitis (CP), alcohol-induced acute pancreatitis, and alcohol-induced chronic pancreatitis. A variety of analytical methods were used to comprehensively evaluate the causal relationship between ADs and various types of pancreatitis, with sensitivity analyses, including Cochran's Q test and MR-Egger intercept test performed to verify the reliability of the results. Finally, a reverse MR analysis was performed to evaluate the possibility of reverse causation. Genetically predicted type 1 diabetes (OR = 1.032, 95% CI = 1.008-1.056, P = .0086) and ulcerative colitis (OR = 1.065, 95% CI = 1.012-1.121, P = .0151) were associated with an increased risk of AP. primary sclerosing cholangitis (OR = 1.080, 95% CI = 1.013-1.153, P = .0194) increased the risk of CP. Reverse MR analysis suggested a potential protective causal association between alcohol-induced acute pancreatitis and hashimoto's thyroiditis (OR = 0.962, 95% CI = 0.936-0.989, P = .0056), although this finding should be regarded as suggestive because it did not remain statistically significant after Bonferroni correction. Sensitivity analysis did not detect horizontal pleiotropy or heterogeneity. Genetic evidence supports a causal link between type 1 diabetes, ulcerative colitis , and AP, as well as between primary sclerosing cholangitis and CP. This analysis provides new insights into ADs as risk factors for pancreatitis, but further experimental research is needed to explore the potential causal relationships between these factors.

Thyroid dysfunction and diabetes mellitus (DM) are two common endocrine disorders that share overlapping metabolic pathways. While several studies have explored the association between thyroid function and DM, findings have been inconsistent. Specifically, both elevated and suppressed thyroid-stimulating hormone (TSH) have been variably reported as risk or protective factors for diabetes, and the contribution of thyroid autoimmunity (thyroid peroxides antibody, TPOAb) to diabetes risk remains particularly contested across study populations. This study aimed to evaluate the relationship between thyroid function markers-TSH, free thyroxine (free T4), and TPOAb - and the presence of diabetes in Korean adults. This cross-sectional study analyzed data from 4910 adults aged 19 years or older who participated in the Korea National Health and Nutrition Examination Survey (KNHANES VI) from 2013 to 2015. Serum levels of TSH, free T4, and TPOAb were measured, and DM was defined based on fasting glucose levels, use of antidiabetic medication, or self-reported diagnosis. As KNHANES does not classify diabetes by etiological subtype, the DM group predominantly reflects type 2 diabetes, consistent with its overwhelming predominance among Korean adults; type 1 diabetes could not be separately identified. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for diabetes across thyroid function categories, with subgroup analyses by age and sex. High TSH levels were significantly associated with an increased risk of diabetes (OR = 2.82; 95% CI: 1.26-6.32), especially in men under 65 years (OR = 5.10; 95% CI: 1.65-15.77). Low TSH levels were inversely associated with diabetes risk (OR = 0.35; 95% CI: 0.15-0.86). Low free T4 levels were also linked to an increased risk (OR = 2.08; 95% CI: 1.16-3.75), particularly in younger men. TPOAb positivity showed no significant overall association with diabetes, although a potential protective trend was observed in older men. Altered thyroid function, especially high TSH and low free T4 levels, is associated with increased diabetes risk in Korean adults. These findings suggest the clinical utility of thyroid function screening in diabetes risk assessment and highlight the need for further longitudinal research.

Canine diabetes mellitus (DM) is a relatively common endocrinopathy, and it requires dedication and commitment from an owner to care for a diabetic pet. This study aimed to describe treatment and monitoring habits, perceived owner and veterinary concerns when treating and monitoring a diabetic dog, as well as triggers for and risk of euthanasia in diabetic dogs among Norwegian veterinarians. A questionnaire was designed and made available online.

A total of 125 veterinarians completed the survey. According to the data collected, the cumulative incidence risk for treatment initiation was 71.6% (95% CI 63.2, 80.6), suggesting that the respondents started most of the diabetic dogs seen in their practice on treatment. The majority of the respondents reported that all female entire diabetic dogs were neutered near the time of diagnosis. Main veterinary treatment concerns identified were difficulties in achieving rapid and adequate control. Main respondent-perceived owner concerns were cost and injecting their diabetic dog. About 60% of respondents had never used a continuous glucose monitor. Of respondents having used such monitors, half had experienced owners changing the insulin dose themselves, without consulting a veterinarian. Nearly one third of the veterinarians recalled that issues related to monitoring contributed directly to euthanasia of a diabetic dog in their care. The estimated one month and one year cumulative risk of euthanasia in dogs started on insulin therapy found in our study were 11.5% (95% CI 8.3, 14.6) and 26.9% (95% CI 22.0, 31.8), respectively. In our study population, respondents working in large cities were more likely to report a high probability of starting treatment than respondents in small cities and rural areas. Respondents in small cities and rural areas were also more likely to report medium and high risk of euthanasia compared to respondents in large cities, respectively. Veterinary-perceived owner triggers for euthanasia were dogs' quality of life, monitoring, and owners' lifestyle changes. For the respondents themselves, comorbidities were the leading factor reported for recommending euthanasia.

This questionnaire-based study describes perceived treatment concerns, and reasons for and estimates of euthanasia risk in dogs with DM, based on the experiences of veterinary practitioners working in Norway. The results highlight important aspects of the treatment and monitoring of dogs with DM, as well as triggers for euthanasia. Further investigations into the aspects identified could be useful to improve the overall care for diabetic dogs.

Gut microbial dysbiosis has been implicated in metabolic dysfunction-associated steatotic liver disease (MASLD) and diabetes, but the metabolic effects of candidate probiotic strains across this disease continuum remain incompletely understood. Based on the validation of disease-associated microbial patterns in a clinical cohort, Lactobacillus acidophilus as selected as a candidate strain, and its effects were systematically investigated across multiple complementary models, including Western diet, fructose-palmitate-cholesterol diet, high-fat diet, and leptin-deficient ob/ob mice. L. acidophilus supplementation attenuated hepatic steatosis and inflammatory injury in multiple complementary models and improved glucose tolerance in ob/ob mice. These effects were accompanied by reduced hepatic expression of pro-inflammatory cytokines, changes in AMPK-associated signaling, decreased expression of lipogenic (Srebf1 and Acc) and gluconeogenic (Pepck and G6pc) genes, and increased Ppara expression, suggesting coordinated regulation of glucose and lipid metabolism. Transcriptomic profiling further indicated that L. acidophilus influenced broader metabolic networks, including altered expression of Lpin1 and enrichment of pathways related to nutrient sensing and metabolic regulation. In addition, L. acidophilus supplementation altered gut microbial community structure in mouse models, while human cohort analyzes revealed context-dependent microbial patterns involving Lactobacillus, Akkermansia, and butyrate-producing Firmicutes across metabolic disease states. Collectively, these findings suggest that L. acidophilus may improve metabolic dysfunction through coordinated hepatic metabolic regulation and gut microbial modulation, supporting its potential as a probiotic candidate for MASLD and diabetes-associated metabolic disease.