Treatment-resistant depression (TRD) is a heterogeneous condition in which symptoms such as anhedonia, rumination, and anxiety contribute to persistent disability. Esketamine nasal spray (ESK-NS), accelerated repetitive transcranial magnetic stimulation (arTMS), and adjunctive brexpiprazole represent novel therapeutic options with distinct mechanisms, though their domain-specific effects in real-world settings remain unclear.

To compare short-term changes in depressive severity across ESK-NS, arTMS, and brexpiprazole, and to explore treatment-related effects on anhedonia, rumination, anxiety, and item-level depressive symptoms.

One hundred and one individuals with TRD were enrolled in a prospective, naturalistic, three-arm study and treated with ESK-NS, arTMS (accelerated left DLPFC protocol), or brexpiprazole augmentation (1-2 mg/day). Assessments were conducted at baseline and after one month.

All treatments produced significant reductions in overall depressive severity and anhedonia. Rumination showed a significant time-by-treatment interaction, with greater improvement under brexpiprazole. Item-level analyses suggested partially distinct profiles, with brexpiprazole preferentially improving pessimistic and ruminative symptoms, ESK-NS enhancing affective responsiveness and cognitive symptoms, and both ESK-NS and arTMS contributing to anxiolysis.

In routine clinical practice, ESK-NS, arTMS, and brexpiprazole were associated with short-term improvement in TRD, with exploratory signals of partially distinct symptom-domain profiles. These findings support the value of dimensional assessment in TRD and warrant confirmation in randomized studies with longer follow-up.

Ecological momentary interventions (EMIs) can deliver coping skills in real time. Experiential avoidance (EA), the tendency to evade distressing internal experiences, is a transdiagnostic process linked to emotional disorders and suicide risk that may influence responsiveness to momentary interventions. This study examined whether baseline EA moderated changes in momentary affect during a four-week Cognitive Behavioral Therapy (CBT)-based EMI among adults recently discharged from psychiatric hospitalization.

Adults hospitalized for emotional difficulties and/or suicide risk (N = 76) completed up to three sessions of CBT skills while hospitalized or shortly after discharge via telehealth, followed by a 28-day EMI protocol prompting skill use via smart phone app. The Brief Experiential Avoidance Questionnaire measured EA. Positive and negative affect were assessed before and after each EMI prompt.

EA significantly moderated changes in positive and negative affect. Individuals with high EA showed greater increases in positive affect and greater decreases in negative affect following skill practice. Effects were significant across all levels of EA for negative affect but only at average and high EA levels for positive affect. Sensitivity analyses suggested that all-in-person participation and calendar time partially accounted for EA-related differences in negative affect.

There is preliminary evidence that CBT-based interventions may be associated with greater within-episode improvements in affect among individuals high in experiential avoidance following psychiatric hospitalization. Targeting avoidance-related processes via interventions that include digital components may offer preliminary affective benefits for high-risk clinical populations.

The Shugan Tongbian Decoction (SGTBD), a Traditional Chinese Medicine (TCM), has demonstrated potential efficacy in alleviating constipation with anxiety and depression; however, its pharmacological action on functional constipation (FC) with anxiety and depression has received little attention.

FC is increasing, and its course is positively correlated with emotional disorders, which affect the quality of life of patients. We studied brain and intestine protective effects of SGTBD and explored its underlying molecular mechanisms using network pharmacology analyses and experimental validation.

Network pharmacology analyses were performed. SGTBD composition was determined using analytical methods, and its main compounds were identified using high-performance liquid chromatography coupled with mass spectrometry (HPLC- MS). A rat model of FC with anxiety and depression was established using compound diphenoxylate combined with chronic unpredictable mild stress (CUMS) to evaluate SGTBD effects on constipation and behavioral indicators and pathological changes [hematoxylin and eosin (HE), alcian blue stain, periodic acid schiff (AB-PAS) and Nissl staining]. Neurotransmitter testing was performed using an enzyme linked immunosorbent assay (ELISA) for 5-HT. Mitochondrial damage was evaluated using western blotting (WB) and transmission electron microscopy. The impact of SGTBD on the Wnt/retromer pathway was evaluated using WB and quantitative real-time polymerase chain reaction (qRT-PCR).

SGTBD may have pharmacological effects, including the regulation of neurodevelopment and oxidative stress-induced cell apoptosis. SGTBD significantly improved behavioral indicators, reduced constipation, and mitigated pathological damage. It inhibited mitochondrial unfolded protein response (UPR^mt) and enhanced neurotransmitter. qRT-PCR, Transmission electron microscopy (TEM), and WB results revealed that SGTBD could inhibit mitochondrial damage by repairing mitochondrial structures, with the Wnt/Retromer signaling pathway playing a key role in this process.

SGTBD regulates the balance between brain and gut UPR^mt. It reduces mitochondrial damage and is associated with restoring the levels of the Wnt/Retromer pathway. This improved the mitochondrial structures of the brain-gut axis, providing multifaceted protective effects in FC rats with anxiety and depression. This study provides a new perspective on the development of protective measures and the prevention of constipation in patients with emotional disorders and diseases in daily life.

Major depressive disorder (MDD) is characterized by interacting neuro-immune, metabolic, and oxidative stress pathways. Here, we examine the interactions between the acute phase (AP) response and serum lipids in Chinese MDD patients.

This case-control study assessed serum lipids and the AP response in 125 MDD patients and 40 healthy controls (HC), while controlling for metabolic confounders, including metabolic syndrome.

We found an impaired lipid profile in MDD, characterized by reduced levels of high-density lipoprotein cholesterol (HDL), apolipoprotein (Apo) A1, chloromethyl phenylacetate (CMPA)ase activity, a reverse cholesterol transport (RCT) index, and increased ApoB/ApoA1 index. MDD was characterized by an AP response as conceptualized by lower serum albumin and transferrin and increased monomeric C-reactive protein (mCRP). The AP response was significantly and inversely associated with total cholesterol, HDL, low-density lipoprotein cholesterol, ApoA1, ApoB, lecithin cholesterol acyltransferase, CMPAase activity, and RCT index. After adjusting for the AP response, MDD diagnosis maintained significant independent associations with lower HDL-C, ApoA1, RCT, and higher ApoB/ApoA1 ratio. Multivariate (logistic) regression analyses confirmed that these lipid-inflammatory alterations strongly predict MDD diagnosis and clinical symptom severity. We found that around 81.5% of the MDD patients showed metabolic-inflammatory aberrations with a specificity of 82.1% and an area under the receiver operating characteristic (ROC) curve of 0.873. Lower ApoA1 emerged as a particularly robust protective biomarker, showing significant inverse relationships with affective and chronic fatigue severity scores.

These findings illuminate the complex interplay between a smoldering inflammatory response and lipid metabolism in many patients with MDD.

Hypophosphatasia (HPP) is the rare inborn-error-of-metabolism that features impaired mineralization of the skeleton and teeth due to a deactivating mutation or mutations of the gene ALPL which encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). We report 17-year follow-up of twin sisters and a brother referred in middle-age for painful proximal femoral "stress fractures" and then diagnosed with HPP. They reported generalized muscle and bone pain, metatarsal fractures, arthropathy and, since childhood, tooth loss. Their concordant findings were explained by compound heterozygosity in ALPL for a rare maternal missense mutation (c.1403C > T, p.Ala468Val) in exon 12, together with a novel presumably paternal change (c.863-14G > A) predicting a cryptic mRNA splice site in intron 8. Fractures continued during follow-up until one sister received a three-and-one-half-year course of hydroxyapatite-targeted TNSALP supplementation therapy (asfotase alfa) during which substantial improvement occurred in her clinical, biochemical, and functional parameters as well as quality of life. Following subsequent unplanned treatment cessation she suffered significant clinical deterioration, including new fractures and loss of mobility. Her bone histopathology documented osteomalacia. Treatment resumption restored its benefits. Among ten asymptomatic family members evaluated in this four-generation kindred, eight were carriers heterozygous for either ALPL mutation. Those harboring the maternal missense defect manifested mild hypophosphatasemia, suggesting a dominant-negative mutation effect. This experience underscores the importance of in-depth phenotyping and then clinical follow-up to characterize ALPL variant combinations, and for maintaining effective asfotase alfa treatment.

Alcohol intake is known to influence serum high-density lipoprotein cholesterol (HDL-C), yet how drinking patterns shape this association is less researched. We examined whether frequency of drinking versus amount per occasion was differently related to HDL-C in a large population sample. Data were taken from a cross-sectional study of 18,614 respondents aged 40-79 years in the Tromsø general population health study. Alcohol use was assessed by self-report. Fasting HDL-C was measured using standardized laboratory protocols. Mean alcohol intake was 6.7 g/day and mean HDL-C 1.57 mmol/L. Total alcohol consumption correlated positively with HDL-C (r = 0.075; p < 0.001). In regression models, each additional gram/day was associated with an increase of 0.005 mmol/L HDL-C (95% CI 0.004-0.005; p < 0.001). Drinking frequency showed a positive correlation to HDL-C (r = 0.183; p < 0.001), whereas amount per occasion was inversely related to HDL-C (r = -0.128; p < 0.001). A significant frequency × amount interaction indicated that higher amounts per occasion were linked to lower HDL-C primarily among the infrequent drinkers (p < 0.001). The results indicate that the alcohol-HDL-C association was driven by how often alcohol was consumed rather than how much was consumed per occasion. Frequent, lower-dose drinking related to higher HDL-C, whereas infrequent, higher-dose occasions related to lower HDL-C. These findings underscore the need to consider drinking patterns, beyond average intake, when interpreting HDL-C and appraising alcohol-related cardiovascular risk.

Brain disorder diagnosis and prediction remain challenging because neuroimaging, electrophysiological, behavioral, and multimodal data are high-dimensional, noisy, heterogeneous, and limited by small clinical cohorts. This systematic review synthesised applications of quantum artificial intelligence (QAI) for brain disorder diagnosis, prediction, detection, and monitoring.

Following PRISMA guidelines, studies published from 2016 to 13 January 2026 were retrieved from Scopus, Web of Science, and IEEE Xplore. After screening, 36 studies met the eligibility criteria and were qualitatively analysed according to disorder category, data modality, QAI method, implementation setting, validation strategy, and performance.

At the broader disease-group level, neurodegenerative disorders were the most frequently investigated, followed by mental health and psychiatric disorders. At the individual level, Parkinson's disease and schizophrenia were the leading applications, followed by depression, anxiety, Alzheimer's disease, and stress-related tasks. MRI-based modalities were the most frequently used data source, followed by multimodal data and EEG. Methodologically, primary QAI approaches were dominated by quantum neural and QDL architectures, followed by quantum-inspired optimization or feature-selection methods and quantum-kernel/conventional QML classifiers. Qiskit/IBM Quantum and PennyLane were the most frequently reported quantum software frameworks. However, most studies relied on simulators, classical quantum-inspired implementations, or unclear implementation settings, with limited real-hardware evaluation.

QAI shows emerging potential for brain disorder analysis, particularly through hybrid quantum-classical learning, quantum neural architectures, quantum-kernel methods, and quantum-inspired optimization. Nevertheless, current evidence remains preliminary and requires larger datasets, subject-level and external validation, fair classical benchmarking, noise-resilient circuits, real quantum hardware evaluation, explainability, and clinical validation.

Maternal syphilis rates in the United States have risen dramatically, from 87.2 per 100,000 births in 2016 to 357.9 per 100,000 births in 2024, according to Centers for Disease Control and Prevention (CDC) reports. Congenital syphilis rates have also been on the upswing, increasing from 60.0 to 109.6 per 100,000 births between 2020 and 2024, with cases on the rise for the twelfth consecutive year. This trend poses a pressing public health concern. Diagnosing syphilis, particularly in pregnancy, can be challenging due to its variable and often nonspecific presentation. Delayed recognition and treatment, however, can result in severe maternal and fetal complications.

We report a 28-year-old patient in her third trimester of pregnancy who presented to a rural emergency department (ED) with abdominal cramping, malodorous vaginal discharge, fever, hypotension, and altered mental status concerning for sepsis secondary to intrauterine infection. Pertinent social history included homelessness, an absence of prenatal care, and substance use. Fetal distress ultimately necessitated emergent delivery, after which testing confirmed maternal syphilis infection and congenital syphilis in the neonate. Later histopathologic analysis of the placenta revealed spirochete invasion consistent with syphilitic chorioamnionitis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Histopathologic confirmation of syphilitic chorioamnionitis is seldom available to emergency clinicians in real time; however, this should not be taken as evidence of rarity. EDs are likely already encountering patients experiencing the downstream consequences of unrecognized syphilis infection. Because emergency physicians often represent the sole point of medical contact for pregnant patients without prenatal care-those most at risk-strong clinical suspicion is required to prompt appropriate testing and initiation of penicillin therapy. Notably, standard empiric antibiotic regimens for chorioamnionitis do not reliably treat syphilis. As incidence rates rise, failure to recognize and treat this infection in the ED may result in preventable adverse maternal and fetal outcomes. Further, incorporating syphilis screening into ED protocols is increasingly warranted, particularly in high-prevalence regions.

The climacteric period is associated with endocrine changes and multisystem symptoms that may adversely affect health-related quality of life and psychological well-being. This systematic review and meta-analysis aimed to evaluate the effects of conventional and mind-body exercise interventions on menopausal symptomatology, health-related quality of life, anxiety, and depression in women during the climacteric period.

A systematic search and meta-analysis of randomized controlled trials were conducted according to the PRISMA 2020 statement and prospectively registered in PROSPERO (CRD420251148069). PubMed (MEDLINE), Scopus, and Web of Science were searched from January 2020 to September 2025. Risk of bias was assessed using the Cochrane RoB tool, certainty of evidence using the GRADE approach, and random-effects meta-analyses, prespecified subgroup analyses, and leave-one-out sensitivity analyses were performed.

Twelve randomized controlled trials including 1,050 participants were included in the systematic review. Exercise was associated with significant improvements in menopausal symptomatology (Hedges' g = -2.10; 95% CI [-4.14, -0.06]), health-related quality of life (Hedges' g = 1.41; 95% CI [0.46, 2.36]), anxiety (MD = -1.20; 95% CI [-1.52, -0.88]), and depressive symptoms (MD = -1.17; 95% CI [-1.40, -0.94]) compared with control conditions. Exploratory subgroup analyses suggested that the effects of exercise may differ according to exercise modality. Sensitivity analyses supported the robustness of the pooled estimates.

The available evidence suggests that physical exercise represents an effective non-pharmacological strategy for improving menopausal symptomatology, health-related quality of life, anxiety, and depressive symptoms in women during the climacteric period. These findings support its incorporation into routine clinical care and highlight the importance of individualised exercise prescription.

Family caregivers of burn survivors commonly experience psychological distress, yet longitudinal evidence describing heterogeneous adaptation patterns and the timing of clinically meaningful risk development remains limited.

We analyzed 256 caregivers assessed at baseline and 6-, 12-, and 24-month follow-ups. Latent class growth analysis was used to identify caregiver distress trajectories based on Depression Anxiety Stress Scales-21 total scores. Baseline demographic, injury, treatment-burden, and psychological characteristics were compared across classes, and a prespecified piecewise mixed-effects model examined whether class separation changed over follow-up. PTSD and posttraumatic growth were summarized secondarily to contextualize adaptation under distress-defined classes.

Three distress trajectories were identified: Low distress & lower burn severity and burden (n = 201, 78.5%), Moderate distress & higher treatment burden (n = 23, 9.0%), and High distress & higher burn severity (n = 32, 12.5%). In the piecewise model, the 0-6 month slope was not significant (β=-0.243/month; p = 0.459). During 6-24 months, trajectories diverged: Moderate distress & higher treatment burden worsened (β=2.111/month; p < 0.001), high distress & higher burn severity phenotype improved (β=-2.831/month; p < 0.001), and low distress & lower burn severity and burden phenotype remained relatively stable with a slight increase (β=0.372/month; p = 0.004). Findings were robust to alternative time specification and adjustment for baseline time since injury and burn severity. PTSD mirrored the distress-defined patterns, whereas posttraumatic growth showed a distinct pattern.

Caregiver distress after burn injury is heterogeneous, and clinically meaningful separation emerged during later follow-up. Later worsening was observed in the phenotype characterized by higher treatment-burden indicators, supporting sustained monitoring and tailored psychosocial support beyond early follow-up.