Acute ischemic stroke (AIS) is one of the leading causes of death and disabilities, and as such, it is of utmost importance to identify novel treatment options. Remote ischemic conditioning (RIC) is a promising non-invasive treatment that is thought to activate the body's own protective mechanisms against damaging ischemia. Here, we study the transcriptomic impact of microRNAs (miRNAs) that are upregulated by RIC.

Using RNA sequencing, we investigated the transcriptional changes in human brain microvascular endothelial cells (HBMECs) transfected with four selected RIC-upregulated miRNAs (RIC-miRNAs), miR-16-5p, miR-144-3p, miR-182-5p, and miR-451a, under oxygen and glucose deprivation (OGD) and reoxygenation-mimicking the initial stages of AIS.

Pronounced transcriptional changes were present after RIC-miRNA transfection, with 149 unique downregulated and 212 upregulated differentially expressed genes in HBMECs after OGD and RIC-miRNA transfection compared to all other conditions. These genes were involved in pathways of energy metabolism and cell cycle regulation.

Our study suggests that the selected RIC-miRNAs regulate pathways that may facilitate endothelial cell survival, recovery, and remodeling events from ischemic damage, adding to the knowledge of the pathways affected by RIC during stroke.

Persistent pelvic pain (PPP) is often regarded as multifactorial and complex. There is limited knowledge on how patients with PPP resemble and differ from those with persistent non-pelvic pain (PNPP). The specific aims of this study were to compare self-reported background and pain characteristics, affective symptoms, and quality of life at baseline between patients with PPP and those with PNPP at three multidisciplinary pain clinics in Norway, and to explore differences between men and women with PPP.

This is a cross-sectional study, using registry data from three tertiary, multidisciplinary pain clinics. Patients ≥17 years answered web-based questionnaires on background, baseline pain symptoms, mental health, and quality of life. We used t-tests, chi square, and multivariable logistic regression.

Of 934 consenting patients (71 % of those attending), 30 had missing diagnoses, and 127 (13.6 %) were diagnosed with PPP. PPP patients less often reported widespread pain than PNPP patients (adjusted odds ratio (AOR) 0.2, 95 % confidence interval (CI) 0.2-0.4). We found high prevalence of fatigue, insomnia, and anxiety among all the pain patients, but PPP patients were more likely to report depression (AOR 1.6, 95 % CI 1.0-2.6) and pain catastrophizing (AOR 1.8, 95 % CI 1.2-2.8). All the pain patients had a low health-related quality of life. Women with PPP had higher prevalence of severe fatigue than men with PPP.

This study confirms that pain clinic patients generally experience high levels of emotional distress and poor health-related quality of life. PPP patients tend to exhibit higher rates of pain catastrophizing, yet less widespread pain. Understanding the specific symptom profile of PPP patients is crucial for effective treatment in pain clinics. The potential underutilization of pain clinics in the treatment of PPP patients warrants further investigation.

Child maltreatment is a significant risk factor for mental and metabolic health, with negative effects that can persist into adulthood. Using data from a U.S.-nationwide study, the National Longitudinal Study of Adolescent to Adult Health (Add Health), this study examined the associations between child maltreatment, specifically childhood threat (i.e., harm or threat of harm) and deprivation (i.e., absence of expected environmental inputs), and young adult mental (i.e., depressive symptoms) and metabolic health (i.e., metabolic risk). The moderating effect of social support was also examined, focusing on both quality of different types of support (i.e., from teachers, friends, and other adults) and variety of support sources. Results showed that young adults who experienced more threat during childhood exhibited higher levels of depressive symptoms in young adulthood, and those exposed to more deprivation reported elevated levels of metabolic risk. This study also highlighted the protective-stabilizing role of quality of teacher support in buffering the impact of deprivation on depressive symptoms, and the protective-stabilizing role of high-quality other adult support in the link between childhood deprivation and metabolic risk, such that the benefits of social support remained stable across increasing levels of deprivation. Additionally, the variety of social support showed a protective-reactive pattern in moderating the link between deprivation and metabolic risk, wherein the benefits of variety of social support were released under low deprivation but not high deprivation conditions for metabolic risk. These findings underscore the importance of eliminating child maltreatment experiences and highlight potential interventions, such as enhancing teacher-student relationships and broadening adolescents' access to diverse support networks, to buffer the long-term mental and metabolic health consequences associated with early experiences of threat and deprivation.

Previous studies assessed dynamic functional connectivity in obsessive-compulsive disorder (OCD) by the sliding-window approach, limiting sensitivity to rapid neural fluctuations. Moreover, the mechanisms underlying dynamic transitions between brain states also remain unknown. Therefore, the study aimed to explore the dynamic neural mechanisms of OCD by characterizing state dynamic patterns and the underlying energy basis.

The study recruited 198 OCD patients and 109 healthy controls, characterizing altered state dynamic patterns and underlying control energy in OCD by integrating co-activation pattern (CAP) analysis with network control theory (NCT).

OCD patients showed increased occurrences of the states characterized by ventral attention and somatomotor network co-activation with default mode network suppression (VAN-SMN⁺/DMN^-) and default mode network activation with ventral attention network suppression (DMN⁺/VAN^-), reduced persistence of the actively frontoparietal network with suppressively visual network (FPN⁺/VIS^-) state, and elevated transitions among DMN⁺/VAN^-, VAN-SMN⁺/DMN^-, and SMN-VAN⁺/VIS^- states. Moreover, computational enhancement of FPN⁺/VIS^- state persistence via virtual perturbation partially improved abnormal brain-state dynamics in OCD. NCT further revealed that state transitions from DMN⁺/VAN^- to VAN-SMN⁺/DMN^- or SMN-VAN⁺/VIS^- required reduced control energy under modulation by GABAergic signaling and mitochondrial respiratory capacity, forming a "low-cost pathological shortcut" associated with greater symptom severity; state transitions from SMN-VAN⁺/VIS^- to VAN-SMN⁺/DMN^- were intrinsically energy-demanding, modulated by dopaminergic and serotonergic systems, constituting an "inefficient pathological transition" consistent with repetitive behavior observed clinically.

OCD is characterized by a maladaptive brain-state cycle marked by excessive DMN dominance, frequent shifts to VAN/SMN activation states, and attenuated FPN engagement. Computationally enhancing the persistence of the FPN⁺/VIS^- state via virtual perturbation partially improved the dysregulated cycle in OCD. Within this cycle, two distinct pathological transition modes emerged: a "low-cost shortcut" from DMN to VAN/SMN modulated by GABAergic and an "inefficient transition" from SMN to VAN linked to dopaminergic and serotonergic. These reveal neurochemically grounded alterations in the energy control of abnormal brain-state transitions, offering mechanistic insights into the disrupted neural dynamics of OCD.

Policy Points A quarter of a century since bioethicist Edmund Pellegrino warned about the commodification of health and health care, the problem has significantly worsened. Commodification of health and health care objectifies and dehumanizes people and undermines core concepts of holistic person-centered health, much less core human rights, including fulfillment of human potential and comprehensive health care. Multilevel sustained strategies and multisector coalitions are required to decommodify and humanize health and health care based on mental models, national and state policies, practices, resource flow, power dynamics, and relationships and connections.

Edmund Pellegrino warned about the growing commodification of health and health care in the United States. After twenty-five years, it is worth revisiting Pellegrino's critique and examining this critique in the current era.

We conducted a targeted review of the literature to revisit the state of commodification in health and health care as defined by Pellegrino, examined its relationship to dehumanization, and explored prospects for addressing commodification.

The commodification of health and health care substantially worsened in the US, characterized by increased health care corporatization and consolidation, biomedical lobbying, and unaffordable costs. Commodification and dehumanization reinforce each other, undermining rights to health and health care, the provision of holistic person-centered health, and the fulfillment of human potential. Decommodifying and humanizing health and health care requires a paradigm shift towards whole-person definitions of health; the acknowledgement of human relationships as a foundation; the recognition of health as a social good; and the need for society and healthcare to partner to optimize health, including providing health care to all.

This paradigm shift will require collective, cross-sectoral advocacy and mobilization not only by diverse health care professional organizations but also by organizations outside health care that are committed to improving health for all.

Cornelia de Lange syndrome is a rare congenital disorder marked by considerable clinical variability, including intellectual disability, growth retardation, distinctive facial features, limb abnormalities, and multisystem involvement. The condition is primarily linked to mutations in genes encoding components of the cohesin complex that are essential for chromosomal stability and gene regulation. We report a case of a mild type of Cornelia de Lange syndrome caused by a de novo mutation in an Iranian family.

We investigated a 19-year-old Iranian male individual presenting with developmental delay, borderline intellectual disability, dysmorphic facial features, and multisystem involvement. Whole-exome sequencing was performed to identify causative variants. A de novo heterozygous variant affecting the start codon of NIPBL (NM_133433.4:c.2T>A; NP_597677.2:p.Met1Lys) was identified. This variant was absent from population databases and predicted to disrupt normal translation initiation. Sanger sequencing and co-segregation analysis confirmed the genetic findings. In silico tools and population databases were utilized to assess variant pathogenicity. Clinically, the patient exhibited classical Cornelia de Lange syndrome features with relatively mild intellectual impairment compared with typical loss-of-function cases, consistent with the hypothesis of potential use of alternative start sites.

This case shows a known NIPBL start-loss variant's correlation with a relatively mild clinical presentation and offers more genotype-phenotype evidence for it. This finding suggests a possible role for downstream translation initiation as a modifier of disease severity, although further functional validation is required. Comprehensive genetic analysis remains essential for accurate diagnosis, prognosis, and counseling in patients with Cornelia de Lange syndrome.

Despite decades of mass Ivermectin distribution, onchocerciasis transmission persists in Cameroon. Comorbidities with non-communicable diseases (NCDs) and gaps in treatment uptake may contribute to the sustained transmission of this disease. This study assessed the prevalence of onchocerciasis, its comorbidity with selected NCDs, and determinants of continued transmission in Bafut Health District, Cameroon.

A community-based cross-sectional study with health facility-based recruitment was conducted from June to July 2024 among 282 adults aged 30 years or older who had resided in Bafut for at least 5 years. Data on sociodemographic, NCD history, onchocerciasis knowledge, and ivermectin uptake were collected using a structured questionnaire. Laboratory investigations included skin snip microscopy, nodule palpation, blood pressure measurement, and venous blood tests for diabetes and rheumatoid arthritis. The relationship between categorical variables was analysed using the Chi-square test and logistic regression at the 5% significance level.

Of the 282 participants examined, 43 (15.2%) had palpable nodules, 17 (6.0%) were positive on skin snip for Onchocerca volvulus, and 6 (2.1%) had both palpable nodules and positive skin snip results. Onchocerciasis infection showed significant associations with sex, age group, marital status, and educational level (p < 0.05). Hypertension (27.8%) and rheumatoid arthritis (25.9%) were the most common comorbidities among infected individuals. Ivermectin uptake was high, with 94.3% of participants reporting that they had ever taken ivermectin at least once during previous community-directed treatment with ivermectin (CDTI) rounds. In comparison, a small proportion (5.7%) declined due to illness or blurred vision. Participants with tertiary education had approximately five times higher odds of taking ivermectin compared to those with no formal education (aOR = 4.62, 95% CI: 1.18-18.12, p = 0.028). Similarly, individuals who had lived in the community for more than 10 years had five times higher odds of adhering to ivermectin treatment than recent residents (aOR = 5.03, 95% CI: 1.11-22.8, p = 0.036), primarily due to a refusal of ivermectin, mainly because of side effects. Nearly half of the participants (48.9%) demonstrated poor knowledge of onchocerciasis.

Onchocerciasis remains present in Bafut, with ongoing transmission. Infection was associated with socio-demographic and behavioral factors. Non-communicable diseases were observed; however, no causal relationship can be inferred. Strengthening ivermectin uptake and health education may improve control.

Not applicable.

Adolescence is a critical developmental period during which parenting practices interact with temperament and sociocultural context to shape mental health and adaptation. Most parenting models are derived from Western settings, with limited evidence from India.

This simultaneous mixed methods study drew on cross sectional data from the Indian Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA) cohort, including adolescents aged 12-17 years (parent report n = 931; child report n = 836). Exploratory factor analysis was conducted on parent and child versions of the Alabama Parenting Questionnaire. Qualitative data were obtained through in-depth interviews with 31 adolescents and their parents and analysed using thematic analysis. Findings were integrated at the interpretation stage.

The original APQ structure did not replicate. Parent reports yielded three dimensions-Involvement/Positive Parenting, Poor Monitoring, and Corporal Punishment-while child reports yielded five, distinguishing father's and mother's involvement. Inconsistent disciplining did not emerge as a distinct construct. Qualitative findings indicated high involvement and behavioural and psychological control, largely driven by academic goals. Adolescents experienced these practices as both supportive and restrictive, with parental openness shaping communication. Contextual pressures, including resource constraints and urban stressors, contributed to a competency-control paradox.

Parenting of adolescents in India must be understood within its relational and sociocultural ecology. While involvement and control function as primary supports, excessive control may constrain broader competency development. Integrating parent and adolescent perspectives is essential for culturally grounded research and intervention.

Pyogenic liver abscess (PLA) is a life-threatening infection rising in East Asia, especially among patients with type 2 diabetes. Although SGLT2 inhibitors improve glycemic control and offer extraglycemic benefits, their effect on PLA risk is unknown. Using Taiwan's National Health Insurance Research Database, we conducted a nationwide retrospective cohort study of adults with T2DM. After 1:1 propensity score matching, 258,800 SGLT2i users and 258,800 non-users were included. The primary outcome was incident PLA. Incidence rates were calculated per 1,000 person-years, and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models. Additional analyses included subgroup analyses with interaction testing, a time-dependent Cox model, a competing-risks model, and a negative-control outcome analysis using fracture. During follow-up, 1,275 PLA events were identified. The incidence rate of PLA was 0.75 per 1,000 person-years in SGLT2i users and 0.83 per 1,000 person-years in non-users. In the primary multivariable Cox model, SGLT2i use was associated with a lower risk of PLA compared with nonuse (aHR, 0.88; 95% CI, 0.79-0.99). This inverse association was generally consistent across most subgroups. In the time-dependent analysis, SGLT2i use remained associated with a lower PLA risk (aHR, 0.72; 95% CI, 0.64-0.81). SGLT2i therapy was independently associated with reduced PLA risk in T2DM patients, particularly with prolonged exposure. These findings suggest an inverse association between SGLT2i use and the risk of pyogenic liver abscess in patients with T2DM.

Dyslipidemia remains a major modifiable contributor to China's cardiovascular disease (CVD) burden, yet large-scale evidence on risk-stratified management gaps is lacking.

In this nationwide study across 1,785 hospitals in 28 Chinese provinces, 604,250 outpatients with dyslipidemia were enrolled. We analyzed lipid levels, quantified control rate among treated population and rates of requiring lipid-lowering therapy (LLT) among untreated population across regions, socioeconomic status, and demographic groups.

Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were higher among females, middle-aged individuals, and individuals with obesity. LDL-C levels were also higher among urban residents, while TC showed no significant urban-rural difference. Triglyceride (TG) levels were higher in males, middle-aged individuals, individuals with obesity, and rural residents. Among treated population, LDL-C/non-HDL-C control rates reached 95% in low-risk, 70-90% in moderate-risk, 40-50% in high-risk, and 5-15% in very-high-risk groups. Among untreated population, rates of requiring LLT reached about 20% in the low-risk group and over 70% in moderate- and high-risk groups. After adjusting for covariates, males, older individuals, smokers, patients with hypertension or type 2 diabetes mellitus, as well as those in rural and low-gross-domestic-product areas were associated with lower lipid control rates and higher treatment needs.

Our findings highlight the urgent need for risk-stratified lipid management in primary care, improved access to LLT, and policies addressing regional and socioeconomic disparities to enhance lipid control and reduce CVD burden in China. Lessons from China can inform global strategies to improve lipid management and reduce the CVD burden.