Attention-deficit/hyperactivity disorder (ADHD) symptoms and emotional problems frequently co-occur. Longitudinal data provide opportunities to understand how and why they co-develop. Data were drawn from the Twins Early Development Study, which included 27,890 participants. Emotional problems and ADHD symptoms were parent-reported using the Strengths and Difficulties Questionnaire and Conners' Parent Rating scales. We modeled the co-development of ADHD symptoms and emotional problems from ages 4 to 21 using joint trajectory analysis. The predictors included polygenic scores (PGSs) for multiple psychiatric symptoms, maternal depression, family chaos, and socioeconomic status (SES). The outcomes included SES, lifetime psychiatric diagnoses, undergraduate diploma attainment, and entry into parenthood at age 26. A four-class joint trajectory model was selected as best fitting and included: 'Low ADHD, Low emotional problems', 'High-decreasing ADHD, Low emotional problems', 'Mid-decreasing ADHD, Increasing emotional problems', and 'Increasing ADHD, Increasing emotional problems'. The consistently low-symptom group reported lower ADHD and had lower externalizing PGSs, lower maternal depression, higher SES, and less home chaos at baseline, and higher educational attainment and fewer lifetime depression/anxiety diagnoses at 26 than groups with higher symptom levels. Those with high ADHD symptoms in childhood or increasing ADHD symptoms from childhood to adulthood had the lowest educational attainment and SES in adulthood. Groups characterized by increasing ADHD symptoms also tended to show increases in emotional problems, whereas increases in emotional problems did not necessarily coincide with increases in ADHD symptoms. The trajectories had distinct early-life predictors and adult outcomes, highlighting potential intervention targets.
Adolescent interpersonal stress increases depression risk, and chronic low-grade inflammation may act as a potential underlying biological mechanism. We explored longitudinal associations between interpersonal stress, inflammation, and depressive symptoms from adolescence to young adulthood, using DNA methylation (DNAm) indices of C-reactive protein (CRP) from saliva. Data were collected from N = 434 adolescents (RADAR-Y study, 56.4% male) and analyzed in preregistered structural equation models. Interpersonal stress was estimated from repeated measures of parent-adolescent conflict, parental psychological control, parental criticism, and peer victimization. Interpersonal stress was not associated with DNAm indices of CRP at age 17 or age 25, nor with depressive symptoms at age 27. In exploratory analyses examining parent versus peer-related stress separately, higher negative parenting-but not peer victimization-was nominally associated with one out of three DNAm indices of CRP at age 17 (Hillary index, β = .15, p = .035), with no association at age 25. This study did not show an association of either interpersonal stress or inflammation with later depressive symptoms and thereby could not identify inflammation as a potential mediator. Our findings tentatively suggest timing-dependent differential effects of family versus peer-related stress on epigenetic indices of inflammation, which may be further explored in future studies.
Voice disorders affect nearly one in three people during their lifetime and are associated with significant reductions in quality of life. Despite this, limited research has explored the experiences of adults living with voice disorders. This review synthesizes patient-reported experiences and impacts of voice disorders in adulthood. Six databases (PubMed, CINAHL, Web of Science, Embase, Cochrane, and Scopus) were systematically searched, and studies were screened using an established scoping review framework. The included studies were analyzed following recognized principles of qualitative meta-synthesis. From 3525 studies identified, six met study inclusion criteria and underwent thematic synthesis. Five overarching themes emerged: 1) My voice doesn't sound or feel like it used to; 2) My voice disorder has diminished my emotional well-being and self-confidence; 3) My voice disorder impacts my life participation; 4) Stigma hurts, support helps; 5) Living with my voice disorder means learning to adapt. Recurring themes surrounding psychosocial well-being and life participation restriction highlight the need for clinicians to develop counseling skills and knowledge of when and how to refer for additional support. Clinicians are urged to use a more holistic approach to voice assessment and treatment, acknowledging that the impacts of voice disorders often extend well beyond the larynx.
Quadricuspid aortic valve (QAV) is a rare congenital cardiac anomaly characterized by four aortic cusps instead of the normal three. It is most commonly associated with progressive aortic regurgitation and is often diagnosed incidentally on echocardiography. A woman in her fifties presented with palpitations and exertional dyspnea (New York Heart Association Class II). Clinical examination revealed an early diastolic murmur at the left sternal border. Transthoracic echocardiography demonstrated a QAV with Hurwitz and Roberts Type F morphology and moderate aortic regurgitation with preserved left ventricular systolic function. Transoesophageal echocardiography confirmed central cusp malcoaptation. The patient was managed conservatively and remained stable at 6-month follow-up. QAV is an uncommon congenital anomaly that may present in adulthood with aortic regurgitation. Echocardiography is essential for diagnosis and classification. Early recognition has important implications for surveillance and procedural planning. RésuméLa valve aortique quadricuspide (VAQ) est une anomalie cardiaque congénitale rare caractérisée par la présence de quatre cuspides aortiques au lieu de trois. Elle est le plus souvent associée à une insuffisance aortique progressive et est généralement diagnostiquée de manière fortuite à l’échocardiographie. Une femme dans la cinquantaine s’est présentée avec des palpitations et une dyspnée d’effort de classe II selon la New York Heart Association (NYHA). L’examen clinique a révélé un souffle diastolique précoce au bord sternal gauche. L’échocardiographie transthoracique a montré une VAQ de type F selon la classification de Hurwitz et Roberts, associée à une insuffisance aortique modérée avec une fonction systolique ventriculaire gauche préservée. L’échocardiographie transœsophagienne a confirmé une malcoaptation centrale des cuspides. La patiente a été traitée de manière conservatrice et est restée stable après un suivi de six mois. La VAQ est une anomalie congénitale rare pouvant se manifester à l’âge adulte par une insuffisance aortique. L’échocardiographie joue un rôle essentiel dans le diagnostic et la classification. Une reconnaissance précoce a des implications importantes pour la surveillance clinique et la planification des interventions.
The transition to adulthood is a worrying time for female youth with a physical disability and their mothers. We sought to develop an instrument to assess which transition-related worries are most (and least) worrisome to youth and mothers to inform transition preparation interventions. A community-centered approach was used to identify and refine the most common transition-related worries of youth and mothers. A novel best-worst scaling (BWS) instrument was created in partnership with an advisory board of female youth with a physical disability and their mothers. BWS is a theory-driven survey method to identify priorities. The instrument was then pretested, refined, and piloted with youth and mothers. Findings were assessed by consultation with stakeholders. After input from youth and mothers, 11 transition-related worries were included in the pilot instrument using an object case experimental design. Pilot testing was conducted with 22 youth and 16 mothers, including 3 mother-daughter dyads. The completion rate was 86% for youth and 100% for mothers. The instrument was sensitive enough to detect differences between youth and mothers at both the aggregate and dyad level. On aggregate, both youth and mothers worried more about health-related compared to social-related worries but differed on the prioritization of independence-related worries. Discussion of results with participants and an advocacy group confirmed the face validity of the findings. Male youth and fathers were not included. The novel BWS instrument is feasible for female youth and mothers to complete independently and was valid in prioritizing worries on the aggregate and dyad levels. A subsequent large-scale study using the instrument may inform transition initiatives, while use among in a clinical setting may guide decision making.
Major depressive disorder (MDD) is frequently accompanied by self-harm behaviors, including non-suicidal self-injury (NSSI) and suicide attempts (SA), which are important risk factors for suicide and poor clinical outcomes. Although neuroimaging studies have identified structural brain abnormalities related to suicidal behaviors in MDD, the neurobiological distinctions between NSSI and SA remain poorly understood. In particular, few studies have simultaneously compared MDD patients with NSSI, MDD patients with SA, and MDD patients without self-harm behaviors. Therefore, this study aimed to investigate gray matter volume (GMV) alterations and their associations with clinical symptoms in early adulthood (aged 18-30 years) MDD patients using voxel-based morphometry (VBM). A total of 54 MDD patients with NSSI (MDD/NSSI), 68 MDD patients without NSSI (sMDD), 50 MDD patients with SA (MDD/SA), and 66 healthy controls (HCs) were included. VBM was used to examine GMV differences using high-resolution T1-weighted MRI scans. Age, sex, education, and intracranial volume were included as covariates. One-way ANOVA with Gaussian random field (GRF) correction was performed, followed by post-hoc t-tests. Correlations between GMV and clinical measures of depression (HAMD), anxiety (HAMA), and suicide risk (NGASR) were assessed. Significant GMV differences were observed in the superior/middle frontal gyrus, superior frontal gyrus, bilateral caudate, superior/middle temporal gyrus, and middle cingulate gyrus (voxel-level p < 0.001, GRF corrected p < 0.05). Post-hoc analyses showed reduced GMV in the MDD/SA group compared with the MDD/NSSI group in several regions. However, supplementary GLM analyses indicated that NSSI-related characteristics showed more consistent independent associations with regional GMV, whereas SA history was not independently associated with GMV in any examined region. Correlations between GMV and clinical measures did not survive FDR correction. MDD patients with NSSI and SA may exhibit distinct patterns of gray matter alterations; however, these differences likely reflect clinical heterogeneity across self-harm subgroups rather than SA-specific structural abnormalities. Supplementary analyses further suggest that NSSI-related characteristics show stronger independent associations with GMV than SA history. These findings highlight the importance of distinguishing self-harm subtypes in the neurobiological characterization of MDD. All results should be interpreted cautiously given the cross-sectional design and the lack of robust associations after multiple-comparison correction. Not applicable.
Repeated or persistent suicidal ideation (SI) and suicide attempts (SA) are among the most robust risk factors for later suicide mortality, yet few studies have identified factors that consistently predict their recurrence over time. Using data from the U.S. National Longitudinal Study of Adolescent to Adult Health, which followed a nationally representative cohort of U.S. adolescents over 14 years, we examined whether adolescent self-esteem predicts SI and SA across adolescence and young adulthood. A total of 6,504 adolescents were assessed at Wave 1 (1994-1995), with follow-up interviews conducted at one, seven, and fourteen years. Self-esteem and demographic characteristics were measured at baseline, whereas SI, SA, and established risk factors for suicidality (i.e., depressive symptoms, substance use, violent victimization, childhood maltreatment, and recent exposure to suicide attempts) were assessed at each wave. Time-lagged logistic regression models showed that adolescent self-esteem predicted SI at all follow-ups, even after adjusting for demographic factors, concurrent risk factors, and prior suicidality. In contrast, SA was more consistently predicted by concurrent risk factors. We discuss the implications of these findings for suicide prevention and intervention.
The functional network architecture of the aging brain undergoes significant systematic and idiosyncratic changes. Emergent individualized network mapping approaches may yield better or more sensitive explanatory insight about age-related neural and behavioral variability, although most applications have focused on young adults. In the current study, we tested the validity and impact of mapping individual-specific topography in two fMRI datasets comprising 112 young (18-35 years) and 176 older adults (60-92 years). Older adults had more idiosyncratic network topography than young adults. Individualized maps from resting-state fMRI improved network homogeneity and fidelity to social cognitive task fMRI activations and exhibited intra-individual stability and inter-individual discriminability over a 2-year interval. Last, traditional group-averaged (vs. individualized) network mapping had a moderate-to-large impact on individual-level estimates of network segregation, a widely-studied measure of functional brain aging. Therefore, individualized network mapping captures important heterogeneity in older adulthood and may yield more precise characterization of neurocognitive aging.
Previous studies have shown that exposure to famine during early life is associated with long-term health outcomes. However, findings on the association between famine exposure and the risk of hypertension remain inconsistent. This study aimed to investigate the relationship between famine exposure at different early-life stages and the incidence of hypertension among Chinese adults, and further evaluate the interaction effect of Dietary Inflammatory Index (DII) on the risk of incident hypertension. Using data from the China Health and Nutrition Survey (2004-2015), a Chinese population-based cohort, participants were divided into three groups based on their birth year relative to the Great Chinese Famine: the fetal exposure group, the early childhood exposure group, and the non-exposure group. Cox regression was used to assess the association between famine exposure and incident hypertension. To further evaluate the interaction between famine exposure and DII on the risk of incident hypertension, DII was categorized into quartiles and incorporated into the analysis. A total of 603 incident cases of hypertension were identified during the follow-up period. The early childhood exposure group exhibited a significantly higher risk of incident hypertension. Compared with the first DII quartile group, the third quartile group showed a 39% increased risk of incident hypertension. Additionally, a significant interaction was observed between DII and early childhood famine exposure in the fourth quartile group. Early childhood famine exposure showed a significant interaction with the DII, suggesting effect modification in the association between dietary inflammatory potential and adult hypertension. These findings highlight the potential value of targeted nutritional and dietary guidance for Chinese individuals with early-life nutritional adversity.
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Suicide attempts in childhood and adolescence are common, recurrent, and the strongest predictor of death by suicide; yet their developmental antecedents remain poorly understood, particularly in low- and middle-income countries. We aimed to identify childhood factors associated with incidence, onset timing, and number of suicide attempts and to quantify the population impact of modifiable risk factors. We analyzed data from the Brazilian High-Risk Cohort Study, a community-based cohort of 2511 children aged 6-14 years followed for 15 years. Risk factors across genetic, perinatal, sociodemographic, family, adversity, cognitive, and clinical domains were examined using logistic regression (OR), Cox proportional hazards (HR), and quasi-Poisson models (IRR), were examined for three outcomes (cumulative incidence, onset timing, and number of suicide attempts), with all predictors entered simultaneously and bootstrap resampling. Population attributable fractions were calculated for modifiable factors. Of 2060 participants (48.0% female unweighted, 47.3% weighted), 309 (15.0%) reported suicide attempts over 24,756.5 person-years (mean onset 17.8 years). Female sex (OR 3.06, 95% CI 2.28-4.17; HR 2.88, 2.25-3.69; IRR 3.12, 2.19-4.49) and childhood threat (OR 1.26, 1.08-1.47; HR 1.21, 1.06-1.38; IRR 1.26, 1.05-1.51) were associated with all three outcomes. Caregiver suicide attempt (OR 2.07, 1.40-3.14; HR 1.88, 1.34-2.63) and externalizing disorders (OR 1.52, 1.05-2.15; HR 1.50, 1.07-2.08) were associated with incidence and earlier onset. PRS-depression (IRR 1.39, 1.00-1.94) and gestational diabetes (IRR 2.18, 1.13-3.83) were associated with increased attempt frequency. Child-reported bullying (OR 1.73, 1.22-2.45) and parent-reported physical abuse (OR 1.96, 1.24-3.10) retained association after mutual adjustment in threat-component models. Population attributable fractions were substantial for caregiver suicide attempt (14.1%), caregiver internalizing disorders (11.6%), high childhood threat (>1 SD; 11.5%), and externalizing disorders (10.2%). In lethality analyses, PRS-depression (OR 2.21, 1.09-4.43; HR 1.98, 1.13-3.60; IRR 2.68, 1.43-4.97), childhood threat (HR 1.40, 1.09-1.80; IRR 1.34, 1.03-1.90), and maternal alcohol use in pregnancy (HR 1.92, 1.12-3.26) were associated with medically serious attempts. Prediction models showed modest discrimination (mean area under the curve [AUC] 0.665, SD 0.033, across 200 repeated test splits). These findings highlight three potentially modifiable or clinically actionable domains - childhood threat, caregiver suicidal behaviour history, and childhood externalizing disorders - that may be amenable to prevention even when genetic liability is present. Despite multi-domain predictors, predictive performance remained limited, consistent with a complementary role for population-level prevention alongside efforts to improve risk prediction. CNPq, FAPESP, ERC, UK MRC, and Banco Industrial do Brasil S/A. Full grant details are provided in the manuscript.
Congenital pulmonary airway malformation (CPAM) is a rare pulmonary developmental anomaly with heterogeneous clinical manifestations and associated comorbidities. While often diagnosed prenatally, its lifelong clinical spectrum and associated comorbidities remain poorly characterized, as existing evidence is fragmented across individual case reports and small series. To integrate and analyze individual patient data from published cases to delineate the age-stratified spectrum of comorbidities and clinical presentations of CPAM from fetal life to adulthood. We performed a pooled analysis of individual case data extracted from 209 published articles during the period from 1992 to 2025. A total of 832 CPAM cases were stratified by age: fetus (n = 168), infant (n = 272), toddler (n = 70), child (n = 114), adolescent (n = 53), and adult (n = 155). In the 832 CPAM cases, a majority (66.6%; 95% CI 63.3%-69.8%) were asymptomatic at presentation, yet 37.4% (95% CI 34.1%-40.8%) had at least one documented comorbidity. Age-stratified analysis revealed significantly evolving profiles: malignant/pre-malignant lesions increased sharply with age (adults 23.9%; 95% CI 17.5%-31.3% vs. prenatal 2.9%; 95% CI 1.0%-6.9%, p < 0.001), while pulmonary sequestration was more frequent in fetal cases (9.5%). Asymptomatic presentation decreased from 89.4% prenatally to 48.4% in adulthood (p < 0.001), whereas infection-related symptoms, hemoptysis, and cough increased with age. Multivariate analysis identified symptomatic presentation at diagnosis as a strong, independent predictor of clinical outcome (aOR = 10.73, p = 0.004). Among the subset of 119 cases with genetic testing data, 63.0% (95% CI 53.7%-71.7%) harbored genetic findings of potential clinical significance. This large-scale pooled analysis demonstrates that CPAM exhibits a dynamic comorbidity and presentation spectrum across the lifespan, with increasing malignancy risk and symptomatic burden in adulthood. These findings challenge the perception of CPAM as solely a pediatric condition and argue for structured, lifelong follow-up. Specifically, we recommend: (1) age-stratified malignancy surveillance, with low-dose CT screening considered for adults with residual lesions; (2) transition from pediatric to adult care protocols that include patient education on symptom monitoring (e.g., new cough, hemoptysis); and (3) prioritized intervention and genetic counseling for symptomatic patients and those with identified genetic variants, given their higher risk of complications. Implementing these targeted strategies is crucial to optimize long-term outcomes.
Obesity that develops at different life stages may have distinct metabolic consequences, and the mechanisms distinguishing juvenile from adult-onset obesity remain incompletely defined. Thus, we examined how the timing of exposure to a high-fat diet (HFD) affects expansion, lipid metabolism, and insulin signaling in epididymal visceral adipose tissue (eVAT). Male C57BL/6J mice were fed either a control diet or a 60% HFD, initiated immediately after weaning during the juvenile period (3 weeks of age) or at young adulthood (9 weeks of age), and continued until 17 weeks of age. HFD increased both total VAT and subcutaneous adipose tissue (SAT) mass regardless of exposure timing. However, when introduced during adulthood, it led to a higher total VAT to SAT ratio, greater total VAT mass, more severe hyperglycemia, and more pronounced eVAT adipocyte hypertrophy and reduction in PPARγ protein levels. Only adult mice exposed to HFD exhibited impaired eVAT insulin signaling, characterized by increased inhibitory IRS1 phosphorylation, reduced Akt phosphorylation, and lower GLUT4 protein levels. This was associated with increased fatty acid influx, indicated by higher lipoprotein lipase and Cd36 expression, reduced SREBP-1c protein levels, and a shift toward a pro-lipolytic profile with increased Hsl expression. These findings indicate that adult exposure to HFD leads to more adverse effects on eVAT expansion, lipid metabolism, and insulin signaling than juvenile exposure, further supporting the concept that the developmental stage at which caloric overload is initiated shapes adipose tissue plasticity and influences the severity of obesity-related metabolic disturbances.
ObjectiveAlthough opioids are used frequently in pediatric intensive care units (PICUs) for analgesia and safety, the long-term consequences of opioid exposure in PICU are unknown. We performed this exploratory study to examine the relationship between PICU-related opioid exposure and chronic prescription opioid use in adult survivors. Our primary outcome was the prevalence of chronic prescription opioid use, defined as filled opioid prescriptions covering >70% of days within a 3-month period during the adult observation period.Design and setting: We performed a single-center, retrospective cohort study linking PICU admission-based data from childhood with opioid prescription data in adulthood via the Nova Scotia Prescription Monitoring Program (NSPMP).PatientsWe included children (birth to 16 years) who required PICU admission for critical illness that included opioid exposure and ≥48 h of mechanical ventilation after January 1, 1995 and reached adulthood (18 years) by January 1, 2015. We examined adult opioid prescription data for the 5 years from 2015 to 2019.InterventionsNoneMeasurements and main resultsOf 313 eligible participants, we excluded 194 for death, migration, or loss to follow-up; 119 were included. Six (5%) met criteria for chronic prescription opioid use as an adult. Compared with participants who had chronic opioid use, those without chronic opioid use had significantly fewer PICU admissions in childhood (median [IQR] = 3[1-6] vs 1[1-2] respectively, p = 0.040) and a higher mean Therapeutic Intervention Scoring System score (surrogate for severity of illness, mean [SD] = 29.3[6.6] vs 35.9[7.4], p = 0.036), but no difference in cumulative opioid exposure (median [IQR] mg/kg morphine equivalents = 8.4 [3.2-11.4] vs 7.3 [2.8-17.0], p = 0.49).ConclusionAdult survivors of pediatric ICU admissions demonstrated a prevalence of chronic prescription opioid use of 5%. Pediatric critical illness necessitating PICU admission and opioid prescription were not associated with chronic opioid prescription use in our cohort.
Inherited metabolic diseases are genetic diseases that are individually rare but collectively common. Although they are classically considered as pediatric diseases, many patients are seen in adulthood, either due to a misdiagnosis over several years or a late initial presentation. A diagnosis in adulthood is crucial because it can lead to the implementation of specific treatments that improve patients' quality of life. Once a diagnosis is made, specialized genetic counseling helps identify and potentially treat other at-risk family members. Les maladies héréditaires du métabolisme sont des maladies génétiques rares individuellement, mais fréquentes collectivement dans la population générale. Bien qu’elles soient classiquement considérées comme des maladies pédiatriques, de nombreux patients sont diagnostiqués à l’âge adulte, soit après une errance diagnostique de plusieurs années, soit en raison d’une présentation initiale tardive. Le diagnostic à l’âge adulte est très important, car il peut permettre de mettre en place des traitements spécifiques qui améliorent la qualité de vie des patients. Une fois le diagnostic posé, le conseil génétique spécialisé aide à identifier et, le cas échéant, à traiter d’autres membres de la famille à risque.
We examined whether the accumulation of psychosocial risk factors (socioeconomic risks, health behavioural risks, stressful life-events and psycho-emotional risks) in childhood and adolescence contributes to insufficient social relations (loneliness, frequency and heterogeneity of social contacts and social support) in adulthood participants from the longitudinal Young Finns Study with a 38-year follow-up (N = 1787, 56% female). Results from regression models indicated that a higher cumulative number of risks in childhood and adolescence was associated (1-SD increase) with higher loneliness (B = 0.32, 95% CI 0.19 ; 0.45), lower perceived social support (B=-0.32, 95% CI -0.45 ; -0.19), lower frequency of social contacts (B = 0.19, 0.06 ; 0.32), and lower heterogeneity in social contacts (B=-0.33, -0.47 ; -0.20) in midlife. Causal mediation analysis suggested that depressive symptoms partially mediate the relationship between cumulative childhood and adolescent psychosocial risks and adult social relations (mediation proportion range between 7% and 18%). Educational attainment mediated the relationship between cumulative psychosocial risk and social relations heterogeneity by 8%, while income mediated the association with loneliness, social support and social relations heterogeneity by 9% to 11%. In conclusion, this study underscores the potentially profound and lasting impact of psychosocial risks encountered during childhood and adolescence on social relations in adulthood.
Cardiovascular risk factors such as overweight and high cholesterol in childhood are predictive of high disease risk in adulthood. However, the optimal timing and scope of early prevention remains uncertain due to sparse data. Our aim was to identify the earliest age at which adult-like cardiometabolic stratification emerges in population-based time-series of the first five decades of life. Children born in 1962-1992 were included from three European cohorts (local community samples). Suitable measurement series of weight, height and lipoprotein lipids were analyzed for 5683 participants (ages 0-49 years, follow-ups 10-31 years depending on cohort). Longitudinal tracking was quantified by autocorrelation (R2) over the same individuals between two visits at least a decade apart. The pattern of R2 as a function of age at the first visit was examined to identify the earliest age when adult-like plateau was reached. Autocorrelation of body mass index was low in children under four (R2 ≤12%), but reached adult levels at age nine (R2 = 51% for 10-year follow-up and R2 = 27% for 31-year follow-up). Lipoprotein lipids did not exhibit a reduction in autocorrelation at young ages. For circulating cholesterol, 10-year autocorrelation at 15 months of age was R2 = 30%. Adult-like cardiometabolic stratification is detectable in young children, but accuracy (without extreme indication) may be too low for personalized risk prediction. Consequently, we emphasize broad preventative programs that extend into adulthood to reduce the overall prevalence of cardiometabolic risk factors in the population.
Severe combined immunodeficiency (SCID) is classically a pediatric disease, yet rare late-onset forms can present in adulthood with atypical infections. We report a 42-year-old man presenting with febrile illness, hepatosplenomegaly, and pancytopenia. Bone marrow examination revealed intracellular fungal organisms, morphologically suggestive of Cryptococcus infection. The absence of known immunosuppressive states prompted immunophenotyping, which demonstrated profound B, T, and NK cell lymphopenia, consistent with SCID or late-onset combined immunodeficiency. The patient was initiated on systemic antifungal therapy; however, his condition deteriorated rapidly and he succumbed to death within three days. To ascertain the exact cause of death, a postmortem bone marrow biopsy was performed, which revealed progression to hemophagocytic lymphohistiocytosis, explaining the fulminant clinical decline. This case highlights the importance of considering underlying primary immunodeficiency in adults presenting with opportunistic fungal infections, as these conditions can rapidly progress to fulminant, life-threatening complications with high mortality.
There are several lifestyle factors known to increase the risk for age-related cognitive decline and dementia, including chronic alcohol consumption and alcohol use disorder. Chronic alcohol use in adulthood causes decreased gray matter and atrophy in brain regions central to learning and memory, including the hippocampus. Further, people with alcohol use disorder have a high incidence of cerebral white matter hyperintensities, the hallmark of cerebral small vessel disease, suggesting a link between alcohol consumption and cerebrovascular disease. However, how ethanol exposure impacts the cerebral circulation remains unclear. Here, we investigated the effects of a single ethanol vapor exposure (12 hours), repeated ethanol exposures (12 hours/day for 10 days) or air exposure (controls; n=8/group) on cerebrovascular function and structure in adult female Wistar rats, as women are more sensitive to alcohol-related brain injury. Endothelial function and myogenic reactivity of isolated and pressurized posterior cerebral arteries (PCAs), the pial artery responsible for perfusing the hippocampus, were assessed ex-vivo using pressure myography. Both single and repeated ethanol exposure impaired PCA endothelial function, however, had a differential effect on myogenic tone. Repeated ethanol exposure caused oxidative stress, vascular inflammation and reduced myogenic tone of PCAs compared to a single exposure. Further, PCAs from rats repeatedly exposed to ethanol were stiffer than arteries from controls and a single ethanol exposure, which commonly occurs with aging. These findings demonstrate that ethanol exposure rapidly impairs endothelial function in the cerebrovasculature of females and suggest that repeated exposures may result in disrupted hemodynamics and accelerated vascular aging.
Cardiovascular (CV) prevention in young adults is pivotal due to escalating morbidity and mortality rates in this demographic. Assessing CV awareness and its socio-behavioural correlates is essential for developing effective prevention strategies. This study assessed CV awareness and lifestyle behaviours among Polish 18-year-olds, hypothesising that significant gender-specific disparities exist at the threshold of adulthood. A nationwide, representative survey was conducted over 10,000 students in final-year grades from 250 Polish secondary schools. Sampling employed a stratified cluster method. Data were weighted to ensure national representativeness. Awareness of CV risk factors and lifestyle behaviours (diet, physical activity, sleep, and substance use) were evaluated. Of 10,095 participants (6,076 females, 4,019 males), overweight and obesity were recorded at 17.0% and 4.1% in males, and 8.4% and 2.1% in females, respectively (p < 0.001). Only 14.6% of women and 14.3% of men knew their current blood pressure values (p = 0.48). Weekday screen time averaged 5.9 ± 2.7 hours, rising to 6.7 ± 2.8 hours on weekends, with significant gender differences on weekends (p = 0.009). Sleep duration was concerning, with 52.6% of women and 40.5% of men sleeping under seven hours on weekdays (p < 0.001), though 95% slept sufficiently on weekends. Awareness of sleep-related diabetes and obesity risks was minimal. Men had higher alcohol consumption, with 20.5% consuming 100g or more weekly, compared to 12.6% of women (p < 0.001). Smoking was prevalent, with 22.8% of women and 23.7% of men smoking daily. Exercise adherence varied, with only 61.0% of women and 76.7% of men meeting guidelines in summer, declining in winter (p < 0.001). Men generally consumed unhealthy foods more often. While most recognized common myocardial infarction risk factors, under 65% identified high cholesterol as a risk, with women generally performing better in awareness. Polish 18-year-olds exhibit distinct, gender-specific cardiovascular risk profiles. While females possess superior theoretical knowledge, they are more prone to physical inactivity and poor sleep hygiene. In contrast, males are primarily burdened by adverse dietary habits and substance use. These findings indicate that public health interventions should be gender-tailored: prioritising physical activity for young women and focusing on dietary improvements and addiction prevention for young men to effectively mitigate future cardiovascular risk.