As the legalized markets for cannabis and electronic nicotine delivery systems (ENDS; e-cigarettes/vapes) expand, there are growing concerns about increased youth exposure through retail accessibility. However, the extent to which retail placement align with structural neighborhood conditions remains unclear. How do neighborhood-level opportunity and vulnerability, measured through the Child Opportunity Index (COI) and Social Vulnerability Index (SVI), relate to e-cigarette/vape and cannabis retail density in Massachusetts? Using an ecological cross-sectional design, 5,034 licensed e-cigarette/vape (2022-2024) and 483 licensed cannabis (2024) retail locations in Massachusetts were geocoded to census tracts. Spatial analysis identified hot spots (high density clusters) and cold spots (low density clusters). Neighborhood characteristics were captured through the COI and SVI, which encompass a range of demographic, socioeconomic, and household indicators. Descriptive statistics and negative binomial regression models assessed associations between COI, SVI, and retail density. Retailers were concentrated in census tracts with lower COI scores across all domains, indicating lower child opportunity, and higher SVI scores, indicating greater social vulnerability, with largest differences observed in socioeconomic status and household composition. Higher levels of COI were associated with fewer retailers (CR 0.9; 95% CI 0.89-0.93), while greater SVI was associated with more retailers (CR 1.1; 95% CI 1.06-1.11). However, SVI themes of Housing Type/Transportation and Minority Status/Language themes showed minimal variation across retail hot and cold spots. E-cigarette/vape and cannabis retailers were disproportionately clustered in areas of high social vulnerability and low child opportunity in Massachusetts. Clustering aligned most closely with measures of socioeconomic disadvantage, rather than housing structure or racial/ethnic composition, diverging from historical tobacco retail patterns. Monitoring retail density may provide valuable insight into evolving industry strategies, state-specific factors, and the role of neighborhood-level policies in shaping exposure risk in vulnerable communities.
Global climate change is rapidly impacting biodiversity and threatening the sustainable use of medicinal plant species by reducing their availability and increasing harvest uncertainty. Understanding the adaptive genetic variation and genetic vulnerability of medicinal plants under climate change is crucial for effective germplasm management, cultivation, and breeding efforts. In this study, we assessed the genetic differentiation, local adaptation, and genomic vulnerability of the medicinal plant Isodon rubescens (Hemsl.) H. Hara, with the goals of elucidating the impacts of geographic and environmental factors on its genetic structure and identifying at-risk populations for informed conservation and breeding under climate change. We applied restriction site-associated DNA sequencing (RAD-seq) to 17 populations of I. rubescens spanning its central and peripheral ranges, including the Taihang and Qinling-Funiu Mountains. The analysis revealed two distinct genetic groups: one in the Taihang Mountains and the other in the Qinling-Funiu Mountains. Significant patterns of isolation by distance (IBD), environment (IBE), and resistance (IBR) were detected, alongside high niche differentiation. We identified 456 candidate adaptive SNPs, some linked to genes involved in stress responses and biosynthesis. Precipitation was a key environmental driver of local adaptation. Populations in the northern Taihang Mountains and southern Funiu Mountains showed higher genomic vulnerability, indicating a greater risk of maladaptation. Our findings demonstrate that geographic isolation and environmental factors, particularly precipitation, are key drivers of genetic differentiation and local adaptation in I. rubescens. The identified genomic vulnerability pinpoints specific populations at high risk under climate change. These insights provide a crucial genetic basis for formulating targeted conservation strategies and developing climate-resilient breeding programs for this medicinal species.
Asthma is one of the most common chronic conditions in the United States and disproportionately affects racial and ethnic minority populations and low-income communities. While both social and environmental factors are known contributors to asthma prevalence, the extent to which they interact to shape geographic disparities remains insufficiently understood. This study aimed to explore how these factors vary across regions with differing asthma prevalence to identify patterns that may inform targeted public health responses. We used the CDC's 2022 Environmental Justice Index (EJI), which includes standardized social and environmental measures at the census tract level. K-means clustering identified geographic clusters with varying asthma prevalence based on asthma rates and related health outcomes. A random forest model was trained to predict asthma rates using social and environmental variables, and feature importance was analyzed. We identified nine clusters, with three showing the highest asthma prevalence. High-prevalence areas had greater social vulnerability, including higher poverty rate, minority population rate, limited English proficiency, unemployment, and housing cost burden. They also experienced greater environmental exposures, such as elevated PM2.5, ozone, diesel pollution, and more land near hazardous waste sites, chemical facilities, and older housing. The random forest model predicted asthma rates with strong predictive performance (R2 = 0.81). Socioeconomic variables consistently ranked as stronger predictors than environmental exposures. Geographic areas with high asthma prevalence are shaped by overlapping social and environmental vulnerabilities. Socioeconomic disparities emerged as particularly influential. These findings support integrated, data-driven public health strategies to address asthma inequities.
Aging is the primary risk factor for sporadic Alzheimer's disease (AD). While amyloid-beta oligomers (AβOs) accumulation is a key neuropathological process in AD, their specific effects in aged brains and how aging modulates brain response to AβOs remains poorly understood. We investigated how aging contributes to AβO-induced neurotoxicity and cognitive deficits in mice. After biochemical and in vitro characterizations on primary cultures of cortical neurons, AβOs or their vehicle were intracerebrally injected into both 3- and 18-month-old wild-type mice. A broad spectrum of assays including synaptic markers, neuroinflammation, apoptosis and cognitive functions was used to establish a preliminary characterization of the interplay between age and AβOs. In vivo data were analyzed using a multifactorial design (Treatment × Age), with two-way ANOVA or other appropriate statistical models. Old mice had significantly reduced synaptic proteins SNAP-25 and PSD-95, elevated neuroinflammatory markers, and increased neuronal apoptosis in hippocampus and cortex, despite showing cognitive performances similar to young mice. All brain biomarkers were worsened after AβO injection in both young and old mice. Age and AβO effects either accumulated or interacted to promote neuroinflammation and apoptosis, depending on brain areas, whereas their effects on synaptic proteins were strictly additive. Moreover, AβO injection induced only mild spatial memory deficits in young mice, in contrast with those observed in old mice in both episodic and spatial memory tests. Whereas the young brain showed resilience to maintain memory performances after AβO injection, the coping capacities of the aging brain were exceeded by AβO effects. At the neurobiological level, age and AβO effects were mainly additive, but also acted synergistically in a brain region-dependent vulnerability pattern. This study highlights the value of incorporating aging into preclinical models to improve their translational validity and enhance their relevance for drug testing targeting early stages of sporadic AD.
Chemoresistance remains a major cause of treatment failure in colorectal cancer (CRC), yet the metabolic mechanisms sustaining efflux-mediated drug resistance are not fully defined. Here, we identify ATP-citrate lyase (ACLY) as a metabolic regulator linking citrate-dependent acetyl-CoA production to epigenetic control of MDR1/ABCB1 expression. Using genetic and pharmacologic approaches, we show that ACLY catalytic activity contributes to the maintenance of histone acetylation at H3K9 and H4K16 and supports MDR1 transcription in CRC cells. Consistently, ACLY overexpression enhances, whereas its inhibition reduces, MDR1 expression and associated resistance-related transcriptional programs. In human CRC specimens, ACLY and MDR1 levels positively correlate, with a stronger association observed in advanced-stage tumors, supporting clinical relevance of this metabolic-epigenetic axis. Metabolic tracing with 13C-glucose suggests that perturbation of citrate flux influences ACLY-associated pathways and acetyl-CoA availability. In this context, vitamin C treatment reduces citrate-derived acetyl-CoA and ACLY phosphorylation and is associated with global histone deacetylation and decreased MDR1 expression in vitro and in KRAS-mutant patient-derived xenografts. Together, these findings highlight ACLY-dependent acetyl-CoA production as a potential metabolic vulnerability linked to epigenetic regulation of drug efflux programs in CRC. Targeting this metabolic-chromatin axis may represent a strategy to modulate MDR1-associated chemoresistance.
Multi-level factors, including demographic and neighborhood social conditions, related to disparities in oral cavity cancer (OCC) are not fully understood. We examined the association between these factors and survival outcomes among patients diagnosed with OCC. We identified 14,416 patients diagnosed with OCC from 1995 to 2020 using population-based data from the Texas Cancer Registry. Neighborhood-level social vulnerability was measured using the 2010 US Centers for Disease Control and Prevention's Neighborhood Social Vulnerability Index (CDC-SVI). We examined race and ethnicity, CDC-SVI (as sample-based quintiles), and their joint effects with survival outcomes. Five-year survival probability was 38.6% (95% CI: 35.3, 42.0) for non-Hispanic Black patients, 55.1% (95% CI: 54.1, 56.0) for non-Hispanic White patients, 44.8% (95% CI: 42.9, 46.6) for patients in the most vulnerable neighborhoods, and 61.5% (95% CI: 59.6, 63.2) for patients in the least vulnerable neighborhoods. In adjusted models, Non-Hispanic Black patients (hazard ratio (HR) 1.79, 95% CI: 1.63, 1.95) and patients in the most vulnerable neighborhoods (HR 1.50, 95% CI: 1.40, 1.61) had a higher risk of all-cause mortality compared to non-Hispanic White patients and those in the least vulnerable neighborhoods, respectively. There were no racial and ethnic differences in all-cause mortality in the least vulnerable neighborhoods compared to non-Hispanic White patients (Non-Hispanic Black: HR 1.44, 95% CI: 0.95, 2.18). Findings underscore the importance of mitigating inequities in survival outcomes among patients with OCC and demonstrate that racial and ethnic disparities in survival outcomes were largely attenuated among patients living in the least socially vulnerable neighborhoods.
Mitochondrial dysfunction is a hallmark of neurodegenerative diseases, including Alzheimer's disease (AD). While ferroptosis has been implicated in AD through iron accumulation and amyloid β (Aβ)-mediated toxicity, its role in mitochondrial regulation remains unclear. Here, we examined whether mitochondrial dysfunction in AD increases neuronal vulnerability to ferroptosis and whether ferroptosis inhibition can preserve mitochondrial network integrity. Primary cortical neurons were cultured in a multi-compartment microfluidic platform that facilitated high-resolution tracking of mitochondrial dynamics using time-lapse microscopy. Prolonged exposure to the ferroptosis inducer erastin disrupted neuronal networks, whereas acute exposure to erastin or Aβ significantly enhanced retrograde mitochondrial transport. These effects were blocked by the ferroptosis inhibitor ferrostatin-1 (Fer-1). Using a novel mitochondrial calcium probe (mt-Fura 2.3 AM), we further demonstrated that Aβ acutely increased mitochondrial calcium, which was ameliorated by Fer-1 and by inhibition of the mitochondrial calcium uniporter with MCUi4. In contrast, Aβ-induced hyperactivity recorded on a microelectrode array was prevented by MCUi4, but not Fer-1. Together, these results show that ferroptotic stress profoundly impacts mitochondrial movement and calcium regulation in neurons. Our multimodal microfluidic approach establishes a direct mechanistic link between ferroptosis, mitochondrial dysfunction, and neuronal vulnerability in AD, offering new insights into therapeutic targeting of ferroptosis in neurodegeneration.
Aging and biological sex modulate cardiomyopathy through interconnected metabolic, inflammatory and mitochondrial pathways. Aging impairs Sirt1/Sirt3-AMPK signaling, promotes low-grade inflammation and mitochondrial dysfunction, while sex hormones shape dimorphic resilience and vulnerability across the life course. In dilated cardiomyopathy (DCM) and inflammatory cardiomyopathy (DCMI), age aggravates Sirt1 loss, triggers compensatory AMPK activation and reduces mitochondrial proteins (TOM40/TIM23/SOD2), particularly in older men. In DCMI, Sirt1 levels stay stable but processes differ by sex. Older men show increased mitophagy; women have impaired biogenesis. Inflammaging with elevated NF-κB/IL-12 and macrophage infiltration is stronger in men. E2 suppresses NF-κB/ROS via ERα/β and promotes M2 polarization, whereas testosterone enhances PGC-1α-dependent metabolism but amplifies fibrosis. Collectively, these findings define an age-sex framework of cardiomyopathy vulnerability and support precision strategies targeting sirtuins, inflammasomes and hormone-related pathways to slow or modify disease progression.
Stress engages coordinated psychological, neuroendocrine, autonomic, and neural processes that enable adaptation to environmental demands but may contribute to vulnerability when stress is prolonged, uncontrollable, or socially evaluative. Functional neuroimaging has become central to psychoneuroendocrinology by enabling direct investigation of how acute stress shapes brain activation and connectivity and how these neural responses interact with hypothalamic-pituitary-adrenal axis regulation. This editorial introduces the Special Issue "Effects of stress on brain activation changes: Recent developments" and outlines key conceptual and methodological advances in the field. We highlight progress from endocrine-marker-based stress research toward brain-based models of stress, emphasizing evidence from scanner-based paradigms such as the Montreal Imaging Stress Task and ScanSTRESS, as well as emerging multimodal approaches including fNIRS, PET, EEG, and harmonized large-scale analyses. We discuss recent developments concerning exposure-time effects, network-level models of stress processing, and the importance of functional connectivity. We further emphasize the need to account for individual and contextual variability, including sex, gender, developmental stage, clinical vulnerability, and real-world stress relevance. This Special Issue invites contributions that use neuroimaging to advance mechanistic, translational, and reproducible models of stress-related brain function.
While public health and biomedical research have examined how intimate relationships shape chemsex among gay men, little attention has been paid to theorizing the content and limits of chemically mediated intimacy itself. Conventional understandings of intimacy emphasize affective ties that require time, commitment, and care in forging deeper connections. In the context of sexualized drug use, intimacy may emerge through alternative bodily encounters, communal care, and queer world-making organized through shared rituals, infrastructures, and affective labor. Drawing on ethnographic fieldwork conducted in Taiwan, this article conceptualizes chemsex not as a discrete behavior but as an event-based process-a contingent series of negotiations, rituals, and bodily engagements shaped by digital infrastructures, biomedical discourse, and harm reduction services. Grounded in science and technology studies and critical drug studies, it advances a topological reading of chemical practices that moves beyond intimacy as affect or proxy to emphasize intimacy as event. It traces how bodies, substances, and sociotechnical conditions co-produce pleasure, care, and shared vulnerability across chemically mediated encounters. By juxtaposing "fun-gible" intimacy and therapeutic models of "dopamine management" as competing scripts of chemical intimacy, the study resituates intimacy as a performative process of emergence rather than a fixed outcome, thereby contributing to global debates on queer sexual health, affective governance, and the ethics of drug use and care.
Growing evidence links inflammation with major depressive disorder (MDD) and treatment resistance. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a simple peripheral marker of systemic inflammation and immune balance and it may capture clinically meaningful heterogeneity in inflammatory burden, potentially contributing to variability in antidepressant response and vulnerability to treatment resistance. This study exploratively investigated whether baseline NLR values are associated with clinical response in patients with treatment-resistant depression (TRD) treated with intranasal esketamine in routine clinical practice. This retrospective observational study included patients with TRD treated with adjunctive intranasal esketamine at the Mood Disorder Unit of San Raffaele Hospital (Milan, Italy). Baseline NLR was calculated from complete blood count samples collected 1 to 7 days before treatment initiation. Clinical outcome was assessed after 7 months using the Clinical Global Impression-Improvement scale (CGI-I). Patients were classified as responders (CGI-I ≤2) or non-responders (CGI-I ≥3). An analysis of covariance (ANCOVA) was conducted to examine differences in baseline NLR while adjusting for age. The final sample included 16 patients (8 responders and 8 non-responders). Responders showed higher baseline NLR values compared with non-responders (1.81±0.81 vs. 1.23±0.29). After controlling for age, baseline NLR differed significantly between the 2 outcome groups (P=0.003). Higher baseline NLR was associated with sustained clinical improvement after 6 months of esketamine treatment in patients with TRD. Although preliminary and limited by the small sample size and retrospective design, these findings suggest that a patient's inflammatory status at baseline may affect their treatment response. Larger prospective studies are needed to clarify the role of inflammatory markers as predictors of response to esketamine.
Aging is associated with progressive changes in the neuroimmune environment that increase vulnerability to cognitive decline and neurodegenerative disease. Characteristics of this process like immune cell activation and pro-inflammatory signaling can eventually lead to behavioral changes and cognitive decline. Consequently, there is a need to discover approaches that dampen harmful aspects of neuroinflammation with age. Here, we tested the hypothesis that Mycobacterium vaccae (M. vaccae) immunization, a potential immunomodulatory therapy, will reduce age-related neuroinflammation in the rat hippocampus. Using single-nucleus RNA sequencing (snRNA-seq), we identified widespread age-associated transcriptional remodeling across multiple hippocampal cell types. Gene ontology and KEGG pathway analyses revealed prominent enrichment of pathways related to mitochondrial function, oxidative phosphorylation, and cellular stress responses in aged animals. Using immunohistochemistry, we demonstrated increased CD68 in aged Iba1+ microglia, suggesting enhanced phagocytic activity. M. vaccae immunization substantially attenuated many of these age-associated transcriptional and protein-level changes, dampening stress- and immune-related gene expression and reducing microglial phagocytic activity. Our findings highlight the immunomodulatory potential of M. vaccae to attenuate aspects of age-related neuroinflammation and underscore the complex interplay of hippocampal glial cells in shaping the inflammatory milieu during aging.
Achieving strong light-matter interaction to manipulate emission requires integrating colloidal perovskite quantum dots (PQDs) with plasmonic nanocavities, yet this integration is challenged by their vulnerability to polar solvents. We successfully synthesized highly emissive, solvent-resistant CsPbI3 PQDs and integrated them into nanoparticle-on-mirror structures. This integration enabled a 435-fold reduction in emission lifetime and a 250-fold increase in total emission intensity. Key results include a very short radiative lifetime below 12 picoseconds and a record-high single-photon emission rate exceeding 2.3 × 109 counts per second at room temperature. Notably, we also observed nonblinking single-photon emission with high purity arising from nanocavity-enhanced radiative electron-hole recombination. Finite-difference time-domain simulations confirmed ultrasmall mode volumes of ~3 × 10-5 (λ/n)3, effectively enhancing spontaneous emission via the Purcell effect. These ultrabright and nonblinking properties highlight the strong potential of this platform for future quantum technology applications.
The co-stimulatory signaling dyad of CD40 and CD40L is a potent inducer of cardiovascular inflammation and vulnerability of atherosclerotic plaques. A cytosine-to-thymidine transition (-1C > T) in the Kozak sequence of the CD40 gene (rs1883832) lowers CD40 protein expression. Here, we interrogate whether this CD40 gene variant correlates with recurrent cardiovascular events after acute coronary syndromes. The Biomarkers in Acute Cardiac Care (BACC) cohort prospectively enrolled patients presenting to the emergency department with acute chest pain and suspected myocardial infarction. Genotype status (homozygous C/C or T/T, heterozygous: C/T) was determined by a TaqMan assay in 1298 patients with either confirmation of or ruled out acute myocardial infarction (AMI). The CD40 genotype-adjusted risk for major adverse cardiovascular events (MACE) during a median follow-up time of 5.2 years was studied by multivariate Cox regression. Relative abundances of the genotypes among all participants were 55.8% for C/C, 37.1% for C/T, and 7.2% for T/T. None of the genotype variants was associated with diabetes, hypertension, hyperlipoproteinemia, or a history of coronary artery disease (CAD). T/T carriers showed a strong trend towards an increased sex- and age-adjusted risk for AMI at admission (OR 1.58, 95% CI 0.95-2.64, p = 0.078) in logistic regression analysis. MACE occurred more often in patients with the T/T genotype (HR 1.46, 95% CI 1.01-2.11, p = 0.046) compared to C/T (HR 0.96, 95% CI 0.77-1.19, p = 0.70) and C/C (HR 0.94, 95% CI 0.76-1.16, p = 0.54) carriers. This effect was independent of age, sex, diabetes mellitus, hyperlipoproteinemia, arterial hypertension, smoking status and left ventricular ejection fraction in multivariable regression. Our data indicate that - unexpectedly - the T/T genotype of rs1883832 is associated with an enhanced risk for myocardial infarction and subsequent MACE. As this SNP impedes effective CD40 translation, our findings suggest a potentially protective role of CD40 in high-risk patients.
Maternal mortality ratio (MMR) and neonatal mortality rate (NMR) are key indicators of population health and health system performance. Yet longitudinal cross-country evidence on how macroeconomic conditions-such as income growth, inflation, and unemployment-relate to maternal and neonatal mortality remains limited. We assembled a balanced country-level panel of 152 countries for 1991-2023 using World Health Organization mortality series and World Bank World Development Indicators. Outcomes (MMR, NMR) were modelled in natural logarithms; GDP per capita was log-transformed, inflation was expressed as ln(1 + IR/100), and unemployment as the first difference of log unemployment. Cross-sectional dependence was assessed using Pesaran's CD test, and-given dependence-stationarity was evaluated with Pesaran's second-generation CIPS test. Associations were estimated using two-way fixed-effects panel regressions (country and year effects) with Driscoll-Kraay standard errors (lag = 2), with sensitivity analyses using lagged GDP per capita (t - 1, t - 2) and continent-stratified models. In the global two-way Driscoll-Kraay fixed-effects models (country and year fixed effects; Driscoll-Kraay standard errors, maximum lag = 2), GDP per capita was inversely associated with both ln(MMR) (B = - 0.233, p < 0.001) and ln(NMR) (B = - 0.139, p < 0.001), while inflation (LINF) was positively associated with both outcomes (lnMMR: B = 0.055, p < 0.001; lnNMR: B = 0.042, p < 0.001). Changes in unemployment (dLUR) were positively associated with ln(NMR) in the global model (B = 0.102, p < 0.05) and in Asia (B = 0.063, p < 0.05), but were not significant for ln(MMR) in continent-specific models under the contemporaneous income specification (Table 6). This pattern may partly reflect measurement limitations of official unemployment rates in settings with large informal sectors and weaker labour-market registration; however, in the lagged-income specification (GDP per capita t - 1), dLUR was positive and statistically significant in Europe (Supplementary Table S2), suggesting that unemployment effects on maternal mortality may be specification- and context-dependent and should be interpreted cautiously. Macroeconomic conditions were associated with maternal and neonatal survival. Globally, higher GDP per capita was associated with lower maternal and neonatal mortality, and this inverse association remained in sensitivity analyses using lagged GDP per capita (t - 1, t - 2). Although the strength of income-mortality associations varied across continents and some region-outcome models were imprecisely estimated, particularly in Oceania (small number of countries), the overall pattern suggests that macroeconomic conditions may be relevant correlates of RMNCH outcomes. Inflation was related to worse outcomes in some settings, underscoring the importance of growth that preserves purchasing power and protects health-system inputs, but the inflation-mortality relationship was heterogeneous across regions. Unemployment effects appeared context-specific, with evidence most clearly observed for neonatal mortality in Asia, suggesting that labour-market and social-protection responses may be most relevant where vulnerability and out-of-pocket financing are high. These findings should be interpreted as adjusted associations rather than causal effects. Aligning macroeconomic management with RMNCH financing and access policies may help support progress in preventable maternal and neonatal deaths. Not applicable.
Replication stress (RS) and altered metabolism are two hallmarks of cancer, yet how metabolic perturbations contribute to RS remains poorly understood. Lipotransferase 1 (LIPT1) catalyzes the covalent attachment of lipoic acid to mitochondrial 2-ketoacid dehydrogenases, sustaining flux through the tricarboxylic acid (TCA) cycle. Loss of LIPT1 causes accumulation of 2-hydroxyglutarate (2-HG), which is known to inhibit α-ketoglutarate (α-KG)-dependent histone demethylases and promotes heterochromatin formation. Here, we show that 2-HG-driven heterochromatin impedes replication fork progression, causing fork stalling and RS in LIPT1-deficient cancer cells. To bypass stalled forks, PrimPol-mediated repriming resumes DNA synthesis but leaves behind single-stranded DNA (ssDNA), which requires poly(adenosine 5'-diphosphate-ribose) polymerase 1 (PARP1) for repair. Furthermore, nascent DNA at reprimed forks undergoes MRE11-dependent degradation, further destabilizing replication fork integrity. Consequently, LIPT1 deficiency promotes replication and genome instability, and therapeutic vulnerability to PARP inhibitor. Together, these findings reveal a mechanistic link between mitochondrial lipoylation and replication fork stability, uncovering a metabolic basis for genome instability in cancer.
Functional and nutritional impairments adversely affect outcomes in hematologic malignancies; however, the comparative prognostic value of widely available screening instruments remains insufficiently explored. The present study aimed to examine the association between nutritional and functional screening instruments and 12-month mortality in hospitalized patients with hematologic malignancies. In this prospective cohort of 91 patients (median age 53 years [IQR, 35-61]), nutritional screening and assessment tools (PG-SGA, GLIM criteria) and functional screening instruments (SARC-F, SARC-CalF, and Geriatric 8 [G8]) were applied within 72 h of admission. The G8 was pragmatically used as a multidimensional vulnerability screening instrument. Discriminative ability for mortality was evaluated using ROC curve analysis, and Cox regression models (unadjusted and adjusted) were used to examine associations with mortality. During follow-up, 29.7% of patients died. The G8 and SARC-CalF were associated with mortality in adjusted models (HR 4.83, 95% CI 1.13-20.68; HR 2.37, 95% CI 1.08-5.17, respectively). PG-SGA Global showed acceptable discriminative performance in ROC analyses (AUC 0.71) but was not associated with mortality after adjustment. GLIM criteria were not associated with mortality in adjusted models. The G8 and SARC-CalF scores have demonstrated prognostic utility as simple and low-cost screening tools associated with mortality in these patients with hematological malignancies hospitalized in a resource-limited service.
Acute Venous Thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, is one of the leading causes of cardiovascular mortality. Recent studies have shown racial and ethnic disparities in VTE incidence and outcomes. The objective of this review is to identify racial and ethnic disparities present in the incidence, diagnosis, and management of VTE. A comprehensive review was conducted in PubMed and ScienceDirect using the following search terms: pulmonary embolism, deep vein thrombosis, race, ethnicity, racial disparities, ethnic disparities, and social determinants. Papers were included if they were published in English and within the years 2004-2024. Papers were excluded if they studied non-US adult populations, if VTE was not a main outcome of interest, or if they focused on surgery or COVID related VTE. The resultant papers (n=52) included randomized clinical trials, systematic reviews, meta-analyses, and observational studies at single-center, multi-center, and national levels. Quantitative data on the use of Catheter-Based Therapies (CBT) by racial and ethnic groups were extracted from a subsect of papers where it was explicitly reported (n=8). Using this data, a meta-analysis was conducted to compare the utilization of catheter-based therapies for pulmonary embolism across different racial and ethnic groups. Significant racial and ethnic disparities in the diagnosis and treatment of VTE were noted. Black patients had the highest disease incidence, severity, mortality, and inpatient complications. Similar inequities may exist among other racial and ethnic groups, though these remain less well-characterized due to limited ethnic representation in current VTE literature and related clinical trials. Genetic factors contribute more to VTE risk in white patients, whereas comorbidities and socioeconomic disparities have a more significant impact on non-white patients. Several studies have noted disparities in access to catheter-directed thrombolysis for non-white patients compared to white patients. Notably, racial disparities in advanced therapy usage are reduced in the context of high-risk PE, though ethnic disparities persist. Initial studies have suggested that PERT implementation may reduce disparities in VTE management, though further research is needed to evaluate its impact on outcomes. Results of the meta-analysis further supported these findings by revealing increased CBT usage in white and non-Hispanic patients compared to black and Hispanic patients respectively. Socioeconomic vulnerability and comorbid conditions account for disparities in VTE incidence in minority populations, and poor outcomes in these groups may be tied to inequalities in access to catheter-based interventions.
Hyperosmolar-hypernatremic dehydration (HHND) is a life-threatening yet preventable neonatal condition, often due to inadequate breastfeeding. The recent North Indian heat wave heightened dehydration risks, necessitating an evaluation of extreme temperatures' impact on neonatal hydration. This retrospective study analysed neonates admitted to a tertiary care level 3 neonatal intensive care unit (NICU) at AIIMS Jodhpur between April and June 2024. Case records were reviewed, and details on maternal age, feeding practices, presenting complaints, biochemical profile, and outcome were studied. The 2024 (April-May) heat wave led to a threefold increase in NICU admissions for HND compared to the previous 2 years, with cases rising from 2 to 3 per year to 10. Primigravida mothers accounted for 70% of the cases. The mean age of presentation was 6.7 days. Affected neonates experienced weight loss ranging from 11% to 33%, with serum sodium levels between 149 and 185 mEq/l and plasma osmolarity reaching 370-450 mOsm/l. Six neonates required peritoneal dialysis (PD) due to encephalopathy/anuria. One developed aortic thrombosis with lower limb gangrene, necessitating thrombolytic therapy. MRI abnormalities were observed in one case. Despite intensive management, one neonate succumbed to sepsis. Extreme environmental heat significantly heightens the risk of hyperosmolar-hypernatremic dehydration (HND) in neonates. Proactive neonatal monitoring, early breastfeeding support, and parental education are critical to preventing dehydration and its complications, especially in tropical and resource-limited settings, where extreme heat, early discharge, and limited lactation support increase neonatal vulnerability. Judicious fluid management targeting plasma osmolarity and timely intervention with PD in severe cases can optimize survival and neurological outcomes, underscoring the need for heightened vigilance during heat waves.
Depressive disorders are characterized by heterogeneous symptoms and variable treatment response. Current interventions primarily aim to manage symptoms, yet their effectiveness remains limited. This highlights the need for early neurobiological markers to improve understanding of depression pathophysiology and guide treatment development. In this study, 38 healthy participants aged 18-40 years (21 females and 17 males) completed the self-report version of the Montgomery-Åsberg Depression Rating Scale (MADRS-S), followed by proton magnetic resonance spectroscopy (1H-MRS) data acquisition from the anterior cingulate cortex (ACC). Spectra were acquired from the dorsal (dACC) and pregenual (pgACC) subdivisions, and analyses focused on metabolite levels of γ-aminobutyric acid (GABA), glutamate + glutamine (Glx), total N-acetyl aspartate (tNAA), and total creatine (tCr). Simple and multiple linear regression analyses, controlling for age, sex, tobacco use, and alcohol consumption, revealed a negative association between depressive symptom scores and tNAA/tCr levels in both the pgACC and dACC. However, no significant associations were observed for GABA/tCr or Glx/tCr. These findings suggest that reduced tNAA/tCr levels in the dACC and pgACC may be associated with depressive symptom severity in non-clinical individuals. Given that tNAA reflects neuronal integrity and mitochondrial function, its reduction may reflect early neuronal and metabolic variation associated with depressive symptom scores. Thus, tNAA may represent an in vivo biomarker for early affective vulnerability, potentially enabling detection of depressive symptom scores in healthy individuals.