One of the fundamental biological processes underlying aging is the decline in physical performance. Sarcopenia, dynapenia, chronic inflammation, and other factors including the loss of motor units largely account for this decline. Master athletes-individuals who train and compete well beyond early adulthood-represent a valuable model for studying healthy aging. In the general population, physical performance follows a characteristic lifespan trajectory, increasing from childhood to a peak in early adulthood and progressively declining with aging due to a reduction in muscle mass and quality, and in multisystem physiological functions. The seminal studies by Gava and colleagues on master athletes indicate that, under ideal conditions of being disease-free or injury-free, performance loss of these athletes follows an attenuated, linear fashion from early adulthood into advanced age. While lifelong training cannot halt age-related physiological deterioration, it can attenuate the rate of functional decline in cardiovascular, neurocognitive, and musculoskeletal functions. From a sex-based perspective, males demonstrate an absolute advantage in power and strength compared to females, whereas differences in endurance performance are smaller. With age, the physical performance gap between the two sexes tends to narrow, particularly in endurance disciplines. Overall, the master athlete model supports the concept that aging-related performance decay follows predictable biological rules, while its rate remains highly modifiable through sustained physical activity. These insights have important implications for exercise prescription, preventive strategies, and healthy aging.
Malaria remains one of the leading causes of death worldwide, particularly in Africa, where various control interventions such as case management, insecticide-treated nets (ITNs), intermittent preventive treatment in pregnant women and infants, and indoor residual spraying (IRS) have been implemented. Insecticide resistance in malaria vectors poses a major challenge to vector control efforts. This study assessed the insecticide resistance status of Anopheles gambiae s.l. populations in rice agroecosystems of Anambra State, Nigeria. Mosquito larvae were sampled from four rice-farming clusters in Anambra state, reared to adulthood at the National Arbovirus and Vector Research Center (NAVRC) and tested using the WHO susceptibility bioassay against four insecticides namely dichloro-diphenyl-trichloroethane (DDT), pirimiphos-methyl, bendiocarb, and deltamethrin. Knockdown resistance (kdr) mutations were also analyzed. Results revealed confirmed resistance to DDT and deltamethrin, likely due to past agricultural use of DDT and cross-resistance with pyrethroids, which are widely used in ITNs and IRS. However, An. gambiae s.l. populations remained susceptible to bendiocarb and pirimiphos-methyl, except in Umunze, where resistance to pirimiphos-methyl was detected. The L1014F kdr mutation was detected at varying frequencies across locations, a key genetic marker for resistance to pyrethroids and DDT, in both An. gambiae s.s. and An. coluzzii. These findings highlight the importance of continuous insecticide resistance monitoring in rice agroecosystems, improved pesticide regulations and the implementation of integrated vector control management to slow down the spread of resistance in malaria vectors in Anambra.
Lymphatic filariasis (LF) remains a significant public health challenge in many tropical regions where the disease is endemic. In Malaysia, LF is found in small pockets across the country. Asymptomatic carriers play a critical role in transmission but are often undetected. This report details an investigation of an asymptomatic filariasis reported by local health authorities involving an 83-year-old female patient residing in the Bako area, Sarawak. Despite being immobile due to a stroke, routine screening identified an infection with Brugia malayi through microscopy and a rapid diagnostic test. Interestingly, the patient exhibited no acute or chronic symptoms typically associated with filariasis. Contact tracing among her family members revealed that her son was also infected. Both patients received treatment with diethylcarbamazine (DEC) at a dosage of 6 mg/kg, along with albendazole 400 mg and ivermectin 12 mg. Preventive measures included health education, entomological studies, and the implementation of a 'Test & Treat Filariasis' program in the village. By documenting both the index case and a secondary asymptomatic case within the same household, the study provides a strong example of how routine screening and contact tracing can identify hidden sources of infection. This adds significant value to LF elimination strategies and emphasizes the importance of community-level surveillance programs. Coordinated efforts by health authorities, including contact tracing, environmental assessments, and targeted treatment, are essential for controlling the spread of LF and safeguarding public health.
Human T-cell lymphotropic virus type 1 (HTLV-1) is endemic in several regions worldwide and is associated with a wide spectrum of clinical manifestations with complex and still poorly understood pathogenesis. Among the reported outcomes in people living with HTLV-1, oral alterations stand out due to their potential negative impact on quality of life. Here, we reviewed the literature on HTLV-1 oral outcomes through a structured narrative review conducted in accordance with the SANRA principles. The most frequently reported oral complications include xerostomia, hyposalivation, periodontal disease, and mucosal lesions, which are commonly associated with inflammatory processes and salivary gland dysfunction. These findings underscore the importance of oral health within the multidisciplinary care of individuals living with HTLV-1, highlighting the need for preventive and therapeutic strategies that enhance overall well-being. Nevertheless, significant gaps remain in the literature, underscoring the need to expand research efforts, strengthen professional training, and increase awareness regarding oral care in this population.
Research suggests that identification with one's future self-encompassing vividness, connectedness, and valence-plays a key role in motivating future-oriented choices and goal pursuit. Interventions aiming to strengthen future self-identification have been shown to reduce maladaptive behaviors and promote well-being, but traditional approaches often rely heavily on imagination. Emerging technologies offer novel opportunities to make the future self more vivid and tangible, potentially reducing cognitive burden, and enhancing intervention effectiveness. This randomized controlled trial evaluated the effectiveness of a digital intervention on the following primary outcomes: future self-identification, future orientation, consideration of future consequences, self-defeating behavior, goal commitment, and goal achievement. In this parallel, 3-arm randomized controlled trial, 321 first-year students from a large public university in the Netherlands were randomized (1:1:1) with blocks of 9 to a smartphone app-based future-self intervention, an immersive virtual reality (VR) version of the same intervention, or an active goal-setting control condition. Participants assigned to the smartphone or VR condition engaged with the intervention over a 3-week period, during which they interacted with their 10-year-old self, their future self. Participants in the control condition received no further support. Each of the 3 conditions consisted of 107 participants, who were all included in the analyses following the intention-to-treat principle. Due to the nature of the intervention, blinding was not possible. Compared to the goal-setting control condition, both intervention conditions yielded significant short-term improvements on all 3 aspects of future self-identification (smartphone: dvividness=0.49; dvalence=0.44; dconnectedness=0.43; VR: dvividness=0.35; dvalence=0.44; dconnectedness=0.43), and a small decline in vividness (smartphone: d=-0.36; VR: d=-0.23) and connectedness (smartphone: d=-0.36; VR: d=-0.32) at 6-month follow-up. Additionally, the intervention buffered declines in future orientation during the study period (smartphone: d=.16; VR: d=0.18), and VR delivery led to significantly higher weekly goal achievement (d=0.88). However, effects on future orientation were not sustained over time (smartphone: d=-0.18; VR: d=-0.25), resulting in similar levels across conditions at 6-month follow-up. Furthermore, no significant effects emerged for other primary or secondary outcomes, such as self-defeating behavior (smartphone: doverall=-0.10; VR: doverall=-0.03), impulsivity (smartphone: doverall=-0.07; VR: doverall=-0.09), or academic performance (η2partial=0.00). No adverse events were reported in any of the conditions. This randomized controlled trial innovatively compares smartphone and immersive VR future-self interventions. Findings suggest that digital interventions leveraging visual and interactive representations of the future self can strengthen future self-identification and future orientation, and support (short-term) goal pursuit. Together, they highlight the potential of scalable digital future self approaches for educational and preventive health contexts.
Human metapneumovirus (hMPV) is an under-recognized cause of severe respiratory illness in high-risk adults. We conducted a systematic review and meta-analysis to quantify hMPV prevalence and clinical outcomes in adults with chronic underlying conditions predisposing them to severe respiratory illness, including the immunocompromised. We searched MEDLINE, Embase, and BioRelate (January 2010 to February 2025) for studies of laboratory-confirmed hMPV in adults (≥ 18 years) with high-risk chronic or immunocompromising conditions. We extracted data on hMPV positivity and key outcomes (hospitalization, intensive care unit [ICU] admission, respiratory support, length of stay, and mortality). We performed random-effects meta-analyses for outcomes reported in ≥ 3 studies and assessed study quality using an adapted Joanna Briggs Institute checklist. We included 72 studies. Among immunocompromised adults with hMPV infection, 55.2% (95% confidence interval [CI], 42.0-67.7%) required hospital admission. Among immunocompromised patients hospitalized with respiratory illness, hMPV was detected in 5.4% (95% CI, 2.7-10.8%). Among patients with cardiovascular disease, 11.4% (95% CI, 8.0-16.1%) tested positive for hMPV. Regarding patients with chronic respiratory conditions, 3.4% (95% CI, 2.4-5.0%) of patients with chronic obstructive pulmonary disease exacerbations and 7.6% (95% CI, 2.5-20.5%) of patients with asthma exacerbations were hMPV-positive. Among hospitalized hMPV-positive high-risk patients, 13.0% (95% CI, 8.8-18.9%) required ICU admission, 43.6% (95% CI, 34.9-52.7%) required supplemental oxygen, and 7.3% (95% CI, 1.2-33.8%) required mechanical ventilation. The mean length of hospital stay was 10.4 days (95% CI, 3.4-17.4%). The pooled case fatality ratio among hospitalized adults with hMPV infection was 2.4% (95% CI, 0.1-35.1%). hMPV is a substantial cause of severe respiratory illness in high-risk adults. Enhanced detection, surveillance, and preventive strategies are needed to reduce hMPV-associated morbidity in vulnerable populations.
Individuals with mental disorders often experience multiple disease episodes and diagnostic changes after initial psychiatric contact. However, studies that comprehensively investigate heterogeneity in disease development beyond pairs of comorbid diseases and mortality from a transdiagnostic perspective have been lacking. To comprehensively study sex and age patterns of disease development for 7 major groups of mental disorders. This cohort study included data from linkage of national Danish registers of all adult individuals living in Denmark between 2000 and 2018. Adult individuals with 1 of the following first-time mental disorder diagnoses were included: substance use disorder, schizophrenia, psychotic disorder other than schizophrenia, mania and bipolar disorder, major depressive disorder, anxiety-related disorders, or personality disorders. Data were analyzed from August 2023 to December 2025. For each of the 7 mental disorder categories, age- and sex-specific estimates of (1) the number of diagnostic shifts, (2) the absolute risk of pairwise diagnostic shifts, (3) the absolute risk of diagnostic recurrence, and (4) the number of psychiatric contacts encompassing inpatient admissions, outpatient treatment courses, and emergency department visits were calculated using age groups 18 to 24 years, 25 to 39 years, 40 to 59 years, and 60 years or older and male and female sex. A total of 273 400 individuals (mean [SD] age at first contact, 41.4 [18.7] years; 150 349 female [55.0%]) with mental disorders were included and followed up for 2.1 million person-years. Diagnostic shifts were observed among 66 474 individuals (24.3%), and 30 558 (11.8%) had multiple diagnostic shifts. Individuals with psychotic disorders had the highest number of psychiatric contacts and diagnostic shifts. Younger age at first contact was associated with more psychiatric contacts and higher number of diagnostic shifts irrespective of diagnosis given at first contact as well as higher probabilities for most pairwise diagnostic shifts and diagnostic recurrence. Males showed a pattern of higher absolute risk of diagnostic shifts to substance use disorders and schizophrenia spectrum disorders than females, whereas females had a higher probability of diagnostic shifts to mood disorders, anxiety-related disorders, and personality disorders. This study found that disease development across the 4 outcomes was highly dependent on the specific diagnosis given at first contact as well as the patient's sex and age group. These findings are important for treatment planning and follow-up strategies to ensure that preventive initiatives are offered to high-risk individuals.
In utero stenting of the atrial septum has been introduced for fetuses with hypoplastic left heart syndrome (HLHS) and intact atrial septum (IAS) to prevent secondary pulmonary vascular damage caused by left atrial hypertension. Previous reports revealed a high risk of significant or complete in-stent obstruction after successful intervention due to endothelial proliferation. We report a fetus with HLHS and IAS complicated by nutmeg lung who underwent successful fetal atrial septal stenting using an everolimus-eluting stent (Xience Sierra; Abbott). The procedure resulted in immediate left atrial decompression and maintained an unrestrictive interatrial communication until delivery. The use of a drug-eluting stent resulted in sustained stent patency without evidence of endothelial overgrowth and without detectable systemic adverse effects in the fetus. In utero use of an everolimus-eluting stent appears safe and may reduce the risk of in-stent obstruction in fetuses with HLHS and IAS.
Atrial fibrillation (AF) increases cardiovascular risk in patients with chronic kidney disease (CKD). The safety and efficacy of early rhythm control (ERC) in patients with CKD is not fully established. This predefined secondary analysis of the EAST-AFNET 4 trial assessed the effectiveness and safety of ERC in patients with CKD defined by estimated glomerular filtration rate (GFR). EAST-AFNET 4 randomized patients with recently diagnosed AF and comorbidities to ERC or usual care (UC). Key outcomes were analyzed by Kidney Disease Improving Global Outcomes defined CKD groups. The primary efficacy outcome combined cardiovascular death, stroke, hospitalization for worsening heart failure, or acute coronary syndrome. The safety outcome combined death, stroke, and serious rhythm control-related adverse events. Recurrent AF was a secondary outcome. Baseline creatinine was available in 2,742 of 2,789 (98.3%) patients. In this study, 23% had CKD (GFR: <60 mL/min/1.73 m2). Patients with CKD were older (CKD: 74 ± 7.4 years; no CKD: 69 ± 8.3 years; P < 0.001), had higher CHA2DS2-VASc scores (CKD: 4 ± 1.4; no CKD: 3.2 ± 1.2; P < 0.001), and more primary outcome events over 5.1 years of follow-up (HR: 0.98 per mL GFR decrease [95% CI: 0.97-0.99 per mL GFR decrease]). ERC reduced the primary outcome with and without CKD (no CKD: ERC: 3.4%/100 patient-years; UC: 4.1%/100 patient-years; HR: 0.84; P < 0.001; CKD: ERC: 5.8%/100 patient-years; UC: 8.5%/100 patient-years; HR: 0.67; P < 0.001; Pinteraction = 0.133). CKD increased safety outcomes without interaction with ERC (Pinteraction = 0.927). Patients with CKD experienced more AF recurrences with UC (Pinteraction = 0.036). ERC effectively and safely reduces cardiovascular events in patients with recently diagnosed AF and stroke risk factors with and without CKD. (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial (EAST); NCT01288352).
Trauma exposure and posttraumatic stress (PTS) symptoms are well-documented health disparities in Latinx migrants, explaining a diverse array of physical and mental health complaints as well as role limitations for both youth and adults. Few studies have examined the influence of the migration journey on PTS in Latinx migrants. We examined the added effect of migration-related predictors, above and beyond general trauma exposure, of PTS in two samples of Latinx migrants with the broad aim of uncovering unique predictors of PTS in this high-risk population. Both studies investigated predictors of posttraumatic distress using information collected about individuals' demographics (e.g., age, gender, country of birth) and migration journey to the U.S., while controlling for pre-migration trauma exposure. The current studies used one sample of Latinx adult migrants seeking asylum (N = 276) collected at the Texas-Mexico border and one sample of recently immigrated Latinx youth (N = 69) collected at an urban school in the Southwestern United States. Across both samples, hierarchical regression analyses revealed that witnessing or experiencing something frightening during migration (p = 0.009 in youth; p <0.001 in adults) predicted PTS, even after controlling for general trauma exposure. Our results underscore the importance of routinely screening Latinx migrants for migration-related trauma in clinical and community settings. As the U.S. halts asylum processing as part of its sweeping immigration enforcement actions, our findings highlight the urgent need to expand legal paths to entry to prevent migrants from being forced into traumatic and dangerous routes.
Avian necrotic enteritis (NE), caused by Clostridium perfringens, poses a significant threat to the global poultry industry, exacerbated by rising antibiotic resistance. In this study, we applied a pangenome-guided reverse vaccinology approach to design a multi-epitope chimeric vaccine candidate. From the analysis of 45 genomes, our filtering pipeline identified three conserved and functionally synergistic target proteins: the type IV pilus assembly protein PilO and the prepilin peptidase-dependent protein A, both necessary for bacterial adhesion, and the regulatory protein MsrR, which is crucial for cell-wall integrity. High-affinity B-cell epitopes derived from these three proteins were assembled into an optimized chimeric construct. Structural modeling and molecular docking with Gallus gallus Toll-like receptors (TLRs) indicated strong binding affinity, while physicochemical analyses predicted high stability and antigenicity. We also propose an experimental validation plan encompassing recombinant production, formulation timeline, and in vivo endpoints in chickens, aligned with protein-based MEVs that have demonstrated efficacy in bacterial models. This work presents a rationally designed vaccine candidate that simultaneously targets the pathogen's offensive (adhesion) and defensive (cell integrity) mechanisms, offering a robust computational framework to accelerate the development of antibiotic alternatives in poultry production.
Scrub typhus, a zoonotic bacterial infection caused by the arthropod-borne, Gram-negative, obligate intracellular bacillus Orientia tsutsugamushi and transmitted by larval chiggers, is an underdiagnosed cause of acute undifferentiated febrile illness. Its clinical spectrum ranges from a self-limited denguelike illness to rapidly progressive multiorgan dysfunction driven by smallvessel vasculitis, including pneumonitis, acute kidney injury, hepatitis, encephalitis and circulatory shock. Early recognition is frequently missed because the characteristic eschar may be absent or easily overlooked in concealed or pigmented skin sites, and definitive diagnostics such as polymerase chain reaction (PCR) or indirect immunofluorescence assay (IFA) are often unavailable in resource-limited settings. Occupational and environmental exposures, particularly work in oil palm or rubber plantations and contact with forest- estate ecozones, remain key epidemiological clues that may be under-elicited in routine clinical practice. We report a case series of four patients with confirmed scrub typhus presenting to a hospital in Kluang district, Johor, Malaysia. All patients had acute fever and non-specific viral-like symptoms, including malaise, chills, headache and myalgia. Thrombocytopenia and acute kidney injury occurred in 50%, while 75% demonstrated transaminitis. Eschars were identified in all patients following comprehensive dermatological examination. Diagnosis was confirmed by PCR for O. tsutsugamushi DNA, a fourfold rise in IFA titres, or a single high-titre IgM or IgG in a compatible clinical syndrome. Three patients (75%) had clear domiciliary or occupational risk factors, including oil palm work or residence near secondary scrubland. One patient developed organ-threatening complications with acute kidney injury and severe hepatitis, illustrating the vasculitic end-organ involvement of severe scrub typhus. All patients achieved clinical defervescence and symptomatic improvement within 24-48 hours of doxycycline initiation, consistent with the characteristic brisk antimicrobial response. This series underscores the need for a low threshold of clinical suspicion and early empiric rickettsial coverage in undifferentiated febrile illness with relevant exposure in rural Malaysia and highlights the need for larger multicentre studies to define predictors of severity, guide triage and inform prevention in high-risk land-use settings.
Carbon nanostructures (e.g., graphene, CNTs, MXenes) offer high strength and conductivity but suffer from severe agglomeration, instability, and complex synthesis, which hinder their scalable assembly into robust carbon networks. Meanwhile, the current methods for constructing nano carbon-mesh (NCM) show enormous limitations, e.g., complex processes and enormous energy consumption, etc., making it difficult to achieve green, low-carbon, and large-scale applications. Here, an efficient NCM preparation method of hydro-cage de-shielding strategy to implement instantaneous carbonization-polymerization was conceptualized. During the initial stage of hot-pressing, cellulose-based film (CF) carbonized into quasi-spherical carbonized polymer dots (CPDs), where the system is containing enormous water, existed hydro-cage shielding effect, which formed a huge barrier between CPDs, preventing CPDs from further polymerization. As the hot-pressing progresses, water continuously evaporated or transformed from the free water state to the bound water state, the hydro-cage shielding effect gradually weakened, the system formed a core of CPDs and further underwent polymerization and growth through its surface functional groups, gradually forming NCM similar to a dragonfly's wing with excellent toughness and load-bearing capacity. As a result, the final NCM-plywood achieved a wet shear strength of 1.24 ± 0.05 MPa under 63°C, exceeding the Class II plywood requirement (≥ 0.7 MPa).
Ventriculo-pyeloureteral (VPU) shunting is a rare salvage procedure for hydrocephalus when traditional ventriculoperitoneal (VP) and ventriculoatrial (VA) shunts fail. We report the successful use of a self-expanding, nitinol-based ureteral stent (Allium Medical Solutions, Israel) to facilitate VPU shunting in a toddler with complex multicystic hydrocephalus. A premature infant born with duodenal atresia developed severe post-hemorrhagic hydrocephalus resistant to multiple VP and VA shunt revisions due to extensive peritoneal adhesions and recurrent atrial thrombosis. A VPU shunt was attempted as a last resort but was complicated by urinoma formation and obstruction due to the small caliber of the toddler's ureter relative to the catheter. To salvage the procedure, a large-caliber Allium ureteral stent was deployed to passively dilate the ureter, creating a protected channel for the shunt catheter. At 7 months follow-up, the patient demonstrated stable neurological function, effective CSF drainage, and no vesicoureteral reflux. This case highlights that VPU shunting combined with an Allium stent is a viable last-resort option, preventing ureteral obstruction by the shunt catheter.
Cardiovascular disease (CVD) is the leading cause of mortality in patients with psoriasis, yet structured CVD prevention is not routinely embedded in dermatology care. To evaluate the effectiveness of a text-messaging intervention in improving patient activation and cardiovascular risk factors among patients with psoriasis. This single-center, parallel-group randomized clinical trial took place at a tertiary hospital dermatology clinic in Australia from February 2024 to February 2025. Adults with dermatologist-confirmed psoriasis were randomized 1:1 during outpatient dermatology visits between April and July 2024. Data were analyzed from February to April 2025. A 6-month text-messaging intervention (Tobacco, Exercise, and Diet Messages for Psoriasis [TEXTME PSO]), comprising 4 text messages per week, compared with standard care. The primary outcome was score on the 13-item Patient Activation Measure. Secondary outcomes included Mediterranean Diet Score, physical activity, cardiometabolic measures, psoriasis-CVD knowledge, medication adherence, Psoriasis Area and Severity Index, Dermatology Life Quality Index, and user feedback. Analysis of covariance was used to adjust for baseline values under an intention-to-treat framework with multiple imputation. Among 111 participants (mean [SD] age, 51.8 [13.2] years; 71 [65.1%] male), the intervention showed a statistically significant improved patient activation at 6 months compared with usual care (adjusted mean difference, 10.8 points; 95% CI, 7.0-14.6 points; P < .001). Statistically significant improvements were also observed in Mediterranean diet adherence (adjusted mean difference, 1.7; 95% CI, 1.0-2.4; P < .001), medication adherence (adjusted mean difference, 1.6; 95% CI, 0.8-2.5; P < .001), and psoriasis-CVD knowledge (adjusted mean difference, 6.6; 95% CI, 4.7-8.4; P < .001). Minutes per week of physical activity increased (adjusted mean difference, 127.9; 95% CI, 21.9-234.0; P = .02), and body mass index, calculated as weight in kilograms divided by height in meters squared, decreased (adjusted mean difference, -1.0; 95% CI, -1.4 to -0.7; P < .001). No statistically significant between-group differences were observed for lipid parameters, hemoglobin A1c, smoking behavior, dermatology-specific quality of life, or psoriasis severity. In this randomized clinical trial, a text-messaging intervention improved patient activation and cardiovascular risk behaviors in adults with psoriasis. While biomarker changes were modest or not statistically significant, findings support digital tools as an adjunct to cardiovascular risk in dermatology care. ANZCTR Identifier: ACTRN12624000498594.
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Elderly patients exhibit heightened susceptibility to postoperative complications following general anesthesia and surgery, yet the molecular mechanisms driving this age-dependent vulnerability remain poorly defined. We performed RNA sequencing on olfactory bulb (OB), hippocampus (HI), lung, and spleen from young (3-month, m), late middle-aged (17 m), and geriatric (27 m) male C57BL/6 mice 24 h after 2 h of exposure to isoflurane anesthesia and laparotomy (ISO/OP). Short-term ISO/OP elicited pronounced, age-dependent transcriptional remodeling across tissues. Late middle-aged mice exhibited robust activation of stress- and metabolism-associated pathways in the OB and HI, accompanied by suppression of lipid, synaptic, and structural maintenance programs. In contrast, young adults displayed limited responses, characterized by modest and adaptive synaptic remodeling in the HI. Peripheral organs showed a parallel age-dependent divergence. Late middle-aged mice exhibited amplified immune and inflammatory signaling in the lung and spleen alongside suppression of structural, regulatory, and metabolic homeostatic programs, whereas young adults demonstrated attenuated, metabolically adaptive transcriptional responses. Circulating extracellular vesicles (EVs) mirrored tissue-level shifts, indicating a systemic transition from adaptive plasticity in 3 m to stress and immune dominant signaling by 17 m. Geriatric mice displayed a distinct response pattern, characterized by activation of stress and detoxification programs in brain tissues, altered circadian gene expression in lung and spleen, and extensive remodeling of EV protein cargo enriched for inflammatory and growth factor-related signatures. Together, these findings indicate that late middle-age is associated with amplified peri-anesthetic biological reactivity across central and peripheral systems, suggesting an under-recognized window for perioperative risk stratification and preventative intervention.
Obesity is a global health challenge. An increasing number of patients with obesity are admitted to an intensive care unit. Airway management in these patients represents a unique challenge due to significant anatomical and physiological alterations. Increased adipose tissue in the face, cheeks, pharynx, hypopharynx, and neck narrows the upper airway, renders soft tissues more collapsible, and complicates airway management. In addition, the functional residual capacity is reduced, resulting in markedly shortened safe apnea time, contributing to severe hypoxemia during intubation. Non-invasive ventilation is effective in mitigating this risk and should be applied from pre-induction to laryngoscopy. Peri-intubation physiological optimization should include assessment of preload and cardiac contractility, with careful consideration of right ventricular strain. The transition from negative to positive intrathoracic pressure should be closely monitored, with cautious titration of positive end-expiratory pressure. Recognition of these anatomical and physiological challenges may prompt clinicians to consider awake intubation in selected patients. When rapid sequence induction is performed, both ketamine and etomidate are appropriate options; the choice between them should be guided by the clinical context, patient characteristics, local practice patterns and availability. Videolaryngoscopy increases the incidence of successful intubation on the first attempt and should be adopted routinely in the population with obesity. Several questions remain unanswered, including the safety and efficacy of pre-emptive vasopressor use to prevent post-intubation cardiovascular collapse and the optimal dosing of hypnotic agents to achieve ideal intubation conditions, while minimizing adverse events.
This JAMA Insights discusses the transmission, diagnosis, management, and prevention of chikungunya.
Non-high-density-lipoprotein (non-HDL) cholesterol and apolipoprotein B (apoB) are better markers of atherosclerotic cardiovascular disease (ASCVD) risk than low-density-lipoprotein cholesterol, but whether non-HDL cholesterol or apoB is superior to the other is less clear. To assess if non-HDL cholesterol provides information on ASCVD beyond apoB, and vice versa. The Copenhagen General Population Study, a population-based contemporary cohort study in Danish individuals recruited in 2003-2015 with a median of 13.2 (IQR, 10.3-15.8) years of follow-up, included women and men not taking lipid-lowering medication and with non-HDL cholesterol and apoB measurements at baseline. Data were analyzed from January 3 through June 23, 2025. Continuous non-HDL cholesterol and apoB assessed as absolute levels and SDs as well as categories of concordance/discordance between non-HDL cholesterol and apoB defined by medians-(1) concordant low: non-HDL cholesterol and apoB less than the median; (2) discordant high apoB: non-HDL cholesterol less than the median and apoB greater than the median; (3) discordant high non-HDL cholesterol: non-HDL cholesterol greater than the median and apoB less than the median; and (4) concordant high: non-HDL cholesterol and apoB greater than median values. Myocardial infarction and ASCVD events estimated by Cox proportional hazards regressions using age as 19 years the underlying time scale and delayed entry (left truncation) at baseline. This cohort study in 94 398 individuals (53 042 women [56%]) with a total of 2462 first myocardial infarction (MI) and 5723 first ASCVD events found that any higher levels of non-HDL cholesterol or apoB on continuous scales were associated with similar increased risk of MI and ASCVD; for 1-SD higher levels, the multivariable-adjusted hazard ratio (HR) for ASCVD was 1.16 (95% CI, 1.13-1.19) for non-HDL cholesterol (39 mg/dL) and 1.14 (95% CI, 1.12-1.17) for apoB (30 mg/dL). Further adjusting for non-HDL cholesterol in the apoB model, and vice versa, attenuated the HRs, although the findings were still significant. Compared with concordant low non-HDL cholesterol and apoB, the HR for MI was 1.32 (95% CI, 1.10-1.59) for discordant high apoB, 1.30 (95% CI, 1.05-1.60) for discordant high non-HDL cholesterol, and 1.69 (95% CI, 1.53-1.85) for concordant high non-HDL cholesterol and apoB; corresponding values for ASCVD were 1.14 (95% CI, 1.01-1.29), 1.21 (95% CI, 1.06-1.38), and 1.36 (95% CI, 1.28-1.44). In this study, in individuals not taking lipid-lowering medication, non-HDL cholesterol provides information on ASCVD risk beyond apoB, and vice versa, indicating that both cholesterol content and particle number are important for risk.