Global population aging and increased chronic stress due to numerous mass disasters including those related to pandemics, climate change, war, displacement, and political unrest all challenge our collective resilience, with a growing burden of late-life neuropsychiatric and neurodegenerative disorders placing unprecedented demands on health and social systems worldwide. With these considerations in mind, understanding and promoting brain health is becoming a priority for the prevention of neuropsychiatric disorders across the lifespan. Brain health represents a dynamic balance of neural, cognitive, and emotional processes that determine resilience to neuropsychiatric illness. In later life, this balance becomes particularly critical as neurobiological and psychosocial stressors converge to shape trajectories of neuropsychiatric and neurodegenerative disorders. This review synthesizes current evidence on the determinants of brain health in aging, emphasizing resilience as a modifiable pathway linking neuropsychiatric illness risk and prevention. We integrate insights from neuroscience, lifestyle medicine, geroscience, and social determinants of health to emphasize the value of a whole-person, life-course approach. Particular attention is given to the interplay between stress physiology, interoceptive regulation, emotional resilience, and cognitive and brain reserve across the aging continuum. Emerging frameworks including brain clocks, precision biomarkers, digital phenotyping, and artificial intelligence, are considered as tools for risk stratification, early detection, and personalized intervention. By linking resilience mechanisms to measurable biological indices, we argue for the integration of neurobiological, psychological, behavioral, and sociocultural domains to inform next-generation strategies in neuropsychopharmacology, prevention science, and the promotion of healthy brain aging.
Discrepancies in the perception of emotional and behavioral problems between adolescents and their caregivers can lead to ineffective interventions and misunderstandings in mental health care. Understanding these discrepancies and their underlying factors is crucial for improving adolescent mental health. This cross-sectional study aimed to identify distinct patterns (latent profiles) of caregiver- adolescent discrepancies in assessing emotional and behavioral problems using the Strengths and Difficulties Questionnaire (SDQ), and to examine the associations of these profiles with key demographic factors, mental health problems (including depression, self-harm, and suicidal behavior), and family environment factors. This study included 8839 caregiver-adolescent pairs from the School-based Evaluation Advancing Response for Child Health (SEARCH) study in China. Latent profile analysis (LPA) was applied to the SDQ scores reported by both adolescents and caregivers. Three latent profiles were identified: caregiver moderate-estimation adolescent healthy (5598 pairs), caregiver over-estimation adolescent problem (823 pairs), and caregiver under-estimation adolescent problem (2418 pairs). The caregiver moderate-estimation adolescent healthy profile demonstrated the lowest incidence of mental health problems and the smallest perceptual discrepancy. Multinomial logistic regression analysis revealed that male gender, history of drinking, and presence of mental health problems were associated with the caregiver over-estimation profile. Conversely, older age, male gender, residence in middle or high economic regions, mental health problems, and high family conflict were associated with the caregiver under-estimation profile. This study underscores the importance of integrating demographic, mental health problems, and family contextual factors into the assessment and intervention strategies for adolescent mental health to address caregiver-adolescent perceptual discrepancies effectively.
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.
Human milk oligosaccharides (HMOs) are complex sugars in breast milk that protect babies by preventing harmful bacteria from colonizing the gut. Our team extended the study of HMOs beyond the neonatal gut and characterized their antimicrobial activity against group B Streptococcus (GBS), a diplococcus responsible for invasive perinatal infection. To date, the mechanism of action of this antimicrobial activity has remained obscure. To address this key gap, we employed untargeted proteomics, which revealed downregulation of PcsB, an essential murein hydrolase required for cell division. Following successful purification of the active domain of PcsB, we found that this protein domain restores GBS growth in the presence of HMOs, thereby validating PcsB as an HMO protein-interacting partner. In silico docking and molecular dynamics simulations predicted that two fucosylated HMOs, lacto-N-fucopentaose I (LNFPI) and lacto-N-fucopentaose III (LNFPIII), bind to PcsB. In silico predictions were validated using microscale thermophoresis assays, which reported dissociation constants of 5 ± 1 mM for LNFPI and 263 ± 72 μM for LNFPIII. Lastly, to test the hypothesis that HMOs may directly modulate the enzymatic activity of the CHAP domain, we employed a turbidimetric assay with commercial PG as the substrate. This assay provided further evidence that HMOs inhibit CHAP. Together, these data suggest that HMOs inhibit GBS growth by binding PcsB at its catalytic site, disturbing essential cell wall separation and division.
Supervised-exercise therapy (SET) is a cornerstone intervention for management of peripheral artery disease (PAD) and is associated with improvement in ambulatory functional status. Despite strong evidence supporting the benefits of SET, accessibility and adherence remains a challenge, underling its full clinical potential. Home-based exercise therapy (HBET) has emerged as more accessible alternative to SET. This paper reviews the benefits of exercise in PAD, explores the role of home-based exercise therapy in the management of PAD, and describes the essential components of HBET in contemporary clinical practice. HBET programs have demonstrated similar improvements in ambulatory function, including walking distance and pain-free walking distance, as established SET regimens. Recent clinical trials and meta-analysis have established HBET as a reasonable alternative to SET, as reflected in the latest multi-societal clinical guidelines. Functional and quality of life improvements with HBET parallel those with SET and outperform routine exercise education. Successful HBET should include both monitoring and behavioral intervention components to improve adherence and long-term symptomatic improvements. Providers should tailor HBET to the individual patient’s needs and limitations. Ongoing research aims to understand the optimal platform to deliver HBET programs to a wide range of patients with symptomatic PAD.
