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Therapeutic Potential of Extracellular Vesicles: From Biogenesis, Isolation and Molecular Characterization to Addressing Translational Gaps and Regulatory Barriers
No full textExtracellular vesicles (EVs) have emerged as essential mediators of intercellular communication, transporting a complex repertoire of lipids, proteins, and nucleic acids that mirror the physiological and pathological status of their parent cells. This review provides a comprehensive overview of EVs from their biogenesis and molecular composition to their translational potential in human disease. This review outlines the major classes of EVs, including exosomes, microvesicles, apoptotic bodies, and oncosomes, together with recent developments in their isolation, molecular characterization, and omics-based profiling. Special focus is given to the role of EVs in viral infection, inflammation, and immune regulation, as well as their contribution to disease development and cancer biology. Moreover, we highlight the emerging clinical applications of mesenchymal stem cell-derived EVs (MSC-EVs) in regenerative medicine and oncology, alongside the therapeutic modulation of EV signaling by photobiomodulation (PBM). Finally, we address key translational challenges related to standardization, scalability, and regulatory validation. As exosome-based therapeutics fall under strict FDA and EMA oversight, their translation further depends on harmonized quality controls and robust safety evaluation. By integrating molecular mechanisms with clinical applications, this review emphasizes the transformative potential of EVs as next-generation diagnostic and therapeutic tools in precision medicine
Preferences for Game-Based Elements to Increase Preexposure Prophylaxis and HIV Prevention Engagement Among Latino Men Who Have Sex With Men: South Florida, 2022
No full textWe explored gaming elements as a tool to promote engagement in HIV prevention services among Latino men who have sex with men. We conducted thematic content analysis of semistructured interview data that we collected from 12 Latino men who have sex with men (April-August 2022) in South Florida. Themes emerged related to intervention delivery, components, and perceptions. Our findings will guide the development of a game-based intervention to improve preexposure prophylaxis and HIV prevention engagement among Latino men who have sex with men. (. 2026;116(S1):S10-S15. https://doi.org/10.2105/AJPH.2025.308353)
Increased expression of inflammasome signaling genes and proteins in selective brain regions in the intermediate stage of Alzheimer's disease
No full textNeuritic plaques (NP) are a key component of Alzheimer disease (AD) pathology composed of dystrophic neurites that form neurofibrillary tangles (NFTs) and amyloid-β (Aβ) proteins. NP accumulation is one fundamental feature seen in the intermediate stage of AD neuropathological pathology change. NPs are sites for cellular degeneration and can induce the upregulation of inflammatory signals including the inflammasome complex. We analyzed 758 genes using multiplex genomics in samples from the hippocampal, temporal and frontal brain regions that had intermediate AD neuropathological changes and aged-matched controls. In addition, we analyzed NP formation using phosphorylated tau at threonine 217 (pTau217) and Aβ antibodies along with inflammasome sensors using NOD-like receptor protein (NLRP) antibodies, apoptosis-associated speck like protein containing a caspase recruitment domain (ASC) and absent in melanoma-like receptor 2 (AIM2). Finally, we investigated if cell death is occurring cells by pyroptosis using Gasdermin D (GSDMD) antibody to detect pore formation on the membrane. Analyses show that inflammasome signaling genes and proteins are significantly increased in the hippocampus rather than the temporal and frontal lobe at the intermediate stage of AD. NPs are more prevalent in the hippocampus and temporal lobe in cases with intermediate AD pathology. ASC (1C100) immunostaining is colocalized with NLRP1, NLRP3 and AIM2. GSDMD immunostaining detected pericellular pores forming around the membrane of NFTs and in NPs. Messenger RNA and protein analyses demonstrate that inflammasome signaling molecules are elevated in AD suggesting that neuronal death occurs by the induction of pyroptosis
Demographic, Racial and Geographic Disparities in Mortality and Place of Death Among Patients with Gastrointestinal Cancers: A National Population-Based Study
No full textDevelopment of the Rome V Diagnostic Questionnaires
No full textThis article describes the development of the Rome V adult and pediatric diagnostic questionnaires. Important updates from the Rome IV versions included improved response scaling, new questions to diagnose 3 additional adult DGBI and 14 additional pediatric DGBI (compared to the Rome IV questionnaires), extra questions to clarify the context of DGBI symptoms for research purposes, and the addition of anatomical images to enhance response accuracy. The performance of the Rome V adult questionnaire was tested in Internet surveys in 15 countries, and the pediatric questionnaires in 4 countries. The results indicate that the new questionnaires generally identify DGBI to a similar degree and with the same demographic patterns as the prior Rome IV versions. The Rome V Questionnaire Committee concluded that these new diagnostic questionnaire versions are well suited for epidemiologic and clinical research of DGBI in the Rome V era for both adult and pediatric populations
Interrater reliability in pediatric high-resolution anorectal manometry recordings
No full textObjectives High-resolution anorectal manometry (HR-ARM) is a diagnostic test assessing anorectal neuromuscular function in children with constipation and/or fecal incontinence. Interrater reliability of HR-ARM in children has not been previously studied. The aim of this study was to assess the interrater reliability of pediatric HR-ARM studies.Methods Ten pediatric gastroenterologists specialized in neurogastroenterology and motility analyzed ten deidentified pediatric HR-ARM studies using dedicated analysis software (Solar GI HRM v9.1, MMS, Enschede, the Netherlands). Anal canal resting pressure, squeeze pressure and duration, presence of the rectoanal inhibitory reflex (RAIR), bear down maneuver (normal/abnormal), and final interpretation of the study (normal/abnormal) were evaluated. Fleiss' Kappa (kappa) and intraclass correlation coefficient (ICC) were used for categorical and continuous data, respectively.Results Interrater reliability was excellent for resting pressure (ICC 0.97, 95% confidence interval [CI 0.93-0.99), squeeze pressure (ICC 0.97, 95% CI 0.94-0.99), and squeeze duration (ICC 0.93, 95% CI 0.85-0.98). A fair interrater agreement for the RAIR (kappa = 0.35) was seen, and a moderate interrater agreement was seen for interpretation of the bear down maneuver and the final interpretation of the study either being normal or abnormal (kappa = 0.50 and kappa = 0.43, respectively).Conclusions This study demonstrated excellent interrater reliability in assessing HR-ARM anal canal resting pressure, squeeze pressure, and squeeze duration and suboptimal reliability in interpreting the detection of a RAIR and bear down maneuver. These findings highlight the need for standardization of HR-ARM protocols and interpretation criteria in children.</p
AI in geriatric psychiatry: precision meets human experience
No full textArtificial intelligence (AI) and robotics are rapidly transforming geriatric psychiatry, offering powerful tools for early detection, personalized treatment, and enhanced care delivery. As the global population ages, these technologies promise not only greater efficiency but also new avenues for delivering scalable, accessible mental health support. However, as AI increasingly engages with domains once considered uniquely human-emotional intelligence, decision-making, and interpersonal connection-it raises deeper questions about the boundary between AI-simulated interaction and authentic human connection. This review examines the intersection of computational precision and existential complexity, emphasizing how theoretical frameworks such as the Theory of Computing (TOC) and Theory of Mind (ToM) can guide ethical and human-centered integration. While AI systems may convincingly simulate empathy or companionship, they cannot share subjective experience, vulnerability, or existential depth. By contrasting computational precision with the irreducible aspects of human complexity, we advocate for a transdisciplinary approach that embraces both the transformative potential of technology and the irreplaceable richness of human connection-especially in the later stages of life, when questions of purpose, mortality, and selfhood become most profound
