Medicine and Pharmacology

Abstract: Respiratory syncytial virus (RSV) remains a leading cause of infant lower respiratory tract infection, hospitalization, and death in Latin America and the Caribbean, where unequal access to diagnosis, medical care, oxygen, referral, and intensive care worsens outcomes. New passive immunization tools, maternal RSV prefusion F vaccination and long-acting monoclonal antibodies, can protect infants before peak vulnerability. Still, their population impact depends on timing, coverage, equity, financing, surveillance, and program design. Emerging regional experience with hybrid strategies may help close protection gaps among infants missed or insufficiently protected by maternal immunization. Severe early-life RSV disease is consistently associated with recurrent lower respiratory tract infections, wheezing, asthma, impaired lung-function trajectories, and increased health-care use. However, causality and long-term effects of current preventive products remain uncertain. A regional agenda linking maternal-infant cohorts, surveillance, equity analyses, and life-course economic evaluation is needed to define the full public health value of RSV prevention.

Abstract: Teaching is a critical component of medicine. Many institutions offer faculty programs to develop their teaching skills and some offer education electives to medical students. This exploratory study describes the implementation and outcomes of a concentration that was co-created by faculty and medical students using personalized educational approaches. The integration of precision education principles into such a concentration is an unexplored area of study, offering a novel approach for tailoring educator development pathways for medical students. The concentration consists of interactive skill development workshops, educator development sessions, a teaching practicum, one medical education scholarship or research project, and observed structured teaching examinations. The first graduating cohort (n=6) participated in interviews which were iteratively open-coded by 3 coders. The interviews revealed 4 themes: 1) personalization and flexibility supported individualized educator development; 2) professional identity formation and career validation as medical educators; 3) development of teaching skills and approaches; and 4) potential for improvement of the concentration. This pathway combined a core curriculum, individualized learning, authentic teaching experiences, feedback, mentorship, and an educational scholarship or research project. These findings provide insights for institutions internationally seeking to develop student-centered education programming to tackle the educator development gap present in medical training.

Abstract: Premature adult death (PAD) may conceal clinically relevant monogenic disease. We performed exome sequencing in 127 deceased participants of the population-based Polish WOBASZ study (91 males, 36 females; mean age at death 47 years, range 26–55). Reportable variants were identified in 52 individuals (40.9%); after excluding low-penetrance risk factors and speculative findings, 39 (30.7%) remained. Genetic findings were considered highly likely to have contributed to cause of death in 9 (7.1%) and moderately likely in 16 (12.6%). Thirteen participants (10.2%) carried reportable variants in genes on the ACMG secondary findings list. Cancer-predisposition variants were enriched relative to 1,000 reference adults [3.9% vs 1.5%; Odds ratio (OR) 2.7, p=0.065], and genotype–cause-of-death concordance was greater for cancer than non-cancer ACMG findings (3/5 vs 0/8; OR 23.8, p=0.035). Broadly defined genetic cancer predisposition was present in 8 (28.6%) cancer deaths, involving BRCA1, BRCA2, MSH6, EPCAM, RAD51D, CHEK2 and JAK2. Additional findings included dominant neurodevelopmental variants, variants in genes associated with cardiomyopathy and vascular disease, two 22q11.2 deletions, and candidate novel associations implicating DROSHA, KCNQ1 and LZTS1 in germline cancer predisposition and EOLA2 and ARID4A in metabolic or neurodevelopmental disease. These results support broad exome/genome-based molecular autopsy in PAD.

Abstract: This study aimed to evaluate the guidelines for the use of GenAI tools available on the websites of the world's top 200 universities. We collected all publicly available guidelines from the websites of the top 200 universities listed in the 2026 QS World University Rankings. These guidelines were evaluated using the same 24-item checklist developed for our 2024 survey of the top 50 universities worldwide. The assessment revealed that 180 institutions have publicly available guidelines. All universities permit the use of GenAI tools under specific conditions. These policies are primarily established by academic bodies that focus on teaching, learning, and innovation. Most guidelines emphasize the use of university-licensed options to enhance data security. The most cited GenAI tools included ChatGPT, Microsoft Copilot, and Google Gemini (formerly Bard). More than 80% of the guidelines covered academic integrity, the limitations of GenAI tools, data privacy, the integration of GenAI in teaching and assessment, and the need to acknowledge its use. However, the operation of AI algorithms, reporting mechanisms for non-permitted use, documentation of prompts, and adoption of outputs were addressed in fewer than 40% of the guidelines. A comparison with our 2024 data for the subset of 50 universities re-evaluated in 2026 shows progress in guidelines coverage, reflecting institutions’ rapid responses to the evolving AI landscape. Despite the QS top 200's concentration in wealthy nations, our checklist and findings are actionable for universities across the Global South.

Abstract: Acute pancreatitis (AP) is an acute inflammatory disorder of the exocrine pancreas with limited therapies. Whether cuproptosis, a copper-dependent cell death pathway, contributes to AP pathogenesis remains unknown. We integrated single-cell transcriptomics (GSE279876), mouse AP model (GSE188819), and human cohort data (GSE194331) to evaluate 13 cuproptosis-related genes across cell types, along with pseudotime trajectory, regulatory networks, and cell-cell communication. Findings were validated in caerulein-induced Severe acute pancreatitis（SAP） mouse models and acinar cell injury using histopathology, electron microscopy, flow cytometry, immunofluorescence, and biochemical assays. Single-cell analysis showed selective cuproptosis pathway activation in acinar cells, with all 13 genes upregulated, most notably Gls and Fdx1. Cuproptosis score increased along pseudotime, and transcription factors Spi1 and Fos/Jun, alongside MIF/CCL inflammatory signals, were enriched, confirmed in independent datasets. In vitro and in vivo, severe AP pancreata and acinar cells exhibited copper accumulation, FDX1/DLAT upregulation, mitochondrial shrinkage, and cristae loss, which are classic cuproptotic phenotypes, all reversed by tetrathiomolybdate (TTM). We conclude that the inflammatory microenvironment drives acinar cells to selectively activate cuproptosis in AP, and copper chelation with TTM attenuates pancreatic injury, suggesting a potential targeted therapeutic strategy.

Abstract: Microglia are the main effector cells in neuroinflammation, and their chronic activation is a factor in the progressive development of neurological diseases. Evidence has shown that palmatine attenuates the proinflammatory response and reduces oxidative stress in murine microglia by suppressing NF-κB. However, its effect on NF-κB translocation and the production of reactive oxygen species (ROS) in human microglia has not been explored. Consequently, we evaluated the effect of palmatine on NF-κB nuclear translocation and superoxide anion (O2∙-) production in human microglia (HMC3) stimulated by lipopolysaccharide (LPS). Methods: The PyMOL visualization system, molecular docking, and the protein-ligand interaction profiler (PLIP) were used to analyze the affinity of palmatine for NF-κB (p50) and the possible putative binding site. Microglia were stimulated with LPS for 1 h in the absence or presence of palmatine at different concentrations. We quantified NF-κB translocation by immunofluorescence and O2∙- production using the nitroblue tetrazolium assay. Results: In silico analysis suggests that palmatine interacts stably with NF-κB through electrostatic and hydrophobic bonds. Consistently, in vitro studies revealed that palmatine significantly reduced NF-κB translocation after LPS stimulation. We observed that O2∙- production was significantly decreased under the same treatments. Conclusion: Palmatine has important capabilities to reduce NF-κB translocation and O2∙- levels, suggesting a potential regulatory effect on the proinflammatory response. Further research is required to elucidate the expression levels of pro-inflammatory cytokines and to explore the anti-inflammatory effect of palmatine in human microglia.

Abstract: Background: The persistent shortage of donor organs remains a major public health challenge. Medical students are an important target population because knowledge of brain death, emotional responses, and institutional trust may influence personal donation decisions and future clinical practice. This Phase I study developed the seven-item AP-DONOR Score and performed its preliminary psychometric evaluation. Methods: This analytical cross-sectional derivation study included 549 second-year medical students from “Dunărea de Jos” University of Galați, Romania. The questionnaire was administered 7–10 days after a standardized educational module on brain death, organ procurement, consent, and family communication. The sample was randomly divided for exploratory (n=275) and confirmatory (n=274) factor analyses. Internal consistency, factor structure, and associations with donation willingness were assessed. Results: Overall, 77.0% of students were willing to donate their organs post-mortem. Two related dimensions emerged: Diagnostic Fear and Anxiety (DFA; α=0.74) and Institutional and Social Mistrust (ISM; α=0.78), with overall α=0.72. CFA showed good fit (CFI=0.972; RMSEA=0.048; SRMR=0.038). Willing donors had significantly lower DFA and ISM scores and greater perceived clarity of brain death (all p<0.001). Convergent validity remained preliminary. Conclusions: The AP-DONOR Score is a feasible, concise framework capturing two potentially modifiable dimensions of donation-related apprehension. Further independent validation is required to establish reliability, validity, measurement invariance, and clinically meaningful thresholds.

Abstract: Background: Large language models can support clinical work, but their use in high-stakes settings raises risks of over-reliance, opacity, and erosion of professional judgment. Objective: To present MAGI, a conceptual multipersona framework for ethical deliberation and criticality triage in clinical decision support. Approach: The proposal distinguishes constrained analytical personas from autonomous clinical agents and combines legal, personalist bioethical, and biomedical perspectives through a content-analysis-informed synthesis. No empirical implementation or validation results are reported. Proposed framework: A coordinator is intended to document relevant considerations, agreements, disagreements, evidentiary gaps, and reasons for escalation. The proposed output is an auditable deliberation report, not a treatment recommendation. Clinician review is required before any use; high-criticality cases or persistent material disagreement require escalation to the appropriate accountable human process. No convergence threshold or iteration count is established as a safety criterion. Conclusion: A multipersona architecture may help make value conflicts and automation-related risks visible before action is taken. Prospective evaluation is required to determine whether it improves issue detection, appropriate reliance, usability, or safety compared with simpler alternatives.

Abstract: Objective: Little is published on health indices for incarcerated populations. Such information can enhance health services delivery with a view to optimize programming goals and reduce recidivism. Methods: Following IRB approval, the volunteer incarcerated persons' health assessment for rehabilitation and training effectiveness (VIPHARTE) will proceed on two tracks—Array I (retrospective) will comprise de-identified data from previously entered health records on all incarcerated adults in California state prisons (n > 90,000). Redacted weights taken on January 1st (baseline) will be anonymously tracked for each record with weight remeasured on 31st December for cohorts in 2017, 2021, and 2024. Age, gender, and self-identified ethnicity will be matched on each entry to document weight change (if any) before, during, and after COVID-19. Array II (prospective) will estimate current inmate wellness from biomarker tests offered to incarcerated volunteer participants (n=1000). These samples would be collected at previously booked primary care clinic visits, with specimens frozen for off-site batch analysis. VIPHARTE will focus on hematologic, metabolic, endocrine, and epigenomic stress parameters, some of which (20%) are already being collected at California correctional institutions. The remaining items (n = 24) will be completed by research partners from specialty laboratories at no additional cost. Results: Weight change patterns among the incarcerated are well documented but largely ignored, and require further study. Array I will be among the first datasets to clarify this phenomenon. VIPHARTE will also enable cross-comparisons with reference to COVID-19, where prison populations are known to have been particularly impacted. In Array II, new information on anemia, nutrition, infection, systemic inflammation, hepatic/renal function, endocrine status, and oxidative stressors as potential epigenomic modifiers will be aggregated from the volunteer cohort. Conclusion: Health assessments, either historical or real-time, taken directly from the incarcerated are scarce. When available, they bring value in shaping correctional health policy, budget prioritization, public workforce allocations, and overall awareness of needs within a vulnerable population. California operates 31 correctional institutions, including the world's largest women's prison. Treatment and care decisions for these incarcerated individuals develop inside a high-throughput managed care organization functioning as a system-within-a-system. Large tranches of its clinical data will provide raw resources to power Array I of VIPHARTE. Its prospective component (Array II) will gather original data on novel cell signaling elements contributed by representative volunteers, producing a detailed and overdue update concerning wellness strengths and weaknesses in this understudied group.

Abstract: Background: Mesenchymal stromal cell-derived conditioned medium (MSC-CM) represents a promising cell-free approach for regenerative medicine; however, variability in production conditions remains a major challenge for standardization. This study investigated how serum-free conditioning duration influences the proteomic composition and regenerative activity of human dental pulp stem cell-conditioned medium (DPSC-CM). Methods: DPSC-CM was collected after 24, 48, and 72 h of serum-free conditioning and characterized by label-free LC-MS/MS proteomics using donor-blocked differential abundance analysis. DPSC viability and apoptosis were assessed by Annexin V/PI flow cytometry. The angiogenic activity of CM 48 h and CM 72 h was evaluated using the ex ovo chick chorioallantoic membrane (CAM) assay, while all CM groups were assessed for their effects on human exfoliated deciduous teeth (SHED) metabolic activity and osteogenic differentiation. Osteogenesis was evaluated by alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining. PI3K/Akt signaling was investigated for CM 48 h by Western blotting. Results: Serum-free conditioning for up to 72 h did not significantly affect DPSC viability or apoptosis. Proteomic analysis identified 1562 proteins. Differential abundance analysis identified 914 differentially abundant proteins (DAPs) between CM 48 h and CM 24 h and 745 between CM 72 h and CM 24 h, whereas no DAPs were detected between CM 72 h and CM 48 h. Enriched biological processes included extracellular matrix organization, cell-substrate adhesion, cytoskeletal organization, protein folding, and angiogenesis-related pathways. In the CAM assay, CM 48 h in-creased total vessel area, whereas CM 72 h increased total vessel length. CM 48 h en-hanced SHED metabolic activity at day 3. Although ALP staining did not differ significantly among groups, CM 48 h produced greater matrix mineralization than CM 24 h. PI3K inhibition reduced Akt phosphorylation, whereas CM 48 h had no significant effect on the p-Akt/Akt ratio. Conclusion: Serum-free conditioning duration influences DPSC-CM composition and biological activity, with the major proteomic transition occurring between 24 and 48 h. Among the conditioning periods evaluated, 48 h demonstrated the most consistent combination of proteomic and functional effects, supporting further investigation as a candidate conditioning duration for DPSC-CM production.

Abstract: Purpose of Review Exercise is routinely recommended for osteoporosis, yet reviews often merge bone mineral density, falls, function, and fractures as if they were interchangeable. This review updates the evidence through August 2026 and translates it into an outcome-specific, phenotype-stratified prescription for older adults at fragility-fracture risk. Recent Findings Exercise reduces fall rates in community-dwelling older adults by about one quarter, whereas average gains in areal bone mineral density are modest, site-specific, and heterogeneous. High-intensity resistance and impact training can improve lumbar-spine and femoral-neck outcomes in selected, closely supervised postmenopausal women. However, fracture meta-analyses remain limited by sparse events, fractures recorded as secondary outcomes, and low or very low certainty; a 2026 synthesis of heterogeneous fall-prevention interventions did not show a clear reduction in fractures. Newer evidence also supports functional benefit after osteoporotic vertebral fracture, while reinforcing the need for individualized progression, explicit adverse-event reporting, and continued training. Summary Prescription should target two partly independent pathways: progressive resistance and impact loading for skeletal adaptation, and challenging balance, functional, and strength training for falls prevention. Dose, impact exposure, spinal loading, and supervision should be modified by vertebral-fracture status, frailty, fall risk, pain, and training experience. Practical dose ranges should be identified as trial protocols, consensus exemplars, or pragmatic starting points rather than fracture-validated targets. Exercise complements—but does not replace—osteoporosis medication when pharmacotherapy is indicated.

Abstract: The public release of ChatGPT on November 30, 2022 constituted an inflection point in the history of artificial intelligence applied to medicine. Within oncology, a specialty defined by the need to synthesize complex, heterogeneous, and rapidly evolving clinical data, large language models (LLMs) have transitioned within a remarkably compressed timeline from objects of academic curiosity to the threshold of institutional deployment. This narrative review maps the trajectory of LLM integration across the oncological care continuum, from patient-facing information tools to multidisciplinary tumor board decision support. The clinical landscape is organized around a three-tier framework of readiness: domains in which LLMs already demonstrate robust, evidence-supported performance; domains in which early evidence is promising but prospective validation is lacking; and domains that remain aspirational and require substantial technical and regulatory development before adoption can be responsibly recommended. A dedicated analysis is presented of the mechanistic distinction between static parametric knowledge and dynamic retrieval-augmented generation (RAG), the probabilistic origins of factual inaccuracy in language model outputs, and the role of authoritative guideline grounding in constructing trustworthy AI architectures for oncology. The review examines how multimodal LLMs (MLLMs) are beginning to integrate radiomics, whole-slide pathology imaging (WSI), next-generation sequencing (NGS) data, transcriptomics, and proteomics into unified oncological reasoning workflows, and how this convergence informs the precision oncology vision. The structural and linguistic barriers encountered when LLMs are deployed in non-English clinical environments, with particular reference to the healthcare context, are examined as a representative case of the global versus local challenge that confronts any international deployment strategy. The unresolved legal landscape of liability for AI-assisted clinical errors, the regulatory classification of LLMs as software as a medical device (SaMD), and the human-in-the-loop imperative are analyzed as prerequisites for responsible deployment. Our central argument is that LLMs derive their clinical value not from autonomous decision-making but from their capacity to function as perpetually available, rigorously grounded, and cognitively augmentative assistants to the human oncologist.

Abstract: Critical illness is increasingly recognized as a disorder of disrupted systemic homeostasis rather than simply a consequence of maladaptive systemic inflammation or isolated organ failure. Although researchers have extensively investigated adaptive biologic responses to severe physiologic stress, far 2 less attention has been paid to the integrative mechanisms that coordinate these responses across multiple organ systems throughout the course of illness. This review synthesizes current evidence from systems biology, immunology, endocrinology, network physiology, and critical care to present a systems-level conceptual model of homeostatic correction that explains how coordinated adaptive biologic programs restore organismal homeostasis after severe physiologic stress. The model organizes these responses into three dynamic, partially overlapping phases: Priming, which establishes adaptive readiness and immediate survival responses; Modulatory, which limits excessive activation while preserving essential host-defense and physiologic functions; and Restorative, which promotes resolution, tissue repair, regenerative recovery, and the restoration of integrated organ-system function. In this model, glucocorticoid–glucocorticoid receptor alpha (GC–GRα) signaling serves as a central integrative regulator coordinating immune, neuroendocrine, metabolic, mitochondrial, vascular, epithelial, lymphatic, microbiome, and regenerative adaptive biologic programs through context-, tissue-, and phase-specific mechanisms. Rather than acting solely as an anti-inflammatory pathway, GC–GRα signaling functions as a dynamic, systems-level regulator coordinating adaptive capacity, inter-organ communication, disease tolerance, tissue protection, and recovery while preserving essential host-defense functions. The proposed model shifts the focus from isolated pathophysiologic abnormalities to understanding critical illness as a disorder of disrupted organism-wide adaptive coordination. It provides a biologically organized foundation for investigating adaptive capacity, identifying phase-specific biomarkers, and developing precision therapeutic strategies to restore homeostatic resilience across acute and chronic disease states.

Abstract: Introduction: Published scientific articles present the final products of research but often conceal or compress the intellectual, documentary, bibliographic, and methodological processes that produced them. This opacity limits the use of articles as research artifacts, hinders the auditing of their logical genesis, and makes it difficult to transform identified gaps into new lines of inquiry. Objective: To define and develop the Universal Research System with Reverse Itinerary (SUII, the Spanish acronym for Sistema Universal de Investigación con Itinerario Inverso), describe its conceptual foundations, assess its originality in medical literature research, and propose an operational architecture with dual reconstructive and generative outputs. Methods: An original methodological development and conceptual synthesis study was conducted through theoretical formalization and critical integration of previously developed SUII materials and related methodological traditions, including document analysis, process tracing, reverse engineering, provenance, protocol-publication comparison, RIAT, scoping reviews, PRISMA, literature-based discovery, and abductive reasoning. Results: The SUII is defined as a method of documentary, conceptual, and methodological analysis that starts from a finished scientific product and retrospectively reconstructs the foundational question, decisions, concepts, sources, bibliography, transformations, and genesis hypotheses that probably led to the article. Its generative extension transforms these traces into new research questions and hypotheses, rival hypotheses, a preliminary research agenda, and requirements for external validation. Discussion: No single medical precedent equivalent to the full scope of the SUII was identified. Its originality lies in integrating retrospective reconstruction, inferential traceability, and traceable hypothesis generation. Conclusion: The SUII may support metascience, teaching, methodological auditing, medical literature research, and the design of future studies, provided that it clearly distinguishes explicit evidence, reasoned inference, and controlled speculation.

Abstract: Background/Objectives: The stratum corneum restricts passive transport of hydrophilic macromolecules, viscous gels, and particulate suspensions. This exploratory study evaluated whether a roller-based platform combining plasma-mediated surface conditioning, electroporation, and iontophoresis could produce imaging changes consistent with needle-free cutaneous delivery of formulations with distinct physicochemical properties. Methods: Three adults with Fitzpatrick skin types III–IV received one model formulation each: autologous plasma rich in growth factors (PRGF), a dual-molecular-weight hyaluronic acid formulation (LongevHA), or calcium hydroxylapatite (CaHA). In the CaHA participant, adjacent dorsal-hand areas received undiluted, 1:1 diluted, and 1:2 diluted formulations. Each 2 cm treatment field received 0.5 mL. High-frequency micro-ultrasound was acquired at baseline, after PlasmaPeel conditioning, immediately after delivery, and, where available, 30 min later using a Vevo 3100 system with an MX400 38 MHz transducer. Results: PlasmaPeel was followed by changes in the superficial epidermal entry echo while continuity was preserved. PRGF produced increased superficial dermal heterogeneity immediately after treatment and a more diffuse low-echogenic pattern at 30 min. LongevHA produced a new, denser dermal/subdermal echotexture after treatment. CaHA appearance varied with dilution: undiluted product produced focal hyperechoic deposits, 1:1 dilution produced broader heterogeneous distribution, and 1:2 dilution produced the most diffuse pattern. No pain or immediate adverse events were recorded. Conclusions: Sequential ultrasound findings were compatible with formulation-dependent needle-free delivery, but they do not chemically identify the delivered material or independently prove transdermal passage. Controlled studies with quantitative imaging and orthogonal molecular validation are required.

Abstract:

Background: Mandibular fractures are among the most common injuries encountered in oral and maxillofacial trauma and frequently require restoration of occlusion, stabilization of bone fragments, and maintenance of intermaxillary relationships during healing. Conventional Erich arch bars remain a widely used method of maxillomandibular fixation (MMF), but their application is associated with prolonged operative time, gingival and mucosal trauma, plaque accumulation, needle-stick risk to the operator, and reduced patient comfort. Bone-supported intermaxillary fixation (IMF) screws have been introduced as an alternative, yet screw-related complications — including root injury, mucosal overgrowth, loosening, and mechanical failure — continue to limit their universal adoption. Objective: This narrative review synthesizes the clinical, morphological, biomechanical, technical, and practical rationale for a proposed method of mandibular fracture stabilization using self-tapping titanium orthodontic screws, with heads placed intraorally in the alveolar process of the maxilla and mandible, connected by elastic intermaxillary traction. Methods: A narrative literature review was undertaken across five thematic domains: mandibular fracture management, Erich arch bars, intermaxillary fixation screws, orthodontic miniscrews, and the biomechanics of elastic maxillomandibular fixation. The proposed technique was then appraised against these existing fixation concepts and their documented clinical limitations. Results: The reviewed evidence indicates that screw-based intermaxillary fixation can shorten operative time, facilitate oral hygiene, and avoid extensive circumdental wiring relative to conventional arch bars. A closely related precedent already exists in the literature in the form of a published technical report combining IMF screws with orthodontic elastic chains; the present proposal extends this concept by using orthodontic titanium screws placed within explicitly defined interradicular safe zones — approximately 8 mm from the gingival margin and at least one tooth away from the fracture edge — connected by elastic rings applied between opposing screw heads to control the maxillomandibular relationship. Morphologically, placement within interradicular alveolar bone requires careful evaluation of root anatomy, cortical thickness, keratinized mucosa, and fracture configuration. Biomechanically, elastic intermaxillary traction distributes force between the maxilla and mandible while permitting controlled stabilization of the repositioned mandibular fragments. Conclusion: Orthodontic screw-assisted intermaxillary fixation, understood as a refinement of an approach already shown to be feasible in limited clinical use, represents a promising, minimally invasive intraoral strategy for selected mandibular fractures, with potential advantages that include reduced intraoral metal bulk, improved hygiene access, simplified elastic control, and controlled stabilization of mandibular fragments. Prospective clinical trials, cone-beam computed tomography (CBCT)–based anatomical safety studies, and dedicated biomechanical analyses are required before the method can be recommended for broad clinical use.

Abstract: Mucormycosis is a rapidly progressive angioinvasive fungal infection predominantly affecting immunocompromised individuals and is associated with significant morbidity and mortality. Despite advances in standard care involving surgical debridement and systemic antifungal therapy, outcomes remain suboptimal due to recurrence risk, treatment-related toxicity (notably nephrotoxicity with amphotericin B), and substantial economic burden. These limitations justify continued investigation of adjunctive therapies and other novel approaches that may improve outcomes or reduce treatment burden, while established antifungal therapy and surgical management remain the cornerstone of care. Ayurveda, a traditional system of medicine in India, has been utilized by patients with mucormycosis; however, its evidence base remains limited and largely restricted to adjunctive or isolated case reports. This study presents a case series of four mucormycosis patients managed predominantly with Ayurveda-based interventions. Three patients opted to receive stand-alone Ayurveda-based treatment after declining recommended standard biomedical treatment. significant radiological improvement as interpreted by the reporting radiologists with no evidence of recurrence. One case with poor adherence showed no radiological improvement, though survival was maintained for one year. All patients had complex comorbidities, including diabetes mellitus, hypertension, and renal impairment. These observations advance hypothesis generation and provide conceptual and methodological insights for the development of future clinical research protocols. As an uncontrolled descriptive case series, they do not establish clinical efficacy, safety, non-inferiority, or suitability for clinical application, nor should they be interpreted as advocating replacement of the current standard-of-care management of mucormycosis.

Abstract: Background and objectives: Fibromyalgia (FM) is diagnosed using symptom-based criteria, and clinician-assigned labels frequently diverge from them. FM also coexists with pain-generating musculoskeletal disorders. We determined how many patients referred or labeled as having FM fulfilled the 2019 ACTTION-American Pain Society Pain Taxonomy (AAPT) criteria after specialist assessment and compared concomitant pain-related diagnoses and symptom severity by AAPT status. Methods: Single-center cross-sectional pilot study of consecutive adult outpatients attending a pain unit for suspected or previously diagnosed FM. Clinical records were reviewed to determine fulfilment of the AAPT 2019 criteria, identify documented concomitant pain-related diagnoses, and assess symptom severity (FIQR, Zung SAS/SDS, DN4, NRS). Results: Among 76 patients (96.1% female), 28 fulfilled the AAPT criteria (36.8%; 95% CI, 26.9–48.1%). Of these, 25 (89.3%; 95% CI, 72.8–96.3%) had at least one documented concomitant pain-related diagnosis, versus 54.2% of those not fulfilling the criteria (OR, 7.05; 95% CI, 1.87–26.54; p = 0.002). AAPT MET patients had higher FIQR, SAS, SDS and DN4 scores, whereas NRS did not differ significantly. Conclusion: Approximately one-third of patients with an FM label fulfilled the AAPT criteria, and most of those who did also had a concomitant pain-related diagnosis. Comprehensive assessment for coexisting pain generators remains necessary.

Abstract: In this study, the cytotoxicity of the pesticides 2,4-dichlorophenoxyacetic acid (2,4-D) and imidacloprid was evaluated in erythrocytes from different ABO blood groups by measuring partial hemoglobin release. The results showed significant differences in susceptibility to oxidative damage among blood types. In addition, the erythroprotective effect of C-phycocyanin was determined, showing up to 89% inhibition of hemolysis at 1 mg/mL, with significant differences among blood groups. To simulate physiological conditions, an in vitro digestion model was applied to obtain bioavailable fractions of the pesticides and C-phycocyanin. After digestion, the pesticides retained their ability to induce damage, whereas C-phycocyanin preserved its protective effect, although at a reduced level, reaching a maximum inhibition of 24%. At the computational level, molecular docking using AutoDock Vina was performed between the beta subunit of C-phycocyanin and 2,4-D, yielding a binding energy of –4 to –5 kcal/mol at 9 interaction sites, supported by ionic and hydrogen bonds. These results highlight the relevance of C-phycocyanin as a natural candidate for mitigating pesticide-induced cytotoxicity under physiologically relevant conditions.

Abstract: Dengue remains the most important arboviral disease in the Americas and a growing global public health threat. The region experienced the largest dengue epidemic in recorded history during 2023–2024, with more than 13 million reported cases in 2024 alone, reflecting the combined effects of rapid urbanization, climate variability, population mobility, persistent social inequities, and weakened vector-control programs. This review summarizes and expands on the principal discussions of the First Dengue Summit of the Dengue Initiative of the Americas, held in Cartagena, Colombia, in September 2025. Major themes included the changing epidemiology of dengue; implementation and development of new-generation vaccines, including TAK-003 and Butantan-DV; advances in digital surveillance, outbreak forecasting, and clinical management; and integrated vector-control strategies. Particular attention is given to Wolbachia-mediated population replacement, supported by evidence from a cluster-randomized trial in Indonesia and large-scale quasi-experimental evaluations in Colombia and Brazil, which show substantial and sustained reductions in dengue incidence and hospitalization. In the Aburrá Valley, Colombia, city-wide deployment in Bello, Medellín, and Itagüí was associated with reductions exceeding 90% in notified dengue incidence where Wolbachia became established. The review also examines mathematical modeling, artificial intelligence, climate-informed surveillance, and integrated public health approaches. Persistent challenges include financial sustainability, healthcare inequities, climate change, insecticide resistance, and heterogeneous surveillance and health-system capacity. Coordinated, multisectoral, and sustainable strategies that integrate vaccination, vector control, surveillance, community participation, and healthcare strengthening are essential for reducing the dengue burden and improving regional resilience.