Search Results (149)

Background: Klebsiella pneumoniae is a Gram-negative bacterium that is found in human microbiota and in diverse environments. This opportunistic pathogen exhibits a highly variable genetic background and is responsible for a broad range of hospital- and community-acquired, multidrug-resistant infections worldwide. To track transmission pathways and understand genetic diversity, single-nucleotide polymorphism (SNP) clustering has become an essential tool. Methods: This study examines data from 2018 to 2024 in the NCBI Pathogen Detection database to determine the temporal and spatial distribution of SNP clusters in clinical K. pneumoniae across Middle East and North Africa (MENA) countries. Results: Among 1858 isolates, a heterogeneous population structure was observed. Of the 478 identified SNP clusters, a few dominant clusters accounted for 37% of the isolates, and numerous low-frequency lineages were detected. The descriptive yearly snapshot revealed a diverse representation of top clusters. Geographical analysis showed the presence of both localized and limited cross-border distribution patterns. Countries with diverse clusters also exhibit higher diversity of carbapenem- and ESBL-resistant genes. Conclusions: These findings provide valuable insights into the dominant, regionally concentrated K. pneumoniae lineage across MENA countries, assisting future genomic surveillance and efforts to combat clinical K. pneumoniae infections in this region. Full article

Background: Herpes simplex virus (HSV), Epstein–Barr virus (EBV), and cytomegalovirus (CMV) establish lifelong latency in sensory neurons, lymphoid tissue, and myeloid–endothelial cells, respectively. A substantial proportion of adults worldwide are infected with all three viruses and may experience concurrent herpesvirus latency, yet they have largely been studied independently. This review examined whether latent and intermittently reactivating herpesviruses share overlapping inflammatory signatures and whether their combined presence contributes to chronic inflammatory burden. Methods: A narrative integrative review was conducted using MEDLINE, Embase, and Google Scholar (inception–October 2025). Evidence from thirty-one cohort studies and mechanistic investigations spanning virology, immunology, neurology, and clinical medicine was synthesized. Results: Herpesvirus reactivation rates ranged from 23% in general Intensive Care Unit (ICU) populations to 85% in severe COVID-19. Concurrent reactivation of multiple viruses occurred in 34–63% of critically ill patients and was associated with worse clinical outcomes. Notably, simultaneous CMV and EBV reactivation independently predicted mortality (adjusted hazard ratio, 3.17; 95% CI, 1.41–7.13). Across infections, overlapping inflammatory biomarkers, including IL-6, TNF-α, CRP, and PGE₂, were consistently elevated, reflecting convergent activation of IFN and NF-κB signaling pathways. Mechanistic studies suggest cross-compartment immune priming, where CMV-driven T-cell exhaustion facilitates EBV reactivation, and viral cytokine signaling enhances HSV-associated neuroinflammation. Conclusions: HSV, EBV, and CMV triple latency may represent an underrecognized contributor to chronic inflammation in immunocompetent hosts. Understanding this multi-virus inflammatory network may inform mechanistic research, biomarker-guided risk stratification, and therapeutic strategies targeting convergent inflammatory pathways. Prospective interventional studies incorporating concurrent multi-virus monitoring are needed to clarify causal relationships. Full article

The COVID-19 pandemic introduced an additional major stressor for families in the Caribbean, a region already shaped by environmental risk and socioeconomic vulnerability. This study examined changes in family resilience across pandemic phases among English-speaking Caribbean populations, drawing on Walsh’s family resilience framework, which emphasizes belief systems, organizational processes, and communication. Using a convergent parallel mixed methods design, quantitative and qualitative data were integrated from two studies conducted before and during pandemic restrictions and after restrictions were lifted. Survey data were collected from 198 families across English-speaking Caribbean nations, and in-depth interviews were conducted with 31 families from Grenada, Jamaica, and Trinidad. Quantitative analyses indicated a significant decline in family resilience during periods of heightened restrictions, followed by a return to pre-pandemic levels. Qualitative findings identified faith, family connectedness, communication, resourcefulness, and a positive outlook as key processes supporting adaptation during the crisis. Overall, results suggest that while family resilience at the population level was strained during the pandemic, it demonstrated recovery over time. Policies and interventions that strengthen communication supports and community- and faith-based resources may enhance family resilience and preparedness for future public health and environmental disruptions in the Caribbean. Full article

Purpose: Tumor location influences survival in bladder cancer, potentially due to genetic heterogeneity driven by distinct embryological origins and structural compositions. We investigate location-specific somatic gene alterations (GAs) and their potential clinical implications in muscle-invasive bladder cancer (MIBC). Methods: We explored the role of the intra-bladder tumor location in determining survival and underlying genetic alterations in MIBC patients using multiple large independent databases. We analyzed the tumor location’s impact on survival using the Surveillance, Epidemiology, and End Results (SEER) database and validated these findings using cBioPortal (CBP), which also contains gene sequencing data, enabling a comparison of GA frequency by tumor location. We investigated GA combinations to identify potential synthetic lethal (SL) combinations and co-occurrence signatures for survival prediction. Using the ROC Plotter database, we explored how significantly altered genes affect the response to immune checkpoint inhibitors (ICI). Results: An analysis of 6712 SEER and 570 CBP patients revealed significant (p < 0.001) differences in overall survival stratified by tumor location, with trigone tumors showing the worst survival. Genomic analysis identified 35 genes with location-specific alteration frequencies. Three of these genes, CDKN2A, SPTAN1, and BIRC6, were significantly predictive of ICI response, and three genes were uniquely associated with a specific location: BPTF (anterior wall), RYR1, and OBSCN (dome). Furthermore, we identified 349 SL pairs from the 35 significantly altered genes, and a co-occurrence analysis revealed two novel gene pairs associated with improved survival. Conclusions: Intra-bladder tumor location determines survival and distinct genetic profiles in MIBC. These location-specific alterations predict ICI response and identify novel synthetic lethal targets, guiding precision oncology. Full article

Chronic pain imposes a substantial burden on global health and remains challenging to manage, despite ongoing advances in pharmacologic and interventional therapies. Recognition of chronic pain as a condition driven by central sensitization and neuroimmune dysregulation has prompted interest in therapies that target these mechanisms rather than peripheral nociception alone. Low-dose naltrexone (LDN), administered at doses substantially lower than those used for opioid or alcohol use disorders, has emerged as a repurposed treatment with potential analgesic and anti-inflammatory properties. This review summarizes the pharmacologic characteristics of LDN, with emphasis on its proposed mechanisms involving transient opioid receptor blockade, modulation of microglial activation, Toll-like receptor signaling, and central neuroimmune pathways. Available clinical evidence evaluating LDN across a range of chronic pain conditions, such as fibromyalgia, neuropathic pain syndromes, inflammatory and autoimmune disorders, headache disorders, and other centralized pain states, is critically reviewed. Although early trials, observational studies, and case series suggest potential benefit in selected populations, the overall evidence base remains limited, heterogeneous, and characterized by variability in dosing strategies and outcome measures. Safety, tolerability, and practical considerations relevant to contemporary pain practice are discussed, including interactions with opioid therapy and challenges related to off-label use. Finally, key gaps in the current evidence and priorities for future research are highlighted, underscoring the need for larger, well-designed randomized trials and mechanism-informed studies to better define LDN’s role in multimodal chronic pain management. Full article

Wastewater-based epidemiology (WBE) allows for early surveillance of viral pathogens, including SARS-CoV-2. Simplified low-cost approaches are needed to deploy WBE surveillance in resource-limited small-island settings, where high sensitivity must be maintained. In this study, we optimized key upstream steps in an electronegative membrane virus adsorption–elution (VIRADEL) workflow, including sample acidification, composite sampling duration, and RT-qPCR inhibition mitigation. Wastewater influent was sampled at a pump station in Grenada using 12 h and 24 h time-weighted composite samples, concentrated using electronegative membrane VIRADEL with and without sample acidification (pH 3.5), and used Phi 6 (enveloped virus) and MS2 (non-enveloped virus) bacteriophages as process controls and PMMoV as a fecal-derived normalization target. Targets for SARS-CoV-2 N1 and a non-enveloped virus surrogate were measured by RT-qPCR. Quantitative wastewater data were compared to reported clinical cases in the community. Sample acidification significantly increased recovery of the enveloped process control, Phi 6 (p < 0.01) indicating improved efficiency in capturing enveloped viral targets during filtration. Twelve-hour composite samples had a false-negative percentage of 88%, while 24 h samples had only 6% false negatives and were able to mirror clinical case trends. Wastewater viral signals were detected 3–5 days prior to an increase in clinical cases. Hydraulic travel time within the contributing sewer network was not directly measured; therefore, the reported 3–5 day lead time reflects the combined effect of shedding dynamics, sampling integration, and sewer transport. This optimized workflow was deployed for nine months showing sustained analytical performance and operational feasibility. Full article

Chronic pain is a multisystem disorder involving neuroimmune activation, metabolic dysregulation, mitochondrial dysfunction, and alterations in autonomic and sensory signaling, leading to peripheral and central sensitization, reduced responsiveness to standard analgesics, and persistent symptoms. Growing evidence suggests that several widely used systemic drugs, initially developed for metabolic, cardiovascular, immunological, or neurological conditions, interact with biological mechanisms involved in pain pathophysiology. This narrative review examines the mechanistic and emerging clinical evidence describing how systemically administered pharmacological agents interact with pathways implicated in chronic pain, focusing on glucagon-like peptide-1 receptor agonists, sodium–glucose cotransporter-2 inhibitors, metformin, statins, minocycline, ibudilast, low-dose naltrexone, beta-blockers, and cannabinoids. The mechanisms reviewed include glial activation, cytokine signaling, oxidative stress, mitochondrial dysfunction, ion channel sensitization, and autonomic imbalance. The use of these systemic agents may provide additional treatment options for patients with chronic neuropathic, centralized, or mixed pain states who have limited response to conventional therapies, although current clinical evidence remains preliminary. Full article

Professionalism is central to veterinary practice, shaping not only the quality of care provided to animals but also the wellbeing of practitioners, the satisfaction of clients, and the sustainability of the profession. Prior research has catalogued various attributes of professionalism that are important for career success, but few studies have integrated these multiple perspectives into a cohesive framework. This study synthesizes insights from three key veterinary stakeholder groups—students, clinical practitioners, and clients—using a multi-methods approach including surveys, focus groups, critical incident interviews, and client complaint analyses. Across the datasets, ranking of Likert-scale responses and thematic analysis revealed four recurring themes that were identified as essential for career success: ‘Effective communication’; ‘Accountability, integrity, trustworthiness, and honesty’; ‘Personal wellbeing’; and ‘Quality of service’. These themes were organized into a unifying theoretical model of veterinary professionalism, conceptualized as a ‘navigational compass’, comprising three domains of care: patient-centered care, relationship-centered care, and self-care. By conceptualizing professionalism in terms of a compass, the model illustrates how veterinarians can draw on key professionalism attributes, coupled with consideration of the three domains of veterinary care, to navigate the challenges of practice and sustain long-term career success. The compass provides a reflective framework to guide veterinarians and educators, to support the integration of professionalism into curricula and to guide careers toward excellence in care and lasting personal fulfilment. Full article

Renewable energy systems are increasingly critical for achieving decarbonization and long-term energy security, particularly in rural regions with abundant local resources. While solar and wind technologies have become cost-competitive, their intermittency limits reliability when deployed independently. Biomass, by contrast, offers dispatchable renewable power but faces economic challenges related to feedstock logistics. This study evaluates a biomass-led hybrid renewable energy system (HRES) for Grenada County, Mississippi, integrating biomass, solar photovoltaic (PV), and wind resources to enhance system reliability and reduce environmental impacts. System performance and optimization were assessed using the System Advisor Model (SAM) and the Hybrid Optimization of Multiple Energy Resources (HOMER). The proposed configuration comprises approximately 80% biomass, 10% solar PV, and the remaining share from wind, producing a total annual electricity output of about 423 GWh, sufficient to meet regional demand. The subsystem-level levelized cost of energy (LCOE) was estimated at 12.10 cents/kWh for biomass, 4.07 cents/kWh for solar PV, and 8.62 cents/kWh for wind, with the overall hybrid cost influenced primarily by biomass feedstock transportation and storage. Environmental impact assessment based on U.S. EPA eGRID and IPCC factors indicates that the hybrid system achieves a weighted emission intensity of approximately 28.4 kg CO₂-eq/MWh, representing a reduction of over 94% compared to the regional grid. When scaled to annual generation, this corresponds to roughly 197,000 metric tons of avoided CO₂-equivalent emissions per year, alongside 80–95% reductions in acidification and eutrophication impacts. The results demonstrate that biomass-anchored hybrid systems can provide a reliable, low-carbon pathway for rural energy development, with further cost reductions achievable through targeted policy incentives and financing support. Full article

Perioperative pain remains a major clinical challenge, with many surgical patients experiencing inadequate analgesia and progression to chronic postsurgical pain. Conventional opioid-centered strategies are limited by narrow therapeutic windows, systemic toxicity, tolerance, opioid-induced hyperalgesia, and poor efficacy in neuroimmune-driven pain states. Advances in molecular neuroscience and biomedical engineering have catalyzed the development of nonpharmacologic analgesic technologies that modulate pain pathways through biophysical rather than receptor–ligand mechanisms. This narrative review synthesizes emerging nonpharmacologic analgesic platforms relevant to anesthesiology, integrating molecular, cellular, and systems-level mechanisms with clinical evidence. It examines how peripheral sensitization, spinal dorsal horn plasticity, glial and neuroimmune activation, and supraspinal network dysfunction create ideal targets for device-based interventions. Electrical neuromodulation strategies, including peripheral and central techniques, are discussed alongside temperature-based, photonic, and focused-energy modalities. These include cryoneurolysis, radiofrequency techniques, photobiomodulation, and low-intensity focused ultrasound. Clinical integration within enhanced recovery pathways, patient selection, workflow considerations, and limitations of the current human evidence base are reviewed. While many of these technologies are established in chronic pain management, this review emphasizes available human perioperative data and discusses how chronic pain evidence informs perioperative translation within opioid-sparing multimodal anesthesia care. Collectively, these technologies support a mechanism-based, systems-level approach to pain modulation, with perioperative relevance varying by modality and strength of available human evidence. Full article

Dermatomyositis (DM) is an idiopathic inflammatory myopathy (IIM) characterized by distinctive chronic cutaneous manifestations. Although immune-mediated and microvascular mechanisms are well established, the role of metabolic dysfunction, particularly hyperglycemia, is underexplored in dermatological conditions. This review synthesizes mechanistic, clinical, and translational evidence to explore the relationship between dysglycemia and cutaneous disease severity in DM. Hyperglycemia is associated with oxidative stress, advanced glycation end-product formation, endothelial injury, and proinflammatory cytokine signaling. These processes may plausibly amplify DM-associated vasculopathy, impair wound healing, and worsen cutaneous inflammation. Limited DM-specific studies demonstrate increased insulin resistance and a higher prevalence of diabetes compared with healthy controls. Meanwhile, case reports suggest that poor glycemic control can exacerbate cutaneous disease. Evidence from other inflammatory dermatoses supports a biologically plausible role for dysglycemia in increasing flare frequency, infection risk, and delayed tissue repair. Dietary patterns characterized by high glycemic index and coexisting metabolic syndrome may further intensify systemic and cutaneous inflammation. Collectively, these findings suggest hyperglycemia as a biologically plausible contributor to cutaneous disease severity in DM that warrants further investigation. These observations highlight the need for future studies to evaluate whether metabolic screening, dietary patterns, and interdisciplinary care influence cutaneous disease activity and wound healing in DM. Prospective clinical investigation is needed to determine whether targeted glycemic optimization is associated with changes in cutaneous and systemic outcomes in DM. Full article

Background: The anterior cruciate ligament (ACL) and medial collateral ligament (MCL) display strikingly different healing behaviors, despite their similar structural roles within the knee. The epiligament (EL)—a vascular and cellular envelope surrounding each ligament—has emerged as a critical determinant of repair capacity. The aim of this study was to perform a region-specific, comparative analysis of EL molecular profiles in the ACL and MCL to elucidate the mechanisms underlying their contrasting reparative outcomes. Methods: Human ACL and MCL specimens were obtained from 12 fresh knee joints. Immunohistochemical labeling for CD34, α-smooth muscle actin (α-SMA), and vascular endothelial growth factor (VEGF) was performed across proximal, mid-substance, and distal EL regions. Quantitative image analysis using IHC Profiler for ImageJ generated semiquantitative (negative, low-positive, positive) distributions, and inter-ligament comparisons were quantified using t-tests (p  <  0.05). Results: Distinct, region-specific EL signatures were identified. The ACL EL exhibited strong proximal α-SMA expression (0% neg/66.8% low+/33.2%+) and notable distal CD34 positivity (0% neg/83.3% low+/16.7%+), while VEGF expression was confined to the mid-substance (≈55% low+/26%+). In contrast, the MCL EL was largely negative for CD34 and VEGF across all regions, showing a homogeneous but functionally oriented α-SMA profile: proximally negative, sparse mid positivity, and high distal low-positive staining (93.4% low+). Differences in proximal and distal CD34 and α-SMA expression between the ACL and MCL were highly significant (p  <  0.0001–0.001), confirming a mechanistic divergence in EL organization. Conclusions: The ACL EL is regionally heterogeneous, vascularly biased, and enriched in contractile α-SMA+ cells, suggesting localized but poorly coordinated reparative potential. In contrast, the MCL EL is structurally uniform, with distributed α-SMA activity supporting stable wound contraction and tissue continuity, despite limited angiogenic signaling. These findings indicate that the ACL’s failure to heal is not attributable to the absence of progenitor or angiogenic factors, but rather to its fragmented spatial organization and dominant contractile phenotype. Therapeutically, preserving and modulating the EL, particularly its CD34+ and α-SMA+ compartments, could be key to enhancing intrinsic ACL repair and improving outcomes in ligament reconstruction and regeneration. Full article

Chronic pain is increasingly regarded as a condition of glia–neuronal dysregulation driven by persistent neuroinflammatory signaling. Following injury to nerves or tissues, glial cells, including astrocytes or satellite glial cells, undergo changes in their phenotype, thereby amplifying painful stimuli mediated by cytokines, chemokines, or ATP signaling. In response to injuries, activated microglia release several mediators such as BDNF, IL-1β, or TNF-α, thereby disrupting chloride homeostasis and inducing disinhibition in the dorsal horn, and sustaining maladaptive neuroimmune activity. Dysfunction of astrocytes, characterized by impaired glutamate clearance via excitatory amino acid transporter 2 and elevated C-X-C motif chemokine ligand 1 (CXCL1) and ATP release, drives neuronal sensitization, loss of neuroprotective metabolic support, and persistence of pain. In peripheral ganglia, connexin–43–mediated satellite glial cell coupling leads to hyperexcitability, resulting in neuropathic and orofacial pain and contributing to peripheral neuroinflammation. Presently, there is no unified framework for glial cell types, and the molecular mechanisms underlying microglial, astrocyte, and satellite glial cell contributions to the transition to chronic pain from acute pain are not completely elucidated. This review synthesizes current evidence on cellular and molecular mechanisms linking glial reactivity to pain chronification through sustained neuroinflammatory remodeling and impaired neuroprotection. It evaluates therapeutic strategies, including purinergic receptor P2X4 and toll-like receptor 4 antagonists, to metabolic reprogramming, exosome therapy, and neuromodulation, aimed at restoring homeostatic glial function and re-establishing neuroprotective glia–neuron interactions. A deeper understanding of the temporal and spatial dynamics of glial activation may enable personalized, non-opioid interventions that not only achieve durable analgesia but also prevent progressive neuroinflammatory damage and support long-term functional recovery. Full article

Takotsubo syndrome (TTS) is an acute condition involving left ventricular dysfunction that may present clinically as acute coronary syndrome without obstructive coronary disease or congestive heart failure. Initially considered benign, TTS is now recognized as a complex neurocardiac disorder with hospital morbidity rates comparable to those of myocardial infarction, as well as similar long-term risks. Recent evidence establishes TTS as a multifactorial process involving catecholamine overload, coronary microvascular dysfunction, myocardial energetic abnormalities, and dysregulation of the brain and heart axes. Developments in echocardiography, cardiac magnetic resonance imaging, and improvements in diagnostic criteria have enhanced the recognition of syndromic phenotypes. Management of TTS continues to remain primarily supportive; however, recent studies have revealed improved functional outcomes with structured cardiac rehabilitation and cognitive behavioral therapies as the first long-term disease-altering approaches. Future studies should combine neurocardiology, imaging, and therapy-focused research. This review integrates the understanding of the epidemiology, pathophysiology, clinical features, diagnostic work-up, and management of TTS, with particular emphasis on developments emerging from the past decade. Full article

Background/Objectives: To estimate (a) survival after SARS-CoV-2 infection by COVID-19 vaccination status, and (b) COVID-19 vaccine effectiveness in a middle-income country. Methods: In this retrospective cohort study, secondary analysis of data from the national surveillance and vaccination databases was conducted. The primary outcome was COVID-19 death classified based on the WHO criteria. Data were analysed by vaccination status, age, sex, geographic region, and wave period. Kaplan–Meier curves were plotted; log-rank followed by multiple comparison tests were used to compare survival probabilities. Cox proportional-hazards models with time-varying covariates estimated hazard ratios (HR). Vaccine effectiveness was computed as (1-HR) × 100. Results: A total of 55,299 COVID-19 cases were captured by the national surveillance system between 1 April and 31 December 2021. Of these, 45,774 (1581 vaccinated, 44,193 unvaccinated) were included in the analysis. After a follow-up of 327 days, there were 22 deaths (case fatality rate (CFR) 1.5%) among 1581 COVID-19 vaccinated cases and 1821 deaths (CFR 4.1%) among 44,193 unvaccinated cases. There was one COVID-19 death per 10,000 person days in vaccinated cases compared with 2.7 COVID-19 deaths per 10,000 person days in unvaccinated cases. After adjustment for age, sex, and geographic region, the effectiveness against COVID-19 death across all vaccine types (ChAdOx1 nCoV-19, BNT162b2, Ad26.COV2.S, or BBIBP-CorV) was 68% (95% CI: 51–79). Effectiveness was 75% (95% CI: 59–84) for ChAdOx1 nCoV-19. Vaccine effectiveness across all vaccine types was higher in younger cases, (82% (95% CI: 52–93), 18–64 years vs. 63% (95% CI: 41–77), ≥65 years), females (84% (95% CI: 63–93), females vs. 53% (95% CI: 24–71), males) and those vaccinated in the past 3 months (71% (95% CI: 47–85), past 0–3 months vs. 56% (95% CI: 23–75), 3–6 months). Conclusions: COVID-19 vaccines were effective in preventing COVID-19 death in a population with low vaccination coverage. Limitations of the analysis include the use of surveillance data (under-reporting of cases, missing data), exclusion of partially vaccinated cases, and insufficient data on important confounders (circulating variants and comorbidities). Full article