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Understanding Neural Mechanisms and the Use of Targeted Non-Invasive Brain Stimulation for Treatment of Post-Stroke Fatigue: A Scoping Review
No full textBackground: Post-stroke fatigue (PSF) is one of the most prevalent symptoms that affects quality of life and daily function after stroke. Despite a growing body of research, its pathophysiology is poorly understood. Non-invasive brain stimulation (NIBS), such as the transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), can serve as a non-pharmacological intervention for PSF. In this review, we aim to (1) evaluate PSF neuroimaging studies to deduce potential neural mechanisms, (2) describe NIBS as a tool to probe brain structures to further understand pathophysiology of fatigue, and (3) assess NIBS as a treatment intervention for PSF. Methods: A systematic search was conducted for the databases PubMed, Embase, Scopus, CINAHL and Cochrane. Studies were included based on the following inclusion and exclusion criteria: \u3e18 years with PSF, use of neuroimaging and/or NIBS for investigation or as an intervention for PSF, English language, study types including cohort, case control, or randomized controlled trials. Data extracted included participant characteristics, concept, context, study methods, and key findings relevant to the review questions. Results: A total of 30 studies met criteria. Neuroimaging papers that investigated brain structure (MRI) found conflicting associations between lesion location and PSF. Functional methods (fMRI, TMS) revealed altered resting state functional connectivity (rsFC), cortical excitability, and a disruption in interhemispheric inhibitory balance as potential mechanisms of PSF. There were no studies using TMS as an intervention for PSF. Of the six articles that used tDCS, only two reported statistically significant reductions in the severity of PSF. Conclusion: Structural characteristics of stroke lesions had conflicting findings, while functional neuroimaging studies suggested that altered rsFC, cortical excitability and interhemispheric inhibitory balance contribute to the development of PSF. There were inconsistent results on the effectiveness of tDCS as an intervention for PSF, due to varying methodologies and lack of precise targeting of underlying neural mechanisms. Further investigations are needed to determine if NIBS could be a potential treatment to alleviate the effects of PSF
Impact of Enhanced Recovery After Surgery Protocols on Outcomes up to Two Years After Adult Structural Spine Disorder Surgery
No full textStudy Design. Retrospective cohort study of prospectively enrolled database. Objective. We analyze the recovery pattern of patients with adult structural spine disorder (ASD) who underwent corrective surgery with enhanced recovery after surgery (ERAS+) protocol, including physical and psychological prehabilitation components, compared with a non-ERAS protocol (ERAS-) up to 2 years (2Y) after surgery. Background. Spine surgery for ASD is often highly invasive, which can contribute to prolonged recovery. The trajectory of recovery may be accelerated by the application of enhanced recovery principles. Materials and Methods. Inclusion criteria were operative patients with ASD older than 18 years with complete baseline, 90 days perioperative, and 2Y postoperative data. We assessed differences in baseline demographics, surgical details, baseline health-related quality of life (HRQL), and surgical outcomes between ERAS+ and ERAS- patients. Outcomes included adverse events, reoperations, and radiographic parameters such as sacral slope, pelvic tilt, pelvic incidence-lumbar lordosis mismatch, sagittal vertical axis, lumbar lordosis, T2 to T12 kyphosis, and maximum Cobb angle. In addition, HRQL measures included the physical component summary, Oswestry Disability Index, Neck Disability Index, EuroQol 5 dimensions, Scoliosis Research Society Questionnaire 22r total and domain scores, Numeric Pain Rating Scale-back, and Numeric Pain Rating Scale-leg. We used multivariable logistic regression and analysis of covariance to adjust for confounding. Results. A total of 471 patients with ASD met the inclusion criteria, with 59 designated ERAS+. Those individuals with ERAS+ were older (64.1 ± 13.0 vs. 58.0 ± 16.0; P = 0.005), had a higher Charlson Comorbidity Index, (2.4 ± 1.8 vs. 1.4 ± 1.6; P \u3c 0.001), and exhibited a higher modified ASD frailty index (8.2 ± 5.4 vs. 6.3 ± 4.9; P = 0.019). The adjusted analysis demonstrated the ERAS+ cohort demonstrated a lower likelihood of overall reoperations (Odds ratio (OR): 0.3; 95% CI: 0.13-0.89), and a lower likelihood of overall adverse events (OR: 0.4; 95% CI: 0.19-0.93). ERAS+ was more likely to achieve the minimal clinically important difference in the Scoliosis Research Society Questionnaire 22r total scores at 6 months (6M; OR: 3.1; 95% CI: 1.2-8.4), self-image domain at 6M (OR: 9.0; 95% CI: 1.6-50.0), in the pain domain at 6M (OR: 3.5; 95% CI: 1.01-11.9) and 1 year postoperatively (OR: 2.6; 95% CI: 1.03-6.7), and in the SF-36\u27s physical component summary (PCS) scores at 1 year (OR: 2.1; 95% CI: 1.05-4.2). No other statistically significant differences in HRQL were observed at the remaining time points (P \u3e 0.05). Conclusion. Our work is the first to evaluate HRQL metrics and complications over 2Y following ASD correction with ERAS. Despite presenting with more severe baseline frailty and higher comorbidity profiles, patients with ASD who underwent corrective surgery with an ERAS protocol experienced fewer short-term adverse events and improved HRQL. We believe ERAS following ASD surgery leads to faster functional recovery, reduced postoperative deconditioning, and improved quality of life
Letter to the Editor Regarding “Three-Dimensional Microscope Skill Acquisition: A Randomized Controlled Study Comparing Two-Dimensional Laboratory Microscope Training, Video Gaming and Virtual Reality Gaming”
No full textLipidomic and Proteomic Insights From Extracellular Vesicles in the Postmortem Dorsolateral Prefrontal Cortex Reveal Substance Use Disorder-Induced Brain Changes
No full textSubstance use disorder (SUD) significantly increases the risk of neurotoxicity, inflammation, oxidative stress, and impaired neuroplasticity. The activation of inflammatory pathways by substances may lead to reactive astrogliosis and chronic neuroinflammation, potentially mediated by the release of extracellular particles (EPs), such as extracellular condensates (ECs) and extracellular vesicles (EVs). These particles, which reflect the physiological, pathophysiological, and metabolic states of their cells of origin, might carry molecular signatures indicative of SUD. In particular, our study investigated neuroinflammatory signatures in SUD patients by isolating EVs from the dorsolateral prefrontal cortex (dlPFC) Brodmann’s area 9 (BA9) from postmortem subjects. We isolated BA9-derived EVs from postmortem brain tissues of eight individuals (controls: n = 4, SUD: n = 4). The physical properties (concentration, size, zeta potential, morphology) of the EVs were analyzed, and the EVs were subjected to integrative multiomics analysis to profile the lipidomic and proteomic characteristics. We assessed the interactions and bioactivity of EVs by evaluating their uptake by glial cells. We further assessed the effects of EVs on complement mRNA expression in glial cells and on microglial migration. No significant differences in EV concentration, size, zeta potential, or surface markers were observed between the SUD group and the control group. However, lipidomic analysis revealed significant enrichment of glycerophosphoinositol bisphosphate (PIP2) in SUD-derived EVs. Proteomic analysis revealed the downregulation of SERPINB12, ACYP2, CAMK1D, DSC1, and FLNB and the upregulation of C4A, C3, and ALB in SUD-derived EVs. Gene Ontology (GO) and protein‒protein interactome analyses revealed functions associated with the identified proteins, such as cell motility, focal adhesion, and acute phase response signaling. Both control and SUD-derived EVs increased C3 and C4 mRNA expression in microglia, but only SUD-derived EVs upregulated these genes in astrocytes. SUD-EVs also significantly enhanced microglial migration in a wound healing assay. This study successfully isolated EVs from postmortem brains and used a multiomics approach to identify EV-associated lipids and proteins in SUD. Elevated C3 and C4 in SUD-derived EVs and the distinct effects of EVs on glial cells suggest a crucial role for these cells in acute phase response signaling and neuroinflammation. (Figure presented.
Multisystem Endothelial Inflammation: A Key Driver of Adverse Events Following Mrna-Containing COVID-19 Vaccines
No full textmRNA-LNP-based COVID-19 vaccines, namely Pfizer-BioNTech’s Comirnaty and Moderna’s Spikevax, were successfully deployed to help control the SARS-CoV-2 pandemic, and their updated formulations continue to be recommended, albeit only for high-risk populations. One widely discussed aspect of these vaccines is their uniquely broad spectrum and increased incidence of adverse events (AEs), collectively referred to as post-vaccination syndrome (PVS). Although the reported PVS rate is low, the high number of administered doses among healthy individuals has resulted in a substantial number of reported vaccine-related injuries. A prominent manifestation of PVS is multisystem inflammation, hypothesized to result from the systemic transfection of organ cells with genetic instructions for a toxin, the spike protein, delivered with lipid nanoparticles (LNPs). In this narrative review, we focus on endothelial cells in the microcirculatory networks of various organs as primary sites of transfection with mRNA-LNP and consequent PVS. We outline the anatomical variations in the microcirculation contributing to the individual variability of symptoms and examine the molecular and cellular responses to vaccine nanoparticle exposure at the endothelial cell level with a focus on the pathways of a sustained cascade of toxic and autoimmune processes. A deeper understanding of the mechanisms underlying mRNA-LNP-induced AEs and PVS at the organ and cellular levels is critical for improving the safety of future vaccines and other therapeutic applications of this groundbreaking technology
Acute Mastoiditis in Children During the Covid Era: A Systematic Review and Meta-Analysis
No full textObjective: Explore the impact of the COVID-19 pandemic on pediatric acute mastoiditis (AM). Data sources: CINAHL, Cochrane Library, PubMed, Scopus. Methods: Literature was searched from 2014 to 2025 for articles reporting AM in children. Specific outcomes included clinical presentation, bacterial epidemiology, complications, and management. Primary outcome measures included continuous measures (mean), proportions (%), mean difference (Δ), and relative risk (RR) with 95 % confidence intervals (CI). Results: There were seven included studies (N = 1001 children) with 632 patients in the pre-COVID cohort and 369 in the COVID-era cohort. There was a significant difference in the proportion of intracranial complications with a 20 % greater risk of having an intracranial complication after the COVID pandemic than before (RR: 1.2 [95 % CI: 0.6–2.3], p = 0.0097). There was also a significant decrease in the proportion of cases treated conservatively with antibiotics after the pandemic (mean difference 10.8 % [95 % CI: 2.9 %–18.0 %], p \u3c 0.01). Bacterial epidemiology also experienced a significant shift in composition following the pandemic. Conclusion: The COVID-19 pandemic has led to a rise in intracranial complications in pediatric AM, with fewer cases being treated solely with antibiotics. Additionally, the pandemic has altered the bacterial epidemiological patterns of AM, highlighting opportunities for further investigation into the characteristics of AM during and after this period to inform and improve future management strategies
Identifying Risk Groups in 73,000 Patients With Diabetes Receiving Total Hip Replacement: A Machine Learning Clustering Analysis
No full textBackground/Objective: Diabetes mellitus (DM) is a highly prevalent condition that contributes to adverse outcomes in patients undergoing total hip arthroplasty (THA). This study applied machine learning clustering algorithms to identify comorbidity profiles among diabetic THA patients and evaluate their association with postoperative outcomes. Methods: The 2015–2021 National Inpatient Sample was queried using ICD-10 CM/PCS codes to identify DM patients undergoing THA. Forty-nine comorbidities, complications, and clinical covariates were incorporated into clustering analysis. The Davies–Bouldin and Calinski–Harabasz indices determined the optimal number of clusters. Multivariate logistic regression assessed risk of non-routine discharge (NRD), and Kruskal–Wallis H testing evaluated length-of-stay (LOS) differences. Results: A total of 73,606 patients were included. Six clusters were identified, ranging from 107 to 61,505 patients. Cluster 6, enriched for urinary tract infection and sepsis, had the highest risk of NRD (OR 7.83, p \u3c 0.001) and the longest median LOS (9.0 days). Clusters 1–4 had shorter recoveries with median LOS of 2.0 days and narrow variability, while Cluster 5 showed intermediate outcomes. Kruskal–Wallis and post hoc testing confirmed significant differences across clusters (p \u3c 0.001). Conclusions: Machine learning clustering of diabetic THA patients revealed six distinct groups with varied comorbidity profiles. Infection-driven clusters carried the highest risk for non-routine discharge and prolonged hospitalization. This approach provides a novel framework for risk stratification and may inform targeted perioperative management strategies
Brief Primer on the Discovery of New Antifungal Drugs From Plant Sources
No full textRationale: The antifungal armamentarium is shrinking while resistance to licensed agents rises. Historically, actinomycetes and fungi delivered nystatin, amphotericin B, griseofulvin and the echinocandin scaffold, yet plant-derived compounds—despite potent in-vitro activity—have rarely reached the clinic. Objective: To frame the recent in-vivo success of papaya-seed essential oil against fluconazole-sensitive and -resistant Candida albicans within the broader context of plant-based antifungal discovery, and to propose rigorous criteria that can accelerate translation, especially considering varying resource settings. Key Points: Commentary on Ma et al. (Mycopathologia 190(5):1–14, 2025) showing that benzyl-isothiocyanate-rich papaya-seed oil outperforms fluconazole in a murine systemic candidiasis model without acute toxicity; Historical perspective on how soil microbes provided the first broad-spectrum antifungals; An eight-point checklist for future plant-extract studies, with essential and suggested elements to promote high-quality research across different laboratory settings. Conclusion: Adherence to core methodological standards, along with suggested advanced analyses where feasible, will help identify promising plant-derived antifungal leads and support a more inclusive and effective discovery pipeline
Factors Associated With HIV Status Non-Disclosure Among People Entering Care at Iedea Sites in Cameroon: A Cross-Sectional Study
No full textBackground: While non-disclosure of HIV status may protect people living with HIV (PLWH) against stigma, discrimination, and violence, disclosure may facilitate access to social support and improve treatment adherence. This study examined factors associated with non-disclosure among recently-diagnosed PLWH at IeDEA study sites in Cameroon. Methods: We conducted a cross-sectional study of adults ≥ 19 years newly enrolling in HIV care at three Cameroon hospitals from January 2016 to June 2023 with recent (\u3c 1 year) diagnoses and no evidence of prior HIV care. We used logistic regression to identify factors associated with non-disclosure of HIV status at the time of enrolment. Results: Among 2880 participants, the overall prevalence of HIV status non-disclosure at enrolment was 34.4%, ranging from 48.0% among those enrolling on the day of diagnosis to 18.7% among those enrolling \u3e 30 days after diagnosis. Men and single participants had higher odds of non-disclosure compared with women (aOR: 1.68; 95% CI 1.38, 2.04) and those who were married/living with a partner (aOR: 1.66; 95% CI 1.36, 2.02). Those with early-stage HIV disease (WHO Stage 1 or 2 or CD4 ≥ 200 cells/mm3) also had higher odds of non-disclosure (aOR: 1.48; 95% CI 1.20, 1.83) compared with participants with advanced-stage disease. Conclusion: Among those diagnosed with HIV within 1 year prior to enrolment, men, single/unmarried people, and those with early-stage HIV disease were less likely to disclose their status. Further research on barriers to status disclosure among these groups is needed to guide disclosure support and counselling interventions
Efficacy and Safety of Empagliflozin in Acute Heart Failure: A Systematic Review and Meta-Analysis
No full textBackground: Acute heart failure (AHF) is leading cause of hospitalization and mortality. Empagliflozin, a Sodium Glucose Co-transporter 2 inhibitor (SGLT-2i), has demonstrated benefits in HFrEF and HFpEF, but its role in AHF remains under-explored. Objective: Assess safety and efficacy of empagliflozin in AHF. Methods: A systematic review and meta-analysis adhering to PRISMA 2020 guidelines was conducted. A search on 25 February 2025, identified Phase IIb and III randomized controlled trials (RCTs) involving adults with AHF from databases like Medline®, Cochrane CENTRAL, Embase, and ClinicalTrials.gov. Outcomes included all-cause mortality, HF rehospitalization, cardiovascular deaths, and serious adverse events. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was assessed with I2 and Cochrane Q-statistic. Results: Three RCTs (n = 824) were included. Empagliflozin reduced all-cause mortality (OR: 0.47, 95% CI: 0.29–0.78, p = 0.004) and cardiovascular death (OR: 0.56, 95% CI: 0.38–0.82, p = 0.003) compared to placebo. It also lowered serious adverse events risk (OR: 0.62, 95% CI: 0.44–0.87, p = 0.005) without significantly increasing adverse effects such as acute kidney injury, diabetic ketoacidosis, hypotension, or urinary tract infections. Sensitivity analyses confirmed these findings. Conclusion: Empagliflozin reduces mortality in AHF with a favorable safety profile, highlighting need for further trials