Search Results (5,048)

For decades, researchers have explored the therapeutic potential of the vagus nerve through vagus nerve stimulation (VNS). Initially developed for epilepsy, VNS has since been applied to treat resistant depression, stroke recovery, and inflammatory conditions. Transcutaneous VNS (tVNS) now offers a noninvasive alternative, fueling clinical trials in disorders ranging from rheumatoid arthritis and migraines to long COVID-19. Mechanistic studies suggest that afferent and efferent vagal fibers modulate immune responses, mood regulation, and neurotransmitter systems. The SPARC initiative has accelerated mapping of vagal circuits, enabling more precise approaches to stimulation. Despite progress, the results remain mixed: while some patients experience lasting symptom relief, others respond no better than to placebo. Depression studies, in particular, highlight both the promise and the complexity of VNS, as inflammation, motivation circuits, and gut–brain signaling emerge as key modulators. Next-generation closed-loop devices and circuit-specific targeting may improve efficacy and reduce adverse effects. VNS research thus lies at the intersection of neuromodulation, psychiatry, and immunology—offering hope for hard-to-treat conditions, yet demanding rigorous trials to separate myths from medicine. In this article, we review the current clinical and experimental applications of tVNS, analyze its mixed efficacy across psychiatric, immunological, and neurological disorders, and highlight the mechanistic insights, stimulation parameters, and emerging technologies that may shape next-generation therapies. Full article

The COVID-19 pandemic highlighted critical issues in health services and public policy, particularly in long-term care facilities across Canada. Failures in these facilities revolving around chronic underfunding, staffing shortages, inadequate infection control, and inconsistent regulatory oversight, underscore the need to rethink health service interventions, especially considering varying implementation contexts among provinces. The Ontario Long-Term Care COVID-19 Commission Final Report pointed to long-standing systemic issues as the primary causes of the sector’s failures. To explore this issue, a narrative review was conducted with findings indicating that the long-term care crisis in Canada cannot be solved by more privatization, regulation or efficiency measures, as these have contributed to the problem’s root causes. Ontario’s long-term care crisis stems from systemic misalignments in policy, structure and stakeholder dynamics, requiring a shift toward systems thinking and resident-centered care to build an equitable and sustainable long-term care sector. Ultimately, governments must lead a policy redesign that reflects shared responsibility, stakeholder interdependence, and public involvement, offering a model for broader healthcare reform. Full article

Background/Objective: Pulmonary impairments have been identified as some of the most complex and debilitating post-acute sequelae of SARS-CoV-2 infection (PASC) or long COVID. This study identified and characterised the specific forms of pulmonary impairments detected using pulmonary function tests (PFT), chest X-rays (CXR), and computed tomography (CT) scans in patients with long COVID symptoms. Methods: We conducted a single-centre retrospective study to evaluate 60 patients with long COVID who underwent PFT, CXR, and CT scans. Pulmonary function in long COVID patients was assessed using defined thresholds for key test parameters, enabling categorisation into normal, restrictive, obstructive, and mixed lung-function patterns. We applied exact binomial (Clopper–Pearson) 95% confidence intervals to calculate the proportions of patients falling below the defined thresholds. We also assessed the relationships among spirometric indices, lung volumes, and diffusion capacity (DLCO) using scatter plots and corresponding linear regressions. The findings from the CXRs and CT scans were categorised, and their prevalence was calculated. Results: A total of 60 patients with long COVID symptoms (mean age 60 ± 13 years; 57% female) were evaluated. The cohort was ethnically diverse and predominantly non-smokers, with a mean BMI of 32.4 ± 6.3 kg/m². PFT revealed that most patients had preserved spirometry, with mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) above 90% predicted. However, a significant proportion exhibited reductions in lung volumes, with total lung capacity (TLC) decreasing in 35%, and diffusion capacity (DLCO/TLCO) decreasing in 75%. Lung function pattern analysis showed 88% of patients had normal function, while 12% displayed a restrictive pattern; no obstructive or mixed patterns were observed. Radiographic assessment revealed that 58% of chest X-rays were normal, whereas CT scans showed ground-glass opacities (GGO) in 65% of patients and fibrotic changes in 55%, along with findings such as atelectasis, air trapping, and bronchial wall thickening. Conclusions: Spirometry alone is insufficient to detect impairment of gas exchange or underlying histopathological changes in patients with long COVID. Our findings show that, despite normal spirometry results, many patients exhibit significant diffusion impairment, fibrotic alterations, and ground-glass opacities, indicating persistent lung and microvascular damage. These results underscore the importance of comprehensive assessment using multiple diagnostic tools to identify and manage chronic pulmonary dysfunction in long COVID. Full article

Background/Objectives: Evidence on pulmonary rehabilitation (PR) in paediatric post-COVID-19 condition (PPCC) is scarce. This study aimed to evaluate the association of a PR programme with changes in physical and mental health and quality of life in PPCC over a 12-month follow-up. Methods: A quasi-experimental pre–post single-arm study was conducted, with no control group, in PPCC patients attending an outpatient PR unit. The primary outcome was change in exercise capacity (6 min walk test, 6MWT). Secondary outcomes included inspiratory and peripheral muscle strength, quadriceps muscle morphology by ultrasound, fatigue, physical activity, quality of life, and psychiatric symptoms, assessed using validated paediatric instruments. Results: A total of 115 PPCC patients (mean age 13.3 years; 66.1% female) completed the PR. 6MWD distance increased from 509 ± 87 to 546 ± 86 (+37 m; p < 0.001; D: 0.50). Handgrip strength increased by 2.4 kg, maximal inspiratory pressure increased by 15 cmH₂O, physical activity increased by 2.4 points, fatigue score improved by 9.3 points, and quality of life improved by 11 points (all p < 0.001). Rectus femoris thickness increased by 0.56 mm (p = 0.005), psychiatric symptom scores decreased by 4.5 points (p < 0.001), and rectus femoris echo-intensity decreased (p = 0.003). Conclusions: Multidisciplinary PR appears feasible and potentially effective in improving physical function, psychological well-being, and quality of life in PPCC, supporting the need for evidence-based paediatric rehabilitation. Full article

Background/Objectives: This study aimed to determine the prevalence of persistent symptoms and the radiological and laboratory evolution at 6 months and 5 years after discharge in patients hospitalized for SARS-CoV-2 pneumonia during the first wave of the pandemic in Spain and to estimate the healthcare impact of their follow-up. Methods: A retrospective longitudinal observational study was conducted at the “Hospital Central de la Defensa”. A total of 200 patients aged >18 years with a diagnosis of SARS-CoV-2 pneumonia were screened. Clinical, radiological, and laboratory data were collected from electronic medical records. Patients with symptoms or radiological abnormalities at discharge underwent in-person evaluations, while the remainder were assessed by telephone. Results: A total of 182 patients met the inclusion and exclusion criteria. Of these, 112 were assessed in the outpatient setting; 60.7% required in-person evaluations, with normal pulmonary auscultation in 93.6%, complete radiological resolution in 85%, and normalized laboratory parameters in almost all cases. At 6 months, 26.5% presented at least one residual symptom, whereas only three patients (4.5%) reported symptoms at 5 years. No risk factors associated with symptom persistence were identified. The estimated cumulative healthcare cost was EUR 21,627.50. Conclusions: Among patients hospitalized for SARS-CoV-2 pneumonia during the first wave of the pandemic, 26.7% and 4.46% presented at least one persistent symptom at 6 months and 5 years after discharge, respectively. Full article

Standard epidemiological models often treat human behavior as static, failing to capture the dynamic feedback loops that shape epidemic waves. To address this, we developed a compartmental model of COVID-19 that couples the disease dynamics with two co-evolving behavioral games governed by imitation dynamics: an altruistic self-isolation game for infected individuals and a self-interested vaccination game for susceptible individuals. Our simulations reveal a fundamental behavioral paradox: strong adherence to self-isolation, while effective at reducing peak infections, diminishes the perceived risk of disease, thereby undermining the incentive to vaccinate. This dynamic highlights a critical trade-off between managing acute crises through non-pharmaceutical interventions and achieving long-term population immunity. We conclude that vaccination has a powerful stabilizing effect that can prevent the recurrent waves often driven by behavioral responses to non-pharmaceutical interventions. Public health policy must therefore navigate the tension between encouraging short-term mitigation behaviors and communicating the long-term benefits of vaccination to ensure lasting population resilience. Full article

Objective: The aim of this study was to systematically map evidence to inform best practices for sexual and reproductive healthcare delivered via telehealth (TeleSRH) in United States-based Title X-funded clinics. Methods: We searched three databases (2017–2025) for studies evaluating effectiveness, harms, patient and provider experiences, barriers/facilitators, and engagement strategies encompassing TeleSRH for sexually transmitted infections (STIs), contraceptive care/family planning (CC/FP), and sexual wellness, in countries with a human development index of ≥0.8. Results: From 5963 references and 436 articles, we included 142 eligible publications. TeleSRH use declined since the COVID-19 pandemic’s peak but remains higher than pre-pandemic. Evidence comes mostly from poor-quality studies. TeleSRH increases access and adherence to STI prevention (e.g., pre-exposure prophylaxis for HIV). Tele-follow-up may safely facilitate HIV care continuity. For CC/FP, TeleSRH is comparable to in-person care for patient satisfaction and uptake; patients are less likely to select long-acting reversible contraception but post-initiation tele-follow-up may increase its continuation rates. Vasectomy completion rates may be similar between pre-procedural counseling via telehealth versus in-person. TeleSRH’s potential benefits might include reduced travel time, wait times, no-show rates, and clinic human resource burden (via tele-triaging) and increased preventative screening rates for STIs and non-communicable diseases, prescription refill rates, ability to receive confidential care in preferred settings, and rural/marginalized community outreach. Implementation challenges span technological and capital constraints, provider availability, staff capability building, restrictive policies, language incompatibility, and patient mistrust. Supplementing synchronous TeleSRH with asynchronous communication (e.g., mobile application) may improve continued patient engagement. Conclusions: Preventive, diagnostic, and therapeutic TeleSRH can be effective, with high patient acceptability; however, effectiveness and adoption hinge on contextual factors outlined in this review. Full article

Background: Solid organ transplant recipients (SOTRs) are highly vulnerable to severe COVID-19 infection, yet initial vaccine trials provided limited data on efficacy and safety in this immunocompromised population. Heterogeneous seroconversion rates and conflicting safety reports complicate the formulation of clear clinical guidelines. This systematic review and meta-analysis aim to aggregate existing evidence to determine the precise seroconversion and safety profiles of COVID-19 vaccines and identify key factors influencing immune response in SOTRs. Methods: A comprehensive literature search was conducted identifying 125 studies evaluating WHO/FDA-authorized vaccines in SOTRs. Outcomes were the pooled seroconversion proportion and safety profile. Subgroup analyses were performed based on vaccine type, transplanted organ, number of doses, and prior SARS-CoV-2 infection status, confirmed by leave-one-out sensitivity analysis and bootstrap methods. Results: Most studies assessed mRNA-based vaccines (123/125, 98.4%). The overall pooled seroconversion proportion across all SOTRs was significantly blunted at 0.49 (95% CI, 0.43 to 0.55), demonstrating high heterogeneity (I² = 94.2%). Seroconversion showed a clear positive dose–response relationship, increasing from 27% after one dose to 84% after four doses. Prior COVID-19 infection was the strongest predictor of a response, resulting in a pooled seroconversion of 0.90 (95% CI, 0.82 to 0.94; I² = 0%). Organ-specific analyses revealed the highest response in Liver recipients (0.80) and the lowest in Lung recipients (0.29). Vaccine platform analysis showed that the highest response was with mRNA-1273 (0.55) and the lowest with CoronaVac (0.29). The safety profile was limited. Conclusions: SOTRs exhibit profound hypo responsiveness to COVID-19 vaccines; however, the extreme heterogeneity observed across studies necessitates a cautious interpretation of pooled seroconversion estimates. While the data indicates a significant dose–response relationship favoring an aggressive, multi-dose strategy, the apparent safety profile may reflect under-reporting and limited follow-up rather than confirmed safety equivalence. Rare but clinically critical outcomes, such as acute allograft rejection, remain inadequately characterized in the current literature. Consequently, while the prioritization of multi-dose regimens and hybrid immunity is supported to maximize protection, clinicians must recognize that individual responses remain highly variable, and the long-term immunological impact of repeated stimulation requires further standardized investigation. Full article

The Coronavirus Disease 2019 (COVID-19) pandemic and its prolonged effects have been widely discussed on social media, and these discussions have been analyzed in various studies. A long-term analysis of Twitter (now “X”) posts regarding COVID-19 vaccination is essential for informing policy and improving public health communication strategies. In addition, to prevent the spread of infectious diseases, it is crucial to rapidly promote vaccination while mitigating the impact of negative sentiment toward vaccination on social media platforms. Therefore, identifying the key factors behind negative discussions is important for guiding policy decisions and shaping responses. In this study, we collected Japanese tweets (posts) containing the words “Corona” and “vaccine” that were posted from February 2021 to December 2022. The results indicate that negative sentiment was primarily driven by concerns about adverse reactions and general fear and anxiety, which were particularly prominent before vaccination for the general public began, as well as mentions of pain during and after vaccination. While concerns about adverse reactions persisted throughout the analysis period, their prominence decreased over time as positive reactions became more frequent. Our findings provide insights into the characteristics and key factors behind negative discussions on COVID-19 vaccination in the Japanese context and may help improve public health communication strategies. Full article

Background: Although the main target of SARS-CoV-2 is the respiratory system, in some patients, it may affect multiple organ systems, leading to multi-organ failure. Acute kidney injury (AKI) remains one of the most frequent and clinically significant complications of severe COVID-19, with clinical importance extending beyond the acute phase due to its association with long-term renal outcomes and persistent morbidity. The incidence of AKI is particularly high among patients admitted to the intensive care unit (ICU), where its development has been consistently associated with prolonged hospitalization and increased mortality. The primary aim of this study was to determine the incidence of COVID-19-associated AKI, identify factors related to its development and severity, and evaluate mortality as a clinical outcome. Methods: Data from 238 COVID-19 patients monitored in the Intensive Care Unit of Ankara University Ibni Sina Hospital (ISH-ICU) between 1 January 2021 and 1 January 2022 were retrospectively reviewed. Patients were divided into two groups according to the presence of AKI. Those with AKI were staged according to KDIGO criteria (stages 1–2–3). Demographic characteristics, comorbidities, disease severity scores, laboratory parameters, and mortality outcomes were analyzed and compared between groups. Results: AKI was identified in 54.6% of patients. Of the patients with AKI, 32 (13.4%) had stage 1, 25 (10.5%) had stage 2, and 73 (30.7%) had stage 3 AKI. Thirteen patients (5.5%) had already developed AKI at ICU admission. AKI developed at a median of 11 days after symptom onset and 3 days after ICU admission. Advanced age, hypertension, cardiovascular disease, and chronic kidney disease were more frequent in patients with AKI (p < 0.001). Higher Charlson Comorbidity Index (CCI) and Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) scores were observed in patients with stage 3 AKI. Lymphopenia and elevated levels of D-dimer, ferritin, IL-6, CRP, and procalcitonin were significantly higher in patients with stage 3 AKI than in patients with other AKI stages and the non-AKI group. Mortality rates were higher in patients with AKI and increased with advancing AKI stage (p < 0.001). ICU length of stay was significantly longer in the AKI group (p < 0.001). Conclusions: AKI is a common complication among critically ill patients with COVID-19 and is associated with prolonged ICU stay and higher mortality rates, particularly in advanced stages. Early identification of clinical and laboratory factors associated with AKI may support timely risk stratification and targeted management in this high-risk population. Full article

Background/Objectives: Long COVID (LC) has been linked to fatigue, exercise intolerance, and autonomic dysfunction, but sex-stratified data on cardiovascular responses to maximal exercise—an essential component of personalized medicine—are scarce. This study aimed to examine hemodynamic, autonomic, and functional responses during and up to 24 h after a cardiopulmonary exercise test (CPET) in young adults with and without Long COVID (LC). Methods: In this cross-sectional study, we assessed 38 physically active adults, who were allocated into four subgroups stratified by clinical condition (LC or control) and biological sex: control–female (CON-F; n = 10), LC–female (LC-F; n = 10), control–male (CON-M; n = 10), and LC–male (LC-M; n = 8). Outcomes included systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), cardiac output (CO), total (TPR) and peripheral vascular resistance (PVR), pulse wave velocity (PWV), augmentation index (AIx@75), and heart rate variability (HF, LF, LF/HF), assessed at rest, peak effort, recovery (1, 3, 5, 10, 30, and 60 min), and through 24 h ambulatory blood pressure monitoring (ABPM) after CPET. Results: SBP increase appropriately during exercise, with higher peaks in males (p < 0.01), and returned to baseline within 5 min across all groups. HR recovery was preserved; however, LC-F showed lower values than CON-F at 3, 5, and 10 min (126 vs. 144 bpm, p = 0.020; 119 vs. 136 bpm, p = 0.020; 94 vs. 109 bpm, p = 0.011), though all groups normalized by 60 min. PWV, AIx@75, TPR and PVR exhibited expected sex-related patterns without LC-related impairments. HRV indices showed transient post-exercise shifts (HF↓, LF↑, LF/HF↑). Ambulatory monitoring confirmed preserved circadian modulation, with normal systolic dipping (11–13%) and no abnormal nocturnal patterns. Conclusions: Young physically active adults with LC showed preserved hemodynamic, autonomic, and vascular responses during and after maximal exercise. These findings contribute to personalized medicine by showing that individualized, sex-stratified cardiovascular assessments reveal no clinically relevant impairments in this population, supporting tailored clinical decision making and exercise prescription. Full article

This study introduces a nonlinear fractional bi-susceptible model for COVID-19 using the Atangana–Baleanu derivative in Caputo sense (ABC). The fractional framework captures nonlocal effects and temporal decay, offering a realistic presentation of persistent infection cycles and delayed recovery. Within this setting, we investigate multiple transmission modes, determine the major risk factors, and analyze the long-term dynamics of the disease. Analytical results are obtained at equilibrium states, and fundamental properties of the model are validated. Numerical simulations based on the Toufik–Atangana method further endorse the theoretical results and emphasize the effectiveness of the ABC derivative. Bifurcation analysis illustrates that adjusting time-invariant treatment and awareness efforts can accelerate pandemic control. Sensitivity analysis identifies the most significant parameters, which are used to construct an optimal control problem to determine effective disease control strategies. The numerical results reveal that the proposed control interventions minimize both infection levels and associated costs. Overall, this research work demonstrates the modeling strength of the ABC derivative by integrating fractional calculus, bifurcation theory, and optimal control for efficient epidemic management. Full article

COVID-19 has raised significant concern regarding its neurological impact, particularly during the early pandemic waves when severe systemic inflammation and neuroimmune dysregulation were more common. Although SARS-CoV-2 has been extensively studied, the precise mechanisms underlying its neurological effects remain incompletely understood, and much of the available evidence is derived from early variants with higher pathogenicity. Current research indicates that neuroinflammatory processes—driven primarily by systemic cytokine elevation, microglial activation, and blood–brain barrier dysfunction—contribute to a wide range of neurological symptoms. Severe complications such as encephalopathy, stroke, and cognitive impairment were predominantly reported in critically ill patients infected with the Wuhan, Alpha, or Delta variants, while such manifestations are considerably less frequent in the Omicron era. Most proposed mechanisms, including ACE2-mediated viral entry into the central nervous system, are supported mainly by experimental or preclinical studies rather than definitive human evidence. Biomarkers such as IL-6 and TNF-α, along with neuroimaging modalities including MRI and PET, offer useful but indirect indicators of neuroinflammation. Therapeutic approaches continue to focus on controlling systemic inflammation through immunomodulatory agents, complemented by targeted non-pharmacological strategies—such as physical rehabilitation, cognitive support, and psychological interventions—for the minority of patients with persistent neurological deficits. Overall, current evidence supports a variant-dependent neuroinflammatory profile and underscores the need for longitudinal, mechanism-focused studies to better characterize long-term neurological outcomes and refine therapeutic strategies. Full article

This paper examines the impact of fiscal policy responses on unemployment across EU countries from 2019 to 2024, a period marked by the COVID-19 pandemic as a shock event. A detailed monthly panel data set is used in this study, employing a fixed-effects estimation model with government spending, revenue, and debt as core variables, along with the COVID-19 dummy as a control variable. The findings reveal a strong association between government spending and revenue in reducing unemployment, aligned with countercyclical fiscal policy support. Conversely, increasing government debt is strongly linked to higher unemployment, indicating a risk of excessive borrowing that could hinder future labor market recovery. Moreover, uncertain external economic conditions, such as the COVID-19 pandemic, have further intensified labor market distortions. Finally, the results highlight that fiscal policies can effectively mitigate unemployment in the short term; however, excessive debt may pose challenges to long-term fiscal sustainability. This study underscores the importance of well-structured and timely coordinated fiscal policy frameworks that promote employment stabilization, while ensuring long-term debt sustainability. Full article

Numerous studies report cognitive impairment in COVID-19 patients from the acute to post-acute phases, linked to blood inflammation affecting blood–brain barrier (BBB) permeability and causing leakage of glial and neuronal proteins. However, a clear classification of these cognitive deficits and molecular blood events over time is still lacking. This narrative review summarizes the neuropsychological consequences of COVID-19 and evidence of altered cytokines and BBB disruption as potential mediators of cognitive impairment across post-infection phases. Post-COVID-19 cognitive dysfunction appears to follow a temporal course, evolving from acute focal deficits in attention, working memory, and executive function to more persistent multidomain impairments. We reviewed key cytokines released into the blood during COVID-19 infection, including antiviral (IFNγ, CXCL1, CXCL10), inflammatory (IL-1β, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, GM-CSF, TNFα), and monocyte chemoattractants (MCP1/CCL2, MCP3/CCL7, MIP-1α/CCL3, GM-CSF, G-CSF). This analysis shows that several inflammatory and viral cytokines remain elevated beyond the acute phase and are associated with cognitive deficits, including IL-6, IL-13, IL-8, IL-1β, TNFα, and MCP1 in long-term post-COVID-19 patients. In addition, we examined studies analyzing changes over time in neurovascular unit proteins as biomarkers of BBB disruption, including extracellular matrix proteins (PPIA, MMP-9), astrocytes (S100β, GFAP), and neurons (NFL). These proteins are elevated in acute COVID-19 but generally return to control levels within six months, suggesting BBB restoration. However, in patients followed for over a year, BBB disruption persists only in those with cognitive impairment and is associated with systemic inflammation, with TGFβ as a related biomarker. Although cognitive sequelae can persist for over 12 months after SARS-CoV-2 infection, further studies are needed to investigate long-term neurocognitive outcomes and their link to sustained proinflammatory cytokine elevation and brain impact. Full article