Search Results (639)

Cardiorespiratory fitness is a predictor of long-term health, traditionally assessed through structured exercise protocols that require maximal effort and controlled laboratory conditions. These protocols, while clinically validated, are often inaccessible, physically demanding, and unsuitable for unsupervised monitoring. This study proposes a non-invasive, unsupervised alternative—predicting the heart rate a person would reach after completing the step test, using wearable data collected during natural daily activities. Ground truth post-exercise heart rate was obtained through the Queens College Step Test, which is a submaximal protocol widely used in fitness settings. Separately, wearable sensors recorded heart rate (HR), blood oxygen saturation, and motion data during a protocol of lifestyle tasks spanning a range of intensities. Two machine learning models were developed—a Human Activity Recognition (HAR) model that classified daily activities from inertial data with 96.93% accuracy, and a regression model that estimated post step test HR using motion features, physiological trends, and demographic context. The regression model achieved an average root mean squared error (RMSE) of 5.13 beats per minute (bpm) and a mean absolute error (MAE) of 4.37 bpm. These findings demonstrate the potential of test-free methods to estimate standardized test outcomes from daily activity data, offering an accessible pathway to infer cardiorespiratory fitness. Full article

Laparoscopic urological surgery has become a cornerstone in the management of diverse urological pathologies, offering substantial advantages over traditional open approaches. These benefits include minimized incisions, reduced tissue trauma, decreased intraoperative blood loss, lower postoperative pain, shorter hospital stays, superior cosmesis, and accelerated recovery. Despite these advantages, laparoscopic surgery carries inherent risks, with major vascular injury (MVI) representing one of the most severe and potentially life-threatening complications. This review examines the incidence, etiologies, and management strategies for MVI in laparoscopic urological surgery, emphasizing the critical role of early recognition, standardized protocols, and surgical expertise in optimizing patient outcomes. Full article

Background and Clinical Significance: Infective endocarditis (IE) is a serious condition with rising incidence, frequently caused by Staphylococcus aureus. However, cases involving rare congenital anomalies such as Gerbode’s defect are uncommon. Case Presentation: This report presents the first documented case of IE in a patient with a congenital Gerbode defect complicated by DRESS syndrome—a severe, drug-induced hypersensitivity reaction typically triggered by antibiotics like oxacillin. A 65-year-old woman developed infective endocarditis involving vegetations on the cardiac device lead, the tricuspid valve, and adjacent to a Gerbode defect. The diagnosis was confirmed by positive blood cultures and echocardiographic findings. She received treatment with oxacillin. Subsequently, she exhibited clinical features consistent with DRESS syndrome, including rash, eosinophilia, and multi-organ involvement. Rapid recognition and management, including corticosteroid therapy and antibiotic modification, led to clinical improvement. Conclusions: This case highlights the importance of vigilance for DRESS syndrome in prolonged antibiotic therapy for IE, especially in the context of rare congenital cardiac anomalies. In addition, guidelines are needed to optimize the diagnosis and treatment of this potentially lethal complication. Full article

Vitamin A deficiency (VAD) remains a significant cause of preventable blindness worldwide, with ocular surface changes representing early manifestations that require prompt recognition and treatment. Conventional examination methods are capable of detecting advanced changes; however, subtle conjunctival abnormalities may be overlooked, potentially delaying the administration of appropriate interventions. We herein present the case of a 5-year-old Japanese boy with severe VAD due to selective eating patterns. This case demonstrates the utility of infrared photography as a novel diagnostic approach for detecting and monitoring conjunctival surface abnormalities. The patient exhibited symptoms including corneal ulcers, night blindness, and reduced visual acuity. Furthermore, blood tests revealed undetectable levels of vitamin A (5 IU/dL), despite relatively normal physical growth parameters. Conventional slit-lamp examination revealed characteristic sandpaper-like conjunctival changes. However, infrared photography (700–900 nm wavelength) revealed distinct abnormal patterns of conjunctival surface folds and keratinization that were not fully appreciated on a routine examination. Following high-dose vitamin A supplementation (4000 IU/day), complete resolution of ocular abnormalities was achieved within 2 months, with infrared imaging objectively documenting treatment response and normalization of conjunctival surface patterns. This case underscores the potential for severe VAD in developed countries, particularly in the context of dietary restrictions, thereby underscoring the significance of a comprehensive dietary history and a meticulous ocular examination. Infrared photography provides a number of advantages, including the capacity for non-invasive assessment, enhanced visualization of subtle changes, objective monitoring of treatment response, and cost-effectiveness due to the use of readily available equipment. This technique represents an underutilized diagnostic modality with particular promise for screening programs and clinical monitoring of VAD-related ocular manifestations, potentially preventing irreversible visual loss through early detection and intervention. Full article

Although intracranial hypertension (ICH) has traditionally been framed as simply a numerical escalation of intracranial pressure (ICP) and usually dealt with in its clinical form and not in terms of its complex underlying pathophysiology, an emerging body of evidence indicates that ICH is not simply an elevated ICP process but a complex process of molecular dysregulation, glymphatic dysfunction, and neurovascular insufficiency. Our aim in this paper is to provide a complete synthesis of all the new thinking that is occurring in this space, primarily on the intersection of glymphatic dysfunction and cerebral vein physiology. The aspiration is to review how glymphatic dysfunction, largely secondary to aquaporin-4 (AQP4) dysfunction, can lead to delayed cerebrospinal fluid (CSF) clearance and thus the accumulation of extravascular fluid resulting in elevated ICP. A range of other factors such as oxidative stress, endothelin-1, and neuroinflammation seem to significantly impair cerebral autoregulation, making ICH challenging to manage. Combining recent studies, we intend to provide a revised conceptualization of ICH that recognizes the nuance and complexity of ICH that is understated by previous models. We wish to also address novel diagnostics aimed at better capturing the dynamic nature of ICH. Recent advances in non-invasive imaging (i.e., 4D flow MRI and dynamic contrast-enhanced MRI; DCE-MRI) allow for better visualization of dynamic changes to the glymphatic and cerebral blood flow (CBF) system. Finally, wearable ICP monitors and AI-assisted diagnostics will create opportunities for these continuous and real-time assessments, especially in limited resource settings. Our goal is to provide examples of opportunities that exist that might augment early recognition and improve personalized care while ensuring we realize practical challenges and limitations. We also consider what may be therapeutically possible now and in the future. Therapeutic opportunities discussed include CRISPR-based gene editing aimed at restoring AQP4 function, nano-robotics aimed at drug targeting, and bioelectronic devices purposed for ICP modulation. Certainly, these proposals are innovative in nature but will require ethically responsible confirmation of long-term safety and availability, particularly to low- and middle-income countries (LMICs), where the burdens of secondary ICH remain preeminent. Throughout the review, we will be restrained to a balanced pursuit of innovative ideas and ethical considerations to attain global health equity. It is not our intent to provide unequivocal answers, but instead to encourage informed discussions at the intersections of research, clinical practice, and the public health field. We hope this review may stimulate further discussion about ICH and highlight research opportunities to conduct translational research in modern neuroscience with real, approachable, and patient-centered care. Full article

Background and Objectives: Immunodeficiency associated with aging comorbidities increases the vulnerability of geriatric patients to sepsis. Early recognition and management of sepsis are essential in this population. This study evaluated the relationships between RDW, MPV, and MPV/PLT ratios and mortality in geriatric sepsis patients. Materials and Methods: This retrospective study was conducted between 2020 and 2024 in the Intensive Care Unit of the Department of Anesthesiology and Reanimation at a university hospital. Patients aged ≥ 65 years with a SOFA score of ≥2 were included. Demographic data (sex, age, height, weight, and BMI), hemogram parameters (RDW, MPV, and PLT), blood gas, and biochemical values were analyzed. Furthermore, their comorbidities; site of infection; ICU length of stay; vital signs; and SOFA, APACHE II, and SAPS II scores, recorded within the first 24 h following ICU admission, were evaluated. Statistical analysis was performed using the chi-square test, Student’s t-test, the Mann–Whitney U test, the Monte Carlo exact test, and ROC analysis. A p-value of <0.05 was considered statistically significant. Results: A total of 247 patients were included, with 46.2% (n = 114) classified as non-survivors during the 28-day follow-up period. Among them, 64.9% (n = 74) were male, with a mean age of 78.22 ± 8.53 years. Significant differences were also found in SOFA, APACHE-II, and SAPS-II scores between non-survivors and survivors (SOFA: 7.64 ± 3.16 vs. 6.78 ± 2.78, p = 0.023; APACHE-II: 21.31 ± 6.36 vs. 19.27 ± 5.88, p = 0.009; SAPS-II: 53.15 ± 16.04 vs. 46.93 ± 14.64, p = 0.002). On days 1, 3, and 5, the MPV/PLT ratio demonstrated a statistically significant predictive value for 28-day mortality. The optimal cut-off values were >0.03 on day 1 (AUC: 0.580, 95% CI: 0.516–0.642, sensitivity: 72.81%, specificity: 65.91%, p = 0.027), >0.04 on day 3 (AUC: 0.602, 95% CI: 0.538–0.663, sensitivity: 60.53%, specificity: 60.61%, p = 0.005), and >0.04 on day 5 (AUC: 0.618, 95% CI: 0.554–0.790, sensitivity: 66.14%, specificity: 62.88%, p = 0.001). Conclusions: The MPV and MPV/PLT ratios demonstrated statistically significant but limited predictive value for 28-day mortality in geriatric patients with sepsis. In contrast, the limited prognostic value of RDW may be related to variability in the inflammatory response and other underlying conditions. The correlations found between SOFA, APACHE II, and SAPS II scores highlight their importance in mortality risk prediction. Full article

The aim of this study is to assess endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) at the time of type 1 diabetes (T1D) recognition concerning patients’ clinical state, remaining insulin secretion, and further partial remission (PR) occurrence. We recruited 45 children that were admitted to hospital due to newly diagnosed T1D (median age 10.8 yrs), and 20 healthy peers as a control group. EPC and CEC levels were measured at disease onset in PBMC isolated from whole peripheral blood with the use of flow cytometry. Clinical data regarding patients’ condition, C-peptide secretion, and further PR prevalence were analyzed. T1D-diagnosed patients presented higher EPC levels than the control group (p = 0.026), while no statistical differences in CEC levels and EPC/CEC ratio were observed. Considering only T1D patients, those with better clinical conditions presented lower EPCs (p = 0.021) and lower EPC/CEC ratios (p = 0.0002). Patients with C-peptide secretion within a normal range at disease onset presented lower EPC/CEC ratios (p = 0.027). Higher levels of EPCs were observed more frequently in patients with higher glucose, decreased fasting C-peptide, and lower stimulated C-peptide (all p < 0.05). The presence of DKA was related to higher EPC/CEC ratios (p = 0.034). Significantly higher levels of CECs were observed in patients who presented partial remission of the disease at 6 months after diagnosis (p = 0.03) only. In the study group, positive correlations of CECs with age, BMI at onset, and BMI in following years were observed. EPC/CEC ratios correlated positively with glucose levels at hospital admission and negatively with age, BMI, pH, and stimulated C-peptide level. We reveal a new potential for the application of EPCs and CECs as biomarkers, reflecting both endothelial injury and reconstruction processes in children with T1D. There is a need for further research in order to reduce cardiovascular risk in children with T1D. Full article

Background: Hypotension following epidural labor analgesia (ELA) is its most common complication, affecting approximately 20% of patients and posing risks to both maternal and fetal health. As digital tools and predictive analytics increasingly shape perioperative and obstetric anesthesia practices, real-world implementation data are needed to guide their integration into clinical care. Current monitoring practices rely on intermittent non-invasive blood pressure (NIBP) measurements, which may delay recognition and treatment of hypotension. The Hypotension Prediction Index (HPI) algorithm uses continuous arterial waveform monitoring to predict hypotension for potentially earlier intervention. This clinical trial evaluated the feasibility, acceptability, and efficacy of continuous HPI-guided treatment in reducing time-to-treatment for ELA-associated hypotension and improving maternal hemodynamics. Methods: This was a prospective randomized controlled trial design involving healthy pregnant individuals receiving ELA. Participants were randomized into two groups: Group CM (conventional monitoring with NIBP) and Group HPI (continuous noninvasive blood pressure monitoring). In Group HPI, hypotension treatment was guided by HPI output; in Group CM, treatment was based on NIBP readings. Feasibility, appropriateness, and acceptability outcomes were assessed among subjects and their bedside nurse using the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM) instruments. The primary efficacy outcome was time-to-treatment of hypotension, defined as the duration between onset of hypotension and administration of a vasopressor or fluid therapy. This outcome was chosen to evaluate the clinical responsiveness enabled by HPI monitoring. Hypotension is defined as a mean arterial pressure (MAP) < 65 mmHg for more than 1 min in Group CM and an HPI threshold < 75 for more than 1 min in Group HPI. Secondary outcomes included total time in hypotension, vasopressor doses, and hemodynamic parameters. Results: There were 30 patients (Group HPI, n = 16; Group CM, n = 14) included in the final analysis. Subjects and clinicians alike rated the acceptability, appropriateness, and feasibility of the continuous monitoring device highly, with median scores ≥ 4 across all domains, indicating favorable perceptions of the intervention. The cumulative probability of time-to-treatment of hypotension was lower by 75 min after ELA initiation in Group HPI (65%) than Group CM (71%), although this difference was not statistically significant (log-rank p = 0.66). Mixed models indicated trends that Group HPI had higher cardiac output (β = 0.58, 95% confidence interval −0.18 to 1.34, p = 0.13) and lower systemic vascular resistance (β = −97.22, 95% confidence interval −200.84 to 6.40, p = 0.07) throughout the monitoring period. No differences were found in total vasopressor use or intravenous fluid administration. Conclusions: Continuous monitoring and precision hypotension treatment is feasible, appropriate, and acceptable to both patients and clinicians in a labor and delivery setting. These hypothesis-generating results support that HPI-guided treatment may be associated with hemodynamic trends that warrant further investigation to determine definitive efficacy in labor analgesia contexts. Full article

In this paper, screen-printed ion-selective electrodes combined with single-walled carbon nanotubes (SWCNTs) and gold nanoparticles (AuNPs) were used to rapidly and accurately measure serum Ca²⁺ concentration. Due to the susceptibility of cows to hypocalcemia after delivery, this disease can affect the health of cows and reduce milk production. Therefore, the development of an economical and swift detection method holds paramount importance for facilitating early diagnosis and subsequent treatment. In this study, by combining the high electrical conductivity and large surface area of SWCNTs with the strong catalytic activity of AuNPs, a SWCNTs/AuNPs composite with high sensitivity and good stability was prepared, achieving efficient selective recognition and signal conversion of Ca²⁺. The experimental results indicate that the screen-printed electrode modified with SWCNTs/AuNPs exhibited excellent performance in the determination of Ca²⁺ concentration. Its linear response range is 10^−5.5–10⁻¹ M, covering the normal and pathological concentration range of Ca²⁺ in cow blood, and the detection limit is far below the clinical detection requirements. In addition, the electrode also has good anti-interference ability and fast response time (about 15 s), showing good performance in the range of 5–45 °C. In practical applications, the combination of the electrode and portable detection equipment can realize the field rapid determination of cow blood Ca²⁺ concentration. This method is easy to operate, cost-effective, and easy to promote, providing strong technical support for the health management of dairy farms. Full article

T-cell receptors (TCRs) exhibit degeneracy, enabling individual TCRs to recognize multiple altered peptide ligands (APLs) derived from a single cognate antigen. This characteristic has been involved in the pathogenesis of autoimmune diseases through cross-reactivity between microbial and self-antigens. Cytotoxic T lymphocytes (CTLs), which recognize peptide–MHC class I complexes via TCRs, play a critical role in the immune response against viral infections. However, the extent to which TCR degeneracy within a population of virus-specific CTLs contributes to effective viral control remains poorly understood. In this study, we investigated the magnitude and functional relevance of TCR degeneracy in CTLs targeting an immunodominant epitope of human T-cell leukemia virus type 1 (HTLV-1) in patients with HTLV-1-associated myelopathy (HAM). Using peripheral blood mononuclear cells (PBMCs) from these patients, we quantified TCR degeneracy at the population level by comparing CTL responses to a panel of APLs with responses to the cognate epitope. Our findings demonstrated that increased TCR degeneracy, particularly at the primary TCR contact residue at position 5 of the antigen, was inversely correlated with HTLV-1 proviral load (p = 0.038, R = −0.40), despite similar functional avidity across patient-derived CTLs. Viral sequencing further revealed that CTLs with high TCR degeneracy exerted stronger selective pressure on the virus, as indicated by a higher frequency of nonsynonymous substitutions within the epitope-encoding region in patients with highly degenerate TCR repertoires. Moreover, TCR degeneracy was positively correlated with the recognition rate of epitope variants (p = 0.018, R = 0.76), suggesting that CTLs with high TCR degeneracy exhibited enhanced recognition of naturally occurring epitope variants compared to those with low TCR degeneracy. Taken together, these results suggest that virus-specific CTLs with high TCR degeneracy possess superior antiviral capacity, characterized by broadened epitope recognition and more effective suppression of HTLV-1 infection. To our knowledge, this is the first study to systematically quantify TCR degeneracy in HTLV-1-specific CTLs and evaluate its contribution to viral control in HAM patients. These findings establish TCR degeneracy as a critical determinant of antiviral efficacy and provide a novel immunological insight into the mechanisms of viral suppression in chronic HTLV-1 infection. Full article

Cognitive decline is a common complication of diabetes mellitus, driven in part by oxidative stress and impaired glucose–insulin homeostasis. This study examined the neuroprotective effects of agmatine (200 mg/kg intraperitoneally) in female BALB/c diabetic mice. Several receptor pathways were examined using commercially available antagonists. Behavioral performance was evaluated using the novel object recognition test. Metabolic parameters, such as glucose and insulin levels, as well as antioxidants, including catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH), were measured in blood and brain tissue. The diabetic mice exhibited impaired recognition memory (discrimination index = 0.08), hyperglycemia (24.3 mmol/L), decreased insulin levels (38.4 µU/mL), and diminished antioxidant defenses (CAT: 75.4 U/g tissue, SOD: 32.6 U/g tissue, and GSH: 8.3 mmol/g tissue). Agmatine treatment improved cognitive function and reversed the biochemical alterations. However, these effects were reduced when agmatine was co-administered with imidazoline I₂/I₃ receptor antagonists. Correlation analysis revealed that cognitive performance positively correlated with antioxidant enzyme levels and insulin levels and negatively correlated with glucose concentrations. Strong intercorrelations among CAT, SOD, and GSH levels suggest a coordinated antioxidant response. Overall, these results imply that agmatine’s neuroprotective effects are partially mediated by modulation of the oxidative balance and glucose–insulin regulation via imidazoline receptors. Full article

Dengue mortality has traditionally been associated with severe thrombocytopenia and hemorrhagic complications. However, during 2024, dengue virus serotype 3 (DENV-3) increased significantly in western Mexico, leading to the emergence of a distinct clinical pattern. We conducted a retrospective cohort study of hospitalized dengue patients at the General Hospital of Colima (January–August 2024). Clinical features, laboratory parameters, and outcomes were compared between survivors and non-survivors. Among 201 hospitalized patients, 6 (3.0%) died. All deceased patients presented with generalized seizures, polyserositis (pleural effusion and/or ascites), and required mechanical ventilation. Contrary to classical patterns, they did not have severe thrombocytopenia. Instead, they showed significantly higher white blood cell counts and notably increased levels of serum urea and BUN, suggesting early renal impairment. ROC analysis indicated that BUN (AUC 0.904) and urea (AUC 0.906) were good to excellent discriminators of mortality. During 2024, with an increase in DENV-3 circulation, mortality was associated with neurological and systemic complications, including seizures and polyserositis, as well as biochemical evidence of renal dysfunction—but not with severe thrombocytopenia. These findings challenge current paradigms and highlight the need for early recognition of atypical clinical patterns. Full article

Fungi are ubiquitous organisms that are capable of transient or persistent colonization in humans. Their polymorphic nature and complex host–mycobiome interactions remain incompletely understood. Emerging evidence highlights the role of resident fungi in modulating immune responses and adapting to host changes, which can trigger a shift from commensalism to parasitism, particularly in immunocompromised individuals. This study evaluated the effects of two major β-glucans—zymosan and curdlan—on the expression of pattern recognition receptors (Dectin1, Dectin2, TLR2, TLR4) in human peripheral blood mononuclear cells (PBMCs). It also examined their impact on reactive oxygen species (ROS) production, cytokine/chemokine gene expression, and antioxidant enzyme expression. Both β-glucans significantly increased the mRNA levels of all tested receptors and enhanced ROS generation. Curdlan downregulated key antioxidant enzymes (SOD1, CAT, GPX1), while zymosan markedly upregulated SOD1. These findings demonstrate that the β-glucans zymosan and curdlan have a substantial influence on PBMC reactivity and oxidative stress responses. Further studies are needed to deepen our understanding of host–fungal interactions and their implications in health and disease. Full article

Down syndrome (DS), the most common human aneuploidy, is associated with oxidative stress, which contributes to morphological abnormalities, immune dysfunction, cognitive impairment and accelerated ageing. This article aims to provide an overview of the studies on oxidative stress in DS, in particular the investigation of endogenous and exogenous antioxidants, with a focus on endogenous systems. A literature search in MEDLINE and Scopus based on the PRISMA 2020 criteria revealed 41 relevant studies that mainly analysed blood samples (plasma or serum) and occasionally saliva or urine. The findings suggest that oxidative stress in DS is multifactorial and results from an imbalance of superoxide dismutase activity, overexpression of genes on chromosome 21, mitochondrial dysfunction and inflammation. Despite extensive studies over the decades, new sources and mechanisms for oxidative stress in DS continue to emerge, further highlighting the complexity of DS. The recognition that oxidative stress is a hallmark of DS emphasises the need to develop more sensitive and specific methods to detect it and to investigate the associated metabolic pathways in DS in more detail. The expansion of in vivo studies could facilitate the development of targeted interventions aimed at mitigating oxidative damage and ultimately improving outcomes for individuals with DS. Full article

Superparamagnetic iron oxide (SPIO) nanoparticles are a promising platform for drug delivery and magnetic resonance imaging (MRI). However, complement activation and immune recognition remain major barriers to their clinical translation. Previously, we reported that dextran-coated SPIO nanoworms (NWs) trigger potent complement activation and infusion reactions. Here, we systematically map the temporal sequence of immune events following SPIO NW administration, including C3 opsonization, granulocyte uptake, and cytokine release. In both in vitro and in vivo models, C3 deposition occurred rapidly, peaking at approximately 5 min post-incubation or post-injection. Higher Fe/plasma ratios led to reduced C3 deposition per particle, although the absolute amount of C3 bound was greater in vivo than in vitro. Notably, C3 dissociation from the particle surface exhibited a consistent half-life of ~14 min, independent of the NW injected dose and circulation time. Immune uptake by blood granulocytes was delayed relative to opsonization, becoming prominent only at 60 min post-injection. Further, cytokine release, measured by plasma IL-6 levels, displayed an even slower profile, with peak expression at 6 h post-injection. Together, these results reveal a distinct sequential immune response to SPIO NWs: rapid C3 opsonization, delayed cellular uptake, and late cytokine response. Understanding these dynamics provides a basis for developing strategies to inhibit complement activation and improve the hemocompatibility of SPIO-based theranostic agents. Full article