Search Results (1,055)

It is well established that combining exercise with medication may benefit functionality in individuals with PD (Parkinson’s disease). However, the long-term evolution of gait biomechanics under this combination remains poorly understood. Objectives: This study aims to analyze the evolution of spatiotemporal gait parameters, kinetics, and kinematics throughout a long-term exercise program conducted in water and on dry land. Methods: We have compared the trajectories of biomechanical variables across the treatment phases using statistical parametric mapping (SPM). A cohort of fourteen individuals with PD (mean age: 65.6 ± 12.1 years) participated in 24 sessions of aquatic exercises over three months, followed by a three-month retention phase, and then 24 additional sessions of land-based exercises. Three-dimensional gait data and spatiotemporal parameters were collected before and after each phase. Two-way ANOVA with repeated measures was used to compare spatiotemporal parameters. Results: The walking speed increased while the duration of the double support phase decreased. Additionally, the knee extensor moment consistently increased in the entire interval from midstance to midswing (20% to 70% of the stride period), approaching normal gait patterns. Regarding kinematics, significant increases were observed in both hip and knee flexion angles. Furthermore, the abnormal ankle dorsiflexion observed at the foot strike disappeared. Conclusions: These findings collectively suggest positive adaptations in gait biomechanics during the observation period. Full article

Background: Charcot–Marie–Tooth disease (CMT) is a genetically and phenotypically heterogeneous hereditary neuropathy. Axonal CMT type 2 (CMT2) subtypes often exhibit overlapping clinical features, which makes molecular genetic analysis essential for accurate diagnosis and subtype differentiation. Methods: This retrospective study included five pediatric patients who presented with gait disturbance, muscle weakness, and foot deformities and were subsequently diagnosed with axonal forms of CMT. Clinical data, electrophysiological studies, neuroimaging, and genetic analyses were evaluated. Whole exome sequencing (WES) was performed in three sporadic cases, while targeted CMT gene panel testing was used for two siblings. Variants were interpreted using ACMG guidelines, supported by public databases (ClinVar, HGMD, and VarSome), and confirmed by Sanger sequencing when available. Results: All had absent deep tendon reflexes and distal muscle weakness; three had intellectual disability. One patient was found to carry a novel homozygous frameshift variant (c.2568_2569del) in the IGHMBP2 gene, consistent with CMT2S. Other variants were identified in the NEFH (CMT2CC), DYNC1H1 (CMT2O), and MPV17 (CMT2EE) genes. Notably, a previously unreported co-occurrence of MPV17 mutation and congenital heart disease was observed in one case. Conclusions: This study expands the clinical and genetic spectrum of pediatric axonal CMT and highlights the role of early physical examination and molecular diagnostics in detecting rare variants. Identification of a novel IGHMBP2 variant and unique phenotypic associations provides new insights for future genotype–phenotype correlation studies. Full article

Sin Nombre virus (SNV) is the main causative agent of hantavirus cardiopulmonary syndrome (HCPS) in North America. SNV is transmitted via environmental biological aerosols (bioaerosols) produced by infected deer mice (Peromyscus maniculatus). It is similar to other viruses that have environmental transmission routes rather than a person-to-person transmission route, such as avian influenza (e.g., H5N1) and Lassa fever. Despite the lack of person-to-person transmission, these viruses cause a significant public health and economic burden. However, due to the lack of targeted pharmaceutical preventatives and therapeutics, the recommended approach to prevent SNV infections is to avoid locations that have a combination of low foot traffic, receive minimal natural sunlight, and where P. maniculatus may be found nesting. Consequently, gaining insight into the SNV bioaerosol decay profile is fundamental to the prevention of SNV infections. The Biological Aerosol Reaction Chamber (Bio-ARC) is a flow-through system designed to rapidly expose bioaerosols to environmental conditions (ozone, simulated solar radiation (SSR), humidity, and other gas phase species at stable temperatures) and determine the sensitivity of those particles to simulated ambient conditions. Using this system, we examined the bioaerosol stability of SNV. The virus was found to be susceptible to both simulated solar radiation and ozone under the tested conditions. Comparisons of decay between the virus aerosolized in residual media and in a mouse bedding matrix showed similar results. This study indicates that SNV aerosol particles are susceptible to inactivation by solar radiation and ozone, both of which could be implemented as effective control measures to prevent disease in locations where SNV is endemic. Full article

Idiopathic childhood nephrotic syndrome is a common glomerulopathy comprising proteinuria, hypoalbuminemia, and edema. Podocyte dysfunction is central to this disease process. Extracellular vesicles are released from stressed cells and can represent a molecular snapshot of the parent cell of origin. We previously showed that urinary large extracellular vesicles (LEVs) derived from podocytes are increased in patients with nephrotic syndrome relapse. Here, we investigated the role of mitochondrial DNA (mtDNA) within LEVs both in vitro and in vivo, revealing the novel finding that podocytes release LEVs containing mtDNA, driven by mitochondrial stress. A puromycin aminonucleoside nephrosis rat model showed foot process effacement on electron microscopy and urinary LEVs with significantly increased mtDNA. Prednisolone, which drives remission in nephrotic syndrome in children, attenuated mitochondrial stress and reduced the amount of mtDNA content within LEVs in vitro. Lastly, urinary LEVs from children with nephrotic syndrome also contain mtDNA, and it is the podocyte LEV-fraction which is preferentially enriched. Overall, these data support a potential mechanism of podocyte mitochondrial stress in non-genetic, idiopathic pediatric nephrotic syndrome. Full article

The livestock sector is a significant contributor to the economy and rural livelihoods, but it is exposed to high risk across the supply chain, which is detrimental and needs to be addressed for sustainable development. Therefore, this study aimed to identify the major risk mitigation strategies (RMSs) and associated factors that affect their adoption. This study conducted a comprehensive literature review to identify the eight major RMSs and prioritized them through an analytical hierarchical process (AHP). Thereafter, a multivariate probit (MVP) model was developed to identify the factors affecting the adoption of major RMSs. The primary RMSs are livestock insurance, vaccination of livestock, and advisory/extension services. Further, the multivariate probit regression analysis shows that ‘age’, ‘social category’, ‘economic status’, ‘educational level’, ‘income level’, ‘the total number of animals’, and ‘perceived risk of foot and mouth disease’ are significant factors that influence the adoption of RMSs. This study’s findings will be useful for livestock supply chain partners to mitigate the risks along the livestock supply chain. This research will also help policymakers to develop policies/plans for incorporating these RMSs by considering the influencing associated factors. Full article

Background: Huriez syndrome is a rare hereditary skin disorder marked by early-onset sclerodactyly, hyperkeratosis of the palms and soles, and nail dysplasia. A key concern is the early and aggressive development of cutaneous squamous cell carcinoma (SCC), typically affecting the dorsal aspects of the hands. Methods: This narrative review summarizes clinical features, genetic aspects, and oncologic implications of Huriez syndrome. A systematic search was conducted in PubMed and Scopus, including English-language articles published up to May 2025. Relevant case reports and small case series were analyzed. Results: Seven patients (58.3%) underwent multiple surgeries due to recurrent or bilateral disease. Six patients (50%) required amputations, including finger, hand, and arm amputations, with no foot amputations reported. Reconstruction after oncological resection was performed in six patients (50%) using skin grafts (3), pedicled flaps (2), or free flaps (1). Amputation was mainly for advanced disease, with radial forearm flaps used for reconstruction. All flaps remained disease-free. Five cases (41.6%) had a history of local recurrence. Conclusions: The early diagnosis of Huriez syndrome is crucial to enable the surveillance and timely treatment of SCC. A multidisciplinary team including dermatologists, oncologists, plastic surgeons, and geneticists is recommended. Further research is needed to clarify genetic mechanisms and develop early detection strategies to improve outcomes. Full article

Background: Enterovirus A71 (EV-A71) is considered as the primary causative agent of hand, foot, and mouth disease (HFMD) in young children, leading to severe neurological complications and contributing to substantial mortalities in recent HFMD outbreaks across Asia. Despite this, there is currently no effective antiviral treatment available for EV-A71. RNA interference (RNAi) is a powerful mechanism of post-transcriptional gene regulation that utilizes small interfering RNA (siRNA) to target and degrade specific RNA sequences. Objectives: The aim of this study was to design various siRNAs targeting EV-A71 genomic regions and evaluate the RNAi efficacy against a novel, previously genetically uncharacterized EV-A71 strain. Methods: A novel EV-A71 strain was first sequenced to design target-specific siRNAs. The viral titers, viral protein expression, cytopathic effects, and cell viability of EV-A71-infected HeLa cells were examined to evaluate the specific viral inhibition by the siRNAs. Results: A substantial reduction in viral titers and viral protein synthesis was observed in EV-A71-infected HeLa cells treated with specific siRNAs targeting the VP4, VP3, 2B, and 3A genes. siRNAs delayed cytopathic effects and increased cell viability of EV-A71-infected HeLa cells. Nonspecific interferon induction caused by siRNAs was not observed in this study. In contrast, replication of coxsackievirus B3, another important member of the Enterovirus genus, remained unaffected. Conclusions: Overall, the findings demonstrate that RNAi targeting genomic regions of EV-A71 VP4, VP3, 2B, or 3A could become a potential strategy for controlling EV-A71 infection, and this promising result can be integrated into future anti-EV-A71 therapy developments. Full article

Foot-and-mouth disease (FMD), bluetongue (BT), and Peste des Petits Ruminants (PPR) are major emerging and re-emerging viral infections affecting ruminants. These diseases can threaten livestock health, food security, and economic stability in low- and middle-income countries, including Algeria. However, their dynamics remain mostly unknown, limiting the implementation of effective preventive and control measures. We analyzed outbreak data reported by Algerian veterinary authorities and the WAHIS database from 2014 to 2022 for FMD; from 2006 to 2020 for BT; and from 2011 to 2022 for PPR to investigate their spatiotemporal patterns and environmental drivers. Over these periods, Algeria reported 1142 FMD outbreaks (10,409 cases; 0.16/1000 incidence), 167 BT outbreaks (602 cases; 0.018/1000), and 222 PPR outbreaks (3597 cases; 0.096/1000). Small ruminants were the most affected across all diseases, although cattle bore the highest burden of FMD. BT primarily impacted sheep, and PPR showed a higher incidence in goats. Disease peaks occurred in 2014 for FMD, 2008 for BT, and 2019 for PPR. Spatial analyses revealed distinct ecological hotspots: sub-humid and semi-arid zones for FMD and BT, and semi-arid/Saharan regions for PPR. These patterns may be influenced by species susceptibility, animal movement, trade, and climatic factors such as temperature and rainfall. The absence of consistent temporal trends and the persistence of outbreaks suggest multiple drivers, including insufficient vaccination coverage, under-reporting, viral evolution, and environmental persistence. Our findings underscore the importance of targeted species- and region-specific control strategies, including improved surveillance, cross-border coordination, and climate-informed risk mapping. Strengthening One Health frameworks will be essential to mitigate the re-emergence and spread of these diseases. Full article

Exercise is a cornerstone of diabetes management, but the onset of diabetic foot disease (DFD) can significantly limit its implementation. Meanwhile, physical activity (PA) has been shown to reduce the risk of developing DFD through various mechanisms, and emerging evidence also supports the role of exercise in managing the active phase of the condition. Appropriately tailored PA offers both local and systemic benefits—even in clinical contexts where foot offloading is recommended. The research indicates that selected exercises can be safely incorporated into care plans, providing therapeutic effects without compromising wound healing. Drawing from current knowledge based on basic science, clinical research, and relatively general recommendations, this article summarizes the local and systemic effects of properly selected exercises in patients with DFD. It explains the underlying mechanisms and briefly discusses practical examples, integrating the most recently published findings. Full article

Background: Diabetic foot disease is a public health problem. The challenges of its management lie in the complexity of wound healing and, in particular, the high rate of lesion recurrence. Objectives: The primary objective of the study was to evaluate whether optimized post-healing follow-up by a multidisciplinary team can reduce the recurrence rate of foot ulcers in people living with diabetes. The secondary objectives were to assess patient needs in terms of hospitalization for recurrence, the number of amputations, pedicure care, and the use of adapted footwear. Participants: The study included 129 patients with diabetes presenting a healed foot ulcer. A total of 38 patients underwent an annual post-healing follow-up visit with a multidisciplinary team (optimized follow-up), while 91 had a visit every 2 years (minimum follow-up). Results: Of the 38 patients with optimal follow-up, 8 presented a wound recurrence (21.1%) compared with 38 out of 91 patients (41.8%) receiving minimum follow-up. The recurrence rate decreased significantly between the two groups (p < 0.05). The use of adapted shoes was also significantly better in the group with optimized follow-up (p = 0.02). Conclusions: Regular post-healing follow-up with a multidisciplinary team seems to be a contributing factor to reducing the recurrence of diabetic foot ulcers among people living with diabetes. Full article

Although emerging evidence suggests that epigenetic mechanisms contribute to the pathogenesis and progression of type 2 diabetes mellitus (T2DM), data remain limited for patients with suboptimal metabolic control. The aim of this study was to assess global DNA methylation in patients with poorly controlled T2DM and to identify diabetes-related factors associated with DNA methylation levels. The study included 107 patients and 50 healthy controls. Global DNA methylation (5mC) was measured by UHPLC-DAD method. Pro-oxidant and antioxidant biomarkers, advanced glycation end-products, high-sensitivity C-reactive protein (hsCRP) and complete blood count were determined and leukocyte indices calculated. Patients had a significantly lower 5mC than controls (3.56 ± 0.31% vs. 4.00 ± 0.68%; p < 0.001), with further reductions observed in those with longer disease duration and diabetic foot ulcers. Oxidative stress and inflammatory biomarkers were higher in the patient group. DNA hypomethylation was associated with a higher monocyte-to-lymphocyte ratio and hsCRP, pro-oxidant–antioxidant balance, ischemia-modified albumin, and advanced oxidation protein products levels. Conversely, 5mC levels showed positive correlations with total antioxidant status and total sulfhydryl groups. Principal component analysis identified five key factors: proinflammatory, pro-oxidant, aging, hyperglycemic, and antioxidant. The pro-oxidant factor emerged as the sole independent predictor of global DNA hypomethylation in T2DM (OR = 2.294; p = 0.027). Our results indicate that global DNA hypomethylation could be a biomarker of T2DM progression, reflecting the complex interactions between oxidative stress, inflammation, and epigenetic modifications in T2DM. Full article

Background: Charcot-Marie-Tooth (CMT) disease is a hereditary motor and sensory neuropathy that affects foot morphology and gait patterns, potentially leading to abnormal plantar pressure distribution. This systematic review synthesizes the existing literature examining plantar pressure characteristics in CMT patients. Methods: A comprehensive search was conducted across PubMed, Scopus, and Web of Science databases. Risk of bias was assessed using the Newcastle–Ottawa Scale. Results: Six studies comprising 146 patients were included. Four studies employed dynamic baropodometry, and two used in-shoe pressure sensors to evaluate the main plantar pressure parameters. The findings were consistent across different populations and devices, with a characteristic plantar-pressure profile of marked midfoot off-loading with peripheral overload at the forefoot and rearfoot, often accompanied by a lateralized center-of-pressure path and a prolonged pressure–time exposure. These alterations reflect both structural deformities and impaired neuromuscular control. Interventional studies demonstrated a load redistribution of pressure after corrective surgery, though residual lateral overload often persists. Conclusions: Plantar pressure mapping seems to be a valuable tool to identify high-pressure zones of the foot in order to personalize orthotic treatment planning, to objectively monitor disease progression, and to evaluate therapeutic efficacy. Further longitudinal studies with standardized protocols are needed to confirm these results. Full article

Peripheral arterial disease (PAD) is a macrovascular diabetic complication, characterized by atherosclerotic plaque formation due to hyperglycemia and dyslipidemia. The molecular mechanisms involved in PAD-T2DM pathogenesis will help in understanding and early prognosis; therefore, we aim to evaluate FABP4 levels and Nrf2 single-nucleotide polymorphisms (SNPs) among PAD-T2DM patients. In a case-control study, 123 samples (healthy control HC, T2DM, and PAD-T2DM; n = 41 each) were collected from the diabetic foot clinic at Mayo Hospital, Lahore. Baseline and biochemical data were collected. PAD diagnosis was established by measuring the ankle-brachial index with color Doppler ultrasound. Serum FABP4 levels were measured using an ELISA. Nrf2 SNP rs35652124 analysis was performed by restriction fragment length polymorphism. PAD-T2DM prevalence was higher among male subjects (61.1%). Fasting plasma glucose levels (p = 0.02), total cholesterol (p < 0.0001), and LDL-cholesterol (p = 0.01) were significantly higher in PAD-T2DM as compared to T2DM. SNP association analysis showed that homozygous genotype TT (OR: 3.85, 95% (CI): 1.22–12.11, p = 0.02) and T-allele (OR: 1.31, 95% (CI): 1.31–4.67, p = 0.005) were significantly associated with PAD-T2DM. FABP4 levels were higher in the PAD-T2DM group as compared to T2DM (p < 0.0001) and were significantly associated with Nrf2 SNP genotype TT (p < 0.001) and CT (p = 0.01) in PAD-T2DM. Our results showed, for the first time, that the Nrf2 SNP is significantly associated with PAD-T2DM and FABP4 levels compared to T2DM. Full article

Echovirus 30 (E-30), a member of the Enterovirus B species, is frequently linked to neurological illnesses such as aseptic meningitis, encephalitis, and hand, foot, and mouth disease. In this study, we present the complete-genome analysis of an Echovirus 30 strain isolated from cerebrospinal fluid (CSF) and stool samples of a pediatric encephalitis case in Kerala, India, during 2023. A comparative genomic investigation was carried out using a dataset of 111 human E-30 isolates, encompassing 116,991 mutation records. This analysis revealed six distinct non-synonymous amino acid substitutions uniquely present in the isolate PQ472410.1, which may be associated with pathogenicity and/or neurotropic behavior. To the best of our knowledge, this represents the first complete-genome sequence report of E-30 from an encephalitis case in India. These findings contribute valuable information to the understanding of E-30’s molecular epidemiology and evolution and offer vital data for enhancing surveillance and response strategies against enteroviral infections. Full article

Background: Hand, foot, and mouth disease (HFMD) typically exhibits spatiotemporal clustering. This study aimed to analyze the spatiotemporal heterogeneity of HFMD in Fujian Province, China, and to identify the associations of air pollutants and socioeconomic factors with the incidence. Methods: Daily reported HFMD case data, daily air pollutant data, and socioeconomic data in Fujian Province from 2014 to 2023 were collected for analysis. A descriptive analysis was used to describe the epidemiological trends of HFMD. Spatial autocorrelation analysis was applied to explore the spatiotemporal clustering characteristics. The associations between risk factors and HFMD incidence were evaluated using the generalized additive model (GAM). Results: HFMD incidence in Fujian has decreased since 2019, and the peak in each year occurred between May and June. Distinct high–high and low–low clustering areas were identified. The cumulative exposure–response curves for SO₂, NO₂, and CO showed a monotonically increasing trend, with relative risks (RRs) < 1 at concentrations lower than the median levels (SO₂ ≈ 4 μg/m³, NO₂ ≈ 16 μg/m³, CO ≈ 1 mg/m³). In contrast, the curves for O₃ and PM_2.5 showed a decreasing trend, with RR < 1 at concentrations above the median levels (O₃ ≈ 55 μg/m³, PM_2.5 ≈ 20 μg/m³). Among socioeconomic factors, only the proportion of the population under 15 years old was found to be associated with HFMD incidence. Conclusions: HFMD incidence in Fujian exhibited distinct spatiotemporal clustering. The incidence was associated with the concentrations of air pollutants. Targeted interventions should be implemented in high-risk areas to mitigate HFMD transmission, with particular attention given to the environmental and demographic factors. Full article