Search Results (262,310)

Background: The use of inertial measurement units (IMUs) in the Timed Up and Go (TUG) test enables the quantitative assessment of functional performance and mobility. It allows for the determination not only of the total test completion time, but also of the durations of individual phases, as well as the derivation of spatiotemporal gait parameters and turning velocity. The aim of this review article was to compile parameters of the instrumented Timed Up and Go (iTUG) test and to identify the parameters most commonly analyzed in populations of healthy adults, older adults, and patients with neurological disorders. Methods: A systematic literature search was conducted in the PubMed, Scopus, and ScienceDirect databases. The authors included studies in which commercial IMUs were used during the TUG test and quantitative parameters were analyzed. Methodological quality was assessed using the JBI Critical Appraisal Checklist for cross-sectional studies. Results: A total of 36 studies were included in the review. Only those disease entities represented by at least four studies were included in the tabular analysis. The study presents results for a total of 1268 individuals, including 192 healthy adults, 514 older adults, 230 patients with multiple sclerosis (MS), and 332 patients with Parkinson’s disease (PD). The analysis showed that temporal parameters, particularly the total test duration and the durations of individual phases, were the most commonly reported across all populations. Conclusions: Turning-related parameters were analyzed frequently, whereas spatiotemporal parameters were assessed less often. The results indicate a lack of standardization both in the selection of iTUG parameters as well as in the measurement methods and systems used. Full article

Polycystic kidney disease (PKD), the most common inherited kidney disorder, is characterized by progressive cyst growth and eventual organ failure. Although aberrant innate immune activation is a recognized contributor to PKD progression, the underlying molecular mechanisms remain incompletely defined. Here, we showed that Pkd1 deletion increased TLR2 and MyD88 mRNA expression in renal epithelial cells, indicating enhanced innate immune priming. In vivo, administration of Pam3CSK4 (PAM), a synthetic TLR2 agonist, preferentially amplified pro-inflammatory and pro-fibrotic responses in Pkd1^RC/RC mice compared with wild-type controls, despite inducing similar signaling responses in vitro. Acute PAM treatment for one week rapidly enhanced NF-κB activation in cyst-lining epithelial cells, increased renal inflammation and cell proliferation, and was associated with activation of mTOR signaling and upregulation of c-Myc and Wnt proteins. Sustained PAM treatment further accelerated cyst expansion and renal fibrosis in PKD mice. Importantly, the endogenous TLR2 ligands decorin and biglycan were markedly elevated in human PKD kidneys, supporting the translational relevance of enhanced TLR2 signaling in disease progression. Together, these findings suggest that TLR2 signaling is an important contributor to PKD progression and a potential therapeutic target. Full article

Objective: The optimal adjuvant therapy for intermediate-risk endometrial cancer remains controversial. Although radiotherapy is commonly used in Western countries, chemotherapy is preferred in Japan; however, its real-world outcomes remain limited. This study evaluated the survival and safety outcomes of three-cycle adjuvant chemotherapy in patients with intermediate-risk endometrial cancer. Methods: We retrospectively analyzed patients who underwent primary surgery for endometrial cancer at a university hospital between 2008 and 2019. Low- and intermediate-risk patients defined by the 2013 Japan Society of Gynecologic Oncology recurrence risk classification were included. Intermediate-risk patients were classified as receiving chemotherapy (Int-Chemo+) or not (Int-Chemo−). The primary endpoint was disease-free survival (DFS); secondary endpoints included cancer-specific survival (CSS), adverse events, and treatment completion. Results: Among 232 patients, 161 were low-risk and 71 intermediate-risk; 49 intermediate-risk patients received platinum-based combination chemotherapy. The 5-year DFS rates were 92.8% (95% CI, 88.6–96.9) in the low-risk group, 89.4% (95% CI, 80.7–98.2) in the Int-Chemo+ group, and 73.5% (95% CI, 53.5–93.6) in the Int-Chemo− group (log-rank p = 0.005). DFS differed between the Int-Chemo+ and Int-Chemo− groups (HR 0.232, 95% CI 0.062–0.867), whereas the DFS outcomes of the Int-Chemo+ group were numerically similar to those of the low-risk group. CSS did not differ significantly among groups (p = 0.052). Treatment completion was 93.8%, and grade ≥ 3 adverse events were mainly hematologic, without severe late toxicities. Conclusions: Three cycles of adjuvant platinum-based combination chemotherapy for intermediate-risk patients may be associated with improved DFS, while maintaining a high treatment completion rate and manageable toxicity. Full article

Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic chemicals notable for their high persistence and extensive applications. With the advancement of detection technologies in recent years, PFAS have been frequently identified in environmental media and human biological samples, raising significant global concerns about their potential health risks. PFAS exhibit distinctive toxicokinetic behaviors, including efficient absorption, strong protein binding, limited metabolism, and slow excretion, which lead to prolonged biological half-lives and considerable bioaccumulation in humans. These properties contribute to a range of adverse health outcomes, such as endocrine disruption, immune suppression, liver damage, reproductive toxicity, carcinogenic potential, and cardiovascular disease. This review synthesizes evidence on PFAS-associated health risks from a multisystem, multitarget perspective, elucidating the key molecular pathways involved, thereby providing a scientific basis for understanding their complex toxicological effects and for developing targeted prevention and control strategies. Future research should prioritize characterizing the toxicological profiles of individual PFAS compounds, evaluating the health impacts of combined (mixture) exposures, and assessing risks associated with chronic, low-dose exposure to support the development of public health strategies and regulatory decisions. Full article

Leucine-rich repeat extensins (LRXs) are essential regulators of plant development, cell wall integrity, and stress responses. However, genome-wide LRX studies in cotton are limited. Analysis of four Gossypium species identified 29, 28, 16, and 16 LRX genes in G. hirsutum, G. barbadense, G. arboreum, and G. raimondii, respectively. Phylogenetic analysis resolved these 89 genes into four subfamilies (I–IV). Structural annotation revealed that cotton LRX family members exhibit conserved domain architectures. This finding was corroborated by motif analysis, which revealed notable conservation in the motif compositions of most cotton LRX proteins, suggesting functional conservation across evolutionary lineages. Distinct spatiotemporal expression patterns were uncovered between G. hirsutum and G. barbadense. Prolonged exposure to extreme temperatures induced widespread down-regulation of most GhLRX genes, whereas genes in subgroup IV were significantly up-regulated under salt and drought stress conditions, respectively. Notably, GhLRX7 showed a more proactive responding profile to Verticillium wilt (VW) infection, which was therefore selected for functional validation employing virus-induced gene silencing in the cotton cultivars MBI9626 and CCRI36. Phenotypic analysis of silenced plants revealed exacerbated disease symptoms compared to wild-type controls, providing direct evidence implicating GhLRX7 as a key contributor to defense against VW. Full article

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Its main contributors are obesity, insulin resistance, diabetes and metabolic syndrome. Liver pathogenesis exacerbates when oxidative stress, inflammation, lipid accumulation, and attenuated autophagy signals coexist together with the main determinants of the liver disease. These findings may indicate that the suppression of the disease requires multi-targeting compounds to alleviate more than one factor, resulting in improved histopathological outcomes. This review studies natural compounds, given as supplements, with antioxidant and anti-inflammatory properties. The compounds included are vitamins, carotenoids, low-molecular-weight thiol-containing compounds, fatty acids and others that have been investigated for their pleiotropic activity alone or in combination. They act at different pathways and signals, and at gene expression control, modulating oxidative stress and inflammation, such as collagen, TNF-α, NF-κB, Nrf2 and PPARs genes. Their mechanism of action and characteristics may be encouraging treatment options as multi-targeting compounds for NAFLD and other diseases whose pathophysiology is closely related to metabolic syndrome. However, extensive study on their safety, toxicity, mechanisms of action and dosage regimen is needed before their final establishment as potential treatment options. Full article

Ginseng Alternaria leaf and stem blight, caused by Alternaria panax, imposes substantial yield and economic losses to the ginseng cultivation industry. Current diagnostic methods for ginseng diseases primarily rely on pathogen isolation from infected tissues, a procedure that is laborious, time-consuming, and inherently low in sensitivity. This study has therefore developed a rapid, specific and sensitive SYBR Green-based quantitative real-time PCR (qPCR) assay for detecting A. panax in plants, seeds, and soil. The developed qPCR assay exhibited high sensitivity and repeatability, with a detection limit of 0.074 fg/μL of target amplicon DNA (0.619 ng/μL of genomic DNA) and a coefficient of variation below 2%. In artificially inoculated tissues (leaves, stems and seeds), Ct values decreased progressively with increasing incubation time, reflecting pathogen proliferation. Analysis of field-collected leaves and stems showed a strong overall correlation between Ct values and visual disease grades. Surveying of ginseng-growing areas revealed that A. panax was detected in asymptomatic leaves and stems at rates of 12.12% and 14.29%, respectively, and in 14.46% of soil samples and 23.73% of seed samples. This qPCR assay presented here provides a robust tool for forecasting early disease, tracking the primary inoculum of the pathogen and its transmission chains, and screening of both ginseng seed lots and candidate soils for ginseng Alternaria leaf and stem blight prior to planting. Full article

Chronic kidney disease (CKD) is a progressive disorder characterized by declining renal function and increased cardiovascular risk. Experimental models are essential for investigating these mechanisms, and the 5/6 nephrectomy (5/6 Nx) model is widely used to reproduce cardiorenal alterations observed in CKD. This review aims to critically evaluate how effectively the 5/6 Nx model reproduces vasoactive and redox mechanisms relevant for pharmacological testing. A narrative synthesis of experimental studies using the 5/6 Nx model in rodents was performed, focusing on vascular, inflammatory, and oxidative pathways. The 5/6 Nx model reproduces major CKD features, including hypertension, proteinuria, glomerulosclerosis, and cardiovascular remodeling. Early activation of the renin–angiotensin–aldosterone system, endothelin signaling, and sympathetic pathways contributes to vascular dysfunction. Sustained oxidative stress reduces nitric oxide bioavailability and promotes endothelial dysfunction. Dysregulation of natriuretic peptides and increased 20-HETE signaling further contribute to vascular imbalance and remodeling. These alterations occur in a well-defined temporal progression, supporting the use of this model for mechanistic and pharmacological studies. The 5/6 Nx model remains a robust and translationally informative platform for investigating CKD progression, provided that pathway-specific reproducibility and experimental variables are carefully considered. Full article

Leeches (Hirudinea) are ecologically important annelids that interact with a wide range of aquatic vertebrates, yet their diversity, distribution, and epidemiological relevance remain poorly documented in North Africa. Here, we provide a comprehensive synthesis of freshwater and marine leech species reported from the Maghreb (Algeria, Tunisia, and Morocco), based on an extensive review of the available literature. In total, 21 species belonging to 13 genera and four families (Glossiphoniidae, Erpobdellidae, Hirudinidae, and Piscicolidae) are documented, with updated information on their ecology, host associations, and geographic distribution. In addition to this regional checklist, we report the first confirmed case of Batracobdella algira heavy parasitism on the Berber toad (Sclerophrys mauritanica) in Algeria. A single adult toad was found heavily infested by multiple leeches (n = 17), some of which bore spermatophores attached near the reproductive opercula, suggesting possible in situ mating behavior on the host. The high infestation observed in this single specimen may constitute an outlier, requiring further sampling to assess the effect of leeches on the anuran population in the region. By integrating faunistic data with a novel field observation, this study highlights the overlooked leech biodiversity in the Maghreb and suggests their possible ecological and epidemiological significance. Our findings emphasize the need for further investigations into leech–host interactions, pathogen carriage, and their implications for amphibian conservation and One Health in North Africa. Full article

Upper tract urothelial carcinoma (UTUC) accounts for approximately 5–10% of urothelial malignancies and represents a clinically challenging disease due to its frequent presentation at advanced stages and its association with significant morbidity. Radical nephroureterectomy (RNU) with bladder cuff excision remains the standard treatment for high-risk disease; however, this approach inevitably results in loss of renal function and may significantly affect eligibility for cisplatin-based chemotherapy. In patients with imperative indications for renal preservation—including a solitary kidney, bilateral disease, or advanced chronic kidney disease—Kidney-Sparing Surgery (KSS) represents an essential therapeutic strategy. Technological advances in flexible ureteroscopy, improved visualization systems, and laser energy sources have significantly expanded the feasibility of conservative management. Ureteroscopic tumor ablation has become the cornerstone of KSS, allowing local disease control while preserving renal function. Although recurrence rates remain relatively high, repeated endoscopic treatment combined with strict surveillance protocols can achieve acceptable oncological outcomes in carefully selected patients. This narrative review summarizes the current evidence regarding conservative management of UTUC in imperative clinical situations, with particular emphasis on patient selection, endoscopic treatment modalities, laser technologies, economic implications, patient counselling, and follow-up strategies. Full article

Background: Sulfatase 2 (SULF2) is an extracellular enzyme involved in the modulation of multiple oncogenic signaling pathways and has been implicated in tumor progression across several malignancies. However, its prognostic significance in surgically resected non-small cell lung cancer (NSCLC) remains incompletely defined. Methods: SULF2 expression was evaluated by immunohistochemistry in tumor specimens from patients with stage I–III NSCLC who underwent curative-intent surgical resection between 2009 and 2016. Expression levels were quantified using an H-score-based system and categorized as low or high. Associations between SULF2 expression, clinicopathological characteristics, and survival outcomes, including overall survival (OS) and disease-free survival (DFS), were analyzed using Kaplan–Meier estimates and Cox proportional hazards models. Eighty-three patients were included, of whom 65 (78.3%) were male; 42.2% had stage I disease, 32.5% stage II, and 25.3% stage III. Results: SULF2 expression was detected in 94.0% of tumors, with 43 patients (51.8%) classified as high and 40 (48.2%) as low expression based on H-score. Overall survival and DFS did not differ significantly between SULF2-low and SULF2-high groups (log-rank p = 0.213 and p = 0.660, respectively). Median OS was 113.2 months (95% CI: 84.0–142.4) in the SULF2-low group and 54.9 months (95% CI: 39.4–186.9) in the SULF2-high group, while median DFS was 88.3 months (95% CI: 46.5–130.2) and 53.3 months, respectively, with numerically shorter survival in the SULF2-high group. Conclusions: Subgroup analyses stratified by pathological stage and histological subtype revealed no significant associations between SULF2 expression and survival outcomes. In multivariate analysis, SULF2 expression was not independently associated with either OS or DFS. SULF2 expression was highly prevalent in surgically resected NSCLC; although higher expression showed numerically poorer survival, this difference did not reach statistical significance. Full article

Epidemiological and clinical research on neurodegenerative diseases has shown that metabolic dysregulations increase the risk of developing Alzheimer’s Disease (AD). Many metabolic changes can be grouped into metabolic syndrome (MetS), which is defined as the presence of three or more risk factors, including insulin resistance, hyperglycemia, hypertension, central obesity, and dyslipidemia. These changes cause systemic effects that are crucial in triggering neuroinflammation and neurodegeneration, key factors in AD development. All these factors impair energy metabolism in peripheral tissues and the brain by decreasing glucose utilization, leading to alterations in O-GlcNAcylation, glycosylation, mitochondrial function, oxidative stress, chronic inflammation, synaptic dysfunction, autophagy impairment, and blood–brain barrier (BBB) dysfunction. However, these factors are modified and largely influenced by lifestyle choices. A newer perspective emphasizes that regular exercise is vital for maintaining brain metabolism as we age. Current evidence suggests that engaging in physical activity for individuals with metabolic syndrome reduces their risk of Alzheimer’s disease, enhances prognosis, and improves cognitive abilities. This review explores how metabolic syndrome relates to Alzheimer’s and highlights possible strategies for prevention and treatment. Full article

Background: The end of the COVID-19 public health emergency of international concern (PHEIC) in May 2023 marked a transition from disruption to recovery and rebuilding of health systems. The WHO African Region entered this period with declining routine immunization coverage, widening inequities, and fragile surveillance systems. We conducted a critical narrative synthesis of post-PHEIC recovery and the transformation of immunization systems in the region from 2023 to 2025. Methods: We thematically analyzed publicly available data from the WHO and other sources using a systems-oriented framework covering immunization coverage, equity, vaccine introductions, disease control, governance, financing, and data systems. Results: Regional coverage for most antigens was restored to 2019 pre-pandemic levels by 2024, e.g., three doses of diphtheria-tetanus-pertussis-containing vaccines at 76%. However, progress remains insufficient to meet the Immunization Agenda 2030 (IA2030) target of 90% coverage. In addition, there were 6.7 million zero-dose children in the 2024 birth cohort (6.3% higher than the 6.3 million in 2019), concentrated in a few countries. The IA2030 target is a 50% reduction in the number of zero-dose children by 2030, compared to 2019. Recovery initiatives have restored services, while accelerated introductions (e.g., malaria vaccines introduced in 20 new countries in 2024–2025) signal renewed system momentum. Yet, progress has plateaued at pre-pandemic levels, reflecting structural constraints rather than sustained transformation. Concurrently, recurrent outbreaks of measles, yellow fever, and other vaccine-preventable diseases highlight persistent immunity gaps and surveillance limitations. Structural constraints (including financing fragility, subnational inequities, and system fragmentation) continue to limit sustained progress. Conclusion: This study offers important insights that can inform immunization policymaking in the WHO African Region and beyond. Current post-PHEIC trends reflect recovery without transformation. Achieving IA2030 targets will require a shift from broad coverage expansion to precision delivery approaches that prioritize zero-dose and underserved populations. Immunization must be positioned as a central pillar of primary health care and health security systems. Full article

Background: p-Cresyl sulfate (PCS) has been linked to vascular dysfunction through endothelial injury and vascular remodeling. Peripheral artery disease (PAD), identified by a low ankle–brachial index (ABI), is associated with increased mortality in kidney transplant (KT) recipients. This study investigated the association between serum PCS levels and PAD (as defined by ABI) in KT recipients. Methods: This cross-sectional, single-center study included 90 KT recipients. Serum total PCS levels were quantified using liquid chromatography–mass spectrometry. ABI was measured using an automated oscillometric device, and PAD was defined as ABI < 0.9. Results: Among the 90 KT recipients, 20 (22.2%) met the ABI for PAD. Patients with ABI-defined PAD had a significantly higher prevalence of diabetes mellitus (p = 0.036) and serum PCS levels (p = 0.001). Multivariate logistic regression analysis adjusting for potential confounders revealed that serum PCS levels remained independently associated with PAD (odds ratio 1.254, 95% confidence interval 1.108–1.419; p < 0.001). PCS levels were inversely correlated with both left (r = −0.339, p = 0.001) and right (r = −0.357, p < 0.001) ABIs. The association remained consistent in penalized regression models. Conclusions: Higher serum PCS levels were independently associated with ABI-defined PAD in KT recipients. The findings indicate that residual uremic toxin burden may contribute to peripheral vascular disease despite the restoration of renal function following transplantation. Full article

Although numerous studies have focused on the potential application of heterotrophic nitrification–aerobic denitrification (HNAD) bacteria in wastewater treatment, research exploring their potential in aquaculture biofloc systems remains limited. In this study, a promising HNAD strain, identified as Stutzerimonas stutzeri MJ20, was isolated from mature biofloc. This strain efficiently utilized low-cost carbon sources (e.g., glucose) and small-molecule carbon sources (e.g., sodium acetate and sodium succinate). Under conditions with glucose as the carbon source, a carbon-to-nitrogen (C/N) ratio of 15, pH 6–9, temperature 25–35 °C, salinity 0–35‰, and shaker speed of 0–150 rpm, it achieved removal rates of 95–100% for NH₄⁺-N, NO₂⁻-N, and NO₃⁻-N at initial concentrations of 100 mg/L each. Even at higher concentrations (up to 200 mg/L NH₄⁺-N and 500 mg/L for both NO₂⁻-N and NO₃⁻-N), removal rates exceeded 99%. Under mixed nitrogen sources, strain MJ20 demonstrated efficient nitrogen removal, preferentially utilizing NH₄⁺-N, with only minimal and transient accumulation of nitrite and nitrate. Genomic analysis revealed that MJ20 carries key denitrification genes, including napA, nirS, norB and nosZ, and possesses complete pathways for nitrate reduction to nitrogen gas and ammonia assimilation, although typical autotrophic nitrification genes were not detected. Combined genomic data and autotrophic culture experiments indicated that, in addition to utilizing various organic carbon sources, the strain also exhibited certain autotrophic growth capabilities. Furthermore, MJ20 showed strong flocculation ability (flocculation rate > 96% within 16 h), sensitivity to multiple common antibiotics, and no toxicity to zebrafish, demonstrating favorable biosafety. In simulated seawater aquaculture wastewater with a C/N ratio of 5, it achieved a total nitrogen removal rate exceeding 94% within 72 h. These results indicate that strain MJ20 possesses comprehensive advantages, including efficient nitrogen removal, broad carbon source adaptability, strong environmental resilience, minimal accumulation of intermediate nitrogen products, excellent flocculation ability, and high biosafety. These traits highlight its potential for application in biofloc systems and in treating aquaculture tail water with a low C/N ratio. This study provides theoretical insights and practical guidance for screening HNAD bacteria suitable for biofloc systems. Full article