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In patients with heart failure, fluid alteration and low muscle strength frequently coexist because of their reduced physical activity and sedentary behavior; however, few studies have evaluated the effects of this coexistence on the prognosis of these patients. The aim of this study was to examine the independent association between fluid alteration and the low handgrip strength (HGS) index with mortality in patients with chronic heart failure. This observational study included 546 (53.3% male) stable outpatients with heart failure. The presence of an abnormal fluid distribution was determined with a bioelectrical impedance ratio (200/5 kHz) ≥0.85. Handgrip strength (HGS) was measured with a hand dynamometer, and the HGS index was calculated by dividing the HGS (kg) by the squared height (meters). A low HGS index was defined if men had <10.1 and women <7.95 kg/m2. The primary outcome was all-cause mortality. The mean age of the study population was 60.75 ± 17 y, and 30% were classified with a low HGS index, 9.5% with an abnormal fluid distribution, and 29% with both. During the 36 mo of follow-up, 16.5% of the participants reached the endpoint. In men but not in women, coexistence of a low HGS index and abnormal fluid distribution were independently associated with all-cause mortality with a hazard ratio of 2.8 (95% confidence interval, 1.25–6.4; P = 0.01). In men with heart failure, co-existence of a low HGS index and abnormal fluid distribution was independently associated with all-cause mortality. •Low strength and abnormal fluid distribution were associated with mortality in men.•Patients with heart failure should be evaluated for fluid and handgrip strength.•An impedance index can detect fluid shifts from intracellular water to extracellular water.

Exosomes, a specific subgroup of extracellular vesicles that are secreted by cells, have been recognized as important mediators of intercellular communication. They participate in a diverse range of physiological and pathological processes. Given the capability of exosomes to carry molecular cargos and transfer bioactive components, exosome-based disease diagnosis and therapeutics have been extensively studied over the past few decades. Herein, we highlight the emerging applications of exosomes as biomarkers and therapeutic agents in the craniofacial and dental field. Moreover, we discuss the current challenges and future perspectives of exosomes in clinical applications.

Gel-forming mucins, the primary macromolecular components of airway mucus, facilitate airway clearance by mucociliary transport. In cystic fibrosis (CF) altered mucus properties impair mucociliary transport. Airways primarily secrete two closely related gel-forming mucins, MUC5B and MUC5AC. However, their morphologic structures and associations in airways that contain abundant submucosal glands and goblet cells are uncertain. Moreover, there is limited knowledge about mucins in airways not affected by inflammation, infection, or remodeling or in CF airways. Therefore, we examined airways freshly excised from newborn non-CF pigs and CF pigs before secondary manifestations develop. We found that porcine submucosal glands produce MUC5B, whereas goblet cells produce predominantly MUC5AC plus some MUC5B. We found that MUC5B emerged from submucosal gland ducts in the form of strands composed of multiple MUC5B filaments. In contrast, MUC5AC emerged from goblet cells as wispy threads and sometimes formed mucin sheets. In addition, MUC5AC often partially coated the MUC5B strands. Compared with non-CF, MUC5B more often filled CF submucosal gland ducts. MUC5AC sheets also accumulated in CF airways overlying MUC5B strands. These results reveal distinct morphology and interactions for MUC5B and MUC5AC and suggest that the two mucins make distinct contributions to mucociliary transport. Thus, they provide a framework for understanding abnormalities in disease.

Idiopathic scoliosis (IS) is the most common spinal deformity diagnosed in childhood or early adolescence, while the underlying pathogenesis of this serious condition remains largely unknown. Here, we report zebrafish ccdc57 mutants exhibiting scoliosis during late development, similar to that observed in human adolescent idiopathic scoliosis (AIS). Zebrafish ccdc57 mutants developed hydrocephalus due to cerebrospinal fluid (CSF) flow defects caused by uncoordinated cilia beating in ependymal cells. Mechanistically, Ccdc57 localizes to ciliary basal bodies and controls the planar polarity of ependymal cells through regulating the organization of microtubule networks and proper positioning of basal bodies. Interestingly, ependymal cell polarity defects were first observed in ccdc57 mutants at approximately 17 days postfertilization, the same time when scoliosis became apparent and prior to multiciliated ependymal cell maturation. We further showed that mutant spinal cord exhibited altered expression pattern of the Urotensin neuropeptides, in consistent with the curvature of the spine. Strikingly, human IS patients also displayed abnormal Urotensin signaling in paraspinal muscles. Altogether, our data suggest that ependymal polarity defects are one of the earliest sign of scoliosis in zebrafish and disclose the essential and conserved roles of Urotensin signaling during scoliosis progression.

Background and Purpose Precise and timely diagnosis is crucial for the optimal use of emerging disease‐modifying treatments for Alzheimer disease (AD). Electroencephalography (EEG), which is noninvasive and cost‐effective, can capture neural abnormalities linked to various dementias. This study explores the use of individual alpha frequency (IAF) derived from EEG as a diagnostic and prognostic tool in cognitively impaired patients. Methods This retrospective study included 375 patients from the tertiary Memory Clinic of IRCCS San Raffaele Hospital, Milan, Italy. Participants underwent clinical and neuropsychological assessments, brain imaging, cerebrospinal fluid biomarker analysis, and resting‐state EEG. Patients were categorized by amyloid status, the AT(N) classification system, clinical diagnosis, and mild cognitive impairment (MCI) progression to AD dementia. IAF was calculated and compared among study groups. Receiver operating characteristic (ROC) analysis was used to calculate its discriminative performance. Results IAF was higher in amyloid‐negative subjects and varied significantly across AT(N) groups. ROC analysis confirmed IAF's ability to distinguish A–T–N– from the A+T+N+ and A+T–N+ groups. IAF was lower in AD and Lewy body dementia patients compared to MCI and other dementia types, with moderate discriminatory capability. Among A+ MCI patients, IAF was significantly lower in those who converted to AD within 2 years compared to stable MCI patients and predicted time to conversion (p < 0.001, R = 0.38). Conclusions IAF is a valuable tool for dementia diagnosis and prognosis, correlating with amyloid status and neurodegeneration. It effectively predicts MCI progression to AD, supporting its use in early, targeted interventions in the context of disease‐modifying treatments.

In this study, we aimed to investigate the mechanisms underlying oligohydramnios in foetal growth restriction (FGR), focusing on the contribution of renal structural and functional abnormalities. A guinea pig model of maternal nutrient restriction (MNR) was established to induce FGR. Pregnant guinea pigs were divided into control and MNR groups. Foetuses were classified as appropriate for gestational age (AGA) or FGR based on body weight. Amniotic fluid and foetal kidneys were collected at gestational days 60–61. Amniotic fluid biomarkers were measured. Histopathology was performed to evaluate renal morphology. MNR resulted in a 25% reduction in foetal body and placental weights and a 50% reduction in amniotic fluid volume compared with AGA controls. Histological analyses revealed renal injury in FGR foetuses, characterised by podocyte foot process effacement, endothelial damage, and disruption of the tubular basement membrane. These structural abnormalities indicate impaired glomerular filtration and defective tubular reabsorption. Amniotic fluid concentrations of albumin, cystatin C, and liver-type fatty acid–binding protein were higher in FGR than in controls, reflecting glomerular leakage and tubular oxidative stress. These findings are consistent with reduced foetal urine production and development of oligohydramnios. They indicate that oligohydramnios in MNR-induced FGR is associated with compromised renal integrity.

The body fluids are an important clinical diagnostic marker, considered by the physicians for diagnosis, monitoring and treating various diseases. Bilirubin, orange-yellow coloured pigment, an end-product of heme metabolism is a biomarker for liver dysfunction primarily jaundice. Similarly, blood pressure is one amongst the main parameters raised in most of the abnormalities including liver dysfunction. Hence, screening of blood pressure and concentration of bilirubin in the blood stream helps to detect the pathological conditions. In COMSOL Multiphysics, fluid flow simulation task is taken into account to analyze the flow of blood, blood pressure, bilirubin and also their range of concentration. In the present work, liver dysfunction can be detected in early stage with the help of physiological behavior of hepatic artery by measuring the flow rate, blood pressure and bilirubin levels in the arteries with the aid of COMSOL Multiphysics simulation software. Also, the impact of obstruction due to the presence of blocks of various sizes in the arteries on the flow rate, bilirubin as well as blood pressure is explored.

Current guidelines recommend lumbar puncture (LP) in patients with syphilis who have neurologic symptoms. A total of 81 human immunodeficiency virus (HIV)-uninfected individuals and 385 HIV-infected individuals enrolled in a study of cerebrospinal fluid (CSF) abnormalities in syphilis underwent LP and a structured symptom history, including assessment of headache; stiff neck; photophobia; ocular inflammation; vision, hearing, or sensory loss; or gait incoordination. Neurosyphilis was defined as a reactive CSF-Venereal Disease Research Laboratory (VDRL) test. Association between categorical variables was assessed using χ2, Fisher exact test, or logistic regression. Association between continuous and categorical variables was assessed using Mann-Whitney U test. CSF-VDRL was reactive in 20 (24.7%) HIV-uninfected and 68 (17.7%) HIV-infected (P = .14) individuals. No symptom was more common in HIV-uninfected individuals with neurosyphilis. Among the HIV-infected, the odds of a reactive CSF-VDRL were higher in those with mild or greater severity photophobia (2.0 [95% confidence interval [CI], 1.1-3.8]; P = .03), vision loss (2.3 [1.3-4.1]; P = .003), or gait incoordination (2.4 [1.3-4.4]; P = .006); or moderate or greater severity hearing loss (3.1 [1.3-7.5]; P = .01). Diagnostic specificity of these 4 symptoms for neurosyphilis was high when limited to moderate or greater severity (91.6%-100%); however, the diagnostic sensitivity was low (1.5%-38.1%). Among HIV-infected patients with syphilis, 4 specific neurologic symptoms are more common in those with a reactive CSF-VDRL. Lack of symptoms does not guarantee that the CSF-VDRL is nonreactive, regardless of HIV status.

•Patients with cancer are affected by a loss of cell membrane integrity due to electrolyte imbalance between the intra- and extracellular fluid.•Of patients with cancer, 22.5% presented with a risk for sarcopenia.•Low phase angle is associated with the risk for sarcopenia in patients with cancer.•We highlighted the importance of adequate hydration and evaluation of fluid status via bioelectrical impedance analysis as a new recommendation to prevent sarcopenia. Individuals with cancer are affected by a loss of cell membrane integrity due to electrolyte imbalance between the intra- and extracellular fluids. Cell membrane integrity and hydration status can be assessed according to the phase angle (PhA) and the risk for sarcopenia, by using the Strength, Assistance for walking, Rise from a chair, Climb stairs, and Falls (SARC-F) questionnaire. To our knowledge, this approach has not been validated in patients with cancer. The aims of this study were to verify the prevalence of the risk for sarcopenia, and to analyze the association between PhA and the risk for sarcopenia with and without adjustment for extracellular water content. This was a cross-sectional study conducted with 124 male and female cancer patients (77.4% men). PhA and hydration status were assessed using bioelectrical impedance analysis (BIA), and the risk for sarcopenia (cutoff ≥4) was assessed using the SARC-F questionnaire. Of the 124 patients, 28 (22.5%) were at risk for sarcopenia (SARC-F ≥4). There was no association between PhA and the risk for sarcopenia in the crude model, nor in the model adjusted for age, sex, smoking, alcohol consumption, and physical activity, nor after adjusting for use of supplements, body mass index, treatment type, performance status, and type and stage of cancer. However, we found an association between lower PhA values and a higher risk for sarcopenia after adjusting for hydration abnormalities (odds ratio, 1.74; 95% confidence interval, 1.03–2.93; P < 0.035). We found that 22.5% of patients with cancer presented with a risk for sarcopenia. Additionally, an association between lower PhA values and enhanced risk for sarcopenia highlighted the importance of adequate hydration and evaluation of fluid status via BIA as a new recommendation to prevent sarcopenia.

Diagnosing urothelial cancer (UCa) via invasive cystoscopy is painful, specifically in men, and can cause infection and bleeding. Because the UCa risk is higher for male patients, urinary non-invasive UCa biomarkers are highly desired to stratify men for invasive cystoscopy. We previously identified multiple DNA methylation sites in urine samples that detect UCa with a high sensitivity and specificity in men. Here, we identified the most relevant markers by employing multiple statistical approaches and machine learning (random forest, boosted trees, LASSO) using a dataset of 251 male UCa patients and 111 controls. Three CpG sites located in ALOX5, TRPS1 and an intergenic region on chromosome 16 have been concordantly selected by all approaches, and their combination in a single decision matrix for clinical use was tested based on their respective thresholds of the individual CpGs. The combination of ALOX5 and TRPS1 yielded the best overall sensitivity (61%) at a pre-set specificity of 95%. This combination exceeded both the diagnostic performance of the most sensitive bioinformatic approach and that of the best single CpG. In summary, we showed that overlap analysis of multiple statistical approaches identifies the most reliable biomarkers for UCa in a male collective. The results may assist in stratifying men for cystoscopy.