Changes in cognitive function after a 12-week POWER rehabilitation in older adults with schizophrenia and frailty.

BACKGROUND: The effectiveness of isolated resistance training (RT) on cognitive function among older adults with schizophrenia is insufficiently investigated. This study investigated the effectiveness of 12-weeks POWER rehabilitation, a novel RT regimen, on cognitive function among older patients with schizophrenia and frailty. METHODS: Thirty-two older adults with schizophrenia and frailty were enrolled and randomized to receive either a 12-week, twice weekly POWER rehabilitation, or without add-on training. Cognitive functioning was assessed using mini-mental state examination (MMSE), digit symbol substitution test, color trail task (CTT), and digit span task (DST). Physical performance was assessed by walking speed and hand grip strength. The generalized estimating equations was used to compare pre- and post-training outcome measure between groups. RESULTS: Between-group analysis revealed significant improvement in CTT1 and hand grip strength in the intervention group compared to the controls. Subgroup analyses showed CTT1 performance significantly improved after 12 weeks of POWER rehabilitation in the intervention group (time, p < .001), independent of age, educational level, global cognition, depressive symptoms, and psychotropic medication use. Increased hand grip strength was significantly associated with improved performance in MMSE, CTT1, and DST forward at study endpoint. CONCLUSION: A 12-week POWER rehabilitation for older patients with schizophrenia and frailty is safe and feasible, and may benefit physical and some domains of cognitive functioning.

Double synergic chitosan-coated poly (lactic-co-glycolic) acid nanospheres loaded with nucleic acids as an intranasally administered vaccine delivery system to control the infection of foot-and-mouth disease virus.

BACKGROUND & AIMS: The spread of foot-and-mouth disease virus (FMDV) through aerosol droplets among cloven-hoofed ungulates in close contact is a major obstacle for successful animal husbandry. Therefore, the development of suitable mucosal vaccines, especially nasal vaccines, to block the virus at the initial site of infection is crucial. PATIENTS AND METHODS: Here, we constructed eukaryotic expression plasmids containing the T and B-cell epitopes (pTB) of FMDV in tandem with the molecular mucosal adjuvant Fms-like tyrosine kinase receptor 3 ligand (Flt3 ligand, FL) (pTB-FL). Then, the constructed plasmid was electrostatically attached to mannose-modified chitosan-coated poly(lactic-co-glycolic) acid (PLGA) nanospheres (MCS-PLGA-NPs) to obtain an active nasal vaccine targeting the mannose-receptor on the surface of antigen-presenting cells (APCs). RESULTS: The MCS-PLGA-NPs loaded with pTB-FL not only induced a local mucosal immune response, but also induced a systemic immune response in mice. More importantly, the nasal vaccine afforded an 80% protection rate against a highly virulent FMDV strain (AF72) when it was subcutaneously injected into the soles of the feet of guinea pigs. CONCLUSIONS: The nasal vaccine prepared in this study can effectively induce a cross-protective immune response against the challenge with FMDV of same serotype in animals and is promising as a potential FMDV vaccine.

Dual-task training in older adults with cognitive impairment: A meta-analysis and trial sequential analysis of randomized controlled trials.

OBJECTIVE: To determine the effects of simultaneous dual-task training on cognitive function, physical function, and depression in older adults with mild cognitive impairment or dementia. METHODS: Comprehensive database searches were conducted in PubMed, Embase, the Cochrane Library, CINAHL, Ovid-Medline, Web of Science, and Scopus up to December 2022. Randomized controlled trials were included to assess the efficacy of simultaneous dual-task training for older adults with mild cognitive impairment or dementia. The analysis utilized Comprehensive Meta-Analysis version 3.0, presenting Hedges' g and the corresponding 95 % confidence interval (CI) for the pooled effect size and, applying a random-effects model. The I2 and Cochran's Q tests were employed to evaluate heterogeneity. The Cochrane Risk of Bias 2.0 tool was employed to assess study quality. The Copenhagen Trial Unit (version 0.9.5.10 Beta) was employed for trial sequential analysis, providing a rigorous methodology for evaluating cumulative evidence from multiple studies. RESULTS: Of the 1676 studies identified, 20 studies involving 1477 older adults with cognitive impairment were included. Dual-task training significantly enhanced global cognition (0.477, 95 % CI: 0.282 to 0.671), executive function (-0.310, 95 % CI: -0.586 to -0.035), working memory (0.714, 95 % CI: 0.072 to 1.355), gait (0.418, 95 % CI: 0.252 to 0.583), physical activity (0.586, 95 % CI: 0.012 to 1.16), and depression (-0.703, 95 % CI: -1.253 to -0.153). Trial sequential analyses revealed the robustness of this meta-analysis, which was based on a sufficient sample size from the included studies. Moreover, dual-task training demonstrated beneficial effects on global cognition, executive function, working memory, and gait. CONCLUSIONS: Dual-task training improved cognition, physical function, and depression among older adults with cognitive impairment. Accordingly, dual-task training should be considered a clinical nonpharmacological intervention for older adults with mild cognitive impairment or dementia. Nevertheless, the trial sequential analysis results were consistent with those of the pairwise meta-analysis but only global cognition reached significance by crossing the trial sequential analysis boundary. Future studies with higher-quality designs and larger sample sizes are required to obtain more conclusive results regarding other outcomes. REGISTRATION: PROSPERO CRD42023418598.

A body shape index (ABSI) but not body mass index (BMI) is associated with prostate cancer-specific mortality: Evidence from the US NHANES database.

BACKGROUND: Prostate cancer (PCa) is a common malignancy in males and obesity may play a role in its development and progression. Associations between visceral obesity measured by a body shape index (ABSI) and PCa mortality have not been thoroughly investigated. This study assessed the associations between ABSI, body mass index (BMI), and long-term PCa-specific mortality using a nationally representative US database. METHODS: This population-based longitudinal study collected data of males aged ≥40 years diagnosed with PCa and who underwent surgery and/or radiation from the National Health and Nutrition Examination Survey database 2001-2010. All included participants were followed through the end of 2019 using the National Center for Health Statistics Linked Mortality File. Associations between PCa-specific mortality, BMI, and ABSI were determined using Cox proportional hazards regression and receiver operating characteristic (ROC) curve analysis. RESULTS: Data of 294 men (representing 1,393,857 US nationals) were analyzed. After adjusting for confounders, no significant associations were found between BMI (adjusted hazard ratio [aHR] = 1.06, 95% confidence interval [CI]: 0.97-1.16, p = 0.222), continuous ABSI (aHR = 1.29, 95% CI: 0.83-2.02, p = 0.253), or ABSI in category (Q4 vs. Q1-Q3: aHR = 1.52, 95% CI: 0.72-3.24, p = 0.265), and greater risk of PCa-specific mortality. However, among participants who had been diagnosed within 4 years, the highest ABSI quartile but not in BMI was significantly associated with greater risk for PCa-specific mortality (Q4 vs. Q1-Q3: aHR = 5.34, 95% CI: 2.26-12.62, p = 0.001). In ROC analysis for this subgroup, the area under the curve of ABSI alone for predicting PCa-specific mortality was 0.638 (95% CI: 0.448-0.828), reaching 0.729 (95% CI: 0.490-0.968 when combined with other covariates. CONCLUSIONS: In US males with PCa diagnosed within 4 years, high ABSI but not BMI is independently associated with increased PCa-specific mortality.

A simple scoring algorithm based on intrinsic capacity for functional ability in community-dwelling older adults in Taiwan.

BACKGROUND: Intrinsic capacity (IC) is a comprehensive indicator of the overall well-being of older adults, and assessing of IC can help identify early stage of disability and tailor intervention to individual needs. However, there is a lack of effective and simple IC assessment tools. This study aimed to establish predictive scoring algorithms of IC to identify older adults at high risk of impaired functional ability. METHODS: We conducted a cross-sectional study in Southern Taiwan, measuring IC using 7 subitems: cognition, locomotion, vitality, vision, hearing, psychological well-being, and medication usage were measured. Functional ability outcomes included frailty, basic activities of daily living, and instrumental activities of daily living (IADL). The capability of 7 domains of IC in predicting functional ability was assessed by multivariable logistic regression. The prediction of capability of scoring algorithms was indicated by receiver operating characteristic (AUC) curves and measures of sensitivity and specificity. RESULTS: A total of 1,152 older adults were recruited and analyzed. Locomotion emerged as a significant predictor of IADL disability and worsening frailty. The IC-based weighted scoring algorism for predicting IADL demonstrated satisfactory capability (AUC: 0.80), as did the algorithm for predicting worsening frailty (AUC: 0.90). The optimal cutoff points for predicting IADL disability and frailty worse were estimated respectively at 13 and 16, with sensitivity/specificity values of 0.74/0.75 for the IADL prediction algorithm and 0.92/0.77 for the frailty prediction algorithm. CONCLUSION: Our 7-domain IC screening tool proves to be sensitive and practical for early identification of functional disability and frailty among community-dwelling older adults in Taiwan.

Efficacy of resilience-related psychological interventions in patients with long-term diseases: A meta-analysis of randomised controlled trials.

Patients with long-term disease experience low resilience, emphasising the importance of psychological interventions to improve resilience. However, there is no comprehensive evidence on the efficacy of resilience-related psychological interventions (RRPIs) in this population. Therefore, we performed a meta-analysis to evaluate and extend knowledge from previous meta-analyses on the efficacy of RRPIs on resilience, stress, anxiety, depression and quality of life among patients with long-term disease. Cochrane Library, Embase, Ovid-MEDLINE, PubMed, Scopus, Web of Science and CINAHL electronic databases were searched until 3 February 2023. The pooled effect size of the efficacy of RRPIs was calculated using the Hedges' g (g) with random-effects model, while Cochrane Q-statistics and I2 tests assessed heterogeneity in Comprehensive Meta-Analysis 3.0 software. The Cochrane Risk of Bias 2.0 tool evaluated the quality of studies. Moderator analysis was used to explore sources of heterogeneity. Twenty randomised controlled trial studies were identified, representing a total of 1388 individuals with long-term disease. RRPIs significantly enhance resilience (g = 0.79), alleviate stress (g = -0.78), decrease anxiety (g = -1.14), mitigate depression (g = -0.96) and improve quality of life (g = 0.48). Positive psychology, mindfulness, cognitive behavioural therapy, acceptance and commitment-based intervention exhibited medium effects in strengthening resilience. Short-term effects of RRPIs on enhancing resilience were observed at 3-month follow-up period (g = 0.50). The incorporation of RRPIs into the management of patients with long-term disease shows a positive impact on their resilience, stress, anxiety, depression and quality of life. The results offer an evidence-based foundation for nurses in promoting resilience among patients with long-term disease.

Honokiol Suppresses Cell Proliferation and Tumor Migration through ROS in Human Anaplastic Thyroid Cancer Cells.

BACKGROUND: Honokiol is a natural polyphenolic compound extracted from Magnolia officinali, which is commonly used material in Chinese herbal medicine, has a variety of biological functions, including anti-tumor, anti-oxidant, anti-inflammation, anti-microbial and anti-allergy. Although honokiol has numerous beneficial effects on human diseases, the underlying mechanisms of tumor metastasis are still unclear. Previously, we reported that honokiol suppresses thyroid cancer cell proliferation with cytotoxicity through cell cycle arrest, apoptosis, and dysregulation of intracellular hemostasis. Herein, we hypothesized that the antioxidant effect of honokiol might play a critical role in thyroid cancer cell proliferation and migration. METHODS: The cell viability assays, cellular reactive oxygen species (ROS) activity, cell migration, and immunoblotting were performed after cells were treated with honokiol. RESULTS: Based on this hypothesis, we first demonstrated that honokiol suppresses cell proliferation in two human anaplastic thyroid carcinoma (ATC) cell lines, KMH-2 and ASH-3, within a dosage- and time-dependent manner by cell counting kit-8 (CCK-8) assay. Next, we examined that honokiol induced ROS activation and could be suppressed by pre-treated with an antioxidant agent, N-acetyl-l-cysteine (NAC). Furthermore, the honokiol suppressed cell proliferation can be rescued by pre-treated with NAC. Finally, we demonstrated that honokiol inhibited ATC cell migration by modulating epithelial-mesenchymal transition (EMT)-related markers by Western blotting. CONCLUSION: Taken together, we provided the potential mechanism for treating ATC cells with honokiol, which significantly suppresses tumor proliferation and inhibits tumor metastasis in vitro through reactive oxygen species (ROS) induction.

A Noninferiority Trial Comparing 2 Days vs 5 Days of Terlipressin and Ceftriaxone in Terms of 5-Day Rebleeding for Patients With Acute Gastroesophageal Variceal Hemorrhage.

INTRODUCTION: This trial was to shorten the duration of both vasoconstrictors and prophylactic antibiotics to only 2 days in the therapy of acute gastroesophageal variceal hemorrhage. METHODS: After successful endoscopic hemostasis of gastroesophageal variceal hemorrhage, eligible patients were randomized to receive terlipressin infusion 1 mg per 6 hours and ceftriaxone 1 g daily for 5 days (group A) or a similar regimen for 2 days (group B). Primary end points were very early rebleeding at 5 days, and secondary end points included 48-hour hemostasis, 42-day rebleeding, and hospitalization days. RESULTS: Group A comprised 48 patients, and group B comprised 52 patients. Both groups were comparable in the severity of liver disease. Forty-eight-hour initial hemostasis was 95.8% in group A and 100% in group B ( P = 0.13). Very early rebleeding between 3 and 5 days occurred in 1 patient (2.1%) in group A and 2 patients (3.8%) in group B ( P = 0.60). The difference was 1.8% and the 95% confidence interval was -1.31% to 2.08%, which demonstrated noninferiority. Forty-two-day rebleeding occurred in 5 patients (10.4%) in group A and 4 patients (7.7%) in group B ( P = 0.63). The median hospitalization days were 8.5 ± 3.8 days in group A vs 5.6 ± 2.6 days in group B ( P < 0.001). DISCUSSION: After successful endoscopic hemostasis of acute variceal bleeding, combination of 2-day terlipressin infusion and ceftriaxone therapy was not inferior to the 5-day regimen in terms of very early rebleeding, with the advantage of shortening hospitalization stay.

Exome sequencing and genome-wide association analyses unveils the genetic predisposition in hydroxychloroquine retinopathy.

OBJECTIVES: To unveil the candidate susceptibility genes in chloroquine/hydroxychloroquine (CQ/HCQ) retinopathy using whole exome sequencing (WES) and genome-wide association study (GWAS). METHODS: Patients with a diagnosis of CQ/HCQ retinopathy based on the comprehensive demographic and ocular examination were included. The peripheral blood was extracted for WES and GWAS analyses. The Chinese Han Southern database from 1000 genomes was used as control group to compare the affected percentage. Multivariate logistic regression analysis adjusted for age, HCQ dose, duration and renal disease were used to analyze the correlation between genetic variants and visual outcome. A poor vision outcome was defined as visual acuity <6/12. An abnormal anatomical outcome was defined as disruption of ellipsoid zone in the fovea. RESULTS: Twenty-nine patients with an average age of 60.9 ± 13.4 years, treatment duration of 12.1 ± 6.2 years, daily dose of 8.5 ± 4.1 mg/kg, and the cumulative dose of 1637.5 ± 772.5 g, were genotyped. Several candidate genes associated with CQ/HCQ retinopathy were found, including RP1L1, RPGR and RPE65, with a difference of affected percentage over 50% in mutation between the case and control groups. New foci in CCDC66: rs56616026 (OR = 63.43, p = 1.63 × 10-8) and rs56616023 (OR = 104.7, p = 5.02 × 10-10) were identified significantly associated with HCQ retinopathy. Multivariate analysis revealed increased genetic variants were significantly associated with poor functional (OR = 1.600, p = 0.004) and structural outcome (OR = 1.318, p = 0.043). CONCLUSIONS: Several candidate susceptibility genes including RP1L1, RPGR, RPE65 and CCDC66 were identified to be associated with CQ/HCQ retinopathy. In addition to disease susceptibility, patients with increased genetic variants are more vulnerable to poor visual outcomes.

Prevalence of swallowing disorder in different dementia subtypes among older adults: a meta-analysis.

BACKGROUND: Ageing process and abnormal protein accumulation in dementia damage neural pathways affecting the swallowing process and leading to swallowing disorder. OBJECTIVE: To estimate the prevalence of swallowing disorder among older adults with different dementia subtypes. METHODS: We conducted a systematic search across multiple databases, including PubMed, Embase, Scopus, Web of Science and OVID Medline. The meta-analysis employed R (version 4.0.2) and utilised a generalised linear mixed model with a random-effect approach to estimate the pooled prevalence of swallowing disorder among older adults, considering various dementia subtypes. The quality of included studies was assessed using Hoy's criteria. Heterogeneity was identified through Cochrane's Q and I2 statistics. To further explore heterogeneity, moderator analysis was performed to identify the contributing variables among the included studies. RESULTS: Eighteen studies with 12,532 older adults with different dementia subtypes were enrolled in our meta-analysis. The pooled prevalence of swallowing disorder among older adults with dementia was 58%, with 46.5% for Alzheimer's dementia, 34.9% for Parkinson's dementia, 18.8% for vascular dementia, 16.3% for mixed dementia and 12.2% for Lewy body dementia. According to assessment tools, Alzheimer's dementia had the highest prevalence, with 58% in instrumental assessments and 39% in clinical assessments. Medical history, Alzheimer's dementia, moderate-to-severe Clinical Dementia Rating, delayed oral phase, delayed pharyngeal phase and poor tongue motility contributed to the heterogeneity of the included studies. CONCLUSIONS: More than half of older adults with dementia demonstrate to have swallowing disorder. Our findings offer valuable insights to healthcare professionals for the identification of swallowing disorder in ageing population with dementia.

4'-fluorocannabidiol associated with capsazepine restrains L-DOPA-induced dyskinesia in hemiparkinsonian mice: Contribution of anti-inflammatory and anti-glutamatergic mechanisms.

We tested the efficacy of 4'-fluorocannabidiol (4'-F-CBD), a semisynthetic cannabidiol derivative, and HU-910, a cannabinoid receptor 2 (CB2) agonist in resolving l-DOPA-induced dyskinesia (LID). Specifically, we were interested in studying whether these compounds could restrain striatal inflammatory responses and rescue glutamatergic disturbances characteristic of the dyskinetic state. C57BL/6 mice were rendered hemiparkinsonian by unilateral striatal lesioning with 6-OHDA. Abnormal involuntary movements were then induced by repeated i.p. injections of l-DOPA + benserazide. After LID was installed, the effects of a 3-day treatment with 4'-F-CBD or HU-910 in combination or not with the TRPV1 antagonist capsazepine (CPZ) or CB2 agonists HU-308 and JWH015 were assessed. Immunostaining was conducted to investigate the impacts of 4'-F-CBD and HU-910 (with CPZ) on inflammation and glutamatergic synapses. Our results showed that the combination of 4'-F-CBD + CPZ, but not when administered alone, decreased LID. Neither HU-910 alone nor HU-910+CPZ were effective. The CB2 agonists HU-308 and JWH015 were also ineffective in decreasing LID. Both combination treatments efficiently reduced microglial and astrocyte activation in the dorsal striatum of dyskinetic mice. However, only 4'-F-CBD + CPZ normalized the density of glutamate vesicular transporter-1 (vGluT1) puncta colocalized with the postsynaptic density marker PSD95. These findings suggest that 4'-F-CBD + CPZ normalizes dysregulated cortico-striatal glutamatergic inputs, which could be involved in their anti-dyskinetic effects. Although it is not possible to rule out the involvement of anti-inflammatory mechanisms, the decrease in striatal neuroinflammation markers by 4'-F-CBD and HU-910 without an associated reduction in LID indicates that they are insufficient per se to prevent LID manifestations.

A scenario-based web app to facilitate patient education in lung tumor patients undergoing video-assisted thoracoscopic surgery: Development and usability testing.

Background: Patient education (PE) is essential for improving patients' knowledge, anxiety, and satisfaction, and supporting their postoperative recovery. However, the advantages of video-assisted thoracoscopic surgery (VATS)-smaller incisions and faster recovery-can result in shorter hospital stays, making PE more challenging to implement effectively. Multimedia PE can potentially enhance PE, but its effectiveness for patients undergoing VATS is unclear. Objective: This study developed a scenario-based PE web app for lung tumor patients undergoing VATS (SPE-VATS) to facilitate the PE process and evaluated its usability through a clinical trial. Methods: The SPE-VATS provided the experimental group (EG: 32 participants) with interactive scenario, query guidance, diagnostic analysis, experience sharing, and active reminder, while the control group (CG: 32 participants) used pamphlets and videos. The usability of SPE-VATS in terms of postoperative anxiety reduction and patient satisfaction with the app was evaluated using self-reported questionnaires based on the state-trait anxiety inventory, technology acceptance model, system usability scale, and task load index. Results: There was no statistically significant difference in postoperative anxiety reduction between the EG and CG, possibly because 90% of the participants underwent a low-risk surgical type, and VATS is known to be advantageous in alleviating surgical anxiety. However, females and higher educated EG participants showed a non-significant but favorable reduction than their CG counterparts. Moreover, the EG was highly satisfied with the app (rated 4.2 to 4.4 out of 5.0), with no significant gender and education level difference. They particularly valued the interactive scenario, experience sharing, and diagnostic analysis features of SPE-VATS. Conclusions: The SPE-VATS demonstrated its usability and high patient satisfaction, particularly for female and higher educated patients. Low-risk patient predominance and VATS's advantages may explain non-significant postoperative anxiety reduction, warranting further studies on high-risk patients to evaluate the impact of SPE-VATS on clinical practice.

Hospital nurses perceived challenges and opportunities in the care of people with dementia: A mixed-methods systematic review.

AIM: To synthesise evidence from the literature on hospital nurses' perceived challenges and opportunities in the care of people with dementia. BACKGROUND: People with dementia often have longer lengths of hospital stay and poorer health outcomes compared to those without dementia. Nurses play a pivotal role in the care of people with dementia. However, there is a scarcity of systematic reviews that synthesise the challenges and opportunities they perceive. METHODS: A mixed-methods systematic review was conducted with a database search covering Ageline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Emcare, Embase, Medline, PsycINFO, ProQuest, Scopus and Web of Science in April 2022. In total, 27 articles that met the selection criteria were critically reviewed and included in this systematic review. Data from the selected articles were extracted and synthesised using a convergent segregated approach. RESULTS: Three main themes and eight subthemes were identified. Theme 1 described nurse-related factors consisting of the lack of capability in dementia care, experiencing multiple sources of stress and opportunities for nurses to improve dementia care. Theme 2 revealed people living with dementia-related factors including complex care needs and the need to engage family carers in care. Theme 3 explained organisation-related factors comprising the lack of organisational support for nurses and people with dementia and opportunities for quality dementia care. CONCLUSION: Hospital nurses experience multidimensional challenges in the care of people with dementia. Opportunities to overcome those challenges include organisational support for nurses to develop dementia care capability, reduce their stress and partner with the family caregivers. RELEVANCE TO CLINICAL PRACTICE: Hospitals will need to build an enabling environment for nurses to develop their capabilities in the care of people with dementia. Further research in empowering nurses and facilitating quality dementia care in acute care hospitals is needed. REPORTING METHOD: The review followed the PRISMA 2020 checklist. PATIENT OR PUBLIC CONTRIBUTION: No.

Genome-wide association study identifies high-impact susceptibility loci for HCC in North America.

BACKGROUND AND AIMS: Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP). APPROACH AND RESULTS: We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a meta-analysis. All analyses were conducted in the presence and absence of HCV. The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for nonviral HCC: 3p22.1, MOBP , rs9842969, (0.51, [0.40-0.65]); 5p15.33, TERT , rs2242652, (0.70, (0.62-0.79]); 19q13.11, TM6SF2 , rs58542926, (1.49, [1.29-1.72]); 19p13.11 MAU2 , rs58489806, (1.53, (1.33-1.75]); and 22q13.31, PNPLA3 , rs738409, (1.66, [1.51-1.83]). One region was identified for HCV-induced HCC: 6p21.31, human leukocyte antigen DQ beta 1, rs9275224, (0.79, [0.74-0.84]). A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for nonviral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC. CONCLUSIONS: Our GWAS highlights novel genetic susceptibility of nonviral HCC among European descent populations from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.

Clinical Diagnosis and Laboratory Testing of Abnormal Appearing Toenails: A Retrospective Assessment of Confirmatory Testing for Onychomycosis in the United States, 2022-2023.

Onychomycosis is an under-recognized healthcare burden. Despite the risk of misdiagnosis, confirmatory laboratory testing is under-utilized. Histopathologic examination with polymerase chain reaction (PCR) is currently the most effective diagnostic method; it offers direct detection and identification of a fungal invasion. In this retrospective cohort study, we assessed confirmatory testing results, with matching clinical diagnoses, in 96,293 nail specimens submitted during a 9-month period from 2022 to 2023. Toenail specimens were examined using fungal culture, histopathology and/or PCR. Clinical diagnoses were identified using the International Classification of Diseases 10th Revision codes. For clinically diagnosed onychomycosis patients, the overall positivity rate was 59.4%; a similar positivity rate (59.5%) was found in patients with clinically diagnosed non-fungal nail dystrophy. Performing a histopathologic examination with PCR was more likely to provide pathogen identification results than using fungal culture. Male patients had a higher rate of onychomycosis overall; however, female patients had more non-dermatophyte mold onychomycosis caused by Aspergillus. Clinically diagnosed onychomycosis patients with a co-diagnosis of tinea pedis were more likely to test positive for onychomycosis by PCR (odds ratio [OR]: 4.2; 95% confidence interval [CI]: 2.7-6.4), histopathology (OR: 2.5; 95% CI: 2.0-3.1) and fungal culture (OR: 3.2; 95% CI: 1.5-6.6). Our results support the use of confirmatory laboratory testing when there is a clinical diagnosis of onychomycosis.

Female showed favorable left ventricle hypertrophy regression during post-TAVR follow-up.

Transcatheter aortic valve replacement (TAVR) is a well-established procedure using a catheter-introduced valve prosthesis for patients with severe aortic stenosis (AS). This retrospective study investigated sex-related differences in pre- and post-TAVR clinical and hemodynamic outcomes and analyzed data of the first 100 cases at Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH) between December 2013 and December 2021. Baseline characteristics, procedural outcomes, mortality rates, and echocardiographic parameters were analyzed and compared between sexes. Among the 100 patients, male (46%) and female (54%) were of similar age (mean age, male 86.0 years vs. female 84.5 years) and of the same severity of AS (mean pressure gradient, male 47.5 mmHg vs. female 45.7 mmHg) at the time receiving the TAVR procedure. Women had smaller aortic valve areas calculated by continuity equation (0.8 ± 0.3 cm2 vs. 0.7 ± 0.2 cm2, p < 0.001). In addition, women had better left ventricle ejection fraction (59.6 ± 14.0% vs. men 54.7 ± 17.2%, p < 0.01). In the post-TAVR follow-up, regression of left ventricle mass and dimension was better in women than in men. None of the patient died within 30 days after the procedure, and women tended to have a more favorable survival than men (2-year mortality and overall mortality rate in 8.3 year, women 9.1% and 22.2% vs. men 22.2% and 34.8%; p = 0.6385 and 0.1277, respectively). In conclusion, the sex-based difference in post-TAVR regression of LV remodeling suggests a need for sex-based evaluation for patients with severe AS and their post TAVR follow-up.

Systemic immune-inflammation index for predicting postoperative atrial fibrillation following cardiac surgery: a meta-analysis.

Background: Postoperative atrial fibrillation (POAF) is a frequent complication that may increase morbidity and mortality risk following cardiac surgery. The systemic immune-inflammation index (SII) is an emerging biomarker that provides an integrated measure of inflammation by incorporating neutrophil, lymphocyte, and platelet counts. Recent studies have reported associations between elevated SII and increased POAF risk; however, significant heterogeneity exists regarding its predictive efficacy. This meta-analysis aimed to assess SII's diagnostic efficacy for predicting POAF risk. Methods: To synthesize existing evidence on the ability of perioperative SII for predicting POAF in patients undergoing cardiac surgery, a systematic review and meta-analysis was conducted. In August 2023, a comprehensive literature search was performed to identify relevant studies reporting SII cutoff values with corresponding sensitivity and specificity. The primary aim was to evaluate SII's diagnostic utility for predicting POAF, whereas secondary outcomes included the pooled incidence of POAF and the relationship between the SII and POAF. Results: Eight studies published between 2021 and 2023 with 3,245 patients were included. Six studies involved coronary artery bypass grafting (CABG) surgery; one encompassed various cardiac procedures, and another focused solely on mitral valve surgery. The pooled incidence of POAF was 23.6% [95% confidence interval (CI), 18.7%-29.2%]. Elevated SII significantly increased the odds of POAF by 3.24-fold (odds ratio, 3.24; 95% CI, 1.6-6.55; p = 0.001). SII's pooled sensitivity and specificity for predicting POAF were 0.80 (95% CI, 0.68-0.89) and 0.53 (95% CI, 0.23-0.8), respectively. The SII had moderate predictive accuracy based on a hierarchical summary receiver operating characteristic (HSROC) area under the curve of 0.78 (95% CI, 0.74-0.81). Subgroup analyses, whether focusing on CABG alone or CABG with cardiopulmonary bypass (CPB), both indicated an area under the HSROC curve of 0.78 (95% CI, 0.74-0.81). Conclusion: Elevated SII is significantly correlated with an increased POAF risk following cardiac surgery, highlighting its utility as a predictive biomarker. Considering its moderate diagnostic accuracy, further research is essential for clarifying SII's clinical effectiveness, either as an independent predictor or combined with other risk factors, for stratifying patients at high POAF risk. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier [CRD42023456128].

Oral post-treatment supplementation with a combination of glutamine, citrulline, and antioxidant vitamins additively mitigates jejunal damage, oxidative stress, and inflammation in rats with intestinal ischemia and reperfusion.

INTRODUCTION: Intestinal ischemia and reperfusion (IIR) injury is closely associated with oxidative stress. Evidence shows that oral supplementation with glutamine and citrulline alleviates IIR-induced jejunal damage. We investigated the effects of a combination of glutamine, citrulline, and antioxidant vitamins on IIR-induced jejunal damage, oxidative stress, and inflammation. METHOD: Male Wistar rats that underwent 60 min of superior mesenteric artery occlusion were orally administered glutamine plus citrulline (GC), vitamin C plus E (CE), or a combination of GC and CE 15 min before and 3, 9, and 21 h after reperfusion. Healthy rats without IIR were used as controls. RESULTS: After reperfusion for 24 h, rats with IIR showed lower levels of red blood cells, hemoglobin, serum glucose, and jejunal DNA and increased white blood cell counts compared to controls (1-way ANOVA with the least significant difference, P < 0.05). The IIR-induced decrease in serum albumin and increase in plasma interleukin-6 and jejunal thiobarbituric acid-reactive substances (TBARS) were significantly reversed by GC and/or CE. The results of the 2-way ANOVA indicated that GC was the main factor that increased jejunal villus height and muscularis DNA, and CE was the main factor that increased jejunal muscularis protein and decreased jejunal proinflammatory cytokine levels and myeloperoxidase activity. In addition, GC and CE are the main factors that decrease plasma proinflammatory cytokine levels and the jejunal apoptotic index. CONCLUSION: Oral post-treatment supplementation with glutamine and citrulline, combined with vitamins C and E, may alleviate IIR-induced oxidative stress, inflammation, and jejunal damage.

NMNAT2 supports vesicular glycolysis via NAD homeostasis to fuel fast axonal transport.

BACKGROUND: Bioenergetic maladaptations and axonopathy are often found in the early stages of neurodegeneration. Nicotinamide adenine dinucleotide (NAD), an essential cofactor for energy metabolism, is mainly synthesized by Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) in CNS neurons. NMNAT2 mRNA levels are reduced in the brains of Alzheimer's, Parkinson's, and Huntington's disease. Here we addressed whether NMNAT2 is required for axonal health of cortical glutamatergic neurons, whose long-projecting axons are often vulnerable in neurodegenerative conditions. We also tested if NMNAT2 maintains axonal health by ensuring axonal ATP levels for axonal transport, critical for axonal function. METHODS: We generated mouse and cultured neuron models to determine the impact of NMNAT2 loss from cortical glutamatergic neurons on axonal transport, energetic metabolism, and morphological integrity. In addition, we determined if exogenous NAD supplementation or inhibiting a NAD hydrolase, sterile alpha and TIR motif-containing protein 1 (SARM1), prevented axonal deficits caused by NMNAT2 loss. This study used a combination of techniques, including genetics, molecular biology, immunohistochemistry, biochemistry, fluorescent time-lapse imaging, live imaging with optical sensors, and anti-sense oligos. RESULTS: We provide in vivo evidence that NMNAT2 in glutamatergic neurons is required for axonal survival. Using in vivo and in vitro studies, we demonstrate that NMNAT2 maintains the NAD-redox potential to provide "on-board" ATP via glycolysis to vesicular cargos in distal axons. Exogenous NAD+ supplementation to NMNAT2 KO neurons restores glycolysis and resumes fast axonal transport. Finally, we demonstrate both in vitro and in vivo that reducing the activity of SARM1, an NAD degradation enzyme, can reduce axonal transport deficits and suppress axon degeneration in NMNAT2 KO neurons. CONCLUSION: NMNAT2 ensures axonal health by maintaining NAD redox potential in distal axons to ensure efficient vesicular glycolysis required for fast axonal transport.