Assessment of Multidimensional Health Care Parameters Among Adults in Japan for Developing a Virtual Human Generative Model: Protocol for a Cross-sectional Study.

BACKGROUND: Human health status can be measured on the basis of many different parameters. Statistical relationships among these different health parameters will enable several possible health care applications and an approximation of the current health status of individuals, which will allow for more personalized and preventive health care by informing the potential risks and developing personalized interventions. Furthermore, a better understanding of the modifiable risk factors related to lifestyle, diet, and physical activity will facilitate the design of optimal treatment approaches for individuals. OBJECTIVE: This study aims to provide a high-dimensional, cross-sectional data set of comprehensive health care information to construct a combined statistical model as a single joint probability distribution and enable further studies on individual relationships among the multidimensional data obtained. METHODS: In this cross-sectional observational study, data were collected from a population of 1000 adult men and women (aged ≥20 years) matching the age ratio of the typical adult Japanese population. Data include biochemical and metabolic profiles from blood, urine, saliva, and oral glucose tolerance tests; bacterial profiles from feces, facial skin, scalp skin, and saliva; messenger RNA, proteome, and metabolite analyses of facial and scalp skin surface lipids; lifestyle surveys and questionnaires; physical, motor, cognitive, and vascular function analyses; alopecia analysis; and comprehensive analyses of body odor components. Statistical analyses will be performed in 2 modes: one to train a joint probability distribution by combining a commercially available health care data set containing large amounts of relatively low-dimensional data with the cross-sectional data set described in this paper and another to individually investigate the relationships among the variables obtained in this study. RESULTS: Recruitment for this study started in October 2021 and ended in February 2022, with a total of 997 participants enrolled. The collected data will be used to build a joint probability distribution called a Virtual Human Generative Model. Both the model and the collected data are expected to provide information on the relationships between various health statuses. CONCLUSIONS: As different degrees of health status correlations are expected to differentially affect individual health status, this study will contribute to the development of empirically justified interventions based on the population. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47024.

Clinical outcomes of botulinum toxin A management for neurogenic detrusor overactivity: meta-analysis.

The aim of this work was to evaluate the efficacy and safety of botulinum toxin A (BTX-A) treatment in patients with neurogenic detrusor overactivity. PUBMED, EMBASE, and Cochrane Library were identified on 13 May 2017 to identify relevant randomized controlled trials. All data obtained were analyzed using Stata 12.0. Five randomized controlled trials were included in this study. Compared to placebo, the BTX-A groups had significantly fewer urinary incontinence (UI) episodes per day and per week (BTX-A with 300 U for frequency of UI per day at week 2, mean difference (MD): -1.13, 95% confidence interval (CI): -1.89 to -0.37; 200 U; BTX-A with 300 U for frequency of UI per week at week 6, MD: -11.42, 95% CI: -13.91 to -8.93; BTX-A with 200 U for frequency of UI per week at week 6, MD: -10.72, 95% CI: -13.40 to -8.04), increased in maximum cystometric capacity at week 6 (BTX-A with 300 U, MD: 154.88, 95% CI: 133.92-175.84; BTX-A with 200 U, MD: 141.30, 95% CI: 121.28-161.33), decreased maximum detrusor pressure at week 6 (BTX-A with 300 U, MD: -31.72, 95% CI: -37.69 to -25.75; BTX-A with 200 U, MD: -33.47, 95% CI: -39.20 to -27.73). For adverse effects, BTX-A was often associated with more complications and urinary tract infections (BTX-A with 300 U: relative risk (RR):1.42, 95% CI: 1.15-1.76; BTX-A with 200 U: RR: 1.42, 95% CI: 1.11-1.82). This meta-analysis suggests that treatment with BTX-A is effective and safe for neurogenic detrusor overactivity, and recommends using BTX-A with 300 U or with 200 U, as suitable dosage.

Elevated bilirubin levels and risk of developing chronic kidney disease: a dose-response meta-analysis and systematic review of cohort studies.

AIMS: Previous studies have indicated the link of bilirubin levels and risk of developing chronic kidney disease (CKD); however, the findings were inconsistent. METHODS: We searched for cohort studies examining bilirubin as an exposure and CKD as an outcome in the Medline, EMBASE, and Web of Science databases from inception through November 31, 2016. A generalized least-squares approach was applied to assess the dose-response relationship between them by pooling rate ratios with 95% confidence intervals. Subgroup analyses, sensitivity analysis, meta-regression, and publication bias were also conducted. RESULTS: Seven cohort studies with 1316 cases and 21,076 participants were identified for inclusion in the meta-analysis. The combined RR for the highest versus lowest bilirubin level was 0.36 (95% CI 0.19-0.68; P heterogeneity = 0.001; Power = 0.72; n = 6). In the linear dose-response analysis, each 1-µmol/L increase in bilirubin was associated with a 5% reduced risk of CKD (RR = 0.95; 95% CI 0.92-0.97; P for trend test = 0.113; P heterogeneity = 0.001; Power = 0.99; n = 7). The subgroup analyses and sensitivity analyses showed consistent results, and publication bias may exist. CONCLUSION: This meta-analysis suggests that elevated bilirubin level may be associated with decreased risk of developing CKD.

4-HPR impairs bladder cancer cell migration and invasion by interfering with the Wnt5a/JNK and Wnt5a/MMP-2 signaling pathways.

In order to identify the anti-invasive and anti-metastatic effect of the synthetic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR) on the human bladder cancer EJ cell line, and to study its impact on the expression of wingless-type mouse mammary tumor virus integration site family, member 5a (Wnt5a), the phosphorylation of c-Jun N-terminal kinase (JNK), the expression levels of matrix metalloproteinase-2 (MMP-2), and the migration and invasion of EJ cells, migration and Matrigel invasion assays, as well as western blot analyses, were used in the present study. The results of the migration and Matrigel invasion assays indicated that the inhibitor of JNK SP600125 could inhibit the effect of 4-HPR on EJ cells. The expression of Wnt5a and MMP-2, and the phosphorylation of JNK, were analyzed by western blotting. The data revealed that 4-HPR inhibited the migration and invasion of bladder cancer cells through stimulating Wnt5a activation, causing the downregulation of MMP-2 expression and enhancing the phosphorylation of JNK in these cells. However, JNK signaling did not appear to have a direct effect on the expression of MMP-2. The present study demonstrated that 4-HPR may be a potent anti-invasive and anti-metastatic agent that functions via the Wnt5a/JNK and Wnt5a/MMP-2 signaling pathways.

BDNF-ERK1/2 signaling pathway in ketamine-associated lower urinary tract symptoms.

OBJECTIVES: Long-term ketamine abuse can affect the urinary system, resulting in lower urinary tract symptoms (LUTS), but the pathogenesis of this is still unknown. Previous studies have demonstrated that ketamine can change the expression of the brain-derived neurotrophic factor (BDNF) in the serum of ketamine abuse patients. The aim of the present study is to explore the mechanism of the ketamine-mediated BDNF signaling pathway in the bladder of rats on chronic ketamine treatment. METHODS: Rats were randomly assigned to a control (normal saline) or ketamine (30 mg/kg) group, with five rats in each group. The experimental group was given ketamine via intraperitoneal injection daily, while the control group was treated with saline. After 12 weeks of treatment, bladders were excised and samples from the control and ketamine group were examined with transmission electron microscopy (TEM). Phosphoprotein and non-phosphoprotein purification, histopathology, immunohistochemistry, and western blot were carried out in all groups. RESULTS: Histological study showed hyperplastic epithelium and inflammatory cell infiltration in ketamine-treated rat bladders. TEM showed that chronic ketamine treatment results in structural damage to organelles. Immunohistochemical staining and western blot showed that the expression of BDNF was significantly lower in the ketamine group. However, the expression of phosphorylated extracellular signal-regulated kinases ½ (ERK1/2) in the ketamine group was higher, whereas the total ERK1/2 was similar to the control group. CONCLUSIONS: Long-term ketamine abuse reduces expression of BDNF, while inducing phosphorylation of ERK1/2 in the bladder wall. This may play an important role in the pathogenesis of ketamine-associated LUTS.

Fat Intake Is Not Linked to Prostate Cancer: A Systematic Review and Dose-Response Meta-Analysis.

BACKGROUND: Since the late 1960s, the average global supply of fat has increased by 20 g per capita per day. While fat intake has been considered a potential risk factor for prostate cancer (Pca), the hypothesis from previous epidemiologic studies remained equivocal. MATERIALS AND METHODS: Relevant cohort studies were identified through a literature search in PubMed, ScienceDirect and Wiley Online Library up to March 1, 2015. A systematic review and dose-response meta-analysis were used to assess the relationship between fat intake and the risk for Pca. RESULTS: We identified 14 cohort studies, which included 37,349 cases and a total of 751,030 participants. We found no evidence of a non-linear association between fat intake and the risk for Pca. Overall, the summarized relative risks for every 28.35 g increment a day was 0.99 (95%CI: 0.98, 1.01; P=0.94; n=13) for total fat intake, 1.00 (95%CI: 1.00, 1.00; P=0.72; n=9) for saturated fat, 0.99 (95%CI: 0.95, 1.03; P=0.55; n=7) for polyunsaturated fat, and 1.00 (95%CI: 0.95, 1.04; P=0.85; n=8) for monounsaturated fat. Additionally, there was no link to the risk for advanced stage Pca regarding total fat intake (RR=1.02, 95%CI: 0.96, 1.08; P=0.63; n=5), saturated fat (RR=0.96, 95%CI: 0.84, 1.11; P=0.61; n=6), polyunsaturated fat (RR=0.96, 95%CI: 0.79, 1.17; P=0.68; n=6), or monounsaturated fat (RR=0.96, 95%CI: 0.86, 1.07; P=0.42; n=6). Subgroup and sensitively analyses showed consistent results. CONCLUSION: Little evidence from published cohort studies supports the statement that total fat, saturated fat or unsaturated fat intake increases the risk for Pca or advanced stage Pca.