The predictive value of estimated pulse wave velocity (ePWV) combined with BMI for newly diagnosed diabetes.

PURPOSE: Estimated pulse wave velocity (ePWV) and body mass index (BMI) are significant predictors of new-onset diabetes. This study aims to evaluate the impact and predictive value of combining ePWV and BMI on the incidence of new-onset diabetes. METHODS: A secondary analysis was conducted on a cohort study by Rich Healthcare (China), involving 211,833 eligible participants. Logistic regression analysis identified factors influencing diabetes occurrence, while ROC curve analysis assessed the predictive value of ePWV, BMI, and their combination for new-onset diabetes. RESULTS: Over a mean follow-up period of 3.12 years, 3,000 men (1.41%) and 1,174 women (0.55%) were diagnosed with diabetes. Logistic regression revealed that BMI, triglycerides, alanine aminotransferase, blood urea nitrogen, creatinine clearance rate, ePWV, and family history of diabetes are high-risk factors for new-onset diabetes. The combination of ePWV and BMI provided a higher area under the ROC curve (0.822) compared to ePWV or BMI alone. CONCLUSION: Elevated levels of ePWV and BMI are independent risk factors for new-onset diabetes. Combining these measures enhances predictive accuracy compared to using either indicator alone.

Association between estimated pulse wave velocity and all-cause death in patients with heart failure.

BACKGROUND: Arteriosclerosis has been proven to be a risk factor for the development of heart failure and readmission. ePWV is a novel non-invasive and simple indicator of arterial stiffness, and this study aims to investigate its relationship with all-cause mortality rate in patients with heart failure. METHODS: This study is a cohort study that included 1272 patients with heart failure from NHANES data from 1999 to 2018. The ePWV was divided into three groups, and the cumulative mortality rate of heart failure patients was calculated using KM survival curves. The relationship between ePWV and all-cause mortality rate in heart failure patients was represented by a smoothed curve fitting. COX regression analysis was used to assess the association between ePWV and all-cause mortality rate in heart failure patients. RESULTS: The average age of the study population was 67.8 ± 12.6 years, with 862 males and 650 females. During the 12-month follow-up period, there were 790 cases of all-cause mortality. Cox regression analysis was used to validate the relationship between ePWV and all-cause mortality rate in patients with heart failure. Patients with higher levels of ePWV tended to have a higher all-cause mortality rate. After adjustment for multiple factors, an increase in ePWV was positively associated with all-cause mortality rate (HR = 1.17, 95% confidence interval (CI): (1.12, 1.22)). Compared to the lowest tertile, the multivariable-adjusted HR and 95% CI for the highest tertile of ePWV were 1.81 (95% CI: (1.45, 2.27)). Additionally, a smoothed curve fitting was used to observe the relationship between ePWV and mortality rate, where the curve demonstrated a positive correlation between ePWV and all-cause mortality rate. Furthermore, KM survival curves indicated that all-cause mortality rate increased with the increase in ePWV. Subgroup analysis suggested a correlation between ePWV and mortality rate. CONCLUSION: Our study shows that ePWV is positively associated with all-cause mortality in patients with heart failure.

Detecting Genetic Variation of Colonizing Streptococcus agalactiae Genomes in Humans: A Precision Protocol.

Deciphering the genotypic diversity of within-individual pathogens and verifying the evolutionary model can help elucidate resistant genotypes, virulent subpopulations, and the mechanism of opportunistic pathogenicity. However, observed polymorphic mutations (PMs) are rare and difficult to be detected in the "dominant-lineage" model of bacterial infection due to the low frequency. The four pooled group B Streptococcus (GBS) samples were collected from the genital tracts of healthy pregnant women, and the pooled samples and the isogenic controls were genomically sequenced. Using the PMcalling program, we detected the PMs in samples and compared the results between two technical duplicates, GBS-M001T and GBS-M001C. Tested with simulated datasets, the PMcalling program showed high sensitivity especially in low-frequency PMs and reasonable specificity. The genomic sequence data from pooled samples of GBS colonizing carrier pregnant women were analyzed, and few high-frequency PMs and some low-frequency PMs were discovered, indicating a dominant-lineage evolution model. The PMs mainly were nonsynonymous and enriched in quorum sensing, glycolysis/gluconeogenesis, ATP-binding cassette (ABC) transporters, etc., suggesting antimicrobial or environmental selective pressure. The re-analysis of the published Burkholderia dolosa data showed a diverse-community model, and only a few low-frequency PMs were shared between different individuals. Genes of general control non-repressible 5-related N-acetyltransferases family, major facilitator superfamily (MFS) transporter, and ABC transporter were positive selection candidates. Our findings indicate an unreported nature of the dominant-lineage model of GBS colonization in healthy women, and a formerly not observed mutation pool in a colonized microbial community, possibly maintained by selection pressure.

Neuron-Derived ADAM10 Production Stimulates Peripheral Nerve Injury-Induced Neuropathic Pain by Cleavage of E-Cadherin in Satellite Glial Cells.

BACKGROUND: Increasing evidence suggests the potential involvement of metalloproteinase family proteins in the pathogenesis of neuropathic pain, although the underlying mechanisms remain elusive. METHODS: Using the spinal nerve ligation model, we investigated whether ADAM10 proteins participate in pain regulation. By implementing invitro methods, we produced a purified culture of satellite glial cells to study the underlying mechanisms of ADAM10 in regulating neuropathic pain. RESULTS: Results showed that the ADAM10 protein was expressed in calcitonin gene-related peptide (CGRP)-containing neurons of the dorsal root ganglia, and expression was upregulated following spinal nerve ligation surgery invivo. Intrathecal administration of GI254023X, an ADAM10 selective inhibitor, to the rats one to three days after spinal nerve ligation surgery attenuated the spinal nerve ligation-induced mechanical allodynia and thermal hyperalgesia. Intrathecal injection of ADAM10 recombinant protein simulated pain behavior in normal rats to a similar extent as those treated by spinal nerve ligation surgery. These results raised a question about the relative contribution of ADAM10 in pain regulation. Further results showed that ADAM10 might act by cleaving E-cadherin, which is mainly expressed in satellite glial cells. GI254023X reversed spinal nerve ligation-induced downregulation of E-cadherin and activation of cyclooxygenase 2 after spinal nerve ligation. ß-catenin, which creates a complex with E-cadherin in the membranes of satellite glial cells, was also downregulated by spinal nerve ligation surgery in satellite glial cells. Finally, knockdown expression of ß-catenin by lentiviral infection in purified satellite glial cells increased expression of inducible nitric oxide synthase and cyclooxygenase 2. CONCLUSION: Our findings indicate that neuron-derived ADAM10 production stimulates peripheral nerve injury-induced neuropathic pain by cleaving E-cadherin in satellite glial cells.

The genome of serotype VI Streptococcus agalactiae serotype VI and comparative analysis.

Streptococcus agalactiae (GBS) causes serious infections in humans and other species. A total of 25 complete GBS genomes, including the first sequenced serotype VI genome (GBS-M002), were compared in this study. The power law model suggested that the pan-genome of GBS is open, with approximately 1300 genes in the core genome of GBS, accounting for approximately 60% of the average genome content. GBS-M002 has 73 specific genes and is one of the five strains containing >60 specific genes. Based on COG (Cluster of Orthologous Groups of proteins) functional classification, 24% of the genes related to defense mechanisms are specific among the strains. A phylogenetic tree shows that GBS-M002 is closely related to certain strains of serotypes III and V from humans and to isolates of unknown serotype from dog and bovine hosts, suggesting the universal infection potential of GBS from humans to other mammal and fish hosts.

Optimized Exon-Exon Junction Library and its Application on Rodents' Brain Transcriptome Analysis

ABSTRACT Background: Alternative splicing (AS), which plays an important role in gene expression and functional regulation, has been analyzed on genome-scale by various bioinformatic approaches based on RNA-seq data. Compared with the huge number of studies on mouse, the AS researches approaching the rat, whose genome is intermedia between mouse and human, were still limited. To enrich the knowledge on AS events in rodents' brain, we perfomed a comprehensive analysis on four transcriptome libraries (mouse cerebrum, mouse cerebellum, rat cerebrum, and rat cerebellum), recruiting high-throughput sequencing technology. An optimized exon-exon junction library approach was introduced to adapt the longer RNA-seq reads and to improve mapping efficiency. Results: In total, 7,106 mouse genes and 2,734 rat genes were differentially expressed between cerebrum and cerebellum, while 7,125 mouse genes and 1,795 rat genes exhibited varieties on transcript variant level. Only half of the differentially expressed exon-exon junctions could be reflected at gene expression level. Functional cluster analysis showed that 32 pathways in mouse and 9 pathways in rat were significantly enriched, and 6 of them were in both. Interestingly, some differentially expressed transcript variants did not show difference on gene expression level, such as PLCβ1 and Kcnma1. Conclusion: Our work provided a case study of a novel exon-exon junction strategy to analyze the expression of genes and isoforms, helping us understand which transcript contributes to the overall expression and further functional change.

Speeding for fun? Exploring the speeding behavior of riders of heavy motorcycles using the theory of planned behavior and psychological flow theory.

This paper focuses on a special segment of motorcyclists in Taiwan--riders of heavy motorcycles--and investigates their speeding behavior and its affecting factors. It extends the theory of planned behavior (TPB) to explore motorcyclist speeding behavior by including the variables of psychological flow theory. The levels of sensation-seeking and riding experience are also used as grouping variables to investigate group differences from the influences of their affecting factors on speeding behavior. The results reveal that the psychological flow variables have greater predictive power in explaining speeding behavior than the TPB variables, providing useful insights into the unique nature of this group of motorcyclists, who are more prone to engage in speeding. Group differences with regard to both sensation-seeking and rider experience in speeding behavior are highlighted, and the implications of the findings are discussed.

Insufficient response to venous stripping surgery: is the penile vein recurrent or residual?

There is currently controversy on whether the insufficient response to penile venous surgery done in an attempt to restore erectile function is due to recurrent or residual veins. In order to elucidate this issue, we report a study on those patients who failed to respond to the first venous surgery and subsequently underwent or declined a second operation. From July 1996 to July 2003, a total of 83 patients, aged 25 to 83, who were dissatisfied with their first venous surgery and were later diagnosed with a persistent veno-occlusive dysfunction via our dual cavernosography, were recruited into our study. Subsequently, 45 men underwent penile venous stripping surgery for a second time and were assigned to the surgery group, whereas the remaining 38 men were subject to follow-up and routine management and were assigned to the control group. All were evaluated with the abridged 5-item version of the international index of erectile function (IIEF-5) every 6 months for 1 to 5 years and cavernosogram, if necessary. In the surgery group their preoperative IIEF-5 score was 10.1 +/- 3.7, which increased to 17.1 +/- 3.2 (P < .001) after the first surgery and further increased to 20.7 +/- 3.1 (P < .001) after a second venous stripping of the cavernosal vein that was consistently demonstrated on the cavernosogram. Overall, 41 men (91.1%) reported a positive response to further venous surgery, with more satisfactory coitus, after the residual veins were stripped thoroughly, although eventually 4, 3, and 3 men required additional oral sildenafil, penile implant, and intracavernosal injection, respectively. The follow-up period ranged from 12 months to 72 months, with an average of 37.0 +/- 11.5 months. In the control group, however, their corresponding IIEF-5 score changed from 17.4 +/- 2.9 to 16.9 +/- 3.2 (P > .05). Finally, 11, 7, and 8 men required additional oral sildenafil, penile implant, and intracavernosal injection, respectively. Although there was no statistical significance between the 2 groups in the first postoperative IIEF-5 scores, there was a significant difference in their IIEF-5 after further venous surgery. In this study, we propose that the clinical relapse of erectile dysfunction is a result of "residual" veins rather than "recurrent" ones.

Outpatient varicocelectomy performed under local anesthesia.

AIM: To report a series of varicocelectomy performed under pure local anesthesia. METHODS: From July 1988 to June 2003, a total of 575 patients, aged between 15 and 73 years, underwent high ligation of the internal spermatic vein for treatment of a varicocele testis under a regional block in which a precise injection of 0.8 % lidocaine solution was delivered to involved tissues after exact anatomical references were made. A 100-mm visual analog scale (VAS) was used to assess whether the pain level was acceptable. RESULTS: The surgeries were bilateral in 52 cases, and unilateral in 523 cases. All were successfully performed on an outpatient basis except in the case of two patients, who were hospitalized because their surgeries required general anesthesia. Overall, 98.6 % (567/575) of men could go back to work by the end of the first post-operative week and only 8 (1.4 %) men reported feeling physical discomfort on the eighth day. The VAS scores varied from 11 mm to 41 mm with an average of (18.5+/-11.3) mm that was regarded as tolerable. CONCLUSION: This study has shown varicocelectomy under local anesthesia to be possible, simple, effective, reliable and reproducible, and a safe method with minimal complications. It offers the advantages of more privacy, lower morbidity, with no notable adverse effects resulting from anesthesia, and a more rapid return to regular physical activity with minor complications.

[Diisopropylamine dichloroacetate in the treatment of nonalcoholic fatty liver disease: a multicenter random double-blind controlled trial].

OBJECTIVE: To investigate the efficacy and safety of diisopropylamine dichloroacetate in the treatment of nonalcoholic fatty liver diseases (NAFLD). METHODS: A randomized, double-blind, dose-paralleled control trial was carried out with NAFLD patients. The patients were randomly assigned to 2 groups treated with either a high dosage (120 mg/d) or a low dosage (60 mg/d) of diisopropylamine dichloroacetate for 8 weeks and the efficacy and safety of the drug were examined. RESULTS: 127 cases were recruited for the trial, 63 in the high dosage group, and 64 in the low dosage group. No case dropped out in the trial but four cases were eliminated (4/127, 3.1%). The final number in this trial was 123, with 61 in the high dosage group and 62 in the low dosage group. After 8 weeks of treatment, the overall improvement of clinical symptoms in the high dosage and in the low dosage group was 87.8% and 79.6%, respectively. ALT normalization was found in 55.7% and 69.4% of the cases in the two groups, serum lipids were lowered in 67.2% and 67.7% and ultrasound grading of the liver alteration severity was lowered in 51.7% and 43.5% in the two groups. The differences found between the two groups were of no statistical significance. One case from each group was found having an adverse drug reaction of dryness of the mouth (1.6%). No severe adverse drug reactions were found. CONCLUSION: Diisopropylamine dichloroacetate could be used as a safe and effective drug in the treatment of nonalcoholic fatty liver diseases.

Combined intrapleural and intravenous chemotherapy, and pulmonary irradiation, for treatment of patients with lung cancer presenting with malignant pleural effusion. A pilot study.

OBJECTIVES: Patients with non-small-cell lung cancer (NSCLC) and malignant pleural effusion (MPE) are difficult to manage clinically and have a short life expectancy. In this pilot study, we designed a protocol of combined intrapleural (i.p.) and intravenous (i.v.) chemotherapy and pulmonary irradiation to enhance local as well as systemic control of the disease. METHODS: From April 1998 to April 2000, 27 patients with NSCLC and symptomatic MPE were eligible for the study. Patients received pre-radiation chemotherapy (cisplatin 60 mg/m(2) i.p. on day 1; gemcitabine 1,000 mg/m(2) i.v. on days 1, 8, and 15, q4week x 3) after surgical implantation of i.p. and i.v. port-A, followed by radiotherapy (7,020 cGy/39fr), and, finally, post-radiation chemotherapy (docetaxel 60 mg/m(2) q3week x 3-6 i.v.). RESULTS: Grade 1/2 nausea/vomiting and impaired renal function were more common from pre-radiation than post-radiation chemotherapy; however, grade 3/4 toxicities from pre-radiation chemotherapy were minimal. Conversely, grade 3/4 leukopenia and grade 1/2 alopecia, diarrhea, elevation of SGOT/SGPT, and sensory impairment were more common following post-radiation chemotherapy. Only two patients experienced recurrence of pleural effusion. The overall response rate was 55% with 7% complete remission, 48% partial remission, 22% stable disease, and 22% progressive disease. The median failure-free and overall survival was 8 and 16 months, respectively. The one-year survival rate was 63% (95% confidence interval, 45-80%). CONCLUSIONS: We conclude that the combination of i.p. and i.v. chemotherapy and pulmonary irradiation is feasible and should be tested in a larger clinical trial to determine whether survival can be improved for this cohort of patients.