The relationship between klotho, testosterone, and sexual health parameters among US adult men.

BACKGROUND: Klotho is a pleotropic hormone involved in a multitude of biological processes necessary for healthy aging, and affords protection from adverse events such as cardiovascular disease, inflammation, and various cancers. Emerging evidence suggests that klotho is also an important component of biochemical pathways that regulate hormone balance, which may include those pathways governing testosterone production and men's sexual health, though data are limited and results are mixed. OBJECTIVE: Using a cohort of 767 men from the NHANES 2015-2016 survey cycle, we set out to quantify the association between serum klotho levels and serum testosterone levels, as well as clinical markers of men's sexual health (e.g., testosterone:estrogen ratio, bioavailable testosterone, and free testosterone). METHODS: Multivariable linear and logistic regression models while controlling for potential confounders were constructed to quantify the relationship between serum klotho and testosterone, as well as between serum klotho and odds of low testosterone (serum testosterone < 300 ng/dL). RESULTS: A positive association was observed between serum klotho and testosterone (ß = 0.18, p = 0.04). Serum klotho levels were also stratified into quartiles, and we observed statistically significant increases in testosterone for increasing quartile level of klotho using the first quartile as the reference group (ß = 90.51, p = 0.001, ß = 106.93, p = 0.002, ß = 95.33, p = 0.03 for quartiles 2, 3, and 4, respectively). The average testosterone values by quartiles of klotho were 306.9 ng/dL, 390 ng/dL, 409.3 ng/dL, and 436.6 ng/dL, respectively. We modeled important proxies for sexual health including bioavailable and free testosterone, the testosterone:estradiol ratio, and C-reactive protein. Men in the second quartile of klotho had a significantly lower odds of an abnormal testosterone:estradiol ratio compared to the first quartile [OR = 0.18, 95% CI = (0.03, 0.98)].We observed null associations between continuous serum klotho and odds of low testosterone [OR = 1.0, 95% CI = (1.0, 1.0)], and when stratified by quartile, we observed a significant decrease in the odds of low testosterone for individuals in the second quartile of klotho compared to the first quartile [OR = 0.21, 95% CI = (0.05, 0.91)]. In addition, C-reactive protein was inversely associated with testosterone in men (ß = - 4.65, p = 0.001), and inversely associated with quartiles of klotho (ß = - 2.28, p = 0.04, ß = - 2.22, p = 0.04, ß = - 2.28, p = 0.03, for quartiles 2, 3, and 4, respectively). CONCLUSION: Our findings support previous studies suggesting a role for klotho in testosterone levels and sexual function among men. Future studies are warranted to corroborate these findings, determine clinical significance, and elucidate potential mechanisms underlying these associations.

Investigating the prevalence of erectile dysfunction among men exposed to organophosphate insecticides.

INTRODUCTION: Erectile dysfunction (ED) poses a significant disease morbidity and contributor to male infertility, where an estimated 20-40% of men are affected annually. While several risk factors have been identified in the etiology of ED (e.g., aging, heart disease, diabetes, and obesity), the complete pathogenesis remains to be elucidated. Over the last few decades, the contribution of environmental exposures to the pathogenesis of ED has gained some attention, though population studies are limited and results are mixed. Among environmental contaminants, organophosphate (OP) insecticides represent one of the largest chemical classes, and chlorpyrifos is the most commonly used OP in the U.S. OP exposure has been implicated in driving biological processes, including inflammation, reactive oxygen species production, and endocrine and metabolism disruption, which have been demonstrated to adversely affect the hypothalamus and testes and may contribute to ED. Currently, studies evaluating the association between OPs and ED within the U.S. general population are sparse. METHODS: Data were leveraged from the National Health and Nutrition Examination Survey (NHANES), which is an annually conducted, population-based cross-sectional study. Urinary levels of 3,5,6-trichloro-2-pyridinol (TCPy), a specific metabolite of the most pervasive OP insecticide chlorpyrifos, were quantified as measures of OP exposure. ED was defined by responses to questionnaire data, where individuals who replied "sometimes able" or "never able" to achieve an erection were classified as ED. Chi-square, analysis of variance (ANOVA), and multivariable, weighted linear and logistic regression analyses were used to compare sociodemographic variables between quartiles of TCPy exposure, identify risk factors for TCPy exposure and ED, and to analyze the relationship between TCPy and ED. RESULTS: A total of 671 adult men were included in final analyses, representing 28,949,379 adults after survey weighting. Approximately 37% of our cohort had ED. Smoking, diabetes, aging, Mexican-American self-identification, and physical inactivity were associated with higher ED prevalence. Analysis of TCPy modeled as a continuous variable revealed nonsignificant associations with ED (OR = 1.02 95% CI [0.95, 1.09]). Stratification of total TCPy into quartiles revealed increased odds of ED among adults in the second and fourth quartiles, using the first quartile as the reference (OR = 2.04 95% CI [1.11, 3.72], OR = 1.51 95% CI [0.58, 3.93], OR = 2.62 95% CI [1.18, 5.79], for quartiles 2, 3, and 4, respectively). CONCLUSIONS: The results of our study suggest a potential role for chlorpyrifos and other OPs the pathogenesis of ED. Future studies are warranted to validate these findings, determine clinical significance, and to investigate potential mechanisms underlying these associations.

The association between 2,4-D and serum testosterone levels: NHANES 2013-2014.

BACKGROUND: Previous studies have investigated associations between herbicides such as 2,4-Dichlorophenoxyacetic acid (2,4-D) and dyshormonogenesis, specifically low testosterone, in human, rodent, and cell models, but results have been conflicting and inconclusive. METHODS: Using data from a cross-sectional study of 456 adult men in the 2013-2014 NHANES survey cycle, we examined the relationship between urinary concentrations of 2,4-D and serum testosterone levels. RESULTS: Multivariable regression models adjusting for potential confounders revealed a significant, negative association between urinary 2,4-D and mean serum testosterone among U.S. adult males (ß = - 11.4 ng/dL, p = 0.02). Multivariable logistic regression models using a cutoff defining abnormally low testosterone (i.e., serum testosterone < 300 ng/dL) revealed no significant associations between 2,4-D and the odds of low testosterone. CONCLUSION: These findings expand on previous literature implicating a role for 2,4-D in the etiology of low testosterone and dyshormonogenesis. Future studies are warranted to corroborate these findings, determine clinical significance, and to investigate the proposed potential biological mechanisms underlying this association.

Absolute basophil count is associated with time to recurrence in patients with high-grade T1 bladder cancer receiving bacillus Calmette-Guérin after transurethral resection of the bladder tumor.

BACKGROUND: Basophils, eosinophils and monocytes may be involved in BCG-induced immune responses and be associated with outcomes of bladder cancer patients receiving intravesical BCG. Our objective was to explore the association of baseline counts of basophils, eosinophils and monocytes with outcomes of patients with high-grade T1 bladder cancer receiving a standard course of intravesical BCG. METHODS: We retrospectively reviewed medical records of patients with primary T1 HG/G3 bladder cancer. After re-TURBT, patients were treated with a 6-week course of intravesical BCG induction followed by intravesical BCG every week for 3 weeks given at 3, 6, 12, 18, 24, 30 and 36 months from initiation of therapy The analysis of potential risk factors for recurrence, muscle invasion and cancer-specific and overall survival was performed using univariable Cox regression models. Those factors that presented, at univariate analysis, an association with the event at a liberal p < 0.1, have been selected for the development of a multivariable model. RESULTS: A total of 1045 patients with primary T1 HG/G3 were included. A total of 678 (64.9%) recurrences, 303 (29.0%) progressions and 150 (14.3%) deaths were observed during follow-up. Multivariate analysis showed that logarithmic transformation of basophils count was associated with a 30% increment in the hazard of recurrence per unit increase of logarithmic basophils count (HR 1.30; 95% confidence interval 1.09-1.54; p = 0.0026). Basophil count modeled by quartiles was also significantly associated with time to recurrence [second vs. lower quartile HR 1.42 (1.12-1.79); p = 0.003, third vs. lower quartile HR 1.26 (1.01-1.57); p = 0.041; upper vs. lower quartile HR 1.36 (1.1-1.68); p = 0.005]. The limitations of a retrospective study are applicable. CONCLUSION: Baseline basophil count may predict recurrence in BCG-treated HG/G3 T1 bladder cancer patients. External validation is warranted.

Effect of metabolic and antioxidant supplementation on sperm parameters in oligo-astheno-teratozoospermia, with and without varicocele: A double-blind placebo-controlled study.

Since sperm require high energy levels to perform their specialised function, it is vital that essential nutrients are available for spermatozoa when they develop, capacitate and acquire motility. However, they are vulnerable to a lack of energy and excess amounts of reactive oxygen species, which can impair sperm function, lead to immotility, acrosomal reaction impairment, DNA fragmentation and cell death. This monocentric, randomised, double-blind, placebo-controlled trial investigated the effect of 6 months of supplementation with l-carnitine, acetyl-l-carnitine and other micronutrients on sperm quality in 104 subjects with oligo- and/or astheno- and/or teratozoospermia with or without varicocele. In 94 patients who completed the study, sperm concentration was significantly increased in supplemented patients compared to the placebo (p = .0186). Total sperm count also increased significantly (p = .0117) in the supplemented group as compared to the placebo group. Both, progressive and total motility were higher in supplemented patients (p = .0088 and p = .0120, respectively). Although pregnancy rate was not an endpoint of the study, of the 12 pregnancies that occurred during the follow-up, 10 were reported in the supplementation group. In general, all these changes were more evident in varicocele patients. In conclusion, supplementation with metabolic and antioxidant compounds could be efficacious when included in strategies to improve fertility.

From Myo-inositol to D-chiro-inositol molecular pathways.

OBJECTIVE: Inositol is a carbocyclic sugar polyalcohol. By epimerization of its hydroxyl groups, nine possible stereoisomers can be generated, two of major physiological and clinical relevance: myo-inositol and D-chiro-inositol. Myo-inositol and D-chiro-inositol are normally stored in kidney, brain and liver and are necessary for functions, such as signal transduction, metabolic flux, insulin signaling, regulation of ion-channel permeability, stress response and embryo development. In this narrative review, we summarize the mechanisms by which myo-inositol and D-chiro-inositol can be synthesized and absorbed and their possible role in the etiopathogenesis of neural tube defects. MATERIALS AND METHODS: We performed an online search in the PubMed database using the following keywords: "inositol", "D-chiro-inositol", "myo-inositol", "neural tube defects and inositol". RESULTS: Inositol requirements are partly met by dietary intake, while the rest is synthesized endogenously. Inositol deficiency may be involved in the pathogenesis of diseases, such as metabolic syndrome, spina bifida (a neural tube defect), polycystic ovary syndrome and diabetes. Supplementation of the two inositol stereoisomers, D-chiro-inositol and myo-inositol is important to prevent these conditions. CONCLUSIONS: Inositol is fundamental for signal transduction in the brain, kidneys, reproductive organs and other tissues in response to neurotransmitters, hormones and growth factors. Various genes are involved in inositol metabolism and associated pathways. Altered inositol concentrations are observed in several diseases. Analysis of the genes involved in inositol metabolism may provide important information for the clinical management of these conditions.

Ultrathin catalyst-free InAs nanowires on silicon with distinct 1D sub-band transport properties.

Ultrathin InAs nanowires (NW) with a one-dimensional (1D) sub-band structure are promising materials for advanced quantum-electronic devices, where dimensions in the sub-30 nm diameter limit together with post-CMOS integration scenarios on Si are much desired. Here, we demonstrate two site-selective synthesis methods that achieve epitaxial, high aspect ratio InAs NWs on Si with ultrathin diameters below 20 nm. The first approach exploits direct vapor-solid growth to tune the NW diameter by interwire spacing, mask opening size and growth time. The second scheme explores a unique reverse-reaction growth by which the sidewalls of InAs NWs are thermally decomposed under controlled arsenic flux and annealing time. Interesting kinetically limited dependencies between interwire spacing and thinning dynamics are found, yielding diameters as low as 12 nm for sparse NW arrays. We clearly verify the 1D sub-band structure in ultrathin NWs by pronounced conductance steps in low-temperature transport measurements using back-gated NW-field effect transistors. Correlated simulations reveal single- and double degenerate conductance steps, which highlight the rotational hexagonal symmetry and reproduce the experimental traces in the diffusive 1D transport limit. Modelling under the realistic back-gate configuration further evidences regimes that lead to asymmetric carrier distribution and breakdown of the degeneracy depending on the gate bias.

Minimally invasive infrapubic inflatable penile prosthesis implant for erectile dysfunction: evaluation of efficacy, satisfaction profile and complications.

Erectile dysfunction (ED), the second most common male sexual disorder, has an important impact on man sexuality and quality of life affecting also female partner's sexual life. ED is usually related to cardiovascular disease or is an iatrogenic cause of pelvic surgery. Many non-surgical treatments have been developed with results that are controversial, while surgical treatment has reached high levels of satisfaction. The aim is to evaluate outcomes and complications related to prosthesis implant in patients suffering from ED not responding to conventional medical therapy or reporting side effects with such a therapy. One hundred eighty Caucasian male suffering from ED were selected. The patient population were divided into two groups: 84 patients with diabetes and metabolic syndrome (group A) and 96 patients with dysfunction following laparoscopic radical prostatectomy for prostate cancer (group B). All subjects underwent primary inflatable penile prosthesis implant with an infrapubic minimally invasive approach. During 12 months of follow-up, we reported 3 (1.67%) explants for infection, 1 (0.56%) urethral erosion, 1 (0.56%) prosthesis extrusion while no intraoperative complications were reported. Mean International Index of Erectile Function-5 (IIEF-5) was 8.2 ± 4.0 and after the surgery (12 months later) was 20.6 ± 2.7. The improvement after the implant is significant in both groups without a statistically significant difference between the two groups (P-value 0.65). Mean Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) score 1 year after the implant is 72.2 ± 20.7, and there was no statistically significant difference between groups A and B (P-value 0.55). Implantation of an inflatable prosthesis, for treatment of ED, is a safe and efficacious approach; and the patient and partner satisfaction is very high. Surgical technique should be minimally invasive and latest technology equipment should be implanted in order to decrease after surgery common complications (infection and mechanical failure).

Synchronous pattern distinguishes resting tremor associated with essential tremor from rest tremor of Parkinson's disease.

Rest tremor associated with essential tremor (ET) is a condition that poses challenges in diagnosing Parkinson's disease (PD). We investigated tremor parameters in PD and ET patients with rest tremor. Fifteen patients with PD and 15 patients with ET underwent electrophysiological examination to evaluate characteristics of muscle bursting in rest postures. Rest tremor amplitude of PD patients was significantly higher than that of patients with ET (p = 0.002), whereas burst duration and frequency were significantly higher in ET than in PD group (p = 0.002, p < 0.001, respectively). Patients with PD, however, showed some overlap of these electrophysiological values with values from patients with ET. By contrast, rest tremor pattern showed no overlap between the two diseases, because all patients with ET presented a synchronous pattern whereas PD patients had an alternating pattern (p < 0.001), a finding that differentiated the patients on an individual basis. The electromyographic pattern of rest tremor may help to differentiate PD from ET.

CASP-9: A susceptibility locus for multiple sclerosis in Italy.

Caspase-9 is a primary effector CASP that executes programmed cell death, which plays an important role in the development of multiple sclerosis (MS). Polymorphisms in the CASP-9 gene may influence its activity, thereby modulating the susceptibility to MS. To test this hypothesis, we evaluated a SNP in the CASP-9 gene in a set of Italian patients from Southern Italy and healthy control subjects. Our results suggest that the presence of the G/G genotype represents a higher risk factor in our MS population and a differential production of CASP-9 might be a contributory factor in determining the severity of MS.

Cognitive deficits in multiple sclerosis patients with cerebellar symptoms.

BACKGROUND: Cerebellar dysfunction is common in patients with multiple sclerosis (MS). However, neuropsychological studies of this clinical feature are lacking. OBJECTIVE: We investigate the neuropsychological features in relapsing-remitting MS (RR-MS) patients with and without cerebellar dysfunction. METHODS: Twenty-one RR-MS patients with cerebellar dysfunction (RR-MSc), characterized by prevalent ataxic gait and nystagmus, and 21 RR-MS patients without any cerebellar manifestation (RR-MSnc) pair-matched for demographical and clinical variables were studied. All patients from each group underwent an extensive battery of neuropsychological tests. Magnetic resonance imaging analysis included hyperintense fast fluid-attenuated inversion-recovery lesion load in the whole brain as well as in the four lobes separately. RESULTS: Any significant differences were detected in total and regional lesion load measurements between the two groups. RR-MSc group performed equally as well as the RR-MSnc group on many of the cognitive exploration measures. Nevertheless, the RR-MSc group performed more poorly than the RR-MSnc group on attention tests (Symbol Digit Modalities Test) and verbal fluency tests (Controlled Oral Word Association Test); neither of the test results proved to be affected by regional lesion loads. CONCLUSION: These results highlight the importance of considering cognitive deficits associated with the presence of cerebellar symptoms in RR-MS.