The relationship between thyroid and human-associated microbiota: A systematic review of reviews.

In recent years, a growing number of studies have examined the relationship between thyroid pathophysiology and intestinal microbiota composition. The reciprocal influence between these two entities has been proven so extensive that some authors coined the term "gut-thyroid axis". However, since some papers reported conflicting results, several aspects of this correlation need to be clarified. This systematic review was conceived to achieve more robust information about: 1)the characteristics of gut microbiota composition in patients with the more common morphological, functional and autoimmune disorders of the thyroid; 2)the influence of gut microbial composition on micronutrients that are essential for the maintenance of thyroid homeostasis; 3)the effect of probiotics, prebiotics and synbiotics, some of the most popular over-the-counter products, on thyroid balance; 4)the opportunity to use specific dietary advice. The literature evaluation was made by three authors independently. A five steps strategy was a priori adopted. After duplicates removal, 1106 records were initially found and 38 reviews were finally included in the analysis. The systematic reviews of reviews found that: 1) some significant variations characterize the gut microbiota composition in patients with thyroid disorders. However, geographical clustering of most of the studies prevents drawing definitive conclusions on this topic; 2) the available knowledge about the effect of probiotics and synbiotics are not strong enough to suggest the routine use of these compounds in patients with thyroid disorders; 3) specific elimination nutrition should not be routine suggested to patients, which, instead have to be checked for possible micronutrients and vitamins deficiency, often owed to gastrointestinal autoimmune comorbidities.

Long-term efficacy and safety of percutaneous ethanol injection (PEI) in cystic thyroid nodules: A systematic review and meta-analysis.

BACKGROUND: Percutaneous ethanol injection (PEI) is used for the treatment of benign cystic thyroid nodules. This systematic review and meta-analysis aimed to obtain strong evidence of its long-term efficacy and safety. METHODS: PubMed, CENTRAL, Scopus and Web of Science databases were searched until November 2020 for studies reporting data on volume reduction rate (VRR), compressive symptoms and cosmetic concerns. Associated complications were assessed. A random-effects model was designed to pool the data. RESULTS: Out of 385 papers, nine studies evaluating 1667 nodules were finally included. Overall, VRR at 6, 12, 24, 36, 60 and 120 months was 77%, 81%, 72%, 68%, 74% and 69%, respectively. Significant reductions in the compressive symptoms and cosmetic concerns were observed. No permanent complications were observed. CONCLUSIONS: The present meta-analysis showed that PEI could significantly reduce the volume of benign cystic thyroid nodules. This reduction was already effective at 6 months post-treatment, and the effect was stable over time.

Fibrosis-4 Index vs Nonalcoholic Fatty Liver Disease Fibrosis Score in Identifying Advanced Fibrosis in Subjects With Nonalcoholic Fatty Liver Disease: A Meta-Analysis.

INTRODUCTION: In subjects with nonalcoholic fatty liver disease (NAFLD), advanced fibrosis (AF) carries the highest risk of adverse liver-related events. To reduce the number of unnecessary biopsies, several noninvasive tools (NITs) for the risk stratification of fibrosis have been developed. We conducted this meta-analysis to assess the performance of the fibrosis-4 index (FIB-4) and NAFLD fibrosis scores (NFS), the 2 most common NITs, for the appropriate selection of subjects with AF for biopsy. METHODS: Four databases were searched until December 2020 (CRD42021224766). Original articles reporting data on the performance of FIB-4 and NFS, interpreted according to standard cutoffs in subjects with biopsy-proven NAFLD, were included. Separate data extractions were performed according to the lower cutoff, the higher cutoff, and the dual threshold approach. The numbers of subjects classified as true-negative, true-positive, false-negative, and false-positive were extracted. Summary operating points were estimated using a random-effects model. RESULTS: Eighteen studies evaluating 12,604 subjects were included. Participants were adult outpatients with biopsy-proven NAFLD or nonalcoholic steatohepatitis. Overall, a weak-to-moderate performance was found for both scores. The head-to-head comparison showed FIB-4 to be associated with a higher performance in ruling in and NFS in ruling out AF in the single threshold approach, whereas, with the dual threshold approach, a lower prevalence of indeterminate findings was found for FIB-4. DISCUSSION: This meta-analysis suggested that currently available NITs have a limited performance in identifying AF among subjects with NAFLD. Further studies are needed to optimize existing thresholds or develop new NITs.

The ultrasound risk stratification systems for thyroid nodule have been evaluated against papillary carcinoma. A meta-analysis.

Thyroid imaging reporting and data systems (TIRADS) are used to stratify the malignancy risk of thyroid nodule by ultrasound (US) examination. We conducted a meta-analysis to evaluate the pooled cancer prevalence and the relative prevalence of papillary, medullary, follicular thyroid cancer (PTC, MTC, and FTC) and other malignancies among nodules included in studies evaluating their performance. Four databases were searched until February 2020. Original articles with at least 1000 nodules, evaluating the performance of at least one TIRADS among AACE/ACE/AME, ACR-TIRADS, ATA, EU-TIRADS, or K-TIRADS, and reporting data on the histological diagnosis of malignant lesions were included. The number of malignant nodules, PTC, FTC, MTC and other malignancies in each study was extracted. For statistical pooling of data, a random-effects model was used. Nine studies were included, evaluating 19,494 thyroid nodules. The overall prevalence of malignancy was 34% (95%CI 21 to 49). Among 6162 histologically proven malignancies, the prevalence of PTC, FTC, MTC and other malignancies was 95%, 2%, 1%, and 1%, respectively. A high heterogeneity was found for all the outcomes. A limited number of studies generally conducted using a retrospective design was found, with possible selection bias. Acknowledging this limitation, TIRADSs should be regarded as accurate tools to diagnose PTC only. Proposed patterns and/or cut-offs should be revised and other strategies considered to improve their performance in the assessment of FTC, MTC and other malignancies.

Physical exercise, nutrition and hormones: three pillars to fight sarcopenia.

BACKGROUND: Sarcopenia is a pathophysiological condition diffused in elderly people; it represents a social issue due to the longer life expectancy and the growing aging population. It affects negatively quality of life and it represents a risk factor for other pathologies, such as diabetes, cardiovascular disease, and obesity. No silver bullet exists to hinder sarcopenia, but it may be counteracted by physical exercise, nutrition, and a proper endocrine milieu. Indeed, we aim to analyze the scientific literature to give to clinician effective advices to counteract sarcopenia. Main text: Physical exercise, proper nutrition, optimized hormonal homeostasis represent the three pillars to fight sarcopenia. Physical exercise represents the most effective remedy to face sarcopenia, in particular if it is combined with a proper diet and with an adequate endocrine milieu. Consistency in training, adequate daily protein intake and eugonadism seems to be the keys to fight sarcopenia. The combination of these three pillars might act synergistically. CONCLUSIONS: Optimization of these factors may increase their efficiency; however, scientific data may be sometimes confusing so far. Therefore, we aim to give practical advices to clinician to identify and to highlight the most important aspects in each of these three factors that should be addressed.

Sport, doping and male fertility.

It is universally accepted that lifestyle interventions are the first step towards a good overall, reproductive and sexual health. Cessation of unhealthy habits, such as tobacco, alcohol and drug use, poor nutrition and sedentary behavior, is suggested in order to preserve/improve fertility in humans. However, the possible risks of physical exercise per se or sports on male fertility are less known. Being "fit" does not only improve the sense of well-being, but also has beneficial effects on general health: in fact physical exercise is by all means a low-cost, high-efficacy method for preventing or treating several conditions, ranging from purely physical (diabetes and obesity) to psychological (depression and anxiety), highly influencing male reproduction. If male sexual and reproductive health could be positively affected by a proper physical activity, inadequate bouts of strength - both excessive intensity and duration of exercise training - are more likely to have detrimental effects. In addition, the illicit use of prohibited drugs (i.e. doping) has reached pandemic proportions, and their actions, unfortunately very often underestimated by both amateur and professional athletes, are known to disrupt at different levels and throughout various mechanisms the male hypothalamic-pituitary-gonadal axis, resulting in hypogonadism and infertility.

Folate: a possible role in erectile dysfunction?

A growing body of evidence suggests a role for homocysteine (Hcys) and folate (FA) in erectile function (EF): Hcys appears to impair EF affecting endothelium via several mechanism whereas the role of FA remains to be elucidated, besides decreasing Hcys. To assess correlation between erectile dysfunction (ED) and serum levels of FA, Hcys, and B12, we enrolled 31 patients affected by ED (Group A; age 52.83 ± 11.89 years) and 31 healthy adults (Group B; age 49.14 ± 13.63 years). Fasting blood samples were taken for each subject. ED was assessed by the International Index of Erectile Function-5 (IIEF-5). IIEF-5 mean score was significantly lower in Group A than in Group B (10.71 ± 4.24 versus 23.32 ± 1.33, p < .001). Compared to Group B, Group A also showed significantly lower serum FA levels (5.11 ± 1.79 versus 7.9 ± 3.55 ng/ml, p < .001) and significantly higher serum Hcys levels (13.61 ± 3.55 versus 9.17 ± 2.32 µmol/L, p < .001). No significant correlation was observed between Hcys and FA both groups. Our results showed a significant association among ED, FA deficiency and hyperomocisteinemia. Lack of correlation between FA and Hcys suggests that FA deficit may directly impair EF.

Establishing normal values of total testosterone in adult healthy men by the use of four immunometric methods and liquid chromatography-mass spectrometry.

BACKGROUND: The total testosterone (T) cutoffs clinically adopted to define late-onset hypogonadism (LOH) do not consider the differences that exist between different analytical platforms, nor do they consider the body mass index (BMI) or age of the patient. We aimed at providing method, age and BMI-specific normal values for total T in European healthy men. METHODS: A total of 351 eugonadal healthy men were recruited, and total T was measured with four automated immunometric assays (IMAs): ARCHITECT i1000SR (Abbott), UniCel DxI800 (Beckman Coulter), Cobas e601 (Roche), IMMULITE 2000 (Siemens) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Reference ranges (RRs) were calculated for each method. RESULTS: Passing and Bablok regression analysis and Bland-Altman plot showed an acceptable agreement between Abbott and LC-MS/MS, but a poor one between LC-MS/MS and the other IMAs. Age-specific T concentrations in non-obese (BMI <29.9 kg/m2) men were greater than in all men. The total T normal range, in non-obese men aged 18-39 years, measured with LC-MS/MS was 9.038-41.310 nmol/L. RRs calculated with LC-MS/MS statistically differed from the ones calculated with all individual IMAs, except Abbott and among all IMAs. Statistically significant differences for both upper and lower reference limits between our RRs and the ones provided by the manufacturers were also noticed. CONCLUSIONS: We calculated normal ranges in a non-obese cohort of European men, aged 18-39 years, with four commercially available IMAs and LC-MS/MS and found statistically significant differences according to the analytical method used. Method-specific reference values can increase the accuracy of LOH diagnosis and should be standardly used.

Effects of Ketone Bodies on Endurance Exercise.

Priorities for every athlete include improving endurance performance, optimizing training, nutrition, and recovery. Nutritional strategies are crucial to support athletes to perform at the highest level, and considering that muscular and hepatic glycogen stores are limited, alternative strategies to maximize fat metabolism have been suggested. A ketogenic diet has been proposed as a possible method of providing metabolic fuel during prolonged periods of exercise. However, clinical trials and empirical experience have produced contrasting results regarding the ergogenic value of a ketogenic diet. For this reason, using ketone esters and/or salts have been proposed to obtain nutritional ketosis without limiting carbohydrate intake. Exogenous ketones should not only represent an alternative metabolic fuel source, sparing carbohydrates, but they also may increase postexercise glycogen replenishment, decrease proteolysis, and act as metabolic modulators and signaling metabolites. While there are some encouraging results showing an increase in endurance performance, contrasting evidence regarding the efficacy of exogenous ketones for endurance performance is present and further studies should be performed to make a definitive statement.

Relationship Between Use of Videogames and Sexual Health in Adult Males.

BACKGROUND: Videogame use is increasingly prevalent in people of all ages, and despite the wide amount of scientific evidence proving a role for electronic entertainment in human health, there is no evidence about the relation between use of videogames and sexual health. AIM: To investigate the association between use of videogames and male sexual health. METHODS: We administered the two validated questionnaires, the Premature Ejaculation Diagnostic Tool (PEDT) and the International Index of Erectile Function (IIEF-15), to men 18 to 50 years old recruited through social networks and specific websites. In addition to the questionnaires, volunteers were asked to provide information on their gaming habit and lifestyle. OUTCOMES: An extended version of the IIEF-15 and PEDT, including data about gaming habits and relevant lifestyles. RESULTS: From June 18, 2014 through July 31, 2014, 599 men 18 to 50 years old completed the questionnaires. One hundred ninety-nine men reported no sexual activity during the previous 4 weeks; four records were rejected because of inherent errors. The remaining 396 questionnaires were analyzed, with 287 "gamers" (playing >1 hour/day on average) and 109 "non-gamers" providing all the required information. We found a lower prevalence of premature ejaculation in gamers compared with non-gamers (mean PEDT score = 3.57 ± 3.38 vs 4.52 ± 3.7, P < .05, respectively). Analysis of the IIEF-15 showed no significant differences between gamers and non-gamers in the domains of erectile function, orgasmic function, and overall satisfaction. Median scores for the sexual desire domain were higher for non-gamers (median score [interquartile range] 9 [8-9] vs 9 [8-10], respectively; P = .0227). CLINICAL IMPLICATIONS: These results support the correlation between videogame use and male sexual health. Compared with non-gamers, men playing videogames for more than 1 hour/day were less likely to have premature ejaculation but more likely to have decreased sexual desire. STRENGTHS AND LIMITATIONS: This is the first study aimed to assess male sexual health in gamers. We identified an association between PEDT and IIEF scores and videogame use; however, these findings require validation through interventional studies. Furthermore, volunteers were recruited through social networks, thus increasing the risk of recruitment bias. CONCLUSION: To our knowledge, this is the first observational study investigating the link between electronic entertainment and male sexuality, specifically for ejaculatory response and sexual desire. Sansone A, Sansone M, Proietti M, et al. Relationship Between Use of Videogames and Sexual Health in Adult Males. J Sex Med 2017;14:898-903.

Pituitary hyperplasia mimicking macroadenoma associated with primary hypothyroidism in a patient with selective L-thyroxine malabsorption.

We present the case of a 29-year-old woman who developed a severe hypothyroidism induced by a thyroxine malabsorption and a secondary pituitary hyperplasia. We performed thyroxine absorption tests to diagnose the malabsorption and to evaluate the best therapeutic intervention. Once assessed a correct therapy lowering TSH, we observed the regression of pituitary mass confirming our diagnosis of secondary pituitary hyperplasia. We suggest to evaluate any possible reason for thyroxine malabsorption and to consider the hypothesis of pituitary hyperplasia in the presence of pituitary mass together with overt hypothyroidism.

Galectin-3 Performance in Histologic a Cytologic Assessment of Thyroid Nodules: A Systematic Review and Meta-Analysis.

The literature on Galectin-3 (Gal-3) was systematically reviewed to achieve more robust information on its histologic reliability in identifying thyroid cancers and on the concordance between Gal-3 test in histologic and cytologic samples. A computer search of the PubMed and Scopus databases was conducted by combinations of the terms thyroid and Gal-3. Initially, 545 articles were found and, after their critical review, 52 original papers were finally included. They reported 8172 nodules with histologic evaluation of Gal-3, of which 358 with also preoperative FNAC Gal-3 assessment. At histology, Gal-3 sensitivity was 87% (95% confidence intervals [CI] from 86% to 88%), and specificity 87% (95% CI from 86% to 88%); in both cases, we found heterogeneity (I2 85% and 93%, respectively) and significant publication bias (p < 0.001). The pooled rate of positive Gal-3 at fine needle aspiration (FNAC) among cancers with histologically proven Gal-3 positivity was 94% (95% CI from 89% to 97%), with neither heterogeneity (I2 14.5%) nor bias (p = 0.086). These data show high reliability of Gal-3 for thyroid cancer at histology, while its sensitivity on FNAC samples is lower. The limits of cytologic preparations and interpretation of Gal-3 results have to be solved.

BRAF-mutated carcinomas among thyroid nodules with prior indeterminate FNA report: a systematic review and meta-analysis.

BACKGROUND: Several molecular analyses have been investigated for risk stratification of thyroid nodules, with a particular focus on the V600E mutation of the BRAF gene [BRAF(V600E)]. To date, there is no high-level evidence supporting or refuting a role for BRAF analysis in thyroid nodules with prior indeterminate cytology. To obtain more robust evidence, we reviewed and meta-analysed data from published articles. RESEARCH DESIGN AND METHODS: A comprehensive literature search of the PubMed/MEDLINE, Embase and Scopus databases was conducted using the terms 'BRAF', 'thyroid' and 'indeterminate'. The search was updated until March 2015, and references of the retrieved articles were also screened. Only original articles reporting BRAF mutation testing within nodules with indeterminate FNA were eligible for inclusion. RESULTS: The literature search revealed 82 articles, of which 8 were eligible for the study. Five studies were prospective and three retrospective. The majority of authors analysed BRAF mutations in FNA samples which were classified by the British or Bethesda system. Of the initial series of studies, a pooled number of 1361 cases were achieved of which 43 were BRAF mutated. Overall, the BRAF mutation rate was 4·6% (95% CI: 1-10·8%), ranging from 0 to 22·9%. When we included only histological series, 978 thyroid nodules were found. Of these, 245 were cancers. CONCLUSIONS: A very low rate of lesions with indeterminate cytology are BRAF mutated. Thus, the role of this biomarker to detect or exclude cancers in patients with such FNA reports is marginal and should be reconsidered in guidelines.

Early diagnosis by FNA cytology should not influence the outcome of differentiated thyroid cancer.

In oncology, the early cancer detection is recognized as associated with good patient's prognosis. Then, one could expect that differentiated thyroid carcinoma (DTC) undergone fine-needle aspiration cytology (FNA) early have better outcome. Aim of this study was to investigate if DTC prognosis is improved by early FNA diagnosis. DTCs followed-up at our institution were included. Information about initial management of thyroid lesion, FNA, surgery, and postoperative follow-up was collected. Cytologies were classified according to British Thyroid Association (BTA). The final series comprised 219 DTCs, of which 22 (10%) recurred. The length of time between nodule appearance and cancer treatment was significantly (p<0.0001) shorter in patients who had undergone FNA than those who had not. In the FNA group, 73 patients underwent biopsy within six months, 25 at 7-12 months, and 43 after at least one year. Regardless of this highly significant (p<0.0001) difference, the results of TNM staging and cancer recurrence rate were no different between these three subgroups. This result was confirmed in DTCs larger than 1 cm submitted to FNA within 12 months or later. When we evaluated the impact of nodule's presentation on DTC outcome, clinically discovered cancers were significantly associated with relapse (OR 2.81) and advanced TNM stages (p=0.03). These data show a lack of clinical impact of the delayed diagnosis of DTC. Also, the postoperative outcome of these patients should not be influenced by the timing of FNA. Instead, DTC patients with preoperative clinical nodule appearance should be considered at higher risk of relapse.

Detection rate of FNA cytology in medullary thyroid carcinoma: a meta-analysis.

BACKGROUND: The early detection of medullary thyroid carcinoma (MTC) can improve patient prognosis, because histological stage and patient age at diagnosis are highly relevant prognostic factors. As a consequence, delay in the diagnosis and/or incomplete surgical treatment should correlate with a poorer prognosis for patients. Few papers have evaluated the specific capability of fine-needle aspiration cytology (FNAC) to detect MTC, and small series have been reported. This study conducts a meta-analysis of published data on the diagnostic performance of FNAC in MTC to provide more robust estimates. RESEARCH DESIGN AND METHODS: A comprehensive computer literature search of the PubMed/MEDLINE, Embase and Scopus databases was conducted by searching for the terms 'medullary thyroid' AND 'cytology', 'FNA', 'FNAB', 'FNAC', 'fine needle' or 'fine-needle'. The search was updated until 21 March 2014, and no language restrictions were used. RESULTS: Fifteen relevant studies and 641 MTC lesions that had undergone FNAC were included. The detection rate (DR) of FNAC in patients with MTC (diagnosed as 'MTC' or 'suspicious for MTC') on a per lesion-based analysis ranged from 12·5% to 88·2%, with a pooled estimate of 56·4% (95% CI: 52·6-60·1%). The included studies were statistically heterogeneous in their estimates of DR (I-square >50%). Egger's regression intercept for DR pooling was 0·03 (95% CI: -3·1 to 3·2, P = 0·9). The study that reported the largest MTC series had a DR of 45%. Data on immunohistochemistry for calcitonin in diagnosing MTC were inconsistent for the meta-analysis. CONCLUSIONS: The presented meta-analysis demonstrates that FNAC is able to detect approximately one-half of MTC lesions. These findings suggest that other techniques may be needed in combination with FNAC to diagnose MTC and avoid false negative results.

Calcitonin measurement in aspiration needle washout fluids has higher sensitivity than cytology in detecting medullary thyroid cancer: a retrospective multicentre study.

OBJECTIVE: Only few studies analysed the capability of cytology in detecting medullary thyroid cancer (MTC), and they reported a low accuracy of this diagnostic technique. Recently, calcitonin (CT) measurement in aspiration needle washout (FNA-CT) of thyroid and neck lesions has been reported as a sensitive tool for MTC. The aim of this study is to compare the sensitivity of FNA-CT and cytology in detecting MTC and to assess a cut-off value of FNA-CT for clinical practice. PATIENTS: Thirty-eight MTC lesions from 36 patients were retrospectively studied, diagnosed and treated in four different centres. Furthermore, 52 nonmedullary lesions from subjects undergone biopsy following increased serum CT were collected as a control group. RESULTS: Cytology detected MTC in 21/37 lesions with 56·8% sensitivity. The median FNA-CT value was 2000 pg/ml (range 58-10 000 pg/ml) in MTC and 2·7 pg/ml (range <2-13 pg/ml) in controls (P < 0·001). Using a cut-off of 39·6 pg/ml, MTC lesions could be identified with 100% sensitivity and specificity. As the most important finding, 14 histologically proved MTC lesions could be detected by FNA-CT, despite they were cytologically diagnosed as benign or nonconclusive. CONCLUSIONS: This study shows, as the first in a multicentre series, that FNA-CT sensitivity is higher than that of cytology in diagnosing MTC. To avoid false-negative MTC by cytology, CT measurement in aspiration needle washout is to be performed in all patients undergoing biopsy following high serum CT.

The use of core needle biopsy as first-line in diagnosis of thyroid nodules reduces false negative and inconclusive data reported by fine-needle aspiration.

BACKGROUND: The reported reliability of core needle biopsy (CNB) is high in assessing thyroid nodules after inconclusive fine-needle aspiration (FNA) attempts. However, first-line use of CNB for nodules considered at risk by ultrasonography (US) has yet to be studied. The aim of this study were: 1) to evaluate the potential merit of using CNB first-line instead of conventional FNA in thyroid nodules with suspicious ultrasonographic features; 2) to compare CNB and FNA as a first-line diagnostic procedure in thyroid lesions at higher risk of cancer. METHODS: Seventy-seven patients with a suspicious-appearing, recently discovered solid thyroid nodule were initially enrolled as study participants. No patients had undergone prior thyroid fine-needle aspiration/biopsy. Based on study design, all patients were proposed to undergo CNB as first-line diagnostic aspiration, while those patients refusing to do so underwent conventional FNA. RESULTS: Five patients refused the study, and a total of 31 and 41 thyroid nodules were subjected to CNB and FNA, respectively. At follow-up, the overall rate of malignancy was of 80% (CNB, 77%; FNA, 83%). However, the diagnostic accuracy of CNB (97%) was significantly (P < 0.05) higher than that of FNA (78%). In one benign lesion, CNB was inconclusive. Four (12%) of the 34 cancers of the FNA group were not initially diagnosed because of false negative (N = 1), indeterminate (N = 2) or not adequate (N = 1) samples. CONCLUSIONS: CNB can reduce the false negative and inconclusive results of conventional FNA and should be considered a first-line method in assessing solid thyroid nodules at high risk of malignancy.

Experimental and Numerical Analysis of a Pd-Ag Membrane Unit for Hydrogen Isotope Recovery in a Solid Blanket.

The interest of the fusion community in Pd-Ag membranes has grown in the last decades due to the high value of hydrogen permeability and the possibility of continuous operation, making it a promising technology when a gaseous stream of hydrogen isotopes must be recovered and separated from other impurities. This is the case of the Tritium Conditioning System (TCS) of the European fusion power plant demonstrator, called DEMO. This paper presents an experimental and numerical activity aimed at (i) assessing the Pd-Ag permeator performance under TCS-relevant conditions, (ii) validating a numerical tool for scale-up purposes, and (iii) carrying out a preliminary design of a TCS based on Pd-Ag membranes. Experiments were performed by feeding the membrane with a He-H2 gas mixture in a specific feed flow rate ranging from 85.4 to 427.2 mol h-1 m-2. A satisfactory agreement between experiments and simulations was obtained over a wide range of compositions, showing a root mean squared relative error of 2.3%. The experiments also recognized the Pd-Ag permeator as a promising technology for the DEMO TCS under the identified conditions. The scale-up procedure ended with a preliminary sizing of the system, relying on multi-tube permeators with an overall number ranging between 150 and 80 membranes in lengths of 500 and 1000 mm each.

The phosphodiesterases type 5 inhibitor tadalafil reduces the activation of the hypothalamus-pituitary-adrenal axis in men during cycle ergometric exercise.

Phosphodiesterase type 5 inhibitors may influence human physiology, health, and performance by also modulating endocrine pathways. We evaluated the effects of a 2-day tadalafil administration on adenohypophyseal and adrenal hormone adaptation to exercise in humans. Fourteen healthy males were included in a double-blind crossover trial. Each volunteer randomly received two tablets of placebo or tadalafil (20 mg/day with a 36-h interval) before a maximal exercise was performed. After a 2-wk washout, the volunteers were crossed over. Blood samples were collected at -30 and -15 min and immediately before exercise, immediately after, and during recovery (+15, +30, +60, and +90 min) for adrenocorticotropin (ACTH), ß-endorphin, growth hormone (GH), prolactin, cortisol (C), corticosterone, dehydroepiandrosterone-sulfate (DHEAS), and cortisol binding globulin (CBG) assays. C-to-CBG (free cortisol index, FCI) and DHEAS-to-C ratios were calculated. Exercise intensity, perceived exertion rate, O2 consumption, and CO2 and blood lactate concentration were evaluated. ACTH, GH, C, corticosterone, and CBG absolute concentrations and/or areas under the curve (AUC) increased after exercise after both placebo and tadalafil. Exercise increased DHEAS only after placebo. Compared with placebo, tadalafil administration reduced the ACTH, C, corticosterone, and FCI responses to exercise and was associated with higher ß-endorphin AUC and DHEAS-to-C ratio during recovery, without influencing cardiorespiratory and performance parameters. Tadalafil reduced the activation of the hypothalamus-pituitary-adrenal axis during exercise by probably influencing the brain's nitric oxide- and cGMP-mediated pathways. Further studies are necessary to confirm our results and to identify the involved mechanisms, possible health risks, and potential clinical uses.

Concerns about serum androgens monitoring during testosterone replacement treatments in hypogonadal male athletes: a pilot study.

INTRODUCTION: A well-tailored testosterone replacement treatment (TRT) in male hypogonadal athletes plays a pivotal role to restore physiological performances, to reduce health risks, and to guarantee the ethic of competition. Few studies evaluated individual androgens profiles during TRT in trained individuals. AIM: The aim of this article was to verify the efficacy in restoring eugonadal serum and urinary androgens profiles after testosterone enanthate (TE) and gel (TG) administration. METHODS: Ten male Caucasian-trained volunteers affected by severe hypotestosteronemia (<8 nmol/L) were included. Serum androgens and urinary testosterone metabolites were evaluated, in the same subjects, before and weekly for 5 weeks after both a single intramuscular TE injection (250 mg) and during a daily administration of TG (50 mg/die of testosterone), respectively. MAIN OUTCOME MEASURES: The main outcome measures of this article were serum total testosterone (TT), dihydrotestosterone (DHT), calculated free and bioavailable testosterone (cFT, cBioT), 17-ß-estradiol, and urinary glucuronide testosterone metabolites. RESULTS: Supraphysiological TT concentrations were observed in 50% of our volunteers until 7 days after TE and in the 4% of total samples after TG. Serum DHT was high both after TE (all volunteers on day 7 and 50% on day 14) and during TG (32% of total samples). A relatively low number of samples showed normal cFT and cBioT both after TE and TG (20-44%, respectively). Urinary metabolites were related to the type of treatment and to serum androgens profile and resulted in the normal ranges from 15% to 60% of total samples. CONCLUSION: Besides well-known variations of mean serum TT, we showed a high percentage of serum and urinary samples with abnormal androgens, being TG safer than TE. We conclude that monitoring TRT with TT only may be inaccurate because of abnormal fluctuations of other circulating androgens. Further studies to identify the appropriate markers of eugonadism during TRT are highly warranted both in athletes and in non-athletes.