physical activity strategies in this population. Copyright © 2020 Kreidieh, Itani, El Masri, Tannir and El Ghoch.In mammals, local production of tumor necrosis factor α (TNFα) inhibits growth hormone (GH)-induced IGF-I expression at tissue level and contributes to GH resistance caused by sepsis/endotoxemia and inflammation. Although the loss of GH responsiveness can be mediated by a parallel rise in SOCS expression, the signaling mechanisms for TNFα-induced SOCS expression at the hepatic level have not been characterized and the comparative aspects of the phenomenon, especially in lower vertebrates, are still unknown. Recently, type II SOCS, including SOCS1-3 and CISH, have been cloned in grass carp and shown to act as the feedback repressors for GH signaling via JAK2/STAT5 pathway. To shed light on the mechanisms for TNFα-induced GH resistance in fish model, grass carp TNFα was cloned and confirmed to be a single-copy gene expressed in various tissues including the liver. In carp hepatocytes, incubation with the endotoxin LPS induced TNFα expression with parallel rises in SOCS1-3 and CISH mRNA levels. Similar to LPS, TNFα treatment could block GH-induced IGF-I/-II mRNA expression and elevate SOCS1, SOCS3, and CISH transcript levels. However, TNFα was not effective in altering SOCS2 expression. In parallel experiment, LPS blockade of IGF-I/-II signals caused by GH could be partially reverted by TNFα receptor antagonism. At hepatocyte level, TNFα induction also triggered rapid phosphorylation of IκBα, MEK1/2, ERK1/2, MKK3/6, P38 MAPK, Akt, JAK2, and STAT1,3,5, and TNFα-induced SOCS1, SOCS3, and CISH mRNA expression could be negated by inhibiting the IKK/NFκB, MAPK, PI3K/Akt, and JAK/STAT cascades. Our findings, as a whole, suggest that local production of TNFα may interfere with IGF-I/-II induction by GH in the carp liver by up-regulation of SOCS1, SOCS3, and CISH via IKK/NFκB, MAPK, PI3K/Akt, and JAK/STAT-dependent mechanisms, which may contribute to GH resistance induced by endotoxin in carp species. Copyright © 2020 Jiang, He, Bai, Chan and Wong.Purpose In order to understand how thyroid abnormalities emerge over time in adults, we evaluated incidence of thyroid diseases in healthy subjects, after almost 6 years from a previous negative ultrasound. Methods Anamnestic and physical data were collected. Ultrasound neck evaluation was performed by an experienced endocrinologist, recording detailed thyroid and nodules characteristics. Nodules were classified according to American Thyroid Association classification for prediction of cancer risk. Serum samples were collected for subsequent evaluations (TSH, free thyroid hormones, calcitonin, anti-thyroid antibodies). Anamnestic, clinical, sonographic, and serological characteristics were analyzed with logistic regression analysis for subjects with nodules vs. those without. Results One hundred and eleven subjects were enrolled (43M, 68F). Half of them developed nodules, mainly smaller than 1 cm and without suspicious characteristics. Ninety-seven percent were euthyroid. Only 4% had serological diagnosis of thyroiditis. Incidence of thyroid diseases was higher in women, especially nulliparous. Comparing clinical characteristics of subjects with and without nodules, the only statistically significant difference concerned thyroid volume adjusted for body weight or surface (p less then 0.05), but not residual volume excluding nodules. Multivariate logistic regression analysis showed that female gender, higher BMI-adjusted thyroid volume and residual thyroid volume excluding nodules, nulliparity, age, and fT3 increase the risk of developing nodules. Conclusions These results demonstrate that adult thyroid tissue undergoes changes that are already detectable by US after almost 6 years. Half of the enrolled subjects developed de novo nodules or colloid cysts of poor clinical relevance. Copyright © 2020 Brigante, Monzani, Locaso, Gnarini, Graziadei, Kaleci, De Santis, Tagliavini, Simoni, Rochira and Madeo.In this study, we injected cortisol into the protogynous orange-spotted grouper (Epinephelus coioides) to investigate the role of this hormone in sex change. Following injection, we evaluated gonadal changes, serum levels of steroid hormones, and sex-related gene expression during the processes of cortisol-induced sex change and cortisol withdrawal in the orange-spotted grouper. Cortisol treatment caused the degeneration of oocytes and induced sex change in a dose-dependent manner. Over the long-term, we observed a significant increase in serum 11-ketotestosterone (11-KT) levels in all cortisol-treated groups, although levels of 17β-estradiol did not change significantly. Consistent with the elevation of serum 11-KT levels, the expression of genes related to testicular development was also significantly up-regulated in the cortisol-treated groups. Based on our results, we propose that cortisol may trigger masculinization by inducing the synthesis of 11-KT and by directly activating the expression of sex-related genes. Furthermore, we found that cortisol-induced sex change was not permanent and could be reversed after the withdrawal of cortisol treatment. Copyright © 2020 Chen, Peng, Yu, Xiao, Yu, Li, Zhang, Lin and Zhang.For decades researchers have reported men who engaged in intensive exercise training can develop low resting testosterone levels, alterations in their hypothalamic-pituitary-gonadal (HPG) axis, and display hypogonadism. Recently there is renewed interest in this topic since the International Olympic Committee (IOC) Medical Commission coined the term “Relative Energy Deficiency in Sports” (RED-S) as clinical terminology to address both the female-male occurrences of reproductive system health disruptions associated with exercise. This IOC Commission action attempted to move beyond the sex-specific terminology of the “Female Athlete Triad” (Triad) and heighten awareness/realization that some athletic men do have reproductive related physiologic disturbances such as lowered sex hormone levels, HPG regulatory axis alterations, and low bone mineral density similar to Triad women. KRAS G12C inhibitor 19 There are elements in the development and symptomology of exercise-related male hypogonadism that mirror closely that of women experiencing the Triad/RED-S, but evidence also exists that dissimilarities exist between the sexes on this issue.