Thyroid hormones control both metabolic pathways and body composition, whereas little knowledge is available about the possible influence of skeletal muscle mass (MM) on thyroid hormone metabolism and circulating levels. This was a cross-sectional study conducted at the Population Health Unit of the National Institute of Gastroenterology IRCCS "S. de Bellis" (Italy) and investigating the extent to which skeletal MM affects thyroid function in obesity. Two hundred twenty-seven consecutive healthy volunteers (155 women and 72 men) with overweight and obesity (BMI ≥ 25 kg/m2) and taking no medication or supplement were assessed for hormone, metabolic and routine laboratory parameters. Body composition parameters were collected by using bioelectrical impedance analysis (BIA). MM was directly related to the body mass index (BMI), waist circumference (WC), insulin, triglycerides, uric acid and free-triiodothyronine (FT3) serum levels, FT3 to the free-thyroxine (FT4) ratio, and insulin-resistance (HOMA-IR), and inversely related to age, total, and HDL-cholesterol serum levels. Multiple regression models confirmed the relationship between MM and the FT3 to FT4 ratio, independently of age, BMI, TSH, triglycerides, and insulin serum levels. The same analyses run by gender showed that this relationship maintained significance only in men. Increased skeletal MM in obesity results in improved thyroid activity mediated by increased T4 conversion to T3, and higher FT3 circulating levels, particularly in men. In conclusion, preserving a greater skeletal MM in obesity helps to enhance thyroid activity.
ClinicalTrials.gov, identifier NCT04327375.
ClinicalTrials.gov, identifier NCT04327375.GPER-1 is a novel membrane sited G protein-coupled estrogen receptor. Clinical studies have shown that patients suffering an estrogen receptor α (ERα)/GPER-1 positive, breast cancer have a lower survival rate than those who have developed ERα-positive/GPER-1 negative tumors. Moreover, absence of GPER-1 improves the prognosis of patients treated with tamoxifen, the most used selective estrogen receptor modulator to treat ERα-positive breast cancer. MCF-7 breast cancer cells were continuously treated with 1,000 nM tamoxifen for 7 days to investigate its effect on GPER-1 protein expression, cell proliferation and intracellular [Ca2+]i mobilization, a key signaling pathway. Breast cancer cells continuously treated with tamoxifen, exhibited a robust [Ca2+]i mobilization after stimulation with 1,000 nM tamoxifen, a response that was blunted by preincubation of cells with G15, a commercial GPER-1 antagonist. Continuously treated cells also displayed a high [Ca2+]i mobilization in response to a commercial GPER-1 agon.Background Ultrasound-guided radiofrequency ablation (RFA) of thyroid nodules (TNs) is a minimally invasive procedure that has been widely used to induce volume reduction in symptomatic solid benign TNs. The goal of this study was to investigate a novel therapeutic approach for single-session ablation of large thyroid nodules (LTNs, vol > 20 ml). Methods We performed a pilot cohort study of 21 patients with symptomatic solid benign LTNs (vol > 20 ml), who accepted ultrasound-guided RFA treatment between September 2018 and November 2019. RFA was performed using an 18-gauge internally cooled electrode with ultrasonographic guidance in a single session combined with intraoperative hydrodissection and immediate contrast-enhanced ultrasound (CEUS) to optimize safety and efficacy. Nodule volume was evaluated before ablation and at 1, 3, and 6 months after initial ablation, and all patients were asked to assess the cosmetic score (from 1 to 4) and symptom score (from 0 to 10) before ablation and at every follow-up after ablation. Results At the 6 month follow-up, there was significant nodule volume reduction, from 27.49 ml ± 7.9 (standard deviation) to 3.82 ml ± 5.02 (p = 0.001). Cosmetic signs (p = 0.001) and pressure symptoms (p = 0.001) were significantly improved. All patients underwent RFA without any major complications, and very few patients developed a change in voice (2/21). However, the changes subsided within 1 month. https://www.selleckchem.com/products/azd0364.html Almost half of the patients received an additional RFA (11/21) treatment to achieve complete ablation on the intraoperative immediate CEUS evaluation. Conclusion RFA is effective for treating LTNs (vol > 20 ml) and controlling clinical symptoms with a low complication rate. Patients were satisfied with cosmetic sign and pressure symptom improvement. The intraoperative hydrodissection and immediate CEUS represent a novel therapeutic approach for single-session ablation of LTNs.
To evaluate whether metformin use assuredly alters overall all-cause death in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD).

Pubmed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials were systematically searched from inception to Feb. 29, 2020 with no language restriction. All related articles comparing all-cause death of T2DM and CKD patients after metformin use (monotherapy or combination) versus non-metformin treatment were identified. Pooled risk ratios (RR) and 95% confidence intervals (CI)were computed using random-effects models regardless of the heterogeneity quantified by Cochrane χ
and I
statistics.

Totally 13 studies (9 cohort studies Bashir Ahmed, 3 subanalyses or post-hoc analyses of randomized controlled trials [RCTs], and 1 nested case-control article) involving 303,540 patients were included. Metformin-based treatments relative to any other measure displayed significantly lower risks of all-cause mortality (Pooled RRs 0.71, 95%CI 0.61 to 0.84; I
79.0%) and cardiovascular events (Pooled RRs 0.76, 95%CI 0.60 to 0.97; I
87.0%) in CKD patients at stage G1-3, with substantial heterogeneity. Metformin use was not significantly related with these end points in advanced CKD patients.

Metformin use is connected with significantly less risks of all-cause mortality and cardiovascular events in patients with T2DM and mild/moderate CKD. However, RCTs with large sample sizes are warranted in the future to assess whether these key benefits extend to later stages of CKD by dose adjustment.
Metformin use is connected with significantly less risks of all-cause mortality and cardiovascular events in patients with T2DM and mild/moderate CKD. However, RCTs with large sample sizes are warranted in the future to assess whether these key benefits extend to later stages of CKD by dose adjustment.
Thyroid hormones control both metabolic pathways and body composition, whereas little knowledge is available about the possible influence of skeletal muscle mass (MM) on thyroid hormone metabolism and circulating levels. This was a cross-sectional study conducted at the Population Health Unit of the National Institute of Gastroenterology IRCCS "S. de Bellis" (Italy) and investigating the extent to which skeletal MM affects thyroid function in obesity. Two hundred twenty-seven consecutive healthy volunteers (155 women and 72 men) with overweight and obesity (BMI ≥ 25 kg/m2) and taking no medication or supplement were assessed for hormone, metabolic and routine laboratory parameters. Body composition parameters were collected by using bioelectrical impedance analysis (BIA). MM was directly related to the body mass index (BMI), waist circumference (WC), insulin, triglycerides, uric acid and free-triiodothyronine (FT3) serum levels, FT3 to the free-thyroxine (FT4) ratio, and insulin-resistance (HOMA-IR), and inversely related to age, total, and HDL-cholesterol serum levels. Multiple regression models confirmed the relationship between MM and the FT3 to FT4 ratio, independently of age, BMI, TSH, triglycerides, and insulin serum levels. The same analyses run by gender showed that this relationship maintained significance only in men. Increased skeletal MM in obesity results in improved thyroid activity mediated by increased T4 conversion to T3, and higher FT3 circulating levels, particularly in men. In conclusion, preserving a greater skeletal MM in obesity helps to enhance thyroid activity. ClinicalTrials.gov, identifier NCT04327375. ClinicalTrials.gov, identifier NCT04327375.GPER-1 is a novel membrane sited G protein-coupled estrogen receptor. Clinical studies have shown that patients suffering an estrogen receptor α (ERα)/GPER-1 positive, breast cancer have a lower survival rate than those who have developed ERα-positive/GPER-1 negative tumors. Moreover, absence of GPER-1 improves the prognosis of patients treated with tamoxifen, the most used selective estrogen receptor modulator to treat ERα-positive breast cancer. MCF-7 breast cancer cells were continuously treated with 1,000 nM tamoxifen for 7 days to investigate its effect on GPER-1 protein expression, cell proliferation and intracellular [Ca2+]i mobilization, a key signaling pathway. Breast cancer cells continuously treated with tamoxifen, exhibited a robust [Ca2+]i mobilization after stimulation with 1,000 nM tamoxifen, a response that was blunted by preincubation of cells with G15, a commercial GPER-1 antagonist. Continuously treated cells also displayed a high [Ca2+]i mobilization in response to a commercial GPER-1 agon.Background Ultrasound-guided radiofrequency ablation (RFA) of thyroid nodules (TNs) is a minimally invasive procedure that has been widely used to induce volume reduction in symptomatic solid benign TNs. The goal of this study was to investigate a novel therapeutic approach for single-session ablation of large thyroid nodules (LTNs, vol > 20 ml). Methods We performed a pilot cohort study of 21 patients with symptomatic solid benign LTNs (vol > 20 ml), who accepted ultrasound-guided RFA treatment between September 2018 and November 2019. RFA was performed using an 18-gauge internally cooled electrode with ultrasonographic guidance in a single session combined with intraoperative hydrodissection and immediate contrast-enhanced ultrasound (CEUS) to optimize safety and efficacy. Nodule volume was evaluated before ablation and at 1, 3, and 6 months after initial ablation, and all patients were asked to assess the cosmetic score (from 1 to 4) and symptom score (from 0 to 10) before ablation and at every follow-up after ablation. Results At the 6 month follow-up, there was significant nodule volume reduction, from 27.49 ml ± 7.9 (standard deviation) to 3.82 ml ± 5.02 (p = 0.001). Cosmetic signs (p = 0.001) and pressure symptoms (p = 0.001) were significantly improved. All patients underwent RFA without any major complications, and very few patients developed a change in voice (2/21). However, the changes subsided within 1 month. https://www.selleckchem.com/products/azd0364.html Almost half of the patients received an additional RFA (11/21) treatment to achieve complete ablation on the intraoperative immediate CEUS evaluation. Conclusion RFA is effective for treating LTNs (vol > 20 ml) and controlling clinical symptoms with a low complication rate. Patients were satisfied with cosmetic sign and pressure symptom improvement. The intraoperative hydrodissection and immediate CEUS represent a novel therapeutic approach for single-session ablation of LTNs. To evaluate whether metformin use assuredly alters overall all-cause death in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Pubmed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials were systematically searched from inception to Feb. 29, 2020 with no language restriction. All related articles comparing all-cause death of T2DM and CKD patients after metformin use (monotherapy or combination) versus non-metformin treatment were identified. Pooled risk ratios (RR) and 95% confidence intervals (CI)were computed using random-effects models regardless of the heterogeneity quantified by Cochrane χ and I statistics. Totally 13 studies (9 cohort studies [CSs], 3 subanalyses or post-hoc analyses of randomized controlled trials [RCTs], and 1 nested case-control article) involving 303,540 patients were included. Metformin-based treatments relative to any other measure displayed significantly lower risks of all-cause mortality (Pooled RRs 0.71, 95%CI 0.61 to 0.84; I 79.0%) and cardiovascular events (Pooled RRs 0.76, 95%CI 0.60 to 0.97; I 87.0%) in CKD patients at stage G1-3, with substantial heterogeneity. Metformin use was not significantly related with these end points in advanced CKD patients. Metformin use is connected with significantly less risks of all-cause mortality and cardiovascular events in patients with T2DM and mild/moderate CKD. However, RCTs with large sample sizes are warranted in the future to assess whether these key benefits extend to later stages of CKD by dose adjustment. Metformin use is connected with significantly less risks of all-cause mortality and cardiovascular events in patients with T2DM and mild/moderate CKD. However, RCTs with large sample sizes are warranted in the future to assess whether these key benefits extend to later stages of CKD by dose adjustment.
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