Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a potential therapeutic target for different kinds of pathologies including cancer, cardiovascular disease, respiratory disease, and other conditions. Moreover, identification of SIRT modulators and exploring the functions of these different modulators have prompted increased efforts to discover new small molecules, which can modify SIRT activity. Furthermore, several randomized controlled trials have indicated that different interventions might affect the expression of SIRT protein in human samples, and supplementation of SIRT modulators might have diverse impact on physiological function in different participants. In this review, we introduce the history and structure of the SIRT protein family, discuss the molecular mechanisms and biological functions of seven members of the SIRT protein family, elaborate on the regulatory roles of SIRTs in human disease, summarize SIRT inhibitors and activators, and review related clinical studies.

To provide comprehensive estimates of the global, regional, and national burden of infertility from 1990 to 2017, using findings from a 2017 study on the global burden of disease (GBD), we assessed the burden of infertility in 195 countries and territories from 1990 to 2017. DisMod-MR 2.1 is a Bayesian meta-regression method that estimates non-fatal outcomes using sparse and heterogeneous epidemiological data. Globally, the age-standardized prevalence rate of infertility increased by 0.370% per year for females and 0.291% per year for males from 1990 to 2017. Additionally, age-standardized disability-adjusted life-years (DALYs) of infertility increased by 0.396% per year for females and 0.293% per year for males during the observational period. An increasing trend to these burden estimates was observed throughout the all socio-demographic index (SDI) countries. Interestingly, we found that high SDI countries had the lowest level of prevalence and DALYs in both genders. However, the largest increasing trend was observed in high-SDI countries for females. By contrast, low-SDI countries had the largest increasing trend in males. Negative associations were observed between these burden estimates and the SDI level. The global disease burden of infertility has been increasing throughout the period from 1990 to 2017.

Objectives: The burden of gout has been increasing globally. However, little is known about the global, regional and national distribution and time trend of this disease. We present a comprehensive analysis of the Global Burden of Disease Study 2017 on gout burden estimates for 195 countries or territories between 1990 and 2017. Methods: Age-standardized prevalence and disability-adjusted life-years of gout were reported between 1990 and 2017 in 195 countries and territories, and associations between these estimates and sociodemographic index (SDI) were further explored. Total and annual percent change between 1990 and 2017 were calculated to quantify the time trends of gout burden. Results: Age-standardized prevalence rates (95% uncertainty interval) per 100 000 persons were 790.90 (706.10–881.90) and 253.49 (225.69–284.02) in 2017 in males and females, respectively. The annual percent change in age-standardized prevalence (males, 0.22%; females, 0.38%) and disability-adjusted life-years (males, 0.21%; females, 0.38%) of gout increased every year from 1990 to 2017, globally. The highest increase was detected in high-SDI countries, especially in high-income North America. A non-linear association was observed between burden of gout and SDI, with the lowest estimates of gout burden when SDI value was about 0.6. High BMI was the leading risk factor for the burden of gout. Conclusion: These study results suggest a globally rising trajectory of gout burden between 1990 and 2017. More effective interventions, such as detailed and intensive dietary managements and other prevention strategies for reducing obesity, should be carried out to reverse this trend, especially in females and high-SDI countries.

In 2005, the FDA cautioned that exposure to paroxetine, a selective serotonin reuptake inhibitor (SSRI), during the first trimester of pregnancy may increase the risk of cardiac malformations. Since then, the association between maternal use of SSRIs during pregnancy and congenital malformations in infants has been the subject of much discussion and controversy. The aim of this study is to systematically review the associations between SSRIs use during early pregnancy and the risk of congenital malformations, with particular attention to the potential confounding by indication. The study protocol was registered with PROSPERO (CRD42018088358). Cohort studies on congenital malformations in infants born to mothers with first-trimester exposure to SSRIs were identified via PubMed, Embase, Web of Science, and the Cochrane Library databases through 17 January 2018. Random-effects models were used to calculate summary relative risks (RRs). Twenty-nine cohort studies including 9,085,954 births were identified. Overall, use of SSRIs was associated with an increased risk of overall major congenital anomalies (MCAs, RR 1.11, 95% CI 1.03 to 1.19) and congenital heart defects (CHD, RR 1.24, 95% CI 1.11 to 1.37). No significantly increased risk was observed when restricted to women with a psychiatric diagnosis (MCAs, RR 1.04, 95% CI 0.95 to 1.13; CHD, RR 1.06, 95% CI 0.90 to 1.26). Similar significant associations were observed using maternal citalopram exposure (MCAs, RR 1.20, 95% CI 1.09 to 1.31; CHD, RR 1.24, 95% CI 1.02 to 1.51), fluoxetine (MCAs, RR 1.17, 95% CI 1.07 to 1.28; CHD, 1.30, 95% CI 1.12 to 1.53), and paroxetine (MCAs, RR 1.18, 95% CI 1.05 to 1.32; CHD, RR 1.17, 95% CI 0.97 to 1.41) and analyses restricted to using women with a psychiatric diagnosis were not statistically significant. Sertraline was associated with septal defects (RR 2.69, 95% CI 1.76 to 4.10), atrial septal defects (RR 2.07, 95% CI 1.26 to 3.39), and respiratory system defects (RR 2.65, 95% CI 1.32 to 5.32). The evidence suggests a generally small risk of congenital malformations and argues against a substantial teratogenic effect of SSRIs. Caution is advisable in making decisions about whether to continue or stop treatment with SSRIs during pregnancy.