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Summary Background Stillbirths are a major public health issue and a sensitive marker of the quality of care around pregnancy and birth. The UN Global Strategy for Women's, Children's and Adolescents’ Health (2016–30) and the Every Newborn Action Plan (led by UNICEF and WHO) call for an end to preventable stillbirths. A first step to prevent stillbirths is obtaining standardised measurement of stillbirth rates across countries. We estimated stillbirth rates and their trends for 195 countries from 2000 to 2019 and assessed progress over time. Methods For a systematic assessment, we created a dataset of 2833 country-year datapoints from 171 countries relevant to stillbirth rates, including data from registration and health information systems, household-based surveys, and population-based studies. After data quality assessment and exclusions, we used 1531 datapoints to estimate country-specific stillbirth rates for 195 countries from 2000 to 2019 using a Bayesian hierarchical temporal sparse regression model, according to a definition of stillbirth of at least 28 weeks’ gestational age. Our model combined covariates with a temporal smoothing process such that estimates were informed by data for country-periods with high quality data, while being based on covariates for country-periods with little or no data on stillbirth rates. Bias and additional uncertainty associated with observations based on alternative stillbirth definitions and source types, and observations that were subject to non-sampling errors, were included in the model. We compared the estimated stillbirth rates and trends to previously reported mortality estimates in children younger than 5 years. Findings Globally in 2019, an estimated 2·0 million babies (90% uncertainty interval [UI] 1·9–2·2) were stillborn at 28 weeks or more of gestation, with a global stillbirth rate of 13·9 stillbirths (90% UI 13·5–15·4) per 1000 total births. Stillbirth rates in 2019 varied widely across regions, from 22·8 stillbirths (19·8–27·7) per 1000 total births in west and central Africa to 2·9 (2·7–3·0) in western Europe. After west and central Africa, eastern and southern Africa and south Asia had the second and third highest stillbirth rates in 2019. The global annual rate of reduction in stillbirth rate was estimated at 2·3% (90% UI 1·7–2·7) from 2000 to 2019, which was lower than the 2·9% (2·5–3·2) annual rate of reduction in neonatal mortality rate (for neonates aged <28 days) and the 4·3% (3·8–4·7) annual rate of reduction in mortality rate among children aged 1–59 months during the same period. Based on the lower bound of the 90% UIs, 114 countries had an estimated decrease in stillbirth rate since 2000, with four countries having a decrease of at least 50·0%, 28 having a decrease of 25·0–49·9%, 50 having a decrease of 10·0–24·9%, and 32 having a decrease of less than 10·0%. For the remaining 81 countries, we found no decrease in stillbirth rate since 2000. Of these countries...

Skeletal muscle is involved in the homeostasis of glucose and lipid metabolism. We hypothesized that the skeletal muscle produces and secretes bioactive factor(s), similar to adipocytokines secreted by fat tissue. Here, we report the identification of a novel secretory factor, musclin, by signal sequence trap of mouse skeletal muscle cDNAs. Musclin cDNA encoded 130 amino acids, including NH 2 -terminal 30-amino acid signal sequence. Musclin protein contained a region homologous to natriuretic peptide family, and KKKR, a putative serine protease cleavage site, similar to the natriuretic peptide family. Full-length musclin protein and KKKR-dependent cleaved form were secreted in media of musclin cDNA-transfected mammalian cell cultures. Musclin mRNA was expressed almost exclusively in the skeletal muscle of mice. Musclin mRNA levels in skeletal muscle were markedly low in fasted, increased upon re-feeding, and were low in streptozotocin-treated insulin-deficient mice. Musclin mRNA expression was induced at late stage in the differentiation of C2C12 myocytes. In myocytes, insulin increased, while epinephrine, isoproterenol, and forskolin reduced musclin mRNA, all of which are known to increase the cellular content of cyclic AMP, a counter-regulator to insulin. Pathologically, overexpression of musclin mRNA was noted in the muscles of obese insulin-resistant KKAy mice. Functionally, recombinant musclin significantly attenuated insulin-stimulated glucose uptake and glycogen synthesis in myocytes. In conclusion, we identified musclin, a novel skeletal muscle-derived secretory factor. Musclin expression level is tightly regulated by nutritional changes and its physiological role could be linked to glucose metabolism.Adipose tissue has been shown to produce secretory factors conceptualized adipocytekines (1, 2).Muscle-specific glucose transporter GLUT4 1 (3) and peroxisome proliferator-activated receptor-␥ (4, 5) knock-out mice exhibited the alterations in insulin sensitivity in fat and liver. Muscle-specific insulin receptor knockout mice showed adipocyte hyperproliferation (6). These findings suggest that the skeletal muscle may release bioactive factors (myokines), like adipocytokines, to target fat, liver, and potentially skeletal muscle itself.In the present study, we attempted to identify skeletal muscle-derived secretory factors using an efficient signal sequence trap (SST) method (7). Here, we report a novel skeletal musclederived secretory factor, musclin, whose mRNA was dynamically regulated by nutrition and hormonal factors. EXPERIMENTAL PROCEDURES Cloning of Mouse Musclin cDNA-Poly(A)ϩ RNAs were extracted from gastrocnemius muscles of 10-week-old male C57BL/6J mice under ad libitum, 24-h fasting or 24-h refeeding after 24-h fasting condition and ad libitum db/db mice. Equal amounts of poly(A) ϩ RNA from each group were pooled to synthesize cDNA. To selectively clone the genes that possess signal sequence at the NH 2 -terminal end of cDNAs, SST-REX system (signal sequence trap by retrovirus-mediated expressio...

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Summary Background The Sustainable Development Goals (SDGs), set in 2015 by the UN General Assembly, call for all countries to reach an under-5 mortality rate (U5MR) of at least as low as 25 deaths per 1000 livebirths and a neonatal mortality rate (NMR) of at least as low as 12 deaths per 1000 livebirths by 2030. We estimated levels and trends in under-5 mortality for 195 countries from 1990 to 2019, and conducted scenario-based projections of the U5MR and NMR from 2020 to 2030 to assess country progress in, and potential for, reaching SDG targets on child survival and the potential under-5 and neonatal deaths over the next decade. Methods Levels and trends in under-5 mortality are based on the UN Inter-agency Group for Child Mortality Estimation (UN IGME) database on under-5 mortality, which contains around 18 000 country-year datapoints for 195 countries—nearly 10 000 of those datapoints since 1990. The database includes nationally representative mortality data from vital registration systems, sample registration systems, population censuses, and household surveys. As with previous sets of national UN IGME estimates, a Bayesian B-spline bias-reduction model (B3) that considers the systematic biases associated with the different data source types was fitted to these data to generate estimates of under-5 (age 0–4 years) mortality with uncertainty intervals for 1990–2019 for all countries. Levels and trends in the neonatal mortality rate (0–27 days) are modelled separately as the log ratio of the neonatal mortality rate to the under-5 mortality rate using a Bayesian model. Estimated mortality rates are combined with livebirths data to calculate the number of under-5 and neonatal deaths. To assess the regional and global burden of under-5 deaths in the present decade and progress towards SDG targets, we constructed several scenario-based projections of under-5 mortality from 2020 to 2030 and estimated national, regional, and global under-5 mortality trends up to 2030 for each scenario. Findings The global U5MR decreased by 59% (90% uncertainty interval [UI] 56–61) from 93·0 (91·7–94·5) deaths per 1000 livebirths in 1990 to 37·7 (36·1–40·8) in 2019, while the annual number of global under-5 deaths declined from 12·5 (12·3–12·7) million in 1990 to 5·2 (5·0–5·6) million in 2019—a 58% (55–60) reduction. The global NMR decreased by 52% (90% UI 48–55) from 36·6 (35·6–37·8) deaths per 1000 livebirths in 1990, to 17·5 (16·6–19·0) in 2019, and the annual number of global neonatal deaths declined from 5·0 (4·9–5·2) million in 1990, to 2·4 (2·3–2·7) million in 2019, a 51% (47–54) reduction. As of 2019, 122 of 195 countries have achieved the SDG U5MR target, and 20 countries are on track to achieve the target by 2030, while 53 will need to accelerate progress to meet the target by 2030. 116 countries have reached the SDG NMR target with 16 on track, leaving 63 at risk of missing the target. If current trends continue, 48·1 million under-5 d...