Lead and cadmium are known to be potential female reproductive toxins. However, studies on the relationship between these metals and infertility are limited. This study examines the association between self-reported infertility and blood lead and cadmium levels in US women by comparing metal levels in infertile and pregnant women. Data on blood lead, blood cadmium, and infertility from women aged 20–39 years who participated in the 2013–2014 and 2015–2016 National Health and Nutrition Examination Surveys were analyzed (n = 124, ‘pregnant’ n = 42, ‘infertile’ n = 82). Blood lead and cadmium levels were measured using inductively coupled plasma mass spectrometry, and infertility and pregnancy status were assessed using a self-reported questionnaire. Low blood lead and cadmium levels (geometric mean of blood lead = 0.50 µg/dL and blood cadmium = 0.26 µg/L) were positively associated with self-reported infertility after adjusting for confounding effects (odds ratio (OR) for lead per two-fold increase in blood metal levels = 2.60; 95% confidence interval (95% CI), 1.05–6.41 and OR for cadmium per two-fold increase = 1.84; 95% CI, 1.07–3.15). Although our findings require confirmation, they suggest that even low blood cadmium and lead levels may be deleterious to female fecundity.

Background & Aims Activin, a member of the transforming growth factor-β (TGFB) family, might be involved in pancreatic tumorigenesis, like other members of the TGFB family. Human pancreatic ductal adenocarcinomas contain somatic mutations in the activin A receptor type IB (ACVR1B) gene, indicating that ACVR1B could be a suppressor of pancreatic tumorigenesis. Methods We disrupted Acvr1b specifically in pancreata of mice (Acvr1bflox/flox;Pdx1-Cre mice) and crossed them with LSL-KRASG12D mice, which express an activated form of KRAS and develop spontaneous pancreatic tumors. The resulting Acvr1bflox/flox;LSL-KRASG12D;Pdx1-Cre mice were monitored; pancreatic tissues were collected and analyzed by histology and immunohistochemical analyses. We also analyzed p16flox/flox;LSL-KrasG12D;Pdx1-Cre mice and Cre-negative littermates (controls). Genomic DNA, total RNA, and protein were isolated from mouse tissues and primary pancreatic tumor cell lines and analyzed by reverse transcriptase PCR, sequencing, and immunoblot analyses. Human intraductal papillary mucinous neoplasm (IPMN) specimens were analyzed by immunohistochemistry. Results Loss of ACVR1B from pancreata of mice increased proliferation of pancreatic epithelial cells, led to formation of acinar to ductal metaplasia, and induced focal inflammatory changes, compared with control mice. Disruption of Acvr1b in LSL-KRASG12D; Pdx1-Cre mice accelerated growth of pancreatic IPMNs, compared with LSL-KRASG12D;Pdx1-Cre mice, but did not alter growth of pancreatic intraepithelial neoplasias. We associated perinuclear localization of the activated NOTCH4 intracellular domain to the apical cytoplasm of neoplastic cells and with expansion of IPMN lesions in Acvr1bflox/flox;LSL-KRASG12D;Pdx1-Cre mice. Loss of the gene that encodes p16 (Cdkn2a) was required for progression of IPMNs to pancreatic ductal adenocarcinomas in Acvr1bflox/flox;LSL-KrasG12D;Pdx1-Cre mice. We also observed progressive loss of p16 in human IPMNs of increasing grades. Conclusion Loss of ACVR1B accelerates growth of mutant KRAS-induced pancreatic IPMNs in mice; this process appears to involve NOTCH4 and loss of p16. ACVR1B suppresses early stages of pancreatic tumorigenesis; the activin signaling pathway might therefor be a therapeutic target for pancreatic cancer.

Background Complete contact tracing of COVID-19 patients in Korea allows a unique opportunity to investigate cluster characteristics. This study aimed to investigate all the reported COVID-19 clusters in Seoul Metropolitan area from January 23 to September 24, 2020. Methods Publicly available COVID-19 data was collected from the Seoul Metropolitan city and Gyeonggi Province. Community clusters with ≥ 5 cases were characterized by size and duration and then categorized using K-means clustering, and the correlation between the types of clusters and the level of social distancing was investigated. Results A total of 134 clusters including 4,033 cases were identified. The clusters were categorized into small (Type I, II), medium (type III), and large (type IV) clusters. With the same number of daily confirmed cases, cases were composed of different types of clusters by different periods of time. Raising social distancing was related with shifting types of clusters from large to small sized clusters. Conclusions Classification of clusters may provide opportunities to better portray the pattern of COVID-19 outbreaks and implement more effective strategies. Social distancing administered by the government may be effective in suppressing large clusters but may not be effective in controlling small and sporadic clusters.

Objectives: During the coronavirus disease (COVID-19) pandemic, crude incidence and mortality rates have been widely reported; however, age-standardized rates are more suitable for comparison. In this study, we estimated and compared the age-standardized incidence, mortality, and case fatality rates among countries and investigated the relationship between these rates and factors associated with healthcare resources: gross domestic product per capita, number of hospital beds per population, and number of doctors per population. Methods:The incidence, mortality, and case fatality rates of 79 countries were age-standardized using the WHO standard population. The rates for persons 60 years or older were also calculated. The relationships among the rates were analysed using trend lines and coefficients of determination (R 2 ). The Pearson's correlation coefficients between the rates and the healthcare resource-related factors were calculated. Results:The countries with the highest age-standardized incidence, mortality, and case fatality rates were Czechia (14,253 cases/100,000), Mexico (182 deaths/100,000), and Mexico (6.7%), respectively. The R 2 between the incidence and mortality rates was 0.8520 for all ages and 0.9452 for those 60 years or older. The healthcare resources-related factors were associated positively with incidence rates, and negatively with case fatality rates: the correlations were weaker among the elderly.Conclusions: Compared to age-standardized rates, crude rates showed greater variation between countries. Medical resources may be important in preventing COVID-19-related deaths; however, considering the small variation in fatality among the elderly, prevention such as vaccination is more important especially for the elderly population to minimize the mortality rates in the elderly population.

The relationship between caffeine and insulin resistance (IR) has been assessed only in terms of caffeine intake, and the association between caffeine and beta cell function (BCF) remains unclear. This study examines the association between urinary caffeine and its metabolites, IR, and BCF in nondiabetic, noninstitutionalized US adults in order to account for the inter-individual differences in caffeine metabolism. Data on urinary caffeine and its metabolites, IR and BCF from adults aged 20 years and older who participated in the 2009–2010 and 2011–2012 National Health and Nutrition Examination Surveys were analyzed (n for caffeine = 994). IR and BCF were assessed using homeostatic model assessment (HOMA) and urinary caffeine and its metabolites were measured using high-performance liquid chromatography-electrospray ionization-tandem quadrupole mass spectrometry. After adjusting for all covariates, increases in urinary 1,3-DMU, 1,7-DMU, 1,3,7-TMU, theophylline, paraxanthine, caffeine, and AAMU were significantly associated with increased HOMA-IR and HOMA-β (HOMA of insulin resistance and beta cell function). Compared with individuals in the lowest quartile of urinary 1,3-DMU, 1,7-DMU, 1,3,7-TMU, theophylline, paraxanthine, caffeine, and AAMU, the regression coefficients for HOMA-IR and HOMA-β were significantly higher among those in the highest quartile. After stratification by prediabetes status, HOMA-IR and HOMA-β showed significant positive associations with urinary caffeine and its metabolites among subjects with normal fasting plasma glucose levels. Our cross-sectional study showed that caffeine and its metabolites were positively related to IR and BCF.