BACKGROUND-A preliminary safety signal for neural-tube defects was previously reported in association with dolutegravir exposure from the time of conception, which has affected choices of antiretroviral treatment (ART) for human immunodeficiency virus (HIV)-infected women of reproductive potential. The signal can now be evaluated with data from follow-up of additional pregnancies.METHODS-We conducted birth-outcomes surveillance at hospitals throughout Botswana, expanding from 8 to 18 sites in 2018. Trained midwives performed surface examinations of all live-born and stillborn infants. Research assistants photographed abnormalities after maternal consent was obtained. The prevalence of neural-tube defects and major external structural defects according to maternal HIV infection and ART exposure status was determined. In the primary analyses, we used the Newcombe method to evaluate differences in prevalence with 95% confidence intervals. RESULTS-FromAugust 2014 through March 2019, surveillance captured 119,477 deliveries; 119,033 (99.6%) had an infant surface examination that could be evaluated, and 98 neural-tube defects were identified (0.08% of deliveries). Among 1683 deliveries in which the mother was taking dolutegravir at conception, 5 neural-tube defects were found (0.30% of deliveries); the defects included two instances of myelomeningocele, one of anencephaly, one of encephalocele,

Igf2 mRNA binding protein 1 (IMP1, CRD-BP, ZBP-1) is a messenger RNA binding protein that we have shown previously to regulate colorectal cancer (CRC) cell growth in vitro. Furthermore, increased IMP1 expression correlates with enhanced metastasis and poor prognosis in CRC patients. In the current study, we sought to elucidate IMP1-mediated functions in CRC pathogenesis in vivo. Using CRC cell xenografts, we demonstrate that IMP1 overexpression promotes xenograft tumor growth and dissemination into the blood. Furthermore, intestine-specific knockdown of Imp1 dramatically reduces tumor number in the Apc (Min/+) mouse model of intestinal tumorigenesis. In addition, IMP1 knockdown xenografts exhibit a reduced number of tumor cells entering the circulation, suggesting that IMP1 may directly modulate this early metastatic event. We further demonstrate that IMP1 overexpression decreases E-cadherin expression, promotes survival of single tumor cell-derived colonospheres and promotes enrichment and maintenance of a population of CD24+CD44+ cells, signifying that IMP1 overexpressing cells display evidence of loss of epithelial identity and enhancement of a tumor-initiating cell phenotype. Taken together, these findings implicate IMP1 as a modulator of tumor growth and provide evidence for a novel role of IMP1 in early events in CRC metastasis.

This cohort study was designated as not human subjects research by the Mass General Brigham institutional review board because it used anonymous, publicly available data; thus, informed consent was not sought. This study follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines. We compiled weekly SARS-CoV-2 molecular testing data from the Massachusetts Department of Public Health and Boston Public Health Commission for the period May 27 to October 14, 2020, following the initial COVID-19 wave. The Boston Public Health Commission reported tests of unique Boston residents, whereas the Massachusetts Department of Public Health reported total tests, including repeat testing of individuals. Consequently, we performed separate analyses for Massachusetts (351 cities and towns) and for Boston (15 neighborhoods).We defined testing intensity as the number of SARS-CoV-2 tests performed weekly per 100 000 population and epidemic intensity as weekly test positivity. We considered optimal alignment of testing resources to be matching community ranks of testing and positivity. In communities with a testing gap (ie, the testing rank was lower than the positivity rank) in a given week, the gap was calculated as additional testing required to achieve matching ranks. For example, the testing gap for a community with the third highest positivity is the difference between its testing rate and that of the community with the third highest testing intensity.Responses from the American Community Survey (2014-2018) 5 were aggregated to characterize communities. Negative binomial models using robust sandwich estimators to account for repeated measures at the community level were fit to assess associations of the magnitude of the weekly testing gap with time (linearly by week), selected Centers for Disease Control and Prevention Social Vulnerability Index 6 domains (eg, Socioeconomic Status and Minority Status/Language), and large university student population (>10% of residents). Owing to collinearity, the model of Boston neighborhoods only assessed associations with time and socioeconomic vulnerability. Two-sided Wald tests were used to assess significance at a threshold of P < .05. Data analysis was performed using R statistical software version 3.6.1 (R Project for Statistical Computing). ResultsDuring the observation period, 4 262 000 tests were reported. COVID-19 incidence (median [range], 339 [0-6670] cases per 100 000) and testing intensity (median [range], 41 000 [5350-274 000] tests per 100 000) varied considerably between communities, with observed increased testing in Author affiliations and article information are listed at the end of this article.

Background: Recent data suggests clinically significant weight gain among non-pregnant HIV-positive adults after starting dolutegravir-based ART (DTG). Excess or insufficient weight gain in pregnancy could adversely impact pregnancy outcomes, but data for pregnant women receiving DTG are limited. Methods: The Tsepamo Study captured data at delivery sites in Botswana from 2014 to 2019. HIV testing, HIV treatment information, and weight measurements during antenatal care were abstracted from the maternity obstetric record at delivery. HIV-positive women initiating DTG or efavirenz-based ART (EFV) between conception and 17 weeks gestation and HIV-uninfected women first presenting for antenatal care before 17 weeks gestation were included. We evaluated weekly weight gain, total 18-week weight gain, excess weight gain (>0.59 kg/week), insufficient weight gain (<0.18 kg/week), and weight loss between 18 §2 and 36 §2 weeks gestation, adjusting for demographic and clinical variables. Findings: Baseline characteristics were similar by exposure group, including pre-pregnancy and early pregnancy weight. Compared with EFV, mean weekly weight gain between 18 and 36 weeks gestation was 0.05 (95% CI 0.03, 0.07) kg/week higher for women initiating DTG and 0.12 (0.10, 0.14) kg/week higher for HIVuninfected women. Mean 18-week weight gain was 1.05 (95% CI 0.61, 1.49) kg higher for women initiating DTG and 2.31 (1.85, 2.77) kg higher for HIV-uninfected women, compared with EFV. Women initiating DTG were more likely to gain excess weight but less likely to gain insufficient weight or lose weight than women initiating EFV. Interpretation: Women initiating DTG compared with EFV during pregnancy gained more weight between 18 and 36 weeks gestation. Neither group gained as much weight as HIV-uninfected women. Initiating DTG compared with EFV during pregnancy could increase the risk of excess weight gain but decrease the risk of insufficient weight gain and weight loss, which could have positive and negative consequences in pregnancy. Our findings are consistent with prior studies in non-pregnant adults.