Preterm birth is a global health priority. Using a progestogen during high-risk pregnancy could reduce preterm birth and adverse neonatal outcomes.
We did a systematic review of randomised trials ...comparing vaginal progesterone, intramuscular 17-hydroxyprogesterone caproate (17-OHPC), or oral progesterone with control, or with each other, in asymptomatic women at risk of preterm birth. We identified published and unpublished trials that completed primary data collection before July 30, 2016, (12 months before data collection began), by searching MEDLINE, Embase, CINAHL, the Maternity and Infant Care Database, and relevant trial registers between inception and July 30, 2019. Trials of progestogen to prevent early miscarriage or immediately-threatened preterm birth were excluded. Individual participant data were requested from investigators of eligible trials. Outcomes included preterm birth, early preterm birth, and mid-trimester birth. Adverse neonatal sequelae associated with early births were assessed using a composite of serious neonatal complications, and individually. Adverse maternal outcomes were investigated as a composite and individually. Individual participant data were checked and risk of bias assessed independently by two researchers. Primary meta-analyses used one-stage generalised linear mixed models that incorporated random effects to allow for heterogeneity across trials. This meta-analysis is registered with PROSPERO, CRD42017068299.
Initial searches identified 47 eligible trials. Individual participant data were available for 30 of these trials. An additional trial was later included in a targeted update. Data were therefore available from a total of 31 trials (11 644 women and 16185 offspring). Trials in singleton pregnancies included mostly women with previous spontaneous preterm birth or short cervix. Preterm birth before 34 weeks was reduced in such women who received vaginal progesterone (nine trials, 3769 women; relative risk RR 0·78, 95% CI 0·68–0·90), 17-OHPC (five trials, 3053 women; 0·83, 0·68–1·01), and oral progesterone (two trials, 183 women; 0·60, 0·41–0·90). Results for other birth and neonatal outcomes were consistently favourable, but less certain. A possible increase in maternal complications was suggested, but this was uncertain. We identified no consistent evidence of treatment interaction with any participant characteristics examined, although analyses within subpopulations questioned efficacy in women who did not have a short cervix. Trials in multifetal pregnancies mostly included women without additional risk factors. For twins, vaginal progesterone did not reduce preterm birth before 34 weeks (eight trials, 2046 women: RR 1·01, 95% CI 0·84–1·20) nor did 17-OHPC for twins or triplets (eight trials, 2253 women: 1·04, 0·92–1·18). Preterm premature rupture of membranes was increased with 17-OHPC exposure in multifetal gestations (rupture <34 weeks RR 1·59, 95% CI 1·15–2·22), but we found no consistent evidence of benefit or harm for other outcomes with either vaginal progesterone or 17-OHPC.
Vaginal progesterone and 17-OHPC both reduced birth before 34 weeks' gestation in high-risk singleton pregnancies. Given increased underlying risk, absolute risk reduction is greater for women with a short cervix, hence treatment might be most useful for these women. Evidence for oral progesterone is insufficient to support its use. Shared decision making with woman with high-risk singleton pregnancies should discuss an individual's risk, potential benefits, harms and practicalities of intervention. Treatment of unselected multifetal pregnancies with a progestogen is not supported by the evidence.
Patient-Centered Outcomes Research Institute.
ABSTRACT
In this column, the author describes the vaginal birth of her twin daughters. Despite impending complications in the last weeks of her pregnancy that might have required a cesarean, this ...mother was committed to doing everything possible to give birth naturally. With the support of her husband as well as the obstetrician and the nurse, she was able to give birth to her daughters vaginally.
Cable bacteria are centimeter-long filamentous bacteria that conduct electrons via internal wires, thus coupling sulfide oxidation in deeper, anoxic sediment with oxygen reduction in surface ...sediment. This activity induces geochemical changes in the sediment, and other bacterial groups appear to benefit from the electrical connection to oxygen. Here, we report that diverse bacteria swim in a tight flock around the anoxic part of oxygen-respiring cable bacteria and disperse immediately when the connection to oxygen is disrupted (by cutting the cable bacteria with a laser). Raman microscopy shows that flocking bacteria are more oxidized when closer to the cable bacteria, but physical contact seems to be rare and brief, which suggests potential transfer of electrons via unidentified soluble intermediates. Metagenomic analysis indicates that most of the flocking bacteria appear to be aerobes, including organotrophs, sulfide oxidizers, and possibly iron oxidizers, which might transfer electrons to cable bacteria for respiration. The association and close interaction with such diverse partners might explain how oxygen via cable bacteria can affect microbial communities and processes far into anoxic environments.
Research suggests that economic declines contribute to mortality risks from suicide and drug poisoning, but how the economy impacts individuals’ risks of these deaths has been challenging to specify. ...Building on recent theoretical advances, we investigate how adolescent occupational expectations and preparation contribute to suicide and drug poisoning deaths in a shifting economy. We use High School and Beyond data linked to adult mortality records for men that were exposed to a decline in labor market share and wages in predominantly blue-collar occupations during early adulthood. We find that adolescent men who expected these occupations had increased risks of suicide and drug poisoning death as adults net of educational and occupational attainment in early adulthood. Family background and occupational preparation are risk factors for death by drug poisoning but not suicide. Our findings improve our understanding of how labor market uncertainty shapes individuals’ vulnerability to suicide and drug poisoning death.
Breast tumors are inherently heterogeneous, but the evolving cellular organization through neoplastic progression is poorly understood. Here we report a rapid, large-scale single-cell resolution 3D ...imaging protocol based on a one-step clearing agent that allows visualization of normal tissue architecture and entire tumors at cellular resolution. Imaging of multicolor lineage-tracing models of breast cancer targeted to either basal or luminal progenitor cells revealed profound clonal restriction during progression. Expression profiling of clones arising in Pten/Trp53-deficient tumors identified distinct molecular signatures. Strikingly, most clones harbored cells that had undergone an epithelial-to-mesenchymal transition, indicating widespread, inherent plasticity. Hence, an integrative pipeline that combines lineage tracing, 3D imaging, and clonal RNA sequencing technologies offers a comprehensive path for studying mechanisms underlying heterogeneity in whole tumors.
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•A single-step, non-toxic clearing agent for 3D imaging of whole organs and tumors•Derivation of an integrative platform to interrogate intratumoral heterogeneity•Profound clonal restriction occurs during neoplastic progression•The epithelial-mesenchymal transition occurs clonally as a frequent event
Rios et al. develop a rapid, large-scale single-cell resolution 3D imaging protocol and use the protocol together with RNA sequencing to explore the cellular dynamics of mammary tumorigenesis and show that a molecular epithelial-to-mesenchymal transition is a prominent feature of tumor clones.
The mammalian sex chromosomes harbor an abundance of newly acquired ampliconic genes, although their functions require elucidation 1–9. Here, we demonstrate that the X-linked Slx and Slxl1 ampliconic ...gene families represent mouse-specific neofunctionalized copies of a meiotic synaptonemal complex protein, Sycp3. In contrast to the meiotic role of Sycp3, CRISPR-loxP-mediated multi-megabase deletions of the Slx (5 Mb) and Slxl1 (2.3Mb) ampliconic regions result in post-meiotic defects, abnormal sperm, and male infertility. Males carrying Slxl1 deletions sire more male offspring, whereas males carrying Slx and Slxl1 duplications sire more female offspring, which directly correlates with Slxl1 gene dosage and gene expression levels. SLX and SLXL1 proteins interact with spindlin protein family members (SPIN1 and SSTY1/2) and males carrying Slxl1 deletions downregulate a sex chromatin modifier, Scml2, leading us to speculate that Slx and Slxl1 function in chromatin regulation. Our study demonstrates how newly acquired X-linked genes can rapidly evolve new and essential functions and how gene amplification can increase sex chromosome transmission.
•Slx and Slxl1 are mouse lineage-specific copies of their autosomal progenitor Sycp3•Slx and Slxl1 gene families are essential for male fertility•Changes in Slxl1 gene copy number distorts the ratio of male to female offspring•Slxl1 versus Sly competition for spindlin proteins may mediate sex-ratio distortion
A common assumption is that genes essential to a species survival must be deeply conserved. Kruger et al. report how two newly acquired X-linked gene families, Slx and Slxl1, evolved from an autosomal single-copy gene, massively duplicated, became essential for male fertility, and mediated the sex ratio of offspring by gene copy-number changes.
Indoor residual spraying (IRS) is an important part of malaria control. There is a growing list of insecticide classes; pyrethroids remain the principal insecticide used in bednets but recently, ...novel non-pyrethroid IRS products, with contrasting impacts, have been introduced. There is an urgent need to better assess product efficacy to help decision makers choose effective and relevant tools for mosquito control. Here we use experimental hut trial data to characterise the entomological efficacy of widely-used, novel IRS insecticides. We quantify their impact against pyrethroid-resistant mosquitoes and use a Plasmodium falciparum transmission model to predict the public health impact of different IRS insecticides. We report that long-lasting IRS formulations substantially reduce malaria, though their benefit over cheaper, shorter-lived formulations depends on local factors including bednet use, seasonality, endemicity and pyrethroid resistance status of local mosquito populations. We provide a framework to help decision makers evaluate IRS product effectiveness.
Atopic eczema (AE) is an inflammatory skin disorder affecting approximately 20% of children worldwide and early onset can lead to asthma and allergies. Currently, the mechanisms of the disease are ...not fully understood. Metabolomics, the analysis of small molecules in the skin produced by the host and microbes, opens a window to observe the mechanisms of the disease which then may lead to new drug targets for AE treatment. Here, we review the latest advances in AE metabolomics, highlighting both the lipid and non-lipid molecules, along with reviewing the metabolites currently known to reside in the skin.
Deaths from self-injury are increasing. Understanding the sources of risk is important for prevention and treatment.
To estimate the risks of suicide and drug poisoning deaths among adult men whose ...adolescent occupational expectations were not met in adulthood.
This cohort study included a sample of men interviewed as part of the High School and Beyond study, a nationally representative study of US high school sophomores and seniors in 1980, who were interviewed every 2 years through 1986; those who were sophomores in 1980 were reinterviewed in 1992. Men who survived to 1992 and reported occupational expectations were included in the present study. Death records prior to 2018 were linked to mortality databases and released in 2019. Data analysis was conducted from May to October 2020.
Occupational expectations.
Survival or death by suicide, drug poisoning, chronic liver disease, heart disease, cancer, or some other cause, categorized from International Classification of Diseases, Ninth Revision and Tenth Revision codes. Competing risk Fine-Gray survival models regressed cause of death on adolescent occupational expectations and covariates.
The 11 680 men in the High School and Beyond cohort study had a median (interquartile range) age of 29 (28-30) years in 1992, when the analysis of their future mortality began. Most men survived until 2015 (11 060 weighted percentage, 95.0%). Reported causes of death were suicide (60 weighted percentage, 0.5%), drug poisoning (40 weighted percentage, 0.4%), chronic liver disease (20 weighted percentage, 0.2%), heart disease (130 weighted percentage, 1.0%), cancer (100 weighted percentage, 1.0%), and other (280 weighted percentage, 2.0%). Subhazard ratios for death by suicide and drug poisoning were 2.91 (95% CI, 1.07-7.88; P = .04) and 2.62 (95% CI, 1.15-5.94; P = .02) times higher, respectively, among those who in 1980 expected to hold a subbaccalaureate occupation that later declined in labor market share compared with those with professional occupational expectations. The actual job held by men did not attenuate the hazards of deaths from suicide and drug poisoning.
In this cohort study, men whose occupational expectations were not met because of labor market declines were at a higher risk of death from suicide or drug poisoning than men with different occupational expectations. Interventions to mitigate labor market changes should account for individuals' expectational ideals.
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