Maternal smoking causes lower birth weight, birth defects, and other adverse pregnancy outcomes. Epidemiological evidence over the past four decades has grown stronger and the adverse outcomes ...attributed to maternal smoking and secondhand smoke exposure have expanded. This review presents findings of latent and persistent metabolic effects in offspring of smoking mothers like those observed in studies of maternal undernutrition during pregnancy. The phenotype of offspring of smoking mothers is like that associated with maternal undernutrition. Born smaller than offspring of nonsmokers, these children have increased risk of being overweight or obese later. Plausible mechanisms include in utero hypoxia, nicotine‐induced reductions in uteroplacental blood flow, placental toxicity, or toxic growth restriction from the many toxicants in tobacco smoke. Studies have reported increased risk of insulin resistance, type 2 diabetes and hypertension although the evidence here is weaker than for overweight/obesity. Altered DNA methylation has been consistently documented in smoking mothers' offspring, and these epigenetic alterations are extensive and postnatally durable. A causal link between altered DNA methylation and the phenotypic changes observed in offspring remains to be firmly established, yet the association is strong, and mediation analyses suggest a causal link. Studies examining expression patterns of affected genes during childhood development and associated health outcomes should be instructive in this regard. The adverse effects of exposure to tobacco smoke during pregnancy now clearly include permanent metabolic derangements in offspring that can adversely affect life‐long health.
Tobacco and pregnancy Rogers, John M.
Reproductive toxicology (Elmsford, N.Y.),
09/2009, Letnik:
28, Številka:
2
Journal Article, Conference Proceeding
Recenzirano
This paper will review the epidemiology of the impact of cigarette smoking and other forms of tobacco exposure on human development. Sources of exposure described include cigarettes and other forms ...of smoked tobacco, secondhand (environmental) tobacco smoke, several forms of smokeless tobacco, and nicotine from nicotine replacement therapy. Exposure is immense and worldwide, most of it due to smoking, but in some parts of the world and in some populations, smoking is exceeded by smokeless tobacco use. Nicotine and carbon monoxide exposure are of large concern, but cigarette smoke contains over 4000 chemical constituents and additives including known carcinogens, toxic heavy metals, and many chemicals untested for developmental toxicity. The impact of tobacco on human development will be reviewed. Fertility, conception, survival of the conceptus, most phases and aspects of development studied to date, as well as postnatal survival and health are adversely impacted by maternal tobacco use or exposure. Effects in surviving offspring are probably life-long, and are still being elucidated. It is hoped that this review will serve to keep a focus on the critical and continuing problem of tobacco use impacting human development.
Objective To investigate the efficacy and safety of alpha blockers in the treatment of patients with ureteric stones.Design Systematic review and meta-analysis.Data sources Cochrane Central Register ...of Controlled Trials, Web of Science, Embase, LILACS, and Medline databases and scientific meeting abstracts to July 2016.Review methods Randomized controlled trials of alpha blockers compared with placebo or control for treatment of ureteric stones were eligible.Two team members independently extracted data from each included study. The primary outcome was the proportion of patients who passed their stone. Secondary outcomes were the time to passage; the number of pain episodes; and the proportions of patients who underwent surgery, required admission to hospital, and experienced an adverse event. Pooled risk ratios and 95% confidence intervals were calculated for the primary outcome with profile likelihood random effects models. Cochrane Collaboration’s tool for assessing risk of bias and the GRADE approach were used to evaluate the quality of evidence and summarize conclusions.Results 55 randomized controlled trials were included. There was moderate quality evidence that alpha blockers facilitate passage of ureteric stones (risk ratio 1.49, 95% confidence interval 1.39 to 1.61). Based on a priori subgroup analysis, there seemed to be no benefit to treatment with alpha blocker among patients with smaller ureteric stones (1.19, 1.00 to 1.48). Patients with larger stones treated with an alpha blocker, however, had a 57% higher risk of stone passage compared with controls (1.57, 1.17 to 2.27). The effect of alpha blockers was independent of stone location (1.48 (1.05 to 2.10) for upper or middle stones; 1.49 (1.38 to 1.63) for lower stones). Compared with controls, patients who received alpha blockers had significantly shorter times to stone passage (mean difference −3.79 days, −4.45 to −3.14; moderate quality evidence), fewer episodes of pain (−0.74 episodes, −1.28 to −0.21; low quality evidence), lower risks of surgical intervention (risk ratio 0.44, 0.37 to 0.52; moderate quality evidence), and lower risks of admission to hospital (0.37, 0.22 to 0.64; moderate quality evidence). The risk of a serious adverse event was similar between treatment and control groups (1.49, 0.24 to 9.35; low quality evidence).Conclusions Alpha blockers seem efficacious in the treatment of patients with ureteric stones who are amenable to conservative management. The greatest benefit might be among those with larger stones. These results support current guideline recommendations advocating a role for alpha blockers in patients with ureteric stones.Systematic review registration PROSPERO registration No CRD42015024169.
Here, we utilized spontaneous models of pancreatic and lung cancer to examine how neoantigenicity shapes tumor immunity and progression. As expected, neoantigen expression during lung adenocarcinoma ...development leads to T cell-mediated immunity and disease restraint. By contrast, neoantigen expression in pancreatic ductal adenocarcinoma (PDAC) results in exacerbation of a fibro-inflammatory microenvironment that drives disease progression and metastasis. Pathogenic TH17 responses are responsible for this neoantigen-induced tumor progression in PDAC. Underlying these divergent T cell responses in pancreas and lung cancer are differences in infiltrating conventional dendritic cells (cDCs). Overcoming cDC deficiency in early-stage PDAC leads to disease restraint, while restoration of cDC function in advanced PDAC restores tumor-restraining immunity and enhances responsiveness to radiation therapy.
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•Neoantigen expression elicits pathogenic T cell response accelerating PDAC•cDC dysfunction precludes early TH1 and CTL response to PDAC neoantigens•Increasing cDCs in early PDAC lesions restores anti-tumor T cell immunity•Restoring cDC function in advanced PDAC improves efficacy of radiation therapy
Hegde et al. identify divergent T cell responses in lung cancer and pancreatic ductal adenocarcinoma (PDAC) caused by differences in conventional dendritic cell (cDC) infiltration. Mobilization of cDCs in PDAC models enhances CD8+ T cell and TH1 activity to reduce tumor growth and increase response to therapy.
Germline JAK1 gain-of-function mutations cause autosomal dominant immune dysregulation and hypereosinophilia with eosinophilic infiltration of the gastrointestinal tract, massive hepatosplenomegaly ...and severe atopic dermatitis that can be successfully treated with ruxolitinib, an oral JAK1/2 inhibitor.
The short-term (0–3 h) prediction of solar insolation for renewable energy production is a problem well-suited to satellite-based techniques. The spatial, spectral, temporal and radiometric ...resolution of instrumentation hosted on the geostationary platform allows these satellites to describe the current cloud spatial distribution and optical properties. These properties relate directly to the transient properties of the downwelling solar irradiance at the surface, which come in the form of ‘ramps’ that pose a central challenge to energy load balancing in a spatially distributed network of solar farms. The short-term evolution of the cloud field may be approximated to first order simply as translational, but care must be taken in how the advection is handled and where the impacts are assigned. In this research, we describe how geostationary satellite observations are used with operational cloud masking and retrieval algorithms, wind field data from Numerical Weather Prediction (NWP), and radiative transfer calculations to produce short-term forecasts of solar insolation for applications in solar power generation. The scheme utilizes retrieved cloud properties to group pixels into contiguous cloud objects whose future positions are predicted using four-dimensional (space + time) model wind fields, selecting steering levels corresponding to the cloud height properties of each cloud group. The shadows associated with these clouds are adjusted for sensor viewing parallax displacement and combined with solar geometry and terrain height to determine the actual location of cloud shadows. For mid/high-level clouds at mid-latitudes and high solar zenith angles, the combined displacements from these geometric considerations are non-negligible. The cloud information is used to initialize a radiative transfer model that computes the direct and diffuse-sky solar insolation at both shadow locations and intervening clear-sky regions. Here, we describe the formulation of the algorithm and validate its performance against Surface Radiation (SURFRAD; Augustine et al., 2000, 2005) network observations. Typical errors range from 8.5% to 17.2% depending on the complexity of cloud regimes, and an operational demonstration outperformed persistence-based forecasting of Global Horizontal Irradiance (GHI) under all conditions by ∼10 W/m2.
Opitz-Kaveggia syndrome (also known as FG syndrome) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation. We report here that the original ...family for whom the condition is named and five other families have a recurrent mutation (2881C>T, leading to R961W) in MED12 (also called TRAP230 or HOPA), a gene located at Xq13 that functions as a thyroid receptor-associated protein in the Mediator complex.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background The value of narrow-band imaging (NBI) for detecting serrated lesions is unknown. Objective To assess NBI for the detection of proximal colon serrated lesions. Design Randomized, ...controlled trial. Setting Two academic hospital outpatient units. Patients Eight hundred outpatients 50 years of age and older with intact colons undergoing routine screening, surveillance, or diagnostic examinations. Interventions Randomization to colon inspection in NBI versus white-light colonoscopy. Main Outcome Measurements The number of serrated lesions (sessile serrated polyps plus hyperplastic polyps) proximal to the sigmoid colon. Results The mean inspection times for the whole colon and proximal colon were the same for the NBI and white-light groups. There were 204 proximal colon lesions in the NBI group and 158 in the white light group ( P = .085). Detection of conventional adenomas was comparable in the 2 groups. Limitations Lack of blinding, endoscopic estimation of polyp location. Conclusion NBI may increase the detection of proximal colon serrated lesions, but the result in this trial did not reach significance. Additional study of this issue is warranted. (Clinical trial registration number: NCT01572428 .)
Summary Background Seafood is the predominant source of omega-3 fatty acids, which are essential for optimum neural development. However, in the USA, women are advised to limit their seafood intake ...during pregnancy to 340 g per week. We used the Avon Longitudinal Study of Parents and Children (ALSPAC) to assess the possible benefits and hazards to a child's development of different levels of maternal seafood intake during pregnancy. Methods 11 875 pregnant women completed a food frequency questionnaire assessing seafood consumption at 32 weeks' gestation. Multivariable logistic regression models including 28 potential confounders assessing social disadvantage, perinatal, and dietary items were used to compare developmental, behavioural, and cognitive outcomes of the children from age 6 months to 8 years in women consuming none, some (1–340 g per week), and >340 g per week. Findings After adjustment, maternal seafood intake during pregnancy of less than 340 g per week was associated with increased risk of their children being in the lowest quartile for verbal intelligence quotient (IQ) (no seafood consumption, odds ratio OR 1·48, 95% CI 1·16–1·90; some, 1·09, 0·92–1·29; overall trend, p=0·004), compared with mothers who consumed more than 340 g per week. Low maternal seafood intake was also associated with increased risk of suboptimum outcomes for prosocial behaviour, fine motor, communication, and social development scores. For each outcome measure, the lower the intake of seafood during pregnancy, the higher the risk of suboptimum developmental outcome. Interpretation Maternal seafood consumption of less than 340 g per week in pregnancy did not protect children from adverse outcomes; rather, we recorded beneficial effects on child development with maternal seafood intakes of more than 340 g per week, suggesting that advice to limit seafood consumption could actually be detrimental. These results show that risks from the loss of nutrients were greater than the risks of harm from exposure to trace contaminants in 340 g seafood eaten weekly.
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