Vaginal type-II mucosa acts as an inductive site for the generation of primary CD8+ T cell mucosal immune responses

It is widely believed that primary immune T cell induction in type-II mucosa (found in vagina, glans penis & esophagus) occurs only in the draining lymph nodes (DLNs) due to a lack of mucosa-associated lymphoid tissue (MALT)

Hand preference develops across childhood and adolescence in extremely preterm children: The EPICure Study

AimWe attempted to determine how handedness changes with age and its relation to brain injury and cognition following birth before 26 weeks of gestation.MethodsWe used data from the EPICure study of health and development following birth in the British Isles in 1995. Handedness was determined by direct observation during standardized testing at age 2.5, six, and 11 years and by self-report using the Edinburgh Handedness Inventory at 19 years. Control data from term births were included at six, 11, and 19 years.ResultsIn extremely preterm children left handedness increased from 9% to 27% between 2.5 and 19 years, with a progressive reduction in mixed handedness from 59% to 13%. Although individual handedness scores varied over childhood, the between-group effects were consistent through 19 years, with greatest differences in females. In extremely preterm participants, neonatal brain injury was associated with lower right handedness scores at each age and left-handed participants had lower cognitive scores at 19 years after controlling for confounders, but not at other ages.ConclusionIncreasing hand lateralization is seen over childhood in extremely preterm survivors, but consistently more individuals have non-right preferences at each age than control individuals.</div

STRIDER NZAus: A multicentre randomised controlled trial of sildenafil therapy in early-onset fetal growth restriction.

OBJECTIVE: To assess the effect of maternal sildenafil therapy on fetal growth in pregnancies with early-onset fetal growth restriction. DESIGN: A randomised placebo-controlled trial. SETTING: Thirteen maternal-fetal medicine units across New Zealand and Australia. POPULATION: Women with singleton pregnancies affected by fetal growth restriction at 22+0 to 29+6 weeks. METHODS: Women were randomised to oral 25mg sildenafil citrate or visually matching placebo three times daily until 32+0 weeks, birth or fetal death (whichever occurred first). MAIN OUTCOME MEASURES: The primary outcome was the proportion of pregnancies with an increase in fetal growth velocity. Secondary outcomes included livebirth, survival to hospital discharge free of major neonatal morbidity and preeclampsia. RESULTS: Sildenafil did not affect the proportion of pregnancies with an increase in fetal growth velocity; 32/61 (52.5%) sildenafil-treated 39/57 (68.4%) placebo-treated, adjusted OR 0.49, 95% CI 0.23-1.05 and had no effect on abdominal circumference Z-scores (p=0.61). Sildenafil use was associated with a lower mean uterine pulsatility index after 48 hours treatment (1.56 vs 1.81 p=0.02). The livebirth rate was 56/63 (88.9%) sildenafil-treated 47/59 (79.7%) placebo-treated, adjusted OR 2.50 (95%CI 0.80-7.79); survival to hospital discharge free of major neonatal morbidity was 42/63 (66.7%) sildenafil-treated 33/59 (55.9%) placebo-treated, adjusted OR 1.93 (0.84-4.45); and new-onset preeclampsia was 9/51 (17.7%) sildenafil-treated and 14/55 (25.5%) placebo-treated, OR 0.67 (95%CI 0.26-1.75). CONCLUSIONS: Maternal sildenafil use had no effect on fetal growth velocity. Prospectively planned meta-analyses will determine whether sildenafil exerts other effects on maternal and fetal/neonatal wellbeing

Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial

Background Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. Methods In this multicentre, open-label, randomised controlled trial, we recruited women aged 18–40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. Findings Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference −0·19%; 95% CI −0·34 to −0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). Interpretation Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use