Timely symbiosis: circadian control of legume-rhizobia symbiosis.

Legumes house nitrogen-fixing endosymbiotic rhizobia in specialised polyploid cells within root nodules. This results in a mutualistic relationship whereby the plant host receives fixed nitrogen from the bacteria in exchange for dicarboxylic acids. This plant-microbe interaction requires the regulation of multiple metabolic and physiological processes in both the host and symbiont in order to achieve highly efficient symbiosis. Recent studies have showed that the success of symbiosis is influenced by the circadian clock of the plant host. Medicago and soybean plants with altered clock mechanisms showed compromised nodulation and reduced plant growth. Furthermore, transcriptomic analyses revealed that multiple genes with key roles in recruitment of rhizobia to plant roots, infection and nodule development were under circadian control, suggesting that appropriate timing of expression of these genes may be important for nodulation. There is also evidence for rhythmic gene expression of key nitrogen fixation genes in the rhizobium symbiont, and temporal coordination between nitrogen fixation in the bacterial symbiont and nitrogen assimilation in the plant host may be important for successful symbiosis. Understanding of how circadian regulation impacts on nodule establishment and function will identify key plant-rhizobial connections and regulators that could be targeted to increase the efficiency of this relationship.

Characteristics and outcomes of pregnant women with type 1 or type 2 diabetes: a 5-year national population-based cohort study.

BACKGROUND: Diabetes in pregnancy is associated with preterm delivery, birthweight extremes, and increased rates of congenital anomaly, stillbirth, and neonatal death. We aimed to identify and compare modifiable risk factors associated with adverse pregnancy outcomes in women with type 1 diabetes and those with type 2 diabetes and to identify effective maternity clinics. METHODS: In this national population-based cohort study, we used data for pregnancies among women with type 1 or type 2 diabetes collected in the first 5 years of the National Pregnancy in Diabetes audit across 172 maternity clinics in England, Wales, and the Isle of Man, UK. Data for obstetric complications (eg, preterm delivery [<37 weeks' gestation], large for gestational age [LGA] birthweight [>90th percentile]) and adverse pregnancy outcomes (congenital anomaly, stillbirth, neonatal death) were obtained for pregnancies completed between Jan 1, 2014, and Dec 31, 2018. We assessed associations between modifiable (eg, HbA1c, BMI, pre-pregnancy care, maternity clinic) and non-modifiable risk factors (eg, age, ethnicity, deprivation, duration of type 1 diabetes) with pregnancy outcomes in women with type 1 diabetes compared with those with type 2 diabetes. We calculated associations between maternal factors and perinatal deaths using a regression model, including diabetes type and duration, maternal age, BMI, deprivation quintile, first trimester HbA1c, preconception folic acid, potentially harmful medications, and third trimester HbA1c. FINDINGS: Our dataset included 17 375 pregnancy outcomes in 15 290 pregnant women. 8690 (50·0%) of 17 375 pregnancies were in women with type 1 diabetes (median age at delivery 30 years [10-90th percentile 22-37], median duration of diabetes 13 years [3-25]) and 8685 (50·0%) were in women with type 2 diabetes (median age at delivery 34 years [27-41], median duration of diabetes 3 years [0-10]). The rates of preterm delivery (3325 [42·5%] of 7825 pregnancies among women with type 1 diabetes, 1825 [23·4%] of 7815 with type 2 diabetes; p<0·0001), and LGA birthweight (4095 [52·2%] of 7845 with type 1 diabetes, 2065 [26·2%] of 7885 with type 2 diabetes; p<0·0001) were higher in type 1 diabetes. The prevalence of congenital anomaly (among women with type 1 diabetes: 44·8 per 1000 livebirths, terminations, and fetal losses; among women with type 2 diabetes: 40·5 per 1000 livebirths, terminations, and fetal losses; p=0·17) and stillbirth (type 1 diabetes: 10·4 per 1000 livebirths and stillbirths; type 2 diabetes: 13·5 per 1000 livebirths and stillbirths; p=0·072) did not significantly differ between diabetes types, but rates of neonatal death were higher in mothers with type 2 diabetes than in those with type 1 diabetes (type 1 diabetes: 7·4 per 1000 livebirths; type 2 diabetes 11·2 per 1000 livebirths; p=0·013). Across the whole study population, independent risk factors for perinatal death (ie, stillbirth or neonatal death) were third trimester HbA1c of 6·5% (48 mmol/mol) or higher (odds ratio 3·06 [95% CI 2·16-4·33] vs HbA1c <6·5%), being in the highest deprivation quintile (2·29 [1·16-4·52] vs the lowest quintile), and having type 2 diabetes (1·65 [1·18-2·31] vs type 1 diabetes). Variations in HbA1c and LGA birthweight were associated with maternal characteristics (age, diabetes duration, deprivation, BMI) without substantial differences between maternity clinics. INTERPRETATION: Our data highlight persistent adverse pregnancy outcomes in women with type 1 or type 2 diabetes. Maternal glycaemia and BMI are the key modifiable risk factors. No maternity clinics were had appreciably better outcomes than any others, suggesting that health-care system changes are needed across all clinics. FUNDING: None.

Reducing the impact of preterm birth: Preterm birth commissioning in the United Kingdom.

Reducing preterm birth is a priority for Maternity and Children's services. In the recent UK Department of Health publication 'Safer Maternity Care' the Secretary of State for Health aimed to achieve the national maternity safety ambition by pledging to reduce the rate of preterm birth from 8% to 6%. It was proposed that specialist preterm birth services should be established in the UK in order to achieve this aim. In response the Preterm Clinical Network has written Commissioning Guidance aimed to establish best practice pathways and agreed models of care to reduce variation nationally. They have been developed by clinical experts in the field, from within the UK, to provide recommendations for commissioning groups and to recommend pathways to organisations with the aim of reducing the incidence of preterm birth. Three key areas of care provision are focused on: prediction, prevention and preparation of women at high risk of PTB. This Expert Opinion, will summarise the Commissioning Guidance.

Pain scores among emergency department (ED) patients: comparison by ED diagnosis.

BACKGROUND: Treatment for pain and pain-related conditions has been identified as the most common reason for Emergency Department (ED) visits. OBJECTIVE: This study was undertaken to characterize the distribution of self-reported pain scores for common ED diagnoses. METHODS: In this retrospective exploratory chart review, eligible participants included all adult ED patients age 18 years and over, with a self-reported triage pain score of 1 or higher during January-June 2011. Data were collected from ED electronic medical records. RESULTS: Among 1229 patients, the mean age was 44 years; 56% of patients were female, and 59% were white. The mean triage pain score for all patients was 7.1 (interquartile range 6-9). The most common reported diagnoses included: minor injuries (10%), abdominal pain (8%), and respiratory infections (8%). The diagnoses with the highest mean pain scores were: sickle cell crisis (mean pain score 8.7), back/neck/shoulder pain (8.5), and headache/migraine (8.3). Higher pain scores were significantly correlated with younger age (p<0.001) and number of ED visits (p<0.001). Demographic factors including female gender, African American race, and Medicaid insurance reported significantly higher pain scores (p<0.001). Patients with multiple ED visits in the recent 12 months reported significantly higher pain scores (p<0.001). CONCLUSION: ED patients report a wide variety of pain scores. Factors associated with higher pain scores included younger age, female gender, African American race, Medicaid insurance status, multiple ED visits in the past year, and ED diagnoses of sickle cell crisis, back/neck/shoulder pain, and headache.

Risk factors for macrosomia and its clinical consequences: a study of 350,311 pregnancies.

OBJECTIVES: To identify demographic risk factors for either birthweight >4kg or over the 90th centile and to quantify the obstetric risks. STUDY DESIGN: Data from 350,311 completed singleton pregnancies in the North West Thames Region between 1988 and 1997 were analysed using logistic regression. Predisposing factors and pregnancy outcome were compared by birthweight 2.5-4kg (n=259,902) and >4kg (n=36,462) and 10th-90th centile (n=279,780) and >90th centile (n=34,937). RESULTS: Macrosomia defined as birthweight >90th centile was more likely in women whose BMI >30 (kg/m(2)) (odds ratio (OR) 2.08; confidence intervals (CI) 1.99, 2.17), parity >4 (OR 2.20; CI 2.02, 2.40), age >40 (OR 1.22; CI 1.11, 1.35) and in women with pre-existing diabetes (OR 6.97; CI 5.36, 8.16) or who developed gestational diabetes (OR 2.77; CI 2.51, 3.07). Macrosomia defined by birthweight >4kg was better than birthweight >90th centile at predicting morbidity and was associated with a prolonged first and second stage of labour (OR 1.57; CI 1.51, 1.63) and (OR 2.03; CI 1.88, 2.19), respectively, an increased risk of instrumental vaginal delivery (OR 1.76; CI 1.68, 1.85), third degree perineal trauma (OR 2.73; CI 2.30, 3.23), emergency caesarean section (OR 1.84; CI 1.75, 1.93), postpartum haemorrhage (OR 2.01; CI 1.93, 2.10), Apgar score <4 (OR 1.35; CI 1.03, 1.76), and admission to the special care baby unit (OR 1.51; CI 21.38, 1.68). CONCLUSION: Macrosomia is more common in mothers who are obese, older or diabetic and is associated with significant obstetric morbidity.

Serial aggressive platelet transfusion for fetal alloimmune thrombocytopenia: platelet dynamics and perinatal outcome.

OBJECTIVES: Our purpose was to describe the fetal loss rate and platelet dynamics in fetal alloimmune thrombocytopenia managed by serial platelet transfusions. METHODS: Retrospective analysis over 10 years of consecutive pregnancies affected by fetal alloimmune thrombocytopenia requiring in utero platelet transfusions. RESULTS: There were 2 perinatal losses in 12 pregnancies managed by 84 platelet transfusions. One was obviously procedure related from exsanguination despite platelet transfusion. The attributable procedure related fetal loss rate was 1.2% per procedure but 8.3% per pregnancy. The median rate of fall in fetal platelet count per day after transfusion was lower at the placental cord insertion (n = 54) 40.5 x 10(9)/L (range, 5.4-96.1 x 10(9)/L) compared with that at the intrahepatic vein (n = 30) 50.9 x 10(9)/L,(range, 29.5-91 x 10(9)/L) (P = .0009). CONCLUSION: Pooling our results with those previously published yields a cumulative risk of serial weekly transfusions of approximately 6% per pregnancy, indicating the need for development of less invasive approaches.

X-linked inheritance of Dandy-Walker variant.

We report a family in which two sisters had three male fetuses with isolated Dandy-Walker variant (DWV) diagnosed on antenatal ultrasound. DWV is one part of a spectrum of abnormalities related to Dandy-Walker malformation (DWM) which commonly occur in association with other anomalies with or without chromosome abnormalities. The majority of cases are sporadic but rare reports of recurrence in siblings exist. This is the second report suggesting that isolated DWM/DWV can be inherited as an X-linked recessive trait.