Maternal risk factors for gastroschisis: A population‐based case–control study

BackgroundGastroschisis is an open abdominal wall defect with low mortality but significant morbidity. The prevalence has been increasing worldwide for the past decades. Several risk factors for gastroschisis have been identified, but no clear reason for increasing prevalence has been found. In our study, we aimed to assess and identify maternal risk factors for gastroschisis.MethodsIn our nationwide register‐based case–control study, we identified all gastroschisis cases in the Finnish Register of Congenital Malformations from 2004 to 2014. Information on drug prescriptions and purchases was received from Drugs and Pregnancy database. Five healthy age‐matched controls from the same geographical region were randomly selected for each case. Conditional logistic regression was used to evaluate different risk factors.ResultsOne‐hundred‐eighty‐eight cases of gastroschisis were identified and compared with 910 matched controls. Nulliparity was a significant risk factor for gastroschisis, aOR 2.00 (95% CI 1.29–3.11) whereas obesity was protective, aOR 0.35 (95% CI 0.15–0.83). Smoking appeared to increase the risk for gastroschisis, aOR 1.32 (95% CI 0.88–1.97). The mean maternal age of newborns with gastroschisis was significantly lower than average (p  ConclusionAs in previous studies, nulliparity and young maternal age were significant risk factors for gastroschisis. Maternal obesity significantly reduced the risk of gastroschisis regardless of maternal age and gestational diabetes.</p

Omphalocele in Finland from 1993 to 2014: Trends, Prevalence, Mortality, and Associated Malformations-A Population-Based Study

Introduction The aim of this study is to assess the changes in prevalence, mortality and termination pregnancy of omphalocele, and to identify associated anomalies.Materials and Methods A population-based nationwide register study. All cases with omphalocele were identified in the Finnish Register of Congenital Malformations and the Care Register for Health Care from 1993 to 2014 including live births, stillbirths, and terminations of pregnancy due to fetal anomalies. Associated anomalies were recorded and analyzed, and perinatal and infant mortality and prevalence were calculated.Results There were 600 cases with omphalocele including 229 live births, 39 stillbirths, and 332 (55%) abortions. Birth prevalence in Finland was 1.96 per 10,000 births with no consistent trend over time. However, total prevalence was much higher (4.71/10,000) because more than half of these families chose option for the termination of pregnancy. Omphalocele is often complicated with other anomalies; most commonly chromosomal abnormalities (9.3%), heart defects (6.3%), central nervous system anomalies (3.0%), gastrointestinal, and urogenital malformations (both 2.0%). Proportion of chromosomal and central nervous system abnormalities were even higher in terminated pregnancies. Overall infant mortality was 22%. Total 1-year survival rates for isolated omphalocele, cases with multiple anomalies and neonates with chromosomal defects were 80, 88, and 17%, respectively.Conclusion Omphalocele is a rare congenital anomaly, often associated with other malformations. Our data suggest that isolated cases may be more common than previously thought. In the absence of chromosomal defects, survival is reasonably good. Regardless, more than half of these pregnancies are often terminated.</p

Cardiorespiratory Fitness, Physical Activity, and Insulin Resistance in Children

This is the author accepted manuscript. The final version is available from Lippincott, Williams & Wilkins via the DOI in this record.Purpose: Few studies have investigated the independent and joint associations of cardiorespiratory fitness (CRF) and body fat percentage (BF%) with insulin resistance in children. We investigated the independent and combined associations of CRF and BF% with fasting glycaemia and insulin resistance and their interactions with physical activity (PA) and sedentary time among 452 children aged 6¬–8 years. Methods: We assessed CRF with a maximal cycle ergometer exercise test and used allometrically scaled maximal power output (Wmax) for lean body mass (LM1.13) and body mass (BM1) as measures of CRF. BF% and LM were measured by dual-energy X-ray absorptiometry, fasting glycaemia by fasting plasma glucose, and insulin resistance by fasting serum insulin and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). PA energy expenditure (PAEE), moderate-to-vigorous PA (MVPA), and sedentary time were assessed by combined movement and heart rate sensor. Results: Wmax/LM1.13 was not associated with glucose (β=0.065, 95% CI=-0.031 to 0.161), insulin (β=-0.079, 95% CI=-0.172 to 0.015), or HOMA-IR (β=-0.065, 95% CI=-0.161 to 0.030). Wmax/BM1 was inversely associated with insulin (β=-0.289, 95% CI=-0.377 to -0.200) and HOMA-IR (β=-0.269, 95% CI=-0.359 to -0.180). BF% was directly associated with insulin (β=0.409, 95% CI=0.325 to 0.494) and HOMA-IR (β=0.390, 95% CI=0.304 to 0.475). Higher Wmax/BM1, but not Wmax/LM1.13, was associated with lower insulin and HOMA-IR in children with higher BF%. Children with higher BF% and who had lower levels of MVPA or higher levels of sedentary time had the highest insulin and HOMA-IR. Conclusion: Children with higher BF% together with less MVPA or higher levels of sedentary time had the highest insulin and HOMA-IR. CRF appropriately controlled for body size and composition using LM was not related to insulin resistance among children.Medical Research CouncilNIH

Host, Suppressor, and Promoter The Roles of Ni and Fe on Oxygen Evolution Reaction Activity and Stability of NiFe Alloy Thin Films in Alkaline Media

Understanding the oxygen evolution reaction OER activity and stability of the NiFe based materials is important for achieving low cost and highly efficient electrocatalysts for practical water splitting. Here, we report the roles of Ni and Fe on the OER activity and stability of metallic NiFe and pure Ni thin films in alkaline media. Our results support that Ni OH 2 NiOOH does not contribute to the OER directly, but it serves as an ideal host for Fe incorporation, which is essential for obtaining high OER activity. Furthermore, the availability of Fe in the electrolyte is found to be important and necessary for both NiFe and pure Ni thin films to maintain an enhanced OER performance, while the presence of Ni is detrimental to the OER kinetics. The impacts of Fe and Ni species present in KOH on the OER activity are consistent with the dissolution re deposition mechanism we proposed. Stability studies show that the OER activity will degrade under prolonged continuous operation. Satisfactory stability can, however, be achieved with intermittent OER operation, in which the electrocatalyst is cycled between degraded and recovered states. Accordingly, two important ranges, that is, the recovery range and the degradation range, are proposed. Compared to the intermittent OER operation, prolonged continuous OER operation i.e., in the degradation range generates a higher NiOOH content in the electrocatalyst, which is likely related to the OER deactivation. If the electrode works in the recovery range for a certain period, that is, at a sufficiently low reduction potential, where Ni3 is reduced to Ni2 , the OER activity can be maintained and even improved if Fe is also present in the electrolyt

Decreased insulin‐stimulated brown adipose tissue glucose uptake after short‐term exercise training in healthy middle‐aged men

Aims To test the hypothesis that high‐intensity interval training (HIIT) and moderate‐intensity continuous training (MICT) improve brown adipose tissue (BAT) insulin sensitivity. Participants and methods Healthy middle‐aged men (n = 18, age 47 years [95% confidence interval {CI} 49, 43], body mass index 25.3 kg/m2 [95% CI 24.1‐26.3], peak oxygen uptake (VO2peak) 34.8 mL/kg/min [95% CI 32.1, 37.4] ) were recruited and randomized into six HIIT or MICT sessions within 2 weeks. Insulin‐stimulated glucose uptake was measured using 2‐[18F]flouro‐2‐deoxy‐D‐glucose positron‐emission tomography in BAT, skeletal muscle, and abdominal and femoral subcutaneous and visceral white adipose tissue (WAT) depots before and after the training interventions. Results: Training improved VO2peak (P = .0005), insulin‐stimulated glucose uptake into the quadriceps femoris muscle (P = .0009) and femoral subcutaneous WAT (P = .02) but not into BAT, with no difference between the training modes. Using pre‐intervention BAT glucose uptake, we next stratified subjects into high BAT (>2.9 µmol/100 g/min; n = 6) or low BAT (<2.9 µmol/100 g/min; n = 12) groups. Interestingly, training decreased insulin‐stimulated BAT glucose uptake in the high BAT group (4.0 [2.8, 5.5] vs 2.5 [1.7, 3.6]; training*BAT, P = .02), whereas there was no effect of training in the low BAT group (1.5 [1.2, 1.9] vs 1.6 [1.2, 2.0] µmol/100 g/min). Participants in the high BAT group had lower levels of inflammatory markers compared with those in the low BAT group. Conclusions: Participants with functionally active BAT have an improved metabolic profile compared with those with low BAT activity. Short‐term exercise training decreased insulin‐stimulated BAT glucose uptake in participants with active BAT, suggesting that training does not work as a potent stimulus for BAT activation

Influences on pre-hospital delay in the diagnosis of colorectal cancer: a systematic review

Colorectal cancer is a major global health problem, with survival varying according to stage at diagnosis. Delayed diagnosis can result from patient, practitioner or hospital delay. This paper reports the results of a review of the factors influencing pre-hospital delay – the time between a patient first noticing a cancer symptom and presenting to primary care or between first presentation and referral to secondary care. A systematic methodology was applied, including extensive searches of the literature published from 1970 to 2003, systematic data extraction, quality assessment and narrative data synthesis. Fifty-four studies were included. Patients' non-recognition of symptom seriousness increased delay, as did symptom denial. Patient delay was greater for rectal than colon cancers and the presence of more serious symptoms, such as pain, reduced delay. There appears to be no relationship between delay and patients' age, sex or socioeconomic status. Initial misdiagnosis, inadequate examination and inaccurate investigations increased practitioner delay. Use of referral guidelines may reduce delay, although evidence is currently limited. No intervention studies were identified. If delayed diagnosis is to be reduced, there must be increased recognition of the significance of symptoms among patients, and development and evaluation of interventions that are designed to ensure appropriate diagnosis and examination by practitioners

The progestational and androgenic properties of medroxyprogesterone acetate: gene regulatory overlap with dihydrotestosterone in breast cancer cells

INTRODUCTION: Medroxyprogesterone acetate (MPA), the major progestin used for oral contraception and hormone replacement therapy, has been implicated in increased breast cancer risk. Is this risk due to its progestational or androgenic properties? To address this, we assessed the transcriptional effects of MPA as compared with those of progesterone and dihydrotestosterone (DHT) in human breast cancer cells. METHOD: A new progesterone receptor-negative, androgen receptor-positive human breast cancer cell line, designated Y-AR, was engineered and characterized. Transcription assays using a synthetic promoter/reporter construct, as well as endogenous gene expression profiling comparing progesterone, MPA and DHT, were performed in cells either lacking or containing progesterone receptor and/or androgen receptor. RESULTS: In progesterone receptor-positive cells, MPA was found to be an effective progestin through both progesterone receptor isoforms in transient transcription assays. Interestingly, DHT signaled through progesterone receptor type B. Expression profiling of endogenous progesterone receptor-regulated genes comparing progesterone and MPA suggested that although MPA may be a somewhat more potent progestin than progesterone, it is qualitatively similar to progesterone. To address effects of MPA through androgen receptor, expression profiling was performed comparing progesterone, MPA and DHT using Y-AR cells. These studies showed extensive gene regulatory overlap between DHT and MPA through androgen receptor and none with progesterone. Interestingly, there was no difference between pharmacological MPA and physiological MPA, suggesting that high-dose therapeutic MPA may be superfluous. CONCLUSION: Our comparison of the gene regulatory profiles of MPA and progesterone suggests that, for physiologic hormone replacement therapy, the actions of MPA do not mimic those of endogenous progesterone alone. Clinically, the complex pharmacology of MPA not only influences its side-effect profile; but it is also possible that the increased breast cancer risk and/or the therapeutic efficacy of MPA in cancer treatment is in part mediated by androgen receptor

Rasd1 Modulates the Coactivator Function of NonO in the Cyclic AMP Pathway

All living organisms exhibit autonomous daily physiological and behavioural rhythms to help them synchronize with the environment. Entrainment of circadian rhythm is achieved via activation of cyclic AMP (cAMP) and mitogen-activated protein kinase signaling pathways. NonO (p54nrb) is a multifunctional protein involved in transcriptional activation of the cAMP pathway and is involved in circadian rhythm control. Rasd1 is a monomeric G protein implicated to play a pivotal role in potentiating both photic and nonphotic responses of the circadian rhythm. In this study, we have identified and validated NonO as an interacting partner of Rasd1 via affinity pulldown, co-immunoprecipitation and indirect immunofluorescence studies. The GTP-hydrolysis activity of Rasd1 is required for the functional interaction. Functional interaction of Rasd1-NonO in the cAMP pathway was investigated via reporter gene assays, chromatin immunoprecipitation and gene knockdown. We showed that Rasd1 and NonO interact at the CRE-site of specific target genes. These findings reveal a novel mechanism by which the coregulator activity of NonO can be modulated

G-protein signaling: back to the future

Heterotrimeric G-proteins are intracellular partners of G-protein-coupled receptors (GPCRs). GPCRs act on inactive Gα·GDP/Gβγ heterotrimers to promote GDP release and GTP binding, resulting in liberation of Gα from Gβγ. Gα·GTP and Gβγ target effectors including adenylyl cyclases, phospholipases and ion channels. Signaling is terminated by intrinsic GTPase activity of Gα and heterotrimer reformation — a cycle accelerated by ‘regulators of G-protein signaling’ (RGS proteins). Recent studies have identified several unconventional G-protein signaling pathways that diverge from this standard model. Whereas phospholipase C (PLC) β is activated by Gαq and Gβγ, novel PLC isoforms are regulated by both heterotrimeric and Ras-superfamily G-proteins. An Arabidopsis protein has been discovered containing both GPCR and RGS domains within the same protein. Most surprisingly, a receptor-independent Gα nucleotide cycle that regulates cell division has been delineated in both Caenorhabditis elegans and Drosophila melanogaster. Here, we revisit classical heterotrimeric G-protein signaling and explore these new, non-canonical G-protein signaling pathways