Exposure to hypertensive disorders of pregnancy increases the risk of autism spectrum disorder in affected offspring

There is growing awareness that prenatal adversity may increase the risk of autism spectrum disorder (ASD). Here, we examined the association between hypertensive disorders of pregnancy (HDP) and ASD risk at 7 years of age using the Millennium Cohort Study (MCS), a representative cohort of 13,192 children born in the UK from 2000 to 2001. We also sought to examine cytokine expression in the serum of women with pre-eclampsia, which is the most common HDP, and whether exposure of foetal neurons to this serum could change patterns of neuronal growth. HDP were reported by mothers 9 months post-delivery. ASD was parent reported at age seven, based on a doctor or health care professional’s diagnosis. Weighted logistic regression was used for data analysis, adjusting for several potential confounders including maternal alcohol consumption, education, depression, age, and poverty status. Sensitivity analyses were performed excluding pre-term births, small for gestational age (SGA), and pre-pregnancy hypertension and depression. There was a significant association between HDP and a twofold increased risk of ASD (AOR = 2.10 [95% CI 1.20–3.70]). Excluding preterm births, SGA births, and offspring of women who had pre-pregnancy hypertension or over the age of 40 did not change the results materially. At the cellular level, exposure of foetal cortical neurons to 3% serum isolated from women with an established HDP increased neuronal growth and branching in vitro. These findings indicate that HDP exposure may increase the risk of ASD in the offspring

Families, work, and social institutions : a comparative study of immigrants and their children in Waterbury, Connecticut, 1900-1920

145 leaves : ill. ; 29 cm

Monitoring neurointerventional radiation doses using dose-tracking software: implications for the establishment of local diagnostic reference levels

Objectives: There is potential for high radiation exposure during neurointerventional procedures. Increasing regulatory requirements mandate dose monitoring of patients and staff, and justification of high levels of radiation exposure. This paper demonstrates the potential to use radiation dose-tracking software to establish local diagnostic reference levels. Methods: Consecutive neurointerventional procedures, performed in a single institution within a one-year period, were retrospectively studied. Dose area product (DAP) data were collected using dose-tracking software and clinical data obtained from a prospectively generated patient treatment database. Results: Two hundred and sixty-four procedures met the selection criteria. Median DAP was 100 Gy.cm2 for aneurysm coiling procedures, 259 Gy.cm2 for arteriovenous malformation (AVM) embolisation procedures, 87 Gy.cm2 for stroke thrombolysis/thrombectomy, and 74 Gy.cm2 for four-vessel angiography. One hundred and nine aneurysm coiling procedures were further studied. Six significant variables were assessed using stepwise regression analysis to determine effect on DAP. Aneurysm location (anterior vs posterior circulation) had the single biggest effect (p = 0.004). Conclusions: This paper confirms variable radiation exposures during neurointerventional procedures. The 75th percentile (used to define diagnostic reference levels) of DAP measurements represents a reasonable guidance metric for monitoring purposes. Results indicate that aneurysm location has the greatest impact on dose during coiling procedures and that anterior and posterior circulation coiling procedures should have separate diagnostic reference levels. Key Points: Dose-tracking software is useful for monitoring patient radiation dose during neurointerventional procedures; This paper provides a template for methodology applicable to any interventional suite; Local diagnostic reference levels were defined by using the 75th percentile of DAP as per International Commission on Radiological Protection recommendations; Aneurysm location is the biggest determinant of radiation dose during coiling procedures.; Anterior and posterior circulation coiling procedures should have separate diagnostic reference levels

SPOP-Mutated/CHD1-Deleted Lethal Prostate Cancer and Abiraterone Sensitivity.

deletions and mutations frequently cooccur in prostate cancer with lower frequencies reported in castration-resistant prostate cancer (CRPC). We monitored CHD1 expression during disease progression and assessed the molecular and clinical characteristics of -deleted/-mutated metastatic CRPC (mCRPC). We identified 89 patients with mCRPC who had hormone-naive and castration-resistant tumor samples available: These were analyzed for CHD1, PTEN, and ERG expression by IHC. status was determined by targeted next-generation sequencing (NGS). We studied the correlations between these biomarkers and (i) overall survival from diagnosis; (ii) overall survival from CRPC; (iii) duration of abiraterone treatment; and (iv) response to abiraterone. Relationship with outcome was analyzed using Cox regression and log-rank analyses. CHD1 protein loss was detected in 11 (15%) and 13 (17%) of hormone-sensitive prostate cancer (HSPC) and CRPC biopsies, respectively. Comparison of CHD1 expression was feasible in 56 matched, same patient HSPC and CRPC biopsies. CHD1 protein status in HSPC and CRPC correlated in 55 of 56 cases (98%). We identified 22 patients with somatic mutations, with six of these mutations not reported previously in prostate cancer. mutations and/or CHD1 loss was associated with a higher response rate to abiraterone (SPOP: OR, 14.50 = 0.001; CHD1: OR, 7.30, = 0.08) and a longer time on abiraterone (SPOP: HR, 0.37, = 0.002, CHD1: HR, 0.50, = 0.06).-mutated mCRPCs are strongly enriched for CHD1 loss. These tumors appear highly sensitive to abiraterone treatment.