Johnsblankenship8087

00, 1.10] and 26% increased odds of eclampsia (95% CI 1.05, 1.51) in adjusted models. This association dissipates in the 1- to 3-km buffer zones. In restricted models, we find elevated odds ratios among maternal ages ≤35 years at delivery, maternal non-Hispanic White race, ≥30 lbs gained during pregnancy, nulliparous mothers and maternal educational attainment beyond high school.

Living within 1 km of an oil or gas extraction site during pregnancy is associated with increased odds of hypertensive conditions during pregnancy.

Living within 1 km of an oil or gas extraction site during pregnancy is associated with increased odds of hypertensive conditions during pregnancy.

To determine whether expression of efflux pumps and antibiotic susceptibility are altered in Escherichia coli in response to efflux inhibition.

The promoter regions of nine efflux pump genes (acrAB, acrD, acrEF, emrAB, macAB, cusCFBA, mdtK, mdtABC, mdfA) were fused to gfp in pMW82 and fluorescence from each reporter construct was used as a measure of the transcriptional response to conditions in which AcrB was inhibited, absent or made non-functional. Expression was also determined by RT-qPCR. Drug susceptibility of efflux pump mutants with missense mutations known or predicted to cause loss of function of the encoded efflux pump was investigated.

Data from the GFP reporter constructs revealed that no increased expression of the tested efflux pump genes was observed when AcrB was absent, made non-functional, or inhibited by an efflux pump inhibitor/competitive substrate, such as PAβN or chlorpromazine. This was confirmed by RT-qPCR for PAβN and chlorpromazine; however, a small but significant increase in macB gene expression was seen when acrB is deleted. Efflux inhibitors only synergized with antibiotics in the presence of a functional AcrB. When AcrB was absent or non-functional, there was no impact on MICs when other efflux pumps were also made non-functional.

Absence, loss-of-function, or inhibition of E. coli AcrB did not significantly increase expression of other efflux pump genes, which suggests there is no compensatory mechanism to overcome efflux inhibition and supports the discovery of inhibitors of AcrB as antibiotic adjuvants.

Absence, loss-of-function, or inhibition of E. coli AcrB did not significantly increase expression of other efflux pump genes, which suggests there is no compensatory mechanism to overcome efflux inhibition and supports the discovery of inhibitors of AcrB as antibiotic adjuvants.Caecilians are enigmatic limbless amphibians that, with a few exceptions, all have an at least partly burrowing lifestyle. Although it has been suggested that caecilian evolution resulted in sturdy and compact skulls as an adaptation to their head-first burrowing habits, no relationship between skull shape and burrowing performance has been demonstrated to date. However, the unique dual jaw-closing mechanism and the osteological variability of their temporal region suggest a potential relationship between skull shape and feeding mechanics. Here, we explored the relationships between skull shape, head musculature and in vivo bite forces. Although there is a correlation between bite force and external head shape, no relationship between bite force and skull shape could be detected. Whereas our data suggest that muscles are the principal drivers of variation in bite force, the shape of the skull is constrained by factors other than demands for bite force generation. However, a strong covariation between the cranium and mandible exists. Moreover, both cranium and mandible shape covary with jaw muscle architecture. Caecilians show a gradient between species with a long retroarticular process associated with a large and pennate-fibered m. interhyoideus posterior and species with a short process but long and parallel-fibered jaw adductors. Our results demonstrate the complexity of the relationship between form and function of this jaw system. Further studies that focus on factors such as gape distance or jaw velocity will be needed in order to fully understand the evolution of feeding mechanics in caecilians.CDKN2A homozygous deletion has occasionally been reported in atypical and anaplastic meningiomas and is considered as one of the genetic alterations commonly involved in their recurrence and malignant progression. Methylthioadenosine phosphorylase (MTAP) immunohistochemistry is a promising surrogate marker for CDKN2A homozygous deletion in different cancers but has not been examined in meningiomas. We performed CDKN2A FISH and MTAP immunohistochemistry on specimens from 30 patients with CNS WHO grade 2 (n = 27) and 3 (n = 3) meningiomas, including specimens from primary and recurrent tumors and then determined whether MTAP immunohistochemistry correlated with CDKN2A homozygous deletion and clinicopathological features. CDKN2A homozygous deletion was detected in 12% (3/26) of CNS WHO grade 2 and 67% (2/3) of CNS WHO grade 3 meningiomas; 3 cases exhibited temporal and/or spatial heterogeneity. MTAP loss was in excellent concordance with CDKN2A homozygous deletion (sensitivity; 100%, specificity; 100%). MTAP loss/CDKN2A homozygous deletion correlated with cellular proliferation (mitotic rate; p = 0.001, Ki-67 labeling index; p = 0.03) and poor prognosis (overall survival; p = 0.01, progression free survival; p  less then  0.001). Thus, MTAP immunostaining can be a surrogate marker for CDKN2A homozygous deletion in meningiomas, and MTAP loss/CDKN2A homozygous deletion may be an important prognostic factor for meningiomas.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease caused by mutations in the tumor suppressor gene MEN1. The uncertainty of pathogenicity of MEN1 variants complexifies the selection of the patients likely to benefit from specific care.

MEN1-mutated patients should be offered tailored tumor screening and genetic counselling. We present a patient with hyperparathyroidism for whom genetic analysis identified a variant of uncertain significance in the MEN1 gene (NM_130799.2) c.654G>T p.(Arg218=). Additional functional genetic tests were performed to classify the variant as pathogenic and allowed prenatal testing.

Targeted next generation sequencing identified a synonymous variant in the MEN1 gene in a 26-year-old male with symptomatic primary hyperparathyroidism. In silico and in vitro genetic tests were performed to assess variant pathogenicity.

Genetic testing of the proband's unaffected parents showed the variant occurred de novo. Transcript study showed a splicing defect leading to an in-frame deletion. The classification of the MEN1 variant as pathogenic confirmed the diagnosis of MEN1 and recommended an adapted medical care and follow-up. Pathogenic classification also allowed to propose a genetic counselling to the proband and his wife. Non-invasive prenatal diagnosis was performed with a personalized medicine-based protocol by detection of the paternally inherited variant in maternal plasmatic cell free DNA, using digital PCR.

We showed that functional genetic analysis can help to assess the pathogenicity of a MEN1 variant with crucial consequences for medical care and genetic counselling decisions.

We showed that functional genetic analysis can help to assess the pathogenicity of a MEN1 variant with crucial consequences for medical care and genetic counselling decisions.

In the United States, vaccine hesitancy has been identified as a major barrier to vaccination against COVID-19, but attitudes toward COVID-19 vaccination among military personnel are not well understood. We evaluated the prevalence and correlates of COVID-19 vaccine consent or refusal among deployed personnel in a joint environment.

Deidentified data were retrospectively extracted from the electronic medical record of the Military Health System in May 2021. All personnel currently assigned to the deployment area of operations were included in the analysis if their choice to receive the vaccine was known. Personnel characteristics were compared by vaccine acceptance status using chi-square tests, Fisher's exact tests, or correlation coefficients. This analysis was exempted from Institutional Review Board review.

The sample included 1,809 individuals, primarily members of the Army (72%) and members of Reserve (53%) or National Guard (27%) units. In the overall sample, 61% accepted the vaccine, with vaccinhan that reported in the U.S. population as a whole. However, lower vaccine acceptance among personnel from marginalized populations suggests a need to ensure that all service members have sufficient opportunities to have a frank and ongoing discussion with health care providers to address concerns related to vaccination. Additionally, lower vaccine acceptance among Reserve and National Guard personnel indicates a need for innovative educational approaches to counter vaccine hesitancy in the premobilization phase of deployment.

Excessive birth weight is associated with maternal and neonatal complications. However, ultrasonically estimated large for gestational age (LGA; >90th percentile) predicts these complications poorly.

To determine whether a maternal serum metabolite ratio developed for fetal growth restriction (FGR) is predictive of birth weight across the whole range, including LGA at birth.

Metabolites were measured using ultrahigh performance liquid chromatography-tandem mass spectroscopy. The 4-metabolite ratio was previously derived from an analysis of FGR cases and a random subcohort from the Pregnancy Outcome Prediction study. Here, we evaluated its relationship at 36 weeks of gestational age (wkGA) with birth weight in the subcohort (n = 281). External validation in the Born in Bradford (BiB) study (n = 2366) used the metabolite ratio at 24 to 28 wkGA.

The inverse of the metabolite ratio at 36 wkGA predicted LGA at term [the area under the receiver operating characteristic curve (AUROCC) = 0.82, 95% CI 0.73 to 0.91, P = 6.7 × 10-5]. The ratio was also inversely associated with birth weight z score (linear regression, beta = -0.29 SD, P = 2.1 × 10-8). learn more Analysis in the BiB cohort confirmed that the ratio at 24 to 28 wkGA predicted LGA (AUROCC = 0.60, 95% CI 0.54 to 0.67, P = 8.6 × 10-5) and was inversely associated with birth weight z score (beta = -0.12 SD, P = 1.3 × 10-9).

A metabolite ratio which is strongly predictive of FGR is equally predictive of LGA birth weight and is inversely associated with birth weight across the whole range.

A metabolite ratio which is strongly predictive of FGR is equally predictive of LGA birth weight and is inversely associated with birth weight across the whole range.

Screening is one of the effective interventions for the reduction of colorectal cancer mortality. Though the Japanese government recommends faecal occult blood test and colonoscopy as a follow-up examination following a diagnosis, both participation rates have not been so high and the national mortality rate has not shown a clear decreasing trend.

Microsimulation models simulate the life histories of a large population of individuals under various scenarios. In this study, we applied a microsimulation model to estimate the reduction of colorectal cancer mortality based on screening scenarios.

The effect of reducing the age-standardized mortality rate for colorectal cancer was estimated at 9.4% for men and 6.0% for women under the scenario which calls for 50% participation in faecal occult blood test and 90% participation of follow-up examination. This scenario corresponds to the goal setting for screening in the third-term of the Basic Plan to Promote Cancer Control Programs in Japan.

Our microsimulation model was found to be useful in estimating the mortality reduction effect of cancer control policy.