Unplanned hysterectomy: a comprehensive analysis of race, ethnicity, sociodemographic factors, pregnancy complications, and cardiovascular disease risk factors.

OBJECTIVE: To understand the risk of unplanned hysterectomy (UH) in pregnant women better in association with maternal sociodemographic characteristics, cardiovascular disease (CVD) risk factors, and current pregnancy complications. DESIGN: Using Florida birth data from 2005 to 2014, we investigated the possible interactions between known risk factors of having UH, including maternal sociodemographic characteristics, maternal medical history, and other pregnancy complications. Logistic regression models were constructed. Adjusted odds ratios and 95% confidence intervals were reported. RESULTS: Several interactions were observed that significantly affected odds of UH. Compared to non-Hispanic White women, Hispanic minority women were more likely to have an UH. The overall risk of UH for women with preterm birth (<37 weeks) and concurrently had premature rupture of membranes (PRoM), uterine rupture, or a previous cesarean delivery was significantly higher than women who delivered to term and had no pregnancy complications. Women who delivered via cesarean who also had preeclampsia, PRoM, or uterine rupture had an overall increased risk of UH. Significantly decreased risk of UH was seen for Black women less than 20 years old, women of other minority races with either less than a high school degree or a college degree or greater, women of other minority races with PRoM, and women with preterm birth and diabetes compared to respective reference groups. CONCLUSIONS: Maternal race, ethnicity, CVD risk factors, and current pregnancy complications affect the risk of UH in pregnant women through complex interactions that would not be seen in unadjusted models of risk analysis.

Assessing the Risk of Heart Attack: A Bayesian Kernel Machine Regression Analysis of Heavy Metal Mixtures.

Background: The assessment of heavy metals' effects on human health is frequently limited to investigating one metal or a group of related metals. The effect of heavy metals mixture on heart attack is unknown. Methods: This study applied the Bayesian kernel machine regression model (BKMR) to the 2011-2016 National Health and Nutrition Examination Survey (NHANES) data to investigate the association between heavy metal mixture exposure with heart attack. 2972 participants over the age of 20 were included in the study. Results: Results indicate that heart attack patients have higher levels of cadmium and lead in the blood and cadmium, cobalt, and tin in the urine, while having lower levels of mercury, manganese, and selenium in the blood and manganese, barium, tungsten, and strontium in the urine. The estimated risk of heart attack showed a negative association of 0.0030 units when all the metals were at their 25th percentile compared to their 50th percentile and a positive association of 0.0285 units when all the metals were at their 75th percentile compared to their 50th percentile. The results suggest that heavy metal exposure, especially cadmium and lead, may increase the risk of heart attacks. Conclusions: This study suggests a possible association between heavy metal mixture exposure and heart attack and, additionally, demonstrates how the BKMR model can be used to investigate new combinations of exposures in future studies.

Burden of maternal and fetal outcomes among pregnant cancer survivors during delivery hospitalizations in the United States.

Existing studies on pregnancy-related outcomes among cancer survivors are limited by sample size or specificity of the cancer type. This study estimated the burden of adverse maternal and fetal outcomes among pregnant cancer survivors using a national database. This study was a retrospective analysis of National Inpatient Sample collected during 2010-2014. Multivariate regression models were used to calculate odds ratios for maternal and fetal outcomes. The study included a weighted sample of 64,506 pregnant cancer survivors and 18,687,217 pregnant women without cancer. Pregnant cancer survivors had significantly higher odds for death during delivery hospitalization, compared to pregnant women without cancer (58 versus 5 deaths per 100,000 pregnancies). They also had higher odds of severe maternal morbidity (aOR 2.00 [95% CI 1.66-2.41]), cesarean section (aOR 1.27 [95% CI 1.19-1.37]), labor induction (aOR 1.17 [95% CI 1.07-1.29]), pre-eclampsia (aOR 1.18 [95% CI 1.02-1.36]), preterm labor (aOR 1.55 [95% CI 1.36-1.76]), chorioamnionitis (aOR 1.45 [95% CI 1.15-1.82]), postpartum infection (aOR 1.68 [95% CI 1.21-2.33]), venous thromboembolism (aOR 3.62 [95% CI 2.69-4.88]), and decreased fetal movements (aOR 1.67 [95% CI 1.13-2.46]). This study showed that pregnancy among cancer survivors constitutes a high-risk condition requiring advanced care and collective efforts from multiple subspecialties.

Acute exposure to a glyphosate-containing herbicide formulation inhibits Complex II and increases hydrogen peroxide in the model organism Caenorhabditis elegans.

Glyphosate-based herbicides, such as Touchdown (TD) and Roundup, are among the most heavily-used herbicides in the world. While the active ingredient is generally considered non-toxic, the toxicity resulting from exposure to commercially-sold formulations is less clear. In many cases, cell cultures or various model organisms exposed to glyphosate formulations show toxicity and, in some cases, lethality. Using Caenorhabditis elegans, we assessed potential toxic mechanisms through which a highly-concentrated commercial formulation of TD promotes neurodegeneration. Following a 30-min treatment, we assayed mitochondrial electron transport chain function and reactive oxygen species (ROS) production. Initial oxygen consumption studies indicated general mitochondrial inhibition compared to controls (*p < 0.05). When Complex II activity was further assessed, inhibition was observed in all TD-treated groups (*p < 0.05). Complex IV activity, however, was not adversely affected by TD. This electron transport chain inhibition also resulted in reduced ATP levels (*p < 0.05). Furthermore, hydrogen peroxide levels, but not other ROS, were increased (*p < 0.05). Taken together, these data indicate that commercially-available formulations of TD may exert neurotoxicity through Complex II (succinate dehydrogenase) inhibition, decreased ATP levels, and increased hydrogen peroxide production.

Chronic exposure to a glyphosate-containing pesticide leads to mitochondrial dysfunction and increased reactive oxygen species production in Caenorhabditis elegans.

Glyphosate-containing herbicides are among the most widely-used in the world. Although glyphosate itself is relatively non-toxic, growing evidence suggests that commercial herbicide formulations may lead to increased oxidative stress and mitochondrial inhibition. In order to assess these mechanisms in vivo, we chronically (24h) exposed Caenorhabditis elegans to various concentrations of the glyphosate-containing herbicide TouchDown (TD). Following TD exposure, we evaluated the function of specific mitochondrial electron transport chain complexes. Initial oxygen consumption studies demonstrated inhibition in mid- and high-TD concentration treatment groups compared to controls. Results from tetramethylrhodamine ethyl ester and ATP assays indicated reductions in the proton gradient and ATP levels, respectively. Additional studies were designed to determine whether TD exposure resulted in increased reactive oxygen species (ROS) production. Data from hydrogen peroxide, but not superoxide or hydroxyl radical, assays showed statistically significant increases in this specific ROS. Taken together, these data indicate that exposure of Caenorhabditis elegans to TD leads to mitochondrial inhibition and hydrogen peroxide production.

Single low doses of MPTP decrease tyrosine hydroxylase expression in the absence of overt neuron loss.

Parkinson's disease (PD) is the second most common age-related neurodegenerative disease. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a prototypical neurotoxicant used in mice to mimic primary features of PD pathology including striatal dopamine depletion and dopamine neuron loss in the substantia nigra pars compacta (SNc). In the literature, there are several experimental paradigms involving multiple doses of MPTP that are used to elicit dopamine neuron loss. However, a recent study reported that a single low dose caused significant loss of dopamine neurons. Here, we determined the effect of a single intraperitoneal injection of one of three doses of MPTP (0.1, 2 and 20mg/kg) on dopamine neurons, labeled by tyrosine hydroxylase (TH+), and total neuron number (Nissl+) in the SNc using unbiased stereological counting. Data reveal a significant loss of neurons in the SNc (TH+ and Nissl+) only in the group treated with 20mg/kg MPTP. Groups treated with lower dose of MPTP (0.1 and 2mg/kg) only showed significant loss of TH+ neurons rather than TH+ and Nissl+ neurons. Striatal dopamine levels were decreased in the groups treated with 2 and 20mg/kg MPTP and striatal terminal markers including, TH and the dopamine transporter (DAT), were only decreased in the groups treated with 20mg/kg MPTP. These data demonstrate that lower doses of MPTP likely result in loss of TH expression rather than actual dopamine neuron loss in the SN. This finding reinforces the need to measure both total neuron number along with TH+ cells in determining dopamine neuron loss.