Rural and urban differences in prenatal exposure to essential and toxic elements.

Excess or inadequate levels of inorganic ions may induce significant acute and long-term irreversible dysfunction in humans. The fetus and placenta are particularly vulnerable to toxins due to the immaturity of the blood-brain barrier and diminished biotransformation enzymatic activity. A comparative cross-sectional study was conducted on 172 pregnant women, 79 rural, and 93 urban. Umbilical cord blood was collected at the time of delivery and analyzed for 20 inorganic elements. Significant differences were found between urban and rural samples for two elements where copper (Cu) and molybdenum (Mo) were higher in urban samples. No marked differences between groups occurred for: arsenic, barium, cadmium, calcium, cobalt, lead, lithium, magnesium, manganese, mercury, selenium, strontium, or zinc. All samples were devoid of platinum, silver, thallium or uranium. Data demonstrated significant differences in urban and rural prenatal exposure to Cu and Mo. Further study is needed to determine if there is a causal link between neonatal outcomes and prenatal exposure to these elements.

Discovery of AZD3514, a small-molecule androgen receptor downregulator for treatment of advanced prostate cancer.

Removal of the basic piperazine nitrogen atom, introduction of a solubilising end group and partial reduction of the triazolopyridazine moiety in the previously-described lead androgen receptor downregulator 6-[4-(4-cyanobenzyl)piperazin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (1) addressed hERG and physical property issues, and led to clinical candidate 6-(4-{4-[2-(4-acetylpiperazin-1-yl)ethoxy]phenyl}piperidin-1-yl)-3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazine (12), designated AZD3514, that is being evaluated in a Phase I clinical trial in patients with castrate-resistant prostate cancer.

Structure-activity relationship of a series of non peptidic RGD integrin antagonists targeting α5ß1: part 1.

Potent antagonists of the integrin α(5)ß(1), which are RGD mimetics built from tyrosine are described. This letter describes the optimization of in vitro potency obtained by variation of two parts of the molecule, the basic group and the linker between the basic group and the phenyl central core.

Structure-activity relationship of a series of non peptidic RGD integrin antagonists targeting α5ß1: part 2.

Potent antagonists of the integrin α(5)ß(1), which are RGD mimetics built from tyrosine are described. This paper describes the optimization of in vitro potency obtained by variation of two parts of the molecule, the central aromatic core and the amide moiety.

The effect of impedance cardiography directed antihypertensive therapy on fetal growth restriction rates and perinatal mortality in women with chronic hypertension.

OBJECTIVES: We sought to determine the effect of impedance cardiography directed medical antihypertensive therapy on fetal growth restriction and perinatal mortality in women with chronic hypertension. STUDY DESIGN: A retrospective study was conducted on 958 women referred to the Maternal Hypertension Center at Cabell Huntington Hospital between 2005 and 2014 for the indication of chronic hypertension. MAIN OUTCOME MEASURES: Serial assessments of maternal hemodynamics were obtained using non-invasive impedance cardiography. Vasodilators were initiated for increased systemic vascular resistance. Elevated cardiac output was treated with beta blockade. RESULTS: Blood pressure at initial visit was used to stratify patients into five groups. Initial blood pressure of <130 systolic or <80 diastolic had 24 cases of growth restriction (6.8%) and 6 perinatal deaths (1.7%), 130-139 systolic or 80-89 diastolic resulted in 29 cases of growth restriction (9.3%) and 9 perinatal deaths (2.9%), 140-149 systolic or 90-99 diastolic 14 cases of growth restriction (6.5%) and 3 perinatal deaths (1.4%), 150-159 systolic or 100-109 diastolic had 5 cases of growth restriction (8.6%) and 4 perinatal deaths (6.89%), and >160 systolic or >110 diastolic 3 cases of growth restriction (13%) with no perinatal deaths. There were no differences in growth restriction (p = .59) or perinatal death (p = .15) between the groups. CONCLUSION: The rates of IUGR and perinatal mortality did not increase even with increasing severity of maternal hypertension. This low cost and non-invasive test should be considered for optimizing rates of growth restriction and perinatal mortality in pregnancies complicated by chronic hypertension.

Small-molecule androgen receptor downregulators as an approach to treatment of advanced prostate cancer.

Chemical starting points were investigated for downregulation of the androgen receptor as an approach to treatment of advanced prostate cancer. Although prototypic steroidal downregulators such as 6a designed for intramuscular administration showed insufficient cellular potency, a medicinal chemistry program derived from a novel androgen receptor ligand 8a led to 6-[4-(4-cyanobenzyl)piperazin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (10b), for which high plasma levels following oral administration in a preclinical model compensate for moderate cellular potency.

Uterine arteriovenous malformation leading to postpartum hemorrhage: A case report.

Uterine arteriovenous malformation (AVM) is an uncommon but potentially life-threatening cause of postpartum hemorrhage (PPH). AVMs often present with intermittent or profuse vaginal bleeding in a woman with a history of uterine instrumentation. Transvaginal ultrasound is the initial imaging method used for diagnosis. Management depends on the patient's hemodynamic stability and desire for future pregnancy. Uterine artery embolization (UAE) is the initial treatment option for women of reproductive age. Due to limited evidence, there are no guidelines for the management of failed UAE. Here we report a case of uterine AVM following a cesarean section that failed initial management with UAE and required emergency hysterectomy.

Chemical amplification in an invaded food web: seasonality and ontogeny in a high-biomass, low-diversity ecosystem.

The global spread of invasive species is changing the structure of aquatic food webs worldwide. The North American Great Lakes have proved particularly vulnerable to this threat. In nearshore areas, invasive benthic species such as dreissenid mussels and round gobies (Neogobius melanostomus) have gained dominance in recent years. Such species are driving the flow of energy and material from the water column to the benthic zone, with dramatic effect on nutrient and contaminant cycling. Here, we develop a stage-structured model of a benthified food web in Lake Michigan with seasonal resolution and show how its bioaccumulation patterns differ from expected ones. Our model suggests that contaminant recycling through the consumption of lipid-rich fish eggs and mussel detritus is responsible for these differences. In southern Lake Michigan's Calumet Harbor (Chicago, IL, USA), round gobies have nitrogen isotope signatures with considerable spread, with some values higher than their predators and others lower than their prey. Contrary to patterns observed in linear pelagic systems, we predict that polychlorinated biphenyl (PCB) concentrations in these fish decrease with increasing size due to the lipid- and benthos-enriched diets of smaller fish. We also present here round goby PCB concentrations measured in 2005 after an invasional succession in Calumet Harbor and demonstrate how the change from one invasive mussel species to another may have led to a decrease in round goby PCB accumulation. Our results suggest that benthic-dominated systems differ from pelagic ones chiefly due to the influence of detritus and that these effects are exacerbated in systems with low species diversity and high biomass.

Simulation training in the obstetrics and gynecology clerkship.

OBJECTIVE: The purpose of this study was to determine the effectiveness of obstetrics simulator training for medical students by comparing measures of confidence in normal obstetrics skills of students with and without training. STUDY DESIGN: After a lecture on normal labor and delivery, 33 third-year students practiced their skills either on an obstetrics simulator (n = 17) or received no further formal instruction (n = 16). All students were asked to respond to surveys of their experience and confidence in performing obstetrics procedures. RESULTS: Students who practiced deliveries on the simulator were more likely to believe that they could perform most portions of a vaginal delivery with minimal supervision or independently than were students who did not receive simulator experience. Fifteen students (88%) who received simulator experience felt that they were ready to attempt a vaginal delivery independently or with minimal supervision compared with 2 students (12.5%) who received a lecture only (P < .001). CONCLUSION: Students who practiced deliveries on an obstetrics simulator report higher levels of confidence in their skills to perform vaginal deliveries.