Cervical dilatation over time is a poor predictor of severe adverse birth outcomes: a diagnostic accuracy study.

OBJECTIVE: To assess the accuracy of the World Health Organization (WHO) partograph alert line and other candidate predictors in the identification of women at risk of developing severe adverse birth outcomes. DESIGN: A facility-based, multicentre, prospective cohort study. SETTING: Thirteen maternity hospitals located in Nigeria and Uganda. POPULATION: A total of 9995 women with spontaneous onset of labour presenting at cervical dilatation of ≤6 cm or undergoing induction of labour. METHODS: Research assistants collected data on sociodemographic, anthropometric, obstetric, and medical characteristics of study participants at hospital admission, multiple assessments during labour, and interventions during labour and childbirth. The alert line and action line, intrapartum monitoring parameters, and customised labour curves were assessed using sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and the J statistic. OUTCOMES: Severe adverse birth outcomes. RESULTS: The rate of severe adverse birth outcomes was 2.2% (223 women with severe adverse birth outcomes), the rate of augmentation of labour was 35.1% (3506 women), and the caesarean section rate was 13.2% (1323 women). Forty-nine percent of women in labour crossed the alert line (4163/8489). All reference labour curves had a diagnostic odds ratio ranging from 1.29 to 1.60. The J statistic was less than 10% for all reference curves. CONCLUSIONS: Our findings suggest that labour is an extremely variable phenomenon, and the assessment of cervical dilatation over time is a poor predictor of severe adverse birth outcomes. The validity of a partograph alert line based on the 'one-centimetre per hour' rule should be re-evaluated. FUNDING: Bill & Melinda Gates Foundation, United States Agency for International Development (USAID), UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), and WHO (A65879). TWEETABLE ABSTRACT: The alert line in check: results from a WHO study.

Gender influence on manganese induced depression-like behavior and Mn and Fe deposition in different regions of CNS and excretory organs in intraperitoneally exposed rats.

Manganese (Mn) is an essential metal for mammals. It can modulate the action of endogenous substances, as neurotransmitters, but in excess also can trigger known neurotoxic effects. Many studies have been conducted assessing Mn neurotoxicity. However, Mn bioaccumulation in different brain tissues and behavior effects involving gender-specific studies are conflicted in the literature. Therefore, the aim of this work was to compare Mn effects, after 30days of intraperitoneal treatment, in male and female rats, submitted to forced swim and open field tests. After that, were evaluated Mn and Fe tissue levels in CNS, liver, and kidneys. Wistar rats were divided into saline, Mn 1mg/kg, Mn 5mg/kg, and imipramine (as forced swim control). Then, animals were euthanized by anesthesia overdose followed by decapitation and the collected tissue were striatum, hippocampus, brainstem, cortex, cerebellum, hepatic tissue, and renal tissue. Mn and Fe were determined by ICP-MS. There was a dose-dependent effect on accumulation of Mn in the cerebellum and brainstem to the dosage of 5mg/kg. In hippocampus there were bioaccumulation differences between gender and dose, and an increase of Fe in the groups exposed to Mn. Excess metals in the brain dissected has a strong influence on memory and learning processes and suggests pro-depressive effects, possibly triggered by the reduction of monoamines due to excessive metal bioaccumulation. It was concluded that, under this experimental design, Mn exposure cause metal deposition on dissected CNS, liver and kidney. There an effect at lower doses that was gender-dependent and males had more pronounced behavioral damage compared to females, although with increasing dose, females had an indication of motor damage.

Dipyridamole increases the cytotoxicity of cisplatin in human larynx cancer cells in vitro

This paper describes the effect of dipyridamole (DIP) on the cytotoxicity of cisplatin in HEp-2 human larynx cancer cells in vitro and the nature of the interaction between cisplatin and dipyridamole. Cytotoxic assays were performed to obtain the IC50 for cisplatin. The cells were treated with 0, 20, 40, 80, 120 or 200 µM cisplatin, with or without a single concentration of DIP and incubated for 60 min at 37ºC and 5 percent CO2 for 3 days and then counted with a hemocytometer. The accumulation of cisplatin in the cells was measured by atomic absorption and fluorescence was used to determine the membrane binding constant of DIP. In the presence of 10, 20 and 30 µM DIP, the IC50 of cisplatin was reduced by 25, 60 and 82 percent in HEp-2 cells. Combination index analysis revealed that cisplatin and DIP interact synergistically. In larynx cancer cells, the accumulation of cisplatin increased by 13, 27 and 65 percent as the DIP concentration was increased from 10 to 20 and 30 µM, respectively. The binding constant of DIP to the cell membrane was estimated to be 0.36 ± 0.12 mg/ml (N = 2) by fluorescence and cisplatin did not suppress DIP fluorescence. These results suggest that DIP significantly enhances cisplatin cytotoxicity in HEp-2 cells by increasing cisplatin accumulation, probably by altering the cell membrane as suggested by its binding constant. The results obtained reinforce the importance of combination therapy to reduce the doses of chemotherapeutic drugs and therefore the side effects of chemotherapy.