Anatase titanium dioxide nanoparticles in mice: evidence for induced structural and functional sperm defects after short-, but not long-, term exposure

Titanium dioxide (TiO₂) nanoparticles (TNPs) are widely used commercially and exist in a variety of products. To determine if anatase TNPs (ATNPs) in doses smaller than previously used reach the scrotum after entry in the body at a distant location and induce sperm defects, 100% ATNP (2.5 or 5 mg kg⁻¹ body weight) was administered intraperitoneally to adult males for three consecutive days, followed by sacrifice 1, 2, 3, or 5 weeks later (long-) or 24, 48 or 120 h (short-term exposure). Transmission electron microscopy revealed the presence of ANTP in scrotal adipose tissues collected 120 h postinjection when cytokine evaluation showed an inflammatory response in epididymal tissues and fluid. At 120 h and up to 3 weeks postinjection, testicular histology revealed enlarged interstitial spaces. Significantly increased numbers of terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling-positive (apoptotic) germ (P = 0.002) and interstitial space cells (P = 0.04) were detected in treated males. Caudal epididymal sperm from the short-term, but not a long-term, arm showed significantly (P < 0.001) increased frequencies of flagellar abnormalities, excess residual cytoplasm (ERC), and unreacted acrosomes in treated versus controls (dose-response relationship). A novel correlation between ERC and unreacted acrosomes was uncovered. At 120 h, there were significant decreases in hyperactivated motility (P < 0.001) and mitochondrial membrane potential (P < 0.05), and increased reactive oxygen species levels (P < 0.00001) in treated versus control sperm. These results indicate that at 4–8 days postinjection, ANTP induce structural and functional sperm defects associated with infertility, and DNA damage via oxidative stress. Sperm defects were transient as they were not detected 10 days to 5 weeks postinjection.     

Seasonal trends and maternal characteristics as predictors of maternal undernutrition and low birthweight in Eastern Maharashtra,India

Few studies have assessed whether women and infants in rural and peri‐urban communities in South Asia experience seasonal fluctuations in nutritional status; however, a handful of studies have documented seasonal variability in risk factors for undernutrition including food availability, physical activity and infections. We used data from the Maternal and Newborn Health (MNH) registry, a population‐based pregnancy and birth registry in Eastern Maharashtra, India, to analyse seasonal trends in birthweight and maternal nutritional status—body mass index (BMI) and haemoglobin—in the first trimester of pregnancy. We plotted monthly and seasonal trends in birthweight, and maternal BMI and haemoglobin, and used multivariable regression models to identify seasonal and maternal characteristics that predicted each outcome. Between October 2014 and January 2018, MNH included 29,253 livebirths with recorded birthweight. BMI was assessed in 15,252 women less than 12 weeks of gestation and haemoglobin in 18,278 women less than 13 weeks of gestation. Maternal characteristics (age, education, parity and height) were significantly associated with nutritional status; however, there were minimal seasonal fluctuations in birthweight or maternal nutrition. There were significant secular trends in maternal haemoglobin; between 2014 and 2018, the prevalence of maternal anaemia decreased from 91% to 79% and moderate or severe anaemia from 53% to 37%. The prevalence of maternal underweight (45.3%) and overweight (9.8%) and low birthweight (19.1%) remained relatively constant over the study period. Our findings highlight that in some rural and peri‐urban areas in South Asia, tackling systemic drivers of malnutrition may be more effective than targeted interventions based on season.     

Efectividad de un nuevo modelo de derivación telefónica compartida entre atención primaria y atención hospitalaria

Aim

The purpose of this study is to find out whether telephone referral from Primary Health Care to Internal Medicine Consult manages to reduce waiting days as compared to traditional referral. This study also aims to know how acceptable is the telephone referral to general practitioners and their patients.

Rucaparib in the landscape of PARP inhibition in ovarian cancer

Introduction: The landscape of poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer is rapidly evolving and becoming increasingly complex. Ovarian cancer is leading therapeutic innovation by providing the proof of concept for DNA repair as a target. Three different PARP inhibitors have now received approvals in the US and Europe in different indications. Subtle but crucial differences can be found among the licensed indications for each PARP inhibitor in terms of histology, type of BRCA mutation (germline and/or somatic), number of prior lines of chemotherapy and whether the indication is in the treatment or maintenance settings.

Areas covered: We review the latest clinical data regarding the PARP inhibitor rucaparib in ovarian cancer, provide an update on the evolving landscape of PARP inhibition in ovarian cancer, and summarize avenues of ongoing and future research.

Expert opinion: All eligible patients should be offered a PARP inhibitor. SOLO1 trial results demonstrated an unprecedented benefit maintenance with PARP inhibitors in first line. Results from trials evaluating PARP inhibitors as maintenance in first line regardless of BRCA status and from trials evaluating combinatorial strategies are eagerly awaited.