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Context: There is mounting evidence implicating kisspeptin signalling in placental development and function. Aims: This study aimed to elucidate kisspeptin's role in trophoblast invasion and migration using three experimental models. Methods: First, we examined the mouse fetus and placenta in a kisspeptin receptor (Kiss1r) knockout (KO) model. Fetal/placental weights and gene expression (quantitative polymerase chain reaction) were assessed. Second, we determined kisspeptin effects on a human trophoblast (BeWo) cell line in vitro. Third, we examined KISS1 and KISS1R gene expression in human placenta from term and pre-Term pregnancies. Key results: No difference was found in fetal or placental weight between Kiss1r KO and wildtype mice. However, expression of the trophoblast invasion marker, Mmp2 mRNA, was greater in the placental labyrinth zone of Kiss1r KO mice. BeWo cell models of villus cytotrophoblast and syncytiotrophoblast cells exhibited kisspeptin protein expression, with greater expression in syncytiotrophoblast, consistent with KISS1 mRNA. Kisspeptin treatment inhibited the migratory potential of cytotrophoblast-like cells. Finally, while no difference was seen in KISS1 and KISS1R mRNA between term and pre-Term placentas, we saw a difference in the relative expression of each gene pre-Term. We also observed a positive correlation between KISS1 expression and maternal body mass index. Conclusions: Our results indicate that kisspeptin may inhibit trophoblast invasion. Implications: Further investigation is required to clarify specific regulatory mechanisms.

Background: Slums or informal settlements characterize most large cities in LMIC. Previous evidence suggests pharmacies may be the most frequently used source of primary care in LMICs but that pharmacy services are of variable quality. However, evidence on pharmacy use and availability is very limited for slum populations. Methods: We conducted household, individual, and healthcare provider surveys and qualitative observations on pharmacies and pharmacy use in seven slum sites in four countries (Nigeria, Kenya, Pakistan, and Bangladesh). All pharmacies and up to 1200 households in each site were sampled. Adults and children were surveyed about their use of healthcare services and pharmacies were observed and their services, equipment, and stock documented. Results: We completed 7692 household and 7451 individual adults, 2633 individual child surveys, and 157 surveys of pharmacies located within the seven sites. Visit rates to pharmacies and drug sellers varied from 0.1 (Nigeria) to 3.0 (Bangladesh) visits per person-year, almost all of which were for new conditions. We found highly variable conditions in what constituted a “pharmacy” across the sites and most pharmacies did not employ a qualified pharmacist. Analgesics and antibiotics were widely available but other categories of medications, particularly those for chronic illness were often not available anywhere. The majority of pharmacies lacked basic equipment such as a thermometer and weighing scales. Conclusions: Pharmacies are locally and widely available to residents of slums. However, the conditions of the facilities and availability of medicines were poor and prices relatively high. Pharmacies may represent a large untapped resource to improving access to primary care for the urban poor.

Background: Slums or informal settlements characterize most large cities in LMIC. Previous evidence suggests pharmacies may be the most frequently used source of primary care in LMICs but that pharmacy services are of variable quality. However, evidence on pharmacy use and availability is very limited for slum populations. Methods: We conducted household, individual, and healthcare provider surveys and qualitative observations on pharmacies and pharmacy use in seven slum sites in four countries (Nigeria, Kenya, Pakistan, and Bangladesh). All pharmacies and up to 1200 households in each site were sampled. Adults and children were surveyed about their use of healthcare services and pharmacies were observed and their services, equipment, and stock documented. Results: We completed 7692 household and 7451 individual adults, 2633 individual child surveys, and 157 surveys of pharmacies located within the seven sites. Visit rates to pharmacies and drug sellers varied from 0.1 (Nigeria) to 3.0 (Bangladesh) visits per person-year, almost all of which were for new conditions. We found highly variable conditions in what constituted a “pharmacy” across the sites and most pharmacies did not employ a qualified pharmacist. Analgesics and antibiotics were widely available but other categories of medications, particularly those for chronic illness were often not available anywhere. The majority of pharmacies lacked basic equipment such as a thermometer and weighing scales. Conclusions: Pharmacies are locally and widely available to residents of slums. However, the conditions of the facilities and availability of medicines were poor and prices relatively high. Pharmacies may represent a large untapped resource to improving access to primary care for the urban poor.

Describes hardware that enables the use of an IBM PC microcomputer as a frequency meter or a counter by using the parallel printer port. Eliminates the 16-bit time-day counter through the use of an external time base that can be conveniently set depending on the desired frequency range. (JRH)

BACKGROUND: Impaired stress resilience and a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis are suggested to play key roles in the pathophysiology of illness progression in bipolar disorder (BD), but the mechanisms leading to this dysfunction have never been elucidated. This study aimed to examine HPA axis activity and underlying molecular mechanisms in patients with BD and unaffected siblings of BD patients. METHODS: Twenty-four euthymic patients with BD, 18 siblings of BD patients, and 26 healthy controls were recruited for this study. All subjects underwent a dexamethasone suppression test followed by analyses associated with the HPA axis and the glucocorticoid receptor (GR). RESULTS: Patients with BD, particularly those at a late stage of illness, presented increased salivary post-dexamethasone cortisol levels when compared to controls (p = 0.015). Accordingly, these patients presented reduced ex vivo GR responsiveness (p = 0.008) and increased basal protein levels of FK506-binding protein 51 (FKBP51, p = 0.012), a co-chaperone known to desensitize GR, in peripheral blood mononuclear cells. Moreover, BD patients presented increased methylation at the FK506-binding protein 5 (FKBP5) gene. BD siblings presented significantly lower FKBP51 protein levels than BD patients, even though no differences were found in FKBP5 basal mRNA levels. CONCLUSIONS: Our data suggest that the epigenetic modulation of the FKBP5 gene, along with increased FKBP51 levels, is associated with the GR hyporesponsiveness seen in BD patients. Our findings are consistent with the notion that unaffected first-degree relatives of BD patients share biological factors that influence the disorder, and that such changes are more pronounced in the late stages of the illness.