Comparison of a novel potentiator of CFTR channel activity to ivacaftor in ameliorating mucostasis caused by cigarette smoke in primary human bronchial airway epithelial cells.

Background: Cystic Fibrosis causing mutations in the gene , reduce the activity of the CFTR channel protein, and leads to mucus aggregation, airway obstruction and poor lung function. A role for CFTR in the pathogenesis of other muco-obstructive airway diseases such as Chronic Obstructive Pulmonary Disease (COPD) has been well established. The CFTR modulatory compound, Ivacaftor (VX-770), potentiates channel activity of CFTR and certain CF-causing mutations and has been shown to ameliorate mucus obstruction and improve lung function in people harbouring these CF-causing mutations.

Effectiveness and safety of tenofovir alafenamide in children and adolescents living with HIV: a systematic review.

Introduction: Tenofovir alafenamide (TAF) is approved for paediatric use in fixed-dose combination tablets, but efficacy and safety data in children are limited. We conducted a systematic review on the efficacy/effectiveness and safety of TAF in infants, children and adolescents living with HIV.

Methods: We searched MEDLINE, Embase, the Cochrane Library, clinical trial registries, reference lists and relevant conferences to identify literature published January 2009-March 2021.

Effectiveness and safety of dolutegravir and raltegravir for treating children and adolescents living with HIV: a systematic review.

Introduction: Globally about 1.7 million children were living with HIV in 2020. Two integrase strand transfer inhibitors, dolutegravir and raltegravir, are increasingly used in children.

Prioritising the most needed paediatric antiretroviral formulations: the PADO4 list.

Despite considerable progress in paediatric HIV treatment and timely revision of global policies recommending the use of more effective and tolerable antiretroviral regimens, optimal antiretroviral formulations for infants, children, and adolescents remain limited. The Paediatric Antiretroviral Drug Optimization group reviews medium-term and long-term priorities for antiretroviral drug development to guide industry and other stakeholders on formulations most needed for low-income and middle-income countries. The group convened in December, 2018, to assess progress since the previous meeting and update the list of priority formulations.

Long-acting or extended-release antiretroviral products for HIV treatment and prevention in infants, children, adolescents, and pregnant and breastfeeding women: knowledge gaps and research priorities.

Antiretroviral agents with long-acting properties have potential to improve treatment outcomes substantially for people living with HIV. In November 2017, the Long acting/Extended Release Antiretroviral Resource Program (LEAP) convened a workshop with the aim of shaping the research agenda and promoting early development of long-acting or extended release products for key populations: pregnant and lactating women, children aged up to 10 years, and adolescents aged 10-19 years. Goals included strategies and principles to ensure that the needs of children, adolescents, and pregnant and lactating women are considered when developing long-acting formulations.

Stillbirth in Women Living With HIV Delivering in the United Kingdom and Ireland: 2007-2015.

Background: Women living with HIV have a higher risk of adverse birth outcomes, but questions remain regarding their specific risk factors for stillbirth and the extent to which maternal HIV is associated with stillbirth.

Methods: Using data on pregnant women with HIV reported within population-based surveillance in the United Kingdom/Ireland, we described stillbirth rates in 2007-2015 stratified by type of antiretroviral therapy (ART) and evaluated risk factors using Poisson regression. General population stillbirth rates by maternal world region of origin were derived from national annual birth statistics, and compared with rates in women with HIV, using standardized stillbirth ratios with the general population as the reference.

Diabetes Disparities and Promising Interventions to Address Diabetes in Native Hawaiian and Pacific Islander Populations.

Purpose Of Review: The Native Hawaiian and Pacific Islander (NHPI) population is rapidly growing in the USA. NHPIs face significant health disparities and have a high prevalence of diabetes compared to the general US population.

Recent Findings: Recent culturally-adapted diabetes interventions have shown promise in addressing these disparities among NHPI communities.

Importance of Prospective Studies in Pregnant and Breastfeeding Women Living With Human Immunodeficiency Virus.

Recently, the US Food and Drug Administration and European Medicines Agency issued warnings on the use of dolutegravir and darunavir/cobicistat for treatment of pregnant women living with human immunodeficiency virus (HIV). It took 3-5 years to identify the risks associated with the use of these antiretroviral drugs, during which time pregnant women were exposed to these drugs in clinical care, outside of controlled clinical trial settings. Across all antiretroviral drugs, the interval between registration of new drugs and first data on pharmacokinetics and safety in pregnancy becoming available is around 6 years.

Protease inhibitors and preterm delivery: another piece in the puzzle.

Background: Questions remain regarding preterm delivery (PTD) risk in HIV-infected women on antiretroviral therapy (ART), including the role of ritonavir (RTV)-boosted protease inhibitors, timing of ART initiation and immune status.

Methods: We examined data from the UK/Ireland National Study of HIV in Pregnancy and Childhood on women with HIV delivering a singleton live infant in 2007-2015, including those pregnancies receiving RTV-boosted protease inhibitor-based (n = 4184) or nonnucleoside reverse transcriptase inhibitors-based regimens (n = 1889). We conducted logistic regression analysis adjusted for risk factors associated with PTD and stratified by ART at conception and CD4 cell count to minimize bias by indication for treatment and to assess whether PTD risk differs by ART class and specific drug combinations.

Discovery and electrophysiological characterization of SKF-32802: A novel hERG agonist found through a large-scale structural similarity search.

Despite the importance of the hERG channel in drug discovery and the sizable number of antagonist molecules discovered, only a few hERG agonists have been discovered. Here we report a novel hERG agonist; SKF-32802 and a structural analog of the agonist NS3623, SB-335573. These were discovered through a similarity search of published hERG agonists.

The PILI@Work Program: a translation of the diabetes prevention program to Native Hawaiian-serving worksites in Hawai'i.

A previously translated Diabetes Prevention Program Lifestyle Intervention (DPP-LI) was adapted for delivery as a worksite-based intervention, called PILI@Work, to address obesity disparities in Native Hawaiians/Pacific Islanders. This study examined the effectiveness of PILI@Work and factors associated with weight loss at post-intervention. Overweight/obese employees of 15 Native Hawaiian-serving organizations received the 3-month component of PILI@Work.

Prevalence of depressive symptoms in pregnant and postnatal HIV-positive women in Ukraine: a cross-sectional survey.

Background: Perinatal depression among HIV-positive women has negative implications for HIV-related and other maternal and infant outcomes. The aim of this study was to investigate the burden and correlates of perinatal depression among HIV-positive women in Ukraine, a lower middle income country with one of the largest HIV-positive populations in Europe.

Methods: Cross-sectional surveys nested within the Ukraine European Collaborative Study were conducted of HIV-positive women at delivery and between 1 and 12 months postpartum.

Community-Based Participatory Research Integrates Behavioral and Biological Research to Achieve Health Equity for Native Hawaiians.

Native Hawaiians bear a disproportionate burden of type-2 diabetes and related complications compared to all other groups in Hawai'i (e.g., Whites, Japanese, Korean).

Pregnancy outcomes in HIV-positive women in Ukraine, 2000-12 (European Collaborative Study in EuroCoord): an observational cohort study.

Background: Women living with HIV are potentially at increased risk of adverse pregnancy outcomes, due to a range of factors, including immunosuppression, use of combination antiretroviral therapy (ART), and injecting drug use. Rates of mother-to-child transmission of HIV in Ukraine have declined to around 2-4%, but little is known about other pregnancy outcomes in this setting. We used data from an observational prospective cohort study to assess pregnancy outcomes among HIV-positive women in Ukraine.

The PILI 'Ohana Project: a community-academic partnership to achieve metabolic health equity in Hawai'i.

Native Hawaiians and Pacific Islanders (NHPI) have higher rates of excess body weight and related medical disorders, such as diabetes and cardiovascular disease, compared to other ethnic groups in Hawai'i. To address this metabolic health inequity, the Partnership for Improving Lifestyle Intervention (PILI) 'Ohana Project, a community-academic partnership, was formed over eight years ago and developed two community-placed health promotion programs: the PILI Lifestyle Program (PLP) to address overweight/obesity and the Partners in Care (PIC) to address diabetes self-care. This article describes and reviews the innovations, scientific discoveries, and community capacity built over the last eight years by the PILI 'Ohana Project's (POP) partnership in working toward metabolic health equity.

Adherence to antiretroviral therapy during pregnancy and the first year postpartum among HIV-positive women in Ukraine.

Background: Poor adherence to antiretroviral therapy (ART) is associated with HIV disease progression and, during pregnancy, increased mother-to-child transmission risk. In Ukraine, access to combination ART is expanding but data on adherence are scarce.

Methods: Cross-sectional surveys of HIV-positive women were conducted i) at delivery (on antenatal ART adherence) and ii) during the first year postpartum (on ART adherence in the preceding four weeks).

Ethnic and gender differences in ideal body size and related attitudes among Asians, Native Hawaiians, and Whites.

Often overlooked explanations for the varied obesity rates across ethno-cultural groups include differences in attitudes toward excess weight, with certain populations assumed to have larger ideal body sizes (IBS). Past studies found ethnic and gender difference in IBS across and within different groups. This study examined the effects of ethnicity and gender, and their interaction, in accounting for differences in IBS and attitudes toward those ideals.

Earlier initiation of ART and further decline in mother-to-child HIV transmission rates, 2000-2011.

Objectives: To analyze mother-to-child HIV transmission (MTCT) rates over time in light of changes in management, demographic, and pregnancy characteristics.

Design: Population-based surveillance data on diagnosed HIV-positive women and their infants are routinely collected in the UK and Ireland.

Methods: A total of 12486 singleton pregnancies delivered in 2000-2011 were analyzed.

Impact of expanded access to combination antiretroviral therapy in pregnancy: results from a cohort study in Ukraine.

Objective: To investigate the scale-up of antenatal combination antiretroviral therapy (cART) in Ukraine since this became part of the national policy for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV).

Methods: Data on 3535 HIV-positive pregnant women who were enrolled into the Ukraine European Collaborative Study in 2008-2010 were analysed. Factors associated with receipt of zidovudine monotherapy (AZTm) - rather than cART - and rates of mother-to-child transmission (MTCT) of HIV were investigated.

Predicting drug-induced QT prolongation and torsades de pointes: a review of preclinical endpoint measures.

Compound-induced prolongation of the cardiac QT interval is a major concern in drug development and this unit discusses approaches that can predict QT effects prior to undertaking clinical trials. The majority of compounds that prolong the QT interval block the cardiac rapid delayed rectifier potassium current, IKr (hERG). Described in this overview are different ways to measure hERG, from recent advances in automated electrophysiology to the quantification of channel protein trafficking and binding.