Flexible fluorine-thiol displacement stapled peptides with enhanced membrane penetration for the estrogen receptor/coactivator interaction.

Understanding how natural and engineered peptides enter cells would facilitate the elucidation of biochemical mechanisms underlying cell biology and is pivotal for developing effective intracellular targeting strategies. In this study, we demonstrate that our peptide stapling technique, fluorine-thiol displacement reaction (FTDR), can produce flexibly constrained peptides with significantly improved cellular uptake, particularly into the nucleus. This platform confers enhanced flexibility, which is further amplified by the inclusion of a D-amino acid, while maintaining environment-dependent α helicity, resulting in highly permeable peptides without the need for additional cell-penetrating motifs.

Population assessment of health system performance in 16 countries.

Objective: To demonstrate how the new internationally comparable instrument, the People's Voice Survey, can be used to contribute the perspective of the population in assessing health system performance in countries of all levels of income.

Methods: We surveyed representative samples of populations in 16 low-, middle- and high-income countries on health-care utilization, experience and confidence during 2022-2023. We summarized and visualized data corresponding to the key domains of the World Health Organization universal health coverage framework for health system performance assessment.

Health system quality and COVID-19 vaccination: a cross-sectional analysis in 14 countries.

The social and behavioural determinants of COVID-19 vaccination have been described previously. However, little is known about how vaccinated people use and rate their health system. We used surveys conducted in 14 countries to study the health system correlates of COVID-19 vaccination.

Primary health care in practice: usual source of care and health system performance across 14 countries.

Primary health care (PHC) is central to attainment of the Sustainable Development Goals, yet comparable cross-country data on key aspects of primary care have not been widely available. This study analysed data from the People's Voice Survey, which was conducted in 2022 and 2023 in 14 countries. We documented usual source of care across countries and examined associations of usual source of care with core PHC services, quality ratings, and health system confidence.

The path to universal health coverage in five African and Asian countries: examining the association between insurance status and health-care use.

Despite major efforts to achieve universal health coverage (UHC), progress has lagged in many African and Asian countries. A key strategy pursued by many countries is the use of health insurance to increase access and affordability. However, evidence on insurance coverage and on the association between insurance and UHC is mixed.

User-reported quality of care: findings from the first round of the People's Voice Survey in 14 countries.

High-quality care is essential for improving health outcomes, although many health systems struggle to maintain good quality. We use data from the People's Voice Survey-a nationally representative survey conducted in 14 high-income, middle-income, and low-income countries-to describe user-reported quality of most recent health care in the past 12 months. We described ratings for 14 measures of care competence, system competence, and user experience and assessed the relationship between visit quality factors and user recommendation of the facility.

Site-specific protein conjugates incorporating Para-Azido-L-Phenylalanine for cellular and in vivo imaging.

This work features the use of amber suppression-mediated unnatural amino acid (UAA) incorporation into proteins for various imaging purposes. The site-specific incorporation of the UAA, p-azido-L-phenylalanine (pAzF), provides an azide handle that can be used to complete the strain promoted azide-alkyne click cycloaddition (SPAAC) reaction to introduce an imaging modality such as a fluorophore or a positron emission tomography (PET) tracer on the protein of interest (POI). Such methodology can be pursued directly in mammalian cell lines or on proteins expressed in vitro, thereby conferring a homogeneous pool of protein conjugates.

Measuring people's views on health system performance: Design and development of the People's Voice Survey.

Todd Lewis and co-authors discuss development and use of the People's Voice Survey for health system assessment.

Environmental Conditions and Vehicle Disturbance Influence Stress Behaviors in a Working Harris's Hawk ().

Harris's hawk () is used for pest control, as their presence can deter wild birds such as gulls. Working Harris's hawk on UK waste sites is permitted in accordance with regulations and legislation. This study investigated the general environment of a waste site compound yard where a single Harris's hawk was flown for pest control.

Health service quality in 2929 facilities in six low-income and middle-income countries: a positive deviance analysis.

Background: Primary care is of insufficient quality in many low-income and middle-income countries. Some health facilities perform better than others despite operating in similar contexts, although the factors that characterise best performance are not well known. Existing best-performance analyses are concentrated in high-income countries and focus on hospitals.

Best and worst performing health facilities: A positive deviance analysis of perceived drivers of primary care performance in Nepal.

Primary care services are on average of low quality in Nepal. However, there is marked variation in performance of basic clinical and managerial functions between primary health care centers. The determinants of variation in primary care performance in low- and middle-income countries have been understudied relative to the prominence of primary care in national health plans.

Semi-syntheses and interrogation of indole-substituted terpenoid alkaloids.

We demonstrated here a series of terpenoid alkaloids can be quickly prepared using semisynthesis from naturally sourced tabersonine, featuring multiple oxygen-based substituents on the indole ring such as hydroxy and methoxy groups. This panel of complex compounds enabled the exploration of indole modifications to optimize the indole alkaloids' anticancer activity, generating lead compounds (, with C15-hydroxy, C16-methoxy, and/or C17-methoxy derivatizations) that potently inhibit cancer cell line growth in the single-digit micromolar range. These results can help guide the development of terpenoid alkaloid therapeutics.

Improving health and social systems for all children in LMICs: structural innovations to deliver high-quality services.

Despite health gains over the past 30 years, children and adolescents are not reaching their health potential in many low-income and middle-income countries (LMICs). In addition to health systems, social systems, such as schools, communities, families, and digital platforms, can be used to promote health. We did a targeted literature review of how well health and social systems are meeting the needs of children in LMICs using the framework of The Lancet Global Health Commission on high-quality health systems and we reviewed evidence for structural reforms in health and social sectors.

Associations between women's empowerment, care seeking, and quality of malaria care for children: A cross-sectional analysis of demographic and health surveys in 16 sub-Saharan African countries.

Background: Fever and malaria are highly prevalent among children under five across sub-Saharan Africa, but utilization and quality of care for febrile illness remain insufficient. Many studies examine socioeconomic and demographic determinants of care seeking; however, few assess how women's empowerment influences care seeking and quality. We examine associations of women's empowerment with: a) care utilization for children with fever and malaria and b) the quality of that care in 16 sub-Saharan African countries.

Concentration Dependence of a Hydrogel Phase Formed by the Deprotonation of the Imidazole Side Chain of Glycylhistidylglycine.

Upon deprotonation of its imidazole group at ∼pH 6, the unblocked tripeptide glycylhistidylglycine (GHG) self-assembles into very long crystalline fibrils on a 10-1000 μm scale which are capable of forming a volume spanning network, that is, hydrogel. The critical peptide concentration for self-assembly at a pH of 6 lies between 50 and 60 mM. The fraction of peptides that self-assemble into fibrils depends on the concentration of deprotonated GHG.

A Critical Review of the Efficacy and Safety of Inclisiran.

The association between low-density cholesterol (LDL-C) and cardiovascular disease (CVD) is well-established, with an emphasis on lowering LDL-C levels to reduce cardiovascular events. Statin therapy has been the traditional treatment for LDL-C reduction, in addition to lifestyle modifications, but studies have shown that a substantial proportion of patients does not reach target LDL-C goals despite receiving maximally tolerated statin medications. Additionally, statin therapy is associated with a few shortcomings as many patients initiated on these medications discontinue treatment within 1 year because of lack of tolerability.

Quality in crisis: a systematic review of the quality of health systems in humanitarian settings.

Background: There is a growing concern that the quality of health systems in humanitarian crises and the care they provide has received little attention. To help better understand current practice and research on health system quality, this paper aimed to examine the evidence on the quality of health systems in humanitarian settings.

Methods: This systematic review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol.

The tripeptide GHG as an unexpected hydrogelator triggered by imidazole deprotonation.

The tripeptide glycyl-histidyl-glycine (GHG) self-assembles into long, crystalline fibrils forming a strong hydrogel (G'∼ 50 kPa) above a critical concentration of 40 mM upon the deprotonation of its imidazole group. Spectroscopic data reveal a mixture of helically twisted β-sheets and monomers to coexist in the gel phase.

A Review of the Efficacy and Tolerability of Bempedoic Acid in the Treatment of Hypercholesterolemia.

Despite the widespread use of statins and ezetimibe to decrease low-density lipoprotein cholesterol (LDL-C) levels and associated atherosclerotic cardiovascular disease (ASCVD), many patients do not achieve adequate LDL-C lowering as per the recommended American College of Cardiology (ACC)/American Heart Association (AHA) and European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines and demonstrate residual cardiovascular risk. The introduction of proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors in 2015 was a promising addition to hypercholesterolemia therapies, but their cost and subcutaneous administration has limited their use, and therefore, new affordable and patient friendly treatment strategies are crucial to help reduce ASCVD risk. Bempedoic acid, a drug currently under investigation, is a small molecule that has been shown to upregulate LDL receptors, decrease LDL-C, and reduce atherosclerotic plaque formation in hypercholesterolemic patients.

Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors for Cardiovascular Disease Prevention.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Because of these associated risks, managing diabetes and CVD, including heart failure (HF), has become a joint effort to reduce the risk of adverse outcomes. Although many patients with T2DM are receiving preventive therapies for CVD, their residual risk remains high for atherosclerotic CVD (ASCVD).

Exploring the gel phase of cationic glycylalanylglycine in ethanol/water. I. Rheology and microscopy studies.

Hypothesis: The cationic tripeptide glycylalanylglycine (GAG) self-assembles into long, thick crystalline fibrils in an ethanol/water solution. At sufficiently high concentrations, the fibrils form a volume spanning hydrogel network. We report an extensive rheology and microscopy-based study regarding the self-assembly of GAG in ethanol/water solutions to understand the conditions for fibril formation as well as the thermal stability for future developments of this material.

Analysis of Trinucleotide Repeat Stability by Integration at a Chromosomal Ectopic Site.

Expansions of CNG microsatellite tracts are responsible for several neurodegenerative diseases, including myotonic dystrophy type 1, Huntington disease, and spinocerebellar ataxia type 8. Here we show that expanded (CNG) repeats are susceptible not only to expansions and contractions, but are prone to DNA double strand breaks following replication stress. We describe a general strategy for the construction of clonal cell lines containing CNG repeats of various lengths, in which the microsatellites are integrated using the yeast FLP recombinase at a single ectopic recombination acceptor site in the HeLa genome.

A spotlight on alirocumab in high cardiovascular risk patients with type 2 diabetes and mixed dyslipidemia: a review on the emerging data.

Diabetes is a significant and independent risk factor for atherosclerotic cardiovascular disease (ASCVD), leading to morbidity and mortality among this population. The prevention of macrovascular complications, such as CVD, peripheral arterial disease, and cerebrovascular accident, in patients with diabetes is obtained through multifactorial risk reduction, including mixed dyslipidemia management and adequate glycemic control. For patients with diabetes, it is crucial to initiate adequate dyslipidemia therapy to achieve recommended low-density lipoprotein cholesterol (LDL-C) goal of <70 mg/dL or target non-high-density lipoprotein goal of <100 mg/dL.