Design and implementation of a Primary Health Care (PHC) Toolbox for improving the impact of support from Global Development Partners.

Primary Health Care (PHC) is the most equitable and cost-effective way to enhance the health of populations and improve health security and is a requirement for achieving universal health coverage (UHC). Vital to advancing the PHC agenda is effective global health partnerships, particularly with Global Health Initiatives (GHIs) which provide financial support for improving population health. Despite progress, GHI support at times remained parallel to rather than embedded in national health strategies.

The rate of muscle wasting in liver transplant recipients on waiting list: post-transplant outcomes and associated serum metabolite patterns.

Background: Sarcopenia at the time of liver transplantation (LT) is an established risk factor for mortality following LT. However, most studies in this context have defined sarcopenia by one-time, static measurements. The aims of this study were (I) to determine the impact of the rate of muscle loss in waitlisted LT recipients on post-LT outcomes and (II) to identify patterns of serum metabolites associated with patients with more progressive sarcopenia.

Interlaboratory comparison of standardised metabolomics and lipidomics analyses in human and rodent blood using the MxP Quant 500 kit.

Metabolomics and lipidomics are pivotal in understanding phenotypic variations beyond genomics. However, quantification and comparability of mass spectrometry (MS)-derived data are challenging. Standardised assays can enhance data comparability, enabling applications in multi-center epidemiological and clinical studies.

Discovery, Characterization, and Structure of a Cell Active PAD2 Inhibitor Acting through a Novel Allosteric Mechanism.

Peptidyl arginine deiminases (PADs) are important enzymes in many diseases, especially those involving inflammation and autoimmunity. Despite many years of effort, developing isoform-specific inhibitors has been a challenge. We describe herein the discovery of a potent, noncovalent PAD2 inhibitor, with selectivity over PAD3 and PAD4, from a DNA-encoded library.

Applying a Primary Health Care Approach to Closing the Human Resource for Health Gaps for Immunization.

This perspective is focused on the evidence on human resources for health (HRH) solutions for immunization, as a part of a primary health care (PHC) approach.. In the wake of the COVID-19 pandemic and 50 years since the Expanded Program on Immunization (EPI) clocks 50 years since its inception.

Plasma metabolites and physical function in patients undergoing hemodialysis.

Impaired physical function contributes to falls, fractures, and mortality among patients undergoing dialysis. Using a metabolomic approach, we identified metabolite alterations and effect size-based composite scores for constructs of impaired gait speed and grip strength. 108 participants incident to dialysis had targeted plasma metabolomics via liquid chromatography-mass spectrometry and physical function assessed (i.

Interaction of the C2C12 myotube contractions and glucose availability on transcriptome and extracellular vesicle microRNAs.

Exercise-like electrical pulse stimulation (EL-EPS) of myotubes mimics many key physiological changes induced by in vivo exercise. Besides enabling intracellular research, EL-EPS allows to study secreted factors, including muscle-specific microRNAs (myomiRs) carried in extracellular vesicles (EVs). These factors can participate in contraction-induced intercellular cross talk and may mediate the health benefits of exercise.

Prevalence and Overlap of Cardiac, Renal, and Metabolic Conditions in US Adults, 1999-2020.

Importance: Individually, cardiac, renal, and metabolic (CRM) conditions are common and leading causes of death, disability, and health care-associated costs. However, the frequency with which CRM conditions coexist has not been comprehensively characterized to date.

Objective: To examine the prevalence and overlap of CRM conditions among US adults currently and over time.

Restructuring of olfactory representations in the fly brain around odor relationships in natural sources.

A core challenge of olfactory neuroscience is to understand how neural representations of odor are generated and progressively transformed across different layers of the olfactory circuit into formats that support perception and behavior. The encoding of odor by odorant receptors in the input layer of the olfactory system reflects, at least in part, the chemical relationships between odor compounds. Neural representations of odor in higher order associative olfactory areas, generated by random feedforward networks, are expected to largely preserve these input odor relationships.

Identification of Gut Microbial Lysine and Histidine Degradation and CYP-Dependent Metabolites as Biomarkers of Fatty Liver Disease.

Numerous studies have described specific metabolites as biomarkers of severe liver diseases, but very few have measured gut microbiota (GM)-produced metabolites in fatty liver disease. We aimed at finding GM signatures and metabolite markers in plasma and feces related to high liver fat content. Based on imaging, we divided study participants into low (<5%, LF, =25) and high (>5%, HF, =39) liver fat groups.

Indirect treatment comparison of oral versus injectable azacitidine as maintenance therapy for acute myeloid leukemia.

Evaluate the relative efficacy of oral versus injectable azacitidine (AZA) maintenance therapy in acute myeloid leukemia (AML) after complete remission. Systematic literature review identified QUAZAR AML-001, HOVON 97 AML, UK NCRI AML16 and QoLESS-AZA-AMLE (sensitivity analysis) trials. Network meta-analysis and matching-adjusted indirect comparisons assessed survival outcomes.

Immunization programs to support primary health care and achieve universal health coverage.

Gains in immunization coverage and delivery of primary health care service have stagnated in recent years. Remaining gaps in service coverage reflect multiple underlying reasons that may be amenable to improved health system design. Immunization systems and other primary health care services can be mutually supportive, for improved service delivery and for strengthening of Universal Health Coverage.

Valve-in-Mitral Annular Calcification Transcatheter Mitral Valve Replacement After Thrombosis of Extracardiac Valved Conduit.

We report a patient with severe mitral annular calcification, mitral stenosis/regurgitation, hypertrophic obstructive cardiomyopathy, and subaortic membrane treated with valved left atrium-left ventricle conduit, septal myectomy, and membrane resection. Subsequent thrombosis of the conduit prompted successful valve-in- mitral annular calcification transcatheter mitral valve replacement and laceration of the anterior mitral leaflet to prevent outflow obstruction. ().

Parallel encoding of CO in attractive and aversive glomeruli by selective lateral signaling between olfactory afferents.

We describe a novel form of selective crosstalk between specific classes of primary olfactory receptor neurons (ORNs) in the Drosophila antennal lobe. Neurotransmitter release from ORNs is driven by two distinct sources of excitation: direct activity derived from the odorant receptor and stimulus-selective lateral signals originating from stereotypic subsets of other ORNs. Consequently, the level of presynaptic neurotransmitter release from an ORN can be significantly dissociated from its firing rate.

Metabolomics analysis reveals dysregulation in one carbon metabolism in Friedreich Ataxia.

Friedreich Ataxia (FA) is a rare and often fatal autosomal recessive disease in which a mitochondrial protein, frataxin (FXN), is severely reduced in all tissues. With loss of FXN, mitochondrial metabolism is severely disrupted. Multiple therapeutic approaches are in development, but a key limitation is the lack of biomarkers reflecting the activity of FXN in a timely fashion.

Circulating trimethylamine N-oxide levels following fish or seafood consumption.

Purpose: Some species of fish and seafood are high in trimethylamine N-oxide (TMAO), which accumulates in muscle where it protects against pressure and cold. Trimethylamine (TMA), the metabolic precursor to TMAO, is formed in fish during bacterial spoilage. Fish intake is promoted for its potential cardioprotective effects.

Intramolecular Ring-Opening Decomposition of Aryl Azetidines.

The ring strain present in azetidines can lead to undesired stability issues. Herein, we described a series of N-substituted azetidines which undergo an acid-mediated intramolecular ring-opening decomposition via nucleophilic attack of a pendant amide group. Studies were conducted to understand the decomposition mechanism enabling the design of stable analogues.

Metabolic Biomarkers for the Early Detection of Cancer Cachexia.

Cancer cachexia is a severe metabolic disorder characterized by progressive weight loss along with a dramatic loss in skeletal muscle and adipose tissue. Like cancer, cachexia progresses in stages starting with pre-cachexia to cachexia and finally to refractory cachexia. In the refractory stage, patients are no longer responsive to therapy and management of weight loss is no longer possible.

Metabolic profiles identify circulating biomarkers associated with heart failure in young single ventricle patients.

Background: Children and young adults with single ventricle (SV) heart disease frequently develop heart failure (HF) that is intractable and difficult to treat. Our understanding of the molecular and biochemical reasons underlying this is imperfect. Thus, there is an urgent need for biomarkers that predict outcome and provide a rational basis for treatment, and advance our understanding of the basis of HF.

AMP deamination is sufficient to replicate an atrophy-like metabolic phenotype in skeletal muscle.

Background: Skeletal muscle atrophy, whether caused by chronic disease, acute critical illness, disuse or aging, is characterized by tissue-specific decrease in oxidative capacity and broad alterations in metabolism that contribute to functional decline. However, the underlying mechanisms responsible for these metabolic changes are largely unknown. One of the most highly upregulated genes in atrophic muscle is AMP deaminase 3 (AMPD3: AMP → IMP + NH), which controls the content of intracellular adenine nucleotides (AdN; ATP + ADP + AMP).

Child health and the implementation of Community and District-management Empowerment for Scale-up (CODES) in Uganda: a randomised controlled trial.

Introduction: Uganda's district-level administrative units buttress the public healthcare system. In many districts, however, local capacity is incommensurate with that required to plan and implement quality health interventions. This study investigates how a district management strategy informed by local data and community dialogue influences health services.

Urine and Plasma Metabolome of Healthy Adults Consuming the DASH (Dietary Approaches to Stop Hypertension) Diet: A Randomized Pilot Feeding Study.

We aimed to identify plasma and urine metabolites altered by the Dietary Approaches to Stop Hypertension (DASH) diet in a post-hoc analysis of a pilot feeding trial. Twenty adult participants with un-medicated hypertension consumed a Control diet for one week followed by 2 weeks of random assignment to either Control or DASH diet. Non-missing fasting plasma (n = 56) and 24-h urine (n = 40) were used to profile metabolites using untargeted gas chromatography/mass spectrometry.