Continuing benefits of the Montreal Protocol and protection of the stratospheric ozone layer for human health and the environment.

The protection of Earth's stratospheric ozone (O3) is an ongoing process under the auspices of the universally ratified Montreal Protocol and its Amendments and adjustments. A critical part of this process is the assessment of the environmental issues related to changes in O3. The United Nations Environment Programme's Environmental Effects Assessment Panel provides annual scientific evaluations of some of the key issues arising in the recent collective knowledge base. This current update includes a comprehensive assessment of the incidence rates of skin cancer, cataract and other skin and eye diseases observed worldwide; the effects of UV radiation on tropospheric oxidants, and air and water quality; trends in breakdown products of fluorinated chemicals and recent information of their toxicity; and recent technological innovations of building materials for greater resistance to UV radiation. These issues span a wide range of topics, including both harmful and beneficial effects of exposure to UV radiation, and complex interactions with climate change. While the Montreal Protocol has succeeded in preventing large reductions in stratospheric O3, future changes may occur due to a number of natural and anthropogenic factors. Thus, frequent assessments of potential environmental impacts are essential to ensure that policies remain based on the best available scientific knowledge.

Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci.

Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: "Some College" (yes/no, for any education beyond high school) and "Graduated College" (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10-8) and suggestive (p < 1 × 10-6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals). Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue. Discussion: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.

Providers' Competencies and Management Practices for Traditional Palliative Cancer Care Service Delivery in Kenya.

Background: Many people in developing countries are struggling with chronic diseases yet traditional health services remain under-utilized in the quest for universal health care. Thousands patronize these outlets for care yet little is known about provider's competence and how these competencies inform palliative care decisions and practices. The study documented traditional health practitioners (THPs) competencies and practices for traditional palliative cancer care service delivery in Kenya. Methods: This study utilized mixed-methods design and was undertaken in major towns across Kenya. A total of 201 Traditional health practitioners were purposely sampled, and interviewed. Five in-depth interviews and 6 focus group discussions were conducted. Quantitative data were analyzed using SPSSv22 while thematic and discourse analysis was carried out for qualitative data. Results: Majority (92.7%) of the THPs provided general traditional health services. Nearly half of the respondents (47.7%, n = 92) stated that they had received their knowledge and abilities through divine gifting, 71 (36.8%) lineage, 61 (31.6%) apprenticeship, and 39 (20.2%) formal study. Palliative care was determined by patient state and followed consultation with caregivers for 165 (85.5%) of respondents. For 160 respondents (83%), management practices involved a mix of patient examination, conventional medical tests, herbal medicine administration, follow-up or referral. Positive feedback consisted of symptom reduction and function recovery. Conclusion: Core competencies identified include: knowledge acquisition and specialization, assessment, diagnosis and disclosure, decision making, treatment, follow-up, and referral. Traditional palliative care providers share common health-related beliefs, practices and abilities that influence how they approach and make decisions regarding the health management of their patients, despite marked ethnic diversity. The shared pathways offer a chance to develop a cogent traditional palliative care service delivery model and health policy framework to promote its integration within the health workforce. The leading unmet requirements are knowledge of intellectual property rights, disclosure frameworks, and ethical regulation principles.

Genome sequences of Phasi Charoen-like phasivirus and Fako virus from Aedes aegypti mosquitoes collected in coastal Kenya.

We report the sequencing of two viruses, Phasi Charoen-like phasivirus (PCLV) and Fako virus (FAKV), which were detected in a pool of Aedes aegypti from Kenya. Analysis showed a high similarity of PCLV to publicly available PCLV genomes from Kenya. FAKV showed a high genetic divergence from publicly available FAKV genomes.

Chitosan-PEG Gels Loaded with Jatropha mollissima (Pohl) Baill. Ethanolic Extract: An Efficient and Effective Biomaterial in Hemorrhage Control.

A lack of control over blood loss can have catastrophic implications, including death. Although several hemostatic medications have been employed to reduce bleeding, a vast majority of them are ineffective, expensive, or pose health risks to the patient. To overcome these constraints, chitosan-polyethylene glycol (CS-PEG) hemostatic gels loaded with ethanolic extract of Jatropha mollissima sap (EES) were prepared and their hemostatic, physicochemical, and cytotoxic properties were evaluated. The gels were produced by mixing CS with PEG (an external plasticizer) and EES. The phytochemical analysis revealed a significant concentration of total polyphenols and tannins content in the extract and catechin was identified as one of the key compounds of EES. Infrared spectroscopy analysis revealed the presence of EES in the gels, as well as the chemical interaction between CS and PEG. The gels were thermally stable between 25 and 37 °C (ambient and human body temperature range), had pseudoplastic deformation behavior (rheological properties preserved after shearing), were simple to inject (compression force 30 N), and were biocompatible. In vivo experiments showed that both CS-PEG-EES gels exhibited greater hemostatic action in preventing tail hemorrhage in Wistar rats, with decreased bleeding time and blood weight compared with unloaded CS-PEG gels (control groups) and Hemostank, a commercial product. However, the gel prepared with acetic acid was more efficient in controlling bleeding. These findings reveal that CS-PEG-EES gels can reduce hemorrhages and are a potent, simple, and safe hemostatic agent.

Hepatitis B Virus Epsilon (ε) RNA Element: Dynamic Regulator of Viral Replication and Attractive Therapeutic Target.

Hepatitis B virus (HBV) chronically infects millions of people worldwide, which underscores the importance of discovering and designing novel anti-HBV therapeutics to complement current treatment strategies. An underexploited but attractive therapeutic target is ε, a cis-acting regulatory stem-loop RNA situated within the HBV pregenomic RNA (pgRNA). The binding of ε to the viral polymerase protein (P) is pivotal, as it triggers the packaging of pgRNA and P, as well as the reverse transcription of the viral genome. Consequently, small molecules capable of disrupting this interaction hold the potential to inhibit the early stages of HBV replication. The rational design of such ligands necessitates high-resolution structural information for the ε-P complex or its individual components. While these data are currently unavailable for P, our recent structural elucidation of ε through solution nuclear magnetic resonance spectroscopy marks a significant advancement in this area. In this review, we provide a brief overview of HBV replication and some of the therapeutic strategies to combat chronic HBV infection. These descriptions are intended to contextualize our recent experimental efforts to characterize ε and identify ε-targeting ligands, with the ultimate goal of developing novel anti-HBV therapeutics.

Genome-wide association meta-analysis identifies 17 loci associated with nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is common and partially heritable and has no effective treatments. We carried out a genome-wide association study (GWAS) meta-analysis of imaging (n = 66,814) and diagnostic code (3,584 cases versus 621,081 controls) measured NAFLD across diverse ancestries. We identified NAFLD-associated variants at torsin family 1 member B (TOR1B), fat mass and obesity associated (FTO), cordon-bleu WH2 repeat protein like 1 (COBLL1)/growth factor receptor-bound protein 14 (GRB14), insulin receptor (INSR), sterol regulatory element-binding transcription factor 1 (SREBF1) and patatin-like phospholipase domain-containing protein 2 (PNPLA2), as well as validated NAFLD-associated variants at patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily 2 (TM6SF2), apolipoprotein E (APOE), glucokinase regulator (GCKR), tribbles homolog 1 (TRIB1), glycerol-3-phosphate acyltransferase (GPAM), mitochondrial amidoxime-reducing component 1 (MARC1), microsomal triglyceride transfer protein large subunit (MTTP), alcohol dehydrogenase 1B (ADH1B), transmembrane channel like 4 (TMC4)/membrane-bound O-acyltransferase domain containing 7 (MBOAT7) and receptor-type tyrosine-protein phosphatase δ (PTPRD). Implicated genes highlight mitochondrial, cholesterol and de novo lipogenesis as causally contributing to NAFLD predisposition. Phenome-wide association study (PheWAS) analyses suggest at least seven subtypes of NAFLD. Individuals in the top 10% and 1% of genetic risk have a 2.5-fold to 6-fold increased risk of NAFLD, cirrhosis and hepatocellular carcinoma. These genetic variants identify subtypes of NAFLD, improve estimates of disease risk and can guide the development of targeted therapeutics.

Changes in tropospheric air quality related to the protection of stratospheric ozone in a changing climate.

Ultraviolet (UV) radiation drives the net production of tropospheric ozone (O3) and a large fraction of particulate matter (PM) including sulfate, nitrate, and secondary organic aerosols. Ground-level O3 and PM are detrimental to human health, leading to several million premature deaths per year globally, and have adverse effects on plants and the yields of crops. The Montreal Protocol has prevented large increases in UV radiation that would have had major impacts on air quality. Future scenarios in which stratospheric O3 returns to 1980 values or even exceeds them (the so-called super-recovery) will tend to ameliorate urban ground-level O3 slightly but worsen it in rural areas. Furthermore, recovery of stratospheric O3 is expected to increase the amount of O3 transported into the troposphere by meteorological processes that are sensitive to climate change. UV radiation also generates hydroxyl radicals (OH) that control the amounts of many environmentally important chemicals in the atmosphere including some greenhouse gases, e.g., methane (CH4), and some short-lived ozone-depleting substances (ODSs). Recent modeling studies have shown that the increases in UV radiation associated with the depletion of stratospheric ozone over 1980-2020 have contributed a small increase (~ 3%) to the globally averaged concentrations of OH. Replacements for ODSs include chemicals that react with OH radicals, hence preventing the transport of these chemicals to the stratosphere. Some of these chemicals, e.g., hydrofluorocarbons that are currently being phased out, and hydrofluoroolefins now used increasingly, decompose into products whose fate in the environment warrants further investigation. One such product, trifluoroacetic acid (TFA), has no obvious pathway of degradation and might accumulate in some water bodies, but is unlikely to cause adverse effects out to 2100.

Prevalence of Antimicrobial Resistance and Association with Patient Outcomes in a Rural Kenyan Hospital.

Data on antimicrobial resistance (AMR) and association with outcomes in resource-variable intensive care units (ICU) are lacking. Data currently available are limited to large, urban centers. We attempted to understand this locally through a dual-purpose, retrospective study. Cohort A consisted of adult and pediatric patients who had blood, urine, or cerebrospinal fluid cultures obtained from 2016 to 2020. A total of 3,013 isolates were used to create the Kijabe Hospital's first antibiogram. Gram-negative organisms were found to be less than 50% susceptible to third- and fourth-generation cephalosporins, 67% susceptible to piperacillin-tazobactam, 87% susceptible to amikacin, and 93% susceptible to meropenem. We then evaluated the association between AMR and clinical characteristics, management, and outcomes among ICU patients (Cohort B). Demographics, vital signs, laboratory results, management data, and outcomes were obtained. Antimicrobial resistance was defined as resistance to one or more antimicrobials. Seventy-six patients were admitted to the ICU with bacteremia during this time. Forty complete paper charts were found for review. Median age was 34 years (interquartile range, 9-51), 26 patients were male (65%), and 28 patients were older than 18 years (70%). Septic shock was the most common diagnosis (n = 22, 55%). Six patients had AMR bacteremia; Escherichia coli was most common (n = 3, 50%). There was not a difference in mortality between patients with AMR versus non-AMR infections (P = 0.54). This study found a prevalence of AMR. There was no association between AMR and outcomes among ICU patients. More studies are needed to understand the impact of AMR in resource-variable settings.

Determinants of Patient Satisfaction in Indigenous Cancer Palliative Care Services.

Optimal quality of care remains an integral formal service along the continuum of care pathway. Patient satisfaction is an important health system responsiveness goal which has been shown to influence quality of care except in the indigenous settings. This study identified the determinants of patient satisfaction in the context of indigenous palliative care in Kenya. A descriptive cross-sectional study was conducted among cancer patients exiting indigenous care outlets located in 12 towns across Kenya using a structured modular questionnaire. Exit interviews were undertaken with 433 respondents leaving 193 mapped indigenous outlets. Overall services satisfaction was assessed as the dependent variable using a computed single-item satisfaction mean score. The data was analyzed using IBM Statistical Package for Social Sciences version 22. 0. Bivariate and multivariate analyses were conducted to identify the potential determinants. Against the 433 study respondents, 248 (57.3%) expressed overall satisfaction with indigenous palliative care services: Satisfaction was positively associated with waiting time (AOR = 2.663, 95% CI = 1.235-5.743), provider attention (AOR = 3.698, 95% CI = 1.657-8.254), provider politeness (AOR = 6.774, 95% CI = 3.697-12.413) and provider social communication skills (AOR = 6.520, 95% CI = 3.642-11.673). Good patient-provider interaction, provider social skills and service waiting time influence patient satisfaction with indigenous palliative care. The finding contributes to the understanding of indigenous palliative cancer care and provides scientific evidence for providers and policy makers to redesign and improve their service and outlet setting to provide patient centered holistic palliative care.

The Association Between Microalbuminuria and QTc Prolongation in Patients With Type 2 Diabetes Mellitus: A Single-Centre Study From South India.

BACKGROUND: One of the most significant complications of type 2 diabetes mellitus (T2DM) is diabetic nephropathy, the leading cause of end-stage renal disease. Another important clinical marker in patients with type 2 diabetes is QTc interval prolongation. We aimed to study the association between QTc interval prolongation and microalbuminuria in patients with T2DM. OBJECTIVE: The primary objective of this study was to examine the association between QTc interval prolongation and microalbuminuria in patients with T2DM. The secondary objective was to correlate the prolongation of the QTc interval with the duration of T2DM. MATERIALS AND METHODS: This study was conducted as a single-centre, prospective, observational study in a tertiary-care centre in South India, Amrita Institute of Medical Sciences and Research Center. The study was conducted over two years, between April 2020 and April 2022. Patients aged more than 18 with T2DM with and without microalbuminuria were recruited into the study and control groups, and various parameters, including QTC intervals, were recorded. RESULTS: A total of 120 patients were enrolled in the study, with 60 patients with microalbuminuria forming the study group and 60 patients without microalbuminuria forming the control group. There was a statistically significant association between microalbuminuria with a prolonged QTc interval, hypertension, a longer duration of T2DM, higher haemoglobin AIc (HbA1c) levels, and higher serum creatinine values.

Virtual Screening of Hepatitis B Virus Pre-Genomic RNA as a Novel Therapeutic Target.

The global burden imposed by hepatitis B virus (HBV) infection necessitates the discovery and design of novel antiviral drugs to complement existing treatments. One attractive and underexploited therapeutic target is ε, an ~85-nucleotide (nt) cis-acting regulatory stem-loop RNA located at the 3'- and 5'-ends of the pre-genomic RNA (pgRNA). Binding of the 5'-end ε to the viral polymerase protein (P) triggers two early events in HBV replication: pgRNA and P packaging and reverse transcription. Our recent solution nuclear magnetic resonance spectroscopy structure of ε permits structure-informed drug discovery efforts that are currently lacking for P. Here, we employ a virtual screen against ε using a Food and Drug Administration (FDA)-approved compound library, followed by in vitro binding assays. This approach revealed that the anti-hepatitis C virus drug Daclatasvir is a selective ε-targeting ligand. Additional molecular dynamics simulations demonstrated that Daclatasvir targets ε at its flexible 6-nt priming loop (PL) bulge and modulates its dynamics. Given the functional importance of the PL, our work supports the notion that targeting ε dynamics may be an effective anti-HBV therapeutic strategy.

Superabsorbent Wound Dressing for Management of Patients With Moderate-to-Highly Exuding Chronic Leg Ulcers: An Early Stage Model-Based Benefit-Harm Assessment.

The aim of the research is to assess the benefit-harm of superabsorbent polymers wound dressings based on polyacrylate polymers (SAPs) compared with standard of care (SoC) dressing mix for patients with moderate-to-highly exuding hard-to-heal leg ulcers. The SoC dressings mix was composed of other superabsorbents in 29% of cases, antimicrobials 26%, foams 20%, alginates 5%, and other dressings 19% weighted according to their frequency. We have used the decision-analytic modeling method, Markov process, as an adequate analytical solution for medical prognosis. We have combined the systematic literature search to identify the most relevant inputs for the analysis, with available patient-level clinical data concerning benefits of superabsorbent to generate a robust prediction of patient-relevant outcomes, including healing rates and health-related quality of life. Besides, we have qualitatively described adverse events associated with those treatments. Our research indicates that SAPs when compared with SoC dressing mix in a patient with moderate-to-highly excluding leg ulcers are leading to an improved healing rate with an absolute risk difference of 2.20% in 6 months and a relative risk of 1.07 in favor of SAP dressings. The attributable fraction among those exposed to SAP dressings of 6.6%, meaning that 6.6% of the healed ulcers could be attributed to having had the SAP dressing treatment instead of the SoC dressing treatment. Besides, SAP dressings lead to improved quality of life measured as incremental quality-adjusted life weeks (QALWs) of 0.13 QALWs.

Application of nursing presence to family-centered care: Supporting nursing practice in pediatric oncology.

PURPOSE: In pediatric care settings, family-centered care (FCC) is an integral way to ensure family involvement in their child's care and has been known to improve health outcomes and families' psychosocial well-being. Similarly, nursing presence is deemed beneficial in the formation of authentic nurse-patient relationships and is known to facilitate healing and improve satisfaction for the patient and their family. The objective of this article is to explore how nursing presence supports FCC by closely examining the four concepts of FCC as described by Institute for Patient- and Family-Centered Care: dignity and respect, information sharing, participation, and collaboration. A case study is also presented to demonstrate how nursing presence can be applied in FCC, when caring for a pediatric oncology patient. CONCLUSION: Nursing presence is essential in FCC since it plays a key role in the formation of relationships, a fundamental element in the four concepts. Attributes of nursing presence can be interwoven in the FCC framework and have positive clinical, social, and emotional outcomes for the patient and family. Although literature has explored associations between FCC and nursing presence, there is need for more scientific research to justify this argument to support the improvement of quality of family nursing care and strengthen the FCC model. PRACTICE IMPLICATIONS: The four concepts of FCC lay a foundation for a model of care that can be enhanced by nursing presence, potentially providing a remedy for depersonalization of healthcare by improving nurse patient relationships in pediatric care settings. Nursing presence becomes less ambiguous when enacted in a FCC framework, revealing attributes that may be cultivated in family nursing to improve therapeutic relationships among nurses and family caregivers.

Providers' Understanding of Cancer Aetiology and Supportive Features for Indigenous Palliative Cancer Care Service Provision in Kenya.

Background: Palliative care is a fundamental component of providing people-centred health services to cancer patients. However, the primary pillars of indigenous palliative care such as provider understanding of cancer, its aetiology, and features are undocumented. Objective: We sought to understand Traditional Health Providers (THPs) understanding of cancer aetiology, and the functional features that support indigenous palliative cancer care service provision in Kenya. Method: The study used a mixed methods cross-sectional design. A semi-structured questionnaire was administered to 193 THPs, who self-reported to manage cancer patients. The findings were enriched and validated through member checking in 6 focus group discussions and five journey mapping in-depth interviews. Results: Despite diversity in culture and experience among the indigenous providers in Kenya, their description of cancer etiology and their management practices and primary goal were similar. Cancer was consistently described as a deadly life-deforming disease by 61.1% of THPs (n = 118/193) and attributed to chemicals and toxins in the body 41.5% (n = 80). The indigenous palliative-care system was reported to be characterized by five tiered levels of care, diversity in expertise and experience, shared and consultative process (60%) and family involvement in medical decision (59.5%). Herbal regimen (60.1%) was found to be the cornerstone of informal palliative care blended with nutrition management 78.2% (n = 151), lifestyle changes 63.7% (n = 123) and counseling services 55.9% (n = 108). Payments for service were arbitrarily made in cash or in kind. Conclusion: The features of indigenous palliative care services are informed by the providers' distinctive cultural terms and descriptions of cancer and cancer aetiology. Shared and consultative protocols, regimen exchange, referral to cascaded care, and caregiver involvement were all important palliative-care clues to saving and enhancing lives. The features provide context for development of indigenous palliative care framework, engagement of policy makers, and promotion of culturally-inclusive indigenous palliative care model for adoption.

Patients phenotypes and cardiovascular risk in type 2 diabetes: the Jackson Heart Study.

BACKGROUND: Cardiovascular prognosis related to type 2 diabetes may not be adequately captured by information on comorbid conditions such as obesity and hypertension. To inform the cardiovascular prognosis among diabetic individuals, we conducted phenotyping using a clustering approach based on clinical data, echocardiographic indices and biomarkers. METHODS: We performed a cluster analysis on clinical, biochemical and echocardiographic variables from 529 Blacks with diabetes in the Jackson Heart Study. An association between identified clusters and major adverse cardiovascular events (MACE- composite of coronary heart disease, stroke, heart failure and atrial fibrillation) was assessed using Cox proportional hazards modeling. RESULTS: Cluster analysis separated individuals with diabetes (68% women, mean age 60 ± 10 years) into three distinct clusters (Clusters 1,2 &3 - with Cluster 3 being a hypertrophic cluster characterized by highest LV mass, levels of brain natriuretic peptide [BNP] and high-sensitivity cardiac troponin-I [hs-cTnI]). After a median 12.1 years, there were 141 cardiovascular events. Compared to Cluster1, Clusters 3 had an increased risk of cardiovascular disease (hazard ratio [HR] 1.60; 95% confidence interval [CI] 1.08, 2.37), while Cluster 2 had a similar risk of outcome (HR 1.11; 95% CI 0.73, 168). CONCLUSIONS: Among Blacks with diabetes, cluster analysis identified three distinct echocardiographic and biomarkers phenotypes, with cluster 3 (high LV mass, high cardiac biomarkers) associated with worse outcomes, thus highlighting the prognostic value of subclinical myocardial dysfunction.

Exploring nursing presence as experienced by parents in pediatric oncology.

BACKGROUND: Nursing presence has been viewed as a valuable way to create therapeutic relationships and has been linked to better health outcomes for patients and families. However, whether nursing presence can be described and how parents in pediatric oncology experience this phenomenon remains unanswered. Therefore, the purpose of this study was to explore how parents of children with cancer describe and experience nursing presence. METHODS: This study used Giorgi's phenomenological approach to explore nursing presence as experienced by parents of children with cancer. Ten participants from a pediatric oncology clinic in Canada were interviewed. Giorgi's approach was used to analyze these data. FINDINGS: Based upon participants' descriptions, a structure of nursing presence emerged which included six constituent features: An attitude of presence, a source of encouragement, clinical experience and expertise, therapeutic communication, family involvement, and a sense of home away from home. Most notably, nursing presence as experienced by parents was characterized by the 'being' and 'doing' of presence which were equally important. CONCLUSION: The experiences described by parents provided rich and nuanced insights into what it meant to experience nursing presence in a pediatric oncology setting. This study provides a structure for this meaning making and expounds on its constituent features, describing what nursing presence resembles when experienced by parents of children with cancer. PRACTICE IMPLICATIONS: This study informs nursing practice, policy, and education in ways that are likely to enhance care and the subsequent well-being of pediatric oncology patients and families.

High-density lipoprotein-cholesterol and incident type 2 diabetes mellitus among African Americans: The Jackson Heart Study.

AIMS: Accruing evidence suggests an association between high-density lipoprotein cholesterol (HDL-C) and incident diabetes. However, there is a paucity of data on the link between HDL-C and diabetes, especially among African Americans (AAs). We aimed to assess the association of HDL-C and its fractions with incident type 2 diabetes among AAs. METHODS: We included Jackson Heart Study participants who attended visit 1 (2001-2004), were free from diabetes and were not treated with lipid-modifying medications. Incident diabetes was assessed at two subsequent-yearly visits (2 and 3). We cross-sectionally assessed the association of HDL-C and insulin resistance (IR) using multivariable linear models. We prospectively assessed the association of HDL-C and its fractions with incident diabetes using multivariable Cox regression models. RESULTS: Among 2829 participants (mean age: 51.9 ± 12.4 years, 63.9% female), 487 participants (17%) developed new-onset diabetes, over a median follow-up of 8 years. In adjusted models, a higher HDL-C concentration was associated with a lower odds of IR (odds ratio [OR] per standard deviation [SD] increment: OR 0.56 [95% confidence interval, CI 0.50-0.63], p < 0.001). In adjusted models, a higher HDL-C concentration was associated with a lower risk of diabetes (HR per SD increment: 0.78 [95% CI 0.71, 0.87], p < 0.001; HR for highest vs. the lowest tertile of HDL-C was 0.56 [95% CI: 0.44, 0.71], p < 0.001). CONCLUSION: In a sample of African-American adults not on any lipid-modifying therapy, high HDL-C concentrations were inversely associated with the risk of new-onset diabetes. These findings suggest a strong link between HDL-C metabolism and glucose regulation.

Fluorobenzoic acid coformers to improve the solubility and permeability of the BCS class IV drug naftopidil.

Crystalline salts of the low solubility and low permeability drug naftopidil were investigated with mono-, di-, tri-, and tetrafluorobenzoic acids as coformers to show that 245TFBA (2,4,5-trifluorobenzoic acid) is the optimal salt with faster dissolution and high permeability, thereby opening the study of fluorinated coformers in pharmaceutical cocrystals and salts.

Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential.

Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program (n = 63,302) and UK Biobank (n = 47,080). Bidirectional Mendelian randomization studies were consistent with longer genetically imputed LTL increasing propensity to develop CHIP, but CHIP then, in turn, hastens to shorten measured LTL (mLTL). We also demonstrated evidence of modest mediation between CHIP and CAD by mLTL. Our data promote an understanding of potential causal relationships across CHIP and LTL toward prevention of CAD.