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Abstract The relationship between microbiota, short chain fatty acids (SCFAs), and obesity remains enigmatic. We employ amplicon sequencing and targeted metabolomics in a large (n = 1904) African origin cohort from Ghana, South Africa, Jamaica, Seychelles, and the US. Microbiota diversity and fecal SCFAs are greatest in Ghanaians, and lowest in Americans, representing each end of the urbanization spectrum. Obesity is significantly associated with a reduction in SCFA concentration, microbial diversity, and SCFA synthesizing bacteria, with country of origin being the strongest explanatory factor. Diabetes, glucose state, hypertension, obesity, and sex can be accurately predicted from the global microbiota, but when analyzed at the level of country, predictive accuracy is only universally maintained for sex. Diabetes, glucose, and hypertension are only predictive in certain low-income countries. Our findings suggest that adiposity-related microbiota differences differ between low-to-middle-income compared to high-income countries. Further investigation is needed to determine the factors driving this association.

Objectives Given the increasing prevalence of obesity and need for effective interventions, there is a growing interest in understanding how an individual’s body image can inform obesity prevention and management. This study’s objective was to examine the use of silhouette showcards to measure body size perception compared with measured body mass index, and assess body size dissatisfaction, in three different African-origin populations spanning the epidemiological transition. An ancillary objective was to investigate associations between body size perception and dissatisfaction with diabetes and hypertension.Setting Research visits were completed in local research clinics in respective countries.Participants Seven hundred and fifty-one African-origin participants from the USA and the Republic of Seychelles (both high-income countries), and Ghana (low/middle-income country).Primary and secondary outcome measures Silhouette showcards were used to measure perceived body size and body size dissatisfaction. Objectively measured body size was measured using a scale and stadiometer. Diabetes was defined as fasting blood glucose ≥126 mg/dL and hypertension was defined as ≥130 mm Hg/80 mm Hg.Results Most women and men from the USA and Seychelles had ‘Perceived minus Actual weight status Discrepancy’ scores less than 0, meaning they underestimated their actual body size. Similarly, most overweight or obese men and women also underestimated their body size, while normal weight men and women were accurately able to estimate their body size. Finally, participants with diabetes were able to accurately estimate their body size and similarly desired a smaller body size.Conclusions This study highlights that overweight and obese women and men from countries spanning the epidemiological transition were unable to accurately perceive their actual body size. Understanding people’s perception of their body size is critical to implementing successful obesity prevention programmes across the epidemiological transition.

Summary: Background: Identifying novel epigenetic signatures associated with serum immunoglobulin E (IgE) may improve our understanding of molecular mechanisms underlying asthma and IgE-mediated diseases. Methods: We performed an epigenome-wide association study using whole blood from Framingham Heart Study (FHS; n = 3,471, 46% females) participants and validated results using the Childhood Asthma Management Program (CAMP; n = 674, 39% females) and the Genetic Epidemiology of Asthma in Costa Rica Study (CRA; n = 787, 41% females). Using the closest gene to each IgE-associated CpG, we highlighted biologically plausible pathways underlying IgE regulation and analyzed the transcription patterns linked to IgE-associated CpGs (expression quantitative trait methylation loci; eQTMs). Using prior UK Biobank summary data from genome-wide association studies of asthma and allergy, we performed Mendelian randomization (MR) for causal inference testing using the IgE-associated CpGs from FHS with methylation quantitative trait loci (mQTLs) as instrumental variables. Findings: We identified 490 statistically significant differentially methylated CpGs associated with IgE in FHS, of which 193 (39.3%) replicated in CAMP and CRA (FDR < 0.05). Gene ontology analysis revealed enrichment in pathways related to transcription factor binding, asthma, and other immunological processes. eQTM analysis identified 124 cis-eQTMs for 106 expressed genes (FDR < 0.05). MR in combination with drug-target analysis revealed CTSB and USP20 as putatively causal regulators of IgE levels (Bonferroni adjusted P

Background: Parkland Health is a 900-bed safety-net hospital that serves Dallas County, Texas. It has an OPAT program in which patients are managed via self-administration (S-OPAT), home-health/hemodialysis (H-OPAT), and skilled nursing facilities (SNF-OPAT). We evaluated the reasons for unscheduled emergency department (ED) visits by patients in these groups to identify strategies to decrease unexpected healthcare utilization and to improve safety. Methods: We performed a retrospective chart review of all adult patients discharged from Parkland Health on OPAT between April and June 2021. Demographic, medical, and healthcare utilization information, including the date and reason of first unscheduled ED visit after discharge, was collected utilizing a standardized instrument. The institutional review board approved this study. Results: In total, 184 patients were discharged with OPAT. Among them, 32% were female and 55% identified as Hispanic; 41% were non-English speakers, and 45% were treated for a musculoskeletal infection. Among all OPAT models of care, 43.4% were S-OPAT patients, 31.5% were H-OPAT patients, and 25% were SNF-OPAT patients (Table 1). The groups differed, and fewer African Americans received H-OPAT. Also, 45% were being treated for musculoskeletal infections and were more likely to be discharged with H- or SNF-OPAT. In addition, 41% were being treated for endovascular infections and 21.7% were being treated for genitourinary infections. The total length of stay in the hospital was longer for SNF-OPAT patients and shorter for S-OPAT patients (Table 2). Among 184 OPAT patients, 41 patients (22.2%) had an ED visit: 17.3% SNF-OPAT patients, 27.6% H-OPAT patients, and 21.3% S-OPAT patients (Table 2). ED visits were attributed to intravenous (IV) access–related problems (12 of 41, 29.0%), worsening of known infection (3 of 41, 7.3%), and abnormal blood test results (2 of 41, 4.9%). Also, 24 ED visits (58%) were not related to underlying infection or OPAT. However, when examined by the OPAT care model, 41% of ED visits among S-OPAT patients, 20% among H-OPAT visits, and 25% among SNF-OPAT visits were related to IV access issues. Among S-OPAT ED visits pertaining to IV access, 71% were for minor issues such as dressing changes or line occlusion or malfunction. Conclusions: One-fifth of OPAT patients had an unscheduled ED visit, of whom 20%–41% had issues with IV access. Many of these visits could be avoided with enhanced outreach to patients discharged with OPAT and improved ambulatory capabilities to provide standard services related to maintenance of IV access.

Low total energy expenditure (TEE) has been a hypothesized risk factor for weight gain, but longitudinal repeatability of TEE is incompletely understood. Here the authors report that TEE is repeatable for adults, but not for children, and increases in TEE (adjusted for fat-free mass, fat mass, age and sex) are not associated with body composition changes in short-term longitudinal analyses.

Abstract Background Cardiometabolic (CM) risk affects approximately 25% of adults globally, and is diagnosed by meeting 3 out of 5 of the following CM risk factors: elevated blood pressure, high triglycerides, elevated blood sugar, low high-density lipoprotein (HDL) level, and abdominal obesity. Adults with CM risk are approximately 22% more likely to have higher mortality rates, and alcohol consumption may be associated with higher CM risk. While previous studies have investigated this potential connection, the majority of them did not include African-origin adults. Therefore, the study aimed to explore the association between alcohol intake and CM risk in 5 African-origin cohorts, spanning the epidemiologic transition in Ghana, South Africa, Jamaica, Seychelles and the United States of America. Methods Measurements included clinical measures for CM risk and self-reported alcohol consumption. Each participant was categorized into one of three drinking categories: non-drinker, light drinker (1–3 drinks daily for men and 1–2 drinks daily for women) and heavy drinker (4 or more drinks every day for men and 3 or more drinks per day for women). Using non-drinker status as the reference, the association between alcohol consumption status and prevalence of each of the five CM risk factors and overall elevated CM risk (having 3 out of 5 risk factors) was explored, adjusting for site, age and sex. Associations were explored using logistic regression and significance was determined using odds ratios (OR) and 95% confidence intervals. Results Neither light nor heavy drinking was associated with increased odds for having higher CM risk compared to nondrinkers (OR = 1.05, p = 0.792 and OR = 1.11, p = 0.489, respectively). However, light drinking was associated with lower odds for having low high density lipoproteins (HDL) cholesterol (OR = 0.69, p = 0.002) and increased risk for high triglycerides (OR = 1.48, p = 0.030). Heavy drinking was associated with elevated blood pressure (OR = 1.59, p = 0.002), high triglycerides (OR = 1.73, p = 0.006) and decreased risk of low HDL-cholesterol (OR = 0.621, p

Mycoplasma hyorhinis (M. hyorhinis) lacks a cell wall and resists multiple antibiotics. We describe here the striking > 90% inhibitory effect of hemin, a natural inducer of the cytoprotective enzyme heme oxygenase‐1 (HO‐1), on M. hyorhinis replication in chronically infected LNCaP prostate cancer cells. The role of HO‐1 in interrupting M. hyorhinis replication was confirmed by HO‐1‐specific siRNA suppression of hemin‐induced HO‐1 protein expression, which increased intracellular M. hyorhinis DNA levels in LNCaP cells. Proteomic analysis and transmission electron microscopy of hemin‐treated cells confirmed the complete absence of M. hyorhinis proteins and intact microorganisms, respectively, strongly supporting these findings. Our study is the first to our knowledge suggesting therapeutic potential for activated HO‐1 in cellular innate responses against mycoplasma infection.

Abstract Background Around the world, efforts are underway to include engineering design as part of elementary science instruction. A common rationale for those efforts is that Engineering Design-based Science Teaching (EDST) is a productive pedagogical approach for developing students’ understanding of core science concepts. Effectively utilizing EDST requires that teachers develop design activities that are highly connected to science content so that students can apply and expand their understanding of relevant concepts. In this study, we examine how a group of elementary (grades 3–5) pre-service and in-service teachers incorporated EDST into their planned science instruction. Those teachers were participants in a professional development project aimed at supporting EDST. We examine the ways that participants used EDST, the extent to which engineering design activities were connected to science concepts, and factors associated with those connections. Results Most of the participants in the study developed science units in which an engineering design activity was placed at the end of the unit. Approximately half of those design activities lacked connections to the science concepts in the unit; they were typically related to the topic of the science unit, but did not require the use or development of key science ideas. Eleven percent of participants developed engineering activities with deep connections to science concepts, and 35% developed activities with shallow connections. No differences were found between life science, physical science, and earth/space science units in terms of the extent of conceptual connections. However, we did find that participants who utilized and adapted published engineering curriculum materials rather than make them from scratch were more likely to have unit plans with higher levels of conceptual connections. Conclusions Our findings suggest that elementary teachers need additional support in order to effectively utilize EDST in their classrooms. Even within the context of a supportive professional development project, most of the engineering activities developed by our participants lacked substantial connections to the science concepts in their unit plans. Our findings highlight the value of high-quality curriculum materials to support EDST as well as the need to further expand the curriculum resources that are available to elementary teachers.

Abstract Background Physician shortage is a major barrier to hypertension (HTN) control in Ghana, with only one physician to 10,000 patients in 2015, thus limiting its capacity for HTN control at the primary care level such as the Community Health Planning and Services (CHPS) compounds, where most Ghanaians receive care. A Task-Shifting Strategy for HTN control (TASSH) based on the WHO Cardiovascular (CV) Risk Package is an evidence-based strategy for mitigating provider- and systems-level barriers to optimal HTN control. Despite its effectiveness, TASSH remains untested in CHPS zones. Additionally, primary care practices in low- and middle-income countries (LMICs) lack resources and expertise needed to coordinate multilevel system changes without assistance. The proposed study will evaluate the effectiveness of practice facilitation (PF) as a quality improvement strategy for implementing TASSH within CHPS zones in Ghana. Methods Guided by the Consolidated Framework for Implementation Research and the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework, we will evaluate, in a hybrid clinical effectiveness-implementation design, the effect of PF on the uptake of an evidence-based TASSH, among 700 adults who present to 70 CHPS zones with uncontrolled HTN. Components of the PF strategy include (a) an advisory board that provides leadership support for implementing the intervention within the CHPS zones and (b) trained task-strengthening facilitators (TSFs) who serve as practice coaches to provide training, and performance feedback to community health officers (CHOs) who will deliver TASSH at the CHPS zones. For this purpose, the TSFs are trained to identify, counsel, and refer adults with uncontrolled HTN to community health centers in Bono East Region of Ghana. Discussion Uptake of community-based evidence-supported interventions for hypertension control in Ghana is urgently needed to address the CVD epidemic and its associated morbidity, mortality, and societal costs. Findings from this study will provide policymakers and other stakeholders the “how to do it” empirical literature on the uptake of evidence-based task-strengthening interventions for HTN control in Ghana and will serve as a model for similar action in other low, middle-income countries. Trial registration ClinicalTrials.gov, NCT03490695 . Registered on 6 April 2018. Protocol version and date Version 1, date: 21 August, 2019.

Abstract Background The burden of hypertension in many low-and middle-income countries is alarming and requires effective evidence-based preventative strategies that is carefully appraised and accepted by key stakeholders to ensure successful implementation and sustainability. We assessed nurses’ perceptions of a recently completed Task Shifting Strategy for Hypertension control (TASSH) trial in Ghana, and facilitators and challenges to TASSH implementation. Methods Focus group sessions and in-depth interviews were conducted with 27 community health nurses from participating health centers and district hospitals involved in the TASSH trial implemented in the Ashanti Region, Ghana, West Africa from 2012 to 2017. TASSH evaluated the comparative effectiveness of the WHO-PEN program versus provision of health insurance for blood pressure reduction in hypertensive adults. Qualitative data were analyzed using open and axial coding techniques with emerging themes mapped onto the Consolidated Framework for Implementation Research (CFIR). Results Three themes emerged following deductive analysis using CFIR, including: (1) Patient health goal setting- relative priority and positive feedback from nurses, which motivated patients to make healthy behavior changes as a result of their health being a priority; (2) Leadership engagement (i.e., medical directors) which influenced the extent to which nurses were able to successfully implement TASSH in their various facilities, with most directors being very supportive; and (3) Availability of resources making it possible to implement the TASSH protocol, with limited space and personnel time to carry out TASSH duties, limited blood pressure (BP) monitoring equipment, and transportation, listed as barriers to effective implementation. Conclusion Assessing stakeholders’ perception of the TASSH implementation process guided by CFIR is crucial as it provides a platform for the nurses to thoroughly evaluate the task shifting program, while considering the local context in which the program is implemented. The feedback from the nurses informed barriers and facilitators to implementation of TASSH within the current healthcare system, and suggested system level changes needed prior to scale-up of TASSH to other regions in Ghana with potential for long-term sustainment of the task shifting intervention. Trial registration Trial registration for parent TASSH study: NCT01802372. Registered February 27, 2013.

As online courses become increasingly common at the college level, an ongoing concern is how to ensure academic integrity in the online environment. One area that has received particular attention is that of preventing cheating during unproctored online exams. In this study, we examine students’ behavior during unproctored exams taken in an online introductory biology course. A feature of the learning management platform used for the course gave us the ability to detect cheating behavior involving students leaving the test page and viewing other material on their computers. This allowed us to determine what proportion of students cheated and examine the efficacy of various measures to mitigate cheating. We also explored the relationship between cheating behavior and exam performance. We found that 70% of students were observed cheating, and most of those who cheated did so on the majority of test questions. Appealing to students’ honesty or requiring them to pledge their honesty were found to be ineffective at curbing cheating. However, when students received a warning that we had technology that could detect cheating, coupled with threats of harsh penalties, cheating behavior dropped to 15% of students. Unexpectedly, we did not find evidence that students’ exam performance changed when their cheating behavior changed, indicating that this common form of cheating might not be as effective as students, or their instructors believe it to be.

The Pulvers' silhouette showcards provide a non-invasive and easy-to-use way of assessing an individual's body size perception using nine silhouette shapes. However, their utility across different populations has not been examined. This study aimed to assess: 1) the relationship between silhouette perception and measured anthropometrics, i.e., body mass index (BMI), waist circumference (WC), waist-height-ratio (WHtR), and 2) the ability to predict with silhouette showcards anthropometric adiposity measures, i.e., overweight and obesity (BMI ≥ 25 kg/m2), obesity alone (BMI ≥ 30 kg/m2), elevated WC (men ≥ 94 cm; women ≥ 80 cm), and WHtR (> 0.5) across the epidemiological transition. 751 African-origin participants, aged 20-68 years old, from the United States (US), Seychelles, and Ghana, completed anthropometrics and selected silhouettes corresponding to their perceived body size. Silhouette performance to anthropometrics was examined using a least-squares linear regression model. A receiver operator curve (ROC) was used to investigate the showcards ability to predict anthropometric adiposity measures. The relationship between silhouette ranking and BMI were similar between sexes of the same country but differed between countries: 3.65 [95% CI: 3.34-3.97] BMI units/silhouette unit in the US, 3.23 [2.93-3.74] in Seychelles, and 1.99 [1.72-2.26] in Ghana. Different silhouette cutoffs predicted obesity differently in the three countries. For example, a silhouette ≥ five had a sensitivity/specificity of 77.3%/90.6% to predict BMI ≥ 25 kg/m2 in the US, but 77.8%/85.9% in Seychelles and 84.9%/71.4% in Ghana. Ultimately, silhouettes predicted BMI, WC, and WHtR similarly within each country and sex but not across countries. Our data suggest that Pulvers' silhouette showcards may be a helpful tool to predict anthropometric and adiposity measures in different populations when direct measurement cannot be performed. However, no universal silhouette cutoff can be used for detecting overweight or obesity status, and population-specific differences may stress the need to calibrate silhouette showcards when using them as a survey tool in different countries.

Variants in the Apolipoprotein L1 (APOL1) gene (G1-rs60910145, rs73885319, G2-rs71785313) are common in Africans and in individuals of recent African ancestry and are associated with an increased risk of non-diabetic chronic kidney disease (CKD) and in particular of HIV associated nephropathy (HIVAN). In light of the significantly increased risk of HIVAN in carriers of two APOL1 risk alleles, a role in HIV infectivity has been postulated in the mechanism of APOL1 associated kidney disease. Herein, we aim to explore the association between HIV viremia and APOL1 genotype. In addition, we investigated interaction between BK and JC viruria, CKD and HIV viremia. A total of 199 persons living with HIV/AIDS (comprising 82 CKD cases and 117 controls) from among the participants in the ongoing Human Heredity and Health in Africa (H3Africa) Kidney Disease Research Network case control study have been recruited. The two APOL1 renal risk alleles (RRA) genotypes were associated with a higher risk of CKD (OR 12.6, 95% CI 3.89–40.8, p < 0.0001). Even a single APOL1 RRA was associated with CKD risk (OR 4.42, 95% CI 1.49–13.15, p = 0.007). The 2 APOL1 RRA genotypes were associated with an increased probability of having HIV viremia (OR 2.37 95% CI 1.0–5.63, p = 0.05). HIV viremia was associated with increased CKD risk (OR 7.45, 95% CI 1.66–33.35, P = 0.009) and with a significant reduction of JC virus urine shedding (OR 0.35, 95% CI 0.12–0.98, p = 0.046). In contrast to prior studies, JC viruria was not associated with CKD but was restricted in patients with HIV viremia, regardless of CKD status. These findings suggest a role of APOL1 variants in HIV infectivity and emphasize that JC viruria can serve as biomarker for innate immune system activation.

Sleep disorders are increasingly being characterized in modern society as contributing to a host of serious medical problems, including obesity and metabolic syndrome. Changes to the microbial community in the human gut have been reportedly associated with many of these cardiometabolic outcomes. In this study, we investigated the impact of sleep length on the gut microbiota in a large cohort of 655 participants of African descent, aged 25-45, from Ghana, South Africa (SA), Jamaica, and the United States (US). The sleep duration was self-reported via a questionnaire. Participants were classified into 3 sleep groups: short (

Summary: Side-by-side installations of flat plate photovoltaics and parabolic trough collectors consume significant space and have high system losses; by using an all-in-one, spectrum-splitting hybrid receiver, electricity and high-temperature heat can be generated with a single efficient system. Here, the performance of a transmissive concentrator photovoltaic/thermal (tCPV/T) system is demonstrated on-sun, with a total energy efficiency of 85.1% ± 3.3%, 138 W electric power at 304 suns (with average cell temperatures

Non-communicable disease (NCD) prevention efforts have traditionally targeted high-risk and high-burden populations. We propose an alteration in prevention efforts to also include emphasis and focus on low-risk populations, predominantly younger individuals and low-prevalence populations. We refer to this approach as "proactive prevention." This emphasis is based on the priority to put in place policies, programs, and infrastructure that can disrupt the epidemiological transition to develop NCDs among these groups, thereby averting future NCD crises. Proactive prevention strategies can be classified, and their implementation prioritized, based on a 2-dimensional assessment: impact and feasibility. Thus, potential interventions can be categorized into a 2-by-2 matrix: high impact/high feasibility, high impact/low feasibility, low impact/high feasibility, and low impact/low feasibility. We propose that high impact/high feasibility interventions are ready to be implemented (act), while high impact/low feasibility interventions require efforts to foster buy-in first. Low impact/high feasibility interventions need to be changed to improve their impact while low impact/low feasibility might be best re-designed in the context of limited resources. Using this framework, policy makers, public health experts, and other stakeholders can more effectively prioritize and leverage limited resources in an effort to slow or prevent the evolving global NCD crisis.

Background. Globally, sodium intake has been found to be far above the normal level required by the body. Within countries, variations in salt intake exist between rural communities and urban communities. Experimental and epidemiological studies as well as studies involving clinical trials show the existence of adverse effect of salt consumption on the blood pressure of adults. The study evaluated salt intake among older normotensive adults in Atonsu, a suburb of Kumasi in the Ashanti region of Ghana. Methods. Participants were randomly selected from five churches which constituted cluster samples. A questionnaire was administered to participants for demographic information and dietary and lifestyle assessments. The study targeted 100 participants, twenty from each of the five churches. Eighty-two individuals gave their informed consent. Out of the 82 who gave their informed consent, 15 withdrew and 67 completed the course. The 67 participants comprised 36 (53.7%) men and 31 (46.3%) women. Systolic and diastolic blood pressure, BMI, urinary sodium, urinary potassium, serum creatinine, serum sodium, and serum potassium concentrations were also measured. Results. Participants’ mean age was 52.3 ± 8.7 years. Participants had 24 hr urinary sodium excretion of 153.0 ± 26.9 mmol/day. All participants indicated that they consume foods high in salt even though none of them added salt to their diet at table. Mean 24 hr urinary potassium was 52.5 ± 12.9 mmol/day. Mean systolic blood pressure was 119.9 ± 10.8 mmHg and mean diastolic blood pressure was 72.5 ± 7.3 mmHg. Their mean BMI was 23.7 ± 3.5 kg/m2. Conclusion. The participants who can be described as quite old and normotensive were high salt consumers, indicated by their dietary assessment and urinary sodium excretion, even though they had normal blood pressure.

Abstract Background While some of the variance observed in adiposity and weight change within populations can be accounted for by traditional risk factors, a new factor, the gut microbiota, has recently been associated with obesity. However, the causal mechanisms through which the gut microbiota and its metabolites, short chain fatty acids (SCFAs) influence obesity are unknown, as are the individual obesogenic effects of the individual SCFAs (butyrate, acetate and propionate). This study, METS-Microbiome, proposes to examine the influence of novel risk factors, the gut microbiota and SCFAs, on obesity, adiposity and weight change in an international established cohort spanning the epidemiologic transition. Methods The parent study; Modeling the Epidemiologic Transition Study (METS) is a well-established and ongoing prospective cohort study designed to assess the association between body composition, physical activity, and relative weight, weight gain and cardiometabolic disease risk in five diverse population-based samples in 2500 people of African descent. The cohort has been prospectively followed since 2009. Annual measures of obesity risk factors, including body composition, objectively measured physical activity and dietary intake, components which vary across the spectrum of social and economic development. In our new study; METS-Microbiome, in addition to continuing yearly measures of obesity risk, we will also measure gut microbiota and stool SCFAs in all contactable participants, and follow participants for a further 3 years, thus providing one of the largest gut microbiota population-based studies to date. Discussion This new study capitalizes upon an existing, extensively well described cohort of adults of African-origin, with significant variability as a result of the widespread geographic distributions, and therefore variation in the environmental covariate exposures. The METS-Microbiome study will substantially advance the understanding of the role gut microbiota and SCFAs play in the development of obesity and provide novel obesity therapeutic targets targeting SCFAs producing features of the gut microbiota. Trial registration Registered NCT03378765 Date first posted: December 20, 2017.

Abstract Background Obesity is a major risk factor for hypertension, however, the physiologic mechanisms linking increased adiposity to elevations in blood pressure are not well described. An increase in resting energy expenditure (REE) is an obligatory consequence of obesity. Previous survey research has demonstrated that REE is an independent predictor of blood pressure, and eliminates the co-linear association of body mass index. This observation has received little attention and there have been no attempts to provide a causal explanation. Methods At baseline in an international comparative study on obesity, 289 participants aged 25–44 were recruited from communities in the US, the Seychelles, Ghana and South Africa and had REE measured with indirect calorimetry. All participants were thought to be free of major illness. Results In multivariate regression models, both systolic and diastolic blood pressure were positively associated with REE (p

Abstract Background Cardiovascular risk factors are increasing in most developing countries. To date, however, very little standardized data has been collected on the primary risk factors across the spectrum of economic development. Data are particularly sparse from Africa. Methods In the Modeling the Epidemiologic Transition Study (METS) we examined population-based samples of men and women, ages 25–45 of African ancestry in metropolitan Chicago, Kingston, Jamaica, rural Ghana, Cape Town, South Africa, and the Seychelles. Key measures of cardiovascular disease risk are described. Results The risk factor profile varied widely in both total summary estimates of cardiovascular risk and in the magnitude of component factors. Hypertension ranged from 7% in women from Ghana to 35% in US men. Total cholesterol was well under 200 mg/dl for all groups, with a mean of 155 mg/dl among men in Ghana, South Africa and Jamaica. Among women total cholesterol values varied relatively little by country, following between 160 and 178 mg/dl for all 5 groups. Levels of HDL-C were virtually identical in men and women from all study sites. Obesity ranged from 64% among women in the US to 2% among Ghanaian men, with a roughly corresponding trend in diabetes. Based on the Framingham risk score a clear trend toward higher total risk in association with socioeconomic development was observed among men, while among women there was considerable overlap, with the US participants having only a modestly higher risk score. Conclusions These data provide a comprehensive estimate of cardiovascular risk across a range of countries at differing stages of social and economic development and demonstrate the heterogeneity in the character and degree of emerging cardiovascular risk. Severe hypercholesterolemia, as characteristic in the US and much of Western Europe at the onset of the coronary epidemic, is unlikely to be a feature of the cardiovascular risk profile in these countries in the foreseeable future, suggesting that stroke may remain the dominant cardiovascular event.

Abstract Background The purpose of this study was to explore stakeholders' perception of an on-going evidence-based task-shifting strategy for hypertension (TASSH) in 32 community health centers and district hospitals in Ghana. Methods Using focus group discussions and in-depth interviews, qualitative data were obtained from 81 key stakeholders including patients, nurses, and site directors of participating community health centers involved in the TASSH trial. Qualitative data were analyzed using open and axial coding techniques. Results Analysis of the qualitative data revealed three themes that illustrate stakeholders' perceptions of the ongoing task-shifting strategy for blood pressure control in Ghana and they include: 1) awareness and understanding of the TASSH program; 2) reasons for participation and non-participation in TASSH; and 3) the benefit and drawbacks to the TASSH program. Conclusion The findings support evidence that successful implementation of any task-shifting strategy must focus not only on individual patient characteristics, but also consider the role contextual factors such as organizational and leadership factors play. The findings also demonstrate the importance of understanding stakeholder's perceptions of evidence-based task-shifting interventions for hypertension control as it may ultimately influence the sustainable uptake of these interventions into "real world" settings.

Oral and fecal microbial biomarkers have previously been associated with cardiometabolic (CM) risk, however, no comprehensive attempt has been made to explore this association in minority populations or across different geographic regions. We characterized gut- and oral-associated microbiota and CM risk in 655 participants of African-origin, aged 25-45, from Ghana, South Africa, Jamaica, and the United States (US). CM risk was classified using the CM risk cut-points for elevated waist circumference, elevated blood pressure and elevated fasted blood glucose, low high-density lipoprotein (HDL), and elevated triglycerides. Gut-associated bacterial alpha diversity negatively correlated with elevated blood pressure and elevated fasted blood glucose. Similarly, gut bacterial beta diversity was also significantly differentiated by waist circumference, blood pressure, triglyceridemia and HDL-cholesterolemia. Notably, differences in inter- and intra-personal gut microbial diversity were geographic-region specific. Participants meeting the cut-points for 3 out of the 5 CM risk factors were significantly more enriched with Lachnospiraceae, and were significantly depleted of Clostridiaceae, Peptostreptococcaceae, and Prevotella. The predicted relative proportions of the genes involved in the pathways for lipopolysaccharides (LPS) and butyrate synthesis were also significantly differentiated by the CM risk phenotype, whereby genes involved in the butyrate synthesis via lysine, glutarate and 4-aminobutyrate/succinate pathways and LPS synthesis pathway were enriched in participants with greater CM risk. Furthermore, inter-individual oral microbiota diversity was also significantly associated with the CM risk factors, and oral-associated Streptococcus, Prevotella, and Veillonella were enriched in participants with 3 out of the 5 CM risk factors. We demonstrate that in a diverse cohort of African-origin adults, CM risk is significantly associated with reduced microbial diversity, and the enrichment of specific bacterial taxa and predicted functional traits in both gut and oral environments. As well as providing new insights into the associations between the gut and oral microbiota and CM risk, this study also highlights the potential for novel therapeutic discoveries which target the oral and gut microbiota in CM risk.

Abstract Background Associations between socioeconomic status (SES) and risk factors for noncommunicable diseases (NCD-RFs) may differ in populations at different stages of the epidemiological transition. We assessed the social patterning of NCD-RFs in a study including populations with different levels of socioeconomic development. Methods Data on SES, smoking, physical activity, body mass index, blood pressure, cholesterol and glucose were available from the Modeling the Epidemiologic Transition Study (METS), with about 500 participants aged 25–45 in each of five sites (Ghana, South Africa, Jamaica, Seychelles, United States). Results The prevalence of NCD-RFs differed between these populations from five countries (e.g., lower prevalence of smoking, obesity and hypertension in rural Ghana) and by sex (e.g., higher prevalence of smoking and physical activity in men and of obesity in women in most populations). Smoking and physical activity were associated with low SES in most populations. The associations of SES with obesity, hypertension, cholesterol and elevated blood glucose differed by population, sex, and SES indicator. For example, the prevalence of elevated blood glucose tended to be associated with low education, but not with wealth, in Seychelles and USA. The association of SES with obesity and cholesterol was direct in some populations but inverse in others. Conclusions In conclusion, the distribution of NCD-RFs was socially patterned in these populations at different stages of the epidemiological transition, but associations between SES and NCD-RFs differed substantially according to risk factor, population, sex, and SES indicator. These findings emphasize the need to assess and integrate the social patterning of NCD-RFs in NCD prevention and control programs in LMICs.

Background: There is evidence to suggest that the prevalence of non-communicable diseases (NCDs), in particular cardiovascular diseases and diabetes, are being recognized as forming a substantial proportion of the burden of disease among populations in Low- and Middle-Income Countries (LMICs). Access to treatment is likely a key barrier to the control and prevention of NCD outcomes. Differential pricing, an approach used to price drugs based on the purchasing power of patients in different socioeconomic segments, has been shown to be beneficial and leads to improved access and affordability. Methods: This is a quasi-experimental study, with a pragmatic trial design, to be conducted over the course of three years. A mixed methods design will be used to evaluate the effects of health systems strengthening and differential pricing on the management of diabetes, hypertension and selected cancers in Ghana. A public private partnership was established between all sites that will receive multi-level interventions, including health systems strengthening and access to medicines interventions. Study populations and sites: Study participants will include individuals with new or previously diagnosed hypertension and diabetes (n=3,300), who present to two major referral hospitals, Komfo Anokye Teaching Hospital and Tamale Teaching Hospital, as well as three district hospitals, namely Kings Medical Centre, Agogo Presbyterian District Hospital, and Atua Government Hospital. Discussion: The objective of this study aims to test approaches intended to improve access to drugs for the treatment of hypertension and diabetes, and improve disease control. Patients with these conditions will benefit from health systems strengthening interventions (education, counseling, improved management of disease), and increased access to innovative medicines via differential pricing. Pilot programs also will facilitate health system strengthening at the participating institutions, which includes training of clinicians and updating of guidelines and production of protocols for the treatment of diabetes, hypertension and cancer.

BACKGROUND:Poor access to care and physician shortage are major barriers to hypertension control in sub-Saharan Africa. Implementation of evidence-based systems-level strategies targeted at these barriers are lacking. We conducted a study to evaluate the comparative effectiveness of provision of health insurance coverage (HIC) alone versus a nurse-led task shifting strategy for hypertension control (TASSH) plus HIC on systolic blood pressure (SBP) reduction among patients with uncontrolled hypertension in Ghana. METHODS AND FINDINGS:Using a pragmatic cluster randomized trial, 32 community health centers within Ghana's public healthcare system were randomly assigned to either HIC alone or TASSH + HIC. A total of 757 patients with uncontrolled hypertension were recruited between November 28, 2012, and June 11, 2014, and followed up to October 7, 2016. Both intervention groups received health insurance coverage plus scheduled nurse visits, while TASSH + HIC comprised cardiovascular risk assessment, lifestyle counseling, and initiation/titration of antihypertensive medications for 12 months, delivered by trained nurses within the healthcare system. The primary outcome was change in SBP from baseline to 12 months. Secondary outcomes included lifestyle behaviors and blood pressure control at 12 months and sustainability of SBP reduction at 24 months. Of the 757 patients (389 in the HIC group and 368 in the TASSH + HIC group), 85% had 12-month data available (60% women, mean BP 155.9/89.6 mm Hg). In intention-to-treat analyses adjusted for clustering, the TASSH + HIC group had a greater SBP reduction (-20.4 mm Hg; 95% CI -25.2 to -15.6) than the HIC group (-16.8 mm Hg; 95% CI -19.2 to -15.6), with a statistically significant between-group difference of -3.6 mm Hg (95% CI -6.1 to -0.5; p = 0.021). Blood pressure control improved significantly in both groups (55.2%, 95% CI 50.0% to 60.3%, for the TASSH + HIC group versus 49.9%, 95% CI 44.9% to 54.9%, for the HIC group), with a non-significant between-group difference of 5.2% (95% CI -1.8% to 12.4%; p = 0.29). Lifestyle behaviors did not change appreciably in either group. Twenty-one adverse events were reported (9 and 12 in the TASSH + HIC and HIC groups, respectively). The main study limitation is the lack of cost-effectiveness analysis to determine the additional costs and benefits, if any, of the TASSH + HIC group. CONCLUSIONS:Provision of health insurance coverage plus a nurse-led task shifting strategy was associated with a greater reduction in SBP than provision of health insurance coverage alone, among patients with uncontrolled hypertension in Ghana. Future scale-up of these systems-level strategies for hypertension control in sub-Saharan Africa requires a cost-benefit analysis. TRIAL REGISTRATION:ClinicalTrials.gov NCT01802372.

Background: There is evidence to suggest that the prevalence of non-communicable diseases (NCDs), in particular cardiovascular diseases and diabetes, are being recognized as forming a substantial proportion of the burden of disease among populations in Low- and Middle-Income Countries (LMICs). Access to treatment is likely a key barrier to the control and prevention of NCD outcomes. Differential pricing, an approach used to price drugs based on the purchasing power of patients in different socioeconomic segments, has been shown to be beneficial and leads to improved access and affordability. Methods: This is a quasi-experimental study, with a pragmatic trial design, to be conducted over the course of three years. A mixed methods design will be used to evaluate the effects of health systems strengthening and differential pricing on the management of diabetes, hypertension and selected cancers in Ghana. A public private partnership was established between all sites that will receive multi-level interventions, including health systems strengthening and access to medicines interventions. Study populations and sites: Study participants will include individuals with new or recently diagnosed hypertension and diabetes (n=3,300), who present to two major referral hospitals, Komfo Anokye Teaching Hospital and Tamale Teaching Hospital, as well as three district hospitals, namely Kings Medical Centre, Agogo Presbyterian District Hospital, and Atua Government Hospital. Discussion: The objective of this study aims to test approaches intended to improve access to drugs for the treatment of hypertension and diabetes, and improve disease control. Patients with these conditions will benefit from health systems strengthening interventions (education, counseling, improved management of disease), and increased access to innovative medicines via differential pricing. Pilot programs also will facilitate health system strengthening at the participating institutions, which includes training of clinicians and updating of guidelines and production of protocols for the treatment of diabetes, hypertension and cancer.

Introduction. Hypertension, particularly pulse pressure [PP] is a major risk factor for end-stage renal disease. However, the effect of individual components of hypertension namely PP, systolic [SBP] and diastolic blood pressure [DBP] on kidney function, in the general African population is unknown. Methods. Data were collected on 944 participants [aged 40-75 y], living in villages in the area around the city of Kumasi, Ghana, on demographics, medications, height, weight, BP and 24-hour creatinine clearance (CrCl). Results. The demographic and clinical characteristics were: age 55(11) [mean (SD)] years, females 62%, rural village-dwellers 52%, diabetes 1·5%, BMI 21(4) kg/m2, 24-hourCrCl as a measure of glomerular filtration rate (GFR) 84(23) ml/min/1.73 m2. 29% had BP >140/90 mmHg; SBP and DBP were 125/74(26/14) mmHg, PP was 51(17) mmHg. PP increased with age by 0.55(95% CI: 0.46,0.64) mmHg/year. PP was higher (53(17) v 49(15) mmHg; p < 0.001) in the semiurban participants. GFR decreased both with increasing PP [-0.19 (-0.27,-0.10 ml/min/1.73 m2/mmHg; p < 0.001] and SBP [-0.09 (-0.14,-0.03) ml/min/1.73 m2/mmHg; p < 0.001] but there was no significant relationship with DBP [-0.04 (-0.15,0.06)]. After adjusting for SBP, the relationship between GFR and PP became steeper [-0.31 (-0.50,-0.12) ml/min/1.73 m2/mmHg; p < 0.001]. Using multivariate regression analysis that included PP, age, gender, BMI, only increasing age [-0.75 (-0.88,-0.62)] and decreasing BMI [0.49 (0.16,0.81)] were associated with decreased kidney function. Conclusions. In this homogeneous West-African population, PP increased with age and had a steeper relationship with declining kidney function than SBP or DBP.

Hypertension is the most important risk factor for cardiovascular mortality and morbidity in Sub-Saharan Africa. In western populations, high haemoglobin levels are associated with raised BP unlike in Sub-Saharan Africa where there is a paucity of data. Our study examines the association between haematological indices with BP variables. Weight, height, BP, and whole blood indices of viscosity (Hb, haematocrit, RBC count, and MCV) were measured in 921 adults (340 men, 581 women; aged 40–75) in 12 communities in Ghana. Mean values for Hb (12.3 g/dl ± 1.7 SD), haematocrit (36.7%±5.2), RBC (4.10 million/μL ± 0.64), and MCV were lower than reference values used in Sub-Saharan Africa. Mean BMI was 21.1±4.1 indicating a lean population. Systolic BP increased by 1.0 mmHg (95% CI 0.5–1.5), p

The burden of uncontrolled hypertension in Low-and-Middle Income Countries (LMICs) is high, with an increased risk of cardiovascular diseases and chronic renal failure in these settings.To assess the factors associated with uncontrolled blood pressure control in a cross-section of Ghanaian hypertensive subjects involved in an on-going multicenter epidemiological study aimed at improving access to hypertension treatment.A cross-sectional study involving 2,870 participants with hypertension with or without diabetes who were enrolled at 5 hospitals in Ghana (2 tertiary, 2 district and 1 rural hospital). Data on demographics, medical history, lifestyle factors, anti-hypertensive medications and treatment adherence were collected. The 14-item version of the Hill-Bone compliance to high blood pressure therapy scale was used to assess adherence to treatment in 3 domains namely adherence to medications, salt intake and clinic appointments. Questionnaires on knowledge, attitudes and practices on hypertension, sources of antihypertensive medications and challenges with accessing these medications were also administered. Blood pressure, weight and height were measured for each subject at enrollment. Factors associated with uncontrolled blood pressure (>140/90mmHg) were assessed using a multivariate logistic regression model.The mean ± SD age of study participants was 58.9 ± 16.6 years, with a female preponderance (76.8%). Among study participants, 1,213 (42.3%) study participants had blood pressure measurements under control. Factors that remained significantly associated with uncontrolled blood pressure with adjusted OR (95% CI) included receiving therapy at a tertiary level of care: 2.47 (1.57-3.87), longer duration of hypertension diagnosis: 1.01 (1.00-1.03), poor adherence to therapy: 1.21 (1.09-1.35) for each 5 points higher score on the Hill-Bone scale, reported difficulties in obtaining antihypertensive medications: 1.24 (1.02-1.49) and number of antihypertensive medications prescribed: 1.32 (1.21-1.44).We have found high rates of uncontrolled blood pressure among Ghanaian patients with hypertension accessing healthcare in public institutions. The system-level and individual-level factors associated with poor blood pressure control should be addressed to improve hypertension management among Ghanaians.

INTRODUCTION: The presence of left ventricular hypertrophy (LVH) in patients with Chronic Kidney Disease (CKD) is associated with worsening cardiovascular outcomes. There is a dearth of data on LVH in Ghanaian CKD patients. METHODS: this was a cross sectional study carried out at the Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana. A questionnaire was used to obtain information on clinical features of CKD. The MDRD-4 equation was used to calculate eGFR. Information on the prevalence and factors associated with electrocardiographic left ventricular hypertrophy were obtained during the initial assessment. RESULTS: this was a cross sectional study carried out at the Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana. A questionnaire was used to obtain information on clinical features of CKD. The MDRD-4 equation was used to calculate eGFR. Information on the prevalence and factors associated with electrocardiographic left ventricular hypertrophy were obtained during the initial assessment. CONCLUSION: LVH is common in our cohort. High pulse pressure, high DBP, increased BMI and male gender are significant associated factors. Adequate treatment of high blood pressure as well as early detection of LVH and interventions aimed at prevention and/or regression of LVH are to be encouraged.

Background Increasing population-levels of physical activity (PA) is a controversial strategy for managing the obesity epidemic, given the conflicting evidence for weight loss from PA alone per se. We measured PA and weight change in a three-year prospective cohort study in young adults from five countries (Ghana, South Africa, Jamaica, Seychelles and USA). Methods A total of 1,944 men and women had baseline data, and at least 1 follow-up examination including measures of anthropometry (weight/BMI), and objective PA (accelerometer, 7-day) following the three-year study period. PA was explored as 1-minute bouts of moderate and vigorous PA (MVPA) as well as daily sedentary time. Results At baseline; Ghanaian and South African men had the lowest body weights (63.4 ± 9.5, 64.9 ± 11.8 kg, respectively) and men and women from the USA the highest (93.6 ± 25.9, 91.7 ± 23.4 kg, respectively). Prevalence of normal weight ranged from 85% in Ghanaian men to 29% in USA men and 52% in Ghanaian women to 15% in USA women. Over the two-year follow-up period, USA men and Jamaican women experienced the smallest yearly weight change rate (0.1 ± 3.3 kg/yr; −0.03 ± 3.0 kg/yr, respectively), compared to South African men and Ghanaian women greatest yearly change (0.6.0 ± 3.0 kg/yr; 1.22 ± 2.6 kg/yr, respectively). Mean yearly weight gain tended to be larger among normal weight participants at baseline than overweight/obese at baseline. Neither baseline MVPA nor sedentary time were associated with weight gain. Using multiple linear regression, only baseline weight, age and gender were significantly associated with weight gain. Discussion From our study it is not evident that higher volumes of PA alone are protective against future weight gain, and by deduction our data suggest that other environmental factors such as the food environment may have a more critical role.

In sub-Saharan Africa (SSA), an estimated 74.7 million individuals are hypertensive. Reducing the growing burden of hypertension in sub-Saharan Africa will require a variety of strategies one of which is identifying the extent to which actions originating at the health systems level improves optimal management and control.We conducted a narrative synthesis of available papers examining health systems factors influencing optimal hypertension in SSA. Eligible studies included those that analyzed the impact of health systems on hypertension awareness, treatment, control and medication adherence. Twenty-five articles met the inclusion criteria and the narrative synthesis identified the following themes: 1) how physical resources influence mechanisms supportive of optimal hypertension control; 2) the role of human resources with enabling and/or inhibiting hypertension control goals; 3) the availability and/or use of intellectual resources; 4) how health systems financing facilitate and/or compromise access to products necessary for optimal hypertension control.The findings highlight the need for further research on the health systems factors that influence management and control of hypertension in the region.

Hypertension, once a rare problem in Sub-Saharan Africa (SSA), is predicted to be a major cause of death by 2020 with mortality rates as high as 75%. However, comprehensive knowledge of provider-level factors that influence optimal management is limited. The objective of the current study was to discover physicians’ perceptions of factors influencing optimal management and control of hypertension in SSA. Twelve physicians attending the Cardiovascular Research Training (CaRT) Institute at the University of Ghana, College of Health Sciences, were invited to complete a concept mapping process that included brainstorming the factors influencing optimal management and control of hypertension in patients, sorting and organizing the factors into similar domains, and rating the importance and feasibility of efforts to address these factors. The highest ranked important and feasible factors include helping patients accept their condition and availability of adequate equipment to enable the provision of needed care. The findings suggest that patient self-efficacy and support, physician-related factors, policy factors, and economic factors are important aspects that must be addressed to achieve optimal hypertension management. Given the work demands identified by physicians, future research should investigate cost-effective strategies of shifting physician responsibilities to well-trained no-physician clinicians in order to improve hypertension management.

Objective: To improve the biological and toxicological properties of Mefenamic acid (MA), the galactosylated prodrug of MA named MefeGAL was included in polymeric solid dispersions (PSs) composed of poly(glycerol adipate) (PGA) and Pluronic® F68 (MefeGAL-PS). MefeGAL-PS was compared with polymeric solid formulations of MA (MA-PS) or a mixture of equal ratio of MefeGAL/MA (Mix-PS)., Methods: The in vitro and in vivo pharmacological and toxicological profiles of PSs have been investigated. In detail, we evaluated the anti-inflammatory (carrageenan-induced paw edema test), analgesic (acetic acid-induced writhing test) and ulcerogenic activity in mice after oral treatment. Additionally, the antiproliferative activity of PSs was assessed on in vitro models of colorectal and non-small cell lung cancer., Results: When the PSs were resuspended in water, MefeGAL's, MA's and their mixture's apparent solubilities improved due to the interaction with the polymeric formulation. By comparing the in-vivo biological performance of MefeGAL-PS with that of MA, MefeGAL and MA-PS, it was seen that MefeGAL-PS exhibited the same sustained and delayed analgesic and anti-inflammatory profile as MefeGAL but did not cause gastrointestinal irritation. The pharmacological effect of Mix-PS was present from the first hours after administration, lasting about 44 hours with only slight gastric mucosa irritation. In-vitro evaluation indicated that Mix-PS had statistically significant higher cytotoxicity than MA-PS and MefeGAL-PS., Conclusions: These preliminary data are promising evidence that the galactosylated prodrug approach in tandem with a polymer-drug solid dispersion formulation strategy could represent a new drug delivery route to improve the solubility and biological activity of NSAIDs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Despite the success of polyethylene glycol-based (PEGylated) polyesters in the drug delivery and biomedical fields, concerns have arisen regarding PEG's immunogenicity and limited biodegradability. In addition, inherent limitations, including limited chemical handles as well as highly hydrophobic nature, can restrict their effectiveness in physiological conditions of the polyester counterpart. To address these matters, an increasing amount of research has been focused towards identifying alternatives to PEG. One promising strategy involves the use of bio-derived polyols, such as glycerol. In particular, glycerol is a hydrophilic, non-toxic, untapped waste resource and as other polyols, can be incorporated into polyesters via enzymatic catalysis routes. In the present study, a systematic screening is conducted focusing on the incorporation of 1,6-hexanediol (Hex) (hydrophobic diol) into both poly(glycerol adipate) (PGA) and poly(diglycerol adipate) (PDGA) at different (di)glycerol:hex ratios (30:70; 50:50 and 70:30 mol/mol) and its effect on purification upon NPs formation. By varying the amphiphilicity of the backbone, we demonstrated that minor adjustments influence the NPs formation, NPs stability, drug encapsulation, and degradation of these polymers, despite the high chemical similarity. Moreover, the best performing materials have shown good biocompatibility in both in vitro and in vivo (whole organism) tests. As preliminary result, the sample containing diglycerol and Hex in a 70:30 ratio, named as PDGA-Hex 30%, has shown to be the most promising candidate in this small library analysed. It demonstrated comparable stability to the glycerol-based samples in various media but exhibited superior encapsulation efficiency of a model hydrophobic dye. This in-depth investigation provides new insights into the design and modification of biodegradable (di)glycerol-based polyesters, potentially paving the way for more effective and sustainable PEG-free drug delivery nano-systems in the pharmaceutical and biomedical fields., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Volumetric Additive Manufacturing (VAM) represents a revolutionary advancement in the field of Additive Manufacturing, as it allows for the creation of objects in a single, cohesive process, rather than in a layer-by-layer approach. This innovative technique offers unparalleled design freedom and significantly reduces printing times. A current limitation of VAM is the availability of suitable resins with the required photoreactive chemistry and from sustainable sources. To support the application of this technology, we have developed a sustainable resin based on polyglycerol, a bioderived ( e.g. , vegetable origin), colourless, and easily functionisable oligomer produced from glycerol. To transform polyglycerol-6 into an acrylate photo-printable resin we adopted a simple, one-step, and scalable synthesis route. Polyglycerol-6-acrylate fulfils all the necessary criteria for volumetric printing (transparency, photo-reactivity, viscosity) and was successfully used to print a variety of models with intricate geometries and good resolution. The waste resin was found to be reusable with minimal performance issues, improving resin utilisation and minimising waste material. Furthermore, by incorporating dopants such as poly(glycerol) adipate acrylate (PGA-A) and 10,12-pentacosadyinoic acid (PCDA), we demonstrated the ability to print objects with a diverse range of functionalities, including temperature sensing probes and a polyester excipient, highlighting the potential applications of these new resins., Competing Interests: There are no conflicts of interest concerning this publication., (This journal is © The Royal Society of Chemistry.)

Sustainably derived poly(glycerol adipate) (PGA) has been deemed to deliver all the desirable features expected in a polymeric scaffold for drug-delivery, including biodegradability, biocompatibility, self-assembly into nanoparticles (NPs) and a functionalisable pendant group. Despite showing these advantages over commercial alkyl polyesters, PGA suffers from a series of key drawbacks caused by poor amphiphilic balance. This leads to weak drug-polymer interactions and subsequent low drug-loading in NPs, as well as low NPs stability. To overcome this, in the present work, we applied a more significant variation of the polyester backbone while maintaining mild and sustainable polymerisation conditions. We have investigated the effect of the variation of both hydrophilic and hydrophobic segments upon physical properties and drug interactions as well as self-assembly and NPs stability. For the first time we have replaced glycerol with the more hydrophilic diglycerol, as well as adjusting the final amphiphilic balance of the polyester repetitive units by incorporating the more hydrophobic 1,6-n-hexanediol (Hex). The properties of the novel poly(diglycerol adipate) (PDGA) variants have been compared against known polyglycerol-based polyesters. Interestingly, while the bare PDGA showed improved water solubility and diminished self-assembling ability, the Hex variation demonstrated enhanced features as a nanocarrier. In this regard, PDGAHex NPs were tested for their stability in different environments and for their ability to encode enhanced drug loading. Moreover, the novel materials have shown good biocompatibility in both in vitro and in vivo (whole organism) experiments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

N -Hydroxyethyl acrylamide was used as a functional initiator for the enzymatic ring-opening polymerisation of ε-caprolactone and δ-valerolactone. N -Hydroxyethyl acrylamide was found not to undergo self-reaction in the presence of Lipase B from Candida antarctica under the reaction conditions employed. By contrast, this is a major problem for 2-hydroxyethyl methacrylate and 2-hydroxyethyl acrylate which both show significant transesterification issues leading to unwanted branching and cross-linking. Surprisingly, N -hydroxyethyl acrylamide did not react fully during enzymatic ring-opening polymerisation. Computational docking studies helped us understand that the initiated polymer chains have a higher affinity for the enzyme active site than the initiator alone, leading to polymer propagation proceeding at a faster rate than polymer initiation leading to incomplete initiator consumption. Hydroxyl end group fidelity was confirmed by organocatalytic chain extension with lactide. N -Hydroxyethyl acrylamide initiated polycaprolactones were free-radical copolymerised with PEGMA to produce a small set of amphiphilic copolymers. The amphiphilic polymers were shown to self-assemble into nanoparticles, and to display low cytotoxicity in 2D in vitro experiments. To increase the green credentials of the synthetic strategies, all reactions were carried out in 2-methyl tetrahydrofuran, a solvent derived from renewable resources and an alternative for the more traditionally used fossil-based solvents tetrahydrofuran, dichloromethane, and toluene., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Admixed populations have not been examined in detail in cancer genetic studies. Here, we inferred the local ancestry of cancer-associated single nucleotide polymorphisms (SNPs) and haplotypes of a highly admixed Brazilian population. SNP array was used to genotype 73 unrelated individuals aged 80-102 years. Local ancestry inference was performed by merging genotyped regions with phase three data from the 1000 Genomes Project Consortium using RFmix. The average ancestry tract length was 9.12-81.71 megabases. Strong linkage disequilibrium was detected in 48 haplotypes containing 35 SNPs in 10 cancer driver genes. All together, 19 risk and eight protective alleles were identified in 23 out of 48 haplotypes. Homozygous individuals were mainly of European ancestry, whereas heterozygotes had at least one Native American and one African ancestry tract. Native-American ancestry for homozygous individuals with risk alleles for HNF1B, CDH1, and BRCA1 was inferred for the first time. Results indicated that analysis of SNP polymorphism in the present admixed population has a high potential to identify new ancestry-associated alleles and haplotypes that modify cancer susceptibility differentially in distinct human populations. Future case-control studies with populations with a complex history of admixture could help elucidate ancestry-associated biological differences in cancer incidence and therapeutic outcomes.

Background and Aim: Ototoxicity is a potential adverse effect of chemotherapy with platin drugs, such as cisplatin and carboplatin, in children. Hearing loss (HL) affecting frequencies below 4 kHz can compromise speech perception. The aim of this study was to investigate whether genetic variants previously implicated in ototoxicity are associated with HL overall and HL below 4 kHz in pediatric oncology patients treated with cisplatin or carboplatin., Materials and Methods: Patients given cisplatin or carboplatin for a pediatric cancer at least 5 years prior to the start of the study were enrolled. The patients underwent comprehensive audiological evaluations and genotyping to detect the presence of the GJB2 c.35delG, GSTP1 c.313A>G, and MT-RNR1 m.1555A>G polymorphisms., Results: HL was identified in 31/61 patients (50.8%), including 28/42 treated with cisplatin (66.6%) and 3/19 treated with carboplatin (15.8%). HL was associated with higher mean doses of cisplatin (p = .002) and carboplatin (p = .010). The c.313A>G variant of GSTP1 (heterozygous or homozygous) was detected in 31/61 patients (50.8%). An association between this variant allele and HL involving frequencies ≤ 4 kHz was identified (p = .020; 10-fold vs. non-carriers). No associations with HL were observed for GJB2 or MT-RNR1 gene variants., Conclusion: The GSTP1 c.313A>G variant may increase the risk of low-frequency HL in pediatric oncology patients treated with cisplatin or carboplatin chemotherapy.

Ouabain is a cardiotonic steroid identified as an endogenous substance of human plasma, being produced by the adrenal, pituitary, and hypothalamus. Despite the studies demonstrating the ability of ouabain to modulate inflammation and other aspects of the immune response, the effects of this substance in Leishmaniasis is unknown. The purpose of this work was to understand the immunomodulatory activity of ouabain in experimental Leishmaniasis in Swiss mice. It was demonstrated that ouabain reduced total cell numbers in the peritoneal cavity as a reflex of the inhibition of neutrophil migration induced by Leishmania (L.) Amazonensis. Furthermore, ouabain reduced TNF-α and IFN-γ levels, without cytotoxicity against peritoneal macrophages. These data showed the anti-inflammatory role of ouabain in the early events of the immune response triggered by Leishmania (L.) Amazonensis infection in murine model.