Establishing Reference Intervals for Serum and Salivary Cortisol in a Selected Population in Kano, Nigeria.

OBJECTIVE: Serum cortisol has long been used in the assessment of disorders of the hypothalamic-pituitary-adrenal axis. The reference interval for cortisol in both serum and saliva depends on the analytical methodology and the population studied; hence, a locally derived population-based reference interval is recommended. To our knowledge, there are no studies on reference interval determination in the study area, raising concerns about the use of reference intervals established in European and North American populations. This work aimed to establish reference intervals for baseline serum and salivary cortisol levels among healthy adults in Kano, Nigeria, using methods available in our laboratory. METHODS: A cross-section of 148 apparently healthy reference individuals aged 16 to 67 years were recruited from a local community in Kano, Nigeria, using a systematic sampling technique. Baseline serum cortisol was analyzed using highly sensitive and specific electrochemiluminescence quantitative measurements on an automated immunology analyzer. Salivary cortisol levels were measured using Salimetrics' competitive enzyme-linked immunosorbent assay test kits. Parametric methods with a 95% confidence interval were used to calculate reference intervals. RESULTS: The reference intervals for cortisol in serum and saliva were 72.0 nmo/L to 554.0 nmol/L and 0.40 nmol/L to 18.0 nmol/L, respectively. There was a weak positive correlation between serum and salivary cortisol values, but this association was not statistically significant. CONCLUSION: The development of locally derived adult reference intervals can improve the diagnostic utility of serum and salivary cortisol assessment and strengthen the reliability of adrenal insufficiency diagnoses in our population.

Assessment of Right Ventricular Systolic Function using Tricuspid Annular Plane Systolic Excursion (TAPSE) among HIV Patients on HAART and Its Relationship with Viral Load and CD4 Cell Count.

BACKGROUND: The introduction of highly active antiretroviral therapy (HAART) has decreased the morbidity and mortality associated with HIV infection; however, this survival advantage is not free from complications. HIV patients are more likely to develop cardiovascular disease compared with the general population, and right ventricular systolic dysfunction is said to be associated with worse outcomes. We, therefore, sought to assess right ventricular systolic function using tricuspid annular plain systolic excursion (TAPSE) among HIV patients on HAART and its relationship with viral load and CD4 cell count. METHODS: The study was a cross-sectional conducted among HIV patients receiving HAART at the Federal Medical Centre, Nguru, Yobe State, Northeastern Nigeria. Right ventricular systolic function was assessed using tricuspid annular plane systolic excursion. RESULTS: One hundred and seven (107) subjects were recruited into the study comprising thirty-seven (34.6%) males and seventy (65.4%) females. The mean CD4 cell count and viral load of the studied patients were 612.65 ± 347.62 cells/µL and 315.44±271.11copies/mL, respectively. The distribution of RVSF according to CD4 cell count showed, fifteen (14.01%) patients with CD4 cell count less than 250 had reduced right ventricular systolic function (RVSF), 30 (28.03%) patients with CD4 cell count 250 - 500 had reduced RVSF, 1 (0.93%) patient with CD4 cell count 250 - 500 had normal RVSF, 47 (43.92%) patients with CD4 cell count 501 -1,000 had normal RVSF and 14(13.08%) patients with CD4 cell count greater than 1,000 had normal RVSF. Fourteen (13.08%) patients with undetectable viral load had normal RVSF, 47(43.92%) patients with viral load 50 - 1,500 had normal RVSF, 1(0.93%) patient with viral load 1,501 - 10,000 had normal RVSF, 30(28.03%) patients with viral load 1,501 - 10,000 had reduced RVSF and 15(14.01%) patients with viral load 10,000 - 50,000 had reduced RVSF. There was a positive and significant correlation between tricuspid annular plain systolic excursion with CD4 cell count and a negative but significant correlation HIV viral load. CONCLUSION: We therefore concluded that asymptomatic right ventricular systolic dysfunction exists among patients with HIV infection and there was positive and significant correlation between tricuspid annular plain systolic excursion with CD4 cells count and a negative but significant correlation HIV viral load.

CONTEXTE: L'introduction du traitement antirétroviral hautement actif (HAART) a réduit la morbidité et la mortalité associées à l'infection par le VIH; cependant, cet avantage de survie n'est pas exempt de complications. Les patients VIH ont plus de risques de développer des maladies cardiovasculaires par rapport à la population générale, et une dysfonction systolique ventriculaire droite est dite être associée à des résultats plus graves. Nous avons donc cherché à évaluer la fonction systolique ventriculaire droite à l'aide de l'excursion systolique du plan annulaire tricuspidien (TAPSE) chez les patients VIH sous HAART et sa relation avec la charge virale et le taux de lymphocytes CD4. MÉTHODES: L'étude était une étude transversale menée auprès de patients VIH recevant le HAART au Federal Medical Centre, Nguru, État de Yobe, dans le nord-est du Nigéria. La fonction systolique ventriculaire droite a été évaluée à l'aide de l'excursion systolique du plan annulaire tricuspidien. RÉSULTATS: Cent sept (107) sujets ont été recrutés dans l'étude, dont trente-sept (34,6%) hommes et soixante-dix (65,4%) femmes. Le taux moyen de lymphocytes CD4 et la charge virale des patients étudiés étaient respectivement de 612,65 ± 347,62 cellules/µL et 315,44 ± 271,11 copies/mL. La répartition de la fonction systolique ventriculaire droite selon le taux de lymphocytes CD4 a montré que quinze (14,01%) patients ayant un taux de lymphocytes CD4 inférieur à 250 présentaient une fonction systolique ventriculaire droite réduite, 30 (28,03%) patients ayant un taux de lymphocytes CD4 de 250 à 500 avaient une fonction systolique ventriculaire droite réduite, 1 (0,93%) patient ayant un taux de lymphocytes CD4 de 250 à 500 avait une fonction systolique ventriculaire droite normale, 47 (43,92%) patients ayant un taux de lymphocytes CD4 de 501 à 1 000 avaient une fonction systolique ventriculaire droite normale et 14 (13,08%) patients ayant un taux de lymphocytes CD4 supérieur à 1 000 avaient une fonction systolique ventriculaire droite normale. Quatorze (13,08%) patients avec une charge virale indétectable avaient une fonction systolique ventriculaire droite normale, 47 (43,92%) patients avec une charge virale de 50 à 1 500 avaient une fonction systolique ventriculaire droite normale, 1 (0,93%) patient avec une charge virale de 1 501 à 10 000 avait une fonction systolique ventriculaire droite normale, 30 (28,03%) patients avec une charge virale de 1 501 à 10 000 avaient une fonction systolique ventriculaire droite réduite et 15 (14,01%) patients avec une charge virale de 10 000 à 50 000 avaient une fonction systolique ventriculaire droite réduite. Il y avait une corrélation positive et significative entre l'excursion systolique du plan annulaire tricuspidien et le taux de lymphocytes CD4 et une corrélation négative mais significative avec la charge virale du VIH. CONCLUSION: Nous concluons donc qu'une dysfonction systolique ventriculaire droite asymptomatique existe chez les patients atteints d'une infection par le VIH et qu'il existe une corrélation positive et significative entre l'excursion systolique du plan annulaire tricuspidien et le taux de lymphocytes CD4, ainsi qu'une corrélation négative mais significative avec la charge virale du VIH. MOTS CLÉS: Fonction Systolique Ventriculaire Droite, Excursion Systolique du Plan Annulaire Tricuspidien (TAPSE), CD4, Charge Virale, VIH.

A 2-arm randomized controlled study to improve the oral health of children living with HIV in Nigeria: Protocol and study design.

Background: Good oral health is an integral part of overall child health. However, immune-deficient states like the presence of Human Immunodeficiency Virus (HIV) will compromise oral health and salivary bacterial composition, leading to adverse oral conditions. Nigeria has 1.9 million HIV-positive residents, and 0.2% of incident HIV infections occur among children below 15 years. Aim: This study aims to determine through a randomized control study, the effect of an educational intervention on the oral health status and oral health-related quality of life (OHRQoL) of HIV-positive children presenting to five pediatric HIV clinics in Kano, Nigeria. Methods/Design: This 2-arm randomized control study will be conducted in five pediatric HIV outpatient clinics in Kano State, Nigeria over a period of 6 months. Eligible participants will include 172 HIV-infected frequency matched children aged 8-16 years (they can self-implement the oral health intervention with minimal supervision from the caregivers) who will be randomized and allocated into control and intervention groups. The evaluation and oral health assessment will be carried out by five examiners who will be trained and calibrated. Discussion: Our findings will help inform policies to improve the oral health and OHRQoL of HIV-positive Nigerian children and inform the need to integrate oral health care services into HIV programs in similar settings. Trial registration: ClinicalTrails.gov ID: National Clinical Trial (NCT) NCT05540171. Registered on 12th September 2022.

The V-BRCH Project: Strengthening HIV Research Capacity in Nigeria through Intensive Workshops in Implementation Science and Grant Writing.

As persons with HIV live longer as the result of antiretroviral therapy, morbidity from HIV-associated noncommunicable diseases (NCDs) is increasing. The Vanderbilt-Nigeria Building Research Capacity in HIV and Noncommunicable Diseases program is a training platform created with the goal of training a cohort of successful Nigerian investigators to become leaders in HIV-associated NCD research. We describe survey findings from two week-long workshops in Kano, Nigeria, where trainees received instruction in implementation science and grant writing. Surveys assessed participants' self-perceived knowledge and confidence in topics taught during these workshops. Thirty-seven participants (all assistant professors) attended the implementation science workshop; 30 attended the grant-writing workshop. Response rates for the implementation science workshop were 89.2% for the preworkshop survey and 91.9% for the postworkshop survey. For the grant-writing workshop, these values were 88.2% and 85.3%, respectively. Improvement in participant knowledge and confidence was observed in every domain measured for both workshops. On average, a 101.4% increase in knowledge and a 118.0% increase in confidence was observed across measured domains among participants in the implementation science workshop. For the grant-writing workshop, there was a 68.8% increase in knowledge and a 70.3% increase in confidence observed. Participants rated the workshops and instructors as effective for both workshops. These workshops improved participants' knowledge and competence in implementation science and grant writing, and provide a model for training programs that aim to provide physician scientists with the skills needed to compete for independent funding, conduct locally relevant research, and disseminate research findings.

Prevalence and Determinants of Endothelial Dysfunction among Adults Living with HIV in Northwest Nigeria.

Background: Endothelial dysfunction constitutes an early pathophysiological event in atherogenesis and cardiovascular disease. This study aimed to assess the prevalence, determinants, and degree of endothelial dysfunction in antiretroviral therapy (ART)-treated people living with HIV (PLWH) in northwestern Nigeria using brachial flow-mediated dilatation (FMD). Methods: This was a comparative, cross-sectional study. A total of 200 ART-treated adults living with HIV with no evidence of kidney disease were compared with 200 HIV-negative participants attending a tertiary hospital in Kano, Nigeria, between September 2020 and May 2021. Endothelial function was evaluated by measuring FMD with a high-resolution vascular ultrasound transducer. FMD was calculated as the ratio of the brachial artery diameter after reactive hyperemia to baseline diameter and expressed as a percentage of change. Blood and urine samples were obtained from participants in both arms. Urine albumin-to-creatinine ratio (uACR) was calculated using the 2021 CKD-EPI estimated glomerular filtration rate (eGFR) creatinine-cystatin C equation without the race variable, and low-density lipoprotein (LDL) cholesterol was measured using enzymatic method. Results: The overall mean age (± standard deviation) of the study participants was 42 ± 11 years. Participants in the comparison arm were younger than PLWH (38 ± 11 versus 46 ± 10 years, respectively). The median (interquartile range) uACR was 41.6 (23.2-162.9) mg/g for the ART-treated PLWH versus 14.5 (7.4-27.0) mg/g for healthy controls. PLWH had a significantly lower mean percent FMD when compared to HIV-negative participants (9.8% ± 5.4 versus 12.1% ± 9.2, respectively). Reduced FMD was independently associated with HIV infection (ß = -2.83%, 95% CI, -4.44% to -1.21%, p = 0.001), estimated glomerular filtration rate (ß = -0.04%, 95% CI, -0.07% to -0.01%, p = 0.004) and LDL cholesterol (ß = -1.12%, 95% CI, -2.13% to -0.11%, p = 0.029). Conclusion: HIV-positive status, lower estimated GFR, and higher LDL cholesterol levels were independently associated with endothelial dysfunction. Future prospective studies with larger cohorts of persons living with HIV (and age- and sex-matched HIV-negative controls) are needed to gain further insight into these important findings. In the interim, aggressive management of modifiable risk factors is warranted.

Endogenous l- to d-amino acid residue isomerization modulates selectivity between distinct neuropeptide receptor family members.

The l- to d-amino acid residue isomerization of neuropeptides is an understudied post-translational modification found in animals across several phyla. Despite its physiological importance, little information is available regarding the impact of endogenous peptide isomerization on receptor recognition and activation. As a result, the full roles peptide isomerization play in biology are not well understood. Here, we identify that the Aplysia allatotropin-related peptide (ATRP) signaling system utilizes l- to d-residue isomerization of one amino acid residue in the neuropeptide ligand to modulate selectivity between two distinct G protein-coupled receptors (GPCRs). We first identified a novel receptor for ATRP that is selective for the D2-ATRP form, which bears a single d-phenylalanine residue at position 2. Using cell-based receptor activation experiments, we then characterized the stereoselectivity of the two known ATRP receptors for both endogenous ATRP diastereomers, as well as for homologous toxin peptides from a carnivorous predator. We found that the ATRP system displayed dual signaling through both the Gαq and Gαs pathways, and each receptor was selectively activated by one naturally occurring ligand diastereomer over the other. Overall, our results provide insights into an unexplored mechanism by which nature regulates intercellular communication. Given the challenges in detecting l- to d-residue isomerization from complex mixtures de novo and in identifying receptors for novel neuropeptides, it is likely that other neuropeptide-receptor systems may also utilize changes in stereochemistry to modulate receptor selectivity in a manner similar to that discovered here.

LMIC Research Centers' Experiences Hosting U.S. and LMIC Trainees: Evaluation of the Fogarty Global Health Fellows and Scholars Program, 2012 to 2020.

In this mixed-methods study, we explore themes that emerged from a survey assessing the programmatic experiences of mentors and administrators at institutions in low- and middle-income countries (LMICs) hosting trainees supported by the Fogarty International Center's Global Health Program for Fellows and Scholars. A total of 89 of 170 potential respondents representing 31 countries completed the survey (response rate, 52.4%). There was agreement among respondents that their institutions received sufficient funds to support trainees and had the capacity to manage operational and financial aspects of the program. A majority also agreed that both LMIC and U.S. trainees were beneficial to the host institutions, and that trainee projects were relevant to the needs of the host country. Respondents felt that program benefits to LMIC trainees could be improved by increasing the research consumables budget, increasing the flexibility of program timelines, and increasing engagement between LMIC and U.S. trainees and institutions. Respondents indicated that both U.S. and LMIC trainees behaved professionally (including demonstrating respectful and ethical behavior) and took appropriate initiative to conduct their research projects. Findings from this study will help inform innovations to similar training initiatives that will enhance sustainability and improve program performance, and will be responsive to local needs.

Impact of Climate Change on Management of Systemic Hypertension in North-Eastern Nigeria.

The impact of climate change on health, including changes in epidemiology and heat-related complications, has been variously reported in many parts of the world. Maiduguri, the capital of Borno state in north-eastern Nigeria, has been bearing the brunt of increasing temperatures over the past years, especially during the early months of the year building up to the commencement of the rainy season; with an average daily temperature forecasted to be around 40C. Patients with systemic hypertension and other forms of cardiovascular diseases are vulnerable to heat-related complications including dehydration, hypotension, and orthostatic hypotension (OH). This is particularly true in patients receiving various forms of antihypertensive medication, including diuretics. We present three cases of symptomatic OH occurring during the peak of heat season in Maiduguri among patients receiving various combinations of antihypertensive medication.L'impact du changement climatique sur la santé, y compris les changements dans l'épidémiologie et les complications liées à la chaleur, a été diversement rapporté dans de nombreuses régions du monde. Maiduguri, la capitale de l'État de Borno, dans le nord-est du Nigeria, a subi de plein fouet l'augmentation des températures au cours des dernières années, en particulier au cours des premiers mois de l'année, jusqu'au début de la saison des pluies. Les patients souffrant d'hypertension systémique et d'autres formes de maladies cardiovasculaires sont vulnérables aux complications liées à la chaleur, notamment la déshydratation, l'hypotension et l'hypotension orthostatique (OH). Cela est particulièrement vrai chez les patients recevant diverses formes de médicaments antihypertenseurs, notamment des diurétiques. Nous présentons trois cas d'OH symptomatique survenus pendant le pic de la saison chaude à Maiduguri chez des patients recevant diverses combinaisons de médicaments antihypertenseurs. Mots clés: Changement climatique, Hypertension, Agents antihypertenseurs, Hypotension orthostatique, Zone semiaride, Maiduguri, Nigeria.

Building Physician-Scientist Skills in R Programming:A Short Workshop Report.

Introduction: Statistical analysis programs require coding experience and a basic understanding of programming, skills which are not taught as part of medical school or residency curricula. Methods: We conducted a five-day course for early-career Nigerian physician-scientists interested in learning common statistical tests and acquiring R programming skills. The workshop included didactic presentations, small group learning activities, and interactive discussions. A baseline questionnaire captured participant demographics and solicited participants' level of confidence in understanding/performing common statistical tests. REDCap questionnaires were emailed to obtain feedback on educational format and content. A post-workshop assessment covered participants' overall impression of the program. Results: A total of 23 participants attended the program. Most participants were male (n=14, 60.9%) and at an early stage in their career (assistant professor, n=20, 87.0%). Approximately 70% of respondents indicated having received some prior training in statistics. The proportion of participants without experience using R and SAS software (90% and 85%, respectively) was greater than the corresponding proportions for Stata (55%) and SPSS (20%). Prior to the workshop, most respondents expressed being "not at all confident" in performing one-way ANOVA (60%), logistic regression (68%), simple linear regression (60%), and McNemar's test (80%). There was a statistically significant post-workshop improvement in the level of confidence in understanding and performing common statistical tests. The course was rated on a 0-100 scale as "moderately difficult" (mean ± SD: 51.7 ± 19.5). Most participants felt comfortable in putting the knowledge learned into practice (82.2 ± 17.1). Conclusion and Public Health Implications: Introductory R can be taught to junior physician-scientists in resource-limited settings and can inform the development and implementation of similar training initiatives in analogous settings.

Evaluation of endogenous peptide stereochemistry using liquid chromatography-mass spectrometry-based spiking experiments.

Functional d-amino acid-containing peptides are endogenously found throughout nature, generated through non-ribosomal peptide synthesis or through post-translational modification of ribosome-derived peptides. Despite the high functional importance of peptide stereochemistry in biomolecular recognition, identification of amino acid residue isomerization can be challenging using most common peptide characterization workflows. Here, we describe a relatively simple approach to test hypotheses regarding the stereochemistry of endogenous peptides via liquid chromatography-mass spectrometry (LC-MS) spiking experiments with synthetic isotope-labeled peptide standards. Our protocol details the synthesis of 13C-labeled synthetic peptide diastereomers via solid-phase peptide synthesis, their purification and characterization, and LC-MS experiments to evaluate putative stereochemical assignments. This approach does not require demanding purification of the endogenous peptide and is compatible with small quantities of endogenous extracts. Overall, this procedure complements current endogenous peptide characterization methods, granting the ability to relatively quickly verify the sequence and stereochemistry in endogenous peptide diastereomers directly in complex biological extracts.

Building Research Capacity in HIV and Noncommunicable Diseases in Africa: A Mentorship and Leadership Workshop Report.

INTRODUCTION: Few structured mentoring programs target early-stage investigators in Africa, creating a gap in mentorship skills where HIV burden is greatest. We describe findings from a Nigeria-based workshop for early-career physician scientists to build mentoring and leadership capacity in HIV and noncommunicable disease research. METHODS: Baseline surveys captured participant demographics, confidence in implementing mentoring competencies, and perceived importance of workshop training domains. The workshop included didactic presentations, small group activities, and interactive discussions. Daily surveys evaluated sessions, and postworkshop surveys solicited overall course impressions. RESULTS: Of the 33 participants, most were male (n = 21, 63.6%) and from medicine, laboratory sciences, and surgical specialties. "Building mentees' confidence" and "setting mentees' research goals" were ranked as areas where participants most believed they needed training. Sessions were rated favorably across five areas. Greatest improvements in mean scores were for confidence in identifying personal temperament styles, describing mentoring and leadership theories/frameworks, and developing mentoring plans. Additional identified workshop strengths were content relevance, leadership case series, interactive nature, and collegial atmosphere. All respondents indicated learning something new/useful/helpful in each session. At 6-month postworkshop, most respondents (25 of 26, 96%) had replicated or plan to replicate parts of the workshop in their departments/institutions. DISCUSSION: Effective mentoring training initiatives targeting future academic leaders have the potential to create skilled academicians who can impart mentoring skills and competencies to their mentees.

The CircumVent Project: a CPAP/O2 helmet solution for non-invasive ventilation using an implementation research framework.

BACKGROUND: Acute respiratory failure, a major cause of death in COVID-19, is managed with high-flow oxygen therapy via invasive mechanical ventilation. In resource-limited settings like Nigeria, the shortage of ventilators and oxygen supply makes this option challenging. Evidence-based non-invasive alternatives to mechanical ventilation such as the use of continuous positive airway pressure (CPAP) devices exist, but there have been concerns that non-invasive ventilation may expose healthcare workers to infection from aerosolized dispersion of SARS-CoV-2. We propose to evaluate the feasibility, adaptability and acceptability of a CPAP/O2 helmet solution for non-invasive ventilation among patients with COVID-19 and health workers in eight COVID-19 treatment and isolation centers in Nigeria. METHODS: The study will occur in 4 stages: (1) convene a Steering Committee of key stakeholders and recruit implementation sites; (2) use the integrated Promoting Action on Research Implementation in Health Services (i-PARiHS) framework to guide a needs assessment of treatment centers' capacity to use high-flow oxygen therapy to treat COVID-19 patients and utilize the findings to develop an implementation strategy for the use of a CPAP/O2 helmet solution; (3) build infrastructure to support training and data monitoring processes and to develop implementation protocols to evaluate the adaptability of the strategy for the use of the CPAP/O2 helmet; and (4) train health workers, distribute a CPAP/O2 helmet solution for non-invasive ventilation, pilot test the implementation strategy, and assess feasibility of its use and acceptability that includes monitoring altered risk of SARS-CoV-2 infection among healthcare workers. DISCUSSION: The CPAP/O2 helmet solution for non-invasive ventilation in Nigeria can serve as a scalable model for resource-poor countries, and beyond the COVID-19 pandemic, has the potential to be deployed for the treatment of pneumonia and other respiratory diseases. TRIAL REGISTRATION: NCT04929691. Registered June 18, 2021-retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04929691.

Relationship between CD4 Cell Count, Viral Load and Left Ventricular Function among HIV-1 Infected Patients Asymptomatic for Cardiac Disease on HAART.

INTRODUCTION: Human immunodeficiency virus (HIV) infected patients are at increased risk for myocardial infarction and cardiomyopathy. Low CD4 cell count and high viral load were identified as independent risk factors for cardiac disease. Asymptomatic cardiac dysfunction has also been reported in HIV-infected individuals. METHODS: This was a cross-sectional study conducted among consecutive HIV patients who are asymptomatic for cardiac disease receiving highly active antiretroviral therapy (HAART) at the ART clinic of Federal Medical Centre Nguru, Yobe State Northeastern Nigeria. DATA ANALYSIS: Statistical analysis was done using SPSS version 21.0 (SPSS IBM) Chicago Illinois. Data were presented as mean ± standard deviation (SD) for continuous variables, while categorical variables were expressed as frequencies and proportions. Correlation and regression analyses were done to determine the relationship between CD4 cell count, viral load and left ventricular function. A p-value of d"0.05 was considered significant. RESULTS: Patients with high CD4 cells count (>500 cells/µL) were found to have preserved left ventricular systolic function while those with low CD4 cells count (500 cells/µL while those with low CD4 cell count (1500 copies/mL) were associated with reduced left ventricular systolic function and severe diastolic dysfunction. We therefore suggest that there is need for early evaluation of left ventricular function in HIV patients before developing symptoms of cardiac decompensation.

RÉSUMÉ: Les patients infectés par le virus de l'immunodéficience humaine (VIH) présentent un risque accru d'infarctus du myocarde et de cardiomyopathie. Un faible nombre de cellules CD4 et une charge virale élevée ont été identifiés comme des facteurs de risque indépendants de maladie cardiaque. Un dysfonctionnement cardiaque asymptomatique a également été rapporté chez des personnes infectées par le VIH. MÉTHODES: Il s'agissait d'une étude transversale menée auprès de patients VIH consécutifs asymptomatiques de maladie cardiaque recevant un traitement antirétroviral hautement actif (HAART) à la clinique ART du Federal Medical Center Nguru, dans l'État de Yobe, au nord-est du Nigéria. ANALYSE DES DONNÉES: L'analyse statistique a été effectuée à l'aide de SPSS version 21.0 (SPSS IBM) Chicago Illinois. Les données ont été présentées sous forme de moyenne ± écart-type (SD) pour les variables continues, tandis que les variables catégorielles ont été exprimées sous forme de fréquences et de proportions. Des analyses de corrélation et de régression ont été effectuées pour déterminer la relation entre le nombre de cellules CD4, la charge virale et la fonction ventriculaire gauche. Une valeur p de d"0,05 a été considérée comme significative. RÉSULTATS: Les patients avec un nombre élevé de cellules CD4 (> 500 cellules/µL) ont conservé la fonction systolique ventriculaire gauche tandis que ceux ayant un faible nombre de cellules CD4 (500 cellules/µL tandis que ceux ayant un faible nombre de cellules CD4 (1500 copies/mL) étaient associée à une fonction systolique ventriculaire gauche réduite et à un dysfonctionnement diastolique sévère. Nous suggérons donc qu'il est nécessaire d'évaluer précocement la fonction ventriculaire gauche chez les patients VIH avant de développer des symptômes de décompensation cardiaque. MOTS CLÉS: VIH, fonction ventriculaire gauche, numération des CD4 et charge virale.

Strategies for Successful Clinical Trial Recruitment of People Living with HIV in Low- and Middle-Income Countries: Lessons Learned and Implementation Implications from the Nigeria Renal Risk Reduction (R3) Trial.

PURPOSE OF REVIEW: Clinical trials represent a bedrock for measuring efficacy of interventions in biomedical research, but recruitment into clinical trials remains a challenge. Few data have focused on recruitment strategies from the perspective of clinical trial teams, especially in low- and middle-income countries (LMIC), where HIV is most prevalent. RECENT FINDINGS: We summarized data from the literature and our experience with recruitment for the Renal Risk Reduction trial, aimed at reducing risk of kidney complications among people living with HIV in Nigeria. Using an implementation science framework, we identified strategies that contributed to successful clinical trial recruitment. For strategies that could not be categorized by this framework, we summarized key features according to selected action, actor, target, context, and time. We identified how these identified strategies could map to subsequent implementation outcomes at the patient and provider/health system level, as well as capacity-building efforts to meet needs identified by LMIC partners, which is a priority for success. Our experience highlights the importance of considering implementation outcomes, and the strategies necessary to achieve those outcomes early, in the planning and execution of clinical trials. Clinical trial recruitment can be optimized via methodologies grounded in implementation science.

Apolipoprotein-1 risk variants and associated kidney phenotypes in an adult HIV cohort in Nigeria.

HIV-positive adults are at risk for various kidney diseases, and apolipoprotein 1 (APOL1) high-risk genotypes increase this risk. This study aimed to determine the prevalence and ethnic distribution of APOL1 risk genotypes among a cohort of HIV-positive Nigerian adults and explore the relationship between APOL1 risk variant status with albuminuria and estimated glomerular filtration rate (eGFR). We conducted a cross-sectional study among 2 458 persons living with HIV who attended an HIV clinic in northern Nigeria and had received antiretroviral therapy for a minimum of six months. We collected two urine samples four-eight weeks apart to measure albumin excretion, and blood samples to measure eGFR and determine APOL1 genotype. The frequency of APOL1 high-risk genotype was 6.2%, which varied by ethnic group: Hausa/Fulani (2.1%), Igbo (49.1%), and Yoruba (14.5%). The prevalence of microalbuminuria (urine/albumin creatinine ratio 30- 300 mg/g) was 37%, and prevalence of macroalbuminuria (urine/albumin creatinine ratio over 300 mg/g) was 3%. The odds of microalbuminuria and macroalbuminuria were higher for participants with the APOL1 high-risk genotype compared to those carrying the low-risk genotype ([adjusted odds ratio 1.97, 95% confidence interval 1.37-2.82] and [3.96, 1.95-8.02] respectively). APOL1 high-risk genotype participants were at higher risk of having both an eGFR under 60 ml/min/1.73m2 and urine/albumin creatinine ratio over 300 mg/g (5.56, 1.57-19.69). Thus, we found a high proportion of HIV-positive, antiretroviral therapy-experienced, and largely virologically suppressed adults had microalbuminuria. Hence, although the high-risk APOL1 genotype was less prevalent than expected, it was strongly associated with some level of albuminuria.

The V-BRCH Project: building clinical trial research capacity for HIV and noncommunicable diseases in Nigeria.

Antiretroviral therapy has turned HIV into a chronic condition, with morbidity from HIV-associated noncommunicable diseases (NCDs) becoming more common as HIV-infected individuals live longer. In Nigeria, the additional challenge of an under-capacitated health system highlights the need for skilled clinical investigators who can generate evidence to tackle the double burden of HIV and NCDs. The Vanderbilt-Nigeria Building Research Capacity in HIV and Non-communicable Diseases (V-BRCH) programme is a training platform to create a cohort of skilled Nigerian investigators with the capacity to lead independent clinical trial research focused on the intersection of HIV and NCDs. V-BRCH will solidify an atmosphere of continuous mentoring and skills acquisition for physician faculty at the Aminu Kano Teaching Hospital via short- and medium-term learning opportunities, paired mentoring arrangements, and mentored research projects. Trainees will attend an annual faculty enrichment programme in Nashville, in addition to on-site workshops in Nigeria on HIV-associated NCD epidemiology, clinical trials methodology, evidence synthesis, qualitative research methods, stakeholder engagement, knowledge translation, and grant writing. Research-oriented junior faculty will undergo focused training in clinical trials administration and regulatory oversight. Scholars will share best practices through mentoring panels, regular 'Works in Progress' meetings, and monthly career development seminars. Competitive seed grants will be provided to mentor-mentee teams to promote targeted in-country pilot studies focused on HIV-associated NCDs. For long-term training, physician scientists will be supported to undergo enhanced Master of Public Health (MPH) training at Bayero University in Nigeria and Master of Science in Clinical Investigation (MSCI) training at Vanderbilt. Short-term regional courses, staff development workshops, and MPH curriculum refinement will help to strengthen institutional capacity in HIV-associated NCD clinical trial research. V-BRCH will create a cohort of skilled Nigerian scientists who will be able to compete for independent funding and design and implement high quality research that will generate evidence to inform policy and practice and lead to improved outcomes for Nigerians impacted by HIV-associated NCDs.

A caution for oncologists: chemotherapy can cause chaotic dynamics.

BACKGROUND AND OBJECTIVE: The effect of chemotherapy in cancer models is mostly handled by using a separate equation for chemotherapeutic agent. In this study, we do not consider a separate equation for drug but rather introduce its effect in terms of a parameter m representing the fraction of tumor cells killed by chemotherapeutic drug module. The main objective of this study is to provide conditions on model parameters which when fulfilled the grave consequences of cancer can be avoided. This study also shows that chemotherapy at times can produce unexpected results. METHODS: Linearization method to study the stability of model equilibria. RESULTS: The results obtained in this study are governed by the trichotomy law on the number 1-a12-d1, where a12 represents the negative effect on the growth of cancer cells due to their competition with host cells for resources and d1 is rate of annihilation of cancer cells due to chemotherapy. It is seen that in case of under-dose drug module when d1<1-a12, the complete eradication of cancer is not possible. When d1=1-a12, the model suggests occurrence of chaotic dynamics. When the drug dose is properly adjusted so that d1>1-a12, the complete eradication of cancer is guaranteed. CONCLUSION: The results of the model of this paper given for the post vascular stages of tumor suggest criteria to select a particular drug module (a single drug or a combination of drugs) that the chemotherapy procedure should adapt to eradicate cancer. This study injects a note of caution for oncologists that chemotherapy as cancer treatment can also cause chaotic dynamics in certain situations. This study also presents a plausible explanation to the question why sometimes a tumor grows in the body and then gets cured without any medical intervention.

A mixed therapy minimal model: Some strategies for eradication or minimization of cancer.

BACKGROUND AND OBJECTIVE: In most of the cancer therapeutic models separate equations for consumption of drugs are used, we however use parameters m and s to see the effect of chemotherapy and immunotherapy respectively. The main objective of this theoretical study is to develop strategies for eradication or minimization of cancer. METHODS: Linearization method to study the local stability of model equilibria. RESULTS: The results obtained in this study provide thresholds on m-fraction of cancer cells killed by chemotherapy and s-fraction of immune cells stimulated by immunotherapy. CONCLUSION: The model considered relates to immune-cancer-normal cell interactions in post vascularization process. The study aims to develop strategies for complete eradication or minimization of cancer in terms of model parameters. This paper presents a minimal immuno-chemotherapeutic cancer model by describing interacting dynamics of cancer, immune and normal cells in a system of three ordinary differential equations. The source of the immune cells is considered outside the sytem given by a constant influx rate, s. The minimality of the model lies in not considering a separate equation for the dynamics of the drug but its overall killing effect on the cancer cells represented by a parameter, m. Thus the parameter m relates to chemotherapy and s to immunotherapy. The analysis of the model yields thresholds on these parameters for therapeutic strategies which guarantee either eradication or minimization of cancer from a patient's body.

Factors affecting wool characteristics of sheep reared in Kashmir.

This study was conducted on 82,908 records of purebred and upgraded Kashmir Merino sheep to evaluate the performance of breed over the years. The data pertaining to fiber diameter (FD), staple length (SL), clean wool yield percent (CWY %), number of crimps/cm (NCPC), and medullation percent (MP) spread over a period of 15 years (2013-2017) was collected from Fleece Testing Laboratory Nowshera, Srinagar. The highest CV (%) was observed for MP, whereas the lowest CV (%) was observed for FD (2.07%). The least-squares means were 20.96 ± 0.002 µm, 4.05 ± 0.01 cm, 66.68 ± 0.01%, 4.38 ± 0.02 No/cm and 0.79 ± 0.05% for FD, SL, CWY (%), NCPC and MP, respectively. The year of shearing had highly significant (p < 0.01) effect on all the traits under the study. The study concludes that crossbreeding with exotic fine wool breeds has resulted improved genetic potential of native germplasm with respect to wool quality traits with Merino sheep performing better in the agro-climatic conditions of the State. Environment was also found to play a significant role in expression of wool quality traits during the period of the study.