The influence of viral protein R amino acid substitutions on clinical outcomes in people living with HIV: A systematic review.

BACKGROUND: The HIV viral protein R (Vpr) is a multifunction protein involved in the pathophysiology of HIV-1. Recent evidence has suggested that Vpr amino acid substitutions influence the pathophysiology of HIV-1 and clinical outcomes in people living with HIV (PLWH). Several studies have linked Vpr amino acid substitutions to clinical outcomes in PLWH; however, there is no clear consensus as to which amino acids or amino acid substitutions are most important in the pathophysiology and clinical outcomes in PLWH. We, therefore, conducted a systematic review of studies investigating Vpr amino acid substitutions and clinical outcomes in PLWH. METHODS: PubMed, Scopus and Web of Science databases were searched according to PRISMA guidelines using a search protocol designed specifically for this study. RESULTS: A total of 22 studies were included for data extraction, comprising 14 cross-sectional and 8 longitudinal studies. Results indicated that Vpr amino acid substitutions were associated with specific clinical outcomes, including disease progressions, neurological outcomes and treatment status. Studies consistently showed that the Vpr substitution 63T was associated with slower disease progression, whereas 77H and 85P were associated with no significant contribution to disease progression. CONCLUSIONS: Vpr-specific amino acid substitutions may be contributors to clinical outcomes in PLWH, and future studies should consider investigating the Vpr amino acid substitutions highlighted in this review.

Identifying a metabolomics profile associated with masked hypertension in two independent cohorts: Data from the African-PREDICT and SABPA studies.

Individuals with masked hypertension (MHT) have a greater risk of adverse cardiovascular outcomes than normotensive (NT) individuals. Exploring metabolomic differences between NT and MHT individuals may help provide a better understanding of the etiology of MHT. We analyzed data from 910 young participants (83% NT and 17% MHT) (mean age 24 ± 3 years) from the African-PREDICT and 210 older participants (63% NT and 37% MHT) from the SABPA (mean age 42 ± 9.6 years) studies. Clinic and ambulatory blood pressures (BPs) were used to define BP phenotypes. Urinary amino acids and acylcarnitines were measured using liquid chromatography time-of-flight mass spectrometry in SABPA and liquid chromatography tandem mass spectrometry in the African-PREDICT studies. In the SABPA study, amino acids (leucine/isoleucine, valine, methionine, phenylalanine), free carnitine (C0-carnitine), and acylcarnitines C3 (propionyl)-, C4 (butyryl)-carnitine and total acylcarnitine) were higher in MHT than NT adults. In the African-PREDICT study, C0- and C5-carnitines were higher in MHT individuals. With unadjusted analyses in NT adults from the SABPA study, ambulatory SBP correlated positively with only C3-carnitine. In MHT individuals, positive correlations of ambulatory SBP with leucine/isoleucine, valine, methionine, phenylalanine, C0-carnitine and C3-carnitine were evident (all p < 0.05). In the African-PREDICT study, ambulatory SBP correlated positively with C0-carnitine (r = 0.101; p = 0.006) and C5-carnitine (r = 0.195; p < 0.001) in NT adults and C5-carnitine in MHT individuals (r = 0.169; p = 0.034). We demonstrated differences between the metabolomic profiles of NT and MHT adults, which may reflect different stages in the alteration of branched-chain amino acid metabolism early on and later in life.

The neuropsychiatric manifestations of COVID-19: Interactions with psychiatric illness and pharmacological treatment.

The recent outbreak of the corona virus disease (COVID-19) has had major global impact. The relationship between severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection and psychiatric diseases is of great concern, with an evident link between corona virus infections and various central and peripheral nervous system manifestations. Unmitigated neuro-inflammation has been noted to underlie not only the severe respiratory complications of the disease but is also present in a range of neuro-psychiatric illnesses. Several neurological and psychiatric disorders are characterized by immune-inflammatory states, while treatments for these disorders have distinct anti-inflammatory properties and effects. With inflammation being a common contributing factor in SARS-CoV-2, as well as psychiatric disorders, treatment of either condition may affect disease progression of the other or alter response to pharmacological treatment. In this review, we elucidate how viral infections could affect pre-existing psychiatric conditions and how pharmacological treatments of these conditions may affect overall progress and outcome in the treatment of SARS-CoV-2. We address whether any treatment-induced benefits and potential adverse effects may ultimately affect the overall treatment approach, considering the underlying dysregulated neuro-inflammatory processes and potential drug interactions. Finally, we suggest adjunctive treatment options for SARS-CoV-2-associated neuro-psychiatric symptoms.

BDNF increases associated with constant troponin T levels and may protect against poor cognitive interference control: The SABPA prospective study.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) modulates brain health and cognition, which can interfere with executive cognitive function. BDNF was implicated with microcirculatory ischaemia and may reflect cardiomyocyte injury. We aimed to determine whether prospective changes (%Δ) in BDNF and cardiac troponin T (cTnT) will be associated with executive cognitive function in a bi-ethnic cohort. DESIGN: A prospective investigation was conducted over a three-year period in a bi-ethnic sex cohort (N = 338; aged 20-65 years) from South Africa. Fasting serum samples for BDNF and cTnT were obtained. The STROOP-color-word conflict test (CWT) was applied to assess executive cognitive function at baseline. RESULTS: In Blacks, BDNF (P < 0.001) increased over the three-year period while cTnT did not change. In contrast, in Whites, BDNF and cTnT decreased over three years. In Black men, no change in cTnT was associated with increased ΔBDNF (ß = 0.25; 95% CI 0.05-0.45; P = 0.02). In the Black men, constant cTnT levels were inversely associated with executive cognitive function (ß = -0.33; 95% CI -0.53 to -0.12; P = 0.003). Three-year increases in BDNF increased the likelihood for chronic lower cTnT levels at a pre-established cut-point of <4.2 ng/L [OR = 2.35 (1.12-4.94), P = 0.02]. The above associations were not found in the White sex groups. CONCLUSIONS: Central neural control mechanisms may have upregulated BDNF in Black men as a way to protect against myocardial stress progression and to possibly improve processes related to cognitive interference control. High-sensitive cTnT levels may act as an early predictor of disturbed neural control mechanisms.

Longitudinal changes of cardiac troponin and inflammation reflect progressive myocyte stretch and likelihood for hypertension in a Black male cohort: The SABPA study.

Inflammation was cross-sectionally associated with subclinical wall remodeling and hypertension. Whether longitudinal changes (∆) in inflammation, myocyte injury (troponin T), and stretch (N-terminal-pro-B-type natriuretic peptide) are associated with hypertension and ECG left ventricular hypertrophy (ECG-LVH) is unclear. The first prospective analysis in Africa assessing these associations included a cohort of Black and White teachers (N = 338; aged 20-63 years). Fasting blood samples were obtained to measure tumor necrosis factor-alpha (TNF-α), cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Ambulatory blood pressure, 2-lead ECG and resting 10-lead ECG values were obtained. A higher mean hypertensive status (62%) was evident in Blacks compared to Whites (44%, p < 0.001). Over 3-years, NT-proBNP increased in both ethnic groups. No associations were evident in women or in White men. In Black men, ECG-LVH at follow-up was positively associated with baseline cTnT (Adj R2 0.43; ß = 0.48; 95% CI 0.28-0.68, p < 0.001) and baseline SBP (Adj R2 0.43; ß = 0.29; 95% CI 0.09-0.49, p = 0.006). In Black men, baseline TNF-α (OR = 1.49, 95% CI 1.05-2.14, p = 0.03) and decreased ΔTNF-α (OR = 2.07, 95% CI 1.26-3.40, p = 0.004) increased the likelihood for cTnT levels ≥ 4.2 ng/L. Here, baseline NT-proBNP (OR = 1.12, 95% CI 1.01-1.23, p = 0.03) and ΔNT-proBNP progression (OR = 1.09, 95% CI 1.00-1.81, p = 0.04) increased the likelihood for 24-h hypertension. In conclusion, chronically increased levels of markers of myocyte injury accompanied by progressive myocardial stretch, reflective of cardiac metabolic overdemand, may ultimately increase hypertension and ischemic heart disease risk in a cohort of Black males.

Prospective associations between cardiac stress, glucose dysregulation and executive cognitive function in Black men: The Sympathetic activity and Ambulatory Blood Pressure in Africans study.

OBJECTIVE: Glucose dysregulation is an independent risk factor for cardiovascular and neurodegenerative disease development through synaptic dysfunction resulting in cognitive decline. The aim of this study was to study the interplay between impaired glycaemic metabolism (hyperglycaemia and insulin resistance), cardiac stress (cardiac troponin T and N-terminal brain natriuretic peptide) and executive cognitive function prospectively, in a bi-ethnic sex cohort. METHODS: Black and White teachers (N = 338, aged 20-63 years) from the Sympathetic activity and Ambulatory Blood Pressure in Africans study were monitored over a 3-year period. Fasting blood samples were obtained for cardiac troponin T, N-terminal brain natriuretic peptide, glycated haemoglobin and the homeostatic model assessment-insulin resistance for insulin resistance. The Stroop colour-word conflict test was applied to assess executive cognitive function at baseline. RESULTS: Over the 3-year period, Black men revealed constant high levels of cardiac troponin T (⩾4.2 ng/L), pre-diabetes (glycated haemoglobin > 5.7%) and insulin resistance (homeostatic model assessment-insulin resistance >3). %Δ Glycated haemoglobin was associated with %Δ insulin resistance (p < 0.001) and increases in %ΔN-terminal brain natriuretic peptide (p = 0.02) in Black men only. In the latter, baseline Stroop colour-word conflict test was inversely associated with %Δ cardiac troponin T (p = 0.001) and %Δ insulin resistance levels (p = 0.01). CONCLUSION: Progressive myocyte stretch and chronic myocyte injury, coupled with glucose dysregulation, may interfere with processes related to interference control in Black men.

Fibrosis and coronary perfusion - a cardiovascular disease risk in an African male cohort: The SABPA study.

Low-grade inflammation has been correlated with risk factors of cardiovascular diseases (CVD). Whether the pro-inflammatory and thrombotic ratio (fibrosis) may contribute to CVD is not known. We therefore aimed to assess whether Cornell Product left ventricular hypertrophy (LVH) is associated with fibrosis and coronary perfusion (silent ischemia) in a bi-ethnic male cohort from South Africa. A cross sectional study was conducted including 165 African and Caucasian men between the ages of 20-65. Fasting blood samples were obtained to measure fibrinogen, C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor (TNF-α). Ambulatory blood pressure, ECG and 12 lead ECG measures were obtained to determine silent ischemic events (ST events) and LVH, respectively. Africans revealed more silent ischemia, higher 24 h blood pressure, inflammatory, coagulation as well as fibrosis levels than Caucasians. In a low-grade inflammatory state (CRP > 3 mg/l), Africans revealed higher fibrosis (p ≤ 0.01) values, but lower IL-6 and TNF-α values than Caucasians. Linear regression analyses in several models demonstrated positive associations between silent ischemia and fibrosis [Adj. R(2) 0.23; ß 0.35 (95% CI 0.13, 0.58), p ≤ 0.01]. In a low-grade inflammatory state (CRP>3mg/l), fibrinogen predicted AV-block in African men [OR 3.38 (95% CI 2.24, 4.53); p = 0.04]. Low-grade inflammation may induce AV-block through mechanisms involving fibrosis and ischemia to increase the burden on the heart in African men.