To assess the short-term effects of extended-release niacin (ERN) on endothelial function in HIV-infected patients with low high-density lipoprotein-cholesterol (HDL-c) levels.Randomized controlled study to determine the short-term effects of ERN on endothelial function, measured by flow-mediated vasodilation (FMD) of the brachial artery, in HIV-infected adults with low HDL-c. Participants on stable HAART with fasting HDL-c less than 40 mg/dl and low-density lipoprotein-cholesterol less than 130 mg/dl were randomized to ERN or control arms. ERN treatment started at 500 mg/night and titrated to 1500 mg/night for 12 weeks. Controls received the same follow-up but were not given ERN (no placebo). Participants were excluded if they had a history of cardiac disease, uncontrolled hypertension, diabetes mellitus, or were on lipid-lowering medications such as statins and fibrates. Change in FMD was compared between arms with respect to baseline HDL-c.Nineteen participants were enrolled: 89% men, median age 50 years, 53% white/non-Hispanic, median CD4 cell count 493 cells/microl, and 95% of them had HIV RNA below 50 copies/ml. Participants receiving ERN had a median HDL-c (interquartile range) increase of 3.0 mg/dl (0.75 to 5.0) compared with -1.0 mg/dl in controls (-6.0 to 2.5), a P value is equal to 0.04. The median change in FMD was 0.91% (-2.95 to 2.21) for ERN and -0.48% (-2.65 to 0.98) for controls (P = 0.67). However, end of study FMD for ERN was significantly different from controls after adjusting for baseline differences in FMD and HDL-c, 6.36% (95% confidence interval 4.85-7.87) and 2.73% (95% confidence interval 0.95-4.51) respectively, a P value is equal to 0.048.This pilot study demonstrated that short-term niacin therapy could improve endothelial function in HIV-infected patients with low HDL-c.
Objective High rates of albuminuria are observed among HIV-infected individuals on stable antiretroviral therapy (ART). Though pro-inflammatory and pro-fibrotic responses are described as components of albuminuria in the general population, it is unclear how these responses are associated to albuminuria in ART-treated chronic HIV. We investigated the relationship of monocyte subsets and urine inflammatory and fibrotic biomarkers to albuminuria in ART-treated HIV-infected participants. Design and Methods Cross-sectional analyses were performed on Hawaii Aging with HIV-cardiovascular disease study cohort participants who were required at entry to be ≥40 years old and on ART ≥3 months. Monocyte subpopulations were determined in banked peripheral blood mononuclear cells (PBMC) using multi-parametric flow-cytometry. Entry random urine samples were assessed for albumin-to-creatinine ratios (UACR). Urine samples were measured for inflammatory and fibrotic biomarkers using Luminex technology. Results Among 96 HIV-infected subjects with measured UACR (87% male, 59% Caucasian, and 89% undetectable HIV RNA with median CD4 of 495.5 cells/μL), 18 patients (19%) had albuminuria. Non-classical (CD14low/+CD16++) monocytes were significantly elevated in subjects with albuminuria (p = 0.034) and were correlated to UACR (r = 0.238, p = 0.019). Elevated non-classical monocyte counts were significant predictors of worsening albuminuria, independent of traditional- and ART-associated risk factors (β = 0.539, p = 0.007). Urine TGF-β1 and collagen-IV were significantly higher in albuminuric compared to non-albuminuric participants (TGF-β1; p = 0.039 and collagen-IV; p = 0.042). Urine TGF-β1 was significantly correlated with non-classical monocyte counts (r = 0.464, p = 0.017). Conclusion Alterations in monocyte subpopulations and urine pro-fibrotic factors may play a role in kidney dysfunction during chronic HIV infection and warrants further study.
OBJECTIVES: To determine the autonomic cardiovascular control among residents of Hawaii who are exposed to varying levels of volcanic air pollution (vog), which consists largely of sulfur dioxide (SO(2)) and acid aerosols. METHODS: In a cross-sectional study between April 2006 and June 2008, the authors measured cardiovagal autonomic function by heart-rate variability (HRV) in 72 healthy individuals who lived in four exposure zones on Hawaii Island: vog-free (n=18); episodic exposure to SO(2) >200 ppb and acid aerosol (n=19); chronic exposure to SO(2) ≥30 ppb and acid aerosol (n=15); and chronic exposure to acid aerosols (n=20). Individuals with diabetes or heart disease, or who had smoked in the preceding month were excluded. HRV was measured in all subjects during rest, paced breathing and active standing (Ewing manoeuvre). HRV was analysed in time and frequency domains and compared between the four exposure zones. RESULTS: There were no significant differences between exposure zones in HRV, in either time or frequency domains, even after adjustment for age, gender, ethnicity and body mass index. There was no significant HRV change in three individuals in whom HRV was measured before and during an exposure to combined SO(2) 100-250 ppb and concentration of respirable particles of diameter ≥2.5 μ (PM(2.5)) >500 μg/m(3). Age was significantly correlated with time-domain parameters during paced breathing and the Ewing manoeuvre. CONCLUSIONS: This study of healthy individuals found no appreciable effects of vog on the autonomic nervous system.
Background:
The observed higher prevalence of albuminuria among HIV-infected patients has been strongly associated with cardiovascular disease and higher mortality. In HIV-seronegative patients with metabolic syndrome, malignancies and infections, pro-inflammatory cytokines, and acute phase reactants have been associated with albuminuria. However, the pathophysiology of albuminuria in HIV-seropositive individuals is poorly understood. We investigated the association of albuminuria with inflammatory biomarkers among HIV-infected patients on combination antiretroviral therapy.
Noninvasive prediction of the maximum axial load that a spinal bone screw will be able to withstand after anterior surgical placement would be highly useful. To investigate if this is feasible, we first performed preliminary experiments to distinguish the trabecular and cortical contributions to overall stiffness; the trabecular component was found to dominate. We then used a commercial computed tomography bone mineral package to determine the mineral density of the trabecular region of 41 porcine vertebrae in terms of equivalent K2HPO4 concentration; values ranged from 104 to 343 mg/cm3. A 6.5-mm diameter cancellous bone screw was then inserted laterally in each vertebra, and the ultimate tensile strength (UTS) of the screw/bone interface was measured using a tensile testing machine. The UTS values ranged from 589 to 2,620 Newtons. A superlinear relation was found between UTS and the projected K2HPO4 concentration in the direction of the screw axis, expressed in units of mg/cm2.
Non-exercise (N-EX) questionnaires have been developed to determine maximal oxygen consumption (VO2max) in healthy populations. There are limited reliable and validated N-EX questionnaires for the HIV+ population that provide estimates of habitual physical activity and not VO2max.To determine how well regression equations developed previously on healthy populations, including N-EX prediction equations for VO2max and age-predicted maximal heart rates (APMHR), worked on an HIV+ population; and to develop a specific N-EX prediction equation for VO2max and APMHR for HIV+ individuals.Sixty-six HIV+ participants on stable HAART completed 4 N-EX questionnaires and performed a maximal graded exercise test.Sixty males and 6 females were included; mean (SD) age was 49.2 (8.2) years; CD4 count was 516.0 ± 253.0 cells·mm-3; and 92% had undetectable HIV PCR. Mean VO2max was 29.2 ± 7.6 (range, 14.4-49.4) mL·kg-1·min-1 Despite positive correlations with VO2max, previously published N-EX VO2max equations produced results significantly different than actual VO2 scores (P < .0001). An HIV+ specific N-EX equation was developed and produced similar mean VO2max values, R = 0.71, when compared to achieved VO2max (P = .53).HIV+ individuals tend to be sedentary and unfit, putting them at increased risk for the development of chronic diseases associated with a sedentary lifestyle. Based on the level of error associated with utilizing APMHR and N-EX VO2max equations with HIV+ individuals, neither should be used in this population for exercise prescription.
Monocytes and macrophages play a pivotal role in inflammation during acute SARS-CoV-2 infection. However, their contribution to the development of pulmonary post-acute sequelae of SARS-CoV-2 infection (PPASC) are not fully elucidated. To determine monocyte dysregulation and cytokines associated with PPASC, we analyzed plasma cytokine expression and circulating monocytes in COVID-19 convalescents [convalescents with PPASC (PG) and no symptoms (RG)], comparing them to uninfected individuals (NG). We found elevated plasma level of IL-1Ra expression, but FGF expression was reduced in PG, compared to NG. COVID-19 convalescents displayed increased monocyte levels and CD169+ monocytes. CD169+ monocyte subsets correlated with DLCOc% inversely and IL-1α, IL-1β, MIP-1α, Eotaxin, and IFNγ expression positively in PG. This study present evidence that COVID convalescents exhibit monocyte alteration beyond the acute COVID-19 infection period even in convalescents with no residual symptoms. Furthermore, monocyte alteration and increased activated monocyte subsets may impact pulmonary function in COVID-19 convalescents.
