The epidemic of loneliness and social isolation has been recognized as a public health crisis warranting the same prioritization as other public health issues today, such as obesity, substance use ...disorders, and tobacco use. Social disconnection is particularly prevalent and disabling among individuals with anxiety and depression, yet it is inadequately evaluated and addressed in most clinical psychology treatment research. Studies generally employ global measures of perceived connectedness, loneliness, or relationship satisfaction, limiting understanding about elements of one's social network that may change with treatment. This study examined changes in the degree (number of people nominated) and quality of one's social network from pre-to post-treatment using an egocentric social network approach in 59 adults (mean age = 30.8 years, range = 18 to 54) with clinically elevated anxiety or depression who were randomized to a cognitive and behavioral positive valence treatment versus waitlist. Participants (egos) named people in their lives (alters) with whom they discussed important issues or spent free time. For each alter, participants rated how close they felt, how close they thought the alter felt to them, and how frequently they communicated. Linear regressions, which included treatment group as a predictor, revealed no group differences in changes in network degree, perceived alter feelings of closeness, or communication frequency, despite prior findings from this sample indicating larger increases in perceived global connectedness in the treatment group. Unexpectedly, the control group reported a greater increase in perceived closeness to alters. Post-hoc analyses revealed this was explained by the treatment group identifying more distal social ties (e.g., extended family, colleagues, roommates) as alters following treatment – an outcome positively associated with global improvements in connectedness. This proof-of-concept study suggests egocentric social network surveys may provide unique information on treatment-related changes in social functioning. Suggestions are provided for adaptations to facilitate application of social network surveys to mental health treatment research.
•Social disconnection is common and disabling in people with anxiety and depression.•Clinical sample randomized to positive emotion treatment or waitlist (WL).•Egocentric social network survey examined pre-to post-treatment social changes.•No group differences in network degree or contact; WL increased more in closeness.•Increased distal ties in treatment group related to greater global connectedness.
To evaluate longitudinal changes in 6 inflammatory markers that predict cardiovascular disease events among smokers making a quit attempt and to characterize their cross-sectional associations ...between smoking and smoking heaviness.
In a longitudinal cohort study of contemporary smokers (n=1652), we evaluated (1) independent associations of smoking heaviness markers (exhaled carbon monoxide, cigarettes/d, pack-years) with inflammatory markers (C-reactive protein, D-dimer, fibrinogen, urinary F
isoprostane:creatinine F
:Cr ratio, white blood cell WBC count, myeloperoxidase) and (2) the effects of smoking cessation and continued smoking on these inflammatory markers after 1 year, among the 888 smokers who made an aided quit attempt as part of a randomized comparative effectiveness trial or standard care. There were strong, independent associations between smoking heaviness markers and the F
:Cr ratio, WBC, and myeloperoxidase (all P
<0.001), but not high-sensitivity C-reactive protein, D-dimer, or fibrinogen. Participants were mean (SD) 49.6 years old (11.6), 54% women, 34% non-white, and smoked 16.8 cigarettes/d (8.5) for 27.3 pack-years (18.6). After 1 year, the 344 successful abstainers gained more weight (4.0 6.0 versus 0.4 5.7 pounds; P<0.001) and had larger increases in insulin resistance scores (P=0.02) than continuing smokers. Despite these increases, abstainers had significant decreases in F
:Cr ratio (P<0.001) and WBC counts (P<0.001). Changes in other markers were not related to quitting.
Smoking heaviness is associated with increased F
:Cr ratio, myeloperoxidase, and WBC counts. Cessation improves the F
:Cr ratio and WBC counts independent of weight change, suggesting reduced inflammation related to less oxidant stress.
Background. Specific antiretroviral therapy (ART) medications and the severity of human immunodeficiency virus (HIV) disease before treatment contribute to bone mineral density (BMD) loss after ART ...initiation. Methods. We compared the percentage change in BMD over 96 weeks in 328 HIV-infected, treatment-naive individuals randomized equally to tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) plus atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL). We also determined whether baseline levels of inflammation markers and immune activation were independently associated with BMD loss. Results. At week 96, the mean percentage changes from baseline in spine and hip BMDs were similar in the protease inhibitor (PI) arms (spine: -4.0% in the ATV/r group vs -3.6% in the DRV/r P = .42; hip: -3.9% in the ATV/r group vs -3.4% in the DRV/r group P= .36) but were greater in the combined PI arms than in the RAL arm (spine: -3.8% vs -1.8% P < .001; hip: -3.7% vs -2.4% P = .005). In multivariable analyses, higher baseline concentrations of high-sensitivity C-reactive protein, interleukin 6, and soluble CD14 were associated with greater total hip BMD loss, whereas markers of CD4 + T-cell senescence and exhaustion (CD4⁺ CD28⁻CD57⁺ PD1⁺) and CD4⁺ T-cell activation (CD4⁺ CD38⁺ HLA-DR⁺) were associated with lumbar spine BMD loss. Conclusions. BMD losses 96 weeks after ART initiation were similar in magnitude among patients receiving Pis, ATV/r, or DRV/r but lowest among those receiving RAL. Inflammation and immune activation/senescence before ART initiation independently predicted subsequent BMD loss.
Background and Purpose- Many health effects of sleep apnea (SA) may be mediated through accelerated atherosclerosis. We examined the associations of snoring and several measurements of SA with ...subclinical carotid atherosclerosis in a large multiethnic population sample. Methods- This analysis included 1615 participants (mean age, 68 years) from examination 5 (2010-2013) of the MESA study (Multi-Ethnic Study of Atherosclerosis). Sleep measures including SA (apnea-hypopnea index 4%, ≥15 events/hour) were derived from full in-home polysomnography. Carotid atherosclerosis was measured using high-resolution B-mode ultrasound. Multivariable linear and logistic regression models were used to evaluate the associations between sleep exposures with carotid intima-media thickness and the presence of carotid plaque, respectively. Effect modification by age, sex, and race/ethnicity was examined. Results- In multivariable analysis, SA was associated with an increased odds of carotid plaque presence in individuals aged <68 years (odds ratio, 1.47; 95% CI, 1.05-2.06) but not in older individuals (odds ratio, 0.95; 95% CI, 0.67-1.37;
interaction=0.078). Greater hypoxemia (sleep time <90% saturation) was associated with increasing carotid intima-media thickness in younger (0.028±0.014 mm) but not in older individuals (-0.001±0.013 mm;
interaction=0.106). Self-reported snoring was not associated with carotid atherosclerosis. In assessing race-specific outcomes, greater hypoxemia was associated with increased carotid intima-media thickness in blacks (0.049±0.017 mm;
interaction=0.033). Conclusions- In this large multiethnic population-based sample, sleep disturbances are associated with subclinical carotid atherosclerosis in both men and women, particularly in those <68 years of age. The mechanisms underlying the association between SA and carotid atherosclerosis may differ for carotid plaque and carotid intima-media thickness.
Cocoa and its major flavanol component, epicatechin, have therapeutic properties that may improve limb perfusion and increase calf muscle mitochondrial activity in people with lower extremity ...peripheral artery disease (PAD).
In a phase II randomized clinical trial, to assess whether 6 months of cocoa improved walking performance in people with PAD, compared with placebo.
Six-month double-blind, randomized clinical trial in which participants with PAD were randomized to either cocoa beverage versus placebo beverage. The cocoa beverage contained 15 g of cocoa and 75 mg of epicatechin daily. The identical appearing placebo contained neither cocoa nor epicatechin. The 2 primary outcomes were 6-month change in 6-minute walk distance measured 2.5 hours after a study beverage at 6-month follow-up and 24 hours after a study beverage at 6-month follow-up, respectively. A 1-sided
<0.10 was considered statistically significant. Of 44 PAD participants randomized (mean age, 72.3 years ±7.1; mean ankle brachial index, 0.66 ±0.15), 40 (91%) completed follow-up. Adjusting for smoking, race, and body mass index, cocoa improved 6-minute walk distance at 6-month follow-up by 42.6 m (90% CI, +22.2 to +∞
=0.005) at 2.5 hours after a final study beverage and by 18.0 m (90% CI, -1.7 to +∞
=0.12) at 24 hours after a study beverage, compared with placebo. In calf muscle biopsies, cocoa improved mitochondrial COX (cytochrome c oxidase) activity (
=0.013), increased capillary density (
=0.014), improved calf muscle perfusion (
=0.098), and reduced central nuclei (
=0.033), compared with placebo.
These preliminary results suggest a therapeutic effect of cocoa on walking performance in people with PAD. Further study is needed to definitively determine whether cocoa significantly improves walking performance in people with PAD.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT02876887. Visual Overview: An online visual overview is available for this article.
To identify and characterize an association between persistent asthma and cardiovascular disease (CVD) risk in the Multi-Ethnic Study of Atherosclerosis (MESA).
MESA is a longitudinal prospective ...study of an ethnically diverse cohort of individuals free of known CVD at its inception. The presence and severity of asthma were assessed in the MESA at examination 1. Persistent asthma was defined as asthmatics using controller medications (inhaled corticosteroids, leukotriene inhibitors, and oral corticosteroids) and intermittent asthma as asthmatics not using controller medications. Participants were followed up for a mean (SD) of 9.1 (2.8) years for development of incident CVD (coronary death, myocardial infarction, angina, stroke, and CVD death). Multivariable Cox regression models were used to assess associations of asthma and CVD. The 6792 participants were 62.2 (SD, 10.2) years old: 47% men (28% black, 22% Hispanic, and 12% Chinese). Persistent asthmatics (n=156), compared with intermittent (n=511) and nonasthmatics (n=6125), respectively, had higher C-reactive protein (1.2 1.2 versus 0.9 1.2 versus 0.6 1.2 mg/L) and fibrinogen (379 88 versus 356 80 versus 345 73 mg/dL) levels. Persistent asthmatics had the lowest unadjusted CVD-free survival rate of 84.1%, 95% confidence interval (78.9%-90.3%) compared with intermittent asthmatics 91.1% (88.5%-93.8%) and nonasthmatics 90.2% (89.4%-91%). Persistent asthmatics had greater risk of CVD events than nonasthmatics (hazard ratio 95% confidence interval, 1.6 1.01-2.5; P=0.040), even after adjustment for age, sex, race, CVD risk factors, and antihypertensive and lipid medication use.
In this large multiethnic cohort, persistent asthmatics had a higher CVD event rate than nonasthmatics.
Background. It is unclear whether the integrase inhibitor raltegravir (RAL) reduces inflammation and immune activation compared with ritonavir-boosted protease inhibitors (PIs). Methods. In a ...prospective, randomized, multicenter clinical trial that included 328 human immunodeficiency type 1 (HIV-1)–infected, treatment-naive participants were randomized to receive tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) plus atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or RAL. A total of 234 participants (71%) with HIV-1 RNA levels <50 copies/mL by week 24 were included. Plasma biomarkers of inflammation and coagulation that were analysed included high-sensitivity C-reactive protein, interleukin-6 (IL-6), GlycA, D-dimer, soluble CD14 (sCD14), sCD163, and sIL-2r; blood cellular markers included %CD38+DR+ of T-cell subsets and %CD14+CD16+ and%CD14(dim)CD16+ monocyte subsets. Changes from baseline were examined at earlier (24 or 48 weeks) and later (96 weeks) time points, with 95% confidence intervals on fold-change. Pairwise treatment groups were compared using Wilcoxon rank sum tests, with P values adjusted for false discovery rate control. Results. Changes in biomarkers varied by regimen during the 96 weeks of follow-up as follows: hsCRP declined with ATV/r and RAL, IL-6 declined only with RAL, and GLycA decreased in all groups. D-dimer declined with ATV/r and DRV/r and was unchanged with RAL. Markers of T-cell activation and sCD163 (but not sCD14 and CD14-+CD16+) declined in all groups. Conclusions. Despite some differences in specific markers of inflammation and immune activation between the antiretroviral therapy (ART) regimens, we found no consistent evidence that the reduction of inflammation and immune activation with ART initiation was different between RAL and PI-based regimens. Clinical Trials Registration. NCT00811954 and NCT00851799.
Abstract Bone morphogenetic protein-2 (BMP-2) is a potent osteoinductive factor, yet its clinical use is limited by a short biological half-life, rapid local clearance and propensity for side ...effects. Heparin (HP), a highly sulfated glycosaminoglycan (GAG) that avidly binds BMP-2, has inherent biological properties that may circumvent these limitations. Here, we compared hyaluronan-based hydrogels formulated to include heparin (Heprasil™) with similar gels without heparin (Glycosil™) for their ability to deliver bioactive BMP-2 in vitro and in vivo . The osteogenic activity of BMP-2 released from the hydrogels was evaluated by monitoring alkaline phosphatase (ALP) activity and SMAD 1/5/8 phosphorylation in mesenchymal precursor cells. The osteoinductive ability of these hydrogels was determined in a rat ectopic bone model by 2D radiography, 3D μ-CT and histological analyses at 8 weeks post-implantation. Both hydrogels sustain the release of BMP-2. Importantly, the inclusion of a small amount of heparin (0.3% w/w) attenuated release of BMP-2 and sustained its osteogenic activity for up to 28 days. In contrast, hydrogels lacking heparin released more BMP-2 initially but were unable to maintain BMP-2 activity at later time points. Ectopic bone-forming assays using transplanted hydrogels emphasized the therapeutic importance of the initial burst of BMP-2 rather than its long-term osteogenic activity. Thus, tuning the burst release phase of BMP-2 from hydrogels may be advantageous for optimal bone formation.
Little is known regarding the epigenetic basis of atherosclerosis. Here we present the CD14+ blood monocyte transcriptome and epigenome signatures associated with human atherosclerosis. The ...transcriptome signature includes transcription coactivator, ARID5B, which is known to form a chromatin derepressor complex with a histone H3K9Me2-specific demethylase and promote adipogenesis and smooth muscle development. ARID5B CpG (cg25953130) methylation is inversely associated with both ARID5B expression and atherosclerosis, consistent with this CpG residing in an ARID5B enhancer region, based on chromatin capture and histone marks data. Mediation analysis supports assumptions that ARID5B expression mediates effects of cg25953130 methylation and several cardiovascular disease risk factors on atherosclerotic burden. In lipopolysaccharide-stimulated human THP1 monocytes, ARID5B knockdown reduced expression of genes involved in atherosclerosis-related inflammatory and lipid metabolism pathways, and inhibited cell migration and phagocytosis. These data suggest that ARID5B expression, possibly regulated by an epigenetically controlled enhancer, promotes atherosclerosis by dysregulating immunometabolism towards a chronic inflammatory phenotype.The molecular mechanisms mediating the impact of environmental factors in atherosclerosis are unclear. Here, the authors examine CD14+ blood monocyte's transcriptome and epigenome signatures to find differential methylation and expression of ARID5B to be associated with human atherosclerosis.
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