Reduced Sympathetic Innervation Underlies Adjacent Noninfarcted Region Dysfunction During Left Ventricular Remodeling

AbstractObjectives. We examined the association of sympathetic denervation and reduced blood flow with mechanical dysfunction in adjacent noninfarcted regions late after myocardial infarction (MI).Background. Using a well characterized ovine model of left ventricular (LV) remodeling after transmural anteroapical MI, we previously showed that histologically normal adjacent noninfarcted regions demonstrate mechanical dysfunction.Methods. Ten sheep underwent coronary ligation. Magnetic resonance imaging was performed before and 8 weeks after infarction for measurement of LV mass, volumes, ejection fraction and regional intramyocardial circumferential shortening (%S). Iodine-123 metaiodobenzylguanidine (I-123 MIBG) and fluorescent microspheres before and after administration of adenosine were infused before death for measurement of sympathetic innervation, blood flow and blood flow reserve from matched postmortem regions.Results. From baseline to 8 weeks after infarction, LV end-diastolic volume increased from (mean ± SD) 1.5 ± 0.3 to 2.6 ± 0.5 ml/kg (p < 0.001), and LV mass increased from 2.0 ± 0.3 to 2.6 ± 0.5 g/kg (p = 0.001). Regionally, the decline in subendocardial %S was greater in adjacent (19 ± 5% to 8 ± 5%) than in remote noninfarcted regions (20 ± 6% to 19 ± 6%, p < 0.002). No difference in regional blood flow or blood flow reserve was found between adjacent and remote regions, whereas I-123 MIBG uptake was lower in adjacent than in remote myocardium (1.09 ± 0.30 vs. 1.31 ± 0.40 nmol/g, p < 0.003). Topographically, from apex to base at 8 weeks after infarction, %S correlated closely with I-123 MIBG uptake (r = 0.93, p = 0.003).Conclusions. In mechanically dysfunctional noninfarcted regions adjacent to chronic transmural myocardial infarction in the remodeled left ventricle, blood flow and blood flow reserve are preserved, yet sympathetic innervation is reduced. Chronic sympathetic denervation in adjacent noninfarcted regions, in association with regional mechanical dysfunction, may contribute to LV remodeling after infarction

Correlated effects of ocean acidification and warming on behavioral and metabolic traits of a large pelagic fish

Ocean acidification and warming are co-occurring stressors, yet their effects on early life stages of large pelagic fishes are not well known. Here, we determined the effects of elevated CO2 and temperature at levels projected for the end of the century on activity levels, boldness, and metabolic traits (i.e., oxygen uptake rates) in larval kingfish (Seriola lalandi), a large pelagic fish with a circumglobal distribution. We also examined correlations between these behavioral and physiological traits measured under different treatments. Kingfish were reared from the egg stage to 25 days post-hatch in a full factorial design of ambient and elevated CO2 (~500 &micro;atm and ~1000 &micro;atm) and temperature (21 &deg;C and 25 &deg;C). Activity levels were higher in fish from the elevated temperature treatment compared with fish reared under ambient temperature. However, elevated CO2 did not affect activity, and boldness was not affected by either elevated CO2 or temperature. Both elevated CO2 and temperature resulted in increased resting oxygen uptake rates compared to fish reared under ambient conditions, but neither affected maximum oxygen uptake rates nor aerobic scope. Resting oxygen uptake rates and boldness were negatively correlated under ambient temperature, but positively correlated under elevated temperature. Maximum oxygen uptake rates and boldness were also negatively correlated under ambient temperature. These findings suggest that elevated temperature has a greater impact on behavioral and physiological traits of larval kingfish than elevated CO2. However, elevated CO2 exposure did increase resting oxygen uptake rates and interact with temperature in complex ways. Our results provide novel behavioral and physiological data on the responses of the larval stage of a large pelagic fish to ocean acidification and warming conditions, demonstrate correlations between these traits, and suggest that these correlations could influence the direction and pace of adaptation to global climate change

A smartphone-based technique to detect dynamic user preferences for tailoring behavioral interventions: Observational utility study of ecological daily needs assessment

BACKGROUND: Mobile health apps are promising vehicles for delivering scalable health behavior change interventions to populations that are otherwise difficult to reach and engage, such as young adults with psychiatric conditions. To improve uptake and sustain consumer engagement, mobile health interventions need to be responsive to individuals\u27 needs and preferences, which may change over time. We previously created an ecological daily needs assessment to capture microprocesses influencing user needs and preferences for mobile health treatment adaptation. OBJECTIVE: The objective of our study was to test the utility of a needs assessment anchored within a mobile app to capture individualized, contextually relevant user needs and preferences within the framework of a weight management mobile health app. METHODS: Participants with an iOS device could download the study app via the study website or links from social media. In this fully remote study, we screened, obtained informed consent from, and enrolled participants through the mobile app. The mobile health framework included daily health goal setting and self-monitoring, with up to 6 daily prompts to determine in-the-moment needs and preferences for mobile health-assisted health behavior change. RESULTS: A total of 24 participants downloaded the app and provided e-consent (22 female; 2 male), with 23 participants responding to at least one prompt over 2 weeks. The mean length of engagement was 5.6 (SD 4.7) days, with a mean of 2.8 (1.1) responses per day. We observed individually dynamic needs and preferences, illustrating daily variability within and between individuals. Qualitative feedback indicated preferences for self-adapting features, simplified self-monitoring, and the ability to personalize app-generated message timing and content. CONCLUSIONS: The technique provided an individually dynamic and contextually relevant alternative and complement to traditional needs assessment for assessing individually dynamic user needs and preferences during treatment development or adaptation. The results of this utility study suggest the importance of personalization and learning algorithms for sustaining app engagement in young adults with psychiatric conditions. Further study in broader user populations is needed

Reversion of the ELISPOT test after treatment in Gambian tuberculosis cases

BACKGROUND: New tools are required to improve tuberculosis (TB) diagnosis and treatment, including enhanced ability to compare new treatment strategies. The ELISPOT assay uses Mycobacterium tuberculosis-specific antigens to produce a precise quantitative readout of the immune response to pathogen. We hypothesized that TB patients in The Gambia would have reduced ELISPOT counts after successful treatment. METHODS: We recruited Gambian adults with sputum smear and culture positive tuberculosis for ELISPOT assay and HIV test, and followed them up one year later to repeat testing and document treatment outcome. We used ESAT-6, CFP-10 and Purified Protein Derivative (PPD) as stimulatory antigens. We confirmed the reliability of our assay in 23 volunteers through 2 tests one week apart, comparing within and between subject variation. RESULTS: We performed an ELISPOT test at diagnosis and 12 months later in 89 patients. At recruitment, 70/85 HIV-negative patients (82%) were ESAT-6 or CFP-10 (EC) ELISPOT positive, 77 (90%) were PPD ELISPOT positive. Eighty-two cases (96%) successfully completed treatment: 44 (55%; p < 0.001) were EC ELISPOT negative at 12 months, 17 (21%; p = 0.051) were PPD ELISPOT negative. Sixty (73%) cured cases had a CFP-10 ELISPOT count decrease, 64 (78%) had an ESAT-6 ELISPOT count decrease, 58 (70%) had a PPD ELISPOT count decrease. There was a mean decline of 25, 44 and 47 SFU/2 × 10(5 )cells for CFP-10, ESAT-6 and PPD respectively (p < 0.001 for all). Three of 4 HIV positive patients were cured, all 3 underwent ELISPOT reversion; all 4 not cured subjects (3 HIV-negative, 1 HIV positive) were ESAT-6, CFP-10 and PPD ELISPOT positive at 12 months. CONCLUSION: Successful tuberculosis treatment is accompanied by a significant reduction in the M. tuberculosis-specific antigen ELISPOT count. The ELISPOT has potential as a proxy measure of TB treatment outcome. Further investigation into the decay kinetics of T-cells with treatment is warranted

Longitudinal Assessment of an ELISPOT Test for Mycobacterium tuberculosis Infection

Philip Hill and colleagues report that both ELISPOT conversion and reversion occur afterM. tuberculosis exposure in an endemic country and that the ELISPOT results agree poorly with results from the tuberculin skin test

Decay Kinetics of an Interferon Gamma Release Assay with Anti-Tuberculosis Therapy in Newly Diagnosed Tuberculosis Cases

Qualitative and quantitative changes in IGRA response offer promise as biomarkers to monitor Tuberculosis (TB) drug therapy, and for the comparison of new interventions. We studied the decay kinetics of TB-specific antigen T-cell responses measured with an in-house ELISPOT assay during the course of therapy.Newly diagnosed sputum smear positive TB cases with typical TB chest radiographs were recruited. All patients were given standard anti-TB treatment. Each subject was followed up for 6 months and treatment outcomes were documented. Blood samples were obtained for the ESAT-6 and CFP-10 (EC) ELISPOT at diagnosis, 1-, 2-, 4- and 6-months. Qualitative and quantitative reversion of the ELISPOT results were assessed with McNemar test, conditional logistic regression and mixed-effects hierarchical Poisson models.A total of 116 cases were recruited and EC ELISPOT was positive for 87% (95 of 109) at recruitment. There was a significant decrease in the proportion of EC ELISPOT positive cases over the treatment period (p<0.001). Most of the reversion occurred between the start and first month of treatment and at completion at 6 months. ESAT-6 had higher median counts compared to CFP-10 at all time points. Counts for each antigen declined significantly with therapy (p<0.001). Reverters had lower median SFUs at the start of treatment compared to non-Reverters for both antigens. Apart from the higher median counts for non-Reverters, no other risk factors for non-reversion were found.TB treatment induces qualitative and quantitative reversion of a positive in-house IGRA in newly diagnosed cases of active TB disease. As this does not occur reliably in the majority of cured individuals, qualitative and quantitative reversion of an IGRA ELISPOT has limited clinical utility as a surrogate marker of treatment efficacy

HIV and Other Sexually Transmitted Infections among Men Who Have Sex with Men Recruited by RDS in Buenos Aires, Argentina: High HIV and HPV Infection

The aim of this study was to estimate the prevalence of HIV and other STIs, among MSM from Buenos Aires (2007-2009).Responding Driven Sampling was used for recruitment of MSM. Participants completed a structured web-based survey and provided biological samples.A total of 496 MSM were studied for HIV, HBV, HCV, and T. pallidum infections. Chlamydia and HPV diagnoses were only performed in 98 and 109 participants, respectively. Prevalence of HIV was 17.3%, HBV 22.9%, HCV 7.5%, T. pallidum 20.5%, HPV 83.5%, and C. trachomatis 1.7%. In the year prior to the evaluation, 71% of the participants had had sex with men and/or trans and women (MMW) while 29% had not had sex with women (MM). Comparing MM to MMW, prevalence of HIV (30.7% vs. 11.9%, p<0.001), HBV (36.4% vs. 17.8%, p<0.001), T. pallidum (32.1% vs. 15.7%, p<0.001), and HPV (88.3% vs. 70.4%, p = 0.039) were significantly higher among MM, whereas no significant differences were found for HCV and C. trachomatis. The MM group had also significantly higher HIV incidence (5.60 vs. 4.28 per 100 persons-year, p = 0.032). HPV genotypes 16, 6, and 11 were the most frequently found; 40.7% of the MSM had more than one genotype and one high risk genotype was detected in 43.6% of participants.Both MM and MMW are at high risk of infection for HIV and other STIs. Rates of HIV, HBV, T. pallidum and HPV infections are higher in the MM group

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms