Employing Respondent Driven Sampling (RDS) to recruit people who inject drugs (PWID) and other hard-to-reach populations during COVID-19: Lessons learned

Background: Respondent Driven Sampling (RDS) is an effective sampling strategy to recruit hard-to-reach populations but the impact of the COVID-19 pandemic on the use of this strategy in the collection of data involving human subjects, particularly among marginalized and vulnerable populations, is not known. Based on an ongoing study using RDS to recruit and study the interactions between HIV infection, injection drug use, and the microbiome in Puerto Rico, this paper explores the eectiveness of RDS during the pandemic and provided potential strategies that could improve recruitment and data collection. Results: RDS was employed to evaluate its effectiveness in recruiting a group of people who inject drugs (PWID) and controls (N = 127) into a study in the midst of the COVID-19 pandemic. The participants were distributed among three subsets: 15 were HIV+ and PWID, 58 were HIV- PWID, and 54 were HIV+ and not PWID. Findings: Results showthat recruitment through peer networks using RDS was possible across all sub-groups. Yet, while those in the HIV+ PWID sub-group managed to recruit from other-sub groups of HIV- PWID and HIV+, this occurred at a lower frequency. Conclusion: Despite the barriers introduced by COVID-19, it is clear that even in this environment, RDS continues to play a powerful role in recruiting hard-to-reach populations. Yet, more attention should be paid at how future pandemics, natural disasters, and other big events might affect RDS recruitment of vulnerable and hard-to-reach populations

Reduced T2* Values in Soleus Muscle of Patients with Type 2 Diabetes Mellitus

Tissue water transverse relaxation times (T2) are highly sensitive to fluid and lipid accumulations in skeletal muscles whereas the related T2* is sensitive to changes in tissue oxygenation in addition to factors affecting T2. Diabetes mellitus (DM) affects muscles of lower extremities progressively by impairing blood flow at the macrovascular and microvascular levels. This study is to investigate whether T2 and T2* are sensitive enough to detect abnormalities in skeletal muscles of diabetic patients in the resting state. T2 and T2* values in calf muscle of 18 patients with type 2 DM (T2DM), 22 young healthy controls (YHC), and 7 age-matched older healthy controls (OHC) were measured at 3T using multi-TE spin echo and gradient echo sequences. Regional lipid levels of the soleus muscle were also measured using the Dixon method in a subset of the subjects. Correlations between T2, T2*, lipid levels, glycated hemoglobin (HbA1c) and presence of diabetes were evaluated. We found that T2 values were significantly higher in calf muscles of T2DM subjects, as were T2* values in anterior tibialis, and gastrocnemius muscles of T2DM participants. However, soleus T2* values of the T2DM subjects were significantly lower than those of the older, age-matched HC cohort $(22.9\pm 0.5 vs 26.7\pm 0.4 ms, p<0.01)$. The soleus T2* values in the T2DM cohort were inversely correlated with the presence of diabetes (t = −3.46, p<0.001) and with an increase in HbA1c, but not with body mass index or regional lipid levels. Although multiple factors may contribute to changes in T2* values, the lowered T2* value observed in the T2DM soleus muscle is most consistent with a combination of high oxygen consumption and poor regional perfusion. This finding is consistent with results of previous perfusion studies and suggests that the soleus in individuals with T2DM is likely under tissue oxygenation stress

Generalized cerebral atrophy seen on MRI in a naturally exposed animal model for creutzfeldt-jakob disease

<p>Abstract</p> <p>Background</p> <p>Magnetic resonance imaging has been used in the diagnosis of human prion diseases such as sCJD and vCJD, but patients are scanned only when clinical signs appear, often at the late stage of disease. This study attempts to answer the questions "Could MRI detect prion diseases before clinical symptoms appear?, and if so, with what confidence?"</p> <p>Methods</p> <p>Scrapie, the prion disease of sheep, was chosen for the study because sheep can fit into a human sized MRI scanner (and there were no large animal MRI scanners at the time of this study), and because the USDA had, at the time of the study, a sizeable sample of scrapie exposed sheep, which we were able to use for this purpose. 111 genetically susceptible sheep that were naturally exposed to scrapie were used in this study.</p> <p>Results</p> <p>Our MRI findings revealed no clear, consistent hyperintense or hypointense signal changes in the brain on either clinically affected or asymptomatic positive animals on any sequence. However, in all 37 PrP^Scpositive sheep (28 asymptomatic and 9 symptomatic), there was a greater ventricle to cerebrum area ratio on MRI compared to 74 PrP^Scnegative sheep from the scrapie exposed flock and 6 control sheep from certified scrapie free flocks as defined by immunohistochemistry (IHC).</p> <p>Conclusions</p> <p>Our findings indicate that MRI imaging can detect diffuse cerebral atrophy in asymptomatic and symptomatic sheep infected with scrapie. Nine of these 37 positive sheep, including 2 one-year old animals, were PrP^Scpositive only in lymph tissues but PrP^Scnegative in the brain. This suggests either 1) that the cerebral atrophy/neuronal loss is not directly related to the accumulation of PrP^Scwithin the brain or 2) that the amount of PrP^Scin the brain is below the detectable limits of the utilized immunohistochemistry assay. The significance of these findings remains to be confirmed in human subjects with CJD.</p

A primer on incorporating sex as a biological variable into the conduct and reporting of basic and clinical research studies

The recent move to require sex as a biological variable (SABV), which includes gender, into the reporting of research published by the American Journal of Physiology-Heart and Circulatory Physiology follows a growing, and much-needed, trend by journals. Understandably, there is concern over how to do this without adding considerable work, especially if one’s primary research focus is not on elucidating sex/gender differences. The purpose of this article is to provide additional guidance and examples on how to incorporate SABV into the conduct and reporting of basic and clinical research. Using examples from our research, which includes both studies focused and not focused on sex/gender differences, we offer suggestions for how to incorporate SABV into basic and clinical research studies. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/incorporating-sex-as-a-biological-variable-into-basic-and-clinical-research-studies/

Examining and evaluating multilevel communication within a mixed-methods, community-based participatory research project in a rural, minority–majority U.S. Town

Community-based participatory research (CBPR) has been shown to improve health and social well-being by including diverse, marginalized community voices within academic–community partnerships. Although CBPR has gained in popularity, an explicit examination and evaluation of communication processes and outcomes throughout an entire CBPR project is lacking. Here, we analyze interviews with 10 stakeholders (i.e. 4 academic and 6 community partners) about their experiences in a three-phase, mixed-methods project exploring Hispanic and Somali community members’ perceptions of healthcare needs and access in a rural U.S. community. Results reflect that CBPR endeavors include communication challenges, successes, and ongoing tensions not simply between the academic group and community partners but also within these groups. We encourage academic– community research partners to devote considerable efforts to strengthening effective communication between and within multiple identity groups throughout an entire CBPR project (including evaluation) as they work to create, complete, and sustain project goals and outcomes

Sympathetic Markers are Different Between Clinical Responders and Nonresponders After Left Ventricular Assist Device Implantation

Background Clinical response to left ventricular assist devices (LVADs), as measured by health-related quality of life, varies among patients after implantation; however, it is unknown which pathophysiological mechanisms underlie differences in clinical response by health-related quality of life. Objective The purpose of this study was to compare changes in sympathetic markers (β-adrenergic receptor kinase-1 [βARK1], norepinephrine [NE], and 3,4-dihydroxyphenylglycol [DHPG]) between health-related quality of life clinical responders and nonresponders from pre– to post–LVAD implantation. Methods We performed a secondary analysis on a subset of data from a cohort study of patients from pre– to 1, 3, and 6 months after LVAD implantation. Clinical response was defined as an increase of 5 points or higher on the Kansas City Cardiomyopathy Questionnaire Clinical Summary score from pre– to 6 months post–LVAD implantation. We measured plasma βARK1 level with an enzyme-linked immunosorbent assay and plasma NE and DHPG levels with high-performance liquid chromatography with electrochemical detection. Latent growth curve modeling was used to compare the trajectories of markers between groups. Results The mean (SD) age of the sample (n = 39) was 52.9 (13.2) years, and most were male (74.4%) and received LVADs as bridge to transplantation (69.2%). Preimplantation plasma βARK1 levels were significantly higher in clinical responders (n = 19) than in nonresponders (n = 20) (P = .001), but change was similar after LVAD (P = .235). Preimplantation plasma DHPG levels were significantly lower in clinical responders than in nonresponders (P = .002), but the change was similar after LVAD (P = .881). There were no significant differences in plasma NE levels. Conclusions Preimplantation βARK1 and DHPG levels are differentiating factors between health-related quality of life clinical responders and nonresponders to LVAD, potentially signaling differing levels of sympathetic stimulation underlying clinical response

Sympathetic markers are different between clinical responders and nonresponders after left ventricular assist device implantation

Background Clinical response to left ventricular assist devices (LVADs), as measured by health-related quality of life, varies among patients after implantation; however, it is unknown which pathophysiological mechanisms underlie differences in clinical response by health-related quality of life. Objective The purpose of this study was to compare changes in sympathetic markers (β-adrenergic receptor kinase-1 [βARK1], norepinephrine [NE], and 3,4-dihydroxyphenylglycol [DHPG]) between health-related quality of life clinical responders and nonresponders from pre– to post–LVAD implantation. Methods We performed a secondary analysis on a subset of data from a cohort study of patients from pre– to 1, 3, and 6 months after LVAD implantation. Clinical response was defined as an increase of 5 points or higher on the Kansas City Cardiomyopathy Questionnaire Clinical Summary score from pre– to 6 months post–LVAD implantation. We measured plasma βARK1 level with an enzyme-linked immunosorbent assay and plasma NE and DHPG levels with high-performance liquid chromatography with electrochemical detection. Latent growth curve modeling was used to compare the trajectories of markers between groups. Results The mean (SD) age of the sample (n = 39) was 52.9 (13.2) years, and most were male (74.4%) and received LVADs as bridge to transplantation (69.2%). Preimplantation plasma βARK1 levels were significantly higher in clinical responders (n = 19) than in nonresponders (n = 20) (P = .001), but change was similar after LVAD (P = .235). Preimplantation plasma DHPG levels were significantly lower in clinical responders than in nonresponders (P = .002), but the change was similar after LVAD (P = .881). There were no significant differences in plasma NE levels. Conclusions Preimplantation βARK1 and DHPG levels are differentiating factors between health-related quality of life clinical responders and nonresponders to LVAD, potentially signaling differing levels of sympathetic stimulation underlying clinical response

Parasympathetic dysfunction and antiarrhythmic effect of vagal nerve stimulation following myocardial infarction

Myocardial infarction causes sympathetic activation and parasympathetic dysfunction, which increase risk of sudden death due to ventricular arrhythmias. Mechanisms underlying parasympathetic dysfunction are unclear. The aim of this study was to delineate consequences of myocardial infarction on parasympathetic myocardial neurotransmitter levels and the function of parasympathetic cardiac ganglia neurons, and to assess electrophysiological effects of vagal nerve stimulation on ventricular arrhythmias in a chronic porcine infarct model. While norepinephrine levels decreased, cardiac acetylcholine levels remained preserved in border zones and viable myocardium of infarcted hearts. In vivo neuronal recordings demonstrated abnormalities in firing frequency of parasympathetic neurons of infarcted animals. Neurons that were activated by parasympathetic stimulation had low basal firing frequency, while neurons that were suppressed by left vagal nerve stimulation had abnormally high basal activity. Myocardial infarction increased sympathetic inputs to parasympathetic convergent neurons. However, the underlying parasympathetic cardiac neuronal network remained intact. Augmenting parasympathetic drive with vagal nerve stimulation reduced ventricular arrhythmia inducibility by decreasing ventricular excitability and heterogeneity of repolarization of infarct border zones, an area with known proarrhythmic potential. Preserved acetylcholine levels and intact parasympathetic neuronal pathways can explain the electrical stabilization of infarct border zones with vagal nerve stimulation, providing insight into its antiarrhythmic benefit