Engaging populations living with vulnerable conditions in community‐based research: A concept mapping approach to understanding positive practices

The goal of this research is to identify positive practices used when conducting community‐based research with people living with vulnerable conditions. Community‐based research practitioners who participated in the research included 37 researchers, community partners, program planners, and government employees, working in health, human services, children and youth, and education sectors. Concept mapping, a participatory stakeholder‐driven process, was used to generate a framework of how community‐based research practitioners responded to the complex environments of people living with vulnerable conditions when conducting research. Respondents generated positive practices, determined relationships among practices, and rated practices on frequency of use and perceived effectiveness. This study revealed 7 clusters of positive practices: ethical practices, participant supports, social accountability, community involvement, language competence, financial compensation, and project management.     

Cyclooxygenase-2 expression during allergic inflammation in guinea-pig lungs

Prostaglandins and thromboxanes are important modulators of airway physiology. The synthesis of these mediators depends on two isoforms of cyclooxygenase (COX), constitutive COX-1 and inducible COX-2. COX-2 expression has been observed in various inflammatory diseases, but not all aspects of the expression and the role of COX-2 in conditions of allergic inflammation such as asthma are clear. In the present study, we examined the 72-h kinetics of the expression of COX-isoform mRNA in ovalbumin-sensitized and -challenged guinea-pig lungs. The sensitized animals showed a robust and transient induction of COX-2 mRNA expression within 1 h after ovalbumin challenge, whereas their COX-1 mRNA levels remained unchanged. Upregulation of the level and activity of COX-2 protein followed the induction of COX-2 mRNA. Lung slices harvested from ovalbumin-challenged animals released more prostaglandin D(2) and prostaglandin E(2) spontaneously or in response to A23187 (10 microM) ex vivo than did those from unchallenged animals. This response was significantly blocked by the COX-2 selective inhibitors, NS-398 and JTE-522. In vivo administration of NS-398 significantly inhibited the accumulation of eosinophils and neutrophils in the lungs. In conclusion, de novo COX-2 expression during allergic inflammation modifies prostanoid synthesis in the lung and airway pathophysiology.     

"Hijacking" the thyrotropin receptor: A chimeric receptor-lysosome associated membrane protein enhances deoxyribonucleic acid vaccination and induces Graves' hyperthyroidism

Naked DNA vaccination with the TSH receptor (TSHR) does not, in most studies, induce TSHR antibodies and never induces hyperthyroidism in BALB/c mice. Proteins expressed endogenously by vaccination are preferentially presented by major histocompatibility complex class I, but optimal T cell help for antibody production requires lysosomal processing and major histocompatibility complex class II presentation. To divert protein expression to lysosomes, we constructed a plasmid with the TSHR ectodomain spliced between the signal peptide and transmembrane-intracellular region of lysosome-associated membrane protein (LAMP)-1, a lysosome-associated membrane protein. BALB/c mice pretreated with cardiotoxin were primed intramuscularly using this LAMP-TSHR chimera and boosted twice with DNA encoding wild-type TSHR, TSHR A-subunit, or LAMP-TSHR. With each protocol, spleen cells responded to TSHR antigen by secreting interferon-gamma, and 60% or more mice had TSHR antibodies detectable by ELISA. TSH binding inhibitory activity was present in seven, four, and two of 10 mice boosted with TSHR A-subunit, LAMP-TSHR, or wild-type TSHR, respectively. Importantly, six of 30 mice had elevated T4 levels and goiter (5 of 6 with detectable thyroid-stimulating antibodies). Injecting LAMP-TSHR intradermally without cardiotoxin pretreatment induced TSHR antibodies detectable by ELISA but not by TSH binding inhibitory activity, and none became hyperthyroid. These findings are consistent with a role for cardiotoxin-recruited macrophages in which (unlike in fibroblasts) LAMP-TSHR can be expressed intracellularly and on the cell surface. In conclusion, hijacking the TSHR to lysosomes enhances T cell responses and TSHR antibody generation and induces Graves'-like hyperthyroidism in BALB/c mice by intramuscular naked DNA vaccination.     

Angiographic estimates of myocardium at risk during acute myocardial infarction: validation study using cardiac magnetic resonance imaging.

AIMS: Global angiographic scores have been developed to determine the extent of myocardium jeopardized by significant coronary stenosis. We adapted these scores to quantify the anatomic area at risk during acute myocardial infarction. We used contrast-enhanced magnetic resonance (CMR) infarct imaging to measure the portion of myocardium that developed necrosis within the so defined angiographic area at risk. METHODS AND RESULTS: In 83 subjects presenting for primary percutaneous intervention, the myocardium at risk was estimated angiographically using the Myocardial Jeopardy Index (BARI) and a modified version of the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) scores. CMR was performed within a week to measure infarct size, infarct endocardial surface area (infarct-ESA), and infarct transmurality. As infarct transmurality increased, the infarct size closely approximated the myocardium at risk by angiography. In 35 subjects with transmural infarcts, the area at risk by BARI and APPROACH scores matched the infarct size (r = 0.90 and r = 0.92, P < 0.001). Additionally, BARI and APPROACH scores matched the infarct-ESA in all subjects independently of collateral flow and time to reperfusion (r = 0.90 and r = 0.87, P < 0.001). The presence of early reperfusion, collaterals, or both was associated with a progressive decrease in infarct transmurality (P < 0.001 for trend) with no difference in the infarct-ESA. CONCLUSION: The myocardium at risk of infarction can be determined angiographically as validated in subjects with transmural myocardial infarcts. Salvage provided by early reperfusion or collaterals occurs by limiting infarct transmurality, thereby the extent of endocardial infarct involved also allows estimation of the myocardium at risk in patients presenting with STEMI.     

Abnormalities of Intestinal Rotation in Patients with Congenital Heart Disease and the Heterotaxy Syndrome

Objective. Abnormalities of intestinal rotation (AIR) are seen in association with congenital heart disease and heterotaxy syndrome. The prevalence of these abnormalities and recommendations for management are unclear. Our objective was to determine the prevalence of screening for AIR by elective imaging among our group and prophylactic vs. emergent surgical intervention for AIR in patients with congenital heart disease and heterotaxy syndrome. Methods. From October 1988 through October 2000, we identified 74 patients with congenital heart disease and heterotaxy syndrome, 44 (59%) asplenia, 30 (41%) polysplenia. Abdominal imaging was performed in 34 patients (45%). Twenty-four (32%) were found to have AIR. Of 34 patients imaged, 22 (65%) were found to have AIR. Two patients not imaged were found to have AIR: one at autopsy, and the other, incidentally during other abdominal surgery. Because imaging was performed based on individual cardiologist’s practice style that did not change over the period of the study and rarely secondary to symptoms, it is likely that the prevalence of AIR in the patients that were not electively imaged would be similar. Results. There was no statistical difference in the presence of AIR between asplenic (34%[15/44]) and polysplenic (30%[9/30]) patients. Of the 22 patients imaged with AIR, 18 underwent Ladd procedure. Five of 12 imaged patients without AIR were found to have other significant gastrointestinal pathologies requiring intervention including gastrostomy tube placement for reflux (3), duodenal web (1), and biliary atresia (1). Of the 40 patients who were not pre-emptively imaged, none suffered acute obstruction solely secondary to AIR. However, in 2 patients intestinal obstruction was suspected and subsequently discovered by imaging and/or laparotomy due to other intestinal anomalies. Conclusions. AIR is common among patients with heterotaxy syndrome and congenital heart disease. We recommend that patients with congenital heart disease and heterotaxy syndrome have routine elective abdominal imaging of their gastrointestinal tract at birth as part of their evaluation.     

The human gut microbiome and health inequities

Individuals who are minoritized as a result of race, sexual identity, gender, or socioeconomic status experience a higher prevalence of many diseases. Understanding the biological processes that cause and maintain these socially driven health inequities is essential for addressing them. The gut microbiome is strongly shaped by host environments and affects host metabolic, immune, and neuroendocrine functions, making it an important pathway by which differences in experiences caused by social, political, and economic forces could contribute to health inequities. Nevertheless, few studies have directly integrated the gut microbiome into investigations of health inequities. Here, we argue that accounting for host–gut microbe interactions will improve understanding and management of health inequities, and that health policy must begin to consider the microbiome as an important pathway linking environments to population health.     

Brief Report: COVID-19 gender policy changes support female scientists and improve research quality

With more time being spent on caregiving responsibilities during the COVID-19 pandemic, female scientists’ productivity dropped. When female scientists conduct research, identity factors are better incorporated in research content. In order to mitigate damage to the research enterprise, funding agencies can play a role by putting in place gender equity policies that support all applicants and ensure research quality. A national health research funder implemented gender policy changes that included extending deadlines and factoring sex and gender into COVID-19 grant requirements. Following these changes, the funder received more applications from female scientists, awarded a greater proportion of grants to female compared to male scientists, and received and funded more grant applications that considered sex and gender in the content of COVID-19 research. Further work is urgently required to address inequities associated with identity characteristics beyond gender.