Isolation and expansion of thymus-derived regulatory T cells for use in pediatric heart transplant patients

Regulatory T-cells (Tregs) are a subset of T cells generated in the thymus with intrinsic immunosuppressive properties. Phase I clinical trials have shown safety and feasibility of Treg infusion to promote immune tolerance and new studies are ongoing to evaluate their efficacy. During heart transplantation, thymic tissue is routinely discarded providing an attractive source of Tregs. In this study, we developed a GMP-compatible protocol for expanding sorted thymus-derived CD3⁺CD4⁺CD25⁺CD127^– (Tregs) as well as CD3⁺CD4⁺CD25⁺CD127^–CD45RA⁺ (RA⁺Tregs) cells. We aimed to understand whether thymic RA⁺Tregs can be isolated and expanded offering an advantage in terms of stability as it has been previously shown for circulating adult CD45RA⁺ Tregs. We show that both Tregs and RA⁺Tregs could be expanded in large numbers and the presence of rapamycin is essential to inhibit the growth of IFN-γ producing cells. High levels of FOXP3, CTLA4, and CD25 expression, demethylation of the FOXP3 promoter, and high suppressive ability were found with no differences between Tregs and RA⁺Tregs. After freezing and thawing, all Treg preparations maintained their suppressive ability, stability, as well as CD25 and FOXP3 expression. The number of thymic Tregs that could be isolated with our protocol, their fold expansion, and functional characteristics allow the clinical application of this cell population to promote tolerance in pediatric heart transplant patients.     

Beginning community engagement at a busy biomedical research programme: experiences from the KEMRI CGMRC-Wellcome Trust Research Programme, Kilifi, Kenya

There is wide acknowledgement of the need for community engagement in biomedical research, particularly in international settings. Recent debates have described theoretical approaches to identifying situations where this is most critical and potential mechanisms to achieve it. However, there is relatively little published experience of community engagement in practice. A major component of the Kenya Medical Research Institute (KEMRI) Wellcome Trust Research Programme is centred on Kilifi District General Hospital and surrounding community of 240,000 local residents. Documented community perceptions of the research centre are generally positive, but many indicate a low understanding of research and therapeutic misconceptions of its activities. As in other settings, these misunderstandings have contributed to concerns and rumours, and potentially undermine ethical aspects of research and local trust in the institution. Through a series of consultative activities, a community engagement strategy has been developed in Kilifi to strengthen mutual understanding between community members and the Centre. One important component is the establishment of a representative local resident network in different geographic locations commonly involved in research, to supplement existing communication channels. Early implementation of the strategy has provided new and diverse opportunities for dialogue, interaction and partnership building. Through the complex social interactions inherent in the community engagement strategy, the centre aims to build context specific ethical relations with local residents and to strengthen understanding of how ethical principles can be applied in practice. Evaluations over time will assess the effectiveness and sustainability of these strategies, provide generalisable information for similar research settings, and contribute to debates on the universality of ethical principles for research. This paper aims to summarise the rationale for community engagement in research, drawing on published literature and local findings, to outline the process of community engagement in Kilifi and to describe issues emerging from its development and early implementation.     

Diastolic Mitral Regurgitation

An 89-year-old female with a history of hypertension presented to the hospital with symptoms of fatigue. Her electrocardiogram (ECG) showed high-grade atrioventricular (AV) block, so a transthoracic echocardiogram was obtained to assess for structural heart abnormalities (Figure 1). Color Doppler showed mild mitral regurgitation (MR) extending into diastole. Temporal interrogation of the MR jet using continuous wave Doppler confirmed the diastolic component.Open in a separate windowFigure 1The hemodynamic elements of this mitral regurgitation (MR) are dissected and explained. MR: mitral regurgitation; LA: left atrial; LV: left ventricle; LVEDP: left ventricular end-diastolic pressure.Diastolic MR is generally described in the setting of AV dissociation. In patients with high-degree AV block and underlying sinus rhythm, the prolonged diastolic time with accompanying superimposed left atrial (LA) contractions will lead to a significant elevation in left ventricular end-diastolic pressure (LVEDP), creating a reverse gradient favoring flow from the left ventricle back into the LA during diastole. Diastolic MR also can occur with substantial elevations in LVEDP in restrictive cardiomyopathies and acute severe aortic regurgitation.     

Psychometric Evaluation of a Revised Scoring Approach for the Children’s Saving Inventory in a Canadian Sample of Youth With Obsessive–Compulsive Disorder

The Children’s Saving Inventory (CSI) was introduced in 2011 and is the first parent-rated questionnaire specifically designed to measure the severity of hoarding symptoms in youth. To date, however, no replication studies of the CSI have been published. Additionally, the total CSI score includes several items measuring acquisition, a behavioural dimension that has since been excluded from DSM-5’s hoarding disorder criteria. Given these limitations, the primary goal of the present study was to test a modified, DSM-5-consistent, total score of the CSI. Because a confirmatory factor analysis did not support the 2011 four-factor model of the CSI, we reviewed the original CSI and excluded all acquisition items. An exploratory factor analysis yielded a strong three-factor solution (difficulty discarding, Clutter, and distress/impairment) with good reliability and validity for a 15-item version of the CSI. Overall, our results support the use of the 15-item CSI in youth with OCD.     

Fear of Negative Evaluation and Rapid Response to Treatment During Cognitive Behaviour Therapy for Social Anxiety Disorder

Cognitive Therapy and Research - Cognitive behavioural therapy (CBT) for Social Anxiety Disorder (SAD) is an effective intervention for SAD, however, many individuals with SAD remain symptomatic at...     

Seroprevalence of SARS-CoV-2 Binding and Neutralizing Antibodies in Healthcare Workers during the Epidemic Peak in Referral Hospitals and Quarantine Sites: Saudi Arabia

Healthcare workers (HCWs) are at high risk for SARS-CoV-2 infection compared to the general population. Here, we aimed to evaluate and characterize the SARS-CoV-2 seropositivity rate in randomly collected samples among HCWs from the largest referral hospitals and quarantine sites during the peak of the COVID-19 epidemic in the city of Jeddah, the second largest city in Saudi Arabia, using a cross-sectional analytic study design. Out of 693 participants recruited from 29 June to 10 August 2020, 223 (32.2%, 95% CI: 28.8–35.8) were found to be confirmed seropositive for SARS-CoV-2 antibodies, and among those 197 (88.3%) had never been diagnosed with COVID-19. Seropositivity was not significantly associated with participants reporting COVID-19 compatible symptoms as most seropositive HCW participants 140 (62.8%) were asymptomatic. The large proportion of asymptomatic SARS-CoV-2 cases detected in our study demands periodic testing as a general hospital policy.