CD19 + CD21lo/neg cells are increased in systemic sclerosis-associated interstitial lung disease

Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21^lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p < 0.0001). While CD21^lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21^lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21^lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD.

     

A systematic review of the methodological quality of economic evaluations in genetic screening and testing for monogenic disorders

PurposeUnderstanding the value of genetic screening and testing for monogenic disorders requires high-quality, methodologically robust economic evaluations. This systematic review sought to assess the methodological quality among such studies and examined opportunities for improvement.MethodsWe searched PubMed, Cochrane, Embase, and Web of Science for economic evaluations of genetic screening/testing (2013-2019). Methodological rigor and adherence to best practices were systematically assessed using the British Medical Journal checklist.ResultsAcross the 47 identified studies, there were substantial variations in modeling approaches, reporting detail, and sophistication. Models ranged from simple decision trees to individual-level microsimulations that compared between 2 and >20 alternative interventions. Many studies failed to report sufficient detail to enable replication or did not justify modeling assumptions, especially for costing methods and utility values. Meta-analyses, systematic reviews, or calibration were rarely used to derive parameter estimates. Nearly all studies conducted some sensitivity analysis, and more sophisticated studies implemented probabilistic sensitivity/uncertainty analysis, threshold analysis, and value of information analysis.ConclusionWe describe a heterogeneous body of work and present recommendations and exemplar studies across the methodological domains of (1) perspective, scope, and parameter selection; (2) use of uncertainty/sensitivity analyses; and (3) reporting transparency for improvement in the economic evaluation of genetic screening/testing.     

Evaluation of selective attention in patients with misophonia

IntroductionMisophonia is characterized by the aversion to very selective sounds, which evoke a strong emotional reaction. It has been inferred that misophonia, as well as tinnitus, is associated with hyperconnectivity between auditory and limbic systems. Individuals with bothersome tinnitus may have selective attention impairment, but it has not been demonstrated in case of misophonia yet.ObjectiveTo characterize a sample of misophonic subjects and compare it with two control groups, one with tinnitus individuals (without misophonia) and the other with asymptomatic individuals (without misophonia and without tinnitus), regarding the selective attention.MethodsWe evaluated 40 normal-hearing participants: 10 with misophonia, 10 with tinnitus (without misophonia) and 20 without tinnitus and without misophonia. In order to evaluate the selective attention, the dichotic sentence identification test was applied in three situations: firstly, the Brazilian Portuguese test was applied. Then, the same test was applied, combined with two competitive sounds: chewing sound (representing a sound that commonly triggers misophonia), and white noise (representing a common type of tinnitus which causes discomfort to patients).ResultsThe dichotic sentence identification test with chewing sound, showed that the average of correct responses differed between misophonia and without tinnitus and without misophonia (p = 0.027) and between misophonia and tinnitus (without misophonia) (p = 0.002), in both cases lower in misophonia. Both, the dichotic sentence identification test alone, and with white noise, failed to show differences in the average of correct responses among the three groups (p ≥ 0.452).ConclusionThe misophonia participants presented a lower percentage of correct responses in the dichotic sentence identification test with chewing sound; suggesting that individuals with misophonia may have selective attention impairment when they are exposed to sounds that trigger this condition.     

The Pedagogical Challenges of Teaching High School Bioethics: Insights from the Exploring Bioethics Curriculum

A belief that high school students have the cognitive ability to analyze and assess moral choices and should be encouraged to do so but have rarely been helped to do so was the motivation for developing Exploring Bioethics, a six‐module curriculum and teacher guide for grades nine through twelve on ethical issues in the life sciences. A multidisciplinary team of bioethicists, science educators, curriculum designers, scientists, and high school biology teachers worked together on the curriculum under a contract between the National Institutes of Health and Education Development Center, a nonprofit research and development organization with a long history of innovation in science education. At the NIH, the Department of Bioethics within the Clinical Center and the Office of Science Education within the Office of the Director guided the project.Our overarching goal for Exploring Bioethics was to introduce students to bioethics as a field of inquiry and to enable them to develop ethical reasoning skills so they could move beyond “gut reactions” to more nuanced positions.     

Large gangliocytic paraganglioma of the duodenum: A rare entity

Gangliocytic paragangliomas are rare tumors that almost exclusively occur within the second portion of the duodenum. Although these tumors generally have a benign clinical course, they have the potential to recur or metastasize to regional lymph nodes. The case report presented here describes a 57-year-old female patient with melena, progressive asthenia, anemia, and a mass in the second-third portion of the duodenum that was treated by local excision. The patient was diagnosed with a friable bleeding tumor. The histologic analysis showed that the tumor was a 4 cm gangliocytic paraganglioma without a malignant cell pattern. In the absence of local invasion or distant metastasis, endoscopic resection represents a feasible, curative therapy. Although endoscopic polypectomy is currently considered the treatment of choice, it is not recommended if the size of the tumor is > 3 cm and/or there is active or recent bleeding. Patients diagnosed with a gangliocytic paraganglioma should be closely followed-up for possible local recurrence.     

The role of the Black Church in the lives of young Black men who have sex with men

In the USA, the Black Church is among the most important institutions in the Black community, offering numerous spiritual, social and health benefits. Yet, the presence of homonegativity in many Black Churches may mitigate those effects for gay Black youth. This research examines the role of the Church in the lives of gay and bisexual Black youth to understand how they reconcile any tension between their religious and sexual identities. Through interviews with pastors of Black churches (n = 21) and young Black men who have sex with men (n = 30), we explored homonegativity and young men’s experiences within the Black Church. Findings reveal that despite the prevalence of homonegativity within Black churches, religious involvement remains important for young men and many remain involved in non-affirming churches. The importance of the Church for young men stems from their significant involvement as youth and the integration of religion, family and community. Young men may not be able to leave their religious homes as readily as other gay youth given the cultural relevance of the Church. As a result, young men made attempts to conceal their sexuality in church to avoid shame and gossip and find opportunities to balance their sexuality and religiosity.     

Making meaning of the virginity experience: young men's perceptions in the United States

ABSTRACT

A qualitative grounded theory approach was used to analyze 34 narratives from young men about their experience of retaining, losing, or giving away their virginity, where 7 said they were virgins, 26 said they were non-virgins, and one did not mention his virginity status. We found that virginity is a multidimensional concept, with two distinct dimensions: the experiential and the developmental. The experiential dimension refers to young men's perception and understanding of their virginity in four overlapping areas: physical, spiritual, relational, and emotional. The developmental dimension refers to young men's perception of their underlying sexual identity growth processes and the gendered and sexual double standards that influence this understanding. Clinical implications of this study are useful in education and counseling. They seek to empower young men with information relating to the multidimensional nature of virginity experience, and minimize the negative effects on romantic relationships, sexual adjustment, and self-identity development. The findings are helpful in designing interventions for young men and women who are at high risk for sexually transmitted infections and can help them negotiate mutually safe and pleasurable experiences regarding their virginity.