Seroprevalence and clinical characteristics of SARS-CoV-2 infection in children with cystic fibrosis.

BACKGROUND: People with cystic fibrosis (PwCF) have chronic lung disease and may be at increased risk of coronavirus disease 2019 (COVID-19)-related morbidity and mortality. This study aimed to determine seroprevalence and clinical characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children with cystic fibrosis (CF), and to assess antibody responses following SARS-CoV-2 infection or vaccination. METHODS: Children and adolescents with CF followed at Seattle Children's Hospital were enrolled between July 20, 2020 and February 28, 2021. SARS-CoV-2 serostatus was determined on enrollment at 6 and 11 months (±2 months) for nucleocapsid and spike IgG. Participants completed intake and weekly surveys inquiring about SARS-CoV-2 exposures, viral/respiratory illnesses, and symptoms. RESULTS: Of 125 PwCF enrolled, 14 (11%) had positive SARS-CoV-2 antibodies consistent with recent or past infection. Seropositive participants were more likely to identify as Hispanic (29% vs. 8%, p = 0.04) and have pulmonary exacerbations requiring oral antibiotics in the year prior (71% vs. 41%, p = 0.04). Five seropositive individuals (35.7%) were asymptomatic, while six (42.9%) reported mild symptoms, primarily cough and nasal congestion. Antispike protein IgG levels were approximately 10-fold higher in participants following vaccination compared with participants who had natural infection alone (p < 0.0001) and resembled levels previously reported in the general population. CONCLUSIONS: A majority of PwCF have mild or no symptoms of SARS-CoV-2 making it difficult to distinguish from baseline respiratory symptoms. Hispanic PwCF may be disproportionately impacted, consistent with racial and ethnic COVID-19 disparities among the general US population. Vaccination in PwCF generated antibody responses similar to those previously reported in the general population.

Augmenting Traditional Support Groups for Adolescents With Type 1 Diabetes Using Instagram: Mixed Methods Feasibility Study.

BACKGROUND: In-person support groups have been shown to benefit adolescents with type 1 diabetes (T1D) by helping to decrease perceived diabetes burden and improving knowledge related to chronic disease management. However, barriers exist to participation in traditional support groups, including the timing and location of meetings and resources needed to attend. Adolescents are increasingly utilizing online support groups, which may provide solutions to some of the challenges faced when implementing in-person support groups. OBJECTIVE: The purpose of this study was to assess the feasibility and acceptability of a hybrid support group model where traditional in-person support groups were augmented with Instagram participation between monthly support group sessions for adolescents with T1D. METHODS: Participants (13-18 years old with T1D for ≥6 months) were asked to post photos each week for 3 months based on predetermined topics related to diabetes management. At the end of each month, participants attended an in-person support group to discuss their photos using the Photovoice method. Feasibility was assessed through enrollment and retention, number of Instagram posts, poststudy questionnaire, and a template analysis of the focus groups. RESULTS: Of 24 eligible participants, 16 (67%) enrolled in the study, with 3 dropping out prior to support group participation. The number of photos posted over 3 months ranged from 14 to 41. Among the 11 participants who completed a follow-up questionnaire, the majority of participants (6/11, 55%) reported that they very much enjoyed participating in the hybrid support group, and more than three-quarters (9/11, 82%) of participants reported that they "related to the photos posted." Over half of participants (8/11, 73%) reported "learning something new from the photos posted," which arose from sharing knowledge and experiences related to navigating the common challenges of diabetes management. Additionally, the use of Instagram posts helped facilitate peer discussions during the in-person support groups. CONCLUSIONS: The novel combination of using Instagram to augment traditional in-person support groups was feasible and acceptable to adolescents with T1D. The overall satisfaction with the hybrid support group model, combined with the observed engagement with peers between support group sessions over social media, suggests that a hybrid support group model may have the potential to provide more pronounced benefits to adolescents than in-person meetings alone. Future research should investigate the use of social media as part of the support group model and examine the potential improvement of self-esteem, benefit-finding, and social support using validated tools in adolescents with diabetes.

Trajectories of Acute Diabetes-Specific Stress in Adolescents With Type 1 Diabetes and Their Caregivers Within the First Year of Diagnosis.

Objectives: Our aims were to describe stress trajectories for newly diagnosed type 1 diabetes (T1D) in adolescents and their parents, explore whether resilience is associated with stress trajectories, and to examine the effects of stress trajectories on diabetes-specific outcomes. Methods: Fifty-nine youth aged 10-18 years with newly diagnosed T1D and a primary caregiver were followed for 12 months. Stress and resilience were assessed using questionnaires every 3 months, and diabetes-specific outcomes (self-care, quality of life, and hemoglobin A1C) at 6 and 12 months. Parent and adolescent stress trajectories were identified using semiparametric group-based modeling. Results: Four stress trajectories emerged for parents and three emerged for adolescents. Adolescent trajectories were stable throughout the 12 months, and those with stable low stress had the highest levels of resilience. Further, the stable low stress group had higher quality of life scores at 12-month postdiagnosis. In contrast, stress for parents changed considerably over the 12-month period, and trajectory groups did not associate with 12-month outcomes. Conclusions: Distinct patterns of stress emerged for both the adolescent and parent cohorts. Resilience at the time of diagnosis was particularly protective for adolescents. These results suggest that stress-reducing and resilience-promoting interventions for newly diagnosed adolescents with T1D may have potential to improve longer-term outcomes.

Do youth with type 1 diabetes exercise safely? A focus on patient practices and glycemic outcomes.

OBJECTIVE: Insulin adjustments have been shown to reduce glycemic excursions during and after exercise, but little is known about their use in youth with type 1 diabetes (T1D). We aimed to assess practices in youth with T1D around exercise, assess factors that influence practices, and examine associations between key behaviors and glycemic outcomes. RESEARCH DESIGN AND METHODS: We developed the 'Type 1 Diabetes Report of Exercise Practices Survey (T1D-REPS)' and piloted this tool in 100 youth with T1D on an insulin pump. Participants completed a 3-day physical activity recall and 30 days of pump/glucose data were collected. Chart review was conducted for key clinical measures. RESULTS: Eighty-four percent of participants modified their insulin regimen around exercise; only 40% reported adjusting prandial insulin immediately before exercise while 68% reported some modification (suspension or decrease) of basal insulin during exercise. Following exercise, only 10% reported reducing overnight basal insulin. Those who performed ≥ 5 glucose checks/day adjusted basal insulin during exercise more frequently than those with fewer daily glucose checks (33% vs. 13%, p = 0.05, chi-squared = 3.7), and were more likely to report decreasing insulin dose for the bedtime snack following exercise (50% vs. 17%, p = 0.004, chi-squared = 8.2). CONCLUSIONS: Despite several studies showing the frequency of hypoglycemia during and after exercise, many youth are not adjusting insulin for exercise. A tool designed to capture patient practices and provide clinicians with a framework for patient education may lead to improved safety around exercise in youth with T1D.

Using Instagram as a Modified Application of Photovoice for Storytelling and Sharing in Adolescents With Type 1 Diabetes.

Photovoice is a research method developed to help communities share images as a tool for discussion of key issues. Although this may be useful to promote healthy behavior, using Photovoice in adolescents has been logistically challenging. Given adolescents' engagement in social media, our study explored the feasibility of using a photo-sharing mobile phone application, Instagram, to accomplish the principles of Photovoice. Twenty adolescents 14 to 18 years old with type 1 diabetes were asked to use Instagram to post any diabetes-related photo for 3 weeks. Individual interviews and a focus group were also offered, and recruitment and retention statistics were tracked. Of those approached (n = 47), 43% agreed to participate. Twelve were actively engaged. Shared photos were most likely to fall into the categories of diabetes care, humor, or food. Engaged participants universally reported the project to be a positive experience; however, there were technological and personal factors to consider for widespread implementation.

Adipose stem cell side population in the mouse.

Adipose tissue has become a reliable source of adult stem cells, which appear to possess a yet-undetermined degree of plasticity. With the difficulties associated with harvesting adult bone marrow stem cells, adipose tissue may represent a valuable and easily acquired source of stem cells. Stem cells have been identified using the DNA binding dye Hoechst 33342 and flow cytometry in various tissues known as the side population (SP). The present study shows, for the first time, the presence of side population stem cells in adult adipose tissues. Flow cytometric identification and isolation of this subpopulation of stem cells revealed that in the mouse there are 2.5% of adipose SP cells within the stromal vascular fraction of adipose tissue. In culture, mouse adipose SP cells showed the capacity to undergo in vitro differentiation into osteogenic, chondrogenic and adipogenic lineages. In NOD/SCID mice, freshly sorted mouse adipose SP cells were able to engraft and assist in wound healing. This animal model study showed that adipose SP cells were able to regenerate epithelial layers and connective tissue with minor scar formation. The ability of this novel cell population within adipose tissue to undergo directional differentiation in vitro and to regenerate skin in vivo has potential impact for uses in surgical dermal applications.

Phenotypic and molecular characterization of spermatogonial stem cells in adult primate testes.

BACKGROUND: Knowledge about the identity and characteristics of spermatogonial stem cells (SSCs) in human is very limited. Here, Rhesus monkey was used as an animal model to investigate molecular and phenotypic characteristics of SSCs in the adult testes. METHODS: A variety of immunohistological, molecular biological and functional assays were used to study different populations of SSCs in the adult testes. RESULTS: In adult primate testes, there are distinct populations of CD90+ CD49f+ CD117- (Triple Stained) cells and a small population of stage-specific embryonic antigen-4 (SSEA-4)+ cells which both localized at the basement membrane of seminiferous tubules. Both SSEA-4+ and Triple Stained cells express germ cell and SSC-specific markers and show high telomerase activity; however, only adult Rhesus monkey SSEA-4+ testis cells appear to contain functional and actively dividing SSCs that can repopulate recipient mouse testes following spermatogonial transplantation. DNA analysis of these populations showed that SSEA-4+ cells contain a DNA profile similar to the actively dividing cells, whereas Triple Stained cells showed an accumulated number of cells arrested in the S phase of the cell cycle. SSEA-4+ cells also showed significantly higher proliferation activity, as shown by proliferating cell nuclear antigen staining, than Triple Stained cells (P < 0.01). Interestingly, SSEA-4+ cells expressed a significantly higher level of promyelocytic leukemia zinc finger, a factor required for SSC self-renewal, than Triple Stained cells (P < 0.001). CONCLUSIONS: Our data indicate that Triple Stained cells may represent a quiescent population of SSCs, whereas SSEA-4 might be expressed on a subpopulation of actively dividing SSCs.

Generation of human islets through expansion and differentiation of non-islet pancreatic cells discarded (pancreatic discard) after islet isolation.

OBJECTIVES: Islet transplantation is hampered by the shortage of donor tissues. Our objective was to generate islet-like cell clusters (ICCs) from cultures of non-islet pancreatic cells. METHODS: The starting cultured cells came from the non-islet fractions of human pancreases after enzymatic digestion and purification for the purpose of islet isolation. Initially, these cells expanded in monolayer cultures and became confluent on collagen-coated flasks. After trypsination and suspension of these cells in a defined islet differentiation medium, the cells aggregated to form ICCs. RESULTS: The initial cell population consisted of less than 1% of insulin-positive cells, 44% amylase-positive cells, and 41% cytokeratin (CK) 7-positive, or CK19 cells, but PDX-1 cells were absent. Cells from later stages of the monolayer cultures showed signs of dedifferentiation/transdifferentiation. At the time of harvesting, more than 90% of the cells were positive for CK 7/19 and PDX-1, but less than 1% of the cells were insulin-positive. After aggregation, the ICCs appeared redifferentiated, and contained glucose-responsive, insulin-secreting cells with an insulin content measuring 20% of that found in freshly isolated islets isolated from the same pancreas. ICCs transplanted into athymic mice and removed after 4 months did acquire the morphology of mature islets, indicating further maturation of the ICCs in vivo after transplantation. Human C-peptide was detected in recipient animal sera. CONCLUSION: Using the specified culture methods, non-islet pancreas cells can generate cell clusters resembling islets. These ICCs, obtained from fractions of the pancreas that are otherwise discarded, continue to differentiate after transplantation to become mature islets.

Inhibition of p38 pathway suppresses human islet production of pro-inflammatory cytokines and improves islet graft function.

Nonspecific inflammation is associated with primary graft nonfunction (PNF). Inflammatory islet damage is mediated at least partially by pro-inflammatory cytokines, such as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) produced by resident islet macrophages. The p38 pathway is known to be involved in cytokine production in the cells of the monocyte-macrophage lineage. Therefore, inhibition of the p38 pathway may prevent pro-inflammatory cytokine production by resident islet macrophages and possibly reduce the incidence of PNF. Our present study has demonstrated that inhibition of the p38 pathway by a chemical p38 inhibitor, SB203580, suppresses IL-1beta and TNF-alpha production in human islets exposed to lipopolysaccharide (LPS) and/or inflammatory cytokines. Although IL-1beta is predominantly produced by resident macrophages, ductal cells and islet vascular endothelial cells were found to be another cellular source of IL-1beta in isolated human islets. SB203580 also inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the treated islets. Furthermore, human islets treated with SB203580 for 1 h prior to transplantation showed significantly improved graft function. These results suggest that inhibition of the p38 pathway may become a new therapeutic strategy to improve graft survival in clinical islet transplantation.