Circulating extracellular vesicles and small non-coding RNAs cargo in idiopathic inflammatory myopathies reveal differences across myositis subsets.

OBJECTIVE: To investigate the epigenetic footprint of idiopathic inflammatory myopathies (IIM) through characterization of circulating extracellular vesicles (EVs) and the expression of EV-derived small non-coding RNAs (sncRNAs). METHODS: In this cross-sectional study, EVs were isolated by size-exclusion chromatography from plasma of patients with IIM and age- and sex-matched healthy donors (HD). EV-derived sncRNAs were sequenced and quantified using Next-Generation Sequencing (NGS). Following quality control and normalization, filtered count reads were used for differential microRNA (miRNA) and piwi-interacting RNA (piRNA) expression analyses. Putative gene targets enriched for pathways implicated in IIM were analyzed. Patients' clinical and laboratory characteristics at the time of sampling were recorded. RESULTS: Forty-seven IIM patients and 45 HD were enrolled. MiR-486-5p (p < 0.01), miR-122-5p, miR-192-5p, and miR-32-5p were significantly upregulated (p < 0.05 for all), while miR-142-3p (p < 0.001), miR-141-3p (p < 0.01), let-7a-5p (p < 0.05) and miR-3613-5p (p < 0.05) downregulated in EVs from IIM patients versus HD. MiR-486-5p was associated with raised muscle enzymes levels. Several target genes of up/downregulated miRNAs in IIM participate in inflammation, necroptosis, interferon and immune signaling. Six piRNAs were significantly dysregulated in IIM EVs versus HD (p < 0.05). Within IIM, miR-335-5p was selectively upregulated and miR-27a-5p downregulated in dermatomyositis (n = 21, p < 0.01). Finally, plasma EV levels were significantly increased in cancer-associated myositis (CAM, n = 12) versus non-CAM IIM (n = 35, p = 0.02) and HD (p < 0.01). EVs cargo in CAM was significantly enriched of let-7f-5p and depleted of miR-143-3p. CONCLUSION: Through an unbiased screening of EV-derived sncRNAs, we characterize miRNAs and piRNAs in the EVs cargo as potential biomarkers and modifiers of diverse IIM phenotypes.

Characterization of Serum Cytokine Profiles of Patients with Active Lupus Nephritis.

Cytokines contribute to the pathogenesis of lupus nephritis (LN), yet their value as prognostic biomarkers is still debated. We aimed to describe the serum cytokines' profiles and prospectively assess correlations with disease features and renal response in a multicentric cohort of consecutive adult patients with biopsy-proven active LN. Cytokine associations with clinical and serological data were performed at LN diagnosis (T0), and at 3 (T3) and 6 months (T6) of follow up. Renal response according to EULAR definition was assessed at T3, T6 and T12. BAFF and interleukin (IL)-37 were measured by ELISA; IL-2, IL-10, IL-17A and IL-18 by a bead-based multiplex cytokine assay (Luminex). Thirty-nine patients with active LN (age 40.5 ± 15.6 years; F 71.8%; 84.6% proliferative LN) were enrolled, of whom twenty-nine displayed complete longitudinal records. At T0, we observed higher levels of IL-37 and IL-17 in proliferative vs. non-proliferative LN (IL-37: 0.0510 (0.0110-0.2300) vs. 0.0000 (0.0000-0.0397) ng/mL, p = 0.0441; IL-17: 2.0920 (0.5125-17.9400) vs. 0.0000 (0.0000-0.6025) pg/mL, p = 0.0026, respectively), and positive correlations between IL-10 and 24 h proteinuria (r = 0.416, p = 0.0249) and anti-dsDNA levels (r = 0.639, p = 0.0003). BAFF was higher in patients with low complement (p < 0.0001). We observed a sustained correlation between BAFF and IL-10 throughout T6 (r = 0.654, p = 0.0210). Higher baseline IL-37 and BAFF levels were associated with renal response at T3 and T6, respectively, while baseline IL-18 levels were higher in patients achieving response at T12. Our study highlights the complexity of the cytokine network and its potential value as a marker of active LN and renal response.

Experiences of Adults Using Continuous Subcutaneous Insulin Infusion: A Qualitative Study.

OBJECTIVES: We aimed to determine the quality of life (QoL) of Kuwaiti adults with type 1 diabetes mellitus (T1DM) who used continuous subcutaneous insulin infusions (CSIIs) and to understand their perception of this treatment. BACKGROUND: CSII is an effective and safe alternative to multiple daily injections for T1DM, with the potential to improve both glycemic control and QoL. Although CSII has been widely used in Kuwait, its effectiveness and benefits have not been properly evaluated. Healthcare providers and patients need more information on CSII before its initiation. METHODS: In this qualitative case study, semi-structured individual interviews were performed using a topic guide. Interviews were stopped at data saturation point. Subsequently, a thematic analysis of transcripts was performed. RESULTS: Eighteen adults with T1DM (8 males and 10 females; age 31.4 ± 6.4 years; diabetes duration 17.7 ± 9.5 years; CSII duration 3.6 ± 2.4 years) were recruited from the CSII clinic. Six main themes were studied: health benefits, lifestyle flexibility, improvement of mood and emotion, practical problems, physical and personal effects, and self-confidence to manage diabetes. CSII positively affected the QoL of participants', most notably by enhancing lifestyle flexibility; however, important negative qualities were also reported. CONCLUSION: The identified themes highlight the complexity of the experiences of participants, and can be used to provide a framework to help healthcare providers understand how people with T1DM become aware of their treatment regimens. It is important to identify the positive aspects of CSII and not focus only on its negative effects.

Piloting a Culturally Adapted Arabic Structured Small-Group Education Program for Adolescents with Type 1 Diabetes.

BACKGROUND: Kuwait has a high prevalence and incidence of type 1 diabetes (T1D). At present there is a need for structured educational programs (SEP) specifically tailored for Arabian youth with T1D. This SEP was locally and culturally adapted from the Kids In Control of Food (KICk-OFF) course delivered at the Dasman Diabetes Institute, Kuwait. AIMS: To explore the psychological and social impact of a pilot SEP for Arabian youth with T1D and their mothers through exploring their respective perspectives. METHODS: All 20 participants were interviewed using semistructured interviews individually, with a duration of approximately 30-45 min. The interviews were recorded and then transcribed verbatim. Data were analyzed using an inductive thematic approach. RESULTS: The adolescents gained more self-confidence in managing their diabetes and their mothers were more confident in allowing their children take the lead in their diabetes self-management. Participants were empowered with adequate knowledge about the underlying pathophysiology of glucose metabolism and the nutritional and pharmacological management which made them feel in control and helped them to better cope with diabetes. It reduced diabetes-related family stress and gave them more social freedom, supporting behavioral change for a better lifestyle. CONCLUSIONS: Attending the adapted SEP had a positive impact on adolescents with T1D and their mothers through enhancement of their knowledge and confidence, thus giving them a sense of disease control. This pilot study has proven effective in terms of enhancement of confidence in diabetes management and psychosocial factors. Therefore, there is a need for a wider implementation.

Evaluation of the impact of a diabetes education eLearning program for school personnel on diabetes knowledge, knowledge retention and confidence in caring for students with diabetes.

AIMS: To study the impact of a novel comprehensive eLearning approach in delivering diabetes related education program that includes knowledge and sets of practices to the school personnel in Kuwait to enable them to provide a supportive environment for students with diabetes. METHODS: The program was designed with three components namely; knowledge, skills and recommendations. The diabetes knowledge was delivered through an interactive eLearning program, the effectiveness of which was assessed using diabetes knowledge questionnaires which were deployed pre- and post-course delivery. Additionally, the participants' knowledge retention and confidence in caring for a student with diabetes were evaluated at 6 or 12 months post-intervention. RESULTS: A total of 124 public schools' personnel participated in the program. Post e-Learning delivery, diabetes knowledge increased significantly from baseline (p < 0.0001) and knowledge was retained over 6 and 12 months. Average of overall confidence scores in caring for students with diabetes was 61.86% in all items of care. CONCLUSIONS: Offering eLearning diabetes education for school personnel increases their knowledge which can be retained for up to 12 months and imparts confidence in caring for students with diabetes. This novel approach of delivering diabetes education will help school personnel in managing students with diabetes.