Decoding of miR-7-5p in Colony Forming Unit-Hill Colonies as a Biomarker of Subclinical Cardiovascular Disease-A MERIT Study.

Colony forming unit-Hill (CFU-Hill) colonies were established to serve as a sensitive biomarker for vascular health. In animals, the overexpression of miR-7-5p was shown to be pro-atherogenic and associated with increased cardiovascular disease (CVD) risk. In a MERIT study, we aimed to explore the role of miR-7-5p expression in CFU-Hill colonies in type 1 diabetes mellitus (T1DM) and the effect of metformin in subclinical CVD. The expression of miR-7-5p in CFU-Hill colonies in 29 T1DM subjects without CVD and 20 healthy controls (HC) was measured. Metformin was administered to T1DM subjects for eight weeks. MiR-7-5p was upregulated in T1DM whereas metformin reduced it to HC levels. MiR-7-5p was positively correlated with c-reactive protein, and C-X-C motif chemokine ligand 10. The receiver operating characteristic curve revealed miR-7-5p as a biomarker of CVD, and upregulated miR-7-5p, defining subclinical CVD at a HbA1c level of 44.3 mmol/mol. Ingenuity pathway analysis predicted miR-7-5p to inhibit the mRNA expression of Krüppel-like factor 4, epidermal growth factor receptor, insulin-like growth factor 1 receptor, v-raf-1 murine leukemia viral oncogene homolog 1 and insulin receptor substrate ½, and insulin receptor, while metformin activated these miRNAs via transforming growth factor-ß1 and Smad2/3. We proved the pro-atherogenic effect of miR-7-5p that maybe used as a prognostic biomarker.

Upregulated miR-18a-5p in Colony Forming Unit-Hill's in Subclinical Cardiovascular Disease and Metformin Therapy; MERIT Study.

Colony forming unit-Hill's (CFU-Hill's) colonies are hematopoietic-derived cells that participate in neovasculogenesis and serve as a biomarker for vascular health. In animals, overexpression of miR-18a-5p was shown to be pro-atherogenic. We had shown that well-controlled type 1 diabetes mellitus (T1DM) is characterized by an inflammatory state, endothelial dysfunction, and reduced number of CFU-Hill's, a model of subclinical cardiovascular disease (CVD). MERIT study explored the role of miR-18a-5p expression in CFU-Hill's colonies in T1DM, and the cardioprotective effect of metformin in subclinical CVD. In T1DM, miR-18a-5p was significantly upregulated whereas metformin reduced it to HC levels. MiR-18a-5p was inversely correlated with CFU-Hill's colonies, CD34+, CD34+CD133+ cells, and positively with IL-10, C-reactive protein, vascular endothelial growth factor-D (VEGF-D), and thrombomodulin. The receiver operating characteristic curve demonstrated, miR-18a-5p as a biomarker of T1DM, and upregulated miR-18a-5p defining subclinical CVD at HbA1c of 44.5 mmol/mol (pre-diabetes). Ingenuity pathway analysis documented miR-18a-5p inhibiting mRNA expression of insulin-like growth factor-1, estrogen receptor-1, hypoxia-inducible factor-1α cellular communication network factor-2, and protein inhibitor of activated STAT 3, whilst metformin upregulated these mRNAs via transforming growth factor beta-1 and VEGF. We confirmed the pro-atherogenic effect of miR-18a-5p in subclinical CVD and identified several target genes for future CVD therapies.

Subclinical Thyrotoxicosis and Cardiovascular Risk: Assessment of Circulating Endothelial Progenitor Cells, Proangiogenic Cells, and Endothelial Function.

Background: Subclinical thyrotoxicosis (SCT) is defined by low or undetectable thyroid-stimulating hormones and normal thyroid hormones. The treatment of SCT is uncertain despite being associated with increased cardiovascular risk (CVR) and mortality. Circulating endothelial progenitor cells (cEPCs) and circulating angiogenic cells (CACs) have been found to be reduced in conditions with CVR. We aimed to evaluate whether endothelial function and cEPC and CAC counts were reduced in SCT and to study the in vitro effect of triiodothyronine (T3) on proangiogenic cell (PAC) function from young healthy controls. Methods: cEPCs (quantified by flow cytometry, 20 SCT/20 controls), CACs following in vitro cultures (15 SCT/14 controls), paracrine function of CACs, endothelial function by flow-mediated dilation (FMD, 9 SCT/9 controls), and the effect of T3 on apoptosis and endothelial nitric oxide synthase (eNOS) expression in PACs were studied. Results: p < 0.001, CD133+/VEGFR-2+ 0.4 (0.0-0.7) vs. 0.6 (0.0-4.6), p = 0.009, CD34+/VEGFR-2+ 0.3 (0.0-1.0) vs. 0.7 (0.1-4.9), p = 0.002; while CAC count was similar. SCT predicted a lower cEPC count after adjustment for conventional CVR factors. FMD was lower in SCT subjects versus controls (% mean ± SD, 2.7 ± 2.3 vs. 6.1 ± 2.3, p = 0.005). In vitro studies showed T3 increased early apoptosis and reduced eNOS expression in PACs. Conclusions: In conclusion, SCT is associated with reduced cEPC count and FMD, confirming increased CVR in SCT. Future outcome trials are required to examine if treatment of this subclinical hyperactive state improves cardiovascular outcome. Clinical Trial Registration: http://www.controlled-trials.com/isrctn/, identifier ISRCTN70334066.

Radioactive Iodine for the Treatment of Subclinical Thyrotoxicosis Grade 1 and 2: Outcome of up to 18-Year Follow Up.

Background: Subclinical thyrotoxicosis (SCT) is associated with significant morbidity and mortality, specifically increased risk of atrial fibrillation and cardiovascular death. The management is ill-defined due to the scarcity of randomised controlled studies. Some clinicians recommend radioiodine (RAI) treatment however its long-term outcome is unknown. Therefore, further data is needed to provide robust evidence-based guidelines. Methods: A prospective, single-protocol analysis of the outcome of SCT patients (Grade 1; 0.1-0.4 mIU/L and Grade 2; <0.1 mIU/L) treated with mean dose of 427 MBq of I131, followed up for up to 18 years. Thyroid function tests were measured at 4-6 weeks, 3-, 6-, and 12-months post-RAI, and annually thereafter. Cure was defined as achieving a euthyroid/hypothyroid state. Results: Seventy-eight patients with a median age of 68 years (range 36-84) and varying aetiology [55 toxic multinodular goitre (TMNG), 10 toxic nodule (TN) and 13 Graves' disease (GD)] were followed up for a median period of 7.5 years (range 1-18). The cure rate was 100%. The rates of hypothyroidism in TMNG, TN and GD were 23.6%, 30% and 38.5% respectively. The median time to hypothyroidism was 6 and 12 months in GD and TMNG/TN respectively. No differences in outcome between Grade 1 versus Grade 2 were observed. Conclusion: RAI using single mean dose of 427 MBq is effective and safe, irrespective of aetiology or grade of TSH suppression. GD patients become hypothyroid within the first year, whilst TMNG/TN for up to 9-years. Thus after 12 months of follow up, annual thyroid function monitoring is advised.

Knowledge, attitude, and practice related to the COVID-19 pandemic among undergraduate medical students in Indonesia: A nationwide cross-sectional study.

INTRODUCTION: The potential role of medical students in raising awareness during public health emergencies has been acknowledged. To further explore their potentials as public educators and role models for the communities during the coronavirus disease 2019 (COVID-19) pandemic, this study aims to assess the knowledge, attitude, and practice of these students toward COVID-19. METHODS: An online cross-sectional survey was conducted among undergraduate medical students in Indonesia. Socio-demographics characteristics, social interaction history, information-seeking behavior, as well as knowledge, attitude, and practice toward COVID-19 were collected through a self-reported questionnaire. A p-value of <0.05 indicated statistical significance. RESULTS: Out of 4870 respondents, 64.9% had positive attitude and 51.5% had positive practice toward COVID-19, while only 29.8% had adequate knowledge. Knowledge was slightly positively correlated with attitude and practice (ρ = 0.074 and ρ = 0.054, respectively; both p<0.001), while attitude was weakly correlated with practice (ρ = 0.234, p<0.001). Several factors including age, sex, place of residence, institution type, academic level, family income, history of chronic illness, prior volunteering experience, and perceptual awareness on COVID-19 were significantly associated with either knowledge, attitude, and/or practice toward COVID-19. Furthermore, health institution's and the government's press releases, as well as health expert opinions were deemed as the most reliable sources of COVID-19-related information-yet trivially none of these sources were associated with knowledge, attitude, and practice in the study population. CONCLUSION: Many undergraduate medical students in Indonesia had positive attitude and practice against COVID-19, yet only a few had adequate knowledge. This warrants further interventions to keep them updated with COVID-19 evidence to maximize their potentials in raising public awareness on COVID-19.

Willingness to volunteer and readiness to practice of undergraduate medical students during the COVID-19 pandemic: a cross-sectional survey in Indonesia.

BACKGROUND: The question to involve or restrict medical students' involvement in the coronavirus disease 2019 (COVID-19) pandemic response remains contentious. As their state of preparation and perceptions in volunteering during this pandemic have yet to be investigated, this study aims to evaluate Indonesian medical students' willingness to volunteer and readiness to practice during the COVID-19 pandemic. METHODS: A web-based survey was conducted among undergraduate medical students throughout Indonesia. Socio-demographic and social interaction information, in addition to willingness to volunteer and readiness to practice, were obtained using a self-reported questionnaire. The significance level was set at 5%. RESULTS: Among 4870 participants, 2374 (48.7%) expressed their willingness to volunteer, while only 906 (18.6%) had adequate readiness to practice. Male students, students with prior volunteering experience in health or non-health sectors, and students from public universities or living in Central Indonesia (vs Java) had higher scores of willingness and readiness to volunteer. Students from Sumatra also had better preparedness (odds ratio [OR] 1.56, 95% confidence interval [CI] 1.15-2.12, p = 0.004), while the opposite occurred for students from Eastern Indonesia (OR 0.63, 95% CI: 0.44-0.89, p = 0.002)-when compared to students from Java. In addition, compared to students with high family income, students from lower-middle income families were less willing to volunteer (OR 0.76, 95% CI: 0.59-0.98, p = 0.034), though those with low family income had better readiness (OR 1.51, 95% CI: 1.10-2.08, p = 0.011). Shortage of medical personnel, sense of duty, and solicitation by stakeholders were the main reasons increasing the students' willingness to volunteer; whereas contrarily fear for own's health, absence of a cure, and fear of harming patients were the primary factors diminishing their willingness to volunteer. CONCLUSION: Our findings indicated that many Indonesian medical students are willing to volunteer, yet only few of them were ready to practice, indicating that further preparations are required to maximize their potentials and minimize their exposure to hazards. We suggest that their potentials as a firm support system during the pandemic should not be overlooked, and that the integration of relevant courses to the medical curricula are imperative to prepare for future public health emergencies.