Differential remodelling of mitochondrial subpopulations and mitochondrial dysfunction are a feature of early stage diabetes.

Mitochondrial dysfunction is a feature of type I and type II diabetes, but there is a lack of consistency between reports and links to disease development. We aimed to investigate if mitochondrial structure-function remodelling occurs in the early stages of diabetes by employing a mouse model (GENA348) of Maturity Onset Diabetes in the Young, exhibiting hyperglycemia, but not hyperinsulinemia, with mild left ventricular dysfunction. Employing 3-D electron microscopy (SBF-SEM) we determined that compared to wild-type, WT, the GENA348 subsarcolemma mitochondria (SSM) are ~ 2-fold larger, consistent with up-regulation of fusion proteins Mfn1, Mfn2 and Opa1. Further, in comparison, GENA348 mitochondria are more irregular in shape, have more tubular projections with SSM projections being longer and wider. Mitochondrial density is also increased in the GENA348 myocardium consistent with up-regulation of PGC1-α and stalled mitophagy (down-regulation of PINK1, Parkin and Miro1). GENA348 mitochondria have more irregular cristae arrangements but cristae dimensions and density are similar to WT. GENA348 Complex activity (I, II, IV, V) activity is decreased but the OCR is increased, potentially linked to a shift towards fatty acid oxidation due to impaired glycolysis. These novel data reveal that dysregulated mitochondrial morphology, dynamics and function develop in the early stages of diabetes.

Medical Students' Perception Regarding the Re-emerging Monkeypox Virus: An Institution-Based Cross-Sectional Study From Saudi Arabia.

INTRODUCTION:  The recent multi-nation outbreaks of human monkeypox in non-endemic areas have created an emerging public health issue. Medical students who will become future healthcare providers are directly associated with community people and can easily sensitize the general population, so it is crucial to assess their degree of knowledge and attitudes regarding recently emerging infections or pathogens. However, studies on medical students' perception of the monkeypox virus are scarce in Saudi Arabia. Therefore, the objective of this study was to assess the monkeypox virus-related knowledge and attitudes among medical students in the country. METHODS: A cross-sectional study was conducted from May to July 2022 among undergraduate medical students at King Khalid University, Abha, Saudi Arabia. A systematic random sampling technique was applied to select the study participants. A self-administered questionnaire was used to gather data on sociodemographic characteristics, knowledge and attitudes toward the monkeypox virus. Descriptive statistics and Chi-square tests were performed. RESULTS: A total of 314 medical students were recruited for this study. The findings from this study showed that the vast majority of medical students (72%) had poor knowledge about the monkeypox virus. Respondents' age, grade point average (GPA), fathers' education level, and training received about the monkeypox virus were significantly associated with the level of knowledge about the monkeypox virus (p < 0.05). Nearly half of the respondents (45.9%) agreed that the monkeypox virus could be transmitted to Saudi Arabia. Overall, this study showed that the awareness levels regarding the monkeypox virus were significantly higher among seniors as compared to junior students. CONCLUSION: The study found poor knowledge of the monkeypox virus among currently enrolled medical students in the country's highest-ranked medical school. This finding emphasizes the urgent need to increase their knowledge because controlling outbreaks requires significant cooperation from knowledgeable and skilled healthcare providers.

Mitochondrial Arrest on the Microtubule Highway-A Feature of Heart Failure and Diabetic Cardiomyopathy?

A pathophysiological consequence of both type 1 and 2 diabetes is remodelling of the myocardium leading to the loss of left ventricular pump function and ultimately heart failure (HF). Abnormal cardiac bioenergetics associated with mitochondrial dysfunction occurs in the early stages of HF. Key factors influencing mitochondrial function are the shape, size and organisation of mitochondria within cardiomyocytes, with reports identifying small, fragmented mitochondria in the myocardium of diabetic patients. Cardiac mitochondria are now known to be dynamic organelles (with various functions beyond energy production); however, the mechanisms that underpin their dynamism are complex and links to motility are yet to be fully understood, particularly within the context of HF. This review will consider how the outer mitochondrial membrane protein Miro1 (Rhot1) mediates mitochondrial movement along microtubules via crosstalk with kinesin motors and explore the evidence for molecular level changes in the setting of diabetic cardiomyopathy. As HF and diabetes are recognised inflammatory conditions, with reports of enhanced activation of the NLRP3 inflammasome, we will also consider evidence linking microtubule organisation, inflammation and the association to mitochondrial motility. Diabetes is a global pandemic but with limited treatment options for diabetic cardiomyopathy, therefore we also discuss potential therapeutic approaches to target the mitochondrial-microtubule-inflammatory axis.