THE ROLE OF HETEROPLASMY IN THE DIAGNOSIS AND MANAGEMENT OF MATERNALLY INHERITED DIABETES AND DEAFNESS.

Objective: Maternally inherited diabetes and deafness (MIDD) is a rare diabetic syndrome mainly caused by a point mutation in the mitochondrial DNA (mtDNA), mt3243 adenine to guanine (A>G). The objective of this paper is to review the genetic inheritance, clinical manifestations, and treatment of patients with MIDD. Methods: The current review used a literature search of scientific papers on this rare syndrome. Results: mtDNA is primarily inherited through the maternal oocyte; therefore, the genetic abnormalities in MIDD are associated with maternal inheritance. Mitochondria contain circular mtDNA, which codes for various mitochondrial genes. The mtDNA can be heteroplasmic, containing more than one type of mtDNA sequence; if one of the mtDNAs contains the mt3243 A>G mutation, a patient may develop MIDD. Patients can inherit different amounts of mutated mtDNA and normal mtDNA that affect the severity of the clinical manifestations of MIDD. The most common clinical manifestations include diabetes mellitus, deafness, ophthalmic disease, cardiac disease, renal disease, gastrointestinal disease, short stature, and myopathies. In order to effectively treat patients with MIDD, it is important to recognize the underlying pathophysiology of this specific form of diabetes and the pathophysiology associated with the organ-specific complications present in this disease. Conclusion: The heteroplasmic inheritance of mutated mtDNA plays an important role in the clinical manifestations of various mitochondrial diseases, specifically MIDD. This review will alert endocrinologists of the signs and symptoms of MIDD and important clinical considerations when managing this disease. Abbreviations: ATP = adenosine triphosphate; CoQ10 = coenzyme Q10; MELAS = mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke; MIDD = maternally inherited diabetes and deafness; mtDNA = mitochondrial DNA; tRNA = transfer ribonucleic acid; ROS = reactive oxygen species; T2DM = type 2 diabetes mellitus.

Pilot study assessing gut microbial diversity among sexual and gender minority young adults.

Evidence supports that people identifying as a sexual or gender minority (SGMs) experience minority-related stress resulting from discrimination or expectations of prejudice, and that this is associated with increased mental and physical health problems compared to cisgender heterosexuals. However, the biological mechanisms driving minority-related stress impacts remain unknown, including the role of the gut microbiome. Thus, the aim of this study was to determine the relationship between SGM status and gut microbiome health among young adults attending a 4-year university. To this end, a prospective pilot study was completed in the fall and spring semesters of 2021-22. Self-identified SGMs (N = 22) and cisgender-heterosexuals (CIS-HET, N = 43) completed in-person interviews to provide mental health data and demographic information. Nail and saliva samples were collected at the time of interview to quantify chronic and acute cortisol. Stool samples were collected within 48 hours of interview for microbiome analysis. Assessment of the gut microbiota identified a significant reduction in alpha diversity among the SGM group, even when adjusting for mental health outcome. SGM group showed trends for higher abundance of microbes in phylum Bacteroidetes and lower abundance of microbes in phyla Firmicutes, Actinobacteria, and Proteobacteria compared to the CIS-HET group. These findings support that the gut microbiome could be contributing to negative health effects among the SGM community.

A systematic review and meta-analysis: Assessment of hospital walking programs among older patients.

AIM: The aim of this study is to assess effect of hospital walking programs on outcomes for older inpatients and to characterize hospital walking dose reported across studies. DESIGN: A systematic review and meta-analysis examining impact of hospital walking and/or reported walking dose among medical-surgical inpatients. For inclusion, studies were observational or experimental, published in English, enrolled inpatients aged ≥ 65 yrs hospitalized for medical or surgical reasons. METHODS: Searches of PubMed, CINAHL, Embase, Scopus, NICHSR, OneSearch, ClinicalTrials.gov, and PsycINFO were completed in December 2020. Two reviewers screened sources, extracted data, and performed quality bias appraisal. RESULTS: Hospital walking dose was reported in 6 studies and commonly as steps/24 hr. Length of stay (LOS) was a common outcome reported. Difference in combined mean LOS between walking and control groups was -5.89 days. Heterogeneity across studies was considerable (I2  = 96%) suggesting poor precision of estimates. Additional, high-quality trials examining hospital walking and patient outcomes of older patients is needed.

An Analysis of Factors That Influence Students to Pursue Immunology.

One considers many factors before choosing a career path, such as interest, accessibility of resources, academic ability, and social network support. As employment around the world in science, technology, engineering, and math (STEM) disciplines continues to increase, there is a need to understand why students select specific majors in an effort to increase overall enrollment and retention of STEM majors. The purpose of this study was to elucidate how undergraduate and graduate students were introduced to immunology, a STEM discipline, and how these experiences influenced their desire to pursue immunology as a major. The findings from this study show that a majority of both immunology and nonimmunology majors were initially exposed to immunology through an educational experience compared with a personal experience. Our data also indicate that the timing of the experience is critical, such that an educational experience at an advanced academic level, for example, in college, or a personal experience as a teen or young adult correlated with the decision to pursue an immunology degree. Moreover, graduate students studying immunology report that having research experiences and/or an experience with a mentor positively influenced their decision to pursue immunology. Overall, the findings from this research highlight the type and timing of exposures that influence individuals to major in the field of immunology, and these data can be used in the future to increase the number of immunology graduates.

Sex Hormone Regulation of Proteins Modulating Mitochondrial Metabolism, Dynamics and Inter-Organellar Cross Talk in Cardiovascular Disease.

Cardiovascular disease (CVD) is the leading cause of death in the U.S. and worldwide. Sex-related disparities have been identified in the presentation and incidence rate of CVD. Mitochondrial dysfunction plays a role in both the etiology and pathology of CVD. Recent work has suggested that the sex hormones play a role in regulating mitochondrial dynamics, metabolism, and cross talk with other organelles. Specifically, the female sex hormone, estrogen, has both a direct and an indirect role in regulating mitochondrial biogenesis via PGC-1α, dynamics through Opa1, Mfn1, Mfn2, and Drp1, as well as metabolism and redox signaling through the antioxidant response element. Furthermore, data suggests that testosterone is cardioprotective in males and may regulate mitochondrial biogenesis through PGC-1α and dynamics via Mfn1 and Drp1. These cell-signaling hubs are essential in maintaining mitochondrial integrity and cell viability, ultimately impacting CVD survival. PGC-1α also plays a crucial role in inter-organellar cross talk between the mitochondria and other organelles such as the peroxisome. This inter-organellar signaling is an avenue for ameliorating rampant ROS produced by dysregulated mitochondria and for regulating intrinsic apoptosis by modulating intracellular Ca2+ levels through interactions with the endoplasmic reticulum. There is a need for future research on the regulatory role of the sex hormones, particularly testosterone, and their cardioprotective effects. This review hopes to highlight the regulatory role of sex hormones on mitochondrial signaling and their function in the underlying disparities between men and women in CVD.

The Apolipoprotein E Mimetic Peptide AEM-2 Attenuates Mitochondrial Injury And Apoptosis In Human THP-1 Macrophages.

Cardiovascular disease, specifically atherosclerosis, is exacerbated by hypercholesterolemia. Current therapies that target lipid lowering, however, are not effective in all patients. Apolipoprotein E (apoE) plays an important role in mediating the clearance of plasma cholesterol and also exerts numerous cytoprotective responses. Our laboratory has synthesized novel therapeutics that mimic the ability of apoE to decrease plasma cholesterol. The apoE mimetic peptide AEM-2 is a dual domain peptide composed of an amphipathic helical region that binds phospholipids and a positively charged region that mediates the hepatic clearance of lipoproteins. Administration of AEM-2 to apoE null mice reduced plasma cholesterol concentration by 80% one hour post-administration. Since apoE is also known to exert anti-inflammatory effects that are independent of its ability to lower cholesterol, we tested effects of AEM-2 on lipopolysaccharide-induced responses in human THP-1 macrophages. Pre-treatment of THP-1 cells with AEM-2 significantly reduced the LPS-induced secretion of IL-6 and TNFα. Since LPS administration is associated with an increase in mitochondrial injury, we monitored effects of AEM-2 on mitochondrial function. AEM-2 significantly reduced mitochondrial superoxide formation, prevented the LPS-induced decrease in mitochondrial membrane potential and attenuated the release of cytochrome c. AEM-2 also inhibited the activities of initiator caspases 8 and 9 and effector caspase 3. The attenuation of apoptosis in AEM-2 treated cells was associated with an increase in cellular autophagy. These data suggest that AEM-2 attenuates cellular injury in LPS-treated THP-1 macrophages and facilitates the removal of cellular debris and damaged organelles via induction of autophagy.