Mitochondrial DNA Copy-Number Assessment Is a Potent Predictor for Prostate Cancer in White but Not Black Individuals.

Unlabelled: Black individuals are disproportionately burdened by prostate cancer compared with White individuals. The mitochondrion is an untapped source for prostate cancer biomarkers, and previous work has shown that altered mitochondrial DNA (mtDNA) copy number is linked to mitochondrial dysfunction and tumorigenesis. We assess whether mtDNA copy number is altered in patients with and without prostate cancer in a racially specific manner.

Outliers of Treatment Frequency in Retinal Vein Occlusion: 24-Month Comparative Analysis of Fight Retinal Blindness! Practitioners.

Background: We aimed to describe a 2-year outcome of eyes managed by practitioners benchmarked using a funnel plot by their frequency of treatment using vascular endothelial growth factor (VEGF) inhibitors for naive retinal vein occlusion (RVO).

Methods: A multicentre, international, observational study of 29 doctors in 12 countries managing 1110 eyes with RVO commencing VEGF inhibitors between 1 January 2012-2022 tracked in the Fight Retinal Blindness! registry.

Results: We identified 3 outlying 'intensive' practitioners (managing 350/1110 eyes [32%]), 22 'typical' practitioners (604/1110, [54%]) and 4 outlying 'relaxed' practitioners (156/1110, [14%]) with respective 24-month outcomes in Branch and Central RVO including the primary outcome, mean adjusted change in visual acuity (VA) in BRVO: +16.

MOTS-c modulates skeletal muscle function by directly binding and activating CK2.

MOTS-c is a mitochondrial microprotein that improves metabolism. Here, we demonstrate CK2 is a direct and functional target of MOTS-c. MOTS-c directly binds to CK2 and activates it in cell-free systems.

Three-Year Outcomes of VEGF Inhibitors in Naive Branch Retinal Vein Occlusion: Fight Retinal Blindness!

Purpose: To evaluate the 3-year outcomes of VEGF inhibitors in the treatment of cystoid macular edema due to branch retinal vein occlusion (BRVO) in an international multicenter cohort of eyes.

Design: Multicenter, international, BRVO database study.

Subjects: Seven hundred forty-seven patients (760 eyes) undergoing intravitreal therapy for BRVO for 3 years in a multicenter international setting.

One-Year Anti-VEGF Therapy Outcomes in Diabetic Macular Edema Based on Treatment Intensity: Data from the Fight Retinal Blindness! Registry.

Purpose: To compare 1-year outcomes of eyes with diabetic macular edema (DME) treated in routine clinical practice based on the proportion of visits where intravitreal VEGF inhibitor injections were delivered.

Design: Cohort study.

Participants: There were 2288 treatment-naive eyes with DME starting intravitreal VEGF inhibitor therapy from October 31, 2015 to October 31, 2021 from the Fight Retinal Blindness! international outcomes registry.

Investigating impacts of the mycothiazole chemotype as a chemical probe for the study of mitochondrial function and aging.

Small molecule inhibitors of the mitochondrial electron transport chain (ETC) hold significant promise to provide valuable insights to the field of mitochondrial research and aging biology. In this study, we investigated two molecules: mycothiazole (MTZ) - from the marine sponge C. mycofijiensis and its more stable semisynthetic analog 8-O-acetylmycothiazole (8-OAc) as potent and selective chemical probes based on their high efficiency to inhibit ETC complex I function.

Humanin variant P3S is associated with longevity in APOE4 carriers and resists APOE4-induced brain pathology.

The APOE4 allele is recognized as a significant genetic risk factor to Alzheimer's disease (AD) and influences longevity. Nonetheless, some APOE4 carriers exhibit resistance to AD even in advanced age. Humanin, a mitochondrial-derived peptide comprising 24 amino acids, has variants linked to cognitive resilience and longevity.

Initial response and 12-month outcomes after commencing dexamethasone or vascular endothelial growth factor inhibitors for retinal vein occlusion in the FRB registry.

To compare baseline characteristics, initial response and 12-month efficacy and safety outcomes in eyes with branch and central retinal vein occlusion (BRVO and CRVO) treated with dexamethasone implants (DEX) or anti-vascular endothelial growth factor (anti-VEGF) we performed a multi-centre, retrospective and observational study using Fight Retinal Blindness! Registry. Of 725 eligible eyes, 10% received DEX initially with very frequent adjunctive anti-VEGF (BRVO-DEX 49%, CRVO-DEX 60%). The primary outcome of mean adjusted change in VA at 12 months with DEX and anti-VEGF initiated groups were not statistically significantly different (BRVO: DEX + 6.

Type 2 Diabetes and Biomarkers of Brain Structure, Perfusion, Metabolism, and Function in Late Mid-Life: A Multimodal Discordant Twin Study.

Background: Type 2 diabetes (T2D) is associated with an increased risk of dementia and early features may become evident even in mid-life. Characterizing these early features comprehensively requires multiple measurement modalities and careful selection of participants with and without T2D.

Objective: We conducted a cross-sectional multimodal imaging study of T2D-discordant twins in late mid-life to provide insights into underlying mechanisms.

Mitochondrial-derived microprotein MOTS-c attenuates immobilization-induced skeletal muscle atrophy by suppressing lipid infiltration.

Mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c), a mitochondrial microprotein, has been described as a novel regulator of glucose and lipid metabolism. In addition to its role as a metabolic regulator, MOTS-c prevents skeletal muscle atrophy in high fat-fed mice. Here, we examined the preventive effect of MOTS-c on skeletal muscle mass, using an immobilization-induced muscle atrophy model, and explored its underlying mechanisms.

Novel Drug Delivery Methods and Approaches for the Treatment of Retinal Diseases.

This review discusses emerging approaches to ocular drug delivery for retinal diseases. Intravitreal injections have proven to be an effective, safe, and commonly used drug delivery method. However, the optimal management of chronic retinal diseases requires frequent intravitreal injections over extended periods of time.

Diabetic Macular Oedema Guidelines: An Australian Perspective.

The number of people living with diabetes is expected to rise to 578 million by 2030 and to 700 million by 2045, exacting a severe socioeconomic burden on healthcare systems around the globe. This is also reflected in the increasing numbers of people with ocular complications of diabetes (namely, diabetic macular oedema (DMO) and diabetic retinopathy (DR)). In one study examining the global prevalence of DR, 35% of people with diabetes had some form of DR, 7% had PDR, 7% had DMO, and 10% were affected by these vision-threatening stages.

Central Retinal Vein Occlusion 36-Month Outcomes with Anti-VEGF: The Fight Retinal Blindness! Registry.

Purpose: To analyze the 3-year outcomes in a broad population of patients starting VEGF inhibitors for central retinal vein occlusion (CRVO) in routine clinical practice.

Design: Observational database study.

Participants: Overall, 527 treatment-naïve CRVO eyes that commenced VEGF inhibitors between December 1, 2010 and 2018 were tracked in the Fight Retinal Blindness! registry.

Outcomes of Over 40,000 Eyes Treated for Diabetic Macula Edema in Routine Clinical Practice: A Systematic Review and Meta-analysis.

Introduction: We investigated effectiveness and safety outcomes of diabetic macula edema (DME) treatment in routine clinical practice.

Methods: A literature search was conducted of peer-reviewed articles published from January 2011 to September 2021. Studies of DME treatment in real-world practice of at least 6 months with at least 50 eyes at baseline were included.

Mitochondrial DNA variation in Alzheimer's disease reveals a unique microprotein called SHMOOSE.

Mitochondrial DNA variants have previously associated with disease, but the underlying mechanisms have been largely elusive. Here, we report that mitochondrial SNP rs2853499 associated with Alzheimer's disease (AD), neuroimaging, and transcriptomics. We mapped rs2853499 to a novel mitochondrial small open reading frame called SHMOOSE with microprotein encoding potential.

Risk Factors Associated with Post-Acute Sequelae of SARS-CoV-2 in an EHR Cohort: A National COVID Cohort Collaborative (N3C) Analysis as part of the NIH RECOVER program.

Background: More than one-third of individuals experience post-acute sequelae of SARS-CoV-2 infection (PASC, which includes long-COVID).

Objective: To identify risk factors associated with PASC/long-COVID.

Design: Retrospective case-control study.

Polypoidal Choroidal Vasculopathy Based on Non-ICGA Criteria in White Patients With Neovascular Age-Related Macular Degeneration.

Purpose: To determine prevalence of probable polypoidal choroidal vasculopathy (PCV) among White patients with neovascular age-related macular degeneration (nAMD) using non-indocyanine green angiography (ICGA) criteria DESIGN: Multicenter, multinational, retrospective, cross-sectional study.

Methods: A total of 208 treatment-naive eyes from Hispanic and non-Hispanic White individuals diagnosed with nAMD were included. All underwent color fundus photography (CFP), optical coherence tomography (OCT), and fluorescein angiography (FFA).

Neuroimaging and cognitive correlates of retinal Optical Coherence Tomography (OCT) measures at late middle age in a twin sample.

Sharing in embryology and function between the eye and brain has led to interest in whether assessments of the eye reflect brain changes seen in neurodegeneration. We aimed to examine the associations between measures of retinal layer thickness using optical coherence tomography (OCT) and multimodal measures of brain structure and function. Using a convenient sample of twins discordant for type 2 diabetes, we performed cognitive testing, structural brain MRI (tissue volumetry), diffusion tensor imaging (white matter microstructure), and arterial spin labelling (cerebral blood flow).

Changes in 12-month outcomes over time for age-related macular degeneration, diabetic macular oedema and retinal vein occlusion.

Objectives: To identify whether the outcomes of neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DMO) and retinal vein occlusion (RVO) in routine clinical practice have changed over time.

Methods: We analysed 12-month outcomes in treatment-naïve eyes that started aflibercept or ranibizumab for nAMD (3802 eyes), DMO (975 eyes), Branch RVO (BRVO, 357 eyes), Central RVO (CRVO, 371 eyes) and Hemi-RVO (HRVO, 54 eyes) from 2015 and 2019 tracked in the prospectively designed observational Fight Retinal Blindness! Registry.

Results: The mean VA change at 12-month for each year between 2015 and 2019 remained stable or otherwise showed no discernible trends over time in eyes with nAMD (+3.

Bladder cancer cells shift rapidly and spontaneously to cisplatin-resistant oxidative phosphorylation that is trackable in real time.

Genetic mutations have long been recognized as drivers of cancer drug resistance, but recent work has defined additional non-genetic mechanisms of plasticity, wherein cancer cells assume a drug resistant phenotype marked by altered epigenetic and transcriptional states. Currently, little is known about the real-time, dynamic nature of this phenotypic shift. Using a bladder cancer model of nongenetic plasticity, we discovered that rapid transition to drug resistance entails upregulation of mitochondrial gene expression and a corresponding metabolic shift towards the tricarboxylic acid cycle and oxidative phosphorylation.