Comparative Evaluation of Efficiency of Different Endodontic File Systems; Protaper Universal, MTWO, Protaper Next, Trunatomy, I-Race in Terms of Remaining Dentin Thickness: An In vitro CBCT Analysis.

Introduction: The longevity of an endodontically treated tooth depends on fracture resistance by preserving more remaining dentin thickness. The aim of this study is to determine which file system preserves more remaining dentin thickness. Materials and Methods: Protaper universal, M-two, Protaper Next, Trunatomy, I-Race and mandibular first premolar. The removed dentin thickness during instrumentation of each file system was noted by taking the difference of RDT of pre-instrumentation and post-instrumentation with the aid of CBCT. Results and Discussion: TRN [Group-4] shows the least aggressive cutting with maximal preservation of remaining dentin thickness at 3 mm and 6 mm from the apex at both mesiodistal and buccolingual dimensions. M-two [Group-2] shows maximum removed dentin thickness at 3 mm from the apex both mesiodistal dimension and buccolingual dimension. PTU [Group-1] shows maximum removed dentin thickness at 6 mm from the apex at mesiodistal dimension. M-two [Group-2] shows maximum removed dentin thickness at 6 mm from the apex at the buccolingual dimension. Conclusion: In this study, it is concluded that the Trunatomy file system preserves more remaining dentin thickness both mesiodistally and buccolingually both 3 mm and 6 mm from the apex.

Comparative Evaluation of Residual Antibacterial Substantivity of Chlorhexidine, MTAD and Chitosan Against Enterococcus Faecalis in Human Root Dentin - An In vitro Study.

Introduction: Complex anatomy of the root canal system results in incomplete debridement with mechanical instrumentation, leaving some areas or root canal walls untouched. There comes the significance of endodontic irrigants with residual antibacterial substantivity which prolongs the post-antibiotic effect, thereby improving the success and predictability of endodontic treatment. Aim: To comparatively evaluate the residual antibacterial substantivity of 2% chlorhexidine, Biopure MTAD and 2% chitosan against Enterococcus faecalis at intervals of 1, 14 and 28 days. Materials and Methods: Seventy-five therapeutically extracted permanent single rooted mandibular premolars teeth were selected. Dentin blocks of 4 mm thickness were prepared and enlarged to 1.6 mm. The autoclaved blocks were inoculated with 24-hour colonies of pure cultures of E. faecalis for 14 days. After the contamination period, canals of each dentin block were irrigated with 5 ml of sterile saline and dried with sterile paper points. A total of 75 dentin blocks were randomly divided into five groups as follows: Group A (21 specimens): 2% chlorhexidine, Group B (21 specimens): Biopure MTAD, Group C (21 specimens): 2% chitosan, Group D (6 specimens): positive control (infected dentin tubes) and Group E (six specimens): negative control (sterile dentin tubes). Then, the lumens of dentin blocks were irrigated with the respective irrigants for 10 mins and were dried using sterile paper points. The specimens were then incubated at 37°C for 28 days to maintain humidity. At experimental intervals of 1, 14 and 28 days, dentin shavings were removed from the canals of respective groups by circumferential filing with sterile no. 35 Hedstrom files. The powdered dentin samples obtained with each dentin block were observed for colony forming units (CFUs) using a Digital Colony counter and were expressed as CFUs/mL. Result: All the irrigants in the study showed a significant decrease in CFUs from day 1 to day 28 indicating that they have residual antibacterial substantivity against E. faecalis. Group B (Biopure MTAD) showed significantly least mean CFUs compared to Group A (2% CHX) and Group C (2% chitosan) against E. faecalis at B1(day 1), B2(day 14) and B3(day 28). Group A (2% CHX) showed significantly higher mean CFUs than Group C (2% chitosan) at A1(day 1). Group C (2% chitosan) showed significantly higher mean CFUs compared to Group A (2% CHX) at C2(day 14) and C3 (day 28). Conclusion: MTAD showed statistically higher residual antibacterial substantivity against E. faecalis at experimental periods of 1, 14 and 28 days. The residual antibacterial effect of 2% chitosan was better compared to 2% CHX at day 1. The residual antimicrobial substantivity of 2% CHX was higher compared to 2% chitosan at intervals of 14 and 28 days.

Automated assessment of cardiac dynamics in aging and dilated cardiomyopathy Drosophila models using machine learning.

The Drosophila model is pivotal in deciphering the pathophysiological underpinnings of various human ailments, notably aging and cardiovascular diseases. Cutting-edge imaging techniques and physiology yield vast high-resolution videos, demanding advanced analysis methods. Our platform leverages deep learning to segment optical microscopy images of Drosophila hearts, enabling the quantification of cardiac parameters in aging and dilated cardiomyopathy (DCM). Validation using experimental datasets confirms the efficacy of our aging model. We employ two innovative approaches deep-learning video classification and machine-learning based on cardiac parameters to predict fly aging, achieving accuracies of 83.3% (AUC 0.90) and 79.1%, (AUC 0.87) respectively. Moreover, we extend our deep-learning methodology to assess cardiac dysfunction associated with the knock-down of oxoglutarate dehydrogenase (OGDH), revealing its potential in studying DCM. This versatile approach promises accelerated cardiac assays for modeling various human diseases in Drosophila and holds promise for application in animal and human cardiac physiology under diverse conditions.

Health literacy and tuberculosis control: systematic review and meta-analysis.

Objective: To identify literature on health literacy levels and examine its association with tuberculosis treatment adherence and treatment outcomes. Methods: Two authors independently searched Pubmed®, Embase, CINAHL, PsycINFO, Scopus, LILACS, Global Health Medicus and ScienceDirect for articles reporting on health literacy levels and tuberculosis that were published between January 2000 and September 2023. We defined limited health literacy as a person's inability to understand, process, and make decisions from information obtained concerning their own health. Methodological quality and the risk of bias was assessed using the JBI critical appraisal tools. We used a random effects model to assess the pooled proportion of limited health literacy, the association between health literacy and treatment adherence, and the relationship between health literacy and tuberculosis-related knowledge. Findings: Among 5813 records reviewed, 22 studies met the inclusion criteria. The meta-analysis revealed that 51.2% (95% confidence interval, CI: 48.0-54.3) of tuberculosis patients exhibit limited health literacy. Based on four studies, patients with lower health literacy levels were less likely to adhere to tuberculosis treatment regimens (pooled odds ratio: 1.95; 95% CI: 1.37-2.78). Three studies showed a significant relationship between low health literacy and inadequate knowledge about tuberculosis (pooled correlation coefficient: 0.79; 95% CI: 0.32-0.94). Conclusion: Health literacy is associated with tuberculosis treatment adherence and care quality. Lower health literacy might hamper patients' ability to follow treatment protocols. Improving health literacy is crucial for enhancing treatment outcomes and is a key strategy in the fight against tuberculosis.

Diurnal expression of Dgat2 induced by time-restricted feeding maintains cardiac health in the Drosophila model of circadian disruption.

Circadian disruption is associated with an increased risk of cardiometabolic disorders and cardiac diseases. Time-restricted feeding/eating (TRF/TRE), restricting food intake within a consistent window of the day, has shown improvements in heart function from flies and mice to humans. However, whether and how TRF still conveys cardiac benefits in the context of circadian disruption remains unclear. Here, we demonstrate that TRF sustains cardiac performance, myofibrillar organization, and regulates cardiac lipid accumulation in Drosophila when the circadian rhythm is disrupted by constant light. TRF induces oscillations in the expression of genes associated with triglyceride metabolism. In particular, TRF induces diurnal expression of diacylglycerol O-acyltransferase 2 (Dgat2), peaking during the feeding period. Heart-specific manipulation of Dgat2 modulates cardiac function and lipid droplet accumulation. Strikingly, heart-specific overexpression of human Dgat2 at ZT 0-10 significantly improves cardiac performance in flies exposed to constant light. We have demonstrated that TRF effectively attenuates cardiac decline induced by circadian disruption. Moreover, our data suggests that diurnal expression of Dgat2 induced by TRF is beneficial for heart health under circadian disruption. Overall, our findings have underscored the relevance of TRF in preserving heart health under circadian disruptions and provided potential targets, such as Dgat2, and strategies for therapeutic interventions in mitigating cardiac aging, metabolic disorders, and cardiac diseases in humans.

Health-related quality of life for pediatric patients with end-stage kidney disease: A systematic review and meta-analysis of the Pediatric Quality of Life Inventory (PedsQL).

INTRODUCTION: Health-related quality of life (HRQoL) studies demonstrate the impact of end-stage renal disease (ESRD) on the physical and psychosocial development of children. While several instruments are used to measure HRQoL, few have standardized domains specific to pediatric ESRD. This review examines current evidence on self and proxy-reported HRQoL among pediatric patients with ESRD, based on the Pediatric Quality of Life Inventory (PedsQL) questionnaires. METHODS: Following PRISMA guidelines, we conducted a systematic review and meta-analysis on HRQoL using the PedsQL 4.0 Generic Core Scale (GCS) and the PedsQL 3.0 ESRD Module among 5- to 18-year-old patients. We queried PubMed, Embase, Web of Science, CINAHL, and Cochrane databases. Retrospective, case-controlled, and cross-sectional studies using PedsQL were included. FINDINGS: Of 435 identified studies, 14 met inclusion criteria administered in several countries. Meta-analysis demonstrated a significantly higher total HRQoL for healthy patients over those with ESRD (SMD:1.44 [95% CI: 0.78-2.09]) across all dimensional scores. In addition, kidney transplant patients reported a significantly higher HRQoL than those on dialysis (PedsQL GCS, SMD: 0.33 [95% CI: 0.14-0.53]) and (PedsQL ESRD, SMD: 0.65 [95% CI: 0.39-0.90]) concordant with parent-proxy reports. DISCUSSION: Patients with ESRD reported lower HRQoL in physical and psychosocial domains compared with healthy controls, while transplant and peritoneal dialysis patients reported better HRQoL than those on hemodialysis. This analysis demonstrates the need to identify dimensions of impaired functioning and produce congruent clinical interventions. Further research on the impact of individual comorbidities in HRQoL is necessary for developing comprehensive, integrated, and holistic treatment programs.

Rapamycin reduces neuronal mutant huntingtin aggregation and ameliorates locomotor performance in Drosophila.

Huntington's disease (HD) is a neurodegenerative disease characterized by movement and cognitive dysfunction. HD is caused by a CAG expansion in exon 1 of the HTT gene that leads to a polyglutamine (PQ) repeat in the huntingtin protein, which aggregates in the brain and periphery. Previously, we used Drosophila models to determine that Htt-PQ aggregation in the heart causes shortened lifespan and cardiac dysfunction that is ameliorated by promoting chaperonin function or reducing oxidative stress. Here, we further study the role of neuronal mutant huntingtin and how it affects peripheral function. We overexpressed normal (Htt-PQ25) or expanded mutant (Htt-PQ72) exon 1 of huntingtin in Drosophila neurons and found that mutant huntingtin caused age-dependent Htt-PQ aggregation in the brain and could cause a loss of synapsin. To determine if this neuronal dysfunction led to peripheral dysfunction, we performed a negative geotaxis assay to measure locomotor performance and found that neuronal mutant huntingtin caused an age-dependent decrease in locomotor performance. Next, we found that rapamycin reduced Htt-PQ aggregation in the brain. These results demonstrate the role of neuronal Htt-PQ in dysfunction in models of HD, suggest that brain-periphery crosstalk could be important to the pathogenesis of HD, and show that rapamycin reduces mutant huntingtin aggregation in the brain.

Time-restricted feeding regulates lipid metabolism under metabolic challenges.

Dysregulation of lipid metabolism is a commonly observed feature associated with metabolic syndrome and leads to the development of negative health outcomes such as obesity, diabetes mellitus, non-alcoholic fatty liver disease, or atherosclerosis. Time-restricted feeding/eating (TRF/TRE), an emerging dietary intervention, has been shown to promote pleiotropic health benefits including the alteration of diurnal expression of genes associated with lipid metabolism, as well as levels of lipid species. Although TRF likely induces a response in multiple organs leading to the modulation of lipid metabolism, a majority of the studies related to TRF effects on lipids have focused only on individual tissues, and furthermore there is a lack of insight into potential underlying mechanisms. In this review, we summarize the current insights regarding TRF effects on lipid metabolism and the potential mechanisms in adipose tissue, liver, skeletal muscle, and heart, and conclude by outlining possible avenues for future exploration.

Effectiveness of rehabilitation strategies in primary fibromyalgia syndrome: A systematic review and meta-analysis.

Objectives: The aim of this review was to (1) summarize evidence on the effectiveness of rehabilitation strategies in fibromyalgia syndrome (FMS) and (2) determine the most effective rehabilitation strategy for reducing pain and depression in people with FMS. Data Sources: PubMed, Ovid (Sp), and Cochrane search engines were used for identifying relevant studies done up to 1st of July 2022. Study Selection: Randomized control trials (RCTs) that have a passive control group and an active control group were included in this review for primary and secondary aim, respectively. The primary outcome measures were pain and depression. Secondary outcome was one from the sleep or fatigue or healthy related quality of life (HRQOL). Data Extraction: Two researchers independently selected the studies and extracted the key information. Data Synthesis: A total of 25 RCTs were included. Studies with passive control group showed moderate to large positive effects on pain (standard mean difference -0.65, 95% confidence interval -0.93 to -0.38; I2 = 72%) and HRQOL (MD -5.40, 95% CI -10.17 to -0.62; I2 = 74%) but were not statistically significant for sleep, fatigue, and depression. Furthermore, on subgroup analysis studies with a short term protocol showed significant effects on pain only, whereas studies with long term protocols showed positive effects on pain and HRQOL only, but no statistical significance at the time of post-trial follow-up. Studies with active control groups gave non-significant results except where there was mixed exercises, which showed a positive effect (mean difference -4.78, 95% CI -7.98 to -1.57; I2 = 0%) for HRQOL. Conclusion: All rehabilitation strategies were effective for pain and HRQOL, and had a marginal effect on depression, sleep, and fatigue but efficacy was not maintained at the time of post-trial follow-up. However, in this review, we could not differentiate any rehabilitation strategies for the best among those used in the included studies.

Differential Expression of Non-Coding RNAs in Stem Cell Development and Therapeutics of Bone Disorders.

Stem cells' self-renewal and multi-lineage differentiation are regulated by a complex network consisting of signaling factors, chromatin regulators, transcription factors, and non-coding RNAs (ncRNAs). Diverse role of ncRNAs in stem cell development and maintenance of bone homeostasis have been discovered recently. The ncRNAs, such as long non-coding RNAs, micro RNAs, circular RNAs, small interfering RNA, Piwi-interacting RNAs, etc., are not translated into proteins but act as essential epigenetic regulators in stem cells' self-renewal and differentiation. Different signaling pathways are monitored efficiently by the differential expression of ncRNAs, which function as regulatory elements in determining the fate of stem cells. In addition, several species of ncRNAs could serve as potential molecular biomarkers in early diagnosis of bone diseases, including osteoporosis, osteoarthritis, and bone cancers, ultimately leading to the development of new therapeutic strategies. This review aims to explore the specific roles of ncRNAs and their effective molecular mechanisms in the growth and development of stem cells, and in the regulation of osteoblast and osteoclast activities. Furthermore, we focus on and explore the association of altered ncRNA expression with stem cells and bone turnover.

Bland Urine Sediment in a Child with Acute Kidney Injury.

Tubulointerstitial nephritis (TIN) or acute interstitial nephritis (AIN) is a renal lesion characterized by inflammatory infiltrate limited to the renal interstitium and tubules. Three-fourths of the cases are drug induced, other causes being systemic and autoimmune diseases, and infections. Various drugs have been implicated, the most common being antibiotics such as ß-lactams. Cephalosporins causing AIN have been reported uncommonly, particularly in children. Although renal biopsy confirms the diagnosis, urinalysis provides pertinent diagnostic clues against the backdrop of the clinico-laboratory profile. The presence of white blood cells, white cell casts, and red blood cells in urine sediment have been described in literature. However, a relatively normal urinalysis may be present in some cases and may pose a diagnostic challenge. We present a case of ceftriaxone-induced AIN in a child with bland urine sediment at initial presentation. To the best of our knowledge, this is the first report of ceftriaxone-induced AIN in the pediatric age group.

The effects of COVID-19 on pediatric and adult solid organ transplant recipients and the emergence of telehealth.

BACKGROUND: The SARS-CoV-2 pandemic and corresponding acute respiratory syndrome have affected all populations and led to millions of deaths worldwide. The pandemic disproportionately affected immunocompromised and immunosuppressed adult patients who had received solid organ transplants (SOTs). With the onset of the pandemic, transplant societies across the world recommended reducing SOT activities to avoid exposing immunosuppressed recipients. Due to the risk of COVID-19-related outcomes, SOT providers adapted the way they deliver care to their patients, leading to a reliance on telehealth. Telehealth has helped organ transplant programs continue treatment regimens while protecting patients and physicians from COVID-19 transmission. This review highlights the adverse effects of COVID-19 on transplant activities and summarizes the increased role of telehealth in the management of solid organ transplant recipients (SOTRs) in both pediatric and adult populations. METHODS: A comprehensive systematic review and meta-analysis were conducted to accentuate the outcomes of COVID-19 and analyze the efficacy of telehealth on transplant activities. This in-depth examination summarizes extensive data on the clinical detriments of COVID-19 in transplant recipients, advantages, disadvantages, patient/physician perspectives, and effectiveness in transplant treatment plans via telehealth. RESULTS: COVID-19 has caused an increase in mortality, morbidity, hospitalization, and ICU admission in SOTRs. Telehealth efficacy and benefits to both patients and physicians have increasingly been reported. CONCLUSIONS: Developing effective systems of telehealth delivery has become a top priority for healthcare providers during the COVID-19 pandemic. Further research is necessary to validate the effectiveness of telehealth in other settings.

Automated evaluation of cardiac contractile dynamics and aging prediction using machine learning in a Drosophila model.

The Drosophila model has proven tremendously powerful for understanding pathophysiological bases of several human disorders including aging and cardiovascular disease. Relevant high-speed imaging and high-throughput lab assays generate large volumes of high-resolution videos, necessitating next-generation methods for rapid analysis. We present a platform for deep learning-assisted segmentation applied to optical microscopy of Drosophila hearts and the first to quantify cardiac physiological parameters during aging. An experimental test dataset is used to validate a Drosophila aging model. We then use two novel methods to predict fly aging: deep-learning video classification and machine-learning classification via cardiac parameters. Both models suggest excellent performance, with an accuracy of 83.3% (AUC 0.90) and 77.1% (AUC 0.85), respectively. Furthermore, we report beat-level dynamics for predicting the prevalence of cardiac arrhythmia. The presented approaches can expedite future cardiac assays for modeling human diseases in Drosophila and can be extended to numerous animal/human cardiac assays under multiple conditions.

Cardiovascular implications of hypertensive autosomal dominant polycystic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is among the most common inherited kidney diseases. Hypertension is a frequent cardiovascular manifestation, especially in adults, but elevated blood pressure is also found in children and adolescents. Acknowledgment of pediatric hypertension early is critical, as it can result in serious complications long-term if left undiagnosed. OBJECTIVE: We aim to identify the influence of hypertension on cardiovascular outcomes, mainly left ventricular hypertrophy, carotid intima media thickness, and pulse wave velocity. METHODS: We performed an extensive search on Medline, Embase, CINAHL, and Web of Science databases through March 2021. Original studies with a mix of retrospective, prospective, case-control studies, cross sectional studies, and observational studies were included in the review. There was no restriction on age group. RESULTS: The preliminary search yielded 545 articles with 15 articles included after inclusion and exclusion criteria. In this meta-analysis, LVMI (SMD: 3.47 (95% CI: 0.53-6.41)) and PWV (SMD: 1.72 (95% CI: 0.08-3.36)) were found to be significantly higher in adults with ADPKD compared to non-ADPKD; however, CIMT was not found to be significantly different. Also, LVMI was observed to be significantly higher among hypertensive adults with ADPKD (n = 56) as compared to adults without ADPKD (SMD: 1.43 (95% CI: 1.08-1.79)). Fewer pediatric studies were available with heterogeneity among patient populations and results. CONCLUSIONS: Adult patients with ADPKD were found to have worse indicators of cardiovascular outcomes, including LVMI and PWV, as compared to non-ADPKD. This study demonstrates the importance of identifying and managing hypertension, especially early, in this population. Further research, particularly in younger patients, is necessary to further elucidate the relationship between hypertension in patients with ADPKD and cardiovascular disease. REGISTRATION NUMBER: PROSPERO REGISTRATION: 343,013.

Time-restricted feeding promotes muscle function through purine cycle and AMPK signaling in Drosophila obesity models.

Obesity caused by genetic and environmental factors can lead to compromised skeletal muscle function. Time-restricted feeding (TRF) has been shown to prevent muscle function decline from obesogenic challenges; however, its mechanism remains unclear. Here we demonstrate that TRF upregulates genes involved in glycine production (Sardh and CG5955) and utilization (Gnmt), while Dgat2, involved in triglyceride synthesis is downregulated in Drosophila models of diet- and genetic-induced obesity. Muscle-specific knockdown of Gnmt, Sardh, and CG5955 lead to muscle dysfunction, ectopic lipid accumulation, and loss of TRF-mediated benefits, while knockdown of Dgat2 retains muscle function during aging and reduces ectopic lipid accumulation. Further analyses demonstrate that TRF upregulates the purine cycle in a diet-induced obesity model and AMPK signaling-associated pathways in a genetic-induced obesity model. Overall, our data suggest that TRF improves muscle function through modulations of common and distinct pathways under different obesogenic challenges and provides potential targets for obesity treatments.

Circadian-mediated regulation of cardiometabolic disorders and aging with time-restricted feeding.

Circadian rhythms are present throughout biology, from the molecular level to complex behaviors such as eating and sleeping. They are driven by molecular clocks within cells, and different tissues can have unique rhythms. Circadian disruption can trigger obesity and other common metabolic disorders such as aging, diabetes, and cardiovascular disease, and circadian genes control metabolism. At an organismal level, feeding and fasting rhythms are key drivers of circadian rhythms. This underscores the bidirectional relationship between metabolism and circadian rhythms, and many metabolic disorders have circadian disruption or misalignment. Therefore, studying circadian rhythms may offer new avenues for understanding the etiology and management of obesity. This review describes how circadian rhythm dysregulation is linked with cardiometabolic disorders and how the lifestyle intervention of time-restricted feeding (TRF) regulates them. TRF reinforces feeding-fasting rhythms without reducing caloric intake and ameliorates metabolic disorders such as obesity and associated cardiac dysfunction, along with reducing inflammation. TRF optimizes the expression of genes and pathways related to normal metabolic function, linking metabolism with TRF's benefits and demonstrating the molecular link between metabolic disorders and circadian rhythms. Thus, TRF has tremendous therapeutic potential that could be easily adopted to reduce obesity-linked dysfunction and cardiometabolic disorders.

Hypertriglyceridemia with pancreatitis at disease onset in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by the presence of several autoantibodies, immune complex formation and multiple organ system involvement. SLE has a wide range of manifestations involving nearly all organ systems. Hypertriglyceridemia (HTG) in SLE is a well-established and a common abnormality, which is generally mild and not included in the diagnostic criteria of SLE. HTG as the initial manifestation of SLE in adult patients in association with acute pancreatitis at levels below 1000 mg/dL has not been previously reported. Here, we report a case of rare presentation of moderate HTG (TG-869 mg/dL) with pancreatitis at disease onset in an adult women which later proved to be due to SLE and progressed to levels of severe HTG during the course of illness. The patient was successfully treated with plasma exchanges and cyclophosphamide.

Mitochondrial epigenetic modifications and nuclear-mitochondrial communication: A new dimension towards understanding and attenuating the pathogenesis in women with PCOS.

Mitochondrial DNA (mtDNA) epigenetic modifications have recently gained attention in a plethora of complex diseases, including polycystic ovary syndrome (PCOS), a common cause of infertility in women of reproductive age. Herein we discussed mtDNA epigenetic modifications and their impact on nuclear-mitochondrial interactions in general and the latest advances indicating the role of mtDNA methylation in the pathophysiology of PCOS. We highlighted epigenetic changes in nuclear-related mitochondrial genes, including nuclear transcription factors that regulate mitochondrial function and may be involved in the development of PCOS or its related traits. Additionally, therapies targeting mitochondrial epigenetics, including time-restricted eating (TRE), which has been shown to have beneficial effects by improving mitochondrial function and may be mediated by epigenetic modifications, have also been discussed. As PCOS has become a major metabolic disorder and a risk factor for obesity, cardiometabolic disorders, and diabetes, lifestyle/behavior intervention using TRE that reinforces feeding-fasting rhythms without reducing caloric intake may be a promising therapeutic strategy for attenuating the pathogenesis. Furthermore, future perspectives in the area of mitochondrial epigenetics are described.