Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Nanofat Grafting for Scar Treatment and Skin Quality Improvement

Background Fat grafting has been gaining attention in tissue augmentation over the past decade, not only for lipofilling, but also for its observed regenerative properties and overall skin texture improvement. Objectives The aim of this study was to analyze the effect of nanofat grafting on scars, wrinkles, and skin discolorations in our clinic. Methods Nanofat was prepared by a standard emulsification and filtration protocol. The resulting liquid was injected intradermally or directly into the scar tissue. Skin quality was evaluated based on a scoring system, and patient satisfaction was documented. Three physicians compared and analyzed standardized pre- and posttreatment photographs in respect to general improvement of skin aesthetics. Results Fifty-two patients were treated with nanofat from November 2013 to April 2016. The mean (± standard deviation) posttreatment follow up was 155 ± 49 days and average volume of harvested fat amounted to 165 cc. The primary harvesting areas were the abdomen and flanks, and the injected volume of nanofat ranged from 1 to 25 mL (mean, 4.6 mL). A total of 40 scars (76% of all patient defects) were effectively treated as well as 6 patients with wrinkles, and 6 patients with discoloration. Posttreatment clinical evaluations showed a marked improvement of scar quality and a high patient satisfaction. The results in our clinic showed that nanofat grafting softened the scars, made discolorations less pronounced, and wrinkles appeared less prominent. Conclusions Nanofat grafting has been shown to have beneficial effects in the treatment of scars, wrinkles, and skin discolorations. Level of Evidence

Protein profiling of mechanically processed lipoaspirates: discovering wound healing and anti-fibrotic biomarkers in nanofat

BACKGROUND: Nanofat is an injectable oily emulsion, rich in adipose derived stem cells (ADSCs) and growth factors. It is prepared from lipoaspirates through mechanical emulsification and filtration. Despite being successfully used in several procedures in regenerative medicine such as scar attenuation, skin rejuvenation and treatment of chronic wounds, little is known about exactly how nanofat induces regeneration in treated skin at the molecular level. METHODS: Microfat and nanofat samples were isolated from 18 healthy patients. Proteomic profiling was performed through untargeted mass spectrometry proteomics and multiplex antibody arrays. Pathway enrichment analysis of differentially expressed proteins between microfat and nanofat was performed using Gene Ontology, Reactome and KEGG as reference databases. RESULTS: Untargeted proteomics showed that upregulated genes in nanofat are involved in innate immunity responses, coagulation and wound healing, while downregulated genes were linked to cellular migration and extracellular matrix (ECM) production. Secretome array screening of microfat and nanofat samples showed no significantly different expression, which strongly suggests that the mechanical emulsification step does not affect the concentration of tissue regeneration biomarkers. The identified proteins are involved in wound healing, cellular migration, extracellular matrix remodelling, angiogenesis, stress response and immune response. CONCLUSIONS: Mechanical processing of lipoaspirates into nanofat significantly influences the proteome profile by enhancing inflammation, antimicrobial and wound healing pathways. Nanofat is extremely rich in tissue repair and tissue remodelling factors. CLINICAL RELEVANCE STATEMENT: This study shows that the effects of Micro- and Nanofat treatment are based on upregulated inflammation, antimicrobial and wound healing pathways. Mechanical emulsification does not alter the concentration of tissue regeneration biomarkers

Nanofat Grafting for Scar Treatment and Skin Quality Improvement

Abstract Background Fat grafting has been gaining attention in tissue augmentation over the past decade, not only for lipofilling, but also for its observed regenerative properties and overall skin texture improvement. Objectives The aim of this study was to analyze the effect of nanofat grafting on scars, wrinkles, and skin discolorations in our clinic. Methods Nanofat was prepared by a standard emulsification and filtration protocol. The resulting liquid was injected intradermally or directly into the scar tissue. Skin quality was evaluated based on a scoring system, and patient satisfaction was documented. Three physicians compared and analyzed standardized pre- and posttreatment photographs in respect to general improvement of skin aesthetics. Results Fifty-two patients were treated with nanofat from November 2013 to April 2016. The mean (± standard deviation) posttreatment follow up was 155 ± 49 days and average volume of harvested fat amounted to 165 cc. The primary harvesting areas were the abdomen and flanks, and the injected volume of nanofat ranged from 1 to 25 mL (mean, 4.6 mL). A total of 40 scars (76% of all patient defects) were effectively treated as well as 6 patients with wrinkles, and 6 patients with discoloration. Posttreatment clinical evaluations showed a marked improvement of scar quality and a high patient satisfaction. The results in our clinic showed that nanofat grafting softened the scars, made discolorations less pronounced, and wrinkles appeared less prominent. Conclusions Nanofat grafting has been shown to have beneficial effects in the treatment of scars, wrinkles, and skin discolorations. Level of Evidence:

Nanofat applications: from clinical esthetics to regenerative research

Nanofat grafting is a relatively new technique that has gained popularity in esthetic surgery in recent years. Since its discovery, it has emerged as an effective treatment to improve scar quality and attenuate wrinkles. Nanofat is produced through the mechanical shuffling and filtration of microfat, which is harvested by liposuction. It is easily injectable, rich in adipose-derived stem cells, microvascular fragments, and rich in growth factors that, put together, contribute to its pleasing clinical results. Compared with other stem cell–based therapies, harvesting and processing of nanofat is cost-effective as it requires no additional devices or culturing time. Moreover, the liquid consistency of nanofat allows for easy application in a broad range of clinical cases. Hence, we propose that nanofat should also be considered for use in translational research. Based on current techniques in biomaterial loading with stem cells and microvascular fragments, nanofat has the potential to be a valuable alternative to lengthy tissue regeneration protocols in translational research

High heparin content surface-modified polyurethane discs promote rapid and stable angiogenesis in full thickness skin defects through VEGF immobilization

Three-dimensional scaffolds have the capacity to serve as an architectural framework to guide and promote tissue regeneration. Parameters such as the type of material, growth factors, and pore dimensions are therefore critical in the scaffold's success. In this study, heparin has been covalently bound to the surface of macroporous polyurethane (PU) discs via two different loading methods to determine if the amount of heparin content had an influence on the therapeutic affinity loading and release of (VEGF165 ) in full thickness skin defects. PU discs (5.4 mm diameter, 300 µm thickness, and interconnected pore size of 150 µm) were produced with either a low (2.5 mg/g) or high (6.6 mg/g) heparin content (LC and HC respectively), and were implanted into the modified dorsal skin chamber (MDSC) of C57BL/6 J mice with and without VEGF. Both low- and high-content discs with immobilized VEGF165 (LCV and HCV, respectively) presented accelerated neovascularization and tissue repair in comparison to heparin discs alone. However, the highest angiogenetic peak was on day 7 with subsequent stabilization for HCV, whereas other groups displayed a delayed peak on day 14. We therefore attribute the superior performance of HCV due to its ability to hold more VEGF165, based on its increased heparin surface coverage, as also demonstrated in VEGF elution dynamics. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2543-2550, 2017