Project description:Mitochondria are cellular organelles of crucial relevance for the survival of metazoan organisms. Damage to the mitochondrial DNA can give rise to a variety of mitochondrial diseases and is thought also to be involved in the aging process. The fate of mtDNA mutants is controlled by their synthesis as well as degradation and mathematical models can help to better understand this complex interplay. We present here a model that combines a replicative advantage for mtDNA mutants with selective degradation enabled by mitochondrial fission and fusion processes. The model not only shows that the cell has efficient means to deal with (many) types of mutants but, surprisingly, also predicts that under certain conditions a stable co-existence of mutant and wild-type mtDNAs is possible. We discuss how this new finding might explain how mitochondria can be at the heart of processes with such different phenotypes as mitochondrial diseases and aging.
Project description:Coronavirus disease 2019 (COVID-19) is spreading rapidly worldwide. Here, we review recently published studies on COVID-19-associated acute kidney injury (AKI) in China. The pooled incidence of AKI in all reported COVID-19 patients was 6.5%, with a much higher rate in patients from the intensive care unit (32.5%). AKI is associated with the severity of COVID-19 and mortality rates, which is similar to other kidney abnormalities including proteinuria and hematuria. The renal tubule is the main site of injury in COVID-19 patients, and the etiology of renal impairment in COVID-19 patients likely is diverse and multifactorial. Apart from direct viral attack via angiotensin-converting enzyme 2 and transmembrane serine proteases 2, hypoxia and hypercoagulability also may contribute to the occurrence of renal injury. To date, there is only randomized controlled trial evidence to support the use of dexamethasone in patients requiring oxygen therapy and remdesivir for shortening the time to recovery, with no specific treatment for COVID-19-associated AKI. Studies researching kidney pathologies or reporting renal outcome and prognosis are in urgent need. Further studies are urgently warranted to identify risk factors, to predict prognosis and renal outcome, to explore the exact mechanisms of renal injury, and to suggest targeted interventions.
Project description:With more than 1,800,000 cases and 110,000 deaths globally, COVID-19 is one of worst infectious disease outbreaks in history. This paper provides a critical review of the available evidence regarding the lessons learned from the Chinese experience with COVID-19 prevention and management. The steps that have led to a near disappearance of new cases in China included rapid sequencing of the virus to establish testing kits, which allowed tracking of infected persons in and out of Wuhan. In addition, aggressive quarantine measures included the complete isolation of Wuhan and then later Hubei Province and the rest of the country, as well as closure of all schools and nonessential businesses. Other measures included the rapid construction of two new hospitals and the establishment of "Fangcang" shelter hospitals. In the absence of a vaccine, the management of COVID-19 included antivirals, high-flow oxygen, mechanical ventilation, corticosteroids, hydroxychloroquine, tocilizumab, interferons, intravenous immunoglobulin, and convalescent plasma infusions. These measures appeared to provide only moderate success. Although some measures have been supported by weak descriptive data, their effectiveness is still unclear pending well controlled clinical trials. In the end, it was the enforcement of drastic quarantine measures that stopped SARS-CoV-2 from spreading. The earlier the implementation, the less likely resources will be depleted. The most critical factors in stopping a pandemic are early recognition of infected individuals, carriers, and contacts and early implementation of quarantine measures with an organised, proactive, and unified strategy at a national level. Delays result in significantly higher death tolls.
Project description:Many countries have passed their first COVID-19 epidemic peak. Traditional epidemiological models describe this as a result of nonpharmaceutical interventions pushing the growth rate below the recovery rate. In this phase of the pandemic many countries showed an almost linear growth of confirmed cases for extended time periods. This new containment regime is hard to explain by traditional models where either infection numbers grow explosively until herd immunity is reached or the epidemic is completely suppressed. Here we offer an explanation of this puzzling observation based on the structure of contact networks. We show that for any given transmission rate there exists a critical number of social contacts, [Formula: see text], below which linear growth and low infection prevalence must occur. Above [Formula: see text] traditional epidemiological dynamics take place, e.g., as in susceptible-infected-recovered (SIR) models. When calibrating our model to empirical estimates of the transmission rate and the number of days being contagious, we find [Formula: see text] Assuming realistic contact networks with a degree of about 5, and assuming that lockdown measures would reduce that to household size (about 2.5), we reproduce actual infection curves with remarkable precision, without fitting or fine-tuning of parameters. In particular, we compare the United States and Austria, as examples for one country that initially did not impose measures and one that responded with a severe lockdown early on. Our findings question the applicability of standard compartmental models to describe the COVID-19 containment phase. The probability to observe linear growth in these is practically zero.
Project description:The goal of this piece is to survey the developing and rapidly growing literature on the economic consequences of COVID-19 and the governmental responses, and to synthetize the insights emerging from a very large number of studies. This survey: (i) provides an overview of the data sets and the techniques employed to measure social distancing and COVID-19 cases and deaths; (ii) reviews the literature on the determinants of compliance with and the effectiveness of social distancing; (iii) mentions the macroeconomic and financial impacts including the modelling of plausible mechanisms; (iv) summarizes the literature on the socioeconomic consequences of COVID-19, focusing on those aspects related to labor, health, gender, discrimination, and the environment; and (v) summarizes the literature on public policy responses.
Project description:IntroductionEast Asian Medicine (EAM) is a Whole System medicine that includes Chinese herbal medicine (CHM). Chinese herbal medicine has been utilized to reduce symptom burden in infectious disease, with notable theoretical reformulations during pandemics of the 3rd, 13th, and 17th centuries. Today, Licensed Acupuncturists trained in CHM have utilized it to treat symptoms and sequelae of COVID-19. However, little is known about its use or efficacy by the public and health practitioners. Understanding and evaluating whole medicine systems of healthcare is inherently complex; there is international consensus for a descriptive, pragmatic approach. We are conducting a feasibility pilot study using a prospective, pragmatic, observational design using Whole Health and Whole Person perspectives. The complexity of COVID-19 reflects the impact on multiple homeoregulatory systems and provides a unique opportunity to assess the impact of interventions such as EAM on whole health. Observation of these EAM encounters will provide valuable qualitative and quantitative data on the interface of an extant Whole System medicine with a novel complex illness as a precursor to a randomized clinical trial.MethodsThis ongoing study observes a CHM clinic offering telehealth consultations to a diverse patient population since April, 2020. Patients who report symptoms potentially related to COVID-19 disease are consented for standardized collection and analysis of demographic and clinical data from each clinical encounter.ResultsTo date, 61 patients engaged in 195 consultations (mean 3.3) with 49 reporting symptom resolution sufficient to complete treatment, and 4 withdrawals. Just over half (62%) were female, with an average age of 45.7 years. A wide variety of CHM formulas and EAM dietary and lifestyle modifications were provided.DiscussionAdequate recruitment and retention suggest feasibility of the intervention and data collection. The rich dataset may facilitate the construction of Whole Health models of CHM's clinical impact, as well as integrative inquiry into CHM's effects on symptoms.