The molecular pathology of pathogenic mitochondrial tRNA variants

Mitochondrial diseases are clinically and genetically heterogeneous disorders, caused by pathogenic variants in either the nuclear or mitochondrial genome. This heterogeneity is particularly striking for disease caused by variants in mitochondrial DNA-encoded tRNA (mt-tRNA) genes, posing challenges for both the treatment of patients and understanding the molecular pathology. In this review, we consider disease caused by the two most common pathogenic mt-tRNA variants: m.3243A>G (within MT-TL1, encoding mt-tRNA(Leu(UUR))) and m.8344A>G (within MT-TK, encoding mt-tRNA(Lys)), which together account for the vast majority of all mt-tRNA-related disease. We compare and contrast the clinical disease they are associated with, as well as their molecular pathologies, and consider what is known about the likely molecular mechanisms of disease. Finally, we discuss the role of mitochondrial-nuclear crosstalk in the manifestation of mt-tRNA-associated disease and how research in this area not only has the potential to uncover molecular mechanisms responsible for the vast clinical heterogeneity associated with these variants but also pave the way to develop treatment options for these devastating diseases.Peer reviewe

Design of Drug-Induced Diseases Elective Utilizing Active Learning

Objectives To describe active learning utilized in a drug-induced diseases (DID) elective and determine inter-rater reliability of the assessment rubric for oral case-based presentations. Methods The design of this DID elective focuses on problem-based learning to enhance students’ critical thinking and problem-solving skills pertaining to the treatment of inducible diseases and general medicine. Each class incorporates active learning, utilization of drug information resources, and group work. The primary course assessment is student developed oral case-based presentations evaluated with a standard rubric. Results The intra-class correlation coefficient (ICC) was calculated amongst evaluators to assess the inter-rater reliability of the DID rubric for 21 case-based presentations during the Fall 2013 semester. Composite scores for the case-based presentations demonstrated good inter-rater reliability with an ICC of 0.628. Conclusions Teaching methods utilizing active learning are described for this DID elective. The rubric for the student developed oral case-based presentations demonstrated good inter-rater reliability amongst evaluators and could be modified for use in other professional courses

The Effectiveness of Health Care Coordinators within a Novel Home Care Model for Elders

Introduction. Our project studied the effectiveness of health care coordinators in a program known as Support and Services at Home (SASH). SASH has been designed to fill the needs of independent, home-bound elders who still need regular access to healthcare.https://scholarworks.uvm.edu/comphp_gallery/1191/thumbnail.jp

Estimated incubation period distributions of mpox using cases from two international European festivals and outbreaks in a club in Berlin, May to June 2022

Background Since May 2022, an mpox outbreak affecting primarily men who have sex with men (MSM) has occurred in numerous non-endemic countries worldwide. As MSM frequently reported multiple sexual encounters in this outbreak, reliably determining the time of infection is difficult; consequently, estimation of the incubation period is challenging. Aim We aimed to provide valid and precise estimates of the incubation period distribution of mpox by using cases associated with early outbreak settings where infection likely occurred. Methods Colleagues in European countries were invited to provide information on exposure intervals and date of symptom onset for mpox cases who attended a fetish festival in Antwerp, Belgium, a gay pride festival in Gran Canaria, Spain or a particular club in Berlin, Germany, where early mpox outbreaks occurred. Cases of these outbreaks were pooled; doubly censored models using the log-normal, Weibull and Gamma distributions were fitted to estimate the incubation period distribution. Results We included data on 122 laboratory-confirmed cases from 10 European countries. Depending on the distribution used, the median incubation period ranged between 8 and 9 days, with 5th and 95th percentiles ranging from 2 to 3 and from 20 to 23 days, respectively. The shortest interval that included 50% of incubation periods spanned 8 days (4–11 days). Conclusion Current public health management of close contacts should consider that in approximately 5% of cases, the incubation period exceeds the commonly used monitoring period of 21 days

COVID-19 and children

There has been substantial research on adult COVID-19 and how to treat it. But how do severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections afflict children? The COVID-19 pandemic has yielded many surprises, not least that children generally develop less severe disease than older adults, which is unusual for a respiratory disease. However, some children can develop serious complications from COVID-19, such as multisystem inflammatory syndrome in children (MIS-C) and Long Covid, even after mild or asymptomatic COVID-19. Why this occurs in some and not others is an important question. Moreover, when children do contract COVID-19, understanding their role in transmission, especially in schools and at home, is crucial to ensuring effective mitigation measures. Therefore, in addition to nonpharmaceutical interventions, such as improved ventilation, there is a strong case to vaccinate children so as to reduce possible long-term effects from infection and to decrease transmission. But questions remain about whether vaccination might skew immune responses to variants in the long term. As the experts discuss below, more is being learned about these important issues, but much more research is needed to understand the long-term effects of COVID-19 in children

Prävention des Eintrags von SARS-CoV-2 in Kitas: Erfahrungen aus dem Berliner Bezirk Treptow-Köpenick, Januar bis März 2021

Das Robert Koch-Institut, das Landesamt für Gesundheit und Soziales Berlin und das Gesundheitsamt des Bezirks Treptow-Köpenick untersuchten im Rahmen eines Amtshilfeersuchens Faktoren, die möglicherweise zum Eintrag und zur Übertragung von SARS-CoV-2 in Kitas des Berliner Bezirks im Zeitraum Januar bis März 2021 beigetragen haben. Im Beitrag werden Präventionsmaßnahmen und potenzielle Risikofaktoren für SARS-CoV-2-Infektionen in Kitas analysiert sowie Einzelfälle und Ausbrüche auf Grundlage der Daten des Gesundheitsamtes epidemiologisch ausgewertet. Aus den Erkenntnissen lassen sich anschließend drei Handlungsempfehlungen ableiten.Peer Reviewe

Effects of 17-α-ethynylestradiol on Hybrid Striped Bass Sperm

Gemstone Team FISHOne of the most potent EDCs in the environment is 17-ethynylestradiol (EE2), the hormone in most birth control pills. EE2 is released into the ecosystem through human wastewater, affecting the environment and its inhabitants. Fish both live and reproduce in these affected ecosystems, which may make them particularly susceptible to the effects of EE2. This study investigates the impacts on reproductive efficacy of acute, direct exposure of male hybrid striped bass sperm cells to EE2. In the study, reproductive efficacy is measured by two endpoints: genetic integrity of sperm DNA and sperm cell viability. Genetic integrity and cell viability were assessed by the comet assay and SYBR-14/Propidium Iodide stains, respectively. The results concerning genetic integrity were not statistically significant, but the results of the sperm viability assay suggest that acute direct exposure to EE2 does not cause significant death within a population of sperm

Outlook and appraisal [June 1993]

First quarter GDP figures signal the end of the recession. Recent falls in unemployment and rising house prices should stimulate greater expenditure from consumers now that the threat of redundancy has receded