Mesenchymal stromal cell (MSC) transplantation ameliorated hepatic lipid load; tissue inflammation; and fibrosis in rodent animal models of non-alcoholic steatohepatitis (NASH) by as yet largely unknown mechanism(s). In a mouse model of NASH; we transplanted bone marrow-derived MSCs into the livers; which were analyzed one week thereafter. Combined metabolomic and proteomic data were applied to weighted gene correlation network analysis (WGCNA) and subsequent identification of key drivers. Livers were analyzed histologically and biochemically. The mechanisms of MSC action on hepatocyte lipid accumulation were studied in co-cultures of hepatocytes and MSCs by quantitative image analysis and immunocytochemistry. WGCNA and key driver analysis revealed that NASH caused the impairment of central carbon; amino acid; and lipid metabolism associated with mitochondrial and peroxisomal dysfunction; which was reversed by MSC treatment. MSC improved hepatic lipid metabolism and tissue homeostasis. In co-cultures of hepatocytes and MSCs; the decrease of lipid load was associated with the transfer of mitochondria from the MSCs to the hepatocytes via tunneling nanotubes (TNTs). Hence; MSCs may ameliorate lipid load and tissue perturbance by the donation of mitochondria to the hepatocytes. Thereby; they may provide oxidative capacity for lipid breakdown and thus promote recovery from NASH-induced metabolic impairment and tissue injury.

Human mitochondrial DNA (mtDNA) is located in discrete DNA-protein complexes, so called nucleoids. These structures can be easily visualized in living cells by utilizing the fluorescent stain PicoGreen^®. In contrary, cells devoid of endogenous mitochondrial genomes (ρ⁰ cells) display no mitochondrial staining in the cytoplasm. A modified restriction enzyme can be targeted to mitochondria to cleave the mtDNA molecules in more than two fragments, thereby activating endogenous nucleases. By applying this novel enzymatic approach to generate mtDNA-depleted cells the destruction of mitochondrial nucleoids in cultured cells could be detected in a time course. It is clear from these experiments that mtDNA-depleted cells can be seen as early as 48 h post-transfection using the depletion system. To prove that mtDNA is degraded during this process, mtDNA of transfected cells was quantified by real-time PCR. A significant decline could be observed 24 h post-transfection. Combination of both results showed that mtDNA of transfected cells is completely degraded and, therefore, ρ⁰ cells were generated within 48 h. Thus, the application of a mitochondrially-targeted restriction endonuclease proves to be a first and fast, but essential step towards a therapy for mtDNA disorders.

The need to minimize bycatch of toothed whales (odontocetes) in gillnets has long been recognized, because they are often top predators and thus essential to ecosystem resilience. It is likely that a key to achieving this goal is the improvement of gillnet acoustic visibility, because these species use underwater sonar for orientation. Previous work on increasing gillnet detectability for echolocating animals by making the nets more recognizable has been based on trial and error, without understanding the fundamental acoustic properties of the tested modifications. Consequently, these studies have produced mixed and sometimes contradictory results. We systematically identified small, passive reflective objects that can improve the visibility of gillnets at a broad range of frequencies, i.e., for many odontocetes. We simulated the acoustic reflectivity of a wide range of materials in different shapes, sizes, and environmental conditions, with a focus on polymer materials. We verified the simulation results experimentally and calculated detection distances of the selected modifications. For example, if 8 mm acrylic glass spheres are attached to the net at intervals smaller than 0.5 m, the spheres have the same target strength (TS) at 130 kHz as the most recognizable part of a gillnet, the floatline. Modifications of the netting material itself, e.g., using barium sulfate additives, do not substantially increase the acoustic reflectivity of the net.

The coronavirus disease 2019 pandemic has been linked to changes in alcohol consumption, access to healthcare services and alcohol-attributable harm. In this contribution, we quantify changes in alcohol-specific mortality and hospitalizations at the onset of the COVID-19 pandemic in March 2020 in Germany. We obtained monthly counts of deaths and hospital discharges between January 2013 and December 2020 (n = 96 months). Alcohol-specific (International Classification of Diseases, tenth revision codes: F10.X; G31.2, G62.1, G72.1, I42.6, K29.2, K70.X, K85.2, K86.0, Q86.0, T51.X) diagnoses were further split into codes reflective of acute vs. chronic harm from alcohol consumption. To quantify the change in alcohol-specific deaths and hospital discharges, we performed sex-stratified interrupted time series analyses using generalized additive mixed models for the population aged 45–74. Immediate (step) and cumulative (slope) changes were considered. Following March 2020, we observed immediate increases in alcohol-specific mortality among women but not among men. Between the years of 2019 and 2020, we estimate that alcohol-specific mortality among women has increased by 10.8%. Hospital discharges were analyzed separately for acute and chronic conditions. The total number of hospital discharges fell by 21.4% and 25.1% for acute alcohol-specific conditions for women and men, respectively. The total number of hospital discharges for chronic alcohol-specific conditions fell by 7.4% and 8.1% for women and men, respectively. Increased consumption among people with heavy drinking patterns and reduced utilization of addiction-specific healthcare services during the pandemic might explain excess mortality. During times of public health crises, access to addiction-specific services needs to be ensured.

Objective: To obtain population based data on prevalence of allergies and to provide insight into allergy care and perceptions among German general population. Methods: A random representative sample of the German population (>18 years) was recruited for a computer assisted telephone survey in Feb. 2012. Descriptive data was stratified by relevant criteria (age, sex, region and health insurance status). Results: For 51% of n=1.004 respondents the topic “allergy” was personally relevant. One third (33%) rated a physician-diagnosed allergy. Prevalence was higher in women (39%; men 27%) and in persons with higher educational level (39% vs. 33% lowest level). The most common allergen (43%) was pollen; 15% reported contact dermatitis (women 21%, men 5%). The majority of allergic persons (53%) felt (highly) burdened, 48% were limited in daily activities due to allergic symptoms. 70% have ever seen a physician/other therapist for their allergy (East: 62%, West 72%); GPs (45%) and dermatologists (41%) were consulted mainly. Self-medication was frequent among allergic persons (58%); and most prevalent in highest income and education groups as well as in West Germany. Medical treatment of acute symptoms was reported by 21% of the respondents who suffered from allergic symptoms in the last 12 months.Regarding allergy perception, 39% appraised allergies as “easily treatable”; this was more prevalent in women and in privately insured. In an open question on potential allergy triggers environmental factors were mentioned most often (26%), chemical agents were stated by 12% of respondents from East- and by 6% from West-Germany. Conclusions: About one third of the German general adult population is affected by allergies and constricted by acute symptoms. There is evidence for need of improvement concerning awareness and appraisal of allergies–which are not distributed evenly over social groups. In particular, there is a gap of using adequate medical treatment of acute symptoms.