Otoconia are bio-crystals which couple mechanic forces to the sensory hair cells in the utricle and saccule, a process essential for us to sense linear acceleration and gravity for the purpose of maintaining bodily balance. In fish, structurally similar bio-crystals called otoliths mediate both balance and hearing. Otoconia abnormalities are common and can cause vertigo and imbalance in humans. However, the molecular etiology of these illnesses is unknown, as investigators have only begun to identify genes important for otoconia formation in recent years. To date, in-depth studies of selected mouse otoconial proteins have been performed, and about 75 zebrafish genes have been identified to be important for otolith development. This review will summarize recent findings as well as compare otoconia and otolith development. It will provide an updated brief review of otoconial proteins along with an overview of the cells and cellular processes involved. While continued efforts are needed to thoroughly understand the molecular mechanisms underlying otoconia and otolith development, it is clear that the process involves a series of temporally and spatially specific events that are tightly coordinated by numerous proteins. Such knowledge will serve as the foundation to uncover the molecular causes of human otoconia-related disorders.

AimsSince the beginning of the SARS-CoV-2 outbreak, hospitals reported declining numbers of patients admitted with ST-segment elevation myocardial infarction (STEMI), indicating that the pandemic might keep patients from seeking urgent medical treatment. However, data on outcomes and mortality rates are inconsistent between studies.MethodsA literature search and meta-analysis were performed on studies reporting the mortality of patients with STEMI admitted before and during the COVID-19 pandemic using PubMed, Embase and Web of Science. Additionally, prehospital and intrahospital delay times were evaluated.ResultsOutcomes of a total of 50 123 patients from 10 studies were assessed. Our study revealed that, despite a significant reduction in overall admission rates of patients with STEMI during the COVID-19 pandemic (incidence rate ratio=0.789, 95% CI 0.730 to 0.852, I2=77%, p<0.01), there was no significant difference in hospital mortality (OR=1.178, 95% CI 0.926 to 1.498, I2=57%, p=0.01) compared with patients with STEMI admitted before the outbreak. Time from the onset of symptoms to first medical contact was similar (mean difference (MD)=33.4 min, 95% CI −10.2 to 77.1, I2=88%, p<0.01) while door-to-balloon time was significantly prolonged in those presenting during the pandemic (MD=7.3 min, 95% CI 3.0 to 11.7, I2=95%, p<0.01).ConclusionThe significant reduction in admission of patients with STEMI was not associated with a significant increase of hospital mortality rates. The causes for reduced incidence rates remain speculative. However, the analysed data indicate that acute and timely medical care of these patients has been maintained during the pandemic in most countries. Long-term data on mortality have yet to be determined.

Aims The coronavirus SARS-CoV-2 outbreak led to the most recent pandemic of the twenty-first century. To contain spread of the virus, many nations introduced a public lockdown. How the pandemic itself and measures of social restriction affect hospital admissions due to acute cardiac events has rarely been evaluated yet. Methods and Results German public authorities announced measures of social restriction between March 21st and April 20th, 2020. During this period, all patients suffering from an acute cardiac event admitted to our hospital (N = 94) were assessed and incidence rate ratios (IRR) of admissions for acute cardiac events estimated, and compared with those during the same period in the previous three years (2017–2019, N = 361). Admissions due to cardiac events were reduced by 22% as compared to the previous years (n = 94 vs. an average of n = 120 per year for 2017–2019). Whereas IRR for STEMI 1.20 (95% CI 0.67–2.14) and out-of-hospital cardiac arrest IRR 0.82 (95% CI 0.33–2.02) remained similar, overall admissions with an IRR of 0.78 (95% CI 0.62–0.98) and IRR for NSTEMI with 0.46 (95% CI 0.27–0.78) were significantly lower. In STEMI patients, plasma concentrations of high-sensitivity troponin T at admission were significantly higher (644 ng/l, IQR 372–2388) compared to 2017–2019 (195 ng/l, IQR 84–1134; p = 0.02). Conclusion The SARS-CoV-2 pandemic and concomitant social restrictions are associated with reduced cardiac events admissions to our tertiary care center. From a public health perspective, strategies have to be developed to assure patients are seeking and getting medical care and treatment in time during SARS-CoV-2 pandemic.

Mutations in the molecular co-chaperone Bcl2-associated athanogene 3 (BAG3) are found to cause dilated cardiomyopathy (DCM), resulting in systolic dysfunction and heart failure, as well as myofibrillar myopathy (MFM), which is characterized by protein aggregation and myofibrillar disintegration in skeletal muscle cells. Here, we generated a CRISPR/Cas9-induced Bag3 knockout zebrafish line and found the complete preservation of heart and skeletal muscle structure and function during embryonic development, in contrast to morpholino-mediated knockdown of Bag3. Intriguingly, genetic compensation, a process of transcriptional adaptation which acts independent of protein feedback loops, was found to prevent heart and skeletal muscle damage in our Bag3 knockout model. Proteomic profiling and quantitative real-time PCR analyses identified Bag2, another member of the Bag protein family, significantly upregulated on a transcript and protein level in bag3 -/- mutants. This implied that the decay of bag3 mutant mRNA in homozygous bag3 -/- embryos caused the transcriptional upregulation of bag2 expression. We further demonstrated that morpholino-mediated knockdown of Bag2 in bag3 -/- embryos evoked severe functional and structural heart and skeletal muscle defects, which are similar to Bag3 morphants. However, Bag2 knockdown in bag3 +/+ or bag3 +/- embryos did not result in (cardio-)myopathy. Finally, we found that inhibition of the nonsense-mediated mRNA decay (NMD) machinery by knockdown of upf1 , an essential NMD factor, caused severe heart and skeletal muscle defects in bag3 -/- mutants due to the blockade of transcriptional adaptation of bag2 expression. Our findings provide evidence that genetic compensation might vitally influence the penetrance of disease-causing bag3 mutations in vivo .

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