Deafness-Associated ADGRV1 Mutation Impairs USH2A Stability through Improper Phosphorylation of WHRN and WDSUB1 Recruitment.

The ankle-link complex (ALC) consists of USH2A, WHRN, PDZD7, and ADGRV1 and plays an important role in hair cell development. At present, its architectural organization and signaling role remain unclear. By establishing Adgrv1 Y6236fsX1 mutant mice as a model of the deafness-associated human Y6244fsX1 mutation, the authors show here that the Y6236fsX1 mutation disrupts the interaction between adhesion G protein-coupled receptor V subfamily member 1 (ADGRV1) and other ALC components, resulting in stereocilia disorganization and mechanoelectrical transduction (MET) deficits. Importantly, ADGRV1 inhibits WHRN phosphorylation through regional cAMP-PKA signaling, which in turn regulates the ubiquitination and stability of USH2A via local signaling compartmentalization, whereas ADGRV1 Y6236fsX1 does not. Yeast two-hybrid screening identified the E3 ligase WDSUB1 that binds to WHRN and regulates the ubiquitination of USH2A in a WHRN phosphorylation-dependent manner. Further FlAsH-BRET assay, NMR spectrometry, and mutagenesis analysis provided insights into the architectural organization of ALC and interaction motifs at single-residue resolution. In conclusion, the present data suggest that ALC organization and accompanying local signal transduction play important roles in regulating the stability of the ALC.

Successful transcatheter arterial embolization treatment for chest wall haematoma following permanent pacemaker implantation: A case report.

BACKGROUND: Haematoma is one of the main complications associated with pacemaker implantation. Pseudoaneurysm is a rare condition that is not easy to identify and is often overlooked. CASE SUMMARY: A female patient diagnosed with high-grade atrioventricular block underwent permanent pacemaker implantation. During the operation, puncturing a small branch of the right subclavian artery developed into a pseudoaneurysm and resulted in further haematoma formation. Conventional treatment of compression haemostasis and haemostatic drugs was not effective. A series of timely transcatheter arterial embolizations avoided serious complications. CONCLUSION: More possible conditions should be taken into consideration as haematoma is discovered, and timely treatment might prevent severe adverse events.

5-min mindfulness audio induction alleviates psychological distress and sleep disorders in patients with COVID-19.

BACKGROUND: Mindfulness meditation is beneficial to mitigate the negative effects of the coronavirus disease 2019 (COVID-19) pandemic in the general population, but no study examined such meditation in the COVID-19 patients themselves. AIM: To explore the short-term efficacy of mindfulness meditation in alleviating psychological distress and sleep disorders in patients with COVID-19. METHODS: This prospective study enrolled patients with mild COVID-19 treated at Wuhan Fangcang Hospital in February 2020. The patients were voluntarily divided into either a mindfulness or a conventional intervention group. The patients were evaluated before/after the intervention using the Short Inventory of Mindfulness Capability (SMI-C), Hospital Anxiety and Depression Scale (HADS), and Pittsburgh Sleep Quality Index (PSQI). RESULTS: Seventy-five participants were enrolled in this study, with 43 and 32 in the mindfulness and conventional groups, respectively. Before the intervention, there were no differences in SMI-C, HADS, or PSQI scores between the two groups. After the 2-wk intervention, the mindfulness level (from 30.16 ± 5.58 to 35.23 ± 5.95, P < 0.001) and sleep quality (from 12.85 ± 3.06 to 9.44 ± 3.86, P < 0.001) were significantly increased in the mindfulness group. There were no differences in the conventional group. After the intervention, the mindfulness level (35.23 ± 5.95 vs 31.17 ± 6.50, P = 0.006) and sleep quality (9.44 ± 3.86 vs 11.87 ± 4.06, P = 0.011) were significantly higher in the mindfulness group than in the conventional group. Depression decreased in the mindfulness group (from 14.15 ± 3.21 to 12.50 ± 4.01, P = 0.038), but there was no difference between the two groups. CONCLUSION: Short-term mindfulness meditation can increase the mindfulness level, improve the sleep quality, and decrease the depression of patients with COVID-19.

A cellular automaton model of Schistosoma japonicum infection.

Due to the life cycle complexity of Schistosoma japonicum and the characteristics of schistosomias is immuno-epidemiology, it is very challenging to give a group of certain rules and thus describe the transmission dynamics of S. japonicum with modelling approaches. Most existing epidemiological models for schistosomias is based on differential equations only track average worm burden without taking into account the individual variations, thus bear limitations on individual infection status monitoring and interpretation. In this paper, an improved stochastic model based on cellular automaton (I-SjCA, briefly) has been introduced to describe the transmission dynamics of human schistosomiasis japonica in an endemic area in China. This model reflects the process of the pathogen invasion from exposure to worm development and worm death when the infection is cleared; it also incorporates seasonality of infection, and stochastic behaviour of each individual in the study field. We show that based on the data collected from the 706 study participants, the model-predicted prevalence and intensity of S. japonicum in the 2nd year of investigation is comparable with the observation. Furthermore, we illustrate the use of model for evaluating possible control strategies for schistosomiasis in context of simulated prevalence and individual infection probability. The simulation results suggest that chemotherapy should cover no less than 85% of the S. japonicum infected population to guarantee an effective drug control program, and the best time for annual chemotherapy with praziquantel is the beginning of spring in the endemic area. Our findings indicate that I-SjCA model based on the cellular automaton can effectively simulate the transmission process. It is anticipated that our cellular automaton transmission model can serve as a tool for understanding schistosomiasis transmission dynamics and thus be conductive to build an effective control program.

[Development of a software standardizing optical density with operation settings related to several limitations].

OBJECTIVE: To develop a software that can be used to standardize optical density to normalize the procedures and results of standardization in order to effectively solve several problems generated during standardization of in-direct ELISA results. METHODS: The software was designed based on the I-STOD method with operation settings to solve the problems that one might encounter during the standardization. Matlab GUI was used as a tool for the development. The software was tested with the results of the detection of sera of persons from schistosomiasis japonica endemic areas. RESULTS: I-STOD V1.0 (WINDOWS XP/WIN 7, 0.5 GB) was successfully developed to standardize optical density. A serial of serum samples from schistosomiasis japonica endemic areas were used to examine the operational effects of I-STOD V1.0 software. The results indicated that the software successfully overcame several problems including reliability of standard curve, applicable scope of samples and determination of dilution for samples outside the scope, so that I-STOD was performed more conveniently and the results of standardization were more consistent. CONCLUSION: I-STOD V1.0 is a professional software based on I-STOD. It can be easily operated and can effectively standardize the testing results of in-direct ELISA.

[Multi-dimensional evaluation system for schistosomiasis japonica transmission dynamic model].

OBJECTIVE: To evaluate the simulation effect of Schistosoma japonicum Cellular Automata (SjCA) model by using the multi-dimensional evaluation system. METHODS: Several selected indicators, including the Youden index, sensitivity, specificity, accuracy rate and prevalence distance were applied to assess the validity of the SjCA model. The effectiveness of each indicator for model evaluation was compared. RESULTS: Different indicators in the multi-dimensional evaluation system generated assorted combination of optimized parameters for the SjCA model. The best model according to prevalence distance (99.97%) did not guarantee the ultimate fit when using accuracy rate (79.70%) as the evaluation indicator. CONCLUSIONS: The multi-dimensional evaluation system is helpful for accurately assessing the simulation results of the discrete stochastic models such as SjCA, and is promising to be universalized to evaluate other similar epidemic dynamics models.

Evaluation of Kato-Katz examination method in three areas with low-level endemicity of schistosomiasis japonica in China: A Bayesian modeling approach.

The Kato-Katz technique is widely used to determine faecal egg counts of intestinal schistosomiasis. Although numerous studies have reported considerable underestimation of the 'true' infection prevalence while using this method, little is known regarding how many infections are missed as a function of the overall endemicity of intestinal schistosomiasis. In the present study, we used a Bayesian modeling approach to assess how much the Kato-Katz technique underestimates the prevalence of Schistosoma japonicum in three low endemic areas, characterized by different levels of infection. We found that up to 83% of S. japonicum infections were missed in an average when only a single Kato-Katz thick smear was examined. We further analyzed inter- and intra-specimen variation using agreement analysis. The results revealed a clear trend of higher agreement with infection intensity. In addition, our data also confirmed that intra-specimen consistency was better than that of inter-specimen. Our results suggest that a single Kato-Katz thick smear could only detect a certain small part of infections in areas with low endemicity; the disagreement of Kato-Katz results are mainly driven by day-to-day variation of eggs in stool; and light intensities are characterized by very high underestimation rates. There is a pressing need to develop more sensitive diagnostic tools for accurate detection of light infection intensities of schistosome infections.

Cloning of a laccase gene from a novel basidiomycete Trametes sp. 420 and its heterologous expression in Pichia pastoris.

The laccase gene lacD, cloned from a novel laccase-producing basidiomycete Trametes sp. 420, contained 2,052 base pairs (bp) interrupted by 8 introns. lacD displayed a relatively high homology with laccase genes from other white rot fungi, whereas the homology between lacD and laccase genes from plants, insects, or bacteria was less than 25%. A 498-amino acid peptide encoded by the lacD cDNA was heterologously expressed in the Pichia pastoris strain GS115, resulting in the highest yield of laccase (8.3 x 10(4) U/l) as determined with ABTS (2,2'-azinobis [3-ethylbenzothia-zoline-6-sulfonic acid]) as the substrate. Additionally, the enzyme activity of recombinant laccase on decolorization of some industrial dyes was assessed.