Our review suggests that movement disorder may help differentiate clinically an episode of HSV-induced anti-NMDAR encephalitis from HSE relapse. Compared with adults, children have shorter latency between HSE and anti-NMDAR encephalitis and, during anti-NMDAR encephalitis, more movement disorder, fewer psychiatric symptoms, and slightly more severe disease. According to our results, immune therapy given for HSV-induced anti-NMDAR encephalitis does not predispose patients to HSE recurrence.

The genetic elements required to tune gene expression are partitioned in active and repressive nuclear condensates. Chromatin compartments include transcriptional clusters whose dynamic establishment and functioning depends on multivalent interactions occurring among transcription factors, cofactors and basal transcriptional machinery. However, how chromatin players contribute to the assembly of transcriptional condensates is poorly understood. By interrogating the effect of KMT2D (also known as MLL4 ) haploinsufficiency in Kabuki Syndrome, we found that MLL4 contributes to the assembly of transcriptional condensates through liquid-liquid phase separation. MLL4 loss-of-function (LoF) impaired Polycomb-dependent chromatin compartmentalization, altering nuclear architecture. By releasing the nuclear mechanical stress through the inhibition of the mechano-sensor ATR, we re-established the mechano-signaling of mesenchymal stem cells (MSCs) and their commitment towards chondrocytes both in vitro and in vivo. This study supports the notion that in Kabuki Syndrome the haploinsufficiency of MLL4 causes an altered functional partitioning of chromatin, which determines the architecture and mechanical properties of the nucleus.

Background Pediatric cardiac arrest (PCA), although rare, is associated with high mortality. Deviations from international management guidelines are frequent and associated with poorer outcomes. Different strategies/devices have been developed to improve the management of cardiac arrest, including cognitive aids. However, there is very limited experience on the usefulness of interactive cognitive aids in the format of an app in PCA. No app has so far been tested for its usability and effectiveness in guiding the management of PCA. Objective To develop a new audiovisual interactive app for tablets, named PediAppRREST, to support the management of PCA and to test its usability in a high-fidelity simulation-based setting. Methods A research team at the University of Padova (Italy) and human–machine interface designers, as well as app developers, from an Italian company (RE:Lab S.r.l.) developed the app between March and October 2019, by applying an iterative design approach (ie, design–prototyping–evaluation iterative loops). In October–November 2019, a single-center nonrandomized controlled simulation–based pilot study was conducted including 48 pediatric residents divided into teams of 3. The same nonshockable PCA scenario was managed by 11 teams with and 5 without the app. The app user’s experience and interaction patterns were documented through video recording of scenarios, debriefing sessions, and questionnaires. App usability was evaluated with the User Experience Questionnaire (UEQ) (scores range from –3 to +3 for each scale) and open-ended questions, whereas participants’ workload was measured using the NASA Raw-Task Load Index (NASA RTLX). Results Users’ difficulties in interacting with the app during the simulations were identified using a structured framework. The app usability, in terms of mean UEQ scores, was as follows: attractiveness 1.71 (SD 1.43), perspicuity 1.75 (SD 0.88), efficiency 1.93 (SD 0.93), dependability 1.57 (SD 1.10), stimulation 1.60 (SD 1.33), and novelty 2.21 (SD 0.74). Team leaders’ perceived workload was comparable (P=.57) between the 2 groups; median NASA RTLX score was 67.5 (interquartile range [IQR] 65.0-81.7) for the control group and 66.7 (IQR 54.2-76.7) for the intervention group. A preliminary evaluation of the effectiveness of the app in reducing deviations from guidelines showed that median time to epinephrine administration was significantly longer in the group that used the app compared with the control group (254 seconds versus 165 seconds; P=.015). Conclusions The PediAppRREST app received a good usability evaluation and did not appear to increase team leaders’ workload. Based on the feedback collected from the participants and the preliminary results of the evaluation of its effects on the management of the simulated scenario, the app has been further refined. The effectiveness of the new version of the app in reducing deviations from guidelines recommendations in the management of PCA and its impact on time to critical actions will be evaluated in an upcoming multicenter simulation-based randomized controlled trial.

Different cognitive aids have been recently developed to support the management of cardiac arrest, however, their effectiveness remains barely investigated. We aimed to assess whether clinicians using any cognitive aids compared to no or alternative cognitive aids for in-hospital cardiac arrest (IHCA) scenarios achieve improved resuscitation performance. PubMed, EMBASE, the Cochrane Library, CINAHL and ClinicalTrials.gov were systematically searched to identify studies comparing the management of adult/paediatric IHCA simulated scenarios by health professionals using different or no cognitive aids. Our primary outcomes were adherence to guideline recommendations (overall team performance) and time to critical resuscitation actions. Random-effects model meta-analyses were performed. Of the 4.830 screened studies, 16 (14 adult, 2 paediatric) met inclusion criteria. Meta-analyses of eight eligible adult studies indicated that the use of electronic/paper-based cognitive aids, in comparison with no aid, was significantly associated with better overall resuscitation performance [standard mean difference (SMD) 1.16; 95% confidence interval (CI) 0.64; 1.69; I2 = 79%]. Meta-analyses of the two paediatric studies, showed non-significant improvement of critical actions for resuscitation (adherence to guideline recommended sequence of actions, time to defibrillation, rate of errors in defibrillation, time to start chest compressions), except for significant shorter time to amiodarone administration (SMD − 0.78; 95% CI − 1.39; − 0.18; I2 = 0). To conclude, the use of cognitive aids appears to have benefits in improving the management of simulated adult IHCA scenarios, with potential positive impact on clinical practice. Further paediatric studies are necessary to better assess the impact of cognitive aids on the management of IHCA scenarios.

The COVID-19 pandemic has now affected around 190 million people worldwide, accounting for more than 4 million confirmed deaths. Besides ongoing global vaccination, finding protective and therapeutic strategies is an urgent clinical need. SARS-CoV-2 mostly infects the host organism via the respiratory system, requiring angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) to enter target cells. Therefore, these surface proteins are considered potential druggable targets. Hydrogen sulfide (H2S) is a gasotransmitter produced by several cell types and is also part of natural compounds, such as sulfurous waters that are often inhaled as low-intensity therapy and prevention in different respiratory conditions. H2S is a potent biological mediator, with anti-oxidant, anti-inflammatory, and, as more recently shown, also anti-viral activities. Considering that respiratory epithelial cells can be directly exposed to H2S by inhalation, here we tested the in vitro effects of H2S-donors on TMPRSS2 and ACE2 expression in human upper and lower airway epithelial cells. We showed that H2S significantly reduces the expression of TMPRSS2 without modifying ACE2 expression both in respiratory cell lines and primary human upper and lower airway epithelial cells. Results suggest that inhalational exposure of respiratory epithelial cells to natural H2S sources may hinder SARS-CoV-2 entry into airway epithelial cells and, consequently, potentially prevent the virus from spreading into the lower respiratory tract and the lung.