Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) are involved in acetylcholine synthesis and degradation at pre- and postsynaptic compartments, respectively. Here we show that their anterograde transport in Drosophila larval ganglion is microtubule-dependent and occurs in two different time profiles. AChE transport is constitutive while that of ChAT occurs in a brief pulse during third instar larva stage. Mutations in the kinesin-2 motor subunit Klp64D and separate siRNA-mediated knock-outs of all the three kinesin-2 subunits disrupt the ChAT and AChE transports, and these antigens accumulate in discrete nonoverlapping punctae in neuronal cell bodies and axons. Quantification analysis further showed that mutations in Klp64D could independently affect the anterograde transport of AChE even before that of ChAT. Finally, ChAT and AChE were coimmunoprecipitated with the kinesin-2 subunits but not with each other. Altogether, these suggest that kinesin-2 independently transports AChE and ChAT within the same axon. It also implies that cargo availability could regulate the rate and frequency of transports by kinesin motors.

Background Cytokine storm triggered by Severe Coronavirus Disease 2019 (COVID-19) is associated with high mortality. With high Interleukin -6 (IL-6) levels reported in COVID-19 related deaths in China, IL-6 is considered to be the key player in COVID-19 cytokine storm. Tocilizumab, a monoclonal antibody against IL-6 receptor, is used on compassionate grounds for treatment of COVID-19 cytokine storm. The aim of this study was to assess effect of tocilizumab on mortality due to COVID-19 cytokine storm. Method This retrospective, observational study included patients of severe COVID-19 pneumonia with persistent hypoxia (defined as saturation 94% or less on supplemental Oxygen of 15 L per minute through non-rebreathing mask or PaO2/FiO2 ratio of less than 200) who were admitted to a tertiary care center in Mumbai, India, between 31st March to 5th July 2020. In addition to standard care, single Inj. Tocilizumab 400 mg was given intravenously to 151 consecutive COVID-19 patients with persistent hypoxia, from 13th May to 5th July 2020. These 151 patients were retrospectively analysed and compared with historic controls, ie consecutive COVID-19 patients with persistent hypoxia, defined as stated above (N = 118, from our first COVID-19 admission on 31st March to 12th May 2020 i.e., till tocilizumab was available in hospital). Univariate and multivariate Cox regression analysis was performed for identifying predictors of survival. Statistical analysis was performed using IBM SPSS version 26. Results Out of 269 (151 in tocilizumab group and 118 historic controls) patients studied from 31st March to 5th July 2020, median survival in the tocilizumab group was significantly longer than in the control group; 18 days (95% CI, 11.3 to 24.7) versus 9 days (95% CI, 5.7 to 12.3); log rank p 0.007. On multivariate Cox regression analysis, independent predictors of survival were use of tocilizumab (HR 0.621, 95% CI 0.427–0.903, P 0.013) and higher oxygen saturation. Conclusion Tocilizumab may improve survival in severe COVID-19 pneumonia with persistent hypoxia. Randomised controlled trials on use of tocilizumab as rescue therapy in patients of severe COVID-19 pneumonia with hypoxia (PaO2/FiO2 less than 200) due to hyperinflammatory state, are warranted.

BackgroundCytokine storm triggered by Severe Corona Virus Disease 2019 (COVID-19) is associated with high mortality. With high ‘Interlukin -6’ (IL-6) levels reported in COVID-19 related deaths in China1, IL-6 is considered to be the key player in COVID-19 cytokine storm. Tocilizumab, a monoclonal antibody against IL-6 receptor, is used on compassionate grounds for treatment of COVID-19 cytokine storm. The aim of this study was to assess effect of tocilizumab on mortality due to COVID-19 cytokine storm.MethodThis retrospective, observational study included patients of severe COVID-19 pneumonia with persistent hypoxia (defined as saturation 94% or less on supplemental Oxygen of 15 L per minute through non-rebreathing mask or PaO2/FiO2 ratio of less than 200) who were admitted to a tertiary care center in Mumbai, India, between 31st March to 5th July 2020. In addition to standard care, single Inj. Tocilizumab 400mg was given intravenously to 151 consecutive COVID-19 patients with persistent hypoxia, from 13th May to 5th July 2020. These 151 patients were retrospectively analysed and compared with historic controls, i.e consecutive COVID-19 patients with persistent hypoxia, defined as stated above (N=118, from our first COVID-19 admission on 31st March to 12th May 2020 i.e, till tocilizumab was available in hospital). Univariate and multivariate Cox regression analysis was performed for identifying predictors of survival. Statistical analysis was performed using IBM SPSS version 26.ResultsOn multivariate Cox regression analysis, independent predictors of survival were use of tocilizumab (HR 0.621, 95% CI 0.427-0.903, P 0.013) and higher oxygen saturation.Interpretation: Tocilizumab improved survival in severe COVID-19 pneumonia with persistent hypoxia

We report an adolescent male with X-linked agammaglobulinemia (XLA) and recurrent episodes of pyogenic meningitis. The workup for proportionate short stature revealed isolated growth hormone deficiency. This patient highlights the delayed presentation of the XLA variant and the need to consider primary immunodeficiency in patients with recurrent serious infections, irrespective of age.

Background: Distraction techniques are suitable measures for pain alleviation in young children during routine invasive procedures like venepuncture, serving as a positive stimulus drawing attention away from a painful experience. Objectives:To evaluate the effectiveness of cartoons animation videos as a pain alleviant during venepuncture along with delineating association of pain with selected variables. Method: This study followed a quasi-experimental design to monitor 60 children in the age group of 3-6 years selected by non-probability purposive sampling technique. The experimental and control group were composed of 30 children each. Baseline Proforma and an r-FLACC pain scale were used to measure and gather data. Cartoon animation video as an intervention was administered to the experimental group participants undergoing venepuncture and its effectiveness was estimated using an unpaired t-test. Association between pain perception and selected variables was analysed by a Chi-square test.Results: Divergence between pain perception among the control and experimental group was highlighted by the mean pain scores of 2.9 ± 0.25 and 2.3±0.46 respectively (p <0.001). Effectiveness of cartoon animation videos as a distraction technique for pain alleviation was found to be significant (p<0.01). No significant association was found between the level of pain perceived by preschool children during venepuncture and the selected variables (p>0.05) _________________________________________