关键词： multisystem inflammatory syndrome in children (MIS-C)   COVID-19   pediatrics   diagnosis   management   New York  

摘要： On March 20, 2021, the Columbia University Department of Anesthesiology hosted the Papper virtual event dedicated to an academic discussion of various aspects of coronavirus disease-2019. Dr. Eva Cheung, a pediatric intensivist and pediatric cardiologist, spoke about the clinical challenges associated with tackling multisystem inflammatory syndrome in children, a novel clinical entity in pediatric patients related to coronavirus disease-2019, and the experience with confronting multisystem inflammatory syndrome in children in New York.

关键词： Genomics   RNA   RNA metabolism   Life Sciences   general   Biochemistry   Protein Structure   Membrane Biology   Biological Microscopy  

摘要： Analogous to alternative splicing, alternative polyadenylation (APA) has long been thought to occur independently at proximal and distal polyA sites. Using fractionation-seq, we unexpectedly identified several hundred APA genes in human cells whose distal polyA isoforms are retained in chromatin/nuclear matrix and whose proximal polyA isoforms are released into the cytoplasm. Global metabolic PAS-seq and Nanopore long-read RNA-sequencing provide further evidence that the strong distal polyA sites are processed first and the resulting transcripts are subsequently anchored in chromatin/nuclear matrix to serve as precursors for further processing at proximal polyA sites. Inserting an autocleavable ribozyme between the proximal and distal polyA sites, coupled with a Cleave-seq approach that we describe here, confirms that the distal polyA isoform is indeed the precursor to the proximal polyA isoform. Therefore, unlike alternative splicing, APA sites are recognized independently, and in many cases, in a sequential manner. This provides a versatile strategy to regulate gene expression in mammalian cells. New data reveal a sequential mode of alternative polyadenylation. Distal polyA sites are processed first and the resultant transcripts are retained in the nuclear-chromatin matrix for subsequent cleavage and polyadenylation at proximal polyA sites.

关键词： mitochondrial potassium channels   cytoprotection   mitochondria   potassium channel openers  

摘要： Mitochondrial potassium channels control potassium influx into the mitochondrial matrix and thus regulate mitochondrial membrane potential, volume, respiration, and synthesis of reactive oxygen species (ROS). It has been found that pharmacological activation of mitochondrial potassium channels during ischemia/reperfusion (I/R) injury activates cytoprotective mechanisms resulting in increased cell survival. In cancer cells, the inhibition of these channels leads to increased cell death. Therefore, mitochondrial potassium channels are intriguing targets for the development of new pharmacological strategies. In most cases, however, the substances that modulate the mitochondrial potassium channels have a few alternative targets in the cell. This may result in unexpected or unwanted effects induced by these compounds. In our review, we briefly present the various classes of mitochondrial potassium (mitoK) channels and describe the chemical compounds that modulate their activity. We also describe examples of the multidirectional activity of the activators and inhibitors of mitochondrial potassium channels.

关键词： Genetics   Molecular biology   Neuroscience   Schizophrenia   Medicine/Public Health   general   Psychiatry   Neurosciences   Behavioral Sciences   Pharmacotherapy   Biological Psychology  

摘要： Alternative splicing of schizophrenia risk genes, such as DRD2, GRM3, and DISC1, has been extensively described. Nevertheless, the alternative splicing characteristics of the growing number of schizophrenia risk genes identified through genetic analyses remain relatively opaque. Recently, transcriptomic analyses in human brains based on short-read RNA-sequencing have discovered many "local splicing" events (e.g., exon skipping junctions) associated with genetic risk of schizophrenia, and further molecular characterizations have identified novel spliced isoforms, such as AS3MT(d2d3) and ZNF804A(E3E4). In addition, long-read sequencing analyses of schizophrenia risk genes (e.g., CACNA1C and NRXN1) have revealed multiple previously unannotated brain-abundant isoforms with therapeutic potentials, and functional analyses of KCNH2-3.1 and Ube3a1 have provided examples for investigating such spliced isoforms in vitro and in vivo. These findings suggest that alternative splicing may be an essential molecular mechanism underlying genetic risk of schizophrenia, however, the incomplete annotations of human brain transcriptomes might have limited our understanding of schizophrenia pathogenesis, and further efforts to elucidate these transcriptional characteristics are urgently needed to gain insights into the illness-correlated brain physiology and pathology as well as to translate genetic discoveries into novel therapeutic targets.

关键词： Language   Functional laterality   Brain neoplasms   Cerebellum   Magnetic resonance imaging  

摘要： Objectives Crossed cerebro-cerebellar BOLD activations have recently come to light as additional diagnostic features for patients with brain tumors. The covert verb generation (VG) task is a widely used language paradigm to determine these language-related crossed activations. Here we demonstrate these crossed activations in two additional language paradigms, the semantic and phonological association tasks. We propose the merit of these tasks to language lateralization determination in the clinic as they are easy to monitor and suitable for patients with aphasia. Methods Patients with brain tumors localized at different cortical sites (n = 71) performed three language paradigms, namely the VG task as well as the semantic (SA) and phonological (PA) association tasks with button-press responses. Respective language activations in disparate cortical regions and the cerebellum were assigned laterality. Agreements in laterality between the two new tasks and the verb generation task were tested using Cohen's kappa. Results Both tasks significantly agreed in cortical and cerebellar lateralization with the verb generation task in patients. Additionally, a McNemar test confirmed the presence of crossed activations in the cortex and the cerebellum in the entire subject population. Conclusion We demonstrated that the semantic and phonological association tasks resulted in crossed cerebro-cerebellar language lateralization activations as those observed due to the covert verb generation task. This may suggest the possibility of these tasks being used conjointly with the traditional verb generation task, especially for subjects that may be unable to perform the latter.

关键词： cicatricial conjunctivitis   corticotropin   mucous membrane pemphigoid   ocular surface disease   refractory  

摘要： Purpose: The purpose of this study was to report the clinical course and outcome of patients with refractory ocular mucous membrane pemphigoid (MMP) treated by repository corticotropin injection (RCI). Methods: Patients with biopsy-proven ocular MMP treated with RCI from 3 tertiary medical centers were evaluated. Medical records between January 2013 and January 2021 were reviewed and deidentified to retrieve relevant disease-related data. Primary outcome measures included conjunctival inflammatory activity, change in Foster clinical conjunctival scarring staging after RCI treatment, and the development of ocular and systemic complications. Results: Included were 15 patients (10 women and 5 men;36-95 yrs of age) with a mean follow-up of 4.5 years. Most of the patients (80%) had Foster stage 3 at presentation, and all patients had active MMP. Each patient had failed to respond to at least 1 immunomodulatory drug during the follow-up, and 9 (60%) patients had treatment failure of at least 2 other agents before the use of RCI. The mean duration of RCI treatment was 21 months (range, 3-54 mo). Foster stage did not change in any of the 15 patients at the last follow-up. Nine patients continued RCI therapy at the last follow-up, and in all of them, the disease activity of MMP was well controlled. No serious adverse events because of RCI were documented during the follow-up in any treated patient. Conclusions: RCI may serve as an alternative or an adjunctive treatment in patients with severe and refractory ocular MMP. Treatment with RCI seems to be safe and well-tolerated.

关键词： C   nutans   medicinal uses   phytochemistry   pharmacology   therapeutic potential  

摘要： The application of natural products and supplements has expanded tremendously over the past few decades. Clinacanthus nutans (C. nutans), which is affiliated to the Acanthaceae family, has recently caught the interest of researchers from the countries of subtropical Asia due to its medicinal uses in alternative treatment for skin infection conditions due to insect bites, microorganism infections and cancer, as well as for health well-being. A number of bioactive compounds from this plant's extract, namely phenolic compounds, sulphur containing compounds, sulphur containing glycosides compounds, terpens-tripenoids, terpens-phytosterols and chlorophyll-related compounds possess high antioxidant activities. This literature search yielded about one hundred articles which were then further documented, including the valuable data and findings obtained from all accessible electronic searches and library databases. The promising pharmacological activities from C. nutans leaves extract, including antioxidant, anti-cancer, anti-viral, anti-bacterial, anti-fungal, anti-venom, analgesic and anti-nociceptive properties were meticulously dissected. Moreover, the authors also discuss a few of the pharmacological aspect of C. nutans leaves extracts against anti-hyperlipidemia, vasorelaxation and renoprotective activities, which are seldom available from the previously discussed review papers. From the aspect of toxicological studies, controversial findings have been reported in both in-vitro and in-vivo experiments. Thus, further investigations on their phytochemical compounds and their mode of action showing pharmacological activities are required to fully grasp both traditional usage and their suitability for future drugs development. Data related to therapeutic activity and the constituents of C. nutans leaves were searched by using the search engines Google scholar, PubMed, Scopus and Science Direct, and accepting literature reported between 2010 to present. On the whole, this

关键词： Scanning transmission electron microscopy   Electron beam damage   Scanning strategies  

摘要： The highly energetic electrons in a transmission electron microscope (TEM) can alter or even completely destroy the structure of samples before sufficient information can be obtained. This is especially problematic in the case of zeolites, organic and biological materials. As this effect depends on both the electron beam and the sample and can involve multiple damage pathways, its study remained difficult and is plagued with irreproducibility issues, circumstantial evidence, rumors, and a general lack of solid data. Here we take on the experimental challenge to investigate the role of the STEM scan pattern on the damage behavior of a commercially available zeolite sample with the clear aim to make our observations as reproducible as possible. We make use of a freely programmable scan engine that gives full control over the tempospatial distribution of the electron probe on the sample and we use its flexibility to obtain multiple repeated experiments under identical conditions comparing the difference in beam damage between a conventional raster scan pattern and a newly proposed interleaved scan pattern that provides exactly the same dose and dose rate and visits exactly the same scan points. We observe a significant difference in beam damage for both patterns with up to 11 % reduction in damage (measured from mass loss). These observations demonstrate without doubt that electron dose, dose rate and acceleration voltage are not the only parameters affecting beam damage in (S)TEM experiments and invite the community to rethink beam damage as an unavoidable consequence of applied electron dose.

关键词： alternative hosts   automation   media blending   media development   Pichia pastoris  

摘要： Developing media to sustain cell growth and production is an essential and ongoing activity in bioprocess development. Modifications to media can often address host or product-specific challenges, such as low productivity or poor product quality. For other applications, systematic design of new media can facilitate the adoption of new industrially relevant alternative hosts. Despite manifold existing methods, common approaches for optimization often remain time and labor-intensive. We present here a novel approach to conventional media blending that leverages stable, simple, concentrated stock solutions to enable rapid improvement of measurable phenotypes of interest. We applied this modular methodology to generate high-performing media for two phenotypes of interest: biomass accumulation and heterologous protein production, using high-throughput, milliliter-scale batch fermentations of Pichia pastoris as a model system. In addition to these examples, we also created a flexible open-source package for modular blending automation on a low-cost liquid handling system to facilitate wide use of this method. Our modular blending method enables rapid, flexible media development, requiring minimal labor investment and prior knowledge of the host organism, and should enable developing improved media for other hosts and phenotypes of interest.

关键词： hyperbaric oxygenation   military medicine   placebo effect   post-traumatic stress disorder   traumatic brain injury   mild  

摘要： Introduction: Hyperbaric oxygen therapy (HBOT) is a commonly used treatment for a variety of medical issues, including more than a dozen currently approved uses. However, there are alternative proposed uses that have significant implications among an active duty military or veteran population as treatments for PTSD, mild traumatic brain injury (mTBI), and traumatic brain injury (TBI). These applications have seen a recent groundswell of support from the operator and veteran communities, raising the visibility of using HBOT for alternative applications. The current review will cover the existing evidence regarding alternative uses of HBOT in military medicine and provide several possibilities to explain the potential conflicting evidence from empirical results. Materials and Methods: There were no inclusion or exclusion criteria for articles addressing currently approved HBOT uses as covered under the military health system. These references were provided for comparison and illustration as needed. For alternative HBOT uses, the review focuses explicitly upon three alternative uses in PTSD, mTBI, and TBI. The review addresses any piece of case study evidence, observational data, quasi-experimental design, or randomized-controlled trial that explored any or a combination of these issues within an active duty population, a veteran population, or a civilian population. Results: The existing medical evidence does not support a consensus viewpoint for these alternative uses of HBOT. Based on the literature review, there are four competing positions to explain the lack of consistency among the empirical results. These possibilities are described in no particular order. First, an explanation suggests that the results are because of placebo effects. The combination of participant expectations and subjective symptom reporting creates the potential that reported improvements are because of placebo rather than casual mechanisms. Second, another position suggests that experiments