Metformin reduces the clonal fitness of Dnmt3aR878H hematopoietic stem and progenitor cells by reversing their aberrant metabolic and epigenetic state.

Clonal hematopoiesis (CH) arises when a hematopoietic stem cell (HSC) acquires a mutation that confers a competitive advantage over wild-type (WT) HSCs, resulting in its clonal expansion. Individuals with CH are at an increased risk of developing hematologic neoplasms and a range of age-related inflammatory illnesses1-3. Therapeutic interventions that suppress the expansion of mutant HSCs have the potential to prevent these CH-related illnesses; however, such interventions have not yet been identified. The most common CH driver mutations are in the DNA methyltransferase 3 alpha (DNMT3A) gene with arginine 882 (R882) being a mutation hotspot. Here we show that murine hematopoietic stem and progenitor cells (HSPCs) carrying the Dnmt3aR878H/+ mutation, which is equivalent to human DNMT3AR882H/+, have increased mitochondrial respiration compared with WT cells and are dependent on this metabolic reprogramming for their competitive advantage. Importantly, treatment with metformin, an oral anti-diabetic drug with inhibitory activity against complex I in the electron transport chain (ETC), reduced the fitness of Dnmt3aR878H/+ HSCs. Through a multi-omics approach, we discovered that metformin acts by enhancing the methylation potential in Dnmt3aR878H/+ HSPCs and reversing their aberrant DNA CpG methylation and histone H3K27 trimethylation (H3K27me3) profiles. Metformin also reduced the fitness of human DNMT3AR882H HSPCs generated by prime editing. Our findings provide preclinical rationale for investigating metformin as a preventive intervention against illnesses associated with DNMT3AR882 mutation-driven CH in humans.

Prominent genetic variants and epigenetic changes in post-traumatic stress disorder among combat veterans.

Post-traumatic stress disorder (PTSD) is one of the most widespread and disabling psychiatric disorders among combat veterans. Substantial interindividual variability in susceptibility to PTSD suggests the presence of different risk factors for this disorder. Twin and family studies confirm genetic factors as important risk factors for PTSD. In addition to genetic factors, epigenetic factors, especially DNA methylation, can be considered as a potential mechanism in changing the risk of PTSD. So far, many genetic and epigenetic association studies have been conducted in relation to PTSD. In genetic studies, many single nucleotide polymorphisms have been identified as PTSD risk factors. Meanwhile, the variations in catecholamines-related genes, serotonin transporter and receptors, brain-derived neurotrophic factor, inflammatory factors, and apolipoprotein E are the most prominent candidates. CpG methylation in the upstream regions of many genes is also considered a PTSD risk factor. Accurate identification of genetic and epigenetic changes associated with PTSD can lead to the presentation of suitable biomarkers for susceptible individuals to this disorder. This study aimed to delineate prominent genetic variations and epigenetic changes associated with post-traumatic stress disorder in military veterans who have experienced combat, focusing on genetic and epigenetic association studies.

Low-temperature acclimation related with developmental regulations of polyamines and ethylene metabolism in wheat recombinant inbred lines.

Winter survival is determined by complicated developmental regulations enabling wheat to adjust their transcriptome and metabolome to develop low temperature (LT) tolerance. The aim of the study was to clarify the metabolic responses developmentally regulated in six F6 recombinant inbred lines from a cross between Pishtaz (spring parent) and Mironovskaya 808 (winter parent). Spring genotypes, including pishtaz, RILs 4006 and 4014 showed lower LT tolerance, PAs (except the spermin), GABA and proline contents and DPPH• scavenging capacity. In these genotypes, genes and enzymes involved in the pathways of PAs and GABA degradation and ethylene biosynthesis were more active than other genotypes. RILs 4012 and 4016 with short vernalization displayed higher tolerance and lower H2O2 content compared to Pishtaz. Strong vernalization requirements in winter and facultative genotypes (Mironovskaya 808 parent and RILs 4003 and 4005) results in up-regulation of the metabolites and genes involved in PAs and GABA biosynthesis pathways (particularly when vernalization fulfillment occurred) to establish high tolerance as compared to genotypes without vernalization requirement. LT tolerance in all genotypes significantly decreased after vernalization fulfillment in February. Results indicated that LT tolerance was partly validated from developmental regulation of PAs, GABA, and ethylene metabolism during venalization and LT acclimation.

Can gamified surgical sets improve surgical instrument recognition and student performance retention in the operating room? A multi-institutional experimental crossover study.

INTRODUCTION: Surgery requires a high degree of precision, speed, and concentration. Owing to the complexity of the modern world, traditional methods cannot meet these requirements. Therefore, in this study, we investigated students' diagnostic skills in the Operating Room in the context of surgical instruments by using gamification of surgical instruments and a crossover design. METHOD: The study design was a multi-institutional quasi-experimental crossover and involved a three-arm intervention (with gender-specific block randomisation: Group A, B, and C) with a pre-test and three post-tests. A total of 90 students fell into three groups of 30 participants each. The surgical sets were learned for one semester through game-based instruction and traditional teaching, and then three OSCE tests were administered with time and location differences. Using one-way ANOVA, OSCE results were compared in the game, traditional, and control groups. The effectiveness of the intervention was tested in each group by repeated measures. RESULT: The pretest scores of all three groups did not differ significantly. In the OSCE tests, both groups, A and B, performed similarly. However, these tests showed a significant difference in grouping between training through games and training in the traditional way. There was no significant difference between OSCE tests 2 and 3 in the game-based training group, indicating that what was learned was retained, while in the traditional method training group, OSCE 3 test scores declined significantly. Furthermore, repeated measures showed the effectiveness of game-based training. CONCLUSION: In this study, gamification has turned out to be very effective in helping learners learn practical skills and leading to more sustainable learning.

Smartwatches in healthcare medicine: assistance and monitoring; a scoping review.

Smartwatches have become increasingly popular in recent times because of their capacity to track different health indicators, including heart rate, patterns of sleep, and physical movements. This scoping review aims to explore the utilisation of smartwatches within the healthcare sector. According to Arksey and O'Malley's methodology, an organised search was performed in PubMed/Medline, Scopus, Embase, Web of Science, ERIC and Google Scholar. In our search strategy, 761 articles were returned. The exclusion/inclusion criteria were applied. Finally, 35 articles were selected for extracting data. These included six studies on stress monitoring, six on movement disorders, three on sleep tracking, three on blood pressure, two on heart disease, six on covid pandemic, three on safety and six on validation. The use of smartwatches has been found to be effective in diagnosing the symptoms of various diseases. In particular, smartwatches have shown promise in detecting heart diseases, movement disorders, and even early signs of COVID-19. Nevertheless, it should be emphasised that there is an ongoing discussion concerning the reliability of smartwatch diagnoses within healthcare systems. Despite the potential advantages offered by utilising smartwatches for disease detection, it is imperative to approach their data interpretation with prudence. The discrepancies in detection between smartwatches and their algorithms have important implications for healthcare use. The accuracy and reliability of the algorithms used are crucial, as well as high accuracy in detecting changes in health status by the smartwatches themselves. This calls for the development of medical watches and the creation of AI-hospital assistants. These assistants will be designed to help with patient monitoring, appointment scheduling, and medication management tasks. They can educate patients and answer common questions, freeing healthcare providers to focus on more complex tasks.

Crossover design in triage education: the effectiveness of simulated interactive vs. routine training on student nurses' performance in a disaster situation.

INTRODUCTION: This study investigates the effectiveness of incorporating simulated interactive guidelines in nursing students' performance during disaster situations, compared to routine training. METHOD: This study was a crossover design with pre-and post-tests for two groups. Each group consisted of 60 students selected using the census method. SIG and routine (Face-to-Face) training sessions were conducted as a crossover design. Triage knowledge questionnaires were used in the pretest to assess triage knowledge. An OSCE test was administered in the posttest to assess student performance, followed by a triage skills questionnaire. Both questionnaires were highly reliable, as indicated by Cronbach's alpha coefficients (0.9 and 0.95, respectively). Statistical analysis was performed using SPSS version 26 software at a significance level 0.05. RESULT: The chi-square test showed that the two groups were homogeneous regarding age. Regarding knowledge level, both groups were homogeneous before the intervention (P = 0.99). Nevertheless, the results of the OSCE test showed that the students in Group A had a higher level of skill than the students in Group B (93% versus 70%). Also, 18% of the students in group B had low skills. DISCUSSION: The study found that student outcomes improved in both groups receiving SIG, suggesting that interaction and simulation improve learning. However, gamification is an ideal precursor to learning and not a substitute for education. Therefore, gamification should not be used as a stand-alone teaching method. CONCLUSIONS: The crossover study found that simulators and games should not be considered stand-alone teaching methods but can contribute to learning sustainability when used alongside instruction.

Dietary and Sleep Quality Association in Hemodialysis Patients.

Background: Poor sleep quality is a common issue among patients with end-stage renal disease (ESRD) who undergo dialysis. Nutritional habits are associated with sleep hygiene in patients undergoing dialysis. The objective of this study was to examine the potential correlation between nutritional status and sleep quality in individuals receiving hemodialysis treatment. Materials and Methods: This cross-sectional study included 160 hemodialysis patients. A food frequency questionnaire (FFQ) was used to measure food intake in participants. The Persian-validated version of the Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. Patients were classified as poor or good sleepers with a PSQI score of <5 and >5, respectively. Results: Eighty-four percent of hemodialysis patients had bad sleep hygiene. There was a significant association between sleep quality and educational status and age (P < 0.001). Poor sleepers were older (61.65 years versus 51.12) and less educated (31.1% versus 4%). However, there was no significant difference in the intake of micro- and macronutrients between poor and good sleepers (P > 0.05). Conclusion: The results of this study suggest that sleep quality has no significant relationship with nutrient intake in hemodialysis patients. Demographic factors, such as age and educational status, have played a more effective role than nutritional factors in patients' sleep quality.

Inverse correlation between vitamin D and CRP levels in alopecia areata: A pilot study.

INTRODUCTION: Alopecia areata (AA) is an autoimmune non-scarring hair loss. The role of micronutrients such as iron, zinc, and vitamins, especially vitamin D, on the natural hair cycle is well defined in literature. This study aims to evaluate the correlation between vitamin D and CRP levels in patients with alopecia areata. METHODS: This cross-sectional study was performed from beginning of October 2020 until end of December 2021. Alopecia areata patients over 18 years of age gave their written consent to participate in the study. The severity of the patients' disease was assessed using the Severity of Alopecia Tool. Serum vitamin D and CRP levels were measured and CBC and LFT were also performed. RESULTS: There were significant differences between the patients with the localized form of AA and its universal form in the following variables: Vitamin D levels, SALT score, WBC, ALKP, and CRP. There was also a significant inverse correlation between CRP and vitamin D levels (p < 0.0001). CONCLUSION: Vitamin D deficiency is associated with higher CRP levels, and patients with low serum vitamin D and high CRP levels are at a higher risk of developing the universalis form of AA; therefore, these patients should undergo more aggressive treatments.

Chromone-embedded peptidomimetics and furopyrimidines as highly potent SARS-CoV-2 infection inhibitors: docking and MD simulation study.

BACKGROUND: COVID-19 is a respiratory illness caused by SARS-CoV-2. Pharmaceutical companies aim to control virus spread through effective drugs. This study investigates chromone compound derivatives' ability to inhibit viral entry and prevent replication. METHOD: This study investigated the inhibitory effect of chromone-embedded peptidomimetics and furopyrimidines on 7BZ5 from Severe Acute Respiratory Syndrome CoV-2, Homo sapiens, and 6LU7 from Bat SARS-like CoV using molecular docking. The crystal structure of these proteins was obtained from the Protein Data Bank, and the inhibition site was determined using ligand binding interaction options. The 3D structure was protonated and energetically minimised using MOE software. Chromone derivatives were designed in three dimensions, and their energy was minimised using MOE 2019. The molecular drug-likeness was calculated using SwissADME, Lipinski and Benigni-Bossa's rule, and toxicity was calculated using Toxtree v3.1.0 software. Compounds with pharmacological properties were selected for molecular docking, and interactions were assessed using MOE 2019. MD simulations of Mpro-ch-p complexes were performed to evaluate root mean square fluctuations (RMSF) and measure protein stability. RESULT: The pharmacokinetic tests revealed that chromone derivatives of the peptidomimetic family have acceptable pharmacokinetic activity in the human body. Some compounds, such as Ch-p1, Ch-p2, Ch-p6, Ch-p7, Ch-p12, and Ch-p13, have pronounced medicinal properties. Molecular docking revealed high affinity for binding to SARS-CoV-2 protease. Ch-p7 had the highest binding energy, likely due to its inhibitory property. A 10 ns molecular dynamics study confirmed the stability of the protein-ligand complex, resulting in minimal fluctuations in the system's backbone. The MM-GBSA analysis revealed free energies of binding of - 19.54 kcal/mol. CONCLUSIONS: The study investigated the inhibition of viral replication using chromone derivatives, finding high inhibitory effects in the peptidomimetic family compared to other studies.

The Aspects of Running Artificial Intelligence in Emergency Care; a Scoping Review.

Introduction: Artificial Inteligence (AI) application in emergency medicine is subject to ethical and legal inconsistencies. The purposes of this study were to map the extent of AI applications in emergency medicine, to identify ethical issues related to the use of AI, and to propose an ethical framework for its use. Methods: A comprehensive literature collection was compiled through electronic databases/internet search engines (PubMed, Web of Science Platform, MEDLINE, Scopus, Google Scholar/Academia, and ERIC) and reference lists. We considered studies published between 1 January 2014 and 6 October 2022. Articles that did not self-classify as studies of an AI intervention, those that were not relevant to Emergency Departments (EDs), and articles that did not report outcomes or evaluations were excluded. Descriptive and thematic analyses of data extracted from the included articles were conducted. Results: A total of 137 out of the 2175 citations in the original database were eligible for full-text evaluation. Of these articles, 47 were included in the scoping review and considered for theme extraction. This review covers seven main areas of AI techniques in emergency medicine: Machine Learning (ML) Algorithms (10.64%), prehospital emergency management (12.76%), triage, patient acuity and disposition of patients (19.15%), disease and condition prediction (23.40%), emergency department management (17.03%), the future impact of AI on Emergency Medical Services (EMS) (8.51%), and ethical issues (8.51%). Conclusion: There has been a rapid increase in AI research in emergency medicine in recent years. Several studies have demonstrated the potential of AI in diverse contexts, particularly when improving patient outcomes through predictive modelling. According to the synthesis of studies in our review, AI-based decision-making lacks transparency. This feature makes AI decision-making opaque.

Super-enhanced evaporation of droplets from porous coatings.

HYPOTHESIS: The addition of a thin, hydrophilic, porous, coating to an impermeable solid will lead to more rapid evaporation of liquid droplets that impinge on the solid. The droplet will imbibe quickly, but the progress normal to the interface will be limited to the thickness of the coating, and therefore the liquid will spread laterally into a broad disk to expose a large liquid-vapor interface for evaporation. EXPERIMENTS: Liquid droplets of volume 2.5-25 µL were placed on solids and then both the mass and area of each droplet were monitored over time. We compared data for smooth, impermeable hydrophilic glass to the same glass that was coated in thin (35-109 µm) porous, hydrophilic-glass layer fabricated from glass beads. FINDINGS: The droplet was imbibed (wicked) into the coating within seconds, and the liquid spread laterally to form a thin, broad, disk. Critically, evaporation of a droplet was enhanced by a factor of 7-8 on the thin coating. The evaporation rate was not proportional to the reciprocal thickness of the coating. The ability to enhance evaporation of small droplets on a solid may have practical applications, for example, in speeding the death of microbes.

Robust and Transparent Silver Oxide Coating Fabricated at Room Temperature Kills Clostridioides difficile Spores, MRSA, and Pseudomonas aeruginosa.

Antimicrobial coatings can inhibit the transmission of infectious diseases when they provide a quick kill that is achieved long after the coating application. Here, we describe the fabrication and testing of a glass coating containing Ag2O microparticles that was prepared from sodium silicate at room temperature. The half-lives of both methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa on this coating are only 2-4 min. The half-life of Clostridioides difficile spores is about 9-12 min, which is extremely short for a spore. Additional tests on MRSA demonstrate that the coating retains its antimicrobial activity after abrasion and that an increased loading of Ag2O leads to a shorter half-life. This coating combines the properties of optical transparency, robustness, fast kill, and room temperature preparation that are highly desirable for an antimicrobial coating.

Normal spirometry prediction equations for the Iranian population.

BACKGROUND: This study aimed to establish normative spirometric equations in a healthy population of Iranian children and adults, and compare these equations with those developed by the Caucasian Global Lung Initiative (GLI) for the first time. METHODS: Spirometric data from healthy Iranian aged 4-82 years sampled in 2019 were used to derive reference equations using the generalized additive model for location (mu), shape (lambda), and scale (sigma). RESULTS: A total of 418 females and 204 males were included in the study. Applying the GLI standards for the Iranian population resulted from the Z scores of FEV1, FVC, FEV1/FVC, and FEF25-75% was not different from zero. Based on the newly calculated LLN, eleven individuals showed significant values below the LLN for FEV1/FVC. In all age groups, this frequency was less than 5%, except for men over 70 years of age, which was 12.5%. There are significant differences between new data and GLI for Caucasian data. CONCLUSION: It is recommended that the values and equations generated from this study should be used by physicians and technicians in their routine practice for the diagnosis and assessment of pulmonary disorders.

Game-based vs. Case-based Training for Increasing Knowledge and Behavioral Fluency of Nurse Students Regarding Crisis and Disaster Management; a Quasi-Experimental Study.

Introduction: Nurses play an active role in disaster response, and the ability of nurses to appropriately apply management principles during large-scale disasters or mass casualty incidents is of critical importance. This study aimed to compare the effect of game-based Training (GBT) and case-based training (CBT) on nursing students' knowledge and behavioral fluency regarding Crisis and Disaster Management. Methods: This is a quasi-experimental study with a pretest-posttest design. Convenience sampling was used to select third-year nursing students who had completed their clinical clerkship at the time of the study (n=60). In the intervention group, disaster-themed games were used, while in the control group, CBT was used. The emergency and crisis management course consisted of this study's theoretical and clinical training phases. After completion of the theoretical phase (five weeks), the practical part (four weeks) is completed as an internship. The data was collected from the disaster Nurses' Knowledge Questionnaire, demographic survey, and measurement checklists for disasters and crises at five stations. Results: GBT students achieved significantly higher knowledge scores than CBT students after training (p< 0.001). CBT and GBT groups had no significant differences in Objective Structured Clinical Examination (OSCE)1 pretest scores. Posttest1-OSCE2 and posttest2-OSCE3 scores showed significant differences after one week (P < 0.001) and one month (P < 0.001). The mean pretest and posttest1 scores were statistically significant in both groups. A comparison of posttest scores between one month after GBT training (69.03 ± 6.09) and one week after it (69.23 ± 6.14) revealed no statistical significance (p = 0.056). Conclusion: Nursing students' knowledge and behavioral fluency regarding crisis management were more effectively improved by using the disaster and crisis game than by using a case-based method.

Targeting STAT5 Signaling Overcomes Resistance to IDH Inhibitors in Acute Myeloid Leukemia through Suppression of Stemness.

Mutant isocitrate dehydrogenase 1 (IDH1) and IDH2 block the differentiation of acute myeloid leukemia (AML) cells through production of R-2-hydroxyglutarate (R-2-HG). IDH inhibitors can induce differentiation of AML cells by lowering R-2-HG but have limited clinical efficacy as single agents. Here, we performed a genome-wide CRISPR knockout screen in an Idh1-mutated hematopoietic progenitor cell line to identify genes that increased the differentiation response to ivosidenib, an IDH1 inhibitor. The screen identified C-type lectin member 5a (Clec5a), which encodes a spleen tyrosine kinase (SYK)-coupled surface receptor, as one of the top hits. Knockout of Clec5a and Syk rendered cells more sensitive to ivosidenib-induced differentiation through a reduction in STAT5-dependent expression of stemness-related genes, including genes in the homeobox (HOX) family. Importantly, direct inhibition of STAT5 activity was sufficient to increase the differentiation response to IDH inhibitors in primary human IDH1- and IDH2-mutated AML cells, including those harboring mutations in receptor tyrosine kinase (RTK) and MAPK genes that have been linked to drug resistance. In patient-derived xenograft models of IDH1-mutated AML, combination treatment with ivosidenib and the STAT5 inhibitor pimozide was superior to each agent alone in inducing differentiation in leukemic cells without compromising normal hematopoiesis. These findings demonstrate that STAT5 is a critical mediator of resistance to IDH inhibitors and provide the rationale for combining STAT5 and IDH inhibitors in the treatment of IDH-mutated AML. SIGNIFICANCE: A CRISPR knockout screen identifies a mechanism of resistance to IDH inhibitors in AML involving activated STAT5 signaling, suggesting a potential strategy to improve the clinical efficacy of IDH inhibitors.

Effect of Surface Porosity on SARS-CoV-2 Fomite Infectivity.

Previous reports indicated the low stability of severe actute respiratory syndrome coronovirus 2 (SARS-CoV-2) on various porous surfaces, but the role of porosity was unclear because there was no direct comparison between porous and nonporous solids of the same chemistry. Through comparing pairs of solids with very similar chemistry, we find that porosity is important: porous glass has a much lower infectivity than nonporous glass. However, porosity is not sufficient to lower infectivity; permeability, which is the ability of a liquid to move through a material, is the important parameter. We show this by comparing a pair of porous CuO coatings where the pores are accessible in one case and inaccessible in the other case. When the pores are inaccessible, the infectivity remains similar to that for nonporous solids. Thus, for both glass and CuO, it is the access to porosity that decreases the infectivity of extracted liquid droplets. Having established the importance of permeability, there is the open question of the mechanism of changing the infectivity of SARS-CoV-2. Several hypotheses are possible, such as increasing the difficulty of extracting the virus from the solid, changing the drying time, increasing the surface area of active ingredient, etc. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) measurements show that less viral DNA is extracted from a permeable surface, suggesting that the virus becomes trapped in the pores. Finally, we consider the effect of drying. We show that permeability and the water contact angle on the solid have effects on the drying time of a contaminated droplet, which may in turn affect infectivity.

Effect of Selenium on Triglyceride and Total Cholesterol, Weight Gain, and Physical Activity on Hemodialysis Patients: A Randomized Double-Blinded Controlled Trial.

Background: End-stage renal disease is one of the most important chronic diseases. Selenium is one of the so-called rare elements which are essential for our body functions. Here, we aimed to investigate and the effects of selenium supplement therapy on weight gain, physical activity, and triglyceride (TG) and total cholesterol in patients under hemodialysis. Methods: The current study is a double-blinded clinical trial performed on patients with ESRD under hemodialysis in 2019. In the beginning, serum selenium levels were assessed. All patients were randomly divided into two groups. The first group was under treatments with tablets of selenium 400 µg. Patients received selenium tablets three times after each hemodialysis session (3 times a week) and the other group received placebo tablets. 3 months after the beginning of the study, blood selenium levels, TG and total cholesterol, and weight and physical activities of patients were evaluated again and compared with the beginning. Results: A total of 78 patients were included. Serum selenium levels at the beginning of our study were 40.06 ± 8.50 in the intervention group and 45.00 ± 8.16 in control groups. Selenium levels and physical activities of patients were increased significantly in intervention group compared to baseline (P < 0.001 for both). Weight, physical activity, total cholesterol, and TG in both intervention and control groups did not change significantly after interventions (P > 0.05). Conclusions: We showed that selenium supplement therapies have beneficial effects in patients under hemodialysis. Furthermore, we showed that selenium supplement therapies have positive effects on serum selenium levels but no effects on total cholesterol and TG.

Does the rubella immunoglobulin G affect the severity of COVID- 19? : Rubella immunoglobulin G and COVID- 19.

OBJECTIVE & AIM: The coronavirus disease, so far (COVID-19) has brought about millions of infections and fatalities throughout the world. Our aim was to determine the correlation between rubella IGG titers with the severity COVID-19.  MATERIALS & METHODS: This study was conducted among COVID-19 confirmed patients over 18 years of age. The disease severity levels were categorized by WHO interim guidance. The rubella-specific IgG antibody-titer spectrum was measured (within first 48 h of hospitalization) by enzyme-linked immunosorbent assay (ELISA). RESULT: In a study of 46 inpatients with varying COVID-19 disease severity (mild, moderate, severe, and critical), we observed a negative correlation between rubella IgG antibody titers and COVID-19 severity (P-Value = 0.017), There was an interaction between COVID-19 vaccination history and rubella IGG on severity COVID-19 (P-Value = 0.0015). There was an interaction between age group under 44 years (including national measles- rubella (MR) vaccination in Iran) and rubella IGG titers on severity COVID-19 too (p-value = 0.014). CONCLUSION: In conclusion, MR vaccination seems to have a positive effect in reducing the severity of the disease, emphasizing that, the important and separate effect of the IGG rubella (due to natural or extrinsic immunity) titers is determining.

Transparent Anti-SARS-CoV-2 and Antibacterial Silver Oxide Coatings.

Transparent antimicrobial coatings can maintain the aesthetic appeal of surfaces and the functionality of a touch-screen while adding the benefit of reducing disease transmission. We fabricated an antimicrobial coating of silver oxide particles in a silicate matrix on glass. The matrix was grown by a modified Stöber sol-gel process with vapor-phase water and ammonia. A coating on glass with 2.4 mg of Ag2O per mm2 caused a reduction of 99.3% of SARS-CoV-2 and >99.5% of Pseudomonas aeruginosa, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus compared to the uncoated glass after 1 h. We envisage that screen protectors with transparent antimicrobial coatings will find particular application to communal touch-screens, such as in supermarkets and other check-out or check-in facilities where a number of individuals utilize the same touch-screen in a short interval.

Multiomic Profiling of Central Nervous System Leukemia Identifies mRNA Translation as a Therapeutic Target.

Central nervous system (CNS) dissemination of B-precursor acute lymphoblastic leukemia (B-ALL) has poor prognosis and remains a therapeutic challenge. Here we performed targeted DNA sequencing as well as transcriptional and proteomic profiling of paired leukemia-infiltrating cells in the bone marrow (BM) and CNS of xenografts. Genes governing mRNA translation were upregulated in CNS leukemia, and subclonal genetic profiling confirmed this in both BM-concordant and BM-discordant CNS mutational populations. CNS leukemia cells were exquisitely sensitive to the translation inhibitor omacetaxine mepesuccinate, which reduced xenograft leptomeningeal disease burden. Proteomics demonstrated greater abundance of secreted proteins in CNS-infiltrating cells, including complement component 3 (C3), and drug targeting of C3 influenced CNS disease in xenografts. CNS-infiltrating cells also exhibited selection for stemness traits and metabolic reprogramming. Overall, our study identifies targeting of mRNA translation as a potential therapeutic approach for B-ALL leptomeningeal disease. SIGNIFICANCE: Cancer metastases are often driven by distinct subclones with unique biological properties. Here we show that in B-ALL CNS disease, the leptomeningeal environment selects for cells with unique functional dependencies. Pharmacologic inhibition of mRNA translation signaling treats CNS disease and offers a new therapeutic approach for this condition.This article is highlighted in the In This Issue feature, p. 1.