Explore the vast range of titles available.

Children and adolescents account for ~ 13% of total COVID-19 cases in the United States. However, little is known about the nature of the illness in children. The reopening of schools underlines the importance of understanding the epidemiology of pediatric COVID-19 infections. We sought to assess the clinical characteristics and outcomes in pediatric COVID-19 patients. We conducted a retrospective cross-sectional analysis of pediatric patients diagnosed with COVID-19 from healthcare organizations in the United States. The study outcomes (hospitalization, mechanical ventilation, critical care) were assessed using logistic regression. The subgroups of sex and race were compared after propensity score matching. Among 12,306 children with lab-confirmed COVID-19, 16.5% presented with respiratory symptoms (cough, dyspnea), 13.9% had gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain), 8.1% had dermatological symptoms (rash), 4.8% had neurological (headache), and 18.8% had other non-specific symptoms (fever, malaise, myalgia, arthralgia and disturbances of smell or taste). In the study cohort, the hospitalization frequency was 5.3%, with 17.6% needing critical care services and 4.1% requiring mechanical ventilation. Following propensity score matching, the risk of all outcomes was similar between males and females. Following propensity score matching, the risk of hospitalization was greater in non-Hispanic Black (RR 1.97 [95% CI 1.49–2.61]) and Hispanic children (RR 1.31 [95% CI 1.03–1.78]) compared with non-Hispanic Whites. In the pediatric population infected with COVID-19, a substantial proportion were hospitalized due to the illness and developed adverse clinical outcomes.

The melting process of two-dimensional (2D) Yukawa crystals for dusty plasma medium induced by external perturbations has been explored using molecular dynamics simulations. A 2D monolayer of particles interacting via Yukawa pair potential is formed in the presence of an external confinement potential. The confinement potential is a combined effect of the gravitational force and an externally applied electric force, which mimics the sheath electric field in dusty plasma experiments. The response of the 2D crystalline layer to an external perturbation is investigated. It is shown that transverse surface waves are generated below a particular threshold value of initial perturbation, but the crystalline order remains. However, above a threshold value of initial disturbance, the crystalline order structure of the 2D layer breaks, and it melts. The melting process is shown to be a first-order phase transition. We have demonstrated that the nonlinear amplitude modulation of initial disturbance through the parametric decay instability is responsible for the melting. Our proposed mechanism of first-order phase transition in the context of 2D dusty plasma crystal is distinctly different from the existing theoretical models. This research can provide a deeper understanding of the experimental observations in the context of plasma crystal.

Toxin–antitoxin (TA) systems are highly conserved in members of the Mycobacterium tuberculosis (Mtb) complex and have been proposed to play an important role in physiology and virulence. Nine of these TA systems belong to the mazEF family, encoding the intracellular MazF toxin and its antitoxin, MazE. By overexpressing each of the nine putative MazF homologues in Mycobacterium bovis BCG, here we show that Rv1102c (MazF3), Rv1991c (MazF6) and Rv2801c (MazF9) induce bacteriostasis. The construction of various single-, double- and triple-mutant Mtb strains reveals that these MazF ribonucleases contribute synergistically to the ability of Mtb to adapt to conditions such as oxidative stress, nutrient depletion and drug exposure. Moreover, guinea pigs infected with the triple-mutant strain exhibits significantly reduced bacterial loads and pathological damage in infected tissues in comparison with parental strain-infected guinea pigs. The present study highlights the importance of MazF ribonucleases in Mtb stress adaptation, drug tolerance and virulence. Mycobacterium tuberculosis possesses several toxin–antitoxin systems of the MazEF family. Here, Tiwari et al . show that these systems contribute to stress adaptation, antibiotic tolerance and virulence.

Transthyretin is a transport protein whose misfolding has been implicated in the development of cardiac amyloidosis. Here, we examine the clinical correlates of transthyretin levels, the differences in transthyretin levels according to the pathogenic V142I TTR variant carrier status, and the association of transthyretin levels with outcomes among 35,206 UK Biobank participants who underwent plasma profiling and were free from prevalent cardiovascular disease and chronic renal disease. Transthyretin levels are lower in females, decrease with increasing C-reactive protein levels, and increase with body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, albumin levels, triglyceride levels, and creatinine levels. V142I non-carriers [n = 35,167, mean: −0.1 (0.3)] have higher adjusted transthyretin levels compared with the carriers [n = 39, mean: −0.5 (0.3)] (p:<0.001). A standard deviation decrease in transthyretin levels increases the risk of heart failure [HR adj : 1.17 (95% Confidence Interval = 1.08–1.26)] and all-cause mortality [HR adj : 1.18 (95% Confidence Interval = 1.14–1.24)]. This study shows that individuals with low transthyretin levels, such as those carrying the V142I variant, are at a higher risk of heart failure and mortality. Though the role of transthyretin (TTR) in the development of cardiac amyloidosis has been recognized, the determinants of TTR levels remain unexplored. Here, the authors present the clinical correlates of transthyretin levels and show that reduced TTR levels are associated with an increase risk of cardiovascular disease and mortality.

Black individuals have lower plasma natriuretic peptide (NP) concentrations than white individuals. However, race-based differences in the NP response to physiological perturbations are unknown. In this physiological trial (NCT#03070184), we measured the NP [mid-regional atrial NP (MR-proANP), N-terminal pro-B-type NP (NT-proBNP), and BNP] response to physiological perturbations among healthy, self-identified Black and white participants aged 18-40 years. The primary and secondary outcomes were the change in plasma NP concentrations at 6 weeks after metoprolol (initiated at 50 mg/day and doubled every 2 weeks) and standardized, aerobic exercise (70% of their maximal oxygen uptake on a salt-standardized background), respectively. Among 40 Black [median age: 27 (22, 32) years; 21 (52.5%) women] and 40 white [median age: 25 (20, 30) years; 19 (47.5%) women] participants, exercise increased MR-proANP (Black: 35%; white: 43%), NT-proBNP (Black: 11%; white: 23%), and BNP (Black: 59%; white: 61%) in both self-reported races. Exercise was associated with an increase in plasma MR-proANP (p interaction : 0.25) and BNP (p interaction : 0.87) concentrations which did not vary by self-reported race. However, the increase in plasma NT-proBNP concentrations were higher in white participants than in Black participants. (p interaction : 0.04) Similarly, metoprolol therapy increased MR-proANP (Black: 18%; white: 16%), NT-proBNP (Black: 95%; white: 99%), and BNP (Black: 45%; white: 74%) in both self-reported races. The metoprolol-associated increase in plasma MR-proANP (p interaction : 0.85), NT-proBNP (p interaction : 0.94), and BNP (p interaction : 0.21) concentrations were similar by self-reported race. In conclusion, the higher increase in plasma NT-proBNP concentrationsamong white patients after exercise suggests that exercise may induce significant physiological variations in NP levels. ClinicalTrials.gov ID: NCT03070184. Although Black individuals have been shown to have lower natriuretic peptide concentrations compared to white individuals, the differences in the NP response to physiological perturbations in these two groups are unknown. Here, the authors conduct a physiological clinical trial among young, healthy, normotensive adults to show that white individuals may have a higher increase in NP concentrations compared to Black participants in response to physiological perturbations such as exercise.

Acute myocardial infarction is one of the leading causes of cardiovascular disease mortality in both men and women. Chest pain, which is often described as chest pressure, tightness, or a squeezing sensation, is the most frequent symptom in patients presenting with acute myocardial infarction. Although the diagnosis of acute myocardial infarction is often based on typical changes on a surface electrocardiogram and on changes in cardiac biomarkers, there is a need to better recognize and understand the impact of sex on symptoms among patients presenting with acute coronary syndrome or acute myocardial infarction. We briefly review the pathophysiology of ischemic symptoms, discuss potential mechanisms for variation in ischemic symptoms by sex, and summarize recent publications that have addressed sex differences in ischemic symptoms.

Inorganic polyphosphate (PolyP) plays an essential role in microbial stress adaptation, virulence and drug tolerance. The genome of Mycobacterium tuberculosis encodes for two polyphosphate kinases (PPK-1, Rv2984 and PPK-2, Rv3232c) and polyphosphatases ( ppx-1 , Rv0496 and ppx-2 , Rv1026) for maintenance of intracellular PolyP levels. Microbial polyphosphate kinases constitute a molecular mechanism, whereby microorganisms utilize PolyP as phosphate donor for synthesis of ATP. In the present study we have constructed ppk-2 mutant strain of M. tuberculosis and demonstrate that PPK-2 enzyme contributes to its ability to cause disease in guinea pigs. We observed that ppk-2 mutant strain infected guinea pigs had significantly reduced bacterial loads and tissue pathology in comparison to wild type infected guinea pigs at later stages of infection. We also report that in comparison to the wild type strain, ppk-2 mutant strain was more tolerant to isoniazid and impaired for survival in THP-1 macrophages. In the present study we have standardized a luciferase based assay system to identify chemical scaffolds that are non-cytotoxic and inhibit M. tuberculosis PPK-2 enzyme. To the best of our knowledge this is the first study demonstrating feasibility of high throughput screening to obtain small molecule PPK-2 inhibitors.

The need for novel vaccination strategies to control tuberculosis (TB) is underscored by the limited and variable efficacy of the currently licensed vaccine, Bacille Calmette-Guerin (BCG). SigH is critical for Mycobacterium tuberculosis (Mtb) to mitigate oxidative stress, and in its absence Mtb is unable to scavenge host oxidative/nitrosative bursts. The MtbΔsigH ( ΔsigH ) isogenic mutant induces signatures of the innate immunity in macrophages and protects rhesus macaques from a lethal Mtb challenge . To understand the immune mechanisms of protection via mucosal vaccination with ΔsigH , we employed the resistant cynomolgus macaque model; and our results show that ΔsigH vaccination significantly protects against lethal Mtb challenge in this species. ΔsigH -vaccinated macaques are devoid of granulomas and instead generate inducible bronchus associated lymphoid structures, and robust antigen-specific CD4 + and CD8 + T cell responses, driven by a hyper-immune, trained immunity-like phenotype in host macrophages with enhanced antigen presentation. Correlates of protection in ΔsigH -vaccinated macaques include gene signatures of T cell activation, IFNG production, including IFN-responsive, activated T cells, concomitant with IFNG production, and suppression of IDO + Type I IFN-responsive macrophage recruitment. Thus, ΔsigH is a promising lead candidate for further development as an antitubercular vaccine. Authors employ a cynomolgus macaque model to explore the protective potential of mucosal vaccination with Mycobacterium tuberculosis ΔsigH.

Cardiovascular disease is a leading cause of death among cancer survivors. While the field of cardiology as a whole is driven by evidence generated through robust clinical trials, data in cardio-oncology is limited to a relatively small number of prospective clinical trials with heterogeneous groups of cancer patients. In addition, many pharmaceutical trials in oncology are flawed from a cardiovascular perspective because they exclude patients with significant cardiovascular (CV) history and have wide variation in the definitions of CV events and cardiotoxicity. Ultimately, oncology trials often underrepresent the possibility of cardiovascular events in a “real world” population. Thus, the signal for CV toxicity from a cancer treatment is often not manifested until phase IV studies; where we are often caught trying to mitigate the CV effects rather than preventing them. Most of the data about cardiotoxicity from cancer therapy and cardioprotective strategies has been developed from our experience in using anthracyclines for over 50 years with dramatic improvement in cancer survivorship. However, as we are in an era where cancer drug discovery is moving at lightning pace with increasing survival rates, it is imperative to move beyond anthracyclines and commit to research on the cardiovascular side effects of all aspects of cancer therapy with a focus on prevention. We emphasize the role of pre-cancer treatment CV assessment to anticipate cardiac issues and ultimately optimizing CV risk prior to cancer therapy as an opportunity to mitigate cardiovascular risk from cancer therapy.