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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.

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.

Contemporary orthodontics entails using advanced materials and devices, simplifying the process of tooth movement. It is well documented that orthodontic materials are subjected to various fluctuations and stresses in the oral environment, such as salivary pH, dietary habits, temperature changes, and masticatory loads. These changes reduce bonding materials' longevity, plasticize resin polymers, and reduce elastic properties. In addition, the corrosion of orthodontic appliances in the oral environment has concerned clinicians for some time. This is focused on two principal issues: whether corrosion products are absorbed into the body and cause either localized or systemic effects, and the results of corrosion on the physical properties and the clinical performance of orthodontic appliances. Recently, another major concern is the potential release of bisphenol-A from materials containing polymers such as thermoplastic aligners and resins, which is known to induce xenoestrogenicity and cytotoxicity when the tissue level exceeds the daily recommended intake. However, most of these findings are based on in vitro studies that suffer from serious drawbacks such as failure to replicate the exact oral environment and process during orthodontic treatment. Therefore, developing clinically relevant methods should be the goal of future research related to the aging of orthodontic materials. The purpose of this review is to outline the impact of the oral environment on contemporary orthodontic materials.

Bacterial citrate lyase activity has been demonstrated in various eukaryotes, bacteria and archaea, underscoring their importance in energy metabolism of the cell. While the bacterial citrate lyase comprises of three different subunits, genome lacks CitD and CitF subunits of citrate lyase complex but encodes for 2 homologs of CitE subunits, Rv2498c and Rv3075c. Using temperature sensitive mycobacteriophages, we were able to generate both single and double mutant strains of . The survival experiments revealed increased susceptibility of the double mutant strain to oxidative stress in comparison to the parental strain. Also, simultaneous deletion of both and in genome resulted in impairment of intracellular replication in macrophages. The double mutant strain displayed reduced growth in lungs and spleens of guinea pigs. This is the first study demonstrating that critically requires CitE subunits of citrate lyase for pathogenesis. Taken together, these findings position these enzymes as potential targets for development of anti-tubercular small molecules.