Parents\u27 Perception of their Children\u27s Asthma, 2002-2008: A Community-Based Study

Childhood asthma is a chronic health condition that is one of the leading causes of hospitalizations and missed school days for children. It also affects the lives of both asthmatic children and their families

2020 Year in Review: Pharmacologic Treatments for COVID-19

COVID-19, caused by SARS-CoV-2 infection, has led to a pandemic of acute respiratory illness. Pharmacologic treatments for COVID-19 have included treatments targeting infection prevention, prevention of viral replication, reducing inflammation and managing symptoms of respiratory failure caused by the disease. This is a review of key pharmacologic treatments for COVID-19 based on peer-reviewed articles from 2020

Molecular Determinants and Dynamics of Hepatitis C Virus Secretion

The current model of hepatitis C virus (HCV) production involves the assembly of virions on or near the surface of lipid droplets, envelopment at the ER in association with components of VLDL synthesis, and egress via the secretory pathway. However, the cellular requirements for and a mechanistic understanding of HCV secretion are incomplete at best. We combined an RNA interference (RNAi) analysis of host factors for infectious HCV secretion with the development of live cell imaging of HCV core trafficking to gain a detailed understanding of HCV egress. RNAi studies identified multiple components of the secretory pathway, including ER to Golgi trafficking, lipid and protein kinases that regulate budding from the trans-Golgi network (TGN), VAMP1 vesicles and adaptor proteins, and the recycling endosome. Our results support a model wherein HCV is infectious upon envelopment at the ER and exits the cell via the secretory pathway. We next constructed infectious HCV with a tetracysteine (TC) tag insertion in core (TC-core) to monitor the dynamics of HCV core trafficking in association with its cellular cofactors. In order to isolate core protein movements associated with infectious HCV secretion, only trafficking events that required the essential HCV assembly factor NS2 were quantified. TC-core traffics to the cell periphery along microtubules and this movement can be inhibited by nocodazole. Sub-populations of TC-core localize to the Golgi and co-traffic with components of the recycling endosome. Silencing of the recycling endosome component Rab11a results in the accumulation of HCV core at the Golgi. The majority of dynamic core traffics in association with apolipoprotein E (ApoE) and VAMP1 vesicles. This study identifies many new host cofactors of HCV egress, while presenting dynamic studies of HCV core trafficking in infected cells.</p

The role of submicroscopic parasitemia in malaria transmission: what is the evidence?

Achieving malaria elimination requires targeting the human reservoir of infection, including those with asymptomatic infection. Smear-positive asymptomatic infections detectable by microscopy are an important reservoir because they often persist for months and harbor gametocytes, the parasite stage infectious to mosquitoes. However, many asymptomatic infections are submicroscopic and can only be detected by molecular methods. While there is some evidence that persons with submicroscopic malaria can infect mosquitoes, transmission is much less likely to occur at submicroscopic gametocyte levels. As malaria elimination programs pursue mass screening and treatment of asymptomatic individuals, further research should strive to define the degree to which submicroscopic malaria contributes to the infectious reservoir, and in turn, what diagnostic detection threshold is needed to effectively interrupt transmission

Reply to Gonçalves et al

TO THE EDITOR—We agree with Goncalves et al that our study was restricted to treat-ment-seeking persons with symptomatic falciparum malaria. As such, the study did not assess the relative infectiousness of what may well be a larger, asymptom-atic, and often submicroscopic malaria transmission reservoir. The absence of studies on the infectiousness of asym-ptomatic persons with submicroscopic malariainlow-transmissionsettings yields little evidence for or against tar-geting these populations as a strategy to accelerate malaria elimination; indeed, further evaluation is warranted

Longitudinal Pooled Deep Sequencing of the Plasmodium vivax K12 Kelch Gene in Cambodia Reveals a Lack of Selection by Artemisinin

The emergence of artemisinin resistance among Plasmodium falciparum in the Greater Mekong subregion threatens malaria control interventions and is associated with multiple unique mutations in K13 (PF3D7_1343700). The aim of this study was to survey Cambodian Plasmodium vivax for mutations in the K13 ortholog (K12, PVX_083080) that might similarly confer artemisinin resistance. Extracted DNA from Cambodian isolates collected between 2009 and 2012 was pooled by province and year and submitted for next-generation sequencing. Single-nucleotide polymorphisms (SNPs) were identified using a pile-up approach that detected minority SNPs. Among the 14 pools, we found six unique SNPs, including three nonsynonymous SNPs, across six codons in K12. However, none of the SNPs were orthologous to artemisinin resistance–conferring mutations in PF3D7_1343700, and nonsynonymous changes did not persist through time within populations. These results suggest a lack of selection in the P. vivax population in Cambodia due to artemisinin drug pressure

Pediatric pulmonology year in review 2020: Physiology

Pulmonary physiology is a core element of pediatric pulmonology care and research. This article reviews some of the notable publications in physiology that were published in Pediatric Pulmonology in 2020

Weight management for individuals with intellectual and developmental disabilities: Rationale and design for an 18 month randomized trial

Weight management for individuals with intellectual and developmental disabilities (IDD) has received limited attention. Studies on weight management in this population have been conducted over short time frames, in small samples with inadequate statistical power, infrequently used a randomized design, and have not evaluated the use of emerging effective dietary strategies such as pre-packaged meals (PMs). Low energy/fat PMs may be useful in individuals with IDD as they simplify meal planning, limit undesirable food choices, teach appropriate portion sizes, are convenient and easy to prepare, and when combined with fruits and vegetables provide a high volume, low energy dense meal. A randomized effectiveness trial will be conducted in 150 overweight/obese adults with mild to moderate IDD, and their study partners to compare weight loss (6 months) and weight maintenance (12 months) between 2 weight management approaches: 1. A Stop Light Diet enhanced with reduced energy/fat PMs (eSLD); and 2. A recommended care reduced energy/fat meal plan diet (RC). The primary aim is to compare weight loss (0–6 months) and weight maintenance (7–18 months) between the eSLD and RC diets. Secondarily, changes in chronic disease risk factors between the eSLD and RC diets including blood pressure, glucose, insulin, LDL-cholesterol, and HDL-cholesterol will be compared during both weight loss and weight maintenance. Finally, potential mediators of weight loss including energy intake, physical activity, data recording, adherence to the diet, study partner self-efficacy and daily stress related to dietary change will be explored

Spitzer view on the evolution of star-forming galaxies from z=0 to z~3

We use a 24 micron selected sample containing more than 8,000 sources to study the evolution of star-forming galaxies in the redshift range from z=0 to z~3. We obtain photometric redshifts for most of the sources in our survey using a method based on empirically-built templates spanning from ultraviolet to mid-infrared wavelengths. The accuracy of these redshifts is better than 10% for 80% of the sample. The derived redshift distribution of the sources detected by our survey peaks at around z=0.6-1.0 (the location of the peak being affected by cosmic variance), and decays monotonically from z~1 to z~3. We have fitted infrared luminosity functions in several redshift bins in the range 0<z<~3. Our results constrain the density and/or luminosity evolution of infrared-bright star-forming galaxies. The typical infrared luminosity (L*) decreases by an order of magnitude from z~2 to the present. The cosmic star formation rate (SFR) density goes as (1+z)^{4.0\pm0.2} from z=0 to z=0.8. From z=0.8 to z~1.2, the SFR density continues rising with a smaller slope. At 1.2<z<3, the cosmic SFR density remains roughly constant. The SFR density is dominated at low redshift (z<0.5) by galaxies which are not very luminous in the infrared (L_TIR<1.e11 L_sun, where L_TIR is the total infrared luminosity, integrated from 8 to 1000 micron). The contribution from luminous and ultraluminous infrared galaxies (L_TIR>1.e11 L_sun) to the total SFR density increases steadily from z~0 up to z~2.5, forming at least half of the newly-born stars by z~1.5. Ultraluminous infrared galaxies (L_TIR>1.e12 L_sun) play a rapidly increasing role for z>~1.3.Comment: 28 pages, 17 figures, accepted for publication in Ap

Sociodemographic characteristics and longitudinal progression of multimorbidity:A multistate modelling analysis of a large primary care records dataset in England

BackgroundMultimorbidity, characterised by the coexistence of multiple chronic conditions in an individual, is a rising public health concern. While much of the existing research has focused on cross-sectional patterns of multimorbidity, there remains a need to better understand the longitudinal accumulation of diseases. This includes examining the associations between important sociodemographic characteristics and the rate of progression of chronic conditions.Methods and findingsWe utilised electronic primary care records from 13.48 million participants in England, drawn from the Clinical Practice Research Datalink (CPRD Aurum), spanning from 2005 to 2020 with a median follow-up of 4.71 years (IQR: 1.78, 11.28). The study focused on 5 important chronic conditions: cardiovascular disease (CVD), type 2 diabetes (T2D), chronic kidney disease (CKD), heart failure (HF), and mental health (MH) conditions. Key sociodemographic characteristics considered include ethnicity, social and material deprivation, gender, and age. We employed a flexible spline-based parametric multistate model to investigate the associations between these sociodemographic characteristics and the rate of different disease transitions throughout multimorbidity development. Our findings reveal distinct association patterns across different disease transition types. Deprivation, gender, and age generally demonstrated stronger associations with disease diagnosis compared to ethnic group differences. Notably, the impact of these factors tended to attenuate with an increase in the number of preexisting conditions, especially for deprivation, gender, and age. For example, the hazard ratio (HR) (95% CI; p-value) for the association of deprivation with T2D diagnosis (comparing the most deprived quintile to the least deprived) is 1.76 ([1.74, 1.78]; p ConclusionsOur results indicate that early phases of multimorbidity development could warrant increased attention. The potential importance of earlier detection and intervention of chronic conditions is underscored, particularly for MH conditions and higher-risk populations. These insights may have important implications for the management of multimorbidity