Rural Alaska children have high rates of hospitalization with lower respiratory tract infections from a variety of pathogens. Past studies of risk factors for respiratory syncytial virus infection associated medically high-risk status, household crowding, and infant feeding practices with hospitalization.

This study reveals the importance of medically high-risk status and infant feeding practices as important factors in respiratory hospitalization. In addition, we identified woodstove use and the absence of 2 or more sinks in household as risk factors for hospitalization. (Read the full article)

Respiratory infectious symptoms are common during the first year of life. Day care attendance, older siblings, and lack of breastfeeding have been considered as possible factors influencing early respiratory tract infections.

Children with early dog contacts seem to have fewer infectious respiratory symptoms and diseases, especially otitis, during the first year of life. (Read the full article)

The US Surgeon General has determined that the relationship between movie smoking exposure (MSE) and youth smoking is causal; however, it is not known whether movie rating influences how adolescents respond.

The response to PG-13–rated MSE was indistinguishable from R-rated MSE. An R rating for smoking could reduce smoking onset in the United States by 18% (by eliminating PG-13 MSE), an effect similar to making all parents maximally authoritative in their parenting. (Read the full article)

A dose-response relationship exists between light irradiance and decrease of total serum bilirubin concentration (TsB) at relatively low irradiances. It has been questioned whether by increasing irradiance a "saturation point" exists, above which no further decrease of TsB is seen.

We found a linear relation between light irradiance in the range of 20 to 55 μW/cm²/nm and decrease in TsB after 24 hours of therapy, with no evidence of a saturation point. (Read the full article)

A growing number of epidemiologic studies suggest that individuals with lower vitamin D levels are at higher risk of acute respiratory tract infection. Randomized controlled trials are needed to determine if vitamin D supplementation would decrease this risk.

In a randomized controlled trial of 247 Mongolian children with vitamin D deficiency in winter, with double-blinding and 99% follow-up, vitamin D supplementation significantly reduced the risk of acute respiratory tract infections. (Read the full article)

Neonatal respiratory distress syndrome is the most common respiratory cause of mortality and morbidity among US infants aged <1 year. Although neonatal respiratory distress syndrome is a heritable disorder, common genetic variants do not fully explain disease heritability.

Single ABCA3 mutations are overrepresented among term and late preterm (≥34 weeks’ gestation) European-descent infants with RDS. Although ABCA3 mutations are individually rare, they are collectively common in the European- and African-descent general population, present in ~4% of individuals. (Read the full article)

Accurately identifying ill hospitalized children with vital signs concerning for clinical deterioration is fundamental to inpatient pediatrics. Normal vital sign ranges for healthy children are useful for outpatient practice but have limited application to detecting deterioration in the hospital setting.

Percentile curves for heart and respiratory rate in hospitalized children were developed and validated. The distributions differed from existing reference ranges and early warning scores. They may be useful to identify vital signs deviating from ranges expected among hospitalized children. (Read the full article)

Acquired widespread pain syndromes of youth are prevalent, disabling, usually unexplained, and untreatable. Small-fiber polyneuropathy causes widespread pain and multisystem complaints in older adults. Some causes are treatable. Neurodiagnostic skin biopsy, autonomic function testing, and nerve biopsy permit objective diagnosis.

It identifies definite (in 59%) and probable (in 17%) small-fiber polyneuropathy among 41 young patients with otherwise-unexplained, childhood-onset widespread pain. It characterizes this new disease’s clinical features, diagnostic, and treatment options. Some cases appeared immune mediated and responded to immunomodulatory therapies. (Read the full article)

Heated, humidified high-flow nasal cannula (HHHFNC) is a noninvasive mode of respiratory support that is commonly used in the majority of US NICUs. No large randomized trial has evaluated safety or efficacy of HHHFNC.

This large randomized controlled trial suggests that HHHFNC is as effective as nCPAP for noninvasive respiratory support and can be safely applied to a wide range of neonates. (Read the full article)

Obesity is associated with cardiometabolic risk factors and chronic conditions, such as type 2 diabetes. However, a proportion of overweight and obese youth remain free from cardiometabolic risk factors and are considered metabolically healthy.

This study provides insight into the determinants of cardiometabolic risk factors and the concept in health promotion of "fitness versus fatness." Hepatic lipid accumulation and not fitness level appears to drive cardiometabolic risk factor clustering among overweight and obese youth. (Read the full article)

Respiratory syncytial virus (RSV) infection is a leading cause of hospitalization among infants. Most estimates of RSV hospitalization rates are imprecise, having been calculated by using retrospective discharge diagnosis data and stratified age groups no narrower than 6 to 12 months.

Prospective, population-based surveillance data for infants hospitalized with laboratory-confirmed RSV infection were combined with birth certificate information to yield more precise age-specific hospitalization rates. These data should help determine priorities for the use of existing and future RSV prophylaxis strategies. (Read the full article)

Respiratory support is commonly given to newborn infants via a face mask in the delivery room. Respiratory support given to preterm infants via a single nasal prong may be more effective.

Compared with a face mask, using a single nasal prong to deliver respiratory support to preterm newborns did not result in less intubation and ventilation in the delivery room. (Read the full article)

Preterm birth is associated with increased morbidity during childhood. Many studies have focused on outcomes for preterm births before 32 weeks’ gestation, but there are few follow-up data for late preterm infants (34–36 weeks’ gestation).

The risk of respiratory admission during childhood decreased with each successive week in gestation up to 40 to 42 weeks. The increased risk is small for late preterm infants, but the number affected is large and has an impact on health care services. (Read the full article)

Bacille Calmette-Guerin (BCG) vaccination may provide benefits beyond protecting against pediatric tuberculosis. Evidence suggests links between cell-mediated immunity from tuberculosis and bacterial/viral-related pneumonia but the impact of BCG on acute lower respiratory infection is not fully known.

BCG-vaccinated children had a lower risk of suspected acute lower respiratory infection. Protection was amplified when children were vaccinated against diphtheria-tetanus-pertussis (DTP). Number of DTP doses did not modify this effect, but order in which vaccines were received did. (Read the full article)

Quantitative real-time polymerase chain reaction allows sensitive detection of respiratory viruses. The clinical significance of detection of specific viruses is not fully understood, however, and several viruses have been detected in the respiratory tract of asymptomatic children.

Our results indicate that quantitative real-time polymerase chain reaction is limited at distinguishing acute infection from detection in asymptomatic children for rhinovirus, bocavirus, adenovirus, enterovirus, and coronavirus. (Read the full article)

Down syndrome is an independent risk factor for severe respiratory syncytial virus infection and subsequent hospitalization.

This observational study suggests that immunoprophylaxis may reduce respiratory syncytial virus-related hospitalization by 3.6-fold (95% confidence interval, 1.5–8.7) in children with Down syndrome overall. (Read the full article)

Inadequate nutrient intake can compromise a child’s nutritional status, which may affect immune function. Improving dietary intake via a follow-up formula may support appropriate immune responses and improve a child’s ability to resist infection.

Children who consumed an experimental follow-up formula had fewer episodes and shorter duration of acute respiratory infections, as well as less antibiotic treatment, and fewer days missed of day care due to illness. (Read the full article)

Caffeine has predictable effects on cardiovascular function in both adults and children. Our previous work has shown that there are gender differences in this cardiovascular response, with boys having a greater change in heart rate and blood pressure than girls.

This study shows that the gender differences in cardiovascular response to caffeine emerge after puberty and there are some differences in postpubertal girls across the menstrual cycle. (Read the full article)

Oral vaccine responses are low in children from less-developed countries perhaps as a result of intestinal dysbiosis. New high-throughput DNA-based methods allow characterization of intestinal microbiota as a predictor of vaccine responses.

High abundance of stool Actinobacteria, including Bifidobacterium, was associated with higher responses to oral and parenteral vaccines and a larger thymus in Bangladeshi infants. Conversely, high abundance of Clostridiales, Enterobacteriales, and Pseudomonadales was associated with neutrophilia and lower vaccine responses. (Read the full article)

Delaying cord clamping beyond 30 to 60 seconds after birth seems beneficial for all infants due to blood transfusion from placenta. Experimental data have demonstrated that ventilation implemented before cord clamping improved cardiovascular stability by increasing pulmonary blood flow.

Healthy self-breathing neonates in a low-resource setting are more likely to die if cord clamping occurs before or immediately after onset of spontaneous respirations. The risk of death/admission decreases by 20% for every 10-second delay in clamping after breathing. (Read the full article)

Lower respiratory tract infections (LRTIs), including pneumonia, are in the top 10 causes of death among children in the United States. In high-income countries, 3% to 14% of LRTI hospitalizations have been reported to require admission to an ICU.

During 2007–2011, approximately 31 289 hospitalizations for severe LRTI occurred in children each year in the United States. Children <1 year of age had the highest rates of severe LRTI and accounted for 30% of severe LRTI hospitalizations. (Read the full article)

Many pediatric acute respiratory tract infections (ARTI) are viral and do not require antimicrobial treatment. Recent estimates of antimicrobial overprescribing for these infections, defined based on the published bacterial disease prevalence among all ARTI, are not available.

Based on the published bacterial prevalence rates for pediatric ARTI, antimicrobial agents are prescribed almost twice as often as expected to outpatients nationally, amounting to an estimated 11.4 million potentially preventable antimicrobial prescriptions annually. (Read the full article)

Rhinoviruses are commonly detected in both acutely ill and asymptomatic infants and children. The finding may represent new infection or prolonged presence of rhinovirus RNA in the respiratory tract.

In young, otherwise healthy infants, shedding of RNA from the same rhinovirus strain rarely persisted longer than 30 days. (Read the full article)

Primary ciliary dyskinesia presents in infancy with unexplained neonatal respiratory distress, yet diagnosis is often delayed until late childhood. Earlier diagnosis facilitates earlier onset of therapy, which may help to reduce long-term pulmonary morbidity and mortality.

A diagnostic workup for primary ciliary dyskinesia should be considered in a term infant presenting with unexplained respiratory distress and either lobar collapse, situs inversus, or a prolonged oxygen therapy requirement (>2 days). (Read the full article)

Respiratory syncytial virus (RSV) infection is a common cause of pediatric hospitalizations. Mortality rates associated with RSV hospitalizations are based on estimates from studies conducted decades ago. Accurate understanding of mortality is required for identifying high-risk infants and children.

Mortality associated with RSV is uncommon in the 21st century, with annual deaths far lower than previous estimates. The majority of deaths occurred in infants with complex chronic conditions or in those with life-threatening conditions in addition to RSV infection. (Read the full article)

Some parents choose to "spread out" the recommended vaccine schedule for their child by decreasing the number of simultaneous vaccines or delaying certain vaccines until an older age. Epidemiologic studies demonstrate increasing numbers of parents are choosing to delay vaccines.

We demonstrate that almost all providers encounter requests to spread out vaccines in a typical month and, despite concerns, increasing numbers are agreeing to do so. Providers report many strategies in response to requests but think few are effective. (Read the full article)

Outbreaks of serogroup B meningococcal disease occur at universities and other organizations. Until October 2014, options for control of serogroup B outbreaks were limited by the absence of a licensed vaccine for serogroup B meningococcal disease in the United States.

We describe a serogroup B outbreak at a university in 2013 and the campaign with investigational serogroup B vaccine held in response. This was the first use of a serogroup B vaccine as an outbreak response in the United States. (Read the full article)

Neonatal coarctation of the aorta (CoA) is a life-threatening cardiac defect, but because symptoms may be lacking initially, newborns with this defect are frequently discharged from the hospital undiagnosed. Delayed diagnosis of CoA is associated with increased morbidity and mortality.

This population-based study analyzes the contribution of prenatal ultrasound and postnatal pulse oximetry screening to the timely diagnosis of neonatal CoA. Both screening methods had low sensitivity for CoA. Nearly half of all newborns with isolated CoA were discharged undiagnosed. (Read the full article)

Making a diagnosis of Kawasaki disease (KD) is often a diagnostic dilemma. This dilemma is confounded when children present with symptoms consistent with known, common respiratory viruses and/or with KD symptoms that could potentially be attributed to a respiratory virus.

Patients with KD commonly have a concurrent respiratory viral infection. Clinicians should not dismiss the diagnosis of KD based on the presence of respiratory symptoms. Furthermore, a positive respiratory virus test result should not be used to exclude the diagnosis of KD. (Read the full article)

Adding second-stage automated auditory brainstem response (ABR) testing for infants who failed the initial OAE test in a two-stage neonatal hearing screening has been shown to reduce false referrals to the hearing clinic.

Infants with hearing loss may be missed by a 2-stage hearing screening because they pass the automated ABR test. In our study, a significant number of infants with hearing loss >45 decibel hearing level passed screening with automated ABR. (Read the full article)

Makeda Brome, Pia Hansen, Linda Gojak, Marian Small, Kenneth Baum and David Krulwich share their thoughts on the biggest challenges facing math teachers.

Boys and girls start out on the same biological footing when it comes to math, finds the first neuroimaging study of math gender differences in children, published this month in the journal Science of Learning.

Boys and girls start out on the same biological footing when it comes to math, finds the first neuroimaging study of math gender differences in children, published this month in the journal Science of Learning.

Nationally, at least five million children have at least one parent who is undocumented. Supporting those children should be a priority if the threat of a raid is not imminent, advocates said.

For a moment, Wall Street seemed to be inching away from Saudi Arabia. Now, it’s already inching back.

Spain. Report on the individual review of the annual submission of Spain submitted in 2017. Note by the expert review team.

The attempt by Congo and Rwanda to end the deadly conflict in eastern Congo by a secret presidential deal and military force is failing and must be changed fundamentally by the Kinshasa government and the international community.

The United Nations Security Council decided on 10 April to deploy a peacekeeping mission in the Central African Republic (CAR) which will take over the mission of the African Union (MISCA), which itself succeeded the mission of the Economic Community of Central African States (MICOPAX).

Background: This study summarizes drug resistance analyses in 4 recent phase 2b trials of the respiratory syncytial virus (RSV) fusion inhibitor presatovir in naturally infected adults.

Methods: Adult hematopoietic cell transplant (HCT) recipients, lung transplant recipients, or hospitalized patients with naturally acquired, laboratory-confirmed RSV infection were enrolled in 4 randomized, double-blind, placebo-controlled studies with study-specific presatovir dosing. Full-length RSV F sequences amplified from nasal swabs obtained at baseline and postbaseline were analyzed by population sequencing. Substitutions at RSV fusion inhibitor resistance-associated positions are reported.

Results: Genotypic analyses were performed on 233 presatovir-treated and 149 placebo-treated subjects. RSV F variant V127A was present in 8 subjects at baseline. Population sequencing detected treatment-emergent substitutions in 10/89 (11.2%) HCT recipients with upper and 6/29 (20.7%) with lower respiratory tract infection, 1/35 (2.9%) lung transplant recipients, and 1/80 (1.3%) hospitalized patients treated with presatovir; placebo-treated subjects had no emergent resistance-associated substitutions. Subjects with substitutions at resistance-associated positions had smaller decreases in viral load during treatment relative to those without, but similar clinical outcomes.

Conclusions: Subject population type and dosing regimen may have influenced RSV resistance development during presatovir treatment. Subjects with vs without genotypic resistance development had decreased virologic responses but comparable clinical outcomes.

Periodontitis as a biofilm-associated inflammatory disease is highly prevalent worldwide. It severely affects oral health and yet closely links to systemic diseases like diabetes and cardiovascular disease. Porphyromonas gingivalis as a ‘keystone' periodontopathogen drives the shift of microbe-host symbiosis to dysbiosis, and critically contributes to the pathogenesis of periodontitis. Persisters are a tiny subset of biofilm-associated microbes highly tolerant to lethal treatment of antimicrobials, and notably metronidazole-tolerant P. gingivalis persisters have recently been identified by our group. This study further explored the interactive profiles of metronidazole-treated P. gingivalis persisters (M-PgPs) with human gingival epithelial cells (HGECs). P. gingivalis cells (ATCC 33277) at stationary phase were treated with lethal dosage of metronidazole (100 μg/ml, 6 hours) for generating M-PgPs. The interaction of M-PgPs with HGECs was assessed by microscopy, flow cytometry, cytokine profiling and qPCR. We demonstrated that the overall morphology and ultra-cellular structure of M-PgPs remained unchanged. Importantly, M-PgPs maintained the capabilities to adhere to and invade into HGECs. Moreover, M-PgPs significantly suppressed pro-inflammatory cytokine expression in HGECs at a comparable level with the untreated P. gingivalis cells, through the thermo-sensitive components. The present study reveals that P. gingivalis persisters induced by lethal treatment of antibiotics could maintain their capabilities to adhere to and invade into human gingival epithelial cells, and perturb the innate host responses. Novel strategies and approaches need to be developed for tackling P. gingivalis and favourably modulating the dysregulated immuno-inflammatory responses for oral/periodontal health and general wellbeing.

The Cpx stress response is widespread among Enterobacteriaceae. We have previously reported a mutation in cpxA in a multidrug resistant strain of Klebsiella aerogenes isolated from a patient treated with imipenem. This mutation yields to a single amino acid substitution (Y144N) located in the periplasmic sensor domain of CpxA. In this work, we sought to characterize this mutation in Escherichia coli by using genetic and biochemical approaches. Here, we show that cpxA^Y144N is an activated allele that confers resistance to β-lactams and aminoglycosides in a CpxR-dependent manner, by regulating the expression of the OmpF porin and the AcrD efflux pump, respectively. We also demonstrate the intimate interconnection between Cpx system and peptidoglycan integrity on the expression of an exogenous AmpC β-lactamase by using imipenem as a cell wall active antibiotic or inactivation of penicillin-binding proteins. Moreover, our data indicate that the Y144N substitution abrogates the interaction between CpxA and CpxP and increase phosphotransfer activity on CpxR. Because the addition of a strong AmpC inducer such as imipenem is known to causes abnormal accumulation of muropeptides (disaccharide-pentapeptide, N-acetylglucosamyl-1,6-anhydro-N-acetylmuramyl-l-alanyl-d-glutamy-meso-diaminopimelic-acid-d-alanyl-d-alanine) in the periplasmic space, we propose these molecules activate the Cpx system by displacing CpxP from the sensor domain of CpxA. Altogether, these data could explain why large perturbations to peptidoglycan caused by imipenem lead to mutational activation of the Cpx system and bacterial adaptation through multidrug resistance. These results also validate the Cpx system, in particular the interaction between CpxA and CpxP, as a promising therapeutic target.

Polymyxins are increasingly used as the critical last-resort therapeutic options for multidrug-resistant gram-negative bacteria. Unfortunately, polymyxin resistance has increased gradually for the last few years. Although studies on mechanisms of polymyxin are expanding, system-wide analyses of the underlying mechanism for polymyxin resistance and stress response are still lacking. To understand how Klebsiella pneumoniae adapt to colistin (polymyxin E) pressure, we carried out proteomic analysis of Klebsiella pneumoniae strain cultured with different concentrations of colistin. Our results showed that the proteomic responses to colistin treatment in Klebsiella pneumoniae involving several pathways, including (i) gluconeogenesis and TCA cycle; (ii) arginine biosynthesis; (iii) porphyrin and chlorophyll metabolism; and (iv) enterobactin biosynthesis. Interestingly, decreased abundance of class A β-lactamases including TEM, SHV-11, SHV-4 were observed in cells treated with colistin. Moreover, we also present comprehensive proteome atlases of paired polymyxin-susceptible and -resistant Klebsiella pneumoniae strains. The polymyxin-resistant strain Ci, a mutant of Klebsiella pneumoniae ATCC BAA 2146, showed missense mutation in crrB. The crrB mutant Ci, which displayed lipid A modification with 4-amino-4-deoxy-L-arabinose (L-Ara4N) and palmitoylation, showed striking increases of CrrAB, PmrAB, PhoPQ, ArnBCADT and PagP. We hypothesize that crrB mutations induce elevated expression of the arnBCADTEF operon and pagP via PmrAB and PhoPQ. Moreover, multidrug efflux pump KexD, which was induced by crrB mutation, also contributed to colistin resistance. Overall, our results demonstrated proteomic responses to colistin treatment and the mechanism of CrrB-mediate colistin resistance, which may further offer valuable information to manage polymyxin resistance.

Multidrug resistant strains belonging to the Enterobacter cloacae complex (ECC) group, and especially those belonging to clusters C-III, C-IV and C-VIII, have increasingly emerged as a leading cause of healthcare-associated infections, with colistin used as one of the last line of treatment. However, colistin-resistant ECC strains have emerged. The aim of this study was to prove that MgrB, the negative regulator of PhoP/PhoQ two-component regulatory system, is involved in colistin resistance in ECC of cluster C-VIII, formerly referred to as Enterobacter hormaechei subsp. steigerwaltii. An in vitro mutant (Eh22-Mut) was selected from a clinical isolate of Eh22. The sequencing analysis of its mgrB gene showed the presence of one nucleotide deletion leading to the formation of a truncated protein of six instead of 47 amino acids. Wild-type mgrB gene from Eh22, as well as that of a clinical strain of Klebsiella pneumoniae used as controls, were cloned and the corresponding recombinant plasmids were used for complementation assays. Results showed a fully restored susceptibility to colistin, and confirmed for the first time that mgrB gene expression plays a key role in acquired resistance to colistin in ECC strains.

Baloxavir marboxil, a prodrug of cap-dependent endonuclease inhibitor, baloxavir acid, reduces the time to improvement of influenza symptoms in patients infected with type A or B influenza virus. To characterize its pharmacokinetics, a population pharmacokinetic model for baloxavir acid was developed using 11846 plasma concentration data items from 1827 subjects including 2341 plasma concentration data items from 664 patients at high risk of influenza complications. A three-compartment model with first-order elimination and first-order absorption with lag time well described the plasma concentration data. Body weight and race were found to be the most important factors influencing clearance and volume of distribution. The exposures in high-risk patients were similar to those in otherwise healthy patients, and no pharmacokinetic difference was identified regarding any risk factors for influenza complications.

Exposure-response analyses were performed regarding the time to improvement of symptoms and the reduction in the influenza virus titer in high-risk patients. The analyses suggested that body weight-based dosage, 40 mg for patients weighing < 80 kg and 80 mg for patients weighing ≥ 80 kg, can shorten the time to improvement of influenza symptoms and reduce virus titer for both type A and B influenza virus regardless of the exposure levels of the high-risk patients as well as for the otherwise healthy influenza patients.

The results of our population pharmacokinetic and exposure-response analyses in patients with risk factors of influenza complications should provide useful information on the pharmacokinetic and pharmacodynamic characteristics of baloxavir marboxil and also for the optimization of dose regimens.

The rand strengthened against the greenback as it peaked at a session high of R18.30 before it was recorded trading 1.41% firmer at R18.32/$ at 17.00

Funders have been both fast and thoughtful about how to work with national and local partners to listen to needs from the field, identify best practices, and deploy resources quickly, says Celine Coggins.

"This pandemic has given us an opportunity to think boldly about students' educational needs and how to creatively respond to them," says Katherine Haley.

Rosario, Argentina :: Church members from a vulnerable community learn about human trafficking and experience care and respect.