Multispecies bacterial invasion of human host cells.

Urinary tract infection (UTI), one of the most common bacterial infections worldwide, is a typical example of an infection that is often polymicrobial in nature. While the overall infection course is known on a macroscale, bacterial behavior is not fully understood at the cellular level and bacterial pathophysiology during multispecies infection is not well characterized. Here, using clinically relevant bacteria, human epithelial bladder cells and human urine, we establish co-infection models combined with high resolution imaging to compare single- and multi-species bladder cell invasion events in three common uropathogens: uropathogenic Escherichia coli (UPEC), Klebsiella pneumoniae and Enterococcus faecalis. While all three species invaded the bladder cells, under flow conditions the Gram-positive E. faecalis was significantly less invasive compared to the Gram-negative UPEC and K. pneumoniae. When introduced simultaneously during an infection experiment, all three bacterial species sometimes invaded the same bladder cell, at differing frequencies suggesting complex interactions between bacterial species and bladder cells. Inside host cells, we observed encasement of E. faecalis colonies specifically by UPEC. During subsequent dispersal from the host cells, only the Gram-negative bacteria underwent infection-related filamentation (IRF). Taken together, our data suggest that bacterial multispecies invasions of single bladder cells are frequent and support earlier studies showing intraspecies cooperation on a biochemical level during UTI.

Comparing Walker's (2008) skull trait sex estimation standard to proteomic sex estimation for a group of South Asian individuals.

This research assesses the potential for misidentification of sex in individuals of South Asian ancestry using the Walker (2008) morphological skull sex estimation standard [1]. Chromosomal sex was assessed using proteomic analysis targeting sex chromosome-specific amylogenic peptides. Results showed that the Walker method produced incorrect classification for 36.7 % of individuals. Overwhelmingly, those incorrectly assigned were chromosomally male. Misidentification was due to males within the group having lower trait scores (i.e., more gracile traits) than the standard would predict. There was also a high level of overlap in trait scores between male and females indicating reduced expression of sexual dimorphism. The use of established multivariate statistical techniques improved accuracy of sex estimation in some cases, but larger osteological data sets from South Asian individuals are required to develop population-specific standards. We suggest that peptide analysis may provide a useful tool for the forensic anthropologist when assessing sex in populations without population specific osteological standards.

A Comparison of Sound Production Treatment and Metrical Pacing Therapy for Apraxia of Speech: A Single-Case Experimental Design.

PURPOSE: The purpose of this investigation was to compare the effects of two specific treatment protocols for acquired apraxia of speech (AOS): Sound Production Treatment (SPT) and Metrical Pacing Therapy (MPT), and to examine changes in communicative participation. METHOD: Four speakers with chronic AOS and aphasia were each administered SPT and MPT in a replicated crossover design (ABACA/ACABA) with nonconcurrent multiple baselines across participants and behaviors. Treatment outcomes were compared with respect to whole word correctness (WWC) for treated and untreated multisyllabic word targets. Speech intelligibility was assessed using the Chapel Hill Multilingual Intelligibility Test, and communicative participation was measured using the Communicative Participation Item Bank at baseline, washout, and follow-up phases. RESULTS: Three of the four participants experienced statistically significant improvements in WWC with SPT, and three of the four participants with MPT. Based on a priori criteria, three participants demonstrated relatively greater benefit from SPT and one participant demonstrated relatively greater benefit from MPT. There were measurable improvements in intelligibility following SPT for three of the four participants. Only one participant in this investigation reported a significant change in communicative participation, and only following MPT. CONCLUSIONS: This study demonstrated that individuals in the chronic stages of AOS can benefit from both SPT and MPT, corroborating prior research on articulatory kinematic and rate and/or rhythm control treatment approaches. It contributes a comparison of two protocols for AOS with respect to whole word targets, intelligibility, and individual self-report of communicative participation changes. More participants showed a relative advantage of SPT over MPT. One individual reported communicative participation improvement after MPT. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.23971929.

Somatic mutations in facial skin from countries of contrasting skin cancer risk.

The incidence of keratinocyte cancer (basal cell and squamous cell carcinomas of the skin) is 17-fold lower in Singapore than the UK1-3, despite Singapore receiving 2-3 times more ultraviolet (UV) radiation4,5. Aging skin contains somatic mutant clones from which such cancers develop6,7. We hypothesized that differences in keratinocyte cancer incidence may be reflected in the normal skin mutational landscape. Here we show that, compared to Singapore, aging facial skin from populations in the UK has a fourfold greater mutational burden, a predominant UV mutational signature, increased copy number aberrations and increased mutant TP53 selection. These features are shared by keratinocyte cancers from high-incidence and low-incidence populations8-13. In Singaporean skin, most mutations result from cell-intrinsic processes; mutant NOTCH1 and NOTCH2 are more strongly selected than in the UK. Aging skin in a high-incidence country has multiple features convergent with cancer that are not found in a low-risk country. These differences may reflect germline variation in UV-protective genes.

For children admitted to hospital, what interventions improve medication safety on ward rounds? A systematic review.

OBJECTIVE: Every year, medication errors harm children in hospitals. Ward rounds are a unique opportunity to bring information together and plan management. There is a need to understand what strategies can improve medication safety on ward rounds. We systematically reviewed published interventions to improve prescribing and safety of medicines on ward rounds. DESIGN: Systematic review of randomised controlled trials and observational studies. SETTING: Studies examining inpatient ward rounds. PATIENTS: Children and young people aged between 0 and 18 years old. INTERVENTIONS: Any intervention or combination of interventions implemented that alters how paediatric ward rounds review inpatient medications. MAIN OUTCOME MEASURE: Primary outcome was improvement in medication safety on paediatric ward rounds. This included reduction in prescribing error rates, healthcare professionals' opinions on prescribing and improvement in documentation on ward rounds. RESULTS: Three studies were eligible for review. One examined the use of an acrostic, one the use of a checklist, and the other a use of a specific prescribing ward round involving a clinical pharmacist and doctor. None of the papers considered weight-based errors or demonstrated reductions in clinical harm. Reductions in prescribing errors were noted by the different interventions. CONCLUSIONS: There are limited data on interventions to improve medication safety in paediatric ward rounds, with all published data being small scale, either quality improvement or audits, and locally derived/delivered. Good-quality interventional or robust quality improvement studies are required to improve medication safety on ward rounds. PROSPERO REGISTRATION NUMBER: CRD42022340201.

Impact of indoor environment on children's pulmonary health.

INTRODUCTION: A child's living environment has a significant impact on their respiratory health, with exposure to poor indoor air quality (IAQ) contributing to potentially lifelong respiratory morbidity. These effects occur throughout childhood, from the antenatal period through to adolescence. Children are particularly susceptible to the effects of environmental insults, and children living in socioeconomic deprivation globally are more likely to breathe air both indoors and outdoors, which poses an acute and long-term risk to their health. Adult respiratory health is, at least in part, determined by exposures and respiratory system development in childhood, starting in utero. AREAS COVERED: This narrative review will discuss, from a global perspective, what contributes to poor IAQ in the child's home and school environment and the impact that indoor air pollution exposure has on respiratory health throughout the different stages of childhood. EXPERT OPINION: All children have the right to a living and educational environment without the threat of pollution affecting their health. Action is needed at multiple levels to address this pressing issue to improve lifelong respiratory health. Such action should incorporate a child's rights-based approach, empowering children, and their families, to have access to clean air to breathe in their living environment.

Deprescribing montelukast in children with asthma: a systematic review.

BACKGROUND: National and international asthma guidelines recommend adjusting asthma treatment based on levels of control, yet no guidance is given regarding the stepping-down of montelukast in children and young people (CYP). OBJECTIVE: To systematically review evidence regarding deprescribing montelukast in CYP with established asthma. DESIGN: Systematic review. DATA SOURCES: Embase, Medline, PubMed and CINAHL were searched up to October 2020. STUDY SELECTION: Eligible studies contained patients aged 0-18 years with a diagnosis of asthma, who had been administering montelukast before it was withdrawn. All reasons for withdrawal were included. RESULTS: The search identified 197 papers. After deduplication, five papers were included (three randomised control studies and two cohort studies). Four studies observed the impact of montelukast withdrawal for 2 weeks, and one study for 8 weeks. The impact of withdrawal was measured in the studies using a combination of lung tests (eg, forced expiratory volume in 1 s (FEV1), fractional exhaled nitric oxide (FeNO)), asthma scoring methods and exercise challenges. Of the 17 domains in the Core Outcome Set for Clinical Trials in Childhood Asthma, eight outcomes were measured in at least one of the five studies, with all five studies measuring the outcome of 'Lung Function'. No significant differences were found between the montelukast and placebo groups following montelukast withdrawal. Significant differences between the comparator points within the test group were found in nine outcomes across four studies; FEV1/forced vital capacity, FEV1, forced expiratory flows (25%-75%), asthma score (study specific), maximum % fall in FEV1 and time to recovery (post exercise) significantly decreased whereas FEV1/bronchodilator response, FeNO and eNO significantly increased. CONCLUSION: Only limited, contradictory and short-term effects of deprescribing montelukast in CYP with established asthma are presented in literature. Definitive studies determining clinical stability, and impact of deprescribing montelukast in CYP are imperative to improve the safety of asthma treatment in CYP. PROSPERO REGISTRATION NUMBER: CRD42020213971.

Pharmacogenomics and asthma treatment: acceptability to children, families and healthcare professionals.

BACKGROUND: Evidence supporting personalised treatment for asthma based on an individual's genetics is mounting. The views of children and young people (CYP), parents and healthcare professionals (HCPs) about this evolution of clinical care are not known. METHODS: A pilot prospective questionnaire-based study was undertaken of CYP with asthma, their parents and HCPs at a secondary/tertiary children's hospital in the UK. RESULTS: Fifty-nine questionnaires were distributed and 50 returned (response rate 84.7%), comprising 26 CYP (10 were 5-11 years, 11 were 12-15 years and 5 were 16-18 years old), 13 parents and 11 HCPs. For all types of data, personal information was ranked as the 'most important' (n=19, 47.5%) and 'most private' (n=16, 40%), but with considerable variation across groups. Within health data, allergies were rated as 'most important' (n=12, 30.8%), and mental health records the 'most private' (n=21, 53.8%), again with variation across groups. A 'personalised genetic asthma plan' was acceptable to the majority overall (n=40, 80.0%). With regard to sharing CYP's genetic data, 23 (46%) of participants were happy for unconditional sharing between HCPs, and 23 (46%) agreed to sharing solely in relation to the CYP's asthma management. Forty-two (84.0%) of participants felt CYP should be informed about genetic data being shared, and the majority felt this should commence by 12 years of age. CONCLUSION: The use of genetic information to guide management of asthma in CYP is largely acceptable to CYP, parents/guardians and HCPs. However, there are key differences between the opinions of CYP, parents and HCPs.

Strontium (87 Sr/86 Sr) isotope analysis of the Namu skeletal assemblage: A study of past human migration on Taumako, a Polynesian Outlier in the eastern Solomon Islands.

OBJECTIVES: This study aims to assess if inter-island mobility can be identified during the Namu period (ca. 1,510-1800 AD) using 87 Sr/86 Sr analysis of dental enamel for individuals from the Namu burial ground on Taumako Island in the eastern Solomon Island Chain. Historic evidence from this region suggests that females migrated between the Duff, Reef, and Santa Cruz islands for marriage purposes. We hypothesize that observable trends in migrational (87 Sr/86 Sr) and dietary (δ13 C and δ15 N) isotopes can reveal the relationship between demographic factors, social status, diet, and female mobility on Taumako. METHODS: This research analyzes enamel 87 Sr/86 Sr for 58 individuals in the Namu skeletal sample. The 87 Sr/86 Sr results were compared with published dietary isotope data (bone collagen and dentin δ13 C and δ15 N values) and type/number of grave goods to assess whether trends within the data may be related to sex, age, or burial wealth. RESULTS: The results show that females display significantly higher 87 Sr/86 Sr values compared to males. One young adult female displayed a 87 Sr/86 Sr value that was +2SD outside the mean for the sampled individuals. A linear mixed-effects model and principle components analysis of 87 Sr/86 Sr, δ13 C, and δ15 N values suggest that wealth, sex, and age-cohort membership have an observable influence on the isotopic variation for the Taumako population. CONCLUSION: We suggest that during the Namu period, Taumako was patrilocal and that some females migrated there from the nearby Santa Cruz and Reef islands. One female immigrated to Taumako from a geologically distinct region outside of the Duff, Reef, and Santa Cruz Island groups.

Selection of Oncogenic Mutant Clones in Normal Human Skin Varies with Body Site.

Skin cancer risk varies substantially across the body, yet how this relates to the mutations found in normal skin is unknown. Here we mapped mutant clones in skin from high- and low-risk sites. The density of mutations varied by location. The prevalence of NOTCH1 and FAT1 mutations in forearm, trunk, and leg skin was similar to that in keratinocyte cancers. Most mutations were caused by ultraviolet light, but mutational signature analysis suggested differences in DNA-repair processes between sites. Eleven mutant genes were under positive selection, with TP53 preferentially selected in the head and FAT1 in the leg. Fine-scale mapping revealed 10% of clones had copy-number alterations. Analysis of hair follicles showed mutations in the upper follicle resembled adjacent skin, but the lower follicle was sparsely mutated. Normal skin is a dense patchwork of mutant clones arising from competitive selection that varies by location. SIGNIFICANCE: Mapping mutant clones across the body reveals normal skin is a dense patchwork of mutant cells. The variation in cancer risk between sites substantially exceeds that in mutant clone density. More generally, mutant genes cannot be assigned as cancer drivers until their prevalence in normal tissue is known.See related commentary by De Dominici and DeGregori, p. 227.This article is highlighted in the In This Issue feature, p. 211.

Pediatric acute asthma scoring systems: a systematic review and survey of UK practice.

BACKGROUND: Acute exacerbations of asthma are common in children. Multiple asthma severity scores exist, but current emergency department (ED) use of severity scores is not known. METHODS: A systematic review was undertaken to identify the parameters collected in pediatric asthma severity scores. A survey of Paediatric Emergency Research in the United Kingdom and Ireland (PERUKI) sites was undertaken to ascertain routinely collected asthma data and information about severity scores. Included studies examined severity of asthma exacerbation in children 5-18 years of age with extractable severity parameters. RESULTS: Sixteen articles were eligible, containing 17 asthma severity scores. The severity scores assessed combinations of 15 different parameters (median, 6; range, 2-8). The most common parameters considered were expiratory wheeze (15/17), inspiratory wheeze (13/17), respiratory rate (10/17), and general accessory muscle use (9/17). Fifty-nine PERUKI centers responded to the questionnaire. Twenty centers (33.1%) currently assess severity, but few use a published score. The most commonly recorded routine data required for severity scores were oxygen saturations (59/59, 100%), heart rate, and respiratory rate (58/59, 98.3% for both). Among well-validated scores like the Pulmonary Index Score (PIS), Pediatric Asthma Severity Score (PASS), Childhood Asthma Score (CAS), and the Pediatric Respiratory Assessment Measure (PRAM), only 6/59 (10.2%), 3/59 (5.1%), 1/59 (1.7%), and 0 (0%) of units respectively routinely collect the data required to calculate them. CONCLUSION: Standardized published pediatric asthma severity scores are infrequently used. Improved routine data collection focusing on the key parameters common to multiple scores could improve this, facilitating research and audit of pediatric acute asthma.

The persistence of high energy burdens: A bibliometric analysis of vulnerability, poverty, and exclusion in the United States.

Using bibliometric methods, we examine the persistently high energy bills borne by low-income households in the U.S. This is a mystifying problem in today's age of abundant and low-priced electricity and fossil fuels. After decades of energy-efficiency programs and targeted policies, the average low-income household still spends a disproportionately large percentage of its income on energy bills. Issues of equity, race and justice are increasingly linked to the problem of persistent energy burdens. In the complex ecosystem of stakeholders that influence energy burden, key gaps still exist in the understanding of causes and solutions. In particular, limited research has examined the role of landlords and property managers in multifamily housing. Over the past decade, research has increasingly illuminated (1) the link between energy burden and health, (2) promising pathways to democratize energy efficiency and rooftop solar, and (3) issues of equity, justice, and African-American populations. Sustainable and affordable household energy is critical today as Covid-19 and climate change introduce new layers of stress that challenge the transition to a clean energy future.

Correction: Pharmacogenomic associations of adverse drug reactions in asthma: systematic review and research prioritization.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A mitochondrial genetic divergence proxy predicts the reproductive compatibility of mammalian hybrids.

Numerous pairs of evolutionarily divergent mammalian species have been shown to produce hybrid offspring. In some cases, F1 hybrids are able to produce F2s through matings with F1s. In other instances, the hybrids are only able to produce offspring themselves through backcrosses with a parent species owing to unisexual sterility (Haldane's Rule). Here, we explicitly tested whether genetic distance, computed from mitochondrial and nuclear genes, can be used as a proxy to predict the relative fertility of the hybrid offspring resulting from matings between species of terrestrial mammals. We assessed the proxy's predictive power using a well-characterized felid hybrid system, and applied it to modern and ancient hominins. Our results revealed a small overlap in mitochondrial genetic distance values that distinguish species pairs whose calculated distances fall within two categories: those whose hybrid offspring follow Haldane's Rule, and those whose hybrid F1 offspring can produce F2s. The strong correlation between genetic distance and hybrid fertility demonstrated here suggests that this proxy can be employed to predict whether the hybrid offspring of two mammalian species will follow Haldane's Rule.