Age-Dependent Reduction in Asthmatic Pathology through Reprogramming of Postviral Inflammatory Responses.

Asthma is a chronic disease of childhood, but for unknown reasons, disease activity sometimes subsides as children mature. In this study, we present clinical and animal model evidence suggesting that the age dependency of childhood asthma stems from an evolving host response to respiratory viral infection. Using clinical data, we show that societal suppression of respiratory virus transmission during coronavirus disease 2019 lockdown disrupted the traditional age gradient in pediatric asthma exacerbations, connecting the phenomenon of asthma remission to virus exposure. In mice, we show that asthmatic lung pathology triggered by Sendai virus (SeV) or influenza A virus is highly age-sensitive: robust in juvenile mice (4-6 wk old) but attenuated in mature mice (>3 mo old). Interestingly, allergen induction of the same asthmatic traits was less dependent on chronological age than viruses. Age-specific responses to SeV included a juvenile bias toward type 2 airway inflammation that emerged early in infection, whereas mature mice exhibited a more restricted bronchiolar distribution of infection that produced a distinct type 2 low inflammatory cytokine profile. In the basal state, aging produced changes to lung leukocyte burden, including the number and transcriptional landscape of alveolar macrophages (AMs). Importantly, depleting AMs in mature mice restored post-SeV pathology to juvenile levels. Thus, aging influences chronic outcomes of respiratory viral infection through regulation of the AM compartment and type 2 inflammatory responses to viruses. Our data provide insight into how asthma remission might develop in children.

Effect of focused protocol on reducing radiation dose for children who require computed tomography for suspected appendicitis.

BACKGROUND: Despite efforts to incorporate ultrasound into the evaluation of children for appendicitis, computed tomography (CT) is often used to aid in its diagnosis. CT scans, however, expose children to a considerable amount of radiation. In 2017, our institution began using a height-based Focused CT protocol for children with suspected appendicitis in need of CT. OBJECTIVE: To compare the radiation dose received by children with suspected appendicitis who underwent a Standard CT of the abdomen and pelvis (CTAP) with that of a Focused CT. METHODS: We conducted a retrospective study of children <18 years who underwent a CT scan for suspected appendicitis (2014-2020). We included all patients whose indication for CT was "appendicitis" or "right lower quadrant pain" and excluded those whose CT scan record lacked a radiation dose report. The effective radiation dose delivered was calculated using the dose-length product from the dose report. We compared the effective dose of those who received a Standard CTAP to those who received a Focused CT. To account for differences in radiation dose over time and by CT scanner, analyses were adjusted for CT dose index volume (CTDIvol) and size-specific dose estimate (SSDE) using quantile regression. RESULTS: A total of 474 patients who underwent CT were included. Prior to CT, 362(76%) had received an ultrasound. In total, 309(65%) patients underwent a Standard CTAP and 165(35%) underwent a Focused CT. The appendix was identified in 259(84%) Standard CTAPs compared to 151(92%) Focused CTs (p = 0.02). Compared to the Standard CTAP, children who received a Focused CT were exposed to a significantly lower effective dose (relative difference: CTDI-adjusted -13%[95% CI:-21,-5]; SSDE-adjusted -14%[95% CI:-24,-3]). CONCLUSIONS: Our height-based Focused CT protocol reduces radiation for children undergoing CT evaluation for suspected appendicitis without sacrificing diagnostic accuracy. Further study is needed to validate these findings at other institutions.

Characterization and genetics of multiple soybean aphid biotype resistance in five soybean plant introductions.

KEY MESSAGE: Five soybean plant introductions expressed antibiosis resistance to multiple soybean aphid biotypes. Two introductions had resistance genes located in the Rag1, Rag2, and Rag3 regions; one introduction had resistance genes located in the Rag1, Rag2, and rag4 regions; one introduction had resistance genes located in the Rag1 and Rag2 regions; and one introduction had a resistance gene located in the Rag2 region. Soybean aphid (Aphis glycines Matsumura) is the most important soybean [Glycine max (L.) Merr.] insect pest in the USA. The objectives of this study were to characterize the resistance expressed in five plant introductions (PIs) to four soybean aphid biotypes, determine the mode of resistance inheritance, and identify markers associated with genes controlling resistance in these accessions. Five soybean PIs, from an initial set of 3000 PIs, were tested for resistance against soybean aphid biotypes 1, 2, 3, and 4 in choice and no-choice tests. Of these five PIs, PI 587663, PI 587677, and PI 587685 expressed antibiosis against all four biotypes, while PI 587972 and PI 594592 expressed antibiosis against biotypes 1, 2, and 3. F2 populations derived from PI 587663 and PI 587972 were evaluated for resistance against soybean aphid biotype 1, and populations derived from PIs 587677, 587685, and 594592 were tested against biotype 3. In addition, F2:3 plants were tested against biotypes 2 and 3. Genomic DNA from F2 plants was screened with markers linked to Rag1, Rag2, Rag3, and rag4 soybean aphid-resistance genes. Results showed that PI 587663 and PI 594592 each had three genes with variable gene action located in the Rag1, Rag2, and Rag3 regions. PI 587677 had three genes with variable gene action located in the Rag1, Rag2 and rag4 regions. PI 587685 had one dominant gene located in the Rag1 region and an additive gene in the Rag2 region. PI 587972 had one dominant gene located in the Rag2 region controlling antixenosis- or antibiosis-type resistance to soybean aphid biotypes 1, 2, or 3. PIs 587663, 587677, and 587685 also showed antibiosis-type resistance against biotype 4. Information on multi-biotype aphid resistance and resistance gene markers will be useful for improving soybean aphid resistance in commercial soybean cultivars.

Inheritance of soybean aphid resistance in 21 soybean plant introductions.

KEY MESSAGE: The Rag2 region was frequently identified among 21 F 2 populations evaluated for soybean aphid resistance, and dominant gene action and single-gene resistance were also commonly identified. The soybean aphid [Aphis glycines Matsumura (Hemiptera: Aphididae)] is one of the most important insect pests of soybean [Glycine max (L.) Merr] in the northern USA and southern Canada, and four resistance loci (Rag1-rag4) have been discovered since the pest was identified in the USA in 2000. The objective of this research was to determine whether resistance expression in recently identified soybean aphid-resistant plant introductions (PIs) was associated with the four Rag loci using a collection of 21 F2 populations. The F2 populations were phenotyped with soybean aphid biotype 1, which is avirulent on plants having any of the currently identified Rag genes, using choice tests in the greenhouse and were tested with genetic markers linked to the four Rag loci. The phenotyping results indicate that soybean aphid resistance is controlled by a single dominant gene in 14 PIs, by two genes in three PIs, and four PIs had no clear Mendelian inheritance patterns. Genetic markers flanking Rag2 were significantly associated with aphid resistance in 20 PIs, the Rag1 region was significantly identified in five PIs, and the Rag3 region was identified in one PI. These results show that single dominant gene action at the Rag2 region may be a major source for aphid resistance in the USDA soybean germplasm collection.

Implementing the Friends and Family Test.

This article discusses the background to the Friends and Family Test, highlighting the commitment to improve the patient experience. It also demonstrates how patient feedback was used to improve services in Aintree University Hospital Foundation Trust.

Assessing Platelet Mitochondrial Dysfunction in a Murine Model of Acute Acetaminophen Toxicity.

INTRODUCTION: Acetaminophen (APAP) toxicity remains a significant cause of adult and pediatric liver failure in North America and Europe. Previous research has evaluated the impaired mitochondrial function associated with APAP toxicity. The primary aim of this study was to evaluate the effects of APAP toxicity on platelet mitochondrial function using platelet oxygen consumption in a murine model in vivo. Our secondary objectives were to determine the effect of 4-MP on platelet mitochondrial function and hepatic toxicity in the setting of APAP overdose, and to correlate platelet mitochondrial function with other markers of APAP toxicity. METHODS: Male C57Bl/6 mice were randomized to receive APAP (300 or 500 mg/kg) or vehicle followed 90 minutes later by either 4-MP (50 mg/kg) or vehicle via intraperitoneal injection. Mice were euthanized 0, 12, or 24 hours later and platelets isolated from cardiac blood and counted. Platelet oxygen consumption (POC) was determined using a closed-system respirometer. Liver injury was assessed by measuring alanine transferase (ALT) and histological evaluation. RESULTS: Injection of 500 mg/kg APAP led to increased POC versus pair-matched control (vehicle) (p < 0.001). Administration of 4-MP did not affect POC in control or 300 mg/kg APAP mice. In mice receiving 500 mg/kg APAP and 4-MP, POC decreased significantly compared to mice receiving 500 mg/kg APAP alone (p < 0.01). Serum and histological analysis confirmed APAP-induced hepatic damage in mice receiving 500 mg/kg APAP and these effects blunted by treatment with 4-MP. CONCLUSIONS: Platelet oxygen consumption as a measure of mitochondrial function may be useful as a biomarker of hepatic APAP toxicity in the setting of moderate to severe overdose. Treatment with 4-MP decreases hepatic necrosis and may mitigate the harmful effects of APAP on platelet mitochondrial function detected via POC.

Age-dependent rebound in asthma exacerbations after COVID-19 lockdown.

Background: Virus mitigation measures enacted early in the coronavirus infectious disease 2019 (COVID-19) pandemic suppressed common respiratory viruses and reduced the number of obstructive lung disease exacerbations. However, many localities began to ease these precautions in the year 2021, leading to a resurgence of non-COVID viruses. How asthma and chronic obstructive pulmonary disease (COPD) activity responded to this upswing in viral abundance is unclear. Objective: Our aim was to examine how viral resurgence during the relaxation of COVID-19 restrictions affected asthma and COPD exacerbations. Methods: We analyzed electronic medical records for emergency department (ED) respiratory virus positivity, asthma visits, and COPD visits. We compared the 52-week interval before the COVID-19 restrictions (the pre-lockdown period [March 22, 2019-March 19, 2020]), the 52-week period immediately following enactment of the restrictions (the lockdown period [March 20, 2020-March 18, 2021]), and the 52-week period thereafter (the post-lockdown period [March 19, 2021-March 18, 2022]). We used MetaCYCLE to analyze seasonal trends in our data. Results: The post-lockdown period was marked by a 400% increase in viral positivity compared with during the lockdown period. Asthma- and COPD-related ED visits each rose 37% compared with during the lockdown, with the rebound in asthma ED visits concentrated in individuals younger than 20 years. Interestingly, after the lockdown period, asthma ED visits overcorrected in children younger than 5 years, rising 81% compared with before the lockdown. Seasonal rhythms in asthma and COPD exacerbations were suppressed during the lockdown and recovered after the lockdown. Conclusions: COVID-19 precautions had the unexpected effect of magnifying early-childhood asthma activity once common respiratory viruses recurred. These results may have implications for the future use of virus mitigation strategies in young children.

Effect of the COVID-19 Lockdown on Asthma Biological Rhythms.

Asthma has a striking temporal character, in which time-of-day, patient age, and season each influence disease activity. The extent to which rhythms in asthma activity reflect exposure to specific disease triggers remains unclear. In this study, we examined how virus mitigation strategies enacted during the COVID-19 pandemic ("lockdown measures") affected rhythms in asthma clinical activity in children. To this end, we retrospectively analyzed asthma clinical presentations in children aged <18 years to our regional academic medical center, comparing 4 years of medical records prior to COVID-19 lockdown measures with the 12 months immediately after the institution of such measures. We correlated these data to positive viral test results, febrile seizures, and allergic clinical surrogates (allergic reaction visits and Emergency Department [ED] antihistamine prescriptions, respectively) over the same time frame. In the 12 months following the institution of the COVID-19 lockdown, positivity rates for common respiratory viruses dropped by 70.2% and ED visits for asthma among children dropped by 62% compared to pre-COVID years. Lockdown suppressed seasonal variation in positive viral tests and asthma ED visits, while diurnal rhythms in asthma visits were unchanged. Asthma seasonality correlated most strongly with rhinovirus positivity both before and after the institution of COVID lockdown measures. Altogether, our data support a causal role for viruses in driving seasonal variability in asthma exacerbations in children.

Pandemic policies and breastfeeding: A cross-sectional study during the onset of COVID-19 in the United States.

The United States is one of the few countries, and the only high-income country, that does not federally mandate protection of postpartum employment through paid postpartum maternity and family leave policies. At the onset of the COVID-19 pandemic in the U.S., stay-at-home orders were implemented nationally, creating a natural experiment in which to document the effects of de facto paid leave on infant feeding practices in the first postpartum year. The purpose of this cross-sectional, mixed-methods study was to describe infant and young child feeding intentions, practices, decision-making, and experiences during the first wave of the COVID-19 pandemic in the U.S. Quantitative and qualitative data were collected March 27-May 31, 2020 via online survey among a convenience sample of respondents, ages 18 years and older, who were currently feeding a child 2 years of age or younger, yielding 1,437 eligible responses. Nearly all (97%) respondents indicated an intention to feed their infant exclusively with human milk in the first 6 months. A majority of respondents who were breastfeeding (66%) reported no change in breastfeeding frequency after the implementation of COVID-19 stay-at-home orders. However, thirty-one percent indicated that they breastfed more frequently due to stay-at-home orders and delayed plans to wean their infant or young child. Key themes drawn from the qualitative data were: emerging knowledge and perceptions of the relationship between COVID-19 and breastfeeding, perceptions of immune factors in human milk, and the social construction of COVID-19 and infant and young child feeding perceptions and knowledge. There were immediate positive effects of stay-at-home policies on human milk feeding practices, even during a time of considerable uncertainty about the safety of breastfeeding and the transmissibility of SARS-CoV-2 via human milk, constrained access to health care services and COVID-19 testing, and no effective COVID-19 vaccines. Federally mandated paid postpartum and family leave are essential to achieving more equitable lactation outcomes.

High-throughput characterization, correlation, and mapping of leaf photosynthetic and functional traits in the soybean (Glycine max) nested association mapping population.

Photosynthesis is a key target to improve crop production in many species including soybean [Glycine max (L.) Merr.]. A challenge is that phenotyping photosynthetic traits by traditional approaches is slow and destructive. There is proof-of-concept for leaf hyperspectral reflectance as a rapid method to model photosynthetic traits. However, the crucial step of demonstrating that hyperspectral approaches can be used to advance understanding of the genetic architecture of photosynthetic traits is untested. To address this challenge, we used full-range (500-2,400 nm) leaf reflectance spectroscopy to build partial least squares regression models to estimate leaf traits, including the rate-limiting processes of photosynthesis, maximum Rubisco carboxylation rate, and maximum electron transport. In total, 11 models were produced from a diverse population of soybean sampled over multiple field seasons to estimate photosynthetic parameters, chlorophyll content, leaf carbon and leaf nitrogen percentage, and specific leaf area (with R2 from 0.56 to 0.96 and root mean square error approximately <10% of the range of calibration data). We explore the utility of these models by applying them to the soybean nested association mapping population, which showed variability in photosynthetic and leaf traits. Genetic mapping provided insights into the underlying genetic architecture of photosynthetic traits and potential improvement in soybean. Notably, the maximum Rubisco carboxylation rate mapped to a region of chromosome 19 containing genes encoding multiple small subunits of Rubisco. We also mapped the maximum electron transport rate to a region of chromosome 10 containing a fructose 1,6-bisphosphatase gene, encoding an important enzyme in the regeneration of ribulose 1,5-bisphosphate and the sucrose biosynthetic pathway. The estimated rate-limiting steps of photosynthesis were low or negatively correlated with yield suggesting that these traits are not influenced by the same genetic mechanisms and are not limiting yield in the soybean NAM population. Leaf carbon percentage, leaf nitrogen percentage, and specific leaf area showed strong correlations with yield and may be of interest in breeding programs as a proxy for yield. This work is among the first to use hyperspectral reflectance to model and map the genetic architecture of the rate-limiting steps of photosynthesis.

Genetic Architecture of Soybean Yield and Agronomic Traits.

Soybean is the world's leading source of vegetable protein and demand for its seed continues to grow. Breeders have successfully increased soybean yield, but the genetic architecture of yield and key agronomic traits is poorly understood. We developed a 40-mating soybean nested association mapping (NAM) population of 5,600 inbred lines that were characterized by single nucleotide polymorphism (SNP) markers and six agronomic traits in field trials in 22 environments. Analysis of the yield, agronomic, and SNP data revealed 23 significant marker-trait associations for yield, 19 for maturity, 15 for plant height, 17 for plant lodging, and 29 for seed mass. A higher frequency of estimated positive yield alleles was evident from elite founder parents than from exotic founders, although unique desirable alleles from the exotic group were identified, demonstrating the value of expanding the genetic base of US soybean breeding.

Letters.

EDUCATIONAL INITIATIVES IN WOUND CARE INTEREST IN A HIGHER DEGREE IN WOUND CARE SUCCESSFUL THERAPIES IN TREATMENT OF KELOID SCARS.

The holistic assessment of a patient with leg ulceration.

Mrs Smith was an 88-year-old woman who presented with a large ulcer on her right leg. Before any medical or nursing intervention took place, a full assessment of the patient and her situation had to take place, which formed the basis for the formulation of a management plan. In this case study, the detailed, systematic, holistic assessment of Mrs Smith and her ulcer is described in detail. The assessment sought to determine the aetiology of Mrs Smith's ulcer, as well as to assess her health needs.

Honey as a dressing for chronic wounds in adults.

The aim of this review was to identify whether in adults with chronic wounds the use of honey as a wound dressing improves wound management outcomes. As no randomized controlled trials or comparative studies comparing the use of honey as a chronic wound dressing with usual treatment could be found, the review is based on case studies and serial case studies. These were reviewed using a framework broadly based on wound care case study guidelines (Nelson, 2000) and cohort study guidelines (Greenhalgh and Donald, 2000). Based on the case studies reviewed, honey appears to be a useful dressing in adults with chronic wounds, but the available evidence is weak and therefore must be interpreted with caution.

Living with a pressure ulcer: a descriptive study of patients' experiences.

This qualitative study explored the perceptions and feelings of patients with pressure ulcers. Five participants who had suffered from pressure ulcers extending into the subcutaneous tissue and deep fascia were interviewed. A semi-structured interview technique was used, in which participants were asked a series of open questions based on the reviewed literature and the author's clinical experience. Content analysis was used to analyse the interview transcripts. The following themes emerged: pain, exudate levels, loss of independence, emotional factors, worry about healing, relationships, body image and social isolation.

Multidisciplinary collaborative development of a plain-language prenatal education book.

During pregnancy, women actively seek out health information that promotes the well-being of themselves and their fetuses. For those with health literacy challenges, access to understandable health information can be difficult. Written information, in particular, needs to be readable and usable by the women served. Plain language is an essential component of effective health education material. In an effort to create standardized prenatal education materials for a diverse population of childbearing women, Boston Medical Center's midwifery service led a multidisciplinary initiative to develop a comprehensive plain-language prenatal education book. Midwives, obstetricians, family physicians, nurses, and community doulas contributed to the content of the book; art students provided graphic design skills; and a literacy consultant assisted in the wording and layout. The Hey Mama! book provides women with woman-centered, readable, comprehensive information about pregnancy, labor, postpartum, and newborn care.