Genetic diversity and candidate genes for transient waterlogging tolerance in mungbean at the germination and seedling stages.

Mungbean [Vigna radiata var. radiata (L.) Wilczek] production in Asia is detrimentally affected by transient soil waterlogging caused by unseasonal and increasingly frequent extreme precipitation events. While mungbean exhibits sensitivity to waterlogging, there has been insufficient exploration of germplasm for waterlogging tolerance, as well as limited investigation into the genetic basis for tolerance to identify valuable loci. This research investigated the diversity of transient waterlogging tolerance in a mini-core germplasm collection of mungbean and identified candidate genes for adaptive traits of interest using genome-wide association studies (GWAS) at two critical stages of growth: germination and seedling stage (i.e., once the first trifoliate leaf had fully-expanded). In a temperature-controlled glasshouse, 292 genotypes were screened for tolerance after (i) 4 days of waterlogging followed by 7 days of recovery at the germination stage and (ii) 8 days of waterlogging followed by 7 days of recovery at the seedling stage. Tolerance was measured against drained controls. GWAS was conducted using 3,522 high-quality DArTseq-derived SNPs, revealing five significant associations with five phenotypic traits indicating improved tolerance. Waterlogging tolerance was positively correlated with the formation of adventitious roots and higher dry masses. FGGY carbohydrate kinase domain-containing protein was identified as a candidate gene for adventitious rooting and mRNA-uncharacterized LOC111241851, Caffeoyl-CoA O-methyltransferase At4g26220 and MORC family CW-type zinc finger protein 3 and zinc finger protein 2B genes for shoot, root, and total dry matter production. Moderate to high broad-sense heritability was exhibited for all phenotypic traits, including seed emergence (81%), adventitious rooting (56%), shoot dry mass (81%), root dry mass (79%) and SPAD chlorophyll content (70%). The heritability estimates, marker-trait associations, and identification of sources of waterlogging tolerant germplasm from this study demonstrate high potential for marker-assisted selection of tolerance traits to accelerate breeding of climate-resilient mungbean varieties.

Alarmins and innate lymphoid cells 2 activation: A common pathogenetic link connecting respiratory syncytial virus bronchiolitis and later wheezing/asthma?

Severe respiratory syncytial virus (RSV) infection in infancy is associated with increased risk of recurrent wheezing in childhood. Both acute and long-term alterations in airway functions are thought to be related to inefficient antiviral immune response. The airway epithelium, the first target of RSV, normally acts as an immunological barrier able to elicit an effective immune reaction but may also be programmed to directly promote a Th2 response, independently from Th2 lymphocyte involvement. Recognition of RSV transcripts and viral replication intermediates by bronchial epithelial cells brings about release of TSLP, IL-33, HMGB1, and IL-25, dubbed "alarmins." These epithelial cell-derived proteins are particularly effective in stimulating innate lymphoid cells 2 (ILC2) to release IL-4, IL-5, and IL-13. ILC2, reflect the innate counterparts of Th2 cells and, when activate, are potent promoters of airway inflammation and hyperresponsiveness in RSV bronchiolitis and childhood wheezing/asthma. Long-term epithelial progenitors or persistent epigenetic modifications of the airway epithelium following RSV infection may play a pathogenetic role in the short- and long-term increased susceptibility to obstructive lung diseases in response to RSV in the young. Additionally, ILC2 function may be further regulated by RSV-induced changes in gut microbiota community composition that can be associated with disease severity in infants. A better understanding of the alarmin-ILC interactions in childhood might provide insights into the mechanisms characterizing these immune-mediated diseases and indicate new targets for prevention and therapeutic interventions.

Genomic heterogeneity underlies multidrug resistance in Pseudomonas aeruginosa: A population-level analysis beyond susceptibility testing.

BACKGROUND: Pseudomonas aeruginosa is a persistent and difficult-to-treat pathogen in many patients, especially those with Cystic Fibrosis (CF). Herein, we describe a longitudinal analysis of a series of multidrug resistant (MDR) P. aeruginosa isolates recovered in a 17-month period, from a young female CF patient who underwent double lung transplantation. Our goal was to understand the genetic basis of the observed resistance phenotypes, establish the genomic population diversity, and define the nature of sequence evolution over time. METHODS: Twenty-two sequential P. aeruginosa isolates were obtained within a 17-month period, before and after a double-lung transplant. At the end of the study period, antimicrobial susceptibility testing, whole genome sequencing (WGS), phylogenetic analyses and RNAseq were performed in order to understand the genetic basis of the observed resistance phenotypes, establish the genomic population diversity, and define the nature of sequence changes over time. RESULTS: The majority of isolates were resistant to almost all tested antibiotics. A phylogenetic reconstruction revealed 3 major clades representing a genotypically and phenotypically heterogeneous population. The pattern of mutation accumulation and variation of gene expression suggested that a group of closely related strains was present in the patient prior to transplantation and continued to change throughout the course of treatment. A trend toward accumulation of mutations over time was observed. Different mutations in the DNA mismatch repair gene mutL consistent with a hypermutator phenotype were observed in two clades. RNAseq performed on 12 representative isolates revealed substantial differences in the expression of genes associated with antibiotic resistance and virulence traits. CONCLUSIONS: The overwhelming current practice in the clinical laboratories setting relies on obtaining a pure culture and reporting the antibiogram from a few isolated colonies to inform therapy decisions. Our analyses revealed significant underlying genomic heterogeneity and unpredictable evolutionary patterns that were independent of prior antibiotic treatment, highlighting the need for comprehensive sampling and population-level analysis when gathering microbiological data in the context of CF P. aeruginosa chronic infection. Our findings challenge the applicability of antimicrobial stewardship programs based on single-isolate resistance profiles for the selection of antibiotic regimens in chronic infections such as CF.

Corticosteroids in the prevention and treatment of infants with bronchopulmonary dysplasia: Part I. systemic corticosteroids.

Bronchopulmonary dysplasia (BPD) is the most significant respiratory complication of prematurity, and its consequences last from birth into adulthood. Unfortunately, the dramatic improvements in the management of premature infants have not led to a decreased incidence of BPD, or to breakthroughs in treatments offered for this long-lasting chronic respiratory disorder. Over recent decades the pathological picture of BPD has changed from inflammation, interstitial fibrosis and emphysema attributed to volu-, barotrauma and oxygen toxicity to larger, simplified alveoli and dysmorphic vessels related to arrested alveolarization and vasculogenesis with inflammation maintaining a central role. Corticosteroids (CSs) play a key role in the development of respiratory epithelial cells and lung maturation. These potent anti-inflammatory agents have long been used for the prevention and treatment of BPD; however, the risk/benefit ratio of their use remains unresolved. CSs administered antenatally have contributed to reduce mortality and respiratory distress syndrome, no such effect on BPD reduction has been observed. Postnatal systemic CSs reduced the rate and severity of BPD, yet their long-term neurodevelopmental and respiratory consequences markedly limit routine administration. This is the first in a two-part State-of-the-Art series that reviews the latest relevant clinical trials investigating the short-term and long-term effects of CSs in the prevention and treatment of BPD.

Corticosteroids in the prevention and treatment of infants with bronchopulmonary dysplasia: Part II. Inhaled corticosteroids alone or in combination with surfactants.

This paper is the second in a two-part State-of-the-Art series that reviews the latest relevant clinical trials investigating the short-term and long-term effects of corticosteroids in the prevention and treatment of bronchopulmonary dysplasia (BPD). Inhaled postnatal corticosteroids demonstrate low systemic bioavailability and rapid systemic clearance with high pulmonary deposition and were expected to reduce the incidence of BPD with reduced adverse effects, however, increased rate of mortality in the neonatal period and at the 18-24 months follow-up was observed. In a milestone study, intratracheal instillation of corticosteroids combined with surfactant decreased the incidence of BPD without increasing the mortality or the long-term neurodevelopmental adverse outcomes. However, subsequent trials using different types of surfactants, different surfactant to budesonide ratio, different time of the drug administration for infants with different severity of respiratory distress syndrome could not reproduce all the beneficial effects. Future perspectives for the identification of premature infants at high risk of BPD and the prevention or treatment of established BPD are discussed.

Malignant middle cerebral artery syndrome with thrombotic thrombocytopenia following vaccination against SARS-CoV-2.

Cases of thromboses at unusual sites with thrombocytopenia have been reported following vaccination against Sars-CoV-2. This new syndrome, christened vaccine-induced thrombotic thrombocytopenia (VITT), mainly results in venous thromboses. We report the case of a young woman with a right middle cerebral artery stroke following vaccination with ChAdOx1 nCoV-19. A diagnosis of VITT was made and platelet counts began to recover shortly after commencing treatment with argatroban, intravenous immunoglobulins and corticosteroids. On day 6 following admission, the patient deteriorated neurologically and decision made to proceed with decompressive hemicraniectomy. There were no perioperative complications and anticoagulation with argatroban was reinitiated on the first postoperative day. VITT is a rare condition resembling auto-immune heparin-induced thrombocytopenia. All critical care staff should be aware of the rare link between vaccination against SARS-CoV-2 and VITT and the need to rapidly commence both anticoagulation, using heparin alternatives, and immunomodulation.

Allergies, Allergic Comorbidities and the Home Environment in Pediatric Asthma in Southern Florida.

Background: Environmental exposure is critical in sensitization to environmental allergens and pediatric asthma morbidity, especially in tropical climates where children are perennially exposed to bioaerosols, such as pollen and mold spores, and endotoxins. Objective: This cross-sectional study examines the association of allergies, associated allergic comorbidities, and the home environment separately and synergistically in pediatric asthma, including in asthma prevalence, severity of asthma, and undiagnosed asthma, in South Florida. Methods: An online survey was administered to the parents of children attending two of the University of Miami pediatric clinics from June to October 2016. Descriptive, factor, and multivariate regression analyses were used to analyze the data. Results: Of 163 children, 22% (36) children had physician-diagnosed asthma; 10% and 32% had allergic rhinitis diagnosis and rhinitis symptoms, respectively, in the past. The allergy diagnosis age was 2.3 years higher than the asthma diagnosis age (p < 0.01). Children with ≥ 2 allergies were 12.8 times more likely to have physician-diagnosed asthma than those without allergies (p < 0.01). Children with allergies and allergic rhinitis were 4.3 (p < 0.05) times more likely to have asthma, and those with asthma were 15 (p < 0.05) times more likely to have an asthma attack than those without known allergies and allergic rhinitis. Conclusion: Allergies and associated comorbidities are risk factors of asthma, asthma persistence, and multiple allergies exacerbate their effects. Early screening for allergies and treatment are warranted to manage asthma. Since the home environment plays an important role in sensitization to allergens, further research is needed to assess home-environment-mediated allergic conditions in the onset and persistence of asthma.

Pediatric Asthma Attack and Home Paint Exposure.

Although asthma mortality has been declining for the past several decades, asthma morbidity is on the rise, largely due to deteriorating indoor air quality and comorbidities, such as allergies. Consumer products and building materials including paints emit volatile organic compounds (VOCs), such as propylene glycol (PG), which is shown to dehydrate respiratory tracts and can contributor to airway remodeling. We hypothesize that paint exposure increases the risk of asthma attacks among children because high levels of VOCs persist indoors for many weeks after painting. Children 1-15 years old visiting two of the University of Miami general pediatric clinics were screened for their history of asthma and paint exposure by interviewing their parents and/or guardians accompanying them to the clinic. They were also asked questions about asthma diagnosis, severity of asthma and allergies and their sociodemographics. The risk of asthma attack among asthmatic children was modeled with respect to paint exposure adjusting for potential confounders using multivariate logistic regressions. Of 163 children, 36 (22%) reported physician-diagnosed asthma and of these, 13 (33%) had an asthma attack during the last one year. Paint exposure was marginally significant in the univariate analysis (OR = 4.04; 95% CI = 0.90-18.87; p < 0.1). However, exposed asthmatic children were 10 times more likely to experience an asthma attack than unexposed asthmatic children (OR = 10.49; CI = 1.16-94.85, p < 0.05) when adjusted for other risk factors. Given paint is one of the sources of indoor VOCs, multiple strategies are warranted to manage the health effects of VOC exposure from paint, including the use of zero-VOC water-based paint, exposure avoidance and clinical interventions.

Respiratory syncytial virus and airway microbiota - A complex interplay and its reflection on morbidity.

The immunopathology of respiratory syncytial virus (RSV) infection varies considerably, severe disease occurring only in a minority of the affected children. The variability of the clinical presentation is in part explained by viral and environmental factors but, in infants and young children, disease severity is certainly linked to the physiologic immaturity of the innate and adaptive immune system. There is evidence that the maturation of the host immune response is positively influenced by the composition of the nasopharyngeal microbiome that, promoting an efficient reaction, can counteract the predisposition to develop viral respiratory infections and lower the risk of disease severity. However, interaction between the nasopharyngeal microbiota and respiratory viruses can be bidirectional since microbial dysbiosis may also represent a reflection of the disease-induced alterations of the local milieu. Moreover, viruses like RSV can also increase the virulence of potential pathogens in nasopharynx, a main reservoir of bacteria, and therefore promote their spread to the lower airways causing superinfection. Moreover, if negative changes in microbial community composition in early life may constitute a heightened risk toward severe RSV respiratory infection, on the contrary specific groups of microorganisms seem to be associated with protection. A better understanding into the potential negative and positive role of the different nasopharyngeal bacterial species on RSV infection may improve primary prevention and possibly care of this highly contagious disorder.

Upregulation of neuropeptides and obstructive airway disorder in infancy: A review with focus on post-RSV wheezing and NEHI.

Obstructive airway disorders, common in infancy and early childhood, include some entities that are recognized to have neuro immune mediators as their underlying pathogenetic mechanisms. The best characterized example amongst post-viral wheezing phenotypes is the disorder that follows respiratory syncytial virus (RSV) infection and leads to intermittent, long-term wheezing. The underlying mechanisms of the airway reactivity related to RSV infection have been extensively studies and are associated with dysregulation of the nonadrenergic-noncholinergic (NANC) system, via upregulation of neurotransmitters, typically Substance P. Neuroendocrine hyperplasia of infancy (NEHI), while a less common entity, is a disorder characterized by more severe and long-term obstructive airway disease. NEHI is pathophysiologically characterized by abundance of neuroendocrine cells in the airways containing the neuroimmune mediator bombesin, the release of which is presumed to be the driver of the persistent small airway obstruction and functional air-trapping. Here we review the NANC and neuroendocrine cells, the neurotransmitter systems and their studied roles in pulmonary diseases with a focus on their role in lung development, and subsequent various pediatric lung diseases. We focus on the juxtaposition of the separate neuroimmune mechanisms underlying the pathogenesis of post-RSV recurrent wheezing and NEHI's persistent small airway obstruction. We finally propose a unifying concept of neuropeptides in obstructive disorders that may encompass these two entities and possibly others.

Complicated pneumonia in children.

Complicated community-acquired pneumonia in a previously well child is a severe illness characterised by combinations of local complications (eg, parapneumonic effusion, empyema, necrotising pneumonia, and lung abscess) and systemic complications (eg, bacteraemia, metastatic infection, multiorgan failure, acute respiratory distress syndrome, disseminated intravascular coagulation, and, rarely, death). Complicated community-acquired pneumonia should be suspected in any child with pneumonia not responding to appropriate antibiotic treatment within 48-72 h. Common causative organisms are Streptococcus pneumoniae and Staphylococcus aureus. Patients have initial imaging with chest radiography and ultrasound, which can also be used to assess the lung parenchyma, to identify pleural fluid; CT scanning is not usually indicated. Complicated pneumonia is treated with a prolonged course of intravenous antibiotics, and then oral antibiotics. The initial choice of antibiotic is guided by local microbiological knowledge and by subsequent positive cultures and molecular testing, including on pleural fluid if a drainage procedure is done. Information from pleural space imaging and drainage should guide the decision on whether to administer intrapleural fibrinolytics. Most patients are treated by drainage and more extensive surgery is rarely needed; in any event, in low-income and middle-income countries, resources for extensive surgeries are scarce. The clinical course of complicated community-acquired pneumonia can be prolonged, especially when patients have necrotising pneumonia, but complete recovery is the usual outcome.

Overview: The history and pediatric perspectives of severe acute respiratory syndromes: Novel or just like SARS.

Many respiratory viral infections such as influenza and measles result in severe acute respiratory symptoms and epidemics. In the spring of 2003, an epidemic of coronavirus pneumonia spread from Guangzhou to Hong Kong and subsequently to the rest of the world. The WHO coined the acronym SARS (severe acute respiratory syndrome) and subsequently the causative virus as SARS-CoV. In the summer of 2012, epidemic of pneumonia occurred again in Saudi Arabia which was subsequently found to be caused by another novel coronavirus. WHO coined the term MERS (Middle East respiratory syndrome) to denote the Middle East origin of the novel virus (MERS-CoV). In the winter of 2019, another outbreak of pneumonia occurred in Wuhan, China which rapidly spread globally. Yet another novel coronavirus was identified as the culprit and has been named SARS-CoV-2 due to its similarities with SARS-CoV, and the disease as coronavirus disease-2019. This overview aims to compare and contrast the similarities and differences of these three major episodes of coronavirus outbreak, and conclude that they are essentially the same viral respiratory syndromes caused by similar strains of coronavirus with different names. Coronaviruses have caused major epidemics and outbreaks worldwide in the last two decades. From an epidemiological perspective, they are remarkably similar in the mode of spread by droplets. Special focus is placed on the pediatric aspects, which carry less morbidity and mortality in all three entities.

Viral infections and wheezing-asthma inception in childhood: is there a role for immunomodulation by oral bacterial lysates?

Severe and recurrent infections of the respiratory tract in early childhood constitute major risk factors for the development of bronchial hyper-responsiveness and obstructive respiratory diseases in later life. In the first years of life, the vast majority of respiratory tract infections (RTI) leading to wheezing and asthma are of a viral origin and severity and recurrence are the consequence of a greater exposure to infectious agents in a period when the immune system is still relatively immature. Therefore, boosting the efficiency of the host immune response against viral infections seems to be a rational preventative approach. In the last decades it has been demonstrated that living in farm environments, i.e. early-life exposure to microbes, may reduce the risk of allergic and infectious disorders, increasing the immune response efficacy. These findings have suggested that treatment with bacterial lysates could promote a nonspecific immunomodulation useful in the prevention of recurrent RTIs and of wheezing inception and persistence. Experimental and clinical studies showing the reduction of RTI frequency and severity in childhood and elucidating the involved mechanisms can support this hypothesis.

Urine antigen-negative disseminated histoplasmosis mimicking post-transplant lymphoproliferative disorder.

A 50-year-old woman with a history of kidney transplant presented with 2 days of abdominal pain after 6 months of recurrent streptococcal pharyngitis, fevers, weight loss and a new rash on her chest and back. Her examination was notable for a unilateral tonsillar exudate and 2-3 mm pink papules with a fine scale over her chest and back. CT of the abdomen and chest demonstrated several large lymph nodes, and laboratory investigation revealed new cytopenias and elevated transaminases. Urine antigen testing for Histoplasma capsulatum was negative, but a fungal complement fixation panel was reactive for Histoplasma antibodies. Skin biopsy revealed intracellular organisms consistent with H. capsulatum She underwent treatment with liposomal amphotericin B but due to nephrotoxicity, drug interactions and worsening transaminitis, therapy was changed to itraconazole. The diagnosis and management of disseminated histoplasmosis presents multiple challenges, which are of particular importance in patients with a history of renal transplantation.

Assessing the Real-Time Mental Health Challenges of COVID-19 in Individuals With Serious Mental Illnesses: Protocol for a Quantitative Study.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has caused significant stress and mental health problems among the general public. However, persons at greatest risk for poor mental health outcomes, such as people with serious mental illness, have been largely overlooked. OBJECTIVE: This paper presents the protocol for a study that aims to examine the mental health impact of COVID-19 and social distancing behaviors in people with serious mental illness and the behaviors undertaken to prevent COVID-19 infection in this group. METHODS: Participants will include individuals with serious mental illness (eg, schizophrenia, bipolar disorder) and nonpsychiatric control participants who are currently participating in or have previously participated in several ongoing parent observational studies. Data will be collected from April 2020 through August 2020. Participants will complete phone interviews at 2 time points to assess their current emotional functioning and discuss the measures they have taken to prevent COVID-19 infection. Baseline (pre-COVID-19) mental health, sampled by ecological momentary assessment over an extended period, will be compared with current mental health, also sampled by ecological momentary assessment over an extended period. Demographic, cognitive, and psychosocial factors at baseline will be used to examine risk and resilience to current mental health and coping. RESULTS: The inclusion of participants for the first round of telephone assessments started on April 3, 2020 and will be completed by May 31, 2020. As of April 30, 2020, 101 individuals had completed these first-round assessments. The second round of telephone assessments will likely occur between June 1, 2020, and August 31, 2020. Study results will be published in peer-reviewed scientific journals. CONCLUSIONS: Our findings will have broad implications for understanding the psychological consequences of COVID-19 among vulnerable persons with serious mental illness and will provide the opportunity to identify targets to reduce negative outcomes in the future. We also hope our efforts will provide a roadmap and resources for other researchers who would like to implement a similar approach. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/19203.

Aneurysmal Dilatation of Ductus Arteriosus and Pulmonary Artery in Association With ACTA2 Mutation.

Actin α2 (ACTA2) is a protein crucial for proper functioning of contractile apparatus in smooth muscles. A specific mutation resulting in substitution of arginine at position 179 by histidine (p.R179 H) in ACTA2 has been shown to be associated with multisystemic smooth muscle dysfunction syndrome. Characteristic features include aneurysmal arterial disease. Due to rarity of this disease, we report a nine-year-old girl with this rare genetic variant in whom cardiovascular manifestations were identified in fetal life and who needed neonatal cardiac surgical intervention.