Arrhythmia patterns during and after hospitalization for COVID-19 infection detected via patch-based mobile cardiac telemetry.

BACKGROUND: Coronavirus infection is the cause of the current world-wide pandemic. Cardiovascular complications occur in 20-30% of patients with COVID-19 infection including myocardial injury and arrhythmias. Current understanding of specific arrhythmia type and frequency is limited. OBJECTIVE: We aimed to analyze arrhythmia type and frequency in patients with COVID infection, identifying arrhythmia patterns over time during hospitalization and post discharge utilizing a patch based mobile cardiac telemetry system. METHODS: A prospective cohort study during the COVID-19 pandemic was performed. We included in our study patients hospitalized with COVID-19 infection who had a patch-based mobile telemetry device placed for cardiac monitoring. RESULTS: Quantitative reports for 59 patients were available for analysis. Arrhythmias were detected in 72.9% of patients and at a consistent frequency throughout the monitoring period in 52.9%-89.5% of patients daily. The majority of arrhythmias were SVT (59.3% of patients) and AF (22.0%). New onset AF was noted in 15.0% of all patients and was significantly associated with older age (OR 1.4 for 5 yrs. difference; 95% CI 1.03-2.13). Of 9 patients who were discharged with continued patch monitoring, 7 (78%) had arrhythmic events during their outpatient monitoring period. CONCLUSION: In COVID-19 patients arrhythmias were observed throughout hospitalization with a consistent daily frequency. Patients continued to exhibit cardiac arrhythmias after hospital discharge of a type and frequency similar to that seen during hospitalization. These findings suggest that the risk of arrhythmia associated with COVID infection remains elevated throughout the hospital course as well as following hospital discharge.

The problem of how fungal and oomycete avirulence proteins enter plant cells.

Recent advances in cloning avirulence genes from a rust fungus and three oomycete species have provided the novel insight that these eukaryotic plant pathogens deliver small proteins into the host cell cytoplasm where they are recognized by resistance proteins. Anne Rehmany et al. have recently identified a potential host-targeting signal in oomycete avirulence proteins from Hyaloperonospora parasitica, Phytophthora sojae and Phytophthora infestans that might be involved in transporting proteins into the host cell. This signal is surprisingly similar to the host targeting signal used by the malaria pathogen Plasmodium fulciparum to target virulence proteins to the mammalian host cell.

Plant pathology: monitoring a pathogen-targeted host protein.

A plant protein RIN4 is targeted and modified by bacterial pathogens as part of the disease process. At least two host resistance proteins monitor this pathogen interference and trigger the plant's defence responses.

Changing the Game: Using Integrative Genomics to Probe Virulence Mechanisms of the Stem Rust Pathogen Puccinia graminis f. sp. tritici.

The recent resurgence of wheat stem rust caused by new virulent races of Puccinia graminis f. sp. tritici (Pgt) poses a threat to food security. These concerns have catalyzed an extensive global effort toward controlling this disease. Substantial research and breeding programs target the identification and introduction of new stem rust resistance (Sr) genes in cultivars for genetic protection against the disease. Such resistance genes typically encode immune receptor proteins that recognize specific components of the pathogen, known as avirulence (Avr) proteins. A significant drawback to deploying cultivars with single Sr genes is that they are often overcome by evolution of the pathogen to escape recognition through alterations in Avr genes. Thus, a key element in achieving durable rust control is the deployment of multiple effective Sr genes in combination, either through conventional breeding or transgenic approaches, to minimize the risk of resistance breakdown. In this situation, evolution of pathogen virulence would require changes in multiple Avr genes in order to bypass recognition. However, choosing the optimal Sr gene combinations to deploy is a challenge that requires detailed knowledge of the pathogen Avr genes with which they interact and the virulence phenotypes of Pgt existing in nature. Identifying specific Avr genes from Pgt will provide screening tools to enhance pathogen virulence monitoring, assess heterozygosity and propensity for mutation in pathogen populations, and confirm individual Sr gene functions in crop varieties carrying multiple effective resistance genes. Toward this goal, much progress has been made in assembling a high quality reference genome sequence for Pgt, as well as a Pan-genome encompassing variation between multiple field isolates with diverse virulence spectra. In turn this has allowed prediction of Pgt effector gene candidates based on known features of Avr genes in other plant pathogens, including the related flax rust fungus. Upregulation of gene expression in haustoria and evidence for diversifying selection are two useful parameters to identify candidate Avr genes. Recently, we have also applied machine learning approaches to agnostically predict candidate effectors. Here, we review progress in stem rust pathogenomics and approaches currently underway to identify Avr genes recognized by wheat Sr genes.

Autoactive alleles of the flax L6 rust resistance gene induce non-race-specific rust resistance associated with the hypersensitive response.

L6 is a nucleotide binding site-leucine rich repeat (NBS-LRR) gene that confers race-specific resistance in flax (Linum usitatissimum) to strains of flax rust (Melampsora lini) that carry avirulence alleles of the AvrL567 gene but not to rust strains that carry only the virulence allele. Several mutant and recombinant forms of L6 were made that altered either the methionine-histidine-aspartate (MHD) motif conserved in the NBS domain of resistance proteins or exchanged the short domain C-terminal to the LRR region that is highly variable among L allele products. In transgenic flax some of these alleles are autoactive; they cause a gene dosage-dependent dwarf phenotype and constitutive expression of genes that are markers for the plant defense response. Their effects and penetrance ranged from extreme to mild in their degree of plant stunting, survival, and reproduction. Dwarf plants were also resistant to flax rust strains virulent to wild-type L6 plants, and this nonspecific resistance was associated with a hypersensitive response (HR) at the site of rust infection. The strongest autoactive allele, expressed in Arabidopsis from an ethanol-inducible promoter, gave rise to plant death dependent on the enhanced disease susceptibility 1 (EDS1) gene, which indicates that the mutant flax (Linaceae) L6 gene can signal cell death through a defined disease-resistance pathway in a different plant family (Brassicaceae).

The wheat Sr50 gene reveals rich diversity at a cereal disease resistance locus.

We identify the wheat stem rust resistance gene Sr50 (using physical mapping, mutation and complementation) as homologous to barley Mla, encoding a coiled-coil nucleotide-binding leucine-rich repeat (CC-NB-LRR) protein. We show that Sr50 confers a unique resistance specificity different from Sr31 and other genes on rye chromosome 1RS, and is effective against the broadly virulent Ug99 race lineage. Extensive haplotype diversity at the rye Sr50 locus holds promise for mining effective resistance genes.

Tobacco transgenic for the flax rust resistance gene L expresses allele-specific activation of defense responses.

Tobacco was transformed with three different alleles (L2, L6, and L10) of the flax rust resistance gene L, a member of the toll interleukin-1 receptor, nucleotide-binding site, leucine-rich repeat (TIR-NBS-LRR) class of plant disease resistance genes. L6 transgenics had a stunted phenotype, expressed several defense response genes constitutively, and had increased resistance to the fungus Cercospora nicotianae and the oomycete Phytophthora parasitica pv. nicotianae. L2 and L10 transgenics, with one exception for L10, did not express these phenotypes, indicating that the activation of tobacco defense responses is L6 allele-specific. The phenotype of the exceptional L10 transgenic plant was associated with the presence of a truncated L10 gene resulting from an aberrant T-DNA integration. The truncated gene consisted of the promoter, the complete TIR region, and 39 codons of the NBS domain fused inframe to a tobacco retrotransposon-like sequence. A similar truncated L10 gene, constructed in vitro, was transiently expressed in tobacco leaves and gave rise to a strong localized necrotic reaction. Together, these results suggest that defense signaling properties of resistance genes can be expressed in an allele-specific and pathogen-independent manner when transferred between plant genera.

Genomic analysis of Xanthomonas translucens pathogenic on wheat and barley reveals cross-kingdom gene transfer events and diverse protein delivery systems.

In comparison to dicot-infecting bacteria, only limited numbers of genome sequences are available for monocot-infecting and in particular cereal-infecting bacteria. Herein we report the characterisation and genome sequence of Xanthomonas translucens isolate DAR61454 pathogenic on wheat and barley. Based on phylogenetic analysis of the ATP synthase beta subunit (atpD) gene, DAR61454 is most closely related to other X. translucens strains and the sugarcane- and banana- infecting Xanthomonas strains, but shares a type III secretion system (T3SS) with X. translucens pv. graminis and more distantly related xanthomonads. Assays with an adenylate cyclase reporter protein demonstrate that DAR61454's T3SS is functional in delivering proteins to wheat cells. X. translucens DAR61454 also encodes two type VI secretion systems with one most closely related to those found in some strains of the rice infecting strain X. oryzae pv. oryzae but not other xanthomonads. Comparative analysis of 18 different Xanthomonas isolates revealed 84 proteins unique to cereal (i.e. rice) infecting isolates and the wheat/barley infecting DAR61454. Genes encoding 60 of these proteins are found in gene clusters in the X. translucens DAR61454 genome, suggesting cereal-specific pathogenicity islands. However, none of the cereal pathogen specific proteins were homologous to known Xanthomonas spp. effectors. Comparative analysis outside of the bacterial kingdom revealed a nucleoside triphosphate pyrophosphohydrolase encoding gene in DAR61454 also present in other bacteria as well as a number of pathogenic Fusarium species, suggesting that this gene may have been transmitted horizontally from bacteria to the Fusarium lineage of pathogenic fungi. This example further highlights the importance of horizontal gene acquisition from bacteria in the evolution of fungi.

The Top 10 fungal pathogens in molecular plant pathology.

The aim of this review was to survey all fungal pathologists with an association with the journal Molecular Plant Pathology and ask them to nominate which fungal pathogens they would place in a 'Top 10' based on scientific/economic importance. The survey generated 495 votes from the international community, and resulted in the generation of a Top 10 fungal plant pathogen list for Molecular Plant Pathology. The Top 10 list includes, in rank order, (1) Magnaporthe oryzae; (2) Botrytis cinerea; (3) Puccinia spp.; (4) Fusarium graminearum; (5) Fusarium oxysporum; (6) Blumeria graminis; (7) Mycosphaerella graminicola; (8) Colletotrichum spp.; (9) Ustilago maydis; (10) Melampsora lini, with honourable mentions for fungi just missing out on the Top 10, including Phakopsora pachyrhizi and Rhizoctonia solani. This article presents a short resumé of each fungus in the Top 10 list and its importance, with the intent of initiating discussion and debate amongst the plant mycology community, as well as laying down a bench-mark. It will be interesting to see in future years how perceptions change and what fungi will comprise any future Top 10.

Constructing haustorium-specific cDNA libraries from rust fungi.

The haustorium is a distinguishing feature of biotrophic plant pathogens. Several highly diverged -pathogen classes have independently evolved haustoria, suggesting that they represent an effective adaptation for growing within living plant tissue. Despite their clear importance in biotrophy, they have been difficult to study due to the close association of biotrophic pathogens with their host and the inability to produce haustoria in vitro. These drawbacks have been circumvented in the study of rust fungi by the development of a haustoria isolation technique. The strong binding of the lectin concanavalin A (ConA) to rust haustoria allows these structures to be purified from infected plant tissue by affinity chromatography on a ConA-Sepharose macrobead column. The isolation process results in substantial yields of intact haustoria that retain their cytoplasmic contents, making them amenable to experimentation. The construction of cDNA libraries from isolated rust haustoria and their subsequent sequence analysis have provided significant insight into haustoria function at a molecular level, revealing important roles in nutrient acquisition and the delivery of pathogenicity effector proteins. The generation of a rust haustorium-specific cDNA library is described in this chapter.

Using telemedicine to provide pediatric subspecialty care to children with special health care needs in an underserved rural community.

OBJECTIVE: For children with special health care needs (CSHCN) that live in rural, medically underserved communities, obtaining subspecialty care is a challenge. Telemedicine is a means of improving access to these children by addressing rural physician shortages and geographic barriers. This article reports a medical-needs assessment of parents/guardians with CSHCN and the status of a telemedicine program for CSHCN as well as the results of parent/guardian and local provider satisfaction with the telemedicine program. DESIGN: We report the results of a pretelemedicine medical-needs survey conducted in March 1999 by using a convenience sample of CSHCN living in a rural, medically underserved community located 90 miles north of the University of California Davis Children's Hospital (Davis, CA). In April 1999, a telemedicine program was initiated to provide consultations to CSHCN and has continued since. We also report the parent/guardian's perceptions of the appropriateness and quality of telemedicine consultations and the local provider's satisfaction with telemedicine consultations completed from April 1999 to April 2002. RESULTS: The pretelemedicine medical-needs assessment demonstrated several barriers in access to subspecialty care including traveling >1 hour for appointments (86% of parents/guardians), missing work for appointments (96% of working parents/guardians), and frequently relying on emergency department services and/or self-regulation of their child's medications. From April 1999 to April 2002, 130 telemedicine consultations were completed on 55 CSHCN. Overall, satisfaction was very high. All the parents/guardians rated satisfaction with telemedicine care as either "excellent" or "very good," and all but 2 of the rural providers' surveys reported satisfaction with telemedicine as "excellent" or "very good." The frequency of telemedicine consultations has increased with time. CONCLUSIONS: Pediatric subspecialty telemedicine consultations can be provided to CSHCN living in a rural, medically underserved community with high satisfaction among local providers and parents/guardians. Telemedicine should be considered as a means of facilitating care to CSHCN that, relative to the customary delivery of health care, is more accessible, family-centered, and coordinated among patients and their health care providers.