Immunoglobulin-like receptors in chickens: identification, functional characterization, and renaming to cluster homolog of immunoglobulin-like receptors.

The cluster homolog of immunoglobulin-like receptors (CHIRs), previously known as the "chicken homolog of immunogloublin-like receptors," represents is a large group of transmembrane glycoproteins that direct the immune response. However, the full repertoire of putatively activating, inhibitory, or dual function CHIRA, CHIRB, and CHIRAB on chickens' immune responses is poorly understood. Herein, the study objective was to determine the genes encoding CHIR proteins and predict their function by searching canonical protein structure. A bioinformatics pipeline based on previous work was employed to search for the CHIRs from the newly updated broiler and layer genomes. The categorization into CHIRA, CHIRB, and CHIRAB types was assigned through motif searches, multiple sequence alignment, and phylogeny. In total, 150 protein-encoding genes on Chromosome 31 were identified as CHIRs. Gene members of each functional group (CHIRA, CHIRB, CHIRAB) were classified in accordance with previously recognized proteins. The genes were renamed to "cluster homolog of immunoglobulin-like receptors" (CHIRs) to allow for the naming of orthologous genes in other avian species. Additionally, expression analysis of the classified CHIRs across various reinforces their importance as immune regulators and activation in inflammatory tissues. Furthermore, over 1,000 diverse and rare CHIRs variants associated with differential Marek's disease response (P < 0.05) emphasize the impact of CHIRs on shaping avian immune responses in diverse contexts. The practical applications of these findings encompass advancing immunology, improving poultry health management, optimizing breeding programs for disease resistance, and enhancing overall animal health through a deeper understanding of the roles and functions of CHIRA, CHIRB, and CHIRAB types in avian immune responses.

Intraoperative Red Blood Cell Transfusion and Primary Graft Dysfunction After Lung Transplantation.

BACKGROUND: In this international, multicenter study of patients undergoing lung transplantation (LT), we explored the association between the amount of intraoperative packed red blood cell (PRBC) transfusion and occurrence of primary graft dysfunction (PGD) and associated outcomes. METHODS: The Extracorporeal Life Support in LT Registry includes data on LT recipients from 9 high-volume (>40 transplants/y) transplant centers (2 from Europe, 7 from the United States). Adult patients who underwent bilateral orthotopic lung transplant from January 2016 to January 2020 were included. The primary outcome of interest was the occurrence of grade 3 PGD in the first 72 h after LT. RESULTS: We included 729 patients who underwent bilateral orthotopic lung transplant between January 2016 and November 2020. LT recipient population tertiles based on the amount of intraoperative PRBC transfusion (0, 1-4, and >4 units) were significantly different in terms of diagnosis, age, gender, body mass index, mean pulmonary artery pressure, lung allocation score, hemoglobin, prior chest surgery, preoperative hospitalization, and extracorporeal membrane oxygenation requirement. Inverse probability treatment weighting logistic regression showed that intraoperative PRBC transfusion of >4 units was significantly ( P < 0.001) associated with grade 3 PGD within 72 h (odds ratio [95% confidence interval], 2.2 [1.6-3.1]). Inverse probability treatment weighting analysis excluding patients with extracorporeal membrane oxygenation support produced similar findings (odds ratio [95% confidence interval], 2.4 [1.7-3.4], P < 0.001). CONCLUSIONS: In this multicenter, international registry study of LT patients, intraoperative transfusion of >4 units of PRBCs was associated with an increased risk of grade 3 PGD within 72 h. Efforts to improve post-LT outcomes should include perioperative blood conservation measures.

Unique Cell Subpopulations and Disease Progression Markers in Canines with Atopic Dermatitis.

Atopic dermatitis (AD) is a common pruritic inflammatory skin disease with unclear molecular and cellular contributions behind the complex etiology. To unravel these differences between healthy control and AD skin we employed single-cell transcriptomics, utilizing the canine AD model for its resemblance to human clinical and molecular phenotypes. In this study, we show that there are overall increases in keratinocytes and T cells and decreases in fibroblast populations in AD dogs. Within immune cell types, we identified an enriched γδ T cell population in AD, which may contribute to cutaneous inflammation. A prominent IL26-positive fibroblast subpopulation in AD was detected, which may activate neighboring cells in the dermal-epidermal niche. Lastly, by comparing dogs with different disease severities, we found genes that follow disease progression and may serve as potential biomarkers. In this study, we characterized key AD cell types and cellular processes that can be further leveraged in diagnosis and treatment.

Textbook outcome in lung transplantation: Planned venoarterial extracorporeal membrane oxygenation versus off-pump support for patients without pulmonary hypertension.

BACKGROUND: Planned venoarterial extracorporeal membrane oxygenation (VA ECMO) is increasingly used during bilateral orthotopic lung transplantation (BOLT) and may be superior to off-pump support for patients without pulmonary hypertension. In this single-institution study, we compared rates of textbook outcome between BOLTs performed with planned VA ECMO or off-pump support for recipients with no or mild pulmonary hypertension. METHODS: Patients with no or mild pulmonary hypertension who underwent isolated BOLT between 1/2017 and 2/2021 with planned off-pump or VA ECMO support were included. Textbook outcome was defined as freedom from intraoperative complication, 30-day reintervention, 30-day readmission, post-transplant length of stay >30 days, 90-day mortality, 30-day acute rejection, grade 3 primary graft dysfunction at 48 or 72 hours, post-transplant ECMO, tracheostomy within 7 days, inpatient dialysis, reintubation, and extubation >48 hours post-transplant. Textbook outcome achievement was compared between groups using multivariable logistic regression. RESULTS: Two hundred thirty-seven BOLTs were included: 68 planned VA ECMO and 169 planned off-pump. 14 (20.6%) planned VA ECMO and 27 (16.0%) planned off-pump patients achieved textbook outcome. After adjustment for prior BOLT, lung allocation score, ischemic time, and intraoperative transfusions, planned VA ECMO was associated with higher odds of textbook outcome than planned off-pump support (odds ratio 3.89, 95% confidence interval 1.58-9.90, p = 0.004). CONCLUSIONS: At our institution, planned VA ECMO for isolated BOLT was associated with higher odds of textbook outcome than planned off-pump support among patients without pulmonary hypertension. Further investigation in a multi-institutional cohort is warranted to better elucidate the utility of this strategy.

The Year in Cardiothoracic Transplant Anesthesia: Selected Highlights From 2020 Part I - Lung Transplantation.

This special article focuses on the highlights in cardiothoracic transplantation literature in the year 2020. Part I encompasses the recent literature on lung transplantation, including the advances in preoperative assessment and optimization, donor management, including the use of ex-vivo lung perfusion, recipient management, including those who have been infected with coronavirus disease 2019, updates on the perioperative management, including the use of extracorporeal membrane oxygenation, and long-term outcomes.

Inhaled Pulmonary Vasodilator Therapy in Adult Lung Transplant: A Randomized Clinical Trial.

Importance: Inhaled nitric oxide (iNO) is commonly administered for selectively inhaled pulmonary vasodilation and prevention of oxidative injury after lung transplant (LT). Inhaled epoprostenol (iEPO) has been introduced worldwide as a cost-saving alternative to iNO without high-grade evidence for this indication. Objective: To investigate whether the use of iEPO will lead to similar rates of severe/grade 3 primary graft dysfunction (PGD-3) after adult LT when compared with use of iNO. Design, Setting, and Participants: This health system-funded, randomized, blinded (to participants, clinicians, data managers, and the statistician), parallel-designed, equivalence clinical trial included 201 adult patients who underwent single or bilateral LT between May 30, 2017, and March 21, 2020. Patients were grouped into 5 strata according to key prognostic clinical features and randomized per stratum to receive either iNO or iEPO at the time of LT via 1:1 treatment allocation. Interventions: Treatment with iNO or iEPO initiated in the operating room before lung allograft reperfusion and administered continously until cessation criteria met in the intensive care unit (ICU). Main Outcomes and Measures: The primary outcome was PGD-3 development at 24, 48, or 72 hours after LT. The primary analysis was for equivalence using a two one-sided test (TOST) procedure (90% CI) with a margin of 19% for between-group PGD-3 risk difference. Secondary outcomes included duration of mechanical ventilation, hospital and ICU lengths of stay, incidence and severity of acute kidney injury, postoperative tracheostomy placement, and in-hospital, 30-day, and 90-day mortality rates. An intention-to-treat analysis was performed for the primary and secondary outcomes, supplemented by per-protocol analysis for the primary outcome. Results: A total of 201 randomized patients met eligibility criteria at the time of LT (129 men [64.2%]). In the intention-to-treat population, 103 patients received iEPO and 98 received iNO. The primary outcome occurred in 46 of 103 patients (44.7%) in the iEPO group and 39 of 98 (39.8%) in the iNO group, leading to a risk difference of 4.9% (TOST 90% CI, -6.4% to 16.2%; P = .02 for equivalence). There were no significant between-group differences for secondary outcomes. Conclusions and Relevance: Among patients undergoing LT, use of iEPO was associated with similar risks for PGD-3 development and other postoperative outcomes compared with the use of iNO. Trial Registration: ClinicalTrials.gov identifier: NCT03081052.

Lung transplantation using allografts with more than 8 hours of ischemic time: A single-institution experience.

BACKGROUND: Six hours was historically regarded as the limit of acceptable ischemic time for lung allografts. However, broader sharing of donor lungs often necessitates use of allografts with ischemic time >6 hours. We characterized the association between ischemic time ≥8 hours and outcomes after lung transplantation using a contemporary cohort from a high-volume institution. METHODS: Patients who underwent primary isolated bilateral lung transplantation between 1/2016 and 5/2020 were included. Patients bridged to transplant with extracorporeal membrane oxygenation or mechanical ventilation, and ex-vivo perfusion cases were excluded. Recipients were stratified by total allograft ischemic time <8 hours (standard) vs ≥8 hours (long). Perioperative outcomes and post-transplant survival were compared between groups. RESULTS: Of 358 patients, 95 (26.5%) received long ischemic time (≥8 hours) lungs. Long ischemic time recipients were more likely to be male and have donation after circulatory death donors than standard ischemic time recipients. On unadjusted analysis, long and standard ischemic time recipients had similar survival, and similar rates of grade 3 primary graft dysfunction at 72 hours, extracorporeal membrane oxygenation post-transplant, acute rejection within 30 days, reintubation, and post-transplant length of stay. After adjustment, long and standard ischemic time recipients had comparable risks of mortality or graft failure. CONCLUSIONS: In a modern cohort, use of lung allografts with "long" ischemic time ≥8 hours were associated with acceptable perioperative outcomes and post-transplant survival. Further investigation is required to better understand how broader use impacts post-lung transplant outcomes and the implications for smarter sharing under an evolving national allocation policy.

Blood product transfusion and lung transplant outcomes: A systematic review.

The perioperative transfusion of blood products has long been linked to development of acute lung injury and associated with mortality across both medical and surgical patient populations.1,2 The need for blood product transfusion during and after lung transplantation is common and, in many instances, unavoidable. However, this practice may potentially be modifiable.3 In this systematic review, we explore and summarize what is known regarding the impact of blood product transfusion on outcomes following lung transplantation, highlighting the most recent work in this area. Overall, the majority of the literature consists of single center retrospective analyses or the work of multicenter working groups referencing the same database. In the end, there are a number of remaining questions regarding blood product transfusion and their downstream effects on graft function and survival.

The Rid family member RutC of Escherichia coli is a 3-aminoacrylate deaminase.

The Rid protein family (PF14588, IPR006175) is divided into nine subfamilies, of which only the RidA subfamily has been characterized biochemically. RutC, the founding member of one subfamily, is encoded in the pyrimidine utilization (rut) operon that encodes a pathway that allows Escherichia coli to use uracil as a sole nitrogen source. Results reported herein demonstrate that RutC has 3-aminoacrylate deaminase activity and facilitates one of the reactions previously presumed to occur spontaneously in vivo. RutC was active with several enamine-imine substrates, showing similarities and differences in substrate specificity with the canonical member of the Rid superfamily, Salmonella enterica RidA. Under standard laboratory conditions, a Rut pathway lacking RutC generates sufficient nitrogen from uracil for growth of E. coli. These results support a revised model of the Rut pathway and provide evidence that Rid proteins may modulate metabolic fitness, rather than catalyzing essential functions.

Correction to: Genome-enabled insights into the biology of thrips as crop pests.

An amendment to this paper has been published and can be accessed via the original article.

Observations of volatile organic and sulfur compounds in ambient air and health risk assessment near a paper mill in rural Idaho, U. S. A.

The Lewis-Clark Valley is a rural area that includes the cities of Lewiston, Idaho and Clarkston, Washington and the surrounding areas. The largest industry in the Lewis-Clark Valley is a pulp paper mill located in Lewiston which emits particulate matter and odorous sulfur air pollutants. This study analyzed the Lewis-Clark Valley air composition and seasonal, temporal and spatial variations of volatile organic compounds (VOCs) from 2017 to 2018 to determine potential health risks of the paper mill emissions to the surrounding community. Both active and passive air sampling via sorbent tubes were analyzed by thermal desorption - gas chromatography-mass spectrometry (TD-GC-MS). Fifty VOCs including benzene, toluene, chloroform, dimethyl sulfide and dimethyl disulfide were measured in the ambient air of the Lewis-Clark Valley at ten different sites, totaling over 800 samples. In addition, passive sorbent tubes were deployed in 2018 to obtain monthly averages in Lewis-Clark Valley and three urban locations in Idaho and Washington for comparison. United States Environmental Protection Agency (2001) methodology was used to assess cancer risks in the community based on the upper confidence levels of five carcinogens and nine air toxics. The Lewis-Clark Valley had similar levels of benzene to urban areas but had a strong signature of chloroform and sulfides from the paper mill. The cumulative cancer risk was 2 x 10-6 - 11 × 10-6 mainly due to the compounds chloroform, benzene and carbon tetrachloride. The hazard index of other air toxics was less than one. Overall, these air pollutants were considered low risk to the local population.

Genome-enabled insights into the biology of thrips as crop pests.

BACKGROUND: The western flower thrips, Frankliniella occidentalis (Pergande), is a globally invasive pest and plant virus vector on a wide array of food, fiber, and ornamental crops. The underlying genetic mechanisms of the processes governing thrips pest and vector biology, feeding behaviors, ecology, and insecticide resistance are largely unknown. To address this gap, we present the F. occidentalis draft genome assembly and official gene set. RESULTS: We report on the first genome sequence for any member of the insect order Thysanoptera. Benchmarking Universal Single-Copy Ortholog (BUSCO) assessments of the genome assembly (size = 415.8 Mb, scaffold N50 = 948.9 kb) revealed a relatively complete and well-annotated assembly in comparison to other insect genomes. The genome is unusually GC-rich (50%) compared to other insect genomes to date. The official gene set (OGS v1.0) contains 16,859 genes, of which ~ 10% were manually verified and corrected by our consortium. We focused on manual annotation, phylogenetic, and expression evidence analyses for gene sets centered on primary themes in the life histories and activities of plant-colonizing insects. Highlights include the following: (1) divergent clades and large expansions in genes associated with environmental sensing (chemosensory receptors) and detoxification (CYP4, CYP6, and CCE enzymes) of substances encountered in agricultural environments; (2) a comprehensive set of salivary gland genes supported by enriched expression; (3) apparent absence of members of the IMD innate immune defense pathway; and (4) developmental- and sex-specific expression analyses of genes associated with progression from larvae to adulthood through neometaboly, a distinct form of maturation differing from either incomplete or complete metamorphosis in the Insecta. CONCLUSIONS: Analysis of the F. occidentalis genome offers insights into the polyphagous behavior of this insect pest that finds, colonizes, and survives on a widely diverse array of plants. The genomic resources presented here enable a more complete analysis of insect evolution and biology, providing a missing taxon for contemporary insect genomics-based analyses. Our study also offers a genomic benchmark for molecular and evolutionary investigations of other Thysanoptera species.

Perioperative Management of Bleeding and Transfusion for Lung Transplantation.

Perioperative allogeneic blood product transfusion is common in lung transplantation and has various implications on the short- and long-term outcomes of lung recipients. This review summarizes the effect of transfusion on outcomes including primary graft dysfunction, chronic lung allograft dysfunction, and all-cause mortality. We outline known risk factors for increased transfusion requirement in lung transplantation and present current evidence regarding the effect of hemostatic agents including antifibrinolytics, recombinant factor VII, and prothrombin complex concentrates. Finally, we highlight the roles of point-of-care coagulation testing and goal-directed transfusion strategies in reducing transfusion requirements in lung transplantation.

Staphylococcus aureus modulates the activity of acetyl-Coenzyme A synthetase (Acs) by sirtuin-dependent reversible lysine acetylation.

Lysine acylation is a posttranslational modification used by cells of all domains of life to modulate cellular processes in response to metabolic stress. The paradigm for the role of lysine acylation in metabolism is the acetyl-coenzyme A synthetase (Acs) enzyme. In prokaryotic and eukaryotic cells alike, Acs activity is downregulated by acetylation and reactivated by deacetylation. Proteins belonging to the bacterial GCN5-related N-acetyltransferase (bGNAT) superfamily acetylate the epsilon amino group of an active site lysine, inactivating Acs. A deacetylase can remove the acetyl group, thereby restoring activity. Here we show the Acs from Staphylococcus aureus (SaAcs) activates acetate and weakly activates propionate, but does not activate >C3 organic acids or dicarboxylic acids (e.g. butyrate, malonate and succinate). SaAcs activity is regulated by AcuA (SaAcuA); a type-IV bGNAT. SaAcuA can acetylate or propionylate SaAcs reducing its activity by >90% and 95% respectively. SaAcuA also succinylated SaAcs, with this being the first documented case of a bacterial GNAT capable of succinylation. Inactive SaAcsAc was deacetylated (hence reactivated) by the NAD+ -dependent (class III) sirtuin protein deacetylase (hereafter SaCobB). In vivo and in vitro evidence show that SaAcuA and SaCobB modulate the level of SaAcs activity in S. aureus.

Frailty in the End-Stage Lung Disease or Heart Failure Patient: Implications for the Perioperative Transplant Clinician.

The syndrome of frailty for patients undergoing heart or lung transplantation has been a recent focus for perioperative clinicians because of its association with postoperative complications and poor outcomes. Patients with end-stage cardiac or pulmonary failure may be under consideration for heart or lung transplantation along with bridging therapies such as ventricular assist device implantation or venovenous extracorporeal membrane oxygenation, respectively. Early identification of frail patients in an attempt to modify the risk of postoperative morbidity and mortality has become an important area of study over the last decade. Many quantification tools and risk prediction models for frailty have been developed but have not been evaluated extensively or standardized in the cardiothoracic transplant candidate population. Heightened awareness of frailty, coupled with a better understanding of distinct cellular mechanisms and biomarkers apart from end-stage organ disease, may play an important role in potentially reversing frailty related to organ failure. Furthermore, the clinical management of these critically ill patients may be enhanced by waitlist and postoperative physical rehabilitation and nutritional optimization.

Climate, forest growing season, and evapotranspiration changes in the central Appalachian Mountains, USA.

We analyzed trends in climatologic, hydrologic, and growing season length variables, identified the important variables effecting growing season length changes, and evaluated the influence of a lengthened growing season on increasing evapotranspiration trends for the central Appalachian Mountains region of the United States. We generated three growing season length variables using remotely sensed GIMMS NDVI3g data, two variables from measured streamflow, and 13 climate parameters from gridded datasets. We included various climate, hydrology, and phenology explanatory variables in two applications of Principle Components Analysis to reduce dimensionality, then utilized the final variables in two Linear Mixed Effects models to evaluate the role of climate on growing season length and evapotranspiration. The results showed that growing season length has increased, on average, by ~22 days and evapotranspiration has increased up to ~12 mm throughout the region. The results also suggest that a suite of climatic variables including temperature, vapor pressure deficit, wind, and humidity are important in growing season length change. The climatic variables work synergistically to produce greater evaporative demand and atmospheric humidity, which is theoretically consistent with intensification of the water cycle and the Clausius-Clapeyron relation, which states that humidity increases nonlinearly by 7%/K. Optimization of the evapotranspiration model was increased by the inclusion of growing season length, suggesting that growing season length is partially responsible for variations in evapotranspiration over time. The results of this research imply that a longer growing season has the potential to increase forest water cycling and evaporative loss in temperate forests, which may lead to decreased freshwater provisioning from forests to downstream population centers. Additionally, results from this study provide important information for runoff and evapotranspiration modelling and forest water management under changing climate.

α-Pyrrolidinopentiophenone ("Flakka") Catalyzing Catatonia: A Case Report and Literature Review.

: Synthetic cathinones are a class of novel psychoactive substances. α-Pyrrolidinopentiophenone (α-PVP), or "Flakka", is one of these substances. Users often present acutely psychotic or agitated. We present the case of a 20-year-old male without prior psychiatric history who was brought to the hospital by his family because of increasingly bizarre and erratic behavior after reported ingestion of Flakka. What ensued was a prolonged course of psychosis and severe catatonia. Synthetic cathinones are thought to cause catatonia in approximately 1% of cases. Awareness of the possible presentations associated with α-PVP intoxication is increasingly important and should be further explored, as they can have important implications in setting expectations for care. Additionally, providers should have a low threshold for asking patients about bath salt ingestion.