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An 8‐year‐old Leonberger receiving immunosuppressive treatment with clinical signs of acute dyspnea, cyanosis, and difficulty standing was referred to our institution (Day 1). Treatment including oxygen, clopidogrel, and low‐molecular‐weight heparin was initiated for suspected pulmonary thrombosis. However, exertional dyspnea persisted until Day 10, and increased tricuspid regurgitation velocity, pulmonary vascular resistance, and McConnell's signs also were observed. Thus, beraprost sodium was administered PO on Day 11 to treat suspected pulmonary hypertension. On Day 13, contrast‐enhanced computed tomography identified extensive contrast defects in the pulmonary arteries, and IV monteplase was administered on Days 14 and 18, with marked improvement in respiratory status and exertional dyspnea on Day 20. Right ventricular function and McConnell signs also improved, and tricuspid regurgitation velocity and pulmonary vascular resistance decreased. On Day 250, echocardiography indicated further improvement in pulmonary hypertension pathophysiology. The patient was still progressing well with antithrombotic and pulmonary vasodilator treatment 400 days later. [ABSTRACT FROM AUTHOR]

With the determination of numerous viral and bacterial genome sequences, sequence‐trait relationships, such as the evolution of virulence and associations to geographic location or host, are now being studied. In these studies, phylogenetic trees were first reconstructed, and trait data were analysed based on the trees. However, in some cases, such as fast evolution sequences and gene‐sharing network data, reconstructing the phylogenetic tree is challenging. Even in such cases, it is possible to quantify the similarity between sequences and construct an similarity network.Here, we propose a novel approach, Network‐Trait association with Graph Fourier Transform (NeTaGFT), to analyse network‐trait associations. NeTaGFT is inspired by graph signalling process techniques. The graph in this study corresponds to a similarity network representing the similarities between virus samples, and the graph signal corresponds to trait data. By using graph Fourier transform, NeTaGFT aims to identify trait signals and associations of various traits from a similarity network.We validated that NeTaGFT can find signals associated with network structures and associations of traits with the simulation dataset. We applied NeTaGFT for influenza type A and virome gene‐sharing datasets. As a result, we identified several network structures and their associated traits.Our approach is expected to provide novel insights into network‐based approach not only for typical sequence‐trait relationships but also for various biological data, such as antibody evolution. [ABSTRACT FROM AUTHOR]

Malaria infection elicits both protective and pathogenic immune responses, and IL‐27 is a critical cytokine that regulate effector responses during infection. Here, we identified a critical window of CD4+ T cell responses that is targeted by IL‐27. Neutralization of IL‐27 during acute infection with Plasmodium chabaudi expanded specific CD4+ T cells, which were maintained at high levels thereafter. In the chronic phase, Plasmodium‐specific CD4+ T cells in IL‐27‐neutralized mice consisted mainly of CD127+KLRG1− and CD127−KLRG1+ subpopulations that displayed distinct cytokine production, proliferative capacity, and are maintained in a manner independent of active infection. Single‐cell RNA‐seq analysis revealed that these CD4+ T cell subsets formed independent clusters that express unique Th1‐type genes. These IL‐27‐neutralized mice exhibited enhanced cellular and humoral immune responses and protection. These findings demonstrate that IL‐27, which is produced during the acute phase of malaria infection, inhibits the development of unique Th1 memory precursor CD4+ T cells, suggesting potential implications for the development of vaccines and other strategic interventions. Synopsis: IL‐27 inhibits the generation of parasite‐specific memory CD4+ T cells in a malaria infection model. Transient blockade of IL‐27 elicits high levels of unique CD127+ and KLRG1+ memory CD4+ T cells, elevates antibody production, and enhances protective immunity against secondary infection. IL‐27 produced during the acute phase of malaria infection is inhibitory for the generation of parasite‐specific memory CD4+ T cells.Two types of unique memory CD4+ T cells are generated in the absence of IL‐27: CD127+ and KLRG1+ cells expressing high levels of Ifng and Tbx21, respectively.Memory CD4+ T cells induced in the absence of IL‐27 can be maintained in the absence of persistent malaria infection.The absence of IL‐27 during the acute phase of malaria infection generates memory immune responses that are protective against challenge infection. [ABSTRACT FROM AUTHOR]

We aimed to elucidate details of comorbid chronic rhinosinusitis (CRS) in chronic eosinophilic pneumonia (CEP) under the collaboration between otolaryngologists and pulmonologists in a prospective study. The CEP diagnosis was performed by pulmonologists based on clinical symptoms, laboratory findings, and/or eosinophilia detected in bronchoalveolar lavage. All patients were referred to otolaryngologists before undergoing oral corticosteroid treatment for CEP. Ten CEP cases visited to otolaryngologists. All cases showed bilateral sinonasal inflammation in computed tomography (CT), indicating comorbid CRS. Nasal polyps (NPs) were observed in 50% of patients on endoscopy. Eighty percent of patients were diagnosed with eosinophilic CRS. In blood eosinophil levels and the mucosal eosinophil count, there were no significant differences between CRS without and with NPs. In Lund–Mackay CT total scores, among‐individual variability was observed in CRS with NPs. The collaboration revealed blood/sinonasal eosinophilia and the variability in Lund–Mackay CT total scores as remarkable findings about the comorbid CRS. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypertension (PH) secondary to respiratory disease is caused by pulmonary vascular remodeling and hypoxia. Severe PH can induce various clinical signs, including syncope and right‐sided heart failure. Hypothesis/Objectives: To investigate the echocardiographic characteristics in dogs with PH secondary to respiratory diseases. Animals: Thirty‐one dogs with respiratory diseases with or without PH and 15 healthy dogs. Methods: Prospective cross‐sectional study. Dogs were classified according to respiratory disease (obstructive airway/lung disease [OALD] or restrictive lung disease [RLD]) and PH‐relevant signs. The association between echocardiographic variables and PH (classified by respiratory disease and PH‐relevant signs) was investigated. Results: Twenty‐one dogs were diagnosed with PH; of these, 11 showed PH‐related signs (OALD, n = 2; RLD, n = 9), 14 had right ventricular hypertrophy, and 19 had pulmonary arterial enlargement. Right ventricular dysfunction and dilatation were observed only in dogs with PH‐related signs (n = 10). Left and right ventricular stroke volumes were significantly lower in dogs with PH (median [interquartile range]: 17.2 [12.4‐20.8] and 16.8 [15.3‐29.5] mL/m2, respectively). Dogs with RLD had higher echocardiography‐estimated pulmonary vascular resistance than those with OALD (median [interquartile range]: 3.1 [1.9‐3.3] and 1.6 [1.3‐2.2], respectively). Conclusions and Clinical Importance: Pulmonary arterial enlargement was the most common echocardiographic finding in dogs with PH secondary to respiratory diseases. Right ventricular dysfunction, dilatation, and decreased left and right ventricular stroke volume were significantly associated with the PH‐related signs, indicating that comprehensive echocardiography is recommended in dogs with respiratory disease. Restricted lung disease might induce more severe PH than OALD. [ABSTRACT FROM AUTHOR]

Background: Progression to combined post‐ and pre‐capillary pulmonary hypertension (PH) provides prognostic information in human patients with post‐capillary PH. Pulmonary vascular resistance estimated by echocardiography (PVRecho) is useful for the stratification of dogs with myxomatous mitral valve disease (MMVD) and detectable tricuspid regurgitation. Objectives: To evaluate the prognostic value of PVRecho in dogs with MMVD. Animals: Fifty‐four dogs with MMVD and detectable tricuspid regurgitation. Methods: Prospective cohort study. All dogs underwent echocardiography. The PVRecho was calculated based on tricuspid regurgitation and the velocity‐time integral of the pulmonary artery flow. To evaluate the influence of echocardiographic variables on cardiac‐related deaths, Cox proportional hazard analysis was performed. Additionally, Kaplan‐Meier curves classified by PVRecho tertiles were made and compared using log‐rank tests to evaluate the influence of PVRecho on all‐cause mortality and cardiac‐related death. Results: The median follow‐up time was 579 days. Forty‐one dogs with MMVD (PH severity [number]: no or mild, 21/33; moderate, 11/11; severe, 9/10) died during the study. In the multivariable Cox proportional hazard analysis adjusted for age, sildenafil administration, and American College of Veterinary Internal Medicine stage of MMVD, left atrial to aortic diameter ratio and PVRecho remained significant (adjusted hazard ratio [95% confidence interval]: 1.2 [1.1‐1.3] and 2.1 [1.6‐3.0], respectively). Higher PVRecho showed a significant association with lower survival rates. Conclusions and Clinical Importance: Left atrial enlargement and high PVRecho were independent prognostic factors in dogs with MMVD and detectable tricuspid regurgitation. [ABSTRACT FROM AUTHOR]

Objective: Parkinson's disease (PD) is a common neurodegenerative disease characterized by initial involvement of the olfactory bulb/amygdala or autonomic nerves followed by nigral degeneration. Although autonomic innervation strictly regulates multiorgan systems, including endocrine functions, circulation, and digestion, how dysautonomia in PD affects systemic metabolism has not been identified. In this study, we tried to estimate the pathogenic linkage of PD by nuclear medicine techniques, trans‐omic analysis of blood samples, and cultured cell experiments. Methods: Thyroid mediastinum ratio of 123I‐metaiodobenzylguanidine (MIBG) scintigraphy was measured in 1,158 patients with PD. Furthermore, serum exosome miRNA transcriptome analysis and plasma metabolome analysis followed by trans‐omic analysis were performed in patients with de novo PD and age‐matched healthy control persons. Additionally, thyroid hormone was administered to skeletal muscle and liver derived cells to evaluate the effect of hypothyroidism for these organs. Results: Sympathetic denervation of thyroid correlating with its cardiac denervation was confirmed in 1,158 patients with PD by MIBG scintigraphy. Among patients with drug‐naïve PD, comprehensive metabolome analysis revealed decreased levels of thyroxine and insufficient fatty acid β‐oxidation, which positively correlate with one another. Likewise, both plasma metabolome data and transcriptome data of circulating exosomal miRNAs, revealed specific enrichment of the peroxisome proliferator‐activated receptor (PPARα) axis. Finally, association of thyroid hormone with PPARα‐dependent β‐oxidation regulation was confirmed by in vitro experiments. Interpretation: Our findings suggest that interorgan communications between the thyroid and liver are disorganized in the early stage of PD, which would be a sensitive diagnostic biomarker for PD. ANN NEUROL 2023;93:303–316 [ABSTRACT FROM AUTHOR]

Background: Tricuspid annular plane systolic excursion (TAPSE) is a common right ventricular (RV) function indicator. However, TAPSE was not decreased in dogs with myxomatous mitral valve disease (MMVD) and postcapillary pulmonary hypertension (PH) because of its load, angle, and body weight dependency, and TAPSE was considered a preload‐dependent index. Objectives: To evaluate the utility of TAPSE normalized by RV size in dogs with postcapillary PH. Animals Twenty healthy dogs and 71 MMVD dogs with or without PH. Methods: In this prospective observational study, end‐diastolic RV internal dimension (RVIDd), end‐diastolic and end‐systolic RV area, and end‐diastolic RV wall thickness were measured as RV size indices. The TAPSE was measured using B‐mode and M‐mode methods. Normalized TAPSE was calculated by dividing TAPSE by each RV size index. The RV strain was obtained as the detailed RV function using 2‐dimensional speckle tracking echocardiography. All indices were compared among the PH severity groups and in the presence of right‐sided congestive heart failure (R‐CHF). Results: Although nonnormalized TAPSE was higher with PH severity progression, each normalized TAPSE showed a significant decrease in the severe PH group (P <.05). The TAPSEB‐mode/RVIDd ratio had high area under the curve to predict R‐CHF and had moderate correlation with RV strain (P <.05). The TAPSEB‐mode/RVIDd and left atrial‐to‐aortic diameter ratios were independent predictors for R‐CHF. Conclusions and Clinical Importance: Normalized TAPSE could reflect RV systolic dysfunction in dogs with severe PH, which could not be detected by nonnormalized TAPSE. The TAPSEB‐mode/RVIDd ratio might predict R‐CHF with high sensitivity and reproducibility. [ABSTRACT FROM AUTHOR]

Background: Hypertrophic cardiomyopathy (HCM), a primary disorder of the myocardium, is the most common cardiac disease in cats. However, determination of layer‐specific myocardial function with 2D speckle‐tracking echocardiography in cats with asymptomatic HCM has not yet been reported. Objectives: To quantitatively measure layer‐specific myocardial function of asymptomatic cats with HCM. Animals Ten client‐owned, asymptomatic cats with obstructive HCM and 13 healthy cats. Methods: A retrospective, case‐control study. Cats underwent assessment of layer‐specific myocardial function (whole, endocardial, and epicardial) in the longitudinal and circumferential directions by using 2D speckle‐tracking echocardiography. Results: Longitudinal strains were significantly lower in cats with HCM than controls in the whole (−15.5% vs −19.1%), endocardial (−18.3% vs −21.8%), and epicardial (−13.1% vs −16.8%) layers. Circumferential strains in whole and epicardial layers also were significantly lower in cats with HCM as compared with controls (−15.0% vs −20.2% and − 4.4% vs −9.4%, respectively). However, no significant difference was found between cats with HCM and controls in the global circumferential strain in the endocardial layer (−31.2% vs −34.2%). The circumferential endocardial‐to‐epicardial strain ratio was significantly higher in cats with HCM than in controls (6.1 vs 3.5). Conclusions and Clinical Importance: Layer‐specific myocardial function assessed by 2D speckle‐tracking echocardiography differed in asymptomatic cats with obstructive HCM compared to controls despite their apparently normal systolic function, as determined by conventional echocardiography. The maintained endocardial circumferential strain and higher circumferential endocardial‐to‐epicardial strain ratio may reflect compensation for occult systolic dysfunction in cats with obstructive HCM. [ABSTRACT FROM AUTHOR]

Dear Editor: We read the article by Soltani et al. with great interest and appreciate the authors' efforts to prove the effectiveness of gabapentin (GPT) and GPT/montelukast (MTL) combination in comparison with dextromethorphan (DXM) for the improvement of COVID-19-related cough.[1] However, we would like to highlight three concerns regarding the randomized controlled trial (RCT) conducted by the authors. Reducing bias in open-label trials where blinded outcome assessment is not feasible: strategies from two randomised trials. Letter to the editor regarding the study "The effectiveness of gabapentin and gabapentin/montelukast combination compared with dextromethorphan in the improvement of COVID-19-related cough: A randomized, controlled clinical trial". [Extracted from the article]

Malaria infection elicits both protective and pathogenic immune responses, and IL-27 is a critical cytokine that regulate effector responses during infection. Here, we identified a critical window of CD4 + T cell responses that is targeted by IL-27. Neutralization of IL-27 during acute infection with Plasmodium chabaudi expanded specific CD4 + T cells, which were maintained at high levels thereafter. In the chronic phase, Plasmodium-specific CD4 + T cells in IL-27-neutralized mice consisted mainly of CD127 + KLRG1 - and CD127 - KLRG1 + subpopulations that displayed distinct cytokine production, proliferative capacity, and are maintained in a manner independent of active infection. Single-cell RNA-seq analysis revealed that these CD4 + T cell subsets formed independent clusters that express unique Th1-type genes. These IL-27-neutralized mice exhibited enhanced cellular and humoral immune responses and protection. These findings demonstrate that IL-27, which is produced during the acute phase of malaria infection, inhibits the development of unique Th1 memory precursor CD4 + T cells, suggesting potential implications for the development of vaccines and other strategic interventions., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)