Airway hyperresponsiveness (AHR) is linked to airway inflammation and is considered a key manifestation of mild/moderate equine asthma (EA). The study purpose was to determine whether two modalities of non-invasive lung function testing (FOM-forced oscillatory mechanics vs. FP-flowmetric plethysmography) establish the same clinical diagnosis of AHR in horses, using histamine bronchoprovocation. Nineteen horses (3-25 years, 335-650 kg) with clinical signs suggestive of mild/moderate equine asthma were enrolled. FOM and FP testing was performed in each horse on two consecutive days, using a randomized cross-over design. AHR was defined by the histamine dose needed to double FOM baseline resistance, or to achieve a 35% increase in FP delta flow. Bronchoalveolar lavage fluid (BALF) was subsequently collected and stained with modified Wright's and toluidine blue stains. Binary statistical tests (related samples T-test, Mann-Whitney U, Chi-square analyses) were performed to compare study groups, with P less then 0.05 considered significant. Abnormal BALF cytology confirmed EA in 14/19 (73.7%) horses. Both FOM and FP revealed AHR in 7/14 (50%) of these EA horses. An additional 4/19 (21.1%) horses showed AHR based on FP but not FOM, including two horses with normal BALF cytology. A diagnosis of AHR was more often associated with FP than FOM (P = 0.013), although the prevalence of AHR was significantly higher in EA vs. non-EA horses, regardless of testing methodology. The phase angle between thoracic and abdominal components of breathing did not differ between test groups. In conclusion, FP diagnosed AHR more frequently than did FOM, including horses with no other diagnostic evidence of EA. Without further evaluation, these two testing modalities of AHR cannot be used interchangeably.Introduction N-terminal-pro-brain natriuretic peptide (NT-pro BNP) is secreted by cardiomyocytes in cases of cardiac structure disorder and volume overload. However, the relationship between NT-pro BNP level and body fluid status in dialysis patients with reduced cardiac ejection function (EF) is uncertain. Therefore, we aimed to investigate this relationship. https://www.selleckchem.com/products/ttnpb-arotinoid-acid.html Methods We enrolled patients who had been receiving hemodialysis for >3 months. Blood sample, transthoracic echocardiographic, and bioimpedance spectroscopy measurements were performed during a midweek non-dialysis day. The predictive value of NT-pro BNP in hemodialysis patients with volume overload was analyzed. Results A total of 129 hemodialysis patients (74 men and 55 women; mean age 59.4 ± 13.0 years) were recruited. The average hemodialysis duration was 55.5 (23.9-93.4) months, the NT-pro BNP level was 4992 (2,033-15,807) pg/mL, and the value of overhydration was 2.68 ± 0.19 (-1.9 to 12.2) L. The NT-pro BNP level was independently correlated with overhydration in both the LVEF ≥ 60% (β = 0.236, P = 0.044) and LVEF less then 60% (β = 0.516, P = 0.032) groups, even after adjustments for potentially confounding variables. In receiver operating characteristic curves of NT-pro BNP for predicting volume overload, the area under the curve was 0.783 [95% CI (0.688-0.879), P less then 0.001) and 0.788 [95% CI (0.586-0.989), P less then 0.001] in the LVEF ≥ 60% and LVEF less then 60% groups, respectively. Conclusions NT-pro BNP is a predictive factor for volume overload in hemodialysis patients with or without EF declines.Aims To evaluate the prognostic value of the preoperative lymphocyte-to-monocyte ratio (LMR) in patients who underwent cardiac surgery. Methods Clinical data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The optimal cutoff value of LMR was determined by X-tile software. The Cox proportional hazard model was applied for the identification of independent prognostic factors of 4-year mortality and survival curves were estimated using the Kaplan-Meier method. In order to balance the influence of potential confounding factors, a 11 propensity score matching (PSM) method was performed. Results A total of 1,701 patients were included. The X-tile software indicated that the optimal cutoff value of the LMR for 4-year mortality was 3.58. After PSM, 489 pairs of score-matched patients were generated. The Cox proportional hazard model showed that patients with an LMR less then 3.58 had a significantly higher 4-year mortality than patients with an LMR ≥ 3.58 in the entire cohort (HR = 1.925, 95%CI 1.509-2.456, p less then 0.001) and the PSM subset (HR = 1.568, 95%CI 1.2-2.05, p = 0.001). The survival curves showed that patients with an LMR less then 3.58 had a significant lower 4-year survival rate in the entire cohort (71.7 vs. 88.5%, p less then 0.001) and the PSM subset (73.2 vs. 81.4%, p = 0.002). Conclusions A lower LMR ( less then 3.58) was associated with a higher risk of 4-year mortality and can serve as a prognostic predictor of the long-term mortality in cardiac surgery patients.Next Generation Sequencing has identified many KCNQ1 genetic variants associated with type 1 long QT or Romano-Ward syndrome, most frequently inherited in an autosomal dominant fashion, although recessive forms have been reported. Particularly in the case of missense variants, functional studies of mutants are of aid to establish variant pathogenicity and to understand the mechanistic basis of disease. Two compound heterozygous KCNQ1 mutations (p.A300T and p.P535T) were previously found in a child who suffered sudden death. To provide further insight into the clinical significance and basis for pathogenicity of these variants, different combinations of wildtype, A300T and P535T alleles were co-expressed with the accessory β-subunit minK in HEK293 cells, to analyze colocalization with the plasma membrane and some biophysical phenotypes of homo and heterotetrameric channels using the patch-clamp technique. A300T homotetrameric channels showed left-shifted activation V1/2 as previously observed in Xenopus oocytes, decreased maximum conductance density, slow rise-time300ms, and a characteristic use-dependent response. A300T slow rise-time300ms and use-dependent response behaved as dominant biophysical traits for all allele combinations. The P535T variant significantly decreased maximum conductance density and Kv7.1-minK-plasma membrane colocalization. P535T/A300T heterotetrameric channels showed decreased colocalization with plasma membrane, slow rise-time300ms and the A300T characteristic use-dependent response. While A300T left shifted activation voltage dependence behaved as a recessive trait when co-expressed with WT alleles, it was dominant when co-expressed with P535T alleles. Conclusions The combination of P535T/A300T channel biophysical properties is compatible with recessive Romano Ward syndrome. Further analysis of other biophysical traits may identify other mechanisms involved in the pathophysiology of this disease.
Airway hyperresponsiveness (AHR) is linked to airway inflammation and is considered a key manifestation of mild/moderate equine asthma (EA). The study purpose was to determine whether two modalities of non-invasive lung function testing (FOM-forced oscillatory mechanics vs. FP-flowmetric plethysmography) establish the same clinical diagnosis of AHR in horses, using histamine bronchoprovocation. Nineteen horses (3-25 years, 335-650 kg) with clinical signs suggestive of mild/moderate equine asthma were enrolled. FOM and FP testing was performed in each horse on two consecutive days, using a randomized cross-over design. AHR was defined by the histamine dose needed to double FOM baseline resistance, or to achieve a 35% increase in FP delta flow. Bronchoalveolar lavage fluid (BALF) was subsequently collected and stained with modified Wright's and toluidine blue stains. Binary statistical tests (related samples T-test, Mann-Whitney U, Chi-square analyses) were performed to compare study groups, with P less then 0.05 considered significant. Abnormal BALF cytology confirmed EA in 14/19 (73.7%) horses. Both FOM and FP revealed AHR in 7/14 (50%) of these EA horses. An additional 4/19 (21.1%) horses showed AHR based on FP but not FOM, including two horses with normal BALF cytology. A diagnosis of AHR was more often associated with FP than FOM (P = 0.013), although the prevalence of AHR was significantly higher in EA vs. non-EA horses, regardless of testing methodology. The phase angle between thoracic and abdominal components of breathing did not differ between test groups. In conclusion, FP diagnosed AHR more frequently than did FOM, including horses with no other diagnostic evidence of EA. Without further evaluation, these two testing modalities of AHR cannot be used interchangeably.Introduction N-terminal-pro-brain natriuretic peptide (NT-pro BNP) is secreted by cardiomyocytes in cases of cardiac structure disorder and volume overload. However, the relationship between NT-pro BNP level and body fluid status in dialysis patients with reduced cardiac ejection function (EF) is uncertain. Therefore, we aimed to investigate this relationship. https://www.selleckchem.com/products/ttnpb-arotinoid-acid.html Methods We enrolled patients who had been receiving hemodialysis for >3 months. Blood sample, transthoracic echocardiographic, and bioimpedance spectroscopy measurements were performed during a midweek non-dialysis day. The predictive value of NT-pro BNP in hemodialysis patients with volume overload was analyzed. Results A total of 129 hemodialysis patients (74 men and 55 women; mean age 59.4 ± 13.0 years) were recruited. The average hemodialysis duration was 55.5 (23.9-93.4) months, the NT-pro BNP level was 4992 (2,033-15,807) pg/mL, and the value of overhydration was 2.68 ± 0.19 (-1.9 to 12.2) L. The NT-pro BNP level was independently correlated with overhydration in both the LVEF ≥ 60% (β = 0.236, P = 0.044) and LVEF less then 60% (β = 0.516, P = 0.032) groups, even after adjustments for potentially confounding variables. In receiver operating characteristic curves of NT-pro BNP for predicting volume overload, the area under the curve was 0.783 [95% CI (0.688-0.879), P less then 0.001) and 0.788 [95% CI (0.586-0.989), P less then 0.001] in the LVEF ≥ 60% and LVEF less then 60% groups, respectively. Conclusions NT-pro BNP is a predictive factor for volume overload in hemodialysis patients with or without EF declines.Aims To evaluate the prognostic value of the preoperative lymphocyte-to-monocyte ratio (LMR) in patients who underwent cardiac surgery. Methods Clinical data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The optimal cutoff value of LMR was determined by X-tile software. The Cox proportional hazard model was applied for the identification of independent prognostic factors of 4-year mortality and survival curves were estimated using the Kaplan-Meier method. In order to balance the influence of potential confounding factors, a 11 propensity score matching (PSM) method was performed. Results A total of 1,701 patients were included. The X-tile software indicated that the optimal cutoff value of the LMR for 4-year mortality was 3.58. After PSM, 489 pairs of score-matched patients were generated. The Cox proportional hazard model showed that patients with an LMR less then 3.58 had a significantly higher 4-year mortality than patients with an LMR ≥ 3.58 in the entire cohort (HR = 1.925, 95%CI 1.509-2.456, p less then 0.001) and the PSM subset (HR = 1.568, 95%CI 1.2-2.05, p = 0.001). The survival curves showed that patients with an LMR less then 3.58 had a significant lower 4-year survival rate in the entire cohort (71.7 vs. 88.5%, p less then 0.001) and the PSM subset (73.2 vs. 81.4%, p = 0.002). Conclusions A lower LMR ( less then 3.58) was associated with a higher risk of 4-year mortality and can serve as a prognostic predictor of the long-term mortality in cardiac surgery patients.Next Generation Sequencing has identified many KCNQ1 genetic variants associated with type 1 long QT or Romano-Ward syndrome, most frequently inherited in an autosomal dominant fashion, although recessive forms have been reported. Particularly in the case of missense variants, functional studies of mutants are of aid to establish variant pathogenicity and to understand the mechanistic basis of disease. Two compound heterozygous KCNQ1 mutations (p.A300T and p.P535T) were previously found in a child who suffered sudden death. To provide further insight into the clinical significance and basis for pathogenicity of these variants, different combinations of wildtype, A300T and P535T alleles were co-expressed with the accessory β-subunit minK in HEK293 cells, to analyze colocalization with the plasma membrane and some biophysical phenotypes of homo and heterotetrameric channels using the patch-clamp technique. A300T homotetrameric channels showed left-shifted activation V1/2 as previously observed in Xenopus oocytes, decreased maximum conductance density, slow rise-time300ms, and a characteristic use-dependent response. A300T slow rise-time300ms and use-dependent response behaved as dominant biophysical traits for all allele combinations. The P535T variant significantly decreased maximum conductance density and Kv7.1-minK-plasma membrane colocalization. P535T/A300T heterotetrameric channels showed decreased colocalization with plasma membrane, slow rise-time300ms and the A300T characteristic use-dependent response. While A300T left shifted activation voltage dependence behaved as a recessive trait when co-expressed with WT alleles, it was dominant when co-expressed with P535T alleles. Conclusions The combination of P535T/A300T channel biophysical properties is compatible with recessive Romano Ward syndrome. Further analysis of other biophysical traits may identify other mechanisms involved in the pathophysiology of this disease.
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