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Pulmonary disease progression in patients with cystic fibrosis (CF) is characterised by inflammation and fibrosis and aggravated by
(Pa). We investigated the impact of Pa specifically on 1) protease/antiprotease balance; 2) inflammation; and 3) the link of both parameters to clinical parameters of CF patients.
Transforming growth factor-β
(TGF-β
), interleukin (IL)-1β, IL-8, neutrophil elastase (NE) and elastase inhibitor elafin were measured (ELISA assays), and gene expression of the NF-κB pathway was assessed (reverse transcriptase PCR) in the sputum of 60 CF patients with a minimum age of 5 years. Spirometry was assessed according to American Thoracic Society guidelines.
Our results demonstrated the following 1) NE was markedly increased in Pa-positive sputum, whereas elafin was significantly decreased; 2) increased IL-1β/IL-8 levels were associated with both Pa infection and reduced forced expiratory volume in 1 s, and sputum TGF-β
was elevated in Pa-infected CF patients and linked to an imp and TGF-β1 might be promising therapeutic strategies in future CF therapy and a possible complement to cystic fibrosis transmembrane conductance regulator (CFTR) modulators.
Pulmonary hypertension (PH) is associated with significant perioperative morbidity and mortality. We hypothesised that pulmonary arterial hypertension (PAH) composite risk assessment scores could estimate perioperative risk for PH patients when adjusted for inherent procedural risk.
We identified patients in the Johns Hopkins PH Center Registry that had noncardiac surgery (including endoscopies) between September 2015 and January 2020. We collected information on preoperative patient-level and procedural variables and used logistic regression to evaluate associations with a composite outcome of death within 30 days or serious postoperative complication. We generated composite patient-level risk assessment scores for each subject and used logistic regression to estimate the association with adverse surgical outcomes. We adjusted multivariable models for inherent procedural risk of major cardiovascular events and used these models to generate a numerical PH perioperative risk (PHPR) score.
Among 150 subjects, 19 (12.7%) reached the primary outcome, including 7 deaths (4.7%). Individual patient-level and procedural variables were associated with the primary outcome (all p<0.05). A composite patient-level risk assessment score built on three noninvasive parameters was strongly associated with reduced risk for poor outcomes (OR=0.4, p=0.03). This association was strengthened after adjusting the model for procedural risk. A PHPR score derived from the multivariable model stratified patients into low (0%), intermediate (≤10%), or high (>10%) risk of reaching the primary outcome.
Composite PAH risk assessment scores can predict perioperative risk for PH patients after accounting for inherent procedural risk. Validation of the PHPR score in a multicentre, prospective cohort is warranted.
Composite PAH risk assessment scores can predict perioperative risk for PH patients after accounting for inherent procedural risk. Validation of the PHPR score in a multicentre, prospective cohort is warranted.Background In rural Tanzania, women and girls disproportionately bear the burden of water scarcity. Gendered social norms on the acceptability of women's participation in the public sphere limit their decision-making power within local water governance structures. The UPWARD (Uplifting Women's Participation in Water-Related Decision-Making) intervention sought to understand how a community-based gendered social norms approach using organized diffusion can lead to changes in the gendered social norms impacting women's participation in water-related governance structures. Methods As part of WARIDI, a 5-years integrated water resource management (IWRM) program, a gendered-social norms change (GSNC) activity (UPWARD Uplifting Women's Participation in Water-Related Decision-Making) was implemented in two villages in Iringa and Kilombero districts. Encouraging organized diffusion, UPWARD promoted gender-equitable norms among a critical mass of community members. WARIDI identified and trained a Community Facilitatioting norm change may be harder to affect where norms are tighter. Conclusion UPWARD provides evidence that gendered social norms change programs can have identifiable impacts on women's participation in water-related decision-making over a short time. While other interventions have used larger, multi-level strategies to affect gender norms, UPWARD has shown that community mobilization with brief (∼4 months) but concentrated engagement with communities can promote changes in social norms that persist at least 6 months after intervention's end.Thrombosis is common in critically ill dogs and causes considerable morbidity and mortality. The direct factor Xa inhibitor apixaban is safe, efficacious, and convenient in humans. This study aimed to determine the pharmacokinetics (PK), bioactivity, protein binding, and bioavailability of apixaban following intravenous (IV) and oral (PO) administration to healthy dogs. Six healthy, adult, mixed-breed dogs were administered apixaban 0.18 mg/kg IV and then following a minimum 2-week washout period administered apixaban 0.2 mg/kg PO. Dogs were monitored using an apixaban-calibrated anti-Xa bioassay, prothrombin time (PT) and activated partial thromboplastin time (aPTT) and tissue-factor thromboelastography (TF-TEG). Plasma apixaban concentrations were measured using liquid chromatography-tandem mass spectrometry. Concentration-time plots were constructed, and PK modeling performed using compartmental methods. Administration of IV and PO apixaban was well-tolerated. Following IV administration, mean half-life wa and establish safe, effective dosing ranges in sick dogs.Background On October 30, 2020, piglets and sows in the farrowing house of a pig farm in Jiangxi showed clinical symptoms such as anorexia, watery diarrhea, and vomiting. Epidemiological test, clinical necropsy, and RT-PCR test were carried out on the pig farm for diagnosis. After comprehensive considerations, the disease was judged as porcine epidemic diarrhea virus infection. Results Thereafter, a series of comprehensive prevention and control measures such as emergency vaccination with autogenous vaccines were adopted. Half a month after inoculation with autogenous vaccines for the farm, the mortality rate of newborn piglets in the farrowing house began to decline, and production gradually returned to being stable. The second-generation sequencing analysis and phylogenetic analysis showed that the porcine epidemic diarrhea virus (PEDV) sequence obtained from the stool and small intestine samples of the diseased pigs on the farm was 97.8% homologous to the vaccine strain. At the same time, antibody testing found that the vaccinated pigs on the pig farm had satisfactory immune response. Conclusion This case indicated that the PEDV outbreak on the pig farm might aggravate owing to the strain being mutated and could escape the immune protection of the existing vaccine. This case has accumulated technical data for the clinical prevention and control of porcine epidemic diarrhea.Autologous protein solution (APS) has been used anecdotally for intralesional treatment of tendon and ligament injuries, however, its use in these injuries has never been studied in vivo. Our objective was to evaluate the effect of APS on tendon healing in an equine superficial digital flexor (SDF) tendonitis model. We hypothesized intralesional injection of APS would result in superior structural and biomechanical healing. SDF tendonitis was induced in both forelimbs of eight horses using collagenase injection. One forelimb was randomly assigned to receive an intralesional injection of APS, while the other was injected with saline. Ultrasonographic examinations were performed at weeks -1, 0, 2, 4, 8, and 12 following treatment. At 12 weeks, horses were euthanized and SDF samples harvested. Histologic evaluation, biomechanical testing, gene expression analysis, total glycosaminoglycan (GAG) and total DNA quantification were performed. Collagen type III (COL3A1) expression was significantly higher (p = 0.028) in saline treated tendon than in normal tendon. Otherwise, there were no significant differences in gene expression. There were no significant differences in histologic or ultrasonographic scores between groups. Mean total DNA content was significantly higher (p = 0.024) in saline treated tendons than normal tendons, whereas total DNA content was not significantly different between APS treated tendon and normal tendon. Elastic modulus was higher in APS treated than saline treated tendon, but the difference was not significant. Reduced expression of COL3A1 in APS treated tendon may indicate superior healing. Increased total DNA content in saline treated tendon may indicate ongoing healing processes, vs. APS treated tendons which may be in the later stages of healing. Limitations include a relatively short study period and inconsistency in size and severity of induced lesions. Intralesional injection of APS resulted in some improvements in healing characteristics.A 4-year-old female Boxer was referred for renal replacement therapy 2 days after observed grape ingestion. An 11-French dual-lumen dialysis catheter was placed into the right jugular vein and continuous renal replacement therapy was initiated for 66 h. Afterwards the patient received enoxaparin subcutaneously as a thromboprophylaxis. Four hours after removal of the dialysis catheter the patient developed severe dyspnea with hypercapnia and signs of hemorrhagic shock. Bedside ultrasound and X-rays of the thorax revealed a soft tissue opacity dorsally of the trachea, located in the mediastinum. The findings were consistent with mediastinal bleeding and hematoma formation. Blood gas examination indicated hypoventilation. The dog was managed conservatively with multiple blood transfusions and mechanical ventilation. The patient survived to discharge, and the hematoma was fully absorbed in the radiographs after 17 days. Patients with impaired kidney function should receive individualized enoxaparin dosage adjusted to anti-Xa levels and should be strictly monitored for complications. Mediastinal hemorrhage and hematoma formation should be considered as a potential complication in patients receiving a jugular vein catheter.Cerebral coenurosis, caused by the larvae of Taenia multiceps (Coenurus cerebralis), is a fatal central nervous system disease in sheep and other herbivores and occasionally humans. click here Comparative transcriptomic profiles of the developmental stages of the parasite remain unknown. In this study, RNA sequencing was used to determine the transcriptome profiles of different stages of the life cycle of T. multiceps, including Oncosphere, Coenurus cerebralis (Pro with Cyst), and Adult (Adu), as well as scolex-neck proglottids (Snp), immature-mature proglottids (Imp), and gravid proglottids (Grp) of the adult stage. A total of 42.6 Gb (average 6.1 Gb) Illumina pair-end reads with a 125-bp read length were generated for seven samples. The total number of differentially expressed genes (DEGs) in the various life stages ranged from 2,577 to 3,879; however, for the tissues of the adult worm, the range was from 1,229 to 1,939. Kyoto Encyclopedia of Genes and Genomes analysis showed that the DEGs mainly participated in cellular and metabolic processes, binding and catalytic activity, genetic information processing, and environmental information processing.