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KEY FINDINGS Euscaphic acid protected vascular endothelial cells against hypoxia-induced apoptosis via ERK1/2 signaling pathway, and Tormentic acid brought its efficacy into full play via PI3K/AKT and ERK1/2 signaling pathways. In addition, PI3K/AKT signaling pathway positively regulated ERK1/2 pathway, and ERK1/2 pathway negatively regulated PI3K/AKT pathway. SIGNIFICANCE This evidence provides theoretical and experimental basis for the following research on anti-hypoxic drugs of Potentilla anserina L. BACKGROUND Non-adherence to oral prednisolone is an important driver of poor control in severe asthma, and its detection is warranted to guide management. RESEARCH QUESTION to study the utility of liquid chromatography and tandem mass spectrometry (LC-MS/MS) in determining the adherence status to oral prednisolone in severe asthma. STUDY DESIGN AND METHODS timeline serum levels of prednisolone, cortisol and metabolites were measured using a validated LC-MS/MS assay following observed intake of prednisolone in patients on maintenance oral prednisolone. Patterns of adherence and non-adherence were determined from analysis of peak blood levels. The performance of a spot test for adherence (detectable prednisolone and suppressed cortisol) was assessed in a second cohort of patients on maintenance prednisolone and a control group. RESULTS In the prednisolone absorption test 27 patients [mean age 38.6 years (17-63), 24 (83%) females] were included. We identified adherence in 13 (48%), non-adherence in 13 (48%), and malabsorption in 1(3.7%). The median (IQR) peak serum assays (nmol/L) of the adherent compared to the non-adherent groups were; cortisol 36(39.5) vs 295(153), prednisolone 1810 (590) vs 1730(727). The spot test cohort included 111 patients [67 on maintenance prednisolone and 44 control, the mean age was 42.4 years and 79% were females. Non-adherence was detected in 40.3% of patients and comparison of the adherent versus non-adherent groups showed; cortisol 27(48) vs 211(130) and prednisolone 259 (622) vs less then 20 respectively. The adherent patients had higher mean BMI (38.4±8.7 vs 32±7.5kg/m2, p= 0.03), lower median blood eosinophils (90 (310) vs 510 (530) cells/μl, p less then 0.001) and a trend towards reduced mean annual severe exacerbations (3.0±2.6 vs 4.3±2.4, p=0.3) than the non-adherent patients. INTERPRETATION non-adherence to oral prednisolone is common in severe asthma and can be reliably detected in the clinic using the LC-MS/MS assay. BACKGROUND Heart failure (HF) is a leading cause of morbidity and mortality and while linked to sleep apnea, it is unclear which physiological stressors most strongly associate with incident disease. Here we tested whether Sleep Apnea-Specific Hypoxic Burden (SASHB) predicts incident HF in two independent cohort studies. METHODS The samples were derived from two cohort studies The Sleep Heart Health Study (SHHS), which included 4881 middle-aged and older adults (54.4% women), age 63.6±11.1 years; and the Outcomes of Sleep Disorders in Older Men (MrOS), which included 2653 men, age 76.2±5.4 years. read more We computed SASHB as the sleep apnea-specific area under the desaturation curve from pre-event baseline. We used Cox models for incident heart Failure (HF) to estimate the adjusted hazard ratios for natural log-transformed SASHB and apnea-hypopnea index (AHI) adjusting for multiple confounders. RESULTS The SASHB predicted incident HF in men in both cohorts while AHI did not. Men in SHHS and MrOS had adjusted hazard ratios (per 1SD increase in SASHB) of 1.18 (95% CI 1.02-1.37) and 1.22 (95% CI 1.02-1.45), respectively. Associations with SASHB were observed in men with both low and high AHI levels. Associations were not significant in women. CONCLUSIONS In men, the hypoxic burden of sleep apnea was associated with incident HF after accounting for demographic factors, smoking, and co-morbidities. The findings suggest that quantification of an easily measured index of sleep apnea related hypoxias may be useful for identifying individuals at risk for heart disease while also suggesting targets for intervention. BACKGROUND In patients with a history suggestive of asthma, diagnosis is usually confirmed by spirometry with bronchodilator response (BDR) or confirmatory methacholine challenge testing (MCT). RESEARCH QUESTION We examined the proportion of participants with negative BDR testing who had a positive MCT (and its predictors), and characteristics of MCT, including effects of controller medication tapering and temporal variability (and predictors of MCT result change); and concordance between MCT and pulmonologist asthma diagnosis. STUDY DESIGN AND METHODS Adults with self-reported physician-diagnosed asthma were recruited by random-digit dialing across Canada. Subjects performed spirometry with BDR testing and returned for MCT if testing was non-diagnostic for asthma. Subjects on controllers underwent medication tapering with serial MCTs over 3-6 weeks. Subjects with a negative MCT (PC20 > 8 mg/mL) off medications were examined by a pulmonologist and had serial MCTs after 6 and 12 months. RESULTS Of 500 subjects exists, repeat testing appears to be warranted. BACKGROUND A paucity of studies have assessed the epidemiology of community-acquired pneumonia (CAP) requiring intensive care unit (ICU) admission. We conducted a study on this group of patients with the primary objective of defining the incidence, epidemiology and mortality of CAP in the ICUs in Louisville, KY. The secondary objective was to estimate the number of patients hospitalized and the number of deaths associated with CAP in ICU in the US. METHODS This was a secondary analysis of a prospective population-based cohort study. The setting was all nine adult hospitals in Louisville, KY. The annual incidence of CAP in the ICU per 100,000 adults was calculated for the whole adult population of Louisville. The number of patients hospitalized due to CAP in ICU in the US was estimated by multiplying the Louisville incidence rate of CAP in ICU by the 2014 US adult population. RESULTS From a total of 7,449 unique patients hospitalized with CAP, 1,707 (23%) were admitted to ICU. The incidence of CAP in the ICU was 145 cases per 100,000 population of adults.
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