Detecting early kidney damage in horses with colic by measuring matrix metalloproteinase -9 and -2, other enzymes, urinary glucose and total proteins

BACKGROUND: The aim of the study was to investigate urine matrix metalloproteinase (MMP-2 and -9) activity, alkaline phosphatase/creatinine (U-AP/Cr) and gamma-glutamyl-transpeptidase/creatinine (U-GGT/Cr) ratios, glucose concentration, and urine protein/creatinine (U-Prot/Cr) ratio and to compare data with plasma MMP-2 and -9 activity, cystatin-C and creatinine concentrations in colic horses and healthy controls. Horses with surgical colic (n = 5) were compared to healthy stallions (n = 7) that came for castration. Blood and urine samples were collected. MMP gelatinolytic activity was measured by zymography. RESULTS: We found out that horses with colic had significantly higher urinary MMP-9 complex and proMMP-9 activities than horses in the control group. Colic horses also had higher plasma MMP-2 activity than the control horses. Serum creatinine, although within reference range, was significantly higher in the colic horses than in the control group. There was no significant increase in urinary alkaline phosphatase, gamma-glutamyltranspeptidase or total proteins in the colic horses compared to the control group. A human cystatin-C test (Dako Cytomation latex immunoassay(® )based on turbidimetry) did not cross react with equine cystatin-C. CONCLUSION: The results indicate that plasma MMP-2 may play a role in the pathogenesis of equine colic and urinary MMP-9 in equine kidney damage

A method to study the effect of bronchodilators on smoke retention in COPD patients: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Chronic obstructive pulmonary disease (COPD) is a common disease, associated with cardiovascular disease. Many patients use (long-acting) bronchodilators, whilst they continue smoking alongside. We hypothesised an interaction between bronchodilators and smoking that enhances smoke exposure, and hence cardiovascular disease. In this paper, we report our study protocol that explores the fundamental interaction, i.e. smoke retention.</p> <p>Method</p> <p>The design consists of a double-blinded, placebo-controlled, randomised crossover trial, in which 40 COPD patients smoke cigarettes during both undilated and maximal bronchodilated conditions. Our primary outcome is the retention of cigarette smoke, expressed as tar and nicotine weight. The inhaled tar weights are calculated from the correlated extracted nicotine weights in cigarette filters, whereas the exhaled weights are collected on Cambridge filters. We established the inhaled weight calculations by a pilot study, that included paired measurements from several smoking regimes. Our study protocol is approved by the local accredited medical review ethics committee.</p> <p>Discussion</p> <p>Our study is currently in progress. The pilot study revealed valid equations for inhaled tar and nicotine, with an R²of 0.82 and 0.74 (p < 0.01), respectively. We developed a method to study pulmonary smoke retentions in COPD patients under the influence of bronchodilation which may affect smoking-related disease. This trial will provide fundamental knowledge about the (cardiovascular) safety of bronchodilators in patients with COPD who persist in their habit of cigarette smoking.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00981851">NCT00981851</a></p

Determination of Therapeutic Equivalence of Generic Products of Gentamicin in the Neutropenic Mouse Thigh Infection Model

Background: Drug regulatory agencies (DRA) support prescription of generic products of intravenous antibiotics assuming therapeutic equivalence from pharmaceutical equivalence. Recent reports of deaths associated with generic heparin and metoprolol have raised concerns about the efficacy and safety of DRA-approved drugs. Methodology/Principal Findings: To challenge the assumption that pharmaceutical equivalence predicts therapeutic equivalence, we determined in vitro and in vivo the efficacy of the innovator product and 20 pharmaceutically equivalent generics of gentamicin. The data showed that, while only 1 generic product failed in vitro (MIC = 45.3 vs. 0.7 mg/L, P,0.05), 10 products (including gentamicin reference powder) failed in vivo against E. coli due to significantly inferior efficacy (E max = 4.81 to 5.32 vs. 5.99 log 10 CFU/g, P#0.043). Although the design lacked power to detect differences in survival after thigh infection with P. aeruginosa, dissemination to vital organs was significantly higher in animals treated with generic gentamicin despite 4 days of maximally effective treatment. Conclusion: Pharmaceutical equivalence does not predict therapeutic equivalence of generic gentamicin. Stricter criteri

Management of chronic obstructive pulmonary disease in India: a systematic review.

OBJECTIVES: Chronic diseases are fast becoming the largest health burden in India. Despite this, their management in India has not been well studied. We aimed to systematically review the nature and efficacy of current management strategies for chronic obstructive pulmonary disease (COPD) in India. METHODS: We used database searches (MEDLINE, EMBASE, IndMED, CENTRAL and CINAHL), journal hand-searches, scanning of reference lists and contact with experts to identify studies for systematic review. We did not review management strategies aimed at chronic diseases more generally, nor management of acute exacerbations. Due to the heterogeneity of reviewed studies, meta-analysis was not appropriate. Thus, narrative methods were used. SETTING: India. PARTICIPANTS: All adult populations resident in India. MAIN OUTCOME MEASURES: 1. Trialled interventions and outcomes 2. Extent and efficacy of current management strategies 3. Above outcomes by subgroup. RESULTS: We found information regarding current management - particularly regarding the implementation of national guidelines and primary prevention - to be minimal. This led to difficulty in interpreting studies of management strategies, which were varied and generally of positive effect. Data regarding current management outcomes were very few. CONCLUSIONS: The current understanding of management strategies for COPD in India is limited due to a lack of published data. Determination of the extent of current use of management guidelines, availability and use of treatment, and current primary prevention strategies would be useful. This would also provide evidence on which to interpret existing and future studies of management outcomes and novel interventions

The Overseeing Mother: Revisiting the Frontal-Pose Lady in the Wu Family Shrines in Second Century China

Located in present-day Jiaxiang in Shandong province, the Wu family shrines built during the second century in the Eastern Han dynasty (25–220) were among the best-known works in Chinese art history. Although for centuries scholars have exhaustively studied the pictorial programs, the frontal-pose female image situated on the second floor of the central pavilion carved at the rear wall of the shrines has remained a question. Beginning with the woman’s eyes, this article demonstrates that the image is more than a generic portrait (“hard motif ”), but rather represents “feminine overseeing from above” (“soft motif ”). This synthetic motif combines three different earlier motifs – the frontal-pose hostess enjoying entertainment, the elevated spectator, and the Queen Mother of the West. By creatively fusing the three motifs into one unity, the Jiaxiang artists lent to the frontal-pose lady a unique power: she not only dominated the center of the composition, but also, like a divine being, commanded a unified view of the surroundings on the lofty building, hence echoing the political reality of the empress mother’s “overseeing the court” in the second century during Eastern Han dynasty

Association of respiratory symptoms and lung function with occupation in the multinational Burden of Obstructive Lung Disease (BOLD) study

Background Chronic obstructive pulmonary disease has been associated with exposures in the workplace. We aimed to assess the association of respiratory symptoms and lung function with occupation in the Burden of Obstructive Lung Disease study. Methods We analysed cross-sectional data from 28 823 adults (≥40 years) in 34 countries. We considered 11 occupations and grouped them by likelihood of exposure to organic dusts, inorganic dusts and fumes. The association of chronic cough, chronic phlegm, wheeze, dyspnoea, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)/FVC with occupation was assessed, per study site, using multivariable regression. These estimates were then meta-analysed. Sensitivity analyses explored differences between sexes and gross national income. Results Overall, working in settings with potentially high exposure to dusts or fumes was associated with respiratory symptoms but not lung function differences. The most common occupation was farming. Compared to people not working in any of the 11 considered occupations, those who were farmers for ≥20 years were more likely to have chronic cough (OR 1.52, 95% CI 1.19–1.94), wheeze (OR 1.37, 95% CI 1.16–1.63) and dyspnoea (OR 1.83, 95% CI 1.53–2.20), but not lower FVC (β=0.02 L, 95% CI −0.02–0.06 L) or lower FEV1/FVC (β=0.04%, 95% CI −0.49–0.58%). Some findings differed by sex and gross national income. Conclusion At a population level, the occupational exposures considered in this study do not appear to be major determinants of differences in lung function, although they are associated with more respiratory symptoms. Because not all work settings were included in this study, respiratory surveillance should still be encouraged among high-risk dusty and fume job workers, especially in low- and middle-income countries.publishedVersio

Cohort Profile: Burden of Obstructive Lung Disease (BOLD) study

The Burden of Obstructive Lung Disease (BOLD) study was established to assess the prevalence of chronic airflow obstruction, a key characteristic of chronic obstructive pulmonary disease, and its risk factors in adults (≥40 years) from general populations across the world. The baseline study was conducted between 2003 and 2016, in 41 sites across Africa, Asia, Europe, North America, the Caribbean and Oceania, and collected high-quality pre- and post-bronchodilator spirometry from 28 828 participants. The follow-up study was conducted between 2019 and 2021, in 18 sites across Africa, Asia, Europe and the Caribbean. At baseline, there were in these sites 12 502 participants with high-quality spirometry. A total of 6452 were followed up, with 5936 completing the study core questionnaire. Of these, 4044 also provided high-quality pre- and post-bronchodilator spirometry. On both occasions, the core questionnaire covered information on respiratory symptoms, doctor diagnoses, health care use, medication use and ealth status, as well as potential risk factors. Information on occupation, environmental exposures and diet was also collected

Timing matters when correcting fake news

© 2021 National Academy of Sciences. All rights reserved. Countering misinformation can reduce belief in the moment, but corrective messages quickly fade from memory. We tested whether the longer-term impact of fact-checks depends on when people receive them. In two experiments (total N = 2,683), participants read true and false headlines taken from social media. In the treatment conditions, “true” and “false” tags appeared before, during, or after participants read each headline. Participants in a control condition received no information about veracity. One week later, participants in all conditions rated the same headlines’ accuracy. Providing fact-checks after headlines (debunking) improved subsequent truth discernment more than providing the same information during (labeling) or before (prebunking) exposure. This finding informs the cognitive science of belief revision and has practical implications for social media platform designers