Peroxisome proliferators-activated alpha agonist treatment ameliorates hepatic damage in rats with obstructive jaundice: an experimental study

<p>Abstract</p> <p>Background</p> <p>Peroxisome proliferators-activated receptor alpha (PPARα) activation modulates cholesterol metabolism and suppresses bile acid synthesis. This study aims to evaluate the effect of short-term administration of fenofibrate, a PPARα agonist, on proinflammatory cytokines, apoptosis, and hepatocellular damage in cholestasis.</p> <p>Methods</p> <p>Forty male Wistar rats were randomly divided into four groups: I = sham operated, II = bile duct ligation (BDL), III = BDL + vehicle (gum Arabic), IV = BDL + fenofibrate (100 mg/kg/day). All rats were sacrificed on 7^thday after obtaining blood samples and liver tissue. Total bilirubin, aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), gamma-glutamyl transferase, (GGT), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1 β), and total bile acid (TBA) in serum, and liver damage scores; portal inflammation, necrosis, bile duct number, in liver tissue were evaluated. Apoptosis in liver was also assessed by immunohistochemical staining.</p> <p>Results</p> <p>Fenofibrate administration significantly reduced serum total bilirubin, AST, ALT, ALP, and GGT, TNF-α, IL-1 β levels, and TBA (<it>P </it>< 0.01). Hepatic portal inflammation, hepatic necrosis, number of the bile ducts and apoptosis in rats with BDL were more prominent than the sham-operated animals (<it>P </it>< 0.01). PPARα induction improved all histopathologic parameters (<it>P </it>< 0.01), except for the number of the bile duct, which was markedly increased by fenofibrate therapy (<it>P </it>< 0.01).</p> <p>Conclusion</p> <p>Short-term administration of fenofibrate to the BDL rats exerts beneficial effects on hepatocellular damage and apoptosis.</p

The relationship between subtypes of depression and cardiovascular disease: a systematic review of biological models

A compelling association has been observed between cardiovascular disease (CVD) and depression, suggesting individuals with depression to be at significantly higher risk for CVD and CVD-related mortality. Systemic immune activation, hypothalamic–pituitary–adrenal (HPA) axis hyperactivity, arterial stiffness and endothelial dysfunction have been frequently implicated in this relationship. Although a differential epidemiological association between CVD and depression subtypes is evident, it has not been determined if this indicates subtype specific biological mechanisms. A comprehensive systematic literature search was conducted using PubMed and PsycINFO databases yielding 147 articles for this review. A complex pattern of systemic immune activation, endothelial dysfunction and HPA axis hyperactivity is suggestive of the biological relationship between CVD and depression subtypes. The findings of this review suggest that diagnostic subtypes rather than a unifying model of depression should be considered when investigating the bidirectional biological relationship between CVD and depression. The suggested model of a subtype-specific biological relationship between depression and CVDs has implications for future research and possibly for diagnostic and therapeutic processes

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

ICAR: endoscopic skull‐base surgery

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Effectiveness of a multidimensional approach for prevention of ventilator-associated pneumonia in 11 adult intensive care units from 10 cities of Turkey: Findings of the International Nosocomial Infection Control Consortium (INICC)

Purpose: To evaluate the impact of the International Nosocomial Infection Control Consortium (INICC) multidimensional approach on the reduction of ventilator-associated pneumonia (VAP) in adult patients hospitalized in 11 intensive care units (ICUs), from 10 hospitals, members of the INICC, in 10 cities of Turkey. Methods: A prospective active before-after surveillance study was conducted to determine the effect of the INICC multidimensional approach in the VAP rate. The study was divided into two phases. In phase 1, active prospective surveillance of VAP was conducted using the definitions of the Centers for Disease Control and Prevention National Health Safety Network, and the INICC methods. In phase 2, we implemented the multidimensional approach for VAP. The INICC multidimensional approach included the following measures: (1) bundle of infection control interventions, (2) education, (3) outcome surveillance, (4) process surveillance, (5) feedback of VAP rates, and (6) performance feedback of infection control practices. We compared the rates of VAP obtained in each phase. A time series analysis was performed to assess the impact of our approach. Results: In phase 1, we recorded 2,376 mechanical ventilator (MV)-days, and in phase 2, after implementing the multidimensional approach, we recorded 28,181 MV-days. The rate of VAP was 31.14 per 1,000 MV-days during phase 1, and 16.82 per 1,000 MV-days during phase 2, amounting to a 46 % VAP rate reduction (RR, 0.54; 95 % CI, 0.42-0.7; P value, 0.0001.) Conclusions: The INICC multidimensional approach was associated with a significant reduction in the VAP rate in these adult ICUs of Turkey. © 2013 Springer-Verlag Berlin Heidelberg

Econometric Modelling: Extensions

AbstractThis chapter is devoted to advanced issues of econometric modelling. The topics covered are, among others, models in willingness to pay space, the meaning of scale heterogeneity in discrete choice models and the application of various information processing rules such as random regret minimisation or attribute non-attendance. Other topics are anchoring and learning effects when respondents move through a sequence of choice tasks as well as different information processing strategies such as lexicographic preferences or choices based on elimination-by-aspects