Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Mekansal adaletsizliğin etkilediği okullar ve bu bağlamda okul ve öğrencinin karşılıklı kimlik üretiminin incelenmesi

Bu araştırmamekansal adaletsizliğin eğitim durumuna nasıl bir tesiri olduğunu belirlemek amacıyla yapılmıştır. Bu vaziyeti tespit etmek için açık uçlu anket tekniği ve gömülü teori yöntemi kullanılarak şu sorulara cevap aranmıştır:• Mekansal adaletsizlik eğitimi nasıl etkilemiştir?• Mekansal adaletsizlik okul ve öğrenci kimliklerinin oluşumunda ne derece etkilidir?• Maddi gen nedir ve araştırma yapılan sahada var mıdır?Araştırmanın çalışma grubu araştırma yapılan sahada yaşayan 11. Sınıf talebeleridir. Çalışma grubu 50 kadar öğrenciden oluşmuştur.Araştırma yapılırken açık uçlu anket tekniği kullanılarak sorular muhatabına yöneltilmiştir. Toplamda ankette 14 açık uçlu soru vardır. Gereken cevaplar gömülü teori yöntemi kullanılarak değerlendirilmiştir.Araştırmada elde edile bulgulara göre öğrenciler kendilerini başarılı-başarısız, olumlu-olumsuz özelliklerle tanımlamışlardır. Okullarını da eski, başarılı, başarısız gibi sıfatlarla tanımlamışlardır. Farklı sorulara verdikleri cevaplarla okulun ve bulundukları yerlerin dezavantajlarından söz etmişlerdir.Araştırmada elde edilen sonuçlara göre araştırma yapılan yerde maddi gen ağırlını hissettirmektedir. Mekansal adaletsizlik bölgede var olurken eğitim koşullarını negatif yönde etkilemiştir. Ve mekansal adaletsizlik okulun ve öğrencinin kimlik oluşumu sürecinde olumsuz etki yapmaktadır.--------------------This research is done with the objective to determine the effect of spatial injustice on educational attainment. To that end, answers are sought to following questions by using open-ended survey technique and grounded theory method:• How does the spatial injustice affect education?• How effective is the spatial injustice on identity formation of schools and students?• What is material gene and is it available in the research field?The study group of the research is composed of 11th grade students residing in the research field. The study group is composed of around 50 students.The questions are asked to respondents by using open-ended survey technique. The survey is composed of 14 open-ended questions. The answers are assessed by using grounded theory method.According to the findings obtained in the study, the students have identified themselves with successful-unsuccessful, positive-negative characteristics. They have defined their school with adjectives such as old, successful, unsuccessful. They have stated the disadvantages of the school and its location when they answered different questions.According to the results obtained in the study, the material gene is influential in the research location. Spatial injustice exists in the location and adversely affect the educational conditions. And spatial injustice has a negative effect in the identity formation process of the school and the student

Synthesis of 3,4-dihydroxypyrrolidine-2,5-dione and 3,5-dihydroxybenzoic acid derivatives and evaluation of the carbonic anhydrase I and II inhibition

WOS:000369915500005PubMed:25744511The inhibition of two human cytosolic carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I and II, with some 3,4-dihydroxypyrrolidine-2,5-dione and 3,5-dihydroxybenzoic acid derivatives, were investigated by using the esterase assay, with 4-nitrophenyl acetate (4-NPA) as substrate. Compounds 10-13 showed K-I values in the range of 112.7-441.5 mu M for hCA I and of 3.5-10.76 mu M against hCA II, respectively. These hydroxyl group containing compounds generally were competitive inhibitors. Some hydroxyl group containing compounds investigated here showed effective hCA II inhibitory effects, in the same range as the clinically used sulfonamide acetazolamide, and might be used as leads for generating enzyme inhibitors possibly targeting other CA isoforms which have not been yet assayed for their interactions with such agents

Predictive value of Neutrophil/Lymphocyte Ratio for the Diagnosis and Severity of Disease in Acute Appendicitis

Objective: Our aim was to investigate the value of neu­trophil/lymphocyte ratio for the diagnosis of acute appen­dicitis, and for the prediction of gangrenous/perforated appendicitis. Methods: The medical records of 162 patients having undergone appendectomies between January 2013 and September 2014 including age, gender, preoperatively as­sessed C-reactive protein (CRP), white blood cell (WBC), neutrophil (NEU), lymphocyte, and neutrophil/lymphocyte ratio (NLR) values were retrospectively evaluated, com­pared with the postoperative histopathological findings, and statistically analyzed. Results: The study group consisted of 97 (59.9%) men, and 65 (40.1%) women with a median age of 36.01 (18-90). Histopathological examinations revealed normal appendix in 21 (12.96%), and acute appendicitis in 141 (87.04%) patients. Appendiceal gangrene/perforation rate was 25.31%. Lymphocyte counts were decreased, while CRP, WBC, NEU, and NLR values were increased in acute appendicitis (p<0.05). NLR ≥4.0 was associated with 16.9 times increased possibility of acute appendicitis [p<0.01, Odds ratio (OR):16.864, 95% Confidence inter­val (CI):4.696-60.568]. In cases with NLR≥4.5, it was de­tected that the risk of appendiceal gangrene/perforation was 3.2 times higher [p<0.01, OR:3.258, 95% CI: 1.468-7.228]. Conclusions: In addition to physical examination and other diagnostic methods, NLR can be considered as a useful auxiliary tool for the diagnosis of acute appendi­citis, and for the prediction of gangrenous/perforated ap­pendicitis

Synthesis and biological evaluation of Au-NHC complexes

New seven Au-N-heterocyclic carbene (NHC) complexes have been synthesized via transmetalation from Ag-NHC complexes. NHC salts, Ag-NHC, and Au-NHC complexes were fully characterized by widely used spectroscopic techniques. The molecular and crystal structures of 3b and 3f Au-NHC complexes were clarified through the single-crystal X-ray diffraction method. According to X-ray diffraction analysis results, the coordination geometry around Au(I) atoms in the complexes are revealed to be almost linear with C-Au-Cl angle. Anticancer activity, DNA binding, xanthine oxidase (XO) inhibitory activity studies, and molecular docking studies were evaluated for all Au-NHC complexes to explore the binding mechanism at the active site. The IC50 value of Au-NHC complexes against human colorectal cancer (Caco-2) and breast cancer (MCF-7) cell lines was defined by MTT assay. The IC50 values for MCF-7 in the range of 5.2 +/- 2 to 152.4 +/- 1 mu M and Caco-2 5.2 +/- 1 to 152.7 +/- 2 mu M showed that 3a, 3b, 3c, 3d, and 3g have better anticancer activity than Cisplatin incredibly complex 3a against both cancer cell line. All Au-NHC complexes showed excellent antimicrobial activity against different bacteria and fungi. 3a was the complex that exhibited the best antimicrobial activity here as well. The XO inhibitory activity experimental results indicated that all gold complexes showed remarkable inhibition activity against XO compared to the generally used standard, allopurinol. The range of IC50 value was determined from 0.407 to 2.681 mu M. 3d complex showed the lowest IC50 value at 0.407 mu M. DNA binding experiments were performed using agarose gel electrophoresis to observe the ability of synthesized Au-NHC complexes to interact with the supercoiled pUC19 plasmid DNA. Molecular docking studies were performed to determine the binding mode of all active compounds against the XO enzyme, antibacterial, antifungal, and MCF-7 cell lines