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

Summary 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 middleincome 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 lowincome 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 lowincome, 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

Antikanser etki göstermesi olası naproksen türevi bileşiklerin sentezi

1. ÖZETAntikanser Etki Göstermesi Olası Naproksen Türevi Bileşiklerin SenteziÖğrencinin Adı: Muhammed İhsan HANDanışmanı: Prof. Dr. Ş. Güniz KüçükgüzelAnabilim Dalı: Farmasötik KimyaAmaç: Son yıllarda yapılan çalışmalar MetAP2 enziminin kanser gelişmesinde rol alan önemli enzimlerden biri olduğunu göstermektedir. Bu çalışmalara dayanarak bu enzimin makromoleküler hedef olarak seçilmesi uygun bulunmuştur. Başta hidrazit-hidrazon yapısı olmak üzere tiyoeter ve 1,2,4-triazol halkasına sahip olan moleküllerin kuvvetli antikanser aktivite gösterdiği tespit edilmiştir. Gereç ve Yöntem: Naproksen ((S)-2-(6-metoksi-2-naftil)propiyonik asit) belirtilen yapıların sentezlenmesi için çalışmamızda başlangıç molekülü seçilmiştir. Naproksenin metanol içerisindeki derişik sülfürik asit katalizörlüğü ile tepkimesinden ester (Bileşik 1), bu bileşiğin hidrazin hidrat ile reaksiyonundan hidrazit (Bileşik 2) bileşiği kazanılmıştır. Bileşik 2 ile 4-fluorofenil izotiyosiyanatın reaksiyonuyla tiyosemikarbazit türevi (Bileşik 3); elde edilen bu tiyosemikarbazit türevi bileşiğin 4N NaOH içerisindeki siklizasyonuyla 1,2,4-triazol bileşiği (Bileşik 4) elde edilmiştir. Etilalfabromoasetat ile K2CO3/Aseton varlığında tiyoester (Bileşik 5) bu bileşiğin hidrazin-hidrat ile etanolik ortamda reaksiyonundan tiyohidrazit (Bileşik 6) bileşikleri elde edilmiştir. Bileşik 6 ile çeşitli aldehitlerin reaksiyonuyla hedef moleküllerimiz olan [7a-z] bileşikleri elde edilmiştir.Bulgular: Naproksen üzerinden sentezlenen bu bileşiklerin yapıları; elementel analiz, FT-IR, 1H-NMR, 13C-NMR, HMBC ve HR-MS ile kanıtlanmış, saflıkları ise İ.T.K. ve HPLC ile kontrol edilmiştir. Moleküler Modelleme çalışmaları ve Biyolojik çalışmalar ile aktiviteleri tespit edilmiştir.Sonuçlar: Yapılan biyolojik aktivite çalışmalarında bileşiklerden 7h bileşiği PC-3, DU-145 ve LNCaP hücrelerinin üçüne de aktivite gösterdiği tespit edilmiştir. 7a, 7v ve 7z Bileşikleri PC-3 ve DU-145 hücrelerine, 7k ve 7l bileşikleri PC-3 hücrelerine, 7c bileşiği PC-3 ve LNCaP hücrelerine, 7b bileşiği ise sadece LNCaP hücrelerine karşı belirgin IC50 değeri göstermiştir.--------------------2. SUMMARYSynthesis of Naproxen Derivatives and Their Possible Anticancer EffectsStudent Name: Muhammed İhsan HANSupervisor: Prof. Dr. Ş. Güniz KüçükgüzelDepartment: Pharmaceutical ChemistryAim: The research conducted in recent years show that MetAP2 is one of the important enzymes involved in the development of cancer. Based on these studies, it has been found appropriate to select this enzyme as a macromolecular target. It has been reported in the literature that molecules having thioether and 1,2,4-triazole ring, especially hydrazide-hydrazone structure, show strong anticancer activity.Materials and Mehtods: Naproxen ((S)-2-(6-methoxy-2-naftyl)propionic acid) was chosen as a starting compound for the synthesis of designed molecules. Naproxen ester (compound 1) was synthesized with metanolic solution of naproxen and sulphuric acid as a catalizor. Naproxen hydrazide (compound 2) was synthesized with naproxen ester and hydrazine hydrate in methanol. Compound 2 was treated with 4-fluorophenyl isothiocyanate for the synthesis of thiosemicarbazide compound (compound 3). The thiosemicarbazide compound 3 was then treated with 4N NaOH resulting with the synthesis of 1,2,4-triazole-3-thione compound (compound 4). Thioester compound (compound 5) was synthesized with ethyl α-bromoacetate, K2CO3/acetone and with the presence of compound 4. Thiohydrazide compound (compound 6) was then synthesized with compound 5 and hydrazine-hydrate in ethanolic medium. Compound 6 was then converted to our target compounds (7a-z) with the addition of substituted aldehydes.Findings: The compounds 5, 6, 7a-z, which are the naproxen hybrid molecules, are the original compounds synthesized in this work. The structures of new Naproxen derivatives were elucidated with, FT-IR, 1H-NMR, 13C-NMR, HMBC and HR-MS methods and their purity were proven by elemental analysis, TLC and HPLC analysis. Molecular modeling studies of the original compounds were made and activities with biological studies were determined.Results: The biological studies indicated that compound 7h showed anticancer activity against PC-3, DU-145 and LNCaP cancer cell lines. Compounds 7a, 7v and 7z showed activity against PC-3 and DU-145 cell lines, Compounds 7k and 7l showed activity againts PC-3 cell line, Compound 7c showed activity against PC-3 and LNCap cell lines, Compound 7b showed activity only against LNCaP cancer cell line with remarkable IC50 values

Kadışehri (Yozgat) yöresinde geleneksel halk ilacı olarak kullanılan bitkileri

1. ÖZET Bu çalışma Kadışehri (Yozgat) yöresinde geleneksel halk ilacı olarak kullanılan bitkileri ortaya çıkarmak amacıyla yapılmıştır. Bu amaçla Mart 2011- Mayıs 2012 tarihleri arasında Mart, Nisan, Mayıs, Haziran ve Temmuz aylarında yörede toplam 43 gün süren arazi çalışmaları yapılmıştır. Bu araştırma esnasında yöredeki 1 belde ve 26 köyün hepsine gidilerek halk ilacı olarak kullanılan bitkilerden örnekler toplanmıştır. Bu bitkilerin yöresel adları, tedavideki kullanılışları, yararlanılan kısımları, ilaçların hazırlanışı, uygulanış şekilleri, dozları, uygulama süreleri hakkında bilgiler derlenmiştir. Toplanan bu örnekler Marmara Üniversitesi Eczacılık Fakültesi Herbaryumu’nda (MARE) bulunmaktadır. Sonuç olarak, yöreden toplanan 84 bitki örneğinin teşhisi sonucunda 56 türden geleneksel halk ilacı olarak yararlanıldığı saptanmıştır. Bunlardan 48’i yabani 8’i ise yörede yetiştirilen bitkilerdir. Bu bitkiler ve bunların tedavideki kullanılışları metin içinde sunulmuştur. Kadışehri yöresinde kaydedilen bitkilerden en çok yara tedavisinde, nefes darlığına karşı, kan şekerini düşürücü olarak, romatizma tedavisinde ve mide rahatsızlıklarının giderilmesinde yararlanılmaktadır. Anahtar Sözcükler: Etnobotanik, Halk İlaçları, Kadışehri, Tıbbi Bitkiler, Yozgat2. SUMMARY FOLK MEDICINAL PLANTS OF KADIŞEHRİ (YOZGAT) This study was made to reveal the plants used as traditional folk medicine in Kadışehri (Yozgat). For this purpose, the field work was done between March 2011- May 2012, in March, April, May, June and July lasting for 43 days in total. During this research all the settlement centers (including 1 small town and 26 villages) was visited. The specimens of the plants used as folk remedies have been collected and the information about local names, ailments treated or therapeutic effects, plant parts used, method of administration, dosage, duration of treatment has been recorded. The collected plant specimens are kept in the Herbarium of the Faculty of Pharmacy, Marmara University (MARE). As a result of identification of 84 plant specimens, 56 species used as a traditional folk medicine, have been determined. Among them 48 species are wild and 8 species are cultivated plants. These plants and their local usage in treatment are presented in the text. The plants recorded in Kadışehri are mostly used for wound, asthma, diabetes, rheumatism and stomach diseases. Key words: Ethnobotany, Folk Medicine, Kadışehri, Medicinal Plants, Yozga

Kadışehri (Yozgat) yöresinde geleneksel halk ilacı olarak kullanılan bitkileri

1. Bu çalışma Kadışehri (Yozgat) yöresinde geleneksel halk ilacı olarak kullanılan bitkileri ortaya çıkarmak amacıyla yapılmıştır. Bu amaçla Mart 2011- Mayıs 2012 tarihleri arasında Mart, Nisan, Mayıs, Haziran ve Temmuz aylarında yörede toplam 43 gün süren arazi çalışmaları yapılmıştır. Bu araştırma esnasında yöredeki 1 belde ve 26 köyün hepsine gidilerek halk ilacı olarak kullanılan bitkilerden örnekler toplanmıştır. Bu bitkilerin yöresel adları, tedavideki kullanılışları, yararlanılan kısımları, ilaçların hazırlanışı, uygulanış şekilleri, dozları, uygulama süreleri hakkında bilgiler derlenmiştir. Toplanan bu örnekler Marmara Üniversitesi Eczacılık Fakültesi Herbaryumu’nda (MARE) bulunmaktadır. Sonuç olarak, yöreden toplanan 84 bitki örneğinin teşhisi sonucunda 56 türden geleneksel halk ilacı olarak yararlanıldığı saptanmıştır. Bunlardan 48’i yabani 8’i ise yörede yetiştirilen bitkilerdir. Bu bitkiler ve bunların tedavideki kullanılışları metin içinde sunulmuştur. Kadışehri yöresinde kaydedilen bitkilerden en çok yara tedavisinde, nefes darlığına karşı, kan şekerini düşürücü olarak, romatizma tedavisinde ve mide rahatsızlıklarının giderilmesinde yararlanılmaktadır. Anahtar Sözcükler: Etnobotanik, Halk İlaçları, Kadışehri, Tıbbi Bitkiler, Yozgat 2. SUMMARY FOLK MEDICINAL PLANTS OF KADIŞEHRİ (YOZGAT) This study was made to reveal the plants used as traditional folk medicine in Kadışehri (Yozgat). For this purpose, the field work was done between March 2011- May 2012, in March, April, May, June and July lasting for 43 days in total. During this research all the settlement centers (including 1 small town and 26 villages) was visited. The specimens of the plants used as folk remedies have been collected and the information about local names, ailments treated or therapeutic effects, plant parts used, method of administration, dosage, duration of treatment has been recorded. The collected plant specimens are kept in the Herbarium of the Faculty of Pharmacy, Marmara University (MARE). As a result of identification of 84 plant specimens, 56 species used as a traditional folk medicine, have been determined. Among them 48 species are wild and 8 species are cultivated plants. These plants and their local usage in treatment are presented in the text. The plants recorded in Kadışehri are mostly used for wound, asthma, diabetes, rheumatism and stomach diseases. Key words: Ethnobotany, Folk Medicine, Kadışehri, Medicinal Plants, Yozga

Synthesis and antimicrobial evaluation of novel tetracain thiosemicarbazide derivatives

In this study, new Tetracaine thiosemicarbazide derivatives were designed, synthesized, and evaluated for their antimicrobial activity. These compounds (2a-l) were characterized using spectroscopic (H-1-C-13 NMR, FT-IR and HR-MS) methods and tested for their antimicrobial activity against various Gram-positive and Gram-negative bacterial strains (Staphylococcus aureus ATCC 29213: Enterococcus faecium ATCC 29212; Escherichia coli ATCC 25922; Pseudomonas aeruginosa ATCC 27853), and fungus (Candida albicans ATCC 10231). The microbroth dilution method was utilized for the determination of the minimum inhibitory concentration (MIC) values of novel molecules. The antimicrobial activities of the molecules were found to have a wide range of MIC values with 4-256 mu g/mL. Among the synthesized molecules, compound 2 h (2-[4-(butylamine)benzoyl]-N-(3,5-bistrifluoromethylphenyl)hydrazine-1-carbothioamide) showed the best MIC value for 4 (mu g/mL) to S. aeurus isolate and 8 (mu g/mL) to C. albicans, respectively. Compounds 2e (2-[4-(butylamine)benzoyl]-N-(2-fluorophenyl)hydrazine-1-carbothioamide) and 2f (2-[4-(butylamine)benzoyl]-N-(4-nitrophenyl)hydrazine-1-carbothioamide) showed moderate activity to C. albicans and S. aeurus with a 16 (mu g/mL) MIC value

The folk-medicinal plants of Kadisehri (Yozgat - Turkey)

This paper contains significant ethnobotanical information on folk-medicinal plants and their ethnopharmacological uses in Kadisehri. The aim of the study was mainly to collect and identify the plants used therapeutically by the local people, and to make available information about traditional herbal medicine. It was undertaken during the period 2011-2012 and is based on plants collected during field work. Fifty-six plants used in folk-medicine and belonging to 34 families were identified in this study. Of these, 48 species were wild, and 8 species were cultivated plants. The most common families were Rosaceae (12.5%), Lamiaceae (8.9%) and Asteraceae (7.1%); and the most common preparations were decoctions (36.7%). In addition, a cultural importance index (CI) and use report (UR) were calculated for each species. Based on the CI, the most important plants were Cydonia oblonga (0.77), Ecballium elaterium (0.66), Urtica urens (0.66), Vitis vinifera (0.66), Plantago lanceolata (0.65), Plantago major subsp. major (0.65) and Rosa canina (0.62). We found three species of plant (Astragalus noaeanus, Populus xcanescens and Salvia cyanescens) which had never before been reported to have medicinal properties