Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

https://deepblue.lib.umich.edu/bitstream/2027.42/138963/1/12987_2017_Article_71.pd

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

Immigration policy of Germany: an analysis within The framework of a common European Immigration policy

"Immigration Policy of Germany: An Analysis Within the Framework of a Common European Immigration Policy" ("Almanya'nın Göç Politikası: Ortak Bir Avrupa Göç Politikası Çerçevesinde Bir Çözümleme") başlığını taşıyan bu yüksek lisans tezi, isminden de anlaşılacağı üzere, Federal Almanya Cumhuriyeti'nin göç politikaları hakkında bir vaka çalışması niteliğindedir. Tutarlılık ve bütünlük sağlayan bir çalışma ortaya koyabilmek amacıyla, ilk olarak bir ulus-devletin göç politikalarına dair temel özellikler dile getirilmiş ve daha sonra bu özellikler vaka çalışmamız bağlamında örneklenmiştir. Konuya dair siyasi ve tarihi verilerin bir arka plan olarak kullanıldığı çalışmada, temel olarak günümüz Almanya'sında göç politikasına dair yaşanan dönüşüm ve tartışmalara odaklanılmıştır. Alman iç politikasındaki değişimlerin detaylı bir sunumu ve Almanya'nın bu konu bağlamında, Avrupa Birliği çerçevesindeki konumunun ortaya konması ile çalışmamız Federal Almanya Cumhuriyeti'nin göç politikalarını hala ulusal ekonomik çıkarları çerçevesinde ürettiği ve bu siyasi alandaki ulusal egemenliğini henüz uluslarüstü bir kuruma devretmeye rıza göstermediği yönündekini görüşü ispatlamaya çalışmaktadır. Bir ulus-devletin göç politikaları hakkındaki bir vaka çalışmasında neden örnek olarak Federal Almanya Cumhuriyeti'nin seçildiğine dair birkaç gerekçemiz vardır. Bir taraftan, Almanya siyasi tarihinde uluslararası göç alanında büyük deneyimleri olan bir ülkedir, ki bu durum bize güncel durumu karşılaştırmalı bir bakış açısı ile daha iyi anlama olanağını vermektedir. Diğer taraftan ise, Almanya Avrupa Birliği'nin en büyük ve siyasi anlamda en etkili üyelerinden birisi olarak karşımıza çıkmaktadır, ki üyelerinden herhangi birinin bir siyasi alanını incelerken, bu kurumun da mutlaka dikkate alınması gereği düşünüldüğünde, bu da bizler için önemli bir noktadır. Çalışmamız dört ana araştırma sorunu üzerine kurulmuştur. Bunlar, "Bir ulus-devletin göç politikasını şekillendiren etmenler nelerdir?", "Savaş sonrası süreçte Alman göç politikasının nitelikleri nelerdir?", "Alman göç politikasındaki güncel dönüşümler nedir ve bu yeni siyasi girişimlerin önemi nedir?" ve "Avrupa Birliği'nin ortak bir göç politikası oluşturma sürecinde Almanya'nın konumu nedir?" şeklinde ifade edilebilir. İlk iki soru, konuya dair uzman görüşleri ve yazın taraması, diğer iki soru ise Federal Alman hükümeti, Alman siyasi partileri ya da Avrupa Birliği'ne ait belgeler gibi kimi birincil siyasi kaynaklar ile güncel gazete makalelerinin incelenmesi ile yanıtlanmaya çalışılmıştır. This MA thesis, titled as "Immigration Policy of Germany: An Analysis Within the Framework of a Common European Immigration Policy", is a case study on the immigration policy of Federal Republic of Germany. In order to present a coherent and integral study, we are first going to have a look at the basic aspects of the immigration policy of a nation-state and then exemplify them within the context of the case study. Taking the historical and political data as the backgrounds of the subject matter, the study will mainly focus on the current changes and debates of the immigration policy in Germany. Through a detailed presentation of the changes in German domestic policy as well as the position of Germany within the European Union, the study will try to demonstrate that Federal Republic of Germany is building its immigration policy still upon its national economic interests and does not consent to give up its national sovereignty on this political area to a supranational body yet. As to the reasons, why Federal Republic of Germany is chosen as the case study of examination of the immigration policy of a nation state, there are several points. On the one side, Germany is a country with big experiences of immigration in its political history, which gives us the opportunity to understand the current situation better in a comparative way. On the other side, Germany is one of the biggest and politically leading countries of the European Union -rather than just being a member-, which definitely should be taken into consideration while studying any political aspect of one of its member states. The study is built upon four main research questions, namely "What are the factors shaping the 'immigration policy' of a nation-state?", "What were the characteristics of the German immigration policy in the post war period?", "What is new in the German immigration policy and what is the importance of the new political attempts?" and "What is the position of Germany within the process of a common immigration policy of the European Union?". In order to answer the first two answers, the views of academics involved in this subject were reviewed and for the last two questions, primary political sources like documents of the Federal government, or the German political parties and those of the European Union as well as actual newspaper articles were examined

Familial acromegaly due to aryl hydrocarbon receptor-interacting protein (AIP) gene mutation in a Turkish cohort

Aryl hydrocarbon receptor-interacting protein (AIP) is associated with 15-20 % of familial isolated pituitary adenomas and 50-80 % of cases with AIP mutation exhibit a somatotropinoma. Herein we report clinical characteristics of a large family where AIP R304X variants have been identified. AIP mutation analysis was performed on a large (n = 52) Turkish family across six generations. Sella MRIs of 30 family members were obtained. Basal pituitary hormone levels were evaluated in 13 family members harboring an AIP mutation. Thirteen of 52 family members (25 %) were found to have a heterozygous nonsense germline R304X mutation in the AIP gene. Seven of the 13 mutation carriers (53.8 %) had current or previous history of pituitary adenoma. Of these 7 mutation carriers, all but one had somatotropinoma/somatolactotropinoma (85.7 % of the pituitary adenomas). Of the 6 acromegaly patients with AIP mutation (F/M: 3/3) the mean age at diagnosis of acromegaly was 32 +/- A 10.3 years while the mean age of symptom onset was 24.8 +/- A 9.9 years. Three of the six (50 %) acromegaly cases with AIP mutation within the family presented with a macroadenoma and none presented with gigantism. Biochemical disease control was achieved in 66.6 % (4/6) of the mutation carriers with acromegaly after a mean follow-up period of 18.6 +/- A 17.6 years. Common phenotypic characteristics of familial pituitary adenoma or somatotropinoma due to AIP mutation vary between families or even between individuals within a family

Smooth Muscle Cells Isolated from Thoracic Aortic Aneurysms Exhibit Increased Genomic Damage, but Similar Tendency for Apoptosis

Aortic aneurysms (AA) are characterized by structural deterioration leading to progressive dilation. During the development of AA, two key structural changes are pronounced, one being degradation of extracellular matrix and the other loss of smooth muscle cells (SMCs) through apoptosis. Reactive oxygen species (ROS) are produced above physiological levels in dilated (aneurismal) part of the aorta compared to the nondilated part and they are known to be associated with both the extracellular matrix degradation and the loss of SMCs. In this study, we hypothesized that aneurismal SMCs are more prone to apoptosis and that at least some cells undergo apoptosis due to elevated ROS in the aortic wall. To test this hypothesis, we first isolated SMCs from thoracic aneurismal tissue and compared their apoptotic tendency with normal SMCs in response to H2O2, oxidized sterol, or UV treatment. Exposed cells exhibited morphological changes characteristic of apoptosis, such as cell shrinkage, membrane blebbing, chromatin condensation, and DNA fragmentation. Terminal deoxynucleotidyl transferased UTP nick end labeling (TUNEL) further confirmed the fragmentation of nuclear DNA in these cells. Vascular SMCs were analyzed for their micronuclei (MN) and binucleate (BN) frequency as indicators of genomic abnormality. These data were then compared to patient parameters, including age, gender, hypertension, or aortic diameter for existing correlations. While the tendency for apoptosis was not significantly different compared to normal cells, both the %MN and %BN were higher in aneurismal SMCs. The data suggest that there is increased DNA damage in TAA samples, which might play a pivotal role in disease development.Wo