The Genetic Aspect of Thalassemia: From Diagnosis to Treatment

Hemoglobinopathies are a group of red blood cell productivity disorders, including α-thalassemia, β-thalassemia, and sickle cell disease (SCD), that are autosomal recessive and very common in Mediterranean, Middle Eastern, East Asian, and African countries. Thalassemia presents with the following clinical signs and symptoms: fatigue, weakness, yellowish skin, facial bone deformities, and abdominal swelling. Genetic studies have successfully characterized the key variants and pathways involved in hemoglobin F (HbF) regulation, providing new therapeutic targets for HbF reactivation. According to the current literature, using lentivirus vector for gene therapy and genome-editing-based treatment strategies for β-thalassemia and SCD have been discussed and well documented. According to current studies, novel treatments are becoming more important for thalassemia patients, because the consequences of supportive treatments are not sufficient for patients and their families. Supportive treatment does not have a positive effect on the survival rate of β-thalassemia patients. New treatments are empowering to develop develop a gene therapy for β-thalassemia and include pharmacological or disruption of BCL11A erythroid enhancer by CRISPR-CAS9 technology in addition to zinc-finger or transcription activator-like effector nuclease, and attempts at repairing the defective β-globin gene in hematopoietic stem cells by genome editing. These approaches are needed to improve for being more successful; gene addition has the advantage of making use of a single product applicable to all cases of β-thalassemia

Orta Anadolu’daki Parkinson Hastalarında Homosistein ve MTHFR Polimorfizmleri Arasındaki İlişkinin Araştırılması ve Tedavi Seçenekleri

Aim In this study, we aimed to investigate the effects of MTHFR C677T and A1298C polymorphisms to homocysteine levels in patients with Parkinson's disease who were treated with levodopa and entekapone. Materials and Methods Plasma homocysteine (hcy), folic acid and vitamin B12 levels and MTHFR (C677T, A1298C) polymorphisms and treatment options were compared in 70 Parkinson's Disease (PD) patients who taking levodopa (n=26), dopamine agonist (n=11) and levodopa and entacapone treatment together (n=33) with 100 controls. Results Although no statistically significant difference was detected, hcy level of the patients was found higher compared to control group (patient 18.29 ± 9.22 µmol /l vs control 15.77 ± 7.58 µmol / l) and hcy level was highest in the patients receiving only levodopa (19.56 ± 10.77 µmol / l). The frequency of TT genotype in the patients was higher compared to the control group (11.4%, 6%). Especially, hcy level for levodopa-receiving patients with 677TT genotype became significantly higher level when compared with other genotypes of levodopareceiving patients (respectively 677TT 36.28 ± 16.17, 677CT 13.5 ± 1.71, 677CC 17.2 ± 6.59). No statistically significant difference was detected between patients and controls regarding their folic acid and vitamin B12 levels and A1298C polymorphism. Conclusion Finally, both 677TT genotype and levodopa treatment might be jointly contributed to the increasing of the plasma hcy levels in PD patients and entacapone limitedly decreased hcy levels during levodopa treatment. It can be said that results need to be supported with larger sample sized comprehensive studies.Amaç Çalışmamızda levodopa ve entekapon kullanan Parkinson hastalarında MTHFR genindeki C677T ve A1298C polimorfizmlerinin homosistein düzeyine etkilerini araştırmayı amaçladık. Materyal ve Metot 70 Parkinson (PD) hastasında; plazma homosisteini (hcy), folik asit, B12 vitamini seviyeleri, MTHFR (C677T, A1298C) polimorfizmleri ve tedavi seçenekleri karşılaştırıldı. 100 kişilik bir kontrol grubunun yer aldığı çalışmada, 70 hastanın 26’sı levodopa (n=26), 11’i dopamin agonisti (n=11) kullanırken, 33 hasta da levodopa ve entakapon tedavisini birliktealmaktaydı. Bulgular İstatistiki olarak anlamlı bir fark gözlenmese de, hastalardaki homosistein seviyesinin kontrol grubunda yer alanlara göre daha fazla olduğu tespit edildi (hasta 18.29 ± 9.22 µmol /l vs kontrol 15.77 ± 7.58 µmol/ l). Ayrıca homosistein seviyesinin en yüksek olduğu hasta grubunun sadece levodopa kullanan hastalar olduğu görüldü (19.56 ± 10.77 µmol / l). Hastalardaki TT genotipinin sıklığının da kontrol grubunda yer alanlara göre daha fazla olduğu görüldü (%11.4, %6). Özellikle, levodopa kullanan ve 677TT genotipine sahip olan hastalardaki homosistein seviyesi, levodopa kullanan ve diğer genotiplere sahip olan hastalardaki homosistein seviyesine göre anlamlı bir şekilde yüksek (sırasıyla 677TT 36.28 ± 16.17, 677CT 13.5 ± 1.71, 677CC 17.2 ± 6.59). Hastalar ve kontrol grubu arasında folik asit ve B12 vitamini seviyeleri ile A1298C polimorfizmi açısından anlamlı bir farka rastlanmadı. Sonuç Sonuç olarak; Parkinson hastalarında 677TT genotipinin ve levodopa kullanımının bir arada olmasının plazma homosistein seviyesini artırdığı, ayrıca entakaponun levodopa tedavisi esnasında sınırlı da olsa homosistein seviyesini düşürdüğü gözlemlenmiştir. Ancak sonuçların daha fazla örnek sayısı içeren kapsamlı çalışmalarla desteklenmesinin gerekli olduğu söylenebilir

Silindirle sıkıştırılmış beton ağırlık barajların sismik performanslarının belirlenmesi için dinamik benzeri deney uygulamaları

TÜBİTAK MAG15.04.2014Su kaynaklarının verimli kullanılmasında en önemli yapılar barajlardır. Barajların, sismik etkiler altındaki davranışları deprem mühendisliğinde karşılaşılan en karmaşık problemlerden birisidir. Ülkemizde son yıllarda tercih edilen en önemli baraj tipi silindirle sıkıştıtılmış beton barajdır. Beton ağırlık barajların sismik davranışı laboratuvar ortamında birkaç sarsma tablası testi dışında deneysel olarak fazla incelenememiştir. Bu çalışma ile literatürde ilk defa dinamik benzeri deney yöntemi ile ölçekli baraj deneyleri gerçekleştirilmiştir. Çalışma kapsamında üç adet numunesi ardışık etki eden üç farklı deprem kaydı altında denenmiştir. Bu numunelerden ikisi farklı çekme dayanımlarına sahip SSB’den ve diğer numune ise geleneksel beton kullanılarak üretilmiştir. Tüm numuneler Türkiye’de tasarlanan en yüksek SSB baraj olan Melen Barajının 1/75 ölçekli halini yansıtmaktadır. Deneysel sonuçlar Türkiye'de tasarlanan en yüksek SSB ağırlık barajlardan birisinin sismik performansı hakkında da değerli deneysel veriler temin edilmesini sağlamaktadır. Ayrıca, baraj sismik performans belirlemesinde sıklıkla kullanılan nonlineer sonlu eleman modelleri ile gözlemlenen hasarın ne ölçüde tahmin edilebileceği de sunulmuştur.Dams are one of the most important structures for the efficient use of water resources. Dam- reservoir-foundation interaction problem under seismic loads is one of the most challenging problems in earthquake engineering. One of the most popular dam type in Turkey in the recent years is roller compacted concrete (RCC) dams. Testing of dams under simulated earthquake loads has only been limited to a few shake table tests. Pseudo dynamic testing method has been employed in this study for the first time in the literature. Three specimens tested in the course of this study were, two RCC specimens with two different concrete strengths and one conventionally vibrated concrete specimen. All the specimens were 1/75 scaled versions of Melen Dam, which is one of the most important RCC dams to be built in Turkey. The results of this study serve as means of observing the expected seismic performance of an actual dam under simulated earthquake loadings. The ability of numerical models in estimating the damage patterns observed in the tests are also evaluated in detail

The genotypes of thalassemia and genotypes frequencies of thalassemia in Hatay

Amaç: Dünyada çok yaygın olarak görülen ?-talasemi, hemoglobindeki ?-globin zincirinin eksikliği ya da azalması ile karakterize olan bir hastalıktır. ?-globin geni 16. kromozomun kısa kolu üzerinde (16p 13.3) bulunur ve dele syon ve tek nokta mutasyonu şeklinde (?3.7 , ?MED , ? COD8( - AA), ?2 IVS 1 -5nt, ?2 poly A1 mutasyonları) mutasyonlar içerir. Biz bu çalışmada Hatay bölgesindeki ?-talasemi gen mutasyonlarının frekansını belirlemeyi amaçladık. Yöntem : Bu amaçla, 2012 -2013 tarihleri arasında Mustafa Kemal Üniversitesi, Tıp Fakültesi, Tıbbi Genetik AD’a gelen ?-talasemili 407 hasta tarandı. ?-globin geninin moleküler analizi multipleks PCR (Polimeraz Zincir Reaksiyonu) teme lli ?-globin Strip Assay yöntemi (Vienna Lab Diagno stics, Vienna, Austria) ile gerçekleştirildi. Bulgular: Buna göre, bölgemizdeki ?3.7 , ?MED , ? COD8(-AA), ?2 IVS 1 -5nt, ?2 poly A1mutasyonlarının frekansları sırası ile %29.48, %5.16, %0.25, %0.25, %0.25 şeklinde bulu nmuştur. Sonuç : Sonuç olarak, mutasyonların görülme sıklığı etnik kökenden ve coğrafik bölgelerden etkilenmektedir. Hatay bölgesi de kendine has bir etnik kökene sahiptir ve bu yüzden ?-talasemi gen mutasyonları frekansları da kend ine has bir özelliktedir.Objective : α-thalassemia, characterized by a decreased or lack of synthesis of α-globin chains of hemoglobin, is very common disease in the world. α-globin gene is located at the short arm of chromosome 16 (16p 13.3) and contains mutations including deletions and single point mutations (α3.7 , αMED , α COD8 (-AA), 1 -5nt IVS α2, α2 poly A1 mutations). In this study, we aimed to determine the frequency of α-thalassemia gene mutations in Hatay region. Method : To do so, study population who referred to Med i- cal Genetic Department of Mustafa Kemal University, M edical School for either detection of α-thalassemia gene mutations between 2012 -2013, 407 individuals with α- thalassemia gene mutations were includud to the study. Molecular screening of the α-globin gene was carried out by an α-globin strip assay (Vienna Lab Diagnostics, Vienna, Austria) which is based on multiplex PCR (Polymerase Chain Reaction) for specific amplification. Results : According to this, it has found that the frequencies of α3.7 , αMED , α COD8 ( -AA), 1 -5nt IVS α2, α2 poly A1 mutations are 29.48%, 5.16%, 0.25%, 0.25%, 0.25%, respectively. Conclusion : Consequently, the frequency of mutation affects ethnic backround and geographic locations. Hatay region also has a unique origin and so, the frequencies of α- thalassemia gene mutations has unique characteristic

The studies about diseases concerning with contemplated MTHFR 677 C>T polymorphism

5,10-Methlenetetrahydrofolate reductase (MTHFR) is one of the most important enzymes for folic acid metabolism. This protein’s gene is mapped on chromosome 1, which is located at the end of the short arm (1p36.3). MTHFR enzyme plays a key role in cell metabolism including folic acid and nucleotide synthesis (DNA, RNA). Polymorphism is also a factor in biodiversity, and is different according to ethnic heritage and racial. The 677 C>T is also MTHFR polymorphisms that decrease MTHFR enzyme activity. The aim of this study is to compile studies are associated with MTHFR C677T polymorphism. PUBMED, Turk Biochemistry and Jornal of Clinical & Experimental Investigations were searched to develop an investigatory pursuit strategy. MTHFR, Turkish population, 677 C>T and polymorphisms were key words including “MTHFR”, “Türk popülasyonu: Turkish population”, “677 C>T” “polimorfizm: polymorphism” used to focus the search. The literature review included all published relevant Turkish population and MTHFR polymorphisms for that all of study. The data of selected polymorphism for Turkish population was listed in tables for easy access and retrieval

Desenvolvimento de programa computacional para deteção de erros de topologia à nível de subestação de um sistema elétrico de potêncial

5,10-Metilentetrahidrofolat redüktaz (MTHFR) folik asit metabolizması için en önemli enzimlerden biridir. Bu proteinin geni 1 numaralı kromozomun kısa kolunda (1p36.3) haritalanmıştır. MTHFR enzimi, folik asit, nükleotid sentezi (DNA, RNA) gibi pek çok reaksiyonu içeren hücre metabolizmasında, kilit rol oynar. Polimorfizmler etnik kö- kene ve ırklara göre farklılık gösteren ve biyoçeşitlilikte rol oynayan bir faktördür. MTHFR 677 C>T polimorfizmi enzim aktivitesini azaltan bir polimorfizmdir. Çalışmanın amacı, Türkiye’de MTHFR C677T polimorfizmi ile ilgili olan çalışmaları derlemektir. Bu nedenle, Türkiye’de yapılmış MTHFR 677 C>T polimorfizmi ile ilgili PUBMED, Türk Biyokimya ve Klinik & Deneysel Araştırmalar dergisinde yayınlanmış bütün çalışmalar derlenmiştir. Araştırma yapılırken “MTHFR”, “Türk popülasyonu: Turkish population”, “677 C>T” “polimorfizm: polymorphism” anahtar kelimeleri kullanılmıştır. Bu çalışmalar, belli başlı hastalık gruplarına göre sınıflandırılmış ve tablolar halinde okuyucunun değerlendirmesine sunulmuştur.5,10-Methlenetetrahydrofolate reductase (MTHFR) is one of the most important enzymes for folic acid metabolism. This protein’s gene is mapped on chromosome 1, which is located at the end of the short arm (1p36.3). MTHFR enzyme plays a key role in cell metabolism including folic acid and nucleotide synthesis (DNA, RNA). Polymorphism is also a factor in biodiversity, and is different according to ethnic heritage and racial. The 677 C>T is also MTHFR polymorphisms that decrease MTHFR enzyme activity. The aim of this study is to compile studies are associated with MTHFR C677T polymorphism. PUBMED, Turk Biochemistry and Jornal of Clinical & Experimental Investigations were searched to develop an investigatory pursuit strategy. MTHFR, Turkish population, 677 C>T and polymorphisms were key words including “MTHFR”, “Türk popülasyonu: Turkish population”, “677 C>T” “polimorfizm: polymorphism” used to focus the search. The literature review included all published relevant Turkish population and MTHFR polymorphisms for that all of study. The data of selected polymorphism for Turkish population was listed in tables for easy access and retrieval

Pseudo-dynamic testing of a concrete gravity dam

Inspired from the simplified single degree of freedom modeling approach used in the preliminary design of concrete gravity dams, a pseudo-dynamic testing method was devised for the seismic testing of a concrete gravity dam section. The test specimen was a 1/75 scaled section of the 120-m-high monolith of the Melen Dam, one of the highest concrete gravity dams to be built in Turkey. The single degree of freedom idealization of the dam section was validated in the first stage of the study using numerical simulations including the dam-reservoir interaction. Afterwards, pseudo-dynamic testing was conducted on the specimen using three ground motions corresponding to different hazard levels. Lateral displacement and base shear demands were measured. The crack propagation at the base of the dam was monitored with the measurement of the crack widths and the base sliding displacements. After the pseudo-dynamic loading, a static pushover test was conducted to determine the reserve capacity of the test specimen. Despite major cracking at the base of the monolith, neither significant sliding nor a stability problem that might jeopardize the stability of the dam was observed. Copyright (c) 2015 John Wiley & Sons, Ltd

Pseudo dynamic test results of a concrete gravity dam

The energy and water demands have constantly been increasing all over the world due to rising population and due to advances in science. This fact obligates the usage of natural resources to supply more and more water and energy. Of course, the most important structures that can serve this purpose are dams. However, the behaviour of dams, especially under the effect of seismic actions, is one of the most complicated problems in earthquake engineering. This is because; dams usually rest on flexible foundations and interact with the water, which necessitates taking the dam-foundation-reservoir interaction into account. Also, complex geometry of the valley and the dam necessitate considering higher mode effects. A number of different linear elastic boundary element and finite element procedures were proposed in the literature to analyze the three dimensional dam-foundation-reservoir interaction problem rigorously. On the other hand, the seismic behaviour of concrete gravity dams has not been investigated experimentally in detail other than a few shaking table test programs because of the difficulties encountered during experimental simulations like hydrodynamic effects, huge sizes, etc. Consequently, the aim of this study is to carry out a pseudo dynamic test on a scaled concrete gravity dam. The base cracking, sliding, base shear capacity and crest displacements of the dam under three different hazard levels will be investigated

Malouf Syndrome with Hypergonadotropic Hypogonadism and Cardiomyopathy: Two-Case Report and Literature Review

Malouf syndrome is a very rarely encountered syndrome which was first diagnosed in 1985 upon the examination of two sisters, with findings of hypergonadotropic hypogonadism, dilated cardiomyopathy, blepharoptosis, and broad nasal base. Later on, Narahara diagnosed another sporadic case with the same findings. A survey of relevant literature leads us to three women cases in total. Here we present two cases of Malouf syndrome and literature review

Investigation of the Association of Homocysteine and MTHFR Polymorphisms and Treatment Options in Parkinson’s Disease in Central Anatolian Region*

AimIn this study, we aimed to investigate the effects of MTHFR C677T and A1298C polymorphisms to homocysteine levels in patients with Parkinson's disease who were treated with levodopa and entekapone.Materials and MethodsPlasma homocysteine (hcy), folic acid and vitamin B12 levels and MTHFR (C677T, A1298C) polymorphisms and treatment options were compared in 70 Parkinson's Disease (PD) patients who taking levodopa (n=26), dopamine agonist (n=11) and levodopa and entacapone treatment together (n=33) with 100 controls.ResultsAlthough no statistically significant difference was detected, hcy level of the patients was found higher compared to control group (patient 18.29 ± 9.22 μmol /l vs control 15.77 ± 7.58 μmol / l) and hcy level was highest in the patients receiving only levodopa (19.56 ± 10.77 μmol / l). The frequency of TT genotype in the patients was higher compared to the control group (11.4%, 6%). Especially, hcy level for levodopa-receiving patients with 677TT genotype became significantly higher level when compared with other genotypes of levodopa-receiving patients (respectively 677TT 36.28 ± 16.17, 677CT 13.5 ± 1.71, 677CC 17.2 ± 6.59). No statistically significant difference was detected between patients and controls regarding their folic acid and vitamin B12 levels and A1298C polymorphism.ConclusionFinally, both 677TT genotype and levodopa treatment might be jointly contributed to the increasing of the plasma hcy levels in PD patients and entacapone limitedly decreased hcy levels during levodopa treatment. It can be said that results need to be supported with larger sample sized comprehensive studies