Vessel tractography using an intensity based tensor model with branch detection

In this paper, we present a tubular structure seg- mentation method that utilizes a second order tensor constructed from directional intensity measurements, which is inspired from diffusion tensor image (DTI) modeling. The constructed anisotropic tensor which is fit inside a vessel drives the segmen- tation analogously to a tractography approach in DTI. Our model is initialized at a single seed point and is capable of capturing whole vessel trees by an automatic branch detection algorithm developed in the same framework. The centerline of the vessel as well as its thickness is extracted. Performance results within the Rotterdam Coronary Artery Algorithm Evaluation framework are provided for comparison with existing techniques. 96.4% average overlap with ground truth delineated by experts is obtained in addition to other measures reported in the paper. Moreover, we demonstrate further quantitative results over synthetic vascular datasets, and we provide quantitative experiments for branch detection on patient Computed Tomography Angiography (CTA) volumes, as well as qualitative evaluations on the same CTA datasets, from visual scores by a cardiologist expert

Prothrombin Complex Concentrates in Life-Threatening Bleeding

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Tip 2 diyabetik hastaların birinci derece yakınlarında total homosistein ve asimetrik dimetilargininin plazma düzeyleri

Amaç: Tip 2 diyabetik hastaların birinci derece yakınlarında, ailesinde diyabet öyküsü olmayan sağlıklı olgulara göre kardiyovasküler hastalıklar daha sık görülmektedir. Asimetrik dimetilarginin (ADMA) ve homosistein (Hcy) plazma düzeyleri kardiyovasküler hastalıklar ve endotel disfonksiyonuyla ilişkili göstergelerdir. Bu çalışmada, tip 2 diyabetik hastaların birinci derece yakınlarında ADMA ve Hcy plazma düzeyleri ile bu göstergelerle kardiyovasküler risk faktörleri arasındaki ilişkilerin incelenmesi amaçlandı. Hastalar ve Yöntemler: Dolaşımdaki ADMA ve Hcy düzeyleri 15 tip 2 diyabet hastasının birinci derece yakınında ve ailesinde diyabet öyküsü olmayan 15 kontrol olgusunda ölçüldü. Bulgular: Her iki grup arasında ADMA ve Hcy plazma düzeyleri açısından anlamlı farklılık saptanmadı (p>0.05). Asimetrik dimetilarginin plazma düzeyi tip 2 diyabetik olguların birinci derece yakınlarında, bel çevresi (p=0.02), açlık insülin düzeyi (p=0.03), insülin direnci (p=0.01), total kolesterol (p=0.04) ve HDL kolesterol (p=0.03) ile ilişkiliydi. Sonuç: Bu sonuçlara göre, kardiyovasküler risk faktörlerine sahip olan tip 2 diyabetik olguların birinci derece yakınlarında, ADMA plazma düzeylerinin doğrudan endotel disfonksiyonunun gelişimine katkıda bulunmadığını düşünmekteyiz.Objectives: Cardiovascular diseases are more common among first degree relatives of type 2 diabetic patients than healthy subjects without a family history of diabetes. Plasma asymmetric dimethylarginine (ADMA) and homocysteine (Hcy) levels are markers of endothelial dysfunction and cardiovascular disease. The objective of this study was to evaluate levels of ADMA, Hcy and their association with cardiovascular risk factors in first degree relatives of type 2 diabetic patients. Patients and Methods: The circulating ADMA and Hcy levels were measured in 15 first degree relatives of type 2 diabetic patients and 15 control subjects without a known family history of diabetes. Results: No statistically significant differences were found in plasma levels of ADMA and Hcy between the two groups (p>0.05). Plasma ADMA levels correlated significantly with waist circumference (p=0.02), fasting insulin levels (p=0.03), insulin resistance (p=0.01), total cholesterol (p=0.04) and HDL-cholesterol (p=0.03) levels in the first degree relatives of type 2 diabetic patients. Conclusion: These results suggest that plasma ADMA levels do not directly contribute to the development of endothelial dysfunction in first degree relatives of type 2 diabetic patients with cardiovascular risk factors

Genetic Diagnosis of Hereditary Hemorrhagic Telangiectasia: Four Novel Pathogenic Variations in Turkish Patients

Aims: Hereditary hemorrhagic telangiectasia is an autosomal dominant disorder characterized by telangiectasia, epistaxis, and vascular malformations. Pathogenic mutations were found in ENG, AVCRL1, SMAD4, and GDF genes. In this study, we present our database of patients with hereditary hemorrhagic telangiectasia regarding the phenotype-genotype relations and discuss two novel ENG gene pathogenic variations in two unrelated families. Methods: Next Generation Sequencing analysis was performed on the peripheral blood of nine patients with hereditary hemorrhagic telangiectasia in four unrelated families. All patients were diagnosed with hereditary hemorrhagic telangiectasia according to the Curaçao criteria. Data on treatment and screenings of visceral involvement were recorded from files. Results: We have found a pathogenic variation in either the ENG or ACVRL1 gene in each family. Two novel pathogenic variations in the ENG gene, including NM_000118.3 (ENG): c.416delC (p.P139fs*24) and NM_000118.3(ENG): c.1139dupT (p.Leu380PhefsTer16), were found in the same family. The NM_000020.2(ACVRL1): c.1298C>T (p.Pro433Leu) pathogenic variation in the ACVRL1 gene in our first family and a novel heterozygous likely pathogenic NM_000020.2(ACVRL1): c.95T>C (p.Val32Ala) variation was found in our second family. Seven of the nine patients were treated with thalidomide for controlling bleeding episodes. All patients responded to thalidomide. In one patient, the response to thalidomide was lost and switched to bevacizumab. Conclusion: In hereditary hemorrhagic telangiectasia, certain types of mutations correlate with disease phenotypes and with next generation sequencing methods. New pathogenic variations can be revealed, which might help manage patients with hereditary hemorrhagic telangiectasi

Obez hastalarda proinflamatuvar sitokinler ile fibrinolitik sistem arasındaki ilişki

Amaç: Obez kişilerde proinflamatuar sitokinlerden TNF-? ve IL-6, fibrinolitik sistem parametrelerinden t-PA ve PAI-1 ve insülin direnci arasındaki ilişki araştırıldı. Hastalar ve Yöntemler: Çalışmaya obez (VKİ ?30 kg/m2) olarak değerlendirilen 54 kişi (41 kadın, 13 erkek; ort. yaş 33.5) ve obezite sorunu olmayan (VKİ <25 kg/m2) 30 kişi (19 kadın, 11 erkek; ort. yaş 22.3) alındı. Fibrinojen düzeyleri koagülometrik olarak ve TNF-?, IL-6, t-PA, PAI-1 düzeyleri ELISA yöntemiyle ölçüldü. Bulgular: Kontrol grubuyla karşılaştırıldığında, obez kişilerde fibrinojen (p<0.01), PAI-1 (p<0.001), TNF-? (p<0.01) ve IL-6 düzeyleri (p<0.001) anlamlı derecede yüksek, t-PA düzeyi (p<0.001) ve t-PA/PAI-1 oranı (p<0.001) anlamlı derecede düşük bulundu. Obezlerde TNF-? ile t-PA (p=0.007) ve t-PA/PAI-1 oranı (p=0.016) arasında ters ilişki saptandı. İnsülin direnci olan ve olmayan obez kişilerde parametreler arasında fark yoktu. Sonuç: Obezitede adipoz dokudan salgılanan özellikle TNF-? gibi inflamatuar sitokinlerin artması fibrinolizde azalmaya yol açar. Obez kişilerde görülen bu değişiklikler, insülin direncinden bağımsız olarak ateroskleroza neden olabilir.Objectives: The aim of this study was to investigate the relationship between proinflammatory cytokines (TNF-&amp;#945; and IL-6), and fibrinolytic system parameters (t-PA, and PAI-1) and insulin resistance in obese individuals. Patients and Methods: The study included 54 obese subjects (BMI &amp;#8805;30 kg/m2; 41 females, 13 males; mean age 33.5 years) and 30 non-obese healthy individuals (BMI &lt;25 kg/m2; 19 females, 11 males; mean age 22.3 years). Fibrinogen levels were measured by the coagulometric method and the measurements of TNF-&amp;#945;, IL-6, t-PA and PAI-1 were carried out by the ELISA method. Results: Compared with non-obese subjects, obese individuals had significantly higher fibrinogen (p&lt;0.01), PAI-1 (p&lt;0.001), TNF-&amp;#945; (p&lt;0.01), and IL-6 (p&lt;0.001) levels, and significantly lower t-PA level (p&lt;0.001) and t-PA/PAI-1 ratio (p&lt;0.001). We also found an inverse relationship between TNF-&amp;#945; and t-PA levels (p=0.007) and t-PA/PAI-1 ratio (p=0.016) in obese individuals. The presence or absence of insulin resistance did not affect proinflammatory cytokines and fibrinolytic system parameters in obese individuals. Conclusion: Our findings indicate increased inflammatory cytokine levels especially in TNF-&amp;#945; level, and decreased fibrinolysis in obese individuals. These changes may contribute to atherosclerotic process independent from insulin resistance in obesity

Wpływ dystrybucji tkanki tłuszczowej oraz wybranych adipokin na insulinooporność w stanie przedcukrzycowym

  Introduction: The risk of developing insulin resistance and metabolic syndrome is particularly high in central obesity. In this study we evaluated the effects of fat distribution and some adipokines on insulin resistance in prediabetic patients. Material and methods: Eighty-seven age- and sex-matched patients were divided into three groups according to their 75-gram oral glucose tolerance test results as follows: impaired fasting glucose group, impaired glucose tolerance group, and normal glucose tolerance group. Fasting insulin levels were measured. Homeostatic model assessment of insulin resistance was calculated. Body fat mass measurements were assessed by bioelectric impedance analyser and abdominal fat thicknesses (subcutaneous, visceral, and preperitoneal) by ultrasonography. The fasting serum levels of several adipokines [adiponectin, leptin, resistin, vaspin, visfatin, retinol-binding protein-4 (RBP-4), tumour necrosis factor-alpha (TNF-alpha)] were measured by ELISA method. Results: The mean body mass index, fat mass measurements, and abdominal fat thicknesses of the groups were similar. There were no differences between groups in terms of the mean fasting insulin, vaspin, RBP-4, leptin, resistin, and TNF-alpha. In comparison of the prediabetic and normal groups, the levels of adiponectin (p &lt; 0.001) and visfatin (p &lt; 0.001) were lower in the prediabetic group. Furthermore, we found that high body mass index (p &lt; 0.01) and fat mass (p &lt; 0.01) and low adiponectin (p &lt; 0.05) levels have roles in the development of insulin resistance in the prediabetic group. Conclusions: We suggested that in the prediabetic period not only obesity but also decreased adiponectin levels play some role in the pathogenesis of insulin resistance. (Endokrynol Pol 2016; 67 (3): 277–282)    Wstęp: Ryzyko rozwoju insulinooporności i zespołu metabolicznego zwiększa się zwłaszcza u osób z otyłością centralną. W niniejszym badaniu oceniono wpływ dystrybucji tkanki tłuszczowej i wybranych adipokin na insulinooporność u osób ze stanem przedcukrzycowym. Materiał i metody: Osiemdziesięciu siedmiu chorych dobranych pod względem wieku I płci podzielono na 3 grupy w zależności od wyniku testu doustnego obciążenia 75 g glukozy: osoby z nieprawidłową glikemią na czczo, osoby z nieprawidłową tolerancją glukozy i osoby z prawidłową tolerancją glukozy. Zmierzono stężenie insulin na czczo. Do oszacowania insulinooporności zastosowano model homeostazy. Masę tkanki tłuszczowej oceniono za pomocą analizatora bioimpedancji elektrycznej, a grubość brzusznej tkanki tłuszczowej (podskórnej, trzewnej i przedotrzewnowej) zmierzono metodą ultrasonograficzną. Stężenie na czczo w surowicy kilku adipokin (adiponektyna, leptyna, rezystyna, waspina, wisfatyna, białko wiążące retinol-4 [RBP-4], czynnik martwicy nowotworów alfa [TNF-alfa]) zmierzono, stosując metodę ELISA. Wyniki: Średni wskaźnik masy ciała, masa tkanki tłuszczowej I grubość brzusznej tkanki tłuszczowej były podobne we wszystkich grupach. Nie stwierdzono różnic między grupami pod względem średniego stężenia insuliny na czczo ani stężeń waspiny, RBP-4, leptyny, rezystyny i TNF-alfa. W porównaniu grup ze stanem cukrzycowym i grupy z prawidłową tolerancją glukozy wykazano, że stężenia adiponektyny (p &lt; 0,001) i wisfatyny (p &lt; 0,001) były niższe u osób ze stanem przedcukrzycowym. Ponadto stwierdzono, że wysoki wskaźnik masy ciała (p &lt; 0,01) i duża masa tkanki tłuszczowej (p &lt; 0,01) oraz niskie stężenie adiponektyny (p &lt; 0,05) przyczyniają się do rozwoju insulinooporności u osób ze stanem przedcukrzycowym. Wnioski: Autorzy sugerują, że nie tylko otyłość, ale również obniżenie stężenia adiponektyny odgrywają pewną rolę w patogenezie insulinooporności w okresie przedcukrzycowym. (Endokrynol Pol 2016; 67 (3): 277–282)

Metaproteogenomic analysis of saliva samples from Parkinson's disease patients with cognitive impairment

Cognitive impairment (CI) is very common in patients with Parkinson's Disease (PD) and progressively develops on a spectrum from mild cognitive impairment (PD-MCI) to full dementia (PDD). Identification of PD patients at risk of developing cognitive decline, therefore, is unmet need in the clinic to manage the disease. Previous studies reported that oral microbiota of PD patients was altered even at early stages and poor oral hygiene is associated with dementia. However, data from single modalities are often unable to explain complex chronic diseases in the brain and cannot reliably predict the risk of disease progression. Here, we performed integrative metaproteogenomic characterization of salivary microbiota and tested the hypothesis that biological molecules of saliva and saliva microbiota dynamically shift in association with the progression of cognitive decline and harbor discriminatory key signatures across the spectrum of CI in PD. We recruited a cohort of 115 participants in a multi-center study and employed multi-omics factor analysis (MOFA) to integrate amplicon sequencing and metaproteomic analysis to identify signature taxa and proteins in saliva. Our baseline analyses revealed contrasting interplay between the genus Neisseria and Lactobacillus and Ligilactobacillus genera across the spectrum of CI. The group specific signature profiles enabled us to identify bacterial genera and protein groups associated with CI stages in PD. Our study describes compositional dynamics of saliva across the spectrum of CI in PD and paves the way for developing non-invasive biomarker strategies to predict the risk of CI progression in PD.FEMS Research and Training Gran

Could ratio of hemoglobin to red cell distribution width and ratio of absolute lymphocyte count to absolute monocyte count be a prognostic tool in newly diagnosed multiple myeloma patients?

IntroductionHemoglobin/red cell distribution width (RDW) ratio (HRR) and lymphocyte-to-monocyte ratio (LMR) are two novel bio-markers associated with overall survival (OS) and prognosis in several types of cancers. The aim of this study is to investigate the value of HRR and LMR in newly diagnosed multiple myeloma (MM) patients. MethodsA total of 180 patients were included in this study. Patients diagnosed with MM between May 2013 and May 2019 at a single center were evaluated. HRR was calculated by dividing hemoglobin to RDW, both measured from the same sample. LMR was calculated by dividing absolute lymphocyte count (ALC) to absolute monocyte count (AMC). ResultsThe cutoff value for HRR was taken as 0.61, and the cutoff value for LMR was taken as 3.28. Patients were divided into low HRR, high HRR, low LMR, and high LMR groups. OS of the patients with low HRR was found lower compared with high HRR (36.7 months for low HRR and 53.2 months for high HRR, < 0.001). Also, OS was found lower in the low LMR group (39.4 months for low LMR and 51.7 months for high LMR, = 0.016). On multivariate analysis, low HRR and low LMR were predictive factors of OS (hazard ratio (HR) 2.08, 95% confidence intervals (CI) 1.31–3.03, and = 0.002 for low HRR; HR 1.47, 95% CI 0.92–2.29, and = 0.010 for low LMR). ConclusionCombining both HRR and LMR could be a prognostic biomarker and it reflects the status of the immune system in newly diagnosed MM patients