Relationship between MPV and paraoxonase-1 activity, brachial artery diameter and IMT in patients with diabetes mellitus

Aims: Higher mean platelet volume (MPV) in diabetic patients has been considered as an emerging risk factor for diabetes related micro- and macrovascular complications. Human paraoxonase 1/arylesterase (PON1), which has antioxidant and antiatherogenic properties, is documented in high oxidative stress conditions like uncontrolled diabetes. The present study aimed to evaluate the relationship between mean platelet volume (MPV) and paraoxonase-1 (PON-1) activity, brachial artery diameter (BAd) and intima media thickness (BA-IMT), in diabetic patients with regard to obesity and diabetic complications.Methods: Two-hundred and one diabetic patients (mean age: 52.4 ± 13.4 years, 73.6% females) were grouped according to obesity and diabetic complications (microvascular and macrovascular). Data on demographics, anthropometrics, diabetic complications, MPV levels, BAd and BA-IMT, and serum paraoxonase and arylesterase activities were recorded. The correlation of MPV values to paraoxonase and arylesterase activities, BAd and BA-IMT was evaluated.Results: Paraoxonase and arylesterase values were 119.8 ± 37.5 U/L and 149.0 ± 39.9 U/L, respectively, with no significant difference in respect of obesity and macrovascular complications. Significantly lower values for paraoxonase (107.5 ± 30.7 vs. 123.9 ± 38.8 U/L, p = 0.007) and arylesterase (132.1 ± 30.2 vs. 154.7 ± 41.2, U/L, p = 0.001) were noted in patients with microvascular complications. MPV values were 9.10 ± 0.87 fL, with no significant difference across the groups and no significant correlation with other parameters.Conclusion: In conclusion, PON-1 activity is more significantly decreased in diabetic patients with microvascular than macrovascular complications with no effects on MPV values. On the other hand, no relationship was found between thrombogenic activity and PON-1 activity, BAd and BA-IMT regardless of obesity and diabetic complications.Keywords: cardiovascular, diabetes, insulin resistance, obesity, vasculatur

Whole Exome Sequencing Reveals DYSF, FKTN, and ISPD Mutations in Congenital Muscular Dystrophy Without Brain or Eye Involvement

Background: Congenital muscular dystrophies (CMDs) are a genetically and clinically heterogeneous group of neuromuscular disorders. Several genes encoding extracellular matrix, nuclear envelope, sarcolemmal proteins and glycosylation enzymes have been implicated in CMDs. The large overlap of clinical presentations due to mutations in different genes poses a challenge for clinicians in determining disease etiology for each patient. Objective: We investigated the use of whole exome sequencing (WES) in identifying the genetic cause of disease in 5 CMD patients from 3 families who presented with highly similar clinical features, including early-onset rapidly progressive weakness without brain or eye abnormalities. Methods: Whole exome sequencing was performed on DNA from affected individuals. Potential functional impacts of mutations were investigated by immunostaining on available muscle biopsies. Results: Pathogenic mutations in 3 different genes, DYSF, FKTN, and ISPD were identified in each family. Mutation in DYSF led to absence of dysferlin protein in patient muscle. Mutations in ISPD led to impaired ISDP function, as demonstrated by deficiency of α-dystroglycan glycosylation in patient muscle. Conclusions: This study highlights the benefit of unbiased genomic approaches in molecular diagnosis of neuromuscular disorders with high clinical heterogeneity, such as the phenotypes observed in our patients. Our results suggest that dysferlin deficiency should be in the differential diagnosis of congenital and rapidly progressive muscular dystrophy, and therefore dysferlin antibody should be in the standard immunohistochemistry panel for muscle biopsies in cases with suspected CMD

Konjenital Myopatilerde Klinik, Histopatolojik ve Genetik Değerlendirme

Congenital myopathies are a group of inherited muscle disorders presenting in childhood and mainly diagnosed by muscle biopsy. Nemaline myopathy, centronuclear myopathy, core myopathy and congenital fiber type disproportion consist the most common forms. A clinical and genetic overlap is frequently seen in different forms of congenital myopathies as well as similar histopathologic features may be seen in different clinical presentations and genetic mutations. Thus, an integrated approach is essential to reach a diagnosis and develop appropriate therapies. The aim of this study is to make clinical and histopathological assessment and identify causative genes and proteins of congenital myopathy patients in our hospital. We have reviewed the patients diagnosed with congenital myopathy between 2003-2013. Clinical information was obtained from medical records. Patients who were able to come to hospital were re-examined and their last clinical status was annotated. Muscle biopsies were reevaluated and reclassified according to most recent literature data. In collaboration with Boston Children’s Hospital Genetics/Genomics department, we have studied the DNA samples to look for known congenital myopathy genes from the patients whose clinical picture and histopathological features are evidently typical. For the patients who did not have such features, their samples were sent for whole exome sequencing in order to identify new causative genes. In the case of exploring an unknown gene, we have planned functional studies to look for any genotype-phenotype correlation. There were 90 non-related cases, whose age of biopsy ranged from 6 days to 17 years. Mean age was different in each congenital myopathy subgroup. There was no significiant difference between males and females. Consanguinity was present in %58 of patients. Histopathological classification yielded 30 patients of nemaline myopathy, 11 with core myopathy, 14 with centronuclear myopathy and 5 with congenital fiber type disproportion. In 30 patients, muscle biopsy showed features suggestive for congenital myopathy but not sufficient to classify into a single subgroup. DNA samples from 43 patients were analysed. Some analyses were culminated with clear results. The genes that were recently shown to cause congenital myopathy (e.g. KLHL40, TTN, SPEG) were identified as well as other known congenital myopathy genes (e.g. RYR1, SEPN1, TPM3, ACTA1). This study is the largest systematic review of the congenital myopathies in Turkey. Genetic studies are explicitly gaining dominancy in these diseases, which help us to identify new genes, elaborate new pathogenetic mechanisms and design new therapeutic approaches. However, it is not always feasible to access genetic tests and to get insufficient data is not rare. In this case, identifying certain clinical phenotypes along with histopathological (and/or genetic) data could obtain substantial information about the prognosis of the disease and therapeutic interventions.Konjenital myopatiler erken çocukluk döneminde bulgu veren, tanısı kas biyopsisiyle konulan genetik bir hastalık grubudur. Nemalin myopati, Sentronükleer myopati, Kor myopatisi ve Konjenital lif tipi uyumsuzluğu en sık görülen alt tiplerdir. Farklı konjenital myopati tipleri benzer genetik ve klinik özellikler taşıyabilmektedirler. Aynı zamanda farklı genetik ve klinik özelliklere sahip hastalarda benzer histopatolojik bulgulara rastlanabilmektedir. Hastalığın tanısının konulması ve uygun tedavi yaklaşımlarının geliştirilmesi için hastaların kas biyopsisi bulgularıyla beraber hem klinik hem de genetik açıdan bütüncül bir yaklaşımla değerlendirilmesi gerekir. Çalışmanın amacı konjenital myopati hastalarının klinik-histopatolojik değerlendirmesinin yapılması ve hastalıktan sorumlu olan genlerin ve proteinlerin tanımlanmasıdır. Hastanemizde 2003-2013 yılları arasında konjenital myopati tanısı alan hastaların retrospektif olarak klinik değerlendirilmesi yapılmış; ulaşılabilen hastalar muayeneye çağırılıp en son klinik durumları gözlenmiştir. Histopatolojik ve klinik bulgular korelasyon yönünden incelenmiş, sınıflandırılamayan vakalar güncel bilgiler ışığında tekrar değerlendirilmiştir. Genetik incelemeler Boston Çocuk Hastanesi Genetik-Genomik bölümünde yapılmıştır. İlk olarak hastalıkla ilişikili olduğu bilinen genlere bakılmış, bilinen bir gende mutasyon saptanmayan hastalarda tüm ekzom sekanslama metoduyla hastalık yapıcı diğer genler araştırılmıştır. Keşfedilen her yeni mutasyon için genotip-fenotip korelasyonu kurulması ve hastalık etkeni olduğunu kanıtlamak için fonksiyonel çalışmalar yapılması planlanmıştır. Çalışmaya alınan 90 hastanın yaş dağılımı 6 gün ile 17 yaş arasında izlenmiş olup, ortalama yaş farklı konjenital myopati tipleri arasında değişiklik göstermiştir. Kız/erkek oranında belirgin fark görülmemiştir. Akraba evliliği %58 oranında rastlanmıştır. Otuz hasta nemalin myopati, 14 hasta sentronükleer myopati, 11 hasta kor myopatisi, 5 hasta konjenital lif tip uyumsuzluğu tanısı almıştır. Otuz hastanın kas biyopsisinde belirgin myopatik değişiklikler görülmesine rağmen herhangi bir yapısal sınıflandırmaya dahil edilememiştir. Kırk üç hastanın DNA örneğinden genetik analiz yapılmıştır. Genetik çalışması sonuçlanan hastalarda bilinen konjenital myopati genlerinin (RYR1, SEPN1, TPM3, ACTA1) yanı sıra konjenital myopati etkeni olduğu yeni gösterilen KLHL40, TTN, SPEG genlerinde mutasyon bulunmuştur. Çalışma konjenital myopatiler konusunda Türkiye’den yapılan en kapsamlı sistematik çalışma olması açısından önem taşımaktadır. Genetik çalışmaların gittikçe hakimiyet kazandığı bu hastalık grubunda, hastalığa neden olan yeni bir gen bulunması, altta yatan patogenetik mekanizmaları açıklamamıza yardımcı olmakta, hastalık hakkında yeni bilgiler kazandırmakta ve olası tedaviler için model oluşturmaktadır. Ancak genetik çalışmanın yapılamadığı ya da sonuç veremediği durumlar nadir değildir. Bu nedenle belli klinik fenotiplerin tanımlanması, histopatolojik ve/veya genetik veriler eşliğinde hastalığın prognozu ve alınabilecek önlemler konusunda önemli bilgi sağlamaktadır

AN IOT BASED APPLICATION ON THE DETECTION OF CAR PARKING AREA BY AN ARTIFICIAL INTELLIGENCE APPROACH

Nowadays, smart cities solutions have been becoming popular day by day. The problem of finding a parking place is one of these implementations. Our study appeals to users who want to park their vehicle quickly and who want to find out whether the parking place is available to park before searching for a parking place. This application aims to find a solution to the problem of searching for a place to park. We have found a novel solution to this problem by using image processing methods and utilizing photographs of streetside parking places in the most effective way. In addition, an Android software has been developed through which we can deliver the results obtained with the image processing module to users via a mobile application. As a result, a parking IoT determination system has been implemented in this study with 92% accuracy value. Thanks to this system, vehicle owners who want to park their vehicles on the side of the street will be able to learn whether the parking places in a street are available in advance and they will be able to save their time by preferring more available streets

Relation of Paraoxonase 1 Activity with Biochemical Variables, Brachial Artery Intima-Media Thickness in Patients with Diabetes with or without Obesity

Aim: The sodium-sparing effect of insulin leads to increase in total sodium pool of the body which is a chronic stimulus for atrial natriuretic peptide (ANP). In our study we aimed to determine the relationship between ANP and microvascular complications of diabetes. Methods: 60 patients, 30-70 years old, with the diagnosis of type 2 diabetes mellitus (DM) are enrolled into the study. Patients with a chronic disease other than DM are excluded. Blood samples for routine biochemical tests are taken after at least 12 h fasting at 8-9 am. Blood samples for glucose and insulin levels are taken 2 h after a standard meal. Blood tubes with EDTA are used for ANP levels. The microvascular complications of the patients are evaluated. Results: 32 of the patients had microvascular complications. Age, BMI, waist and hip circumferences, and ANP levels were significantly higher in the group with microvascular complications. There were no significant differences in waist-to-hip ratio, blood glucose, HbA1c, fasting insulin, postprandial insulin, fasting HOMA, postprandial HOMA as well as sodium, potassium, magnesium, calcium and lipid levels between the two groups. When the relationship between ANP and obesity, retinopathy, neuropathy, nephropathy, diabetes time, HbA1c, or sex are evaluated separately, the only significant parameters related to ANP were obesity and retinopathy. Conclusion: In our study we have found that there was a significant relationship between ANP levels and microvascular complications of diabetes. Future studies are needed to show if ANP is the stimulus of microvascular complication development/progression or only an epiphenomenon

An adaptive bilateral motion estimation algorithm and its hardware architecture

In this paper, we propose an adaptive bilateral motion estimation (Bi-ME) algorithm for frame rate up-conversion of High Definition (HD) video. The proposed algorithm can be used as a refinement step after a true motion estimation algorithm. It refines the motion vector field between successive frames by employing a spiral search pattern and by adaptively assigning weights to candidate search locations. In addition, we propose a high performance hardware architecture for implementing the proposed Bi-ME algorithm. The proposed hardware uses an efficient memory organization and a novel data reuse scheme in order to reduce the memory bandwidth and control overhead. The proposed hardware consumes 24% of the slices in a Xilinx 2V8000FF1517-5 FPGA. It can work at 107 MHz in the same FPGA and is capable of processing 124 1920x1080 full HD frames per second (fps), therefore doubling the frame rate to 248 fps