A fully automatic nerve segmentation and morphometric parameter quantification system for early diagnosis of diabetic neuropathy in corneal images

Diabetic Peripheral Neuropathy (DPN) is one of the most common types of diabetes that can affect the cornea. An accurate analysis of the nerve structures can assist the early diagnosis of this disease. This paper proposes a robust, fast and fully automatic nerve segmentation and morphometric parameter quantification system for corneal confocal microscope images. The segmentation part consists of three main steps. First, a preprocessing step is applied to enhance the visibility of the nerves and remove noise using anisotropic diffusion filtering, specifically a Coherence filter followed by Gaussian filtering. Second, morphological operations are applied to remove unwanted objects in the input image such as epithelial cells and small nerve segments. Finally, an edge detection step is applied to detect all the nerves in the input image. In this step, an efficient algorithm for connecting discontinuous nerves is proposed. In the morphometric parameters quantification part, a number of features are extracted, including thickness, tortuosity and length of nerve, which may be used for the early diagnosis of diabetic polyneuropathy and when planning Laser-Assisted in situ Keratomileusis (LASIK) or Photorefractive keratectomy (PRK). The performance of the proposed segmentation system is evaluated against manually traced ground-truth images based on a database consisting of 498 corneal sub-basal nerve images (238 are normal and 260 are abnormal). In addition, the robustness and efficiency of the proposed system in extracting morphometric features with clinical utility was evaluated in 919 images taken from healthy subjects and diabetic patients with and without neuropathy. We demonstrate rapid (13 seconds/image), robust and effective automated corneal nerve quantification. The proposed system will be deployed as a useful clinical tool to support the expertise of ophthalmologists and save the clinician time in a busy clinical setting

Corneal Sensitivity and Dry Eye Symptoms in Patients with Keratoconus.

PURPOSE: To investigate corneal sensitivity to selective mechanical, chemical, and thermal stimulation and to evaluate their relation to dry eye symptoms in patients with keratoconus. METHODS: Corneal sensitivity to mechanical, chemical, and thermal thresholds were determined using a gas esthesiometer in 19 patients with keratoconus (KC group) and in 20 age-matched healthy subjects (control group). Tear film dynamics was assessed by Schirmer I test and by the non-invasive tear film breakup time (NI-BUT). All eyes were examined with a rotating Scheimpflug camera to assess keratoconus severity. RESULTS: KC patients had significatly decreased tear secretion and significantly higher ocular surface disease index (OSDI) scores compared to controls (5.3+/-2.2 vs. 13.2+/-2.0 mm and 26.8+/-15.8 vs. 8.1+/-2.3; p0.05). The mean threshold for selective mechanical (KC: 139.2+/-25.8 vs. control: 109.1+/-24.0 ml/min), chemical (KC: 39.4+/-3.9 vs. control: 35.2+/-1.9%CO2), heat (KC: 0.91+/-0.32 vs. control: 0.54+/-0.26 Delta degrees C) and cold (KC: 1.28+/-0.27 vs. control: 0.98+/-0.25 Delta degrees C) stimulation in the KC patients were significantly higher than in the control subjects (p0.05), whereas in the control subjects both mechanical (r = 0.52, p = 0.02), chemical (r = 0.47, p = 0.04), heat (r = 0.26, p = 0.04) and cold threshold (r = 0.40, p = 0.03) increased with age. In the KC group, neither corneal thickness nor tear flow, NI-BUT or OSDI correlated significantly with mechanical, chemical, heat or cold thresholds (p>0.05 for all variables). CONCLUSIONS: Corneal sensitivity to different types of stimuli is decreased in patients with keratoconus independently of age and disease severity. The reduction of the sensory input from corneal nerves may contribute to the onset of unpleasant sensations in these patients and might lead to the impaired tear film dynamics

Short-term impact of glycaemic control and intravitreal ranibizumab treatment on serum cytokine levels and diabetic macular edema in patients with unregulated blood glucose

Objective: To evaluate the short-term effect of glycaemic control and intravitreal ranibizumab treatment on diabetic macular edema (DME) and to assess the correlation between HbA1c and certain serum cytokines. Design: A prospective study of 43 participants with HbA1c levels exceeding 53 mmol/mol (7%) and with DME, as detected by spectral domain optical coherence tomography (SDOCT). Subjects: Participants were grouped according to their initial best corrected distance visual acuity (BCVA). Group 1 was treated with three monthly doses of intravitreal ranibizumab (0.5 mg) injections, and Group 2 was followed without treatment. Methods: Serum cytokine levels, including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1(MCP-1), and vascular endothelial growth factor (VEGF) were analysed at the beginning and at the end of 3 months, using enzyme-linked immunosorbent assays (ELISA). Results: A significant decrease in macular thicknesses (except for one quadrant) was observed in Group. Changes in serum cytokine levels were not correlated with HbA1c decrease. Serum VEGF level was significantly increased in Group 1, despite the intravitreal treatment. Conclusion: Short-term glycaemic control alone had limited value in the treatment of DME. The therapeutic effect of intravitreal treatment on DME supports the role of the local cytokine milieu in the pathophysiology

Characteristics of the cornea in patients with pseudoexfoliation syndrome

ABSTRACT Purpose: To quantify the morphological alterations in corneal nerve fibers and cells in patients with pseudoexfoliation syndrome (PEX) and their relationship with the presence of hyperreflective endothelial deposits observed using in vivo confocal microscopy. Methods: One eye each of 37 patients with PEX and 20 age-matched healthy control subjects was evaluated by in vivo corneal confocal microscopy. Patients with PEX were further classified into two groups: those with and without hyperreflective endothelial deposits. We evaluated the densities of basal epithelial cells, anterior and posterior stromal keratocytes, and endothelial cells and structure of sub-basal nerve fibers. Results: The mean anterior and posterior stromal keratocyte and endothelial cell densities and corneal sub-basal nerve plexus variables were significantly lower in patients with PEX compared with those in healthy control subjects. The mean basal epithelial cell density did not significantly differ. Conclusion: Eyes with PEX presented decreased corneal sub-basal nerve plexus variables and cell densities in all corneas, except for the mean basal epithelial cell density. Further, a trend of lower corneal sub-basal nerve plexus measurements in patients with hyperreflective endothelial deposits compared with those without endothelial deposits was observed

Corneal Confocal Microscopy to Image Small Nerve Fiber Degeneration: Ophthalmology Meets Neurology.

Neuropathic pain has multiple etiologies, but a major feature is small fiber dysfunction or damage. Corneal confocal microscopy (CCM) is a rapid non-invasive ophthalmic imaging technique that can image small nerve fibers in the cornea and has been utilized to show small nerve fiber loss in patients with diabetic and other neuropathies. CCM has comparable diagnostic utility to intraepidermal nerve fiber density for diabetic neuropathy, fibromyalgia and amyloid neuropathy and predicts the development of diabetic neuropathy. Moreover, in clinical intervention trials of patients with diabetic and sarcoid neuropathy, corneal nerve regeneration occurs early and precedes an improvement in symptoms and neurophysiology. Corneal nerve fiber loss also occurs and is associated with disease progression in multiple sclerosis, Parkinson's disease and dementia. We conclude that corneal confocal microscopy has good diagnostic and prognostic capability and fulfills the FDA criteria as a surrogate end point for clinical trials in peripheral and central neurodegenerative diseases

Topology-aware Quality-of-Service Support in Highly Integrated Chip Multiprocessors

Current design complexity trends, poor wire scalability, and power limitations argue in favor of highly modular onchip systems. Today’s state-of-the-art CMPs already feature up to a hundred discrete cores. With increasing levels of integration, CMPs with hundreds of cores, cache tiles, and specialized accelerators are anticipated in the near future. Meanwhile, server consolidation and cloud computing paradigms have emerged as profit vehicles for exploiting abundant resources of chip-multiprocessors. As multiple, potentially malevolent, users begin to share virtualized resources of a single chip, CMP-level quality-of-service (QOS) support becomes necessary to provide performance isolation, service guarantees, and security. This work takes a topology-aware approach to on-chip QOS. We propose to segregate shared resources, such as memory controllers and accelerators, into dedicated islands (shared regions) of the chip with full hardware QOS support. We rely on a richly connected Multidrop Express Channel (MECS) topology to connect individual nodes to shared regions, foregoing QOS support in much of the substrate and eliminating its respective overheads. We evaluate several topologies for the QOSenabled shared regions, focusing on the interaction between network-on-chip (NOC) and QOS metrics. We explore a new topology called Destination Partitioned Subnets (DPS), which uses a light-weight dedicated network for each destination node. On synthetic workloads, DPS nearly matches or outperforms other topologies with comparable bisection bandwidth in terms of performance, area overhead, energyefficiency, fairness, and preemption resilience.

Corneal confocal microscopy detects a reduction in corneal endothelial cells and nerve fibres in patients with acute ischemic stroke

YesEndothelial dysfunction and damage underlie cerebrovascular disease and ischemic stroke. We undertook corneal confocal microscopy (CCM) to quantify corneal endothelial cell and nerve morphology in 146 patients with an acute ischemic stroke and 18 age-matched healthy control participants. Corneal endothelial cell density was lower (P<0.001) and endothelial cell area (P<0.001) and perimeter (P<0.001) were higher, whilst corneal nerve fbre density (P<0.001), corneal nerve branch density (P<0.001) and corneal nerve fbre length (P=0.001) were lower in patients with acute ischemic stroke compared to controls. Corneal endothelial cell density, cell area and cell perimeter correlated with corneal nerve fber density (P=0.033, P=0.014, P=0.011) and length (P=0.017, P=0.013, P=0.008), respectively. Multiple linear regression analysis showed a signifcant independent association between corneal endothelial cell density, area and perimeter with acute ischemic stroke and triglycerides. CCM is a rapid non-invasive ophthalmic imaging technique, which could be used to identify patients at risk of acute ischemic stroke.Qatar National Research Fund Grant BMRP2003865

COVID-19 and neuropathy in type 2 diabetes

This study investigated the risk factors for COVID-19 and its impact on diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D). Patients with T2D underwent assessments with the NICE post-COVID questionnaire, DN4 questionnaire, vibration perception threshold (VPT), and corneal confocal microscopy (CCM) before and 11.0 ± 8.9 months after developing COVID-19. Of 76 participants with T2D, 35 (46.1%) developed COVID-19, of whom 8 (22.9%) developed severe COVID-19 and 9 (25.7%) developed long-COVID. The development of COVID-19 was associated with lower systolic blood pressure (P < 0.05). The presence and severity of DPN were not associated with developing COVID-19, severe COVID-19, or long-COVID (P = 0.42–0.94). Women were eight times more likely to develop long-COVID (P < 0.05) and elevated body weight, LDL, and VPT were associated with the development of long-COVID (P < 0.05 − 0.01). The long-COVID group exhibited significant changes in triglycerides and LDL (P < 0.05 for both) and body weight (P < 0.01) at follow-up. Their impact on clinical and neuropathy measures was comparable in patients with and without COVID-19 (P = 0.08–0.99). There was a significant reduction in corneal nerve measures (P < 0.05-0.0001) in patients with and without COVID-19. A low systolic blood pressure, altered lipids, body weight, higher VPT, and gender may determine the impact of COVID-19 in patients with T2D, but there was no evidence of an impact of COVID-19 on the development or progression of DPN

PV dizinin modellenmesi için güneş ışınımı tahmini ve ArcGIS tabanlı güneş enerjisi potansiyeli hesabı.

Tez (yüksek lisans) - Anadolu ÜniversitesiAnadolu Üniversitesi, Fen Bilimleri Enstitüsü, Elektrik-Elektronik Mühendisliği Anabilim DalıKayıt no: 492451Güneş enerjisi, en verimli alternatif enerji kaynaklarından biri olarak bilinir. Yeryüzüne ulaşan güneş ışınımı, güneş enerjisinin bir şeklidir. Güneş enerjisi uygulamaları, seçilen bölgenin güneş ışınımı potansiyeli hakkında tam bir bilgi ve ayrıntılı analiz gerektirir. Bu tezde, altı farklı güneş ışınımı hesaplama modeli kullanılarak Eskişehir için eğimli bir yüzey üzerinde saatlik küresel güneş ışınımı tahmin edilmiştir. Bu modellerin sonuçları, istatistiksel hata yöntemleri kullanılarak saatlik ölçüm verileri ile karşılaştırılmıştır. Tahmin sonuçları, modellerin performansını daha belirgin bir biçimde göstermek için aylık küresel güneş ışınımına dönüştürülmüştür. Uygun güneş ışınımı modeli seçildikten sonra, modeller karşılaştırıldığında, Eskişehir'in enerji potansiyelini hesaplamak için daha doğru sonuçlar veren model kullanılmıştır. MATLAB/Simulink programında ideal bir fotovoltaik panel simülasyonu uygulanmıştır, bunun yanı sıra, saatlik ölçülen rüzgar hızı, hava basıncı, küresel güneş ışınımı ve sıcaklık değerlerine dayalı olası PV panel enerji üretim miktarını hesaplamak için uygun bir algoritma seçilmiştir. PV potansiyelinin belirlenmesinden sonra, ideal PV simülasyonu ve tahmini PV potansiyeli sonuçları meteorolojik koşullar dikkate alınarak PV verimliliğini anlamak için karşılaştırılmıştır. Ayrıca, Anadolu Üniversitesi Mühendislik Fakültesi'nin bina çatı yüzeyinin PV potansiyeli hesaplanmış ve PV kurulumu için uygun çatı alanı ArcGIS yazılımı kullanılarak belirlenmiştir

The levels and relationships of leptin, adiponectin, adropin and endothelin-1 with insulin resistance in children with overweight and obesity

Tıp Fakültesi, Çocuk Sağlığı ve Hastalıkları Ana Bilim DalıGiriş ve Amaç: Çocuk sağlığı ve obezite günümüzde popüler iki konudur. Dünya sağlık örgütü (DSÖ), çocukluk çağı obezitesini 21. yüzyılın en ciddi küresel sağlık sorunlarından birisi olarak ilan etmiştir. Obez çocuklarda ve ergenlerde pek çok sağlık sorununun ortaya çıkma riski artmıştır, ayrıca bu çocukların obez yetişkin olma olasılığı daha yüksektir. Yağ dokusu, insan vücudu için bir enerji deposu olmasının yanında insülin duyarlılığını ve glukoz homeostazını etkileyen ana adipositokinler olan adiponektin ve leptin için de bir kaynaktır. İnsülin duyarlılığını arttırdığı da bilinen bir anti-aterojenik, anti-enflamatuar adipokin olan adiponektin düzeyinin obezitede azaldığı bilinmektedir. Adiponektinin tersine obezitede leptin düzeyleri yükselmektedir. Obezite insülin direnci, proenflamatuar adipokinler ve serbest yağ asitlerinin yağ dokusundan salınımını arttırma gibi mekanizmalar yoluyla endotel disfonksiyon oluşturmaktadır. Vazokonstrüktör ve proaterojenik bir peptid olan Endotelin-1'in sentezinin ve etkinliğinin artışı obezite ile ilişkili endotelyal disfonksiyonun ayırt edici bir özelliğidir. Enerji dengesinin devamlılığı, insülin duyarlılığı ve endotel fonksiyonu için gerekli bir peptid hormon olan adropinin obezitede azaldığı gösterilmiştir. Bu çalışmanın amacı, sağlıklı çocuklarla obez ya da fazla kilolu çocuklar arasında adiponektin, leptin, adropin ve endotelin-1 düzeylerini karşılaştırmak ve dolaşımdaki adipositokinlerle insülin direncinin arasındaki ilişkiyi tanımlamaktır. Materyal ve Metod: Bu çalışma, her iki cinsiyetten (30 erkek 30 kız) yaşları 8 ile 16 arasında olan 30 fazla kilolu (VKİ aralığı: 25-30) ya da obez (VKİ aralığı: 30-44), yaş ve cinsiyet dağılımı yönünden eşleştirilmiş 30 sağlıklı (VKİ aralığı 15-24) olmak üzere toplam 60 çocuk üzerinde yapılmıştır. Antropometrik ölçümler, açlık kan glukoz, insülin, trigliserid, total kolesterol ve HDL kolesterol düzeyleri çalışıldı. Homa insülin direnci indeksi ve TG/HDL oranı, insülin direnci ve kardiyovasküler riski değerlendirmek için hesaplandı. Adipositokinlerin (leptin, adiponektin), adropin ve endotelin-1'in açlık düzeyi ELİSA yöntemi ile ölçüldü. Sağlıklı çocuklar ile fazla kilolu veya obez çocukları insülin direnci (açlık insülin, HDL, TG/HDL, oranları ve HOMA-IR), adipositokinler (leptin ve adiponektin), adropin ve endotelin-1 yönünden karşılaştırdık. Yine obez çocuklarda leptin adiponektin, adropin ve endotelin-1'in insülin direnci ve obezite belirteçleri (VKİ, bel çevresi) ve lipid profilleri ile ilişkilerini araştırdık. Bulgular: Vücut ağırlığı, VKİ, bel çevresi, insülin, HOMA indeksi, leptin, leptin/VKİ oranını ve adiponektin/leptin oranını obez grupta daha yüksek bulduk (hepsi için p=0.001 ). HDL değerleri obez çocuklarda kontrol grubuna göre daha düşük bulundu (p=0.012). Trigliserid (TG)/HDL oranı, obez çocuklarda kontrol grubuna göre daha yüksek bulundu (p=0.005). Adropin düzeyleri obez çocuklarda kontrol gurubuna göre daha düşük bulundu (p=0.003). Leptinin vücut ağırlığı (r=0.712, p=0.041), VKİ (r=0.817, p=0.021), insülin (r=0.881, p=0.012) ve Homa İndeksi ile (r=0.834, p=0.0021) pozitif korelasyon gösterdiği saptandı. Adiponektin/leptin oranının obez grupta kontrol grubuna göre daha düşük olduğu bulundu (p=0.001). Adropin ile hepatosteatoz sıklığı arasında bir ilişki bulunmadı. Erkekler ve kızlar arasında leptin (p=0.66), adiponektin (p=0.740), adropin (p=0.382), endotelin-1 (p=0.355) ve adiponektin/leptin oranında (p=0.350) anlamlı bir farklılık bulunmadı. Leptin/VKİ oranının kızlarda erkeklere göre daha yüksek olduğu bulundu (p=0.022). Sonuç: Bu çalışma, obez ve sağlıklı çocuklarda leptin ve adropinin plazma düzeylerinin farklı olduğunu gösteren bulguları desteklemektedir. HDL kolestrol ve insülin direncinin arasındaki korelasyon, dislipidemi ve metabolik sendrom açısından risk taşıyan çocukların tanımlanmasında faydalı bir indeks olabilir. Obezitesi olan çocukların evaluasyonunda TG/HDL gibi lipid profilleri ve insülin direnci belirteçlerinin yanında adipositokinlerin de değerlendirmeye alınması, çocukluk çağı obezitesi ile ilişkili sağlık problemlerinin daha iyi anlaşılmasını sağlamaktadır. Anahtar Sözckler: Çocuk sağlığı, çocuk, obezite, insülin direnci, adipositokin, leptin, adiponektin, adropin, endotelin-1.Introduction and Purpose:Children's health and obesity are two popular topics around the world. The World Health Organization (WHO) declared childhood obesity one of the most serious global public health problemfor the 21st century. Obese children and adolescents are at an increased risk of developing various health problems, and are also more likely to become obese adults.Adipose tissue, in addition to its role as a energy reservoir for the human body, is also a source of major adipocytokines adiponectin and leptin which affect insulin sensitivity and glucose homeostasis. The levels of adiponectin, which is known as an insulin-sensitizing, anti-inflamatory and antiatherogenic adipokine, are reduced in obesity. Contrary to adiponectin, increased levels of leptin are observed in obesity. Obesity is related to endothelial dysfunction through mechanisms such as insulin resistance, the production of proinflammatory adipokines and elevated levels of free fatty acids by adipose tissue.Abnormal production and activity of endothelin-1, which is a vasoconstrictor and proatherogenic peptide, is also a hallmark of the obesity associated endothelial dysfunction.Adropin,a peptide hormone whichis required in the maintenance of energy homeostasis, insulin response and endothelial function is found decreased in obesity.The objective of this study was to compare the levels of adiponectin, leptin, adropin and endothelin-1 in healthy and obese or overweight children and determine the relationship between circulating adipocytokines and insulin resistance. Material and Method:The study was performed in a group of 60 children and adolescents of both sexes (30 males, 30 females) aged 8-16 years: 30 overweight (BMI range: 25-30) or obese (BMI range: 30-44), 30 age and sex matched healthy children (BMI range: 15-24). Anthropometric measurements and determinations of fasting blood glucose, insulin, triglycerides, total cholesterol, and HDL cholesterolwere performed. The homeostasis model assessment of insulin resistance (HOMA-IR) index and TG/HDL ratio were calculated to assess insulin resistance and cardiovascular risk. The fasting plasma levels of adipocytokines (leptin and adiponectin), adropin, and endothelin-1 were analyzed with ELISA. We compared healthy children group with overweight or obese children group for markers of insülin resistance (fasting insülin, HDL, TG/HDL ratio and HOMA-IR), adipocytokines (leptin and adiponectin), adropin and endothelin-1.We also evaluated interactions among leptin, adiponectin, adropin, endothelin-1, markers of insulin resistance, markers of adiposity (BMI, waist circumference) and lipid profiles in children with obesity. Results:Body weight, BMI, waist circumference, insulin, HOMA index, leptin, leptin/BMI ratio and leptin/adiponectin ratio were higher in the obese group (p=0.001 for all). HDL levels were found lower in children with obesity than control group (p=0.012). Trigliserid (TG)/HDL ratio was higher in children with obesity than control group (p=0.005). Adropin levels were lower in children with obesity than control group (p=0.003). Leptin were positively correlated with body weight (r=0.712, p=0.041), BMI (r=0.817, p=0.021), insülin (r=0.881, p=0.0012) and Homa index (r=0.834, p=0.0021) and adiponectin were negatively correlated with BMI(r =-0.759, p=0.003).Adiponectin/leptin ratio was lower in obesity group than control group (p=0.001). We did not find any significant correlation between hepatosteatosis frequency and adropin. There were no significant difference between males and females for leptin (p=0.66), adiponectin (p=0.740), adropin (p=0.382), endothelin-1 (p=0.355) and adiponectin/leptin ratio (p=0.350). Females were found to have a higher leptin/BMI ratio than males (p=0.022). Conclusion:This study supports evidence thatplasma levels of leptin and adropin are significantly different in obese children compared to healthy controls.The correlation between HDL cholesterol and insulin resistance could be a useful index in identifying children at risk for dyslipidemia, and metabolic syndrome.The understanding of childhood obesity-related health problems is getting improved bythe inclusion of adipocytokines in the evaluation of children with obesity in addition to markers of insulin resistance and lipid profiles like as HDL and TG/HDL. Key Words: Child's health, child, obesity, insulin resistance, adipocytokines, leptin, adiponectin, endothelin-