Variaciones en los parámetros cuantitativos y en la puntuación de la escala de Deauville aplicando diferentes algoritmos de reconstrucción en las imágenes PET/TC con [18F]FDG de pacientes con linfoma / The variation of quantitative parameters and Deauville scores with different reconstruction algorithms in FDG PET/CT imaging of lymphoma patients

Objetivos La escala de Deauville (DS) en la tomografía de emisión de positrones (PET) con [18F]fludeoxiglucosa ([18F]FDG) es un método semicuantitativo único para la evaluación del linfoma. Sin embargo, el tipo de algoritmo de reconstrucción empleado para el cálculo de los valores de captación estándar (max, medio y pico) podría afectar a la DS. Comparamos el algoritmo de reconstrucción de probabilidad penalizada bayesiano (BPL) con el de maximización de expectativas de subconjuntos ordenados (OSEM) respecto a los parámetros cuantitativos y en la DS en el linfoma. Investigamos el efecto del tamaño del ganglio linfático sobre la variación cuantitativa. Métodos Se reconstruyeron por separado los resultados de la PET sin procesar de 255 pacientes con linfoma utilizando la aplicación Q.Clear (General Electric Healthcare, Milwaukee, WI, EE. UU.), un algoritmo BPL, y la aplicación SharpIR (General Electric Healthcare, Milwaukee, WI, EE. UU.), un algoritmo OSEM. En ambas imágenes, para cada paciente, se valoró hígado, el pool sanguíneo mediastínico y los valores de captación estándar (SUV) (SUVmáx, SUVmedio y SUVpico) de un total de 487 lesiones seleccionadas. Se compararon DSmáx, DSmedio y DSpico. Resultados En nuestro estudio hubo un aumento significativo de la DS con el BPL (p<0,001) que pasó a una puntuación de 4 a 5 en 30 pacientes inicialmente catalogados como 1-2-3 mediante el algoritmo OSEM. Se observó que los valores cuantitativos de los ganglios linfáticos aumentaban de forma estadísticamente significativa con el BPL (p<0,001), mientras que la disminución de los valores de hígado fue notable respecto a las regiones de referencia (p<0,001). Además, la diferencia en los ganglios linfáticos se asoció de forma independiente con el tamaño de la lesión y fue considerablemente más pronunciada en las lesiones de pequeño tamaño (p<0,001) (AU)

Introduction and Objectives 18F-FDG PET with the Deauville score (DS) is a unique semiquantitative method for lymphoma. However, type of standard uptake values (max, mean, and peak) reconstruction algorithms could affect DS. We compared the Bayesian Penalized Likelihood reconstruction algorithm (BPL) with Ordered Subsets Expectation Maximization (OSEM) on quantitative parameters and DS in lymphoma. We investigated the effect of the size of the lymph node on quantitative variation. Patients and Methods Raw PET data of 255 lymphoma patients were reconstructed separately with Q.Clear (GE Healthcare), a BPL, and SharpIR (GE Healthcare), an OSEM algorithm. In both images, each patient's liver, mediastinal blood pool, and SUVs (SUVmax, SUVmean, and SUVpeak) of a total of 487 lesions selected from the patients were performed. DSmax, DSmean, and DSpeak were compared. Results In our study, DS increased significantly with BPL (p<0.001), and the DS increased to 4-5 in 30 patients evaluated as 1-2-3 with OSEM. It was found that the quantitative values of the lymph nodes increased statistically with BPL (p<0.001), and the liver from the reference regions were significantly decreased (p<0.001). In addition, difference in lymph node was independently associated with size of lesion and was significantly more pronounced in small lesions (p<0.001). The effects of BPL algorithm were more pronounced in SUVmax than in SUVmean and SUVpeak. DS-mean and DS-peak scores were less changed by BPL than DS-max. Conclusion Different reconstruction algorithms in FDG PET/CT affect the quantitative evaluation. That variation may affect the change in DS in lymphoma patients, thus affecting patient management (AU)

Prevalence and clinical features of pollen-food allergy syndrome in adults with seasonal allergic rhinitis.

OBJECTIVE: Pollen-food allergy syndrome (PFAS) is an IgE-mediated allergic reaction to certain foods due to prior sensitization to pollen allergens. The data about the prevalence of PFAS in adults in Turkey is not sufficiently reported. Our objective was to investigate the frequency and clinical features of PFAS in adult patients with seasonal allergic rhinitis (SAR). PATIENTS AND METHODS: A total of 222 patients with SAR were enrolled in our outpatient allergy clinic at Hacettepe University, during a ten-month period. A questionnaire was used to evaluate patients and to categorize those who experienced obvious allergy symptoms consistent with PFAS. Atopy was assessed by a standard skin prick test panel including common aeroallergen extracts. RESULTS: Among 222 patients with a diagnosis of SAR, 31 had patient reported PFAS (31/222, 14%). Among them, 23 (74.2%) were females, and their mean age was 32.29±9.24 years. The most common symptoms were isolated oropharyngeal symptoms (58.1%), followed by urticaria (51.6%) after culprit food ingestion. The most frequent culprit foods were eggplant, walnut, kiwi, peach, and melon. The predominant sensitizing aeroallergen was grass pollen. CONCLUSIONS: PFAS can be frequently observed in adults who are followed up for SAR. The most frequently involved foods are eggplant, walnut, kiwi, peach, and melon in Ankara Province. The symptoms of PFAS are usually localized in the oropharyngeal area and are self-limited.

Risk factors for brachial plexus injury and permanent sequelae due to shoulder dystocia.

Aim: The primary aim of this study was to determine the risk factors for the occurrence of brachial plexus injury in cases of shoulder dystocia. Secondly, it was aimed to determine the factors affecting the occurrence of permanent sequelae in cases with brachial plexus injury. Subjects and Methods: ICD-10 codes were scanned from the records of patients who gave birth between 2012 and 2018, and the records of patients with brachial plexus injury and shoulder dystocia were reached. Shoulder dystocia cases with brachial plexus damage were accepted as the study group, and shoulder dystocia cases without brachial plexus damage were considered the control group. Shoulder dystocia patients with brachial plexus injury and without injury were compared for 2-year orthopedics clinic follow-up reports, surgical intervention, permanent sequelae status as well as birth data, maternal characteristics, and maneuvers applied to the management of shoulder dystocia. Results: Five hundred sixty births with shoulder dystocia were detected. Brachial plexus injury was observed in 88 of them, and permanent sequelae were detected in 12 of these patients. Maneuvers other than McRobert's (advanced maneuvers) were used more and clavicle fracture was seen more in the group with plexus injury (P < 0.05, P < 0.05, respectively). Logistic regression analysis was performed to determine the risk factors of brachial plexus injury. Brachial plexus injury was observed 4.746 times more in infants who were delivered with advanced maneuvers and 3.58 times more in infants with clavicle fractures at birth. Conclusion: In patients with shoulder dystocia, the risk of brachial plexus injury increased in deliveries in which advanced maneuvers were used and clavicle fracture occurred.

Factores de riesgo independientes asociados al sangrado en la nefrolitotomía percutánea: estudio retrospectivo / Independent risk factors affecting hemorrhage in percutaneous nephrolithotomy: Retrospective study

Introducción: El mayor motivo de preocupación durante el perioperatorio y postoperatorio de la nefrolitotomía percutánea (NLP) es el sangrado. Se determinaron las condiciones relacionadas con la enfermedad (tamaño del cálculo, UH del cálculo, número de trayectos y diámetro) que afectan el desarrollo de esta condición, con el objetivo de conocer los factores de riesgo independientes que pueden afectar el volumen del sangrado en la NLP.Material y método: Se incluyeron en el estudio un total de 308 pacientes adultos (211 hombres y 97 mujeres) sometidos al procedimiento de NLP. La anatomía renal y el tamaño de los cálculos se evaluaron mediante tomografía computarizada de corte fino sin contraste. Esta prueba de imagen se utilizó para evaluar los valores de unidades Hounsfield (UH) de los cálculos renales, la presencia de placas de ateroma y la obesidad. Se registró la diferencia entre el valor preoperatorio de hemoglobina (Hgb) y el valor de Hgb del primer día del postoperatorio. Se evaluó esta variación en función del sexo, la edad, la enfermedad vascular aterosclerótica, el pH y la densidad de la orina, el recuento de leucocitos, de linfocitos, de neutrófilos (NEU) y de plaquetas, el volumen plaquetario medio (VPM), el índice neutrófilo-linfocito (INL), el índice plaqueta-linfocito, el volumen de los cálculos, las UH y la obesidad.Resultados: La variación media de Hgb se identificó como 2,1 (desviación estándar: 1,6). Hubo correlaciones positivas, significativas y débiles entre la variación de Hgb con los valores de NEU (p=0,019), VPM (p=0,000), INL (p=0,005), volumen del cálculo (p=0,041) y UH (p=0,024). Hubo una correlación negativa significativa y débil entre la variación de la Hgb y el recuento PLT (p=0,022). No se identificaron efectos a niveles significativos del sexo (p=0,078), la presencia de placas de ateroma (p=0,949), la obesidad (p=0,869), la edad (AU)

Introduction: The perioperative and postoperative concern in percutaneous nephrolithotomy (PNL) is bleeding. Disease-related conditions (such as stone size, stone HU, tract number, and diameter) affecting this situation were determined. To determine independent risk factors that may affect the amount of hemorrhage in PNL.Material and method: A total of 308 adult patients (211 men, 97 women) undergoing the PNL procedure were included in the study. Renal anatomy and stone size were evaluated using non-contrast thin-section computed tomography (NCCT). NCCT was used to assess Hounsfield unit (HU) values of kidney stones, presence of atheroma plaque and obesity. The difference between preoperative hemoglobin (Hgb) values and postoperative 1st day Hgb values was recorded. This variation was evaluated for the effect of gender, age, atherosclerotic vein disease, urine pH and density, leukocyte count, lymphocyte count, neutrophil count (NEU), platelet count, mean platelet volume (MPV), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), stone volume, HU, and obesity.ResultsThe mean Hgb variation was identified as 2.1 (standard deviation: 1.6). There were positive, significant, and weak correlations between the Hgb variation with NEU (P=.019), MPV (P=.000), NLR (P=.005), stone volume (P=.041) and HU (P=.024) values. There was a negative significant and weak correlation between Hgb variation and PLT (P=.022). No effects at significant levels were identified for gender (P=.078), presence of atheroma plaque (P=.949), obesity (P=.869), age (P=.686), urine pH (P=.746), urine density (P=.421), and PLR (P=.855) on Hgb variations.Conclusion: In addition to HU and stone volume, NEU count, MPV, NLR and PLT count may be used as independent risk factors to predict blood loss during PNL (AU)

A new classification option for NSAID hypersensitivity: Kalyoncu classification

Background The European Network for Drug Allergy (ENDA) proposed a consensus document for hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) in 2011. A subgroup of patients with NSAIDs-exacerbated respiratory disease (NERD) develop urticaria/angioedema type reactions in response to NSAIDs. The Kalyoncu classification might be a novel option to classify patients with NSAID hypersensitivity (NH). In this study, we compare the ENDA and the Kalyoncu classifications. Methods This study enrolled a total of 196 patients. NH reaction types were categorized as asthma, rhinitis, urticaria/angioedema and anaphylaxis. Based on the reaction history and oral provocation test findings, patients were grouped according to ENDA and Kalyoncu classifications. Results The mean age of the 196 patients was 40.32±13.28 years, and 130 (66.3%) of them were female. Under the ENDA and Kalyoncu classifications, the most common NH subgroups were NERD (32%), and isolated NH (34.2%), the least prevalent NH subgroups were single NSAID-induced delayed reactions (SNIDR) (1.5%), and pseudo Samter’s syndrome (11.7%). Conclusions Our research revealed that the Kalyoncu classification is more descriptive of patients with NERD exhibiting urticaria/angioedema-type reactions. It also provides future risk assessment for development of NERD. For controversial cases, the Kalyoncu classification can be utilized as a new complimentary option alone or in conjunction with ENDA classification (AU)

Independent risk factors affecting hemorrhage in percutaneous nephrolithotomy: Retrospective study.

INTRODUCTION: The perioperative and postoperative concern in percutaneous nephrolithotomy (PNL) is bleeding. Disease-related conditions (such as stone size, stone HU, tract number, and diameter) affecting this situation were determined. To determine independent risk factors that may affect the amount of hemorrhage in PNL. MATERIAL AND METHOD: A total of 308 adult patients (211 men, 97 women) undergoing the PNL procedure were included in the study. Renal anatomy and stone size were evaluated using non-contrast thin-section computed tomography (NCCT). NCCT was used to assess Hounsfield unit (HU) values of kidney stones, presence of atheroma plaque and obesity. The difference between preoperative hemoglobin (Hgb) values and postoperative 1st day Hgb values was recorded. This variation was evaluated for the effect of gender, age, atherosclerotic vein disease, urine pH and density, leukocyte count, lymphocyte count, neutrophil count (NEU), platelet count, mean platelet volume (MPV), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), stone volume, HU, and obesity. RESULTS: The mean Hgb variation was identified as 2.1 (standard deviation: 1.6). There were positive, significant, and weak correlations between the Hgb variation with NEU (P=0.019), MPV (P=0.000), NLR (P=0.005), stone volume (P=0.041) and HU (P=0.024) values. There was a negative significant and weak correlation between Hgb variation and PLT (P=0.022). No effects at significant levels were identified for gender (P=0.078), presence of atheroma plaque (P=0.949), obesity (P=0.869), age (P=0.686), urine pH (P=0.746), urine density (P=0.421), and PLR (P=0.855) on Hgb variations. CONCLUSION: In addition to HU and stone volume, NEU count, MPV, NLR and PLT count may be used as independent risk factors to predict blood loss during PNL.

Computational Modeling of TP63-TP53 Interaction and Rational Design of Inhibitors: Implications for Therapeutics.

Tumor protein p63 (TP63) is a member of the TP53 protein family that are important for development and in tumor suppression. Unlike TP53, TP63 is rarely mutated in cancer, but instead different TP63 isoforms regulate its activity. TA isoforms (TAp63) act as tumor suppressors, whereas ΔN isoforms are strong drivers of squamous or squamous-like cancers. Many of these tumors become addicted to ΔN isoforms and removal of ΔN isoforms result in cancer cell death. Furthermore, some TP53 conformational mutants (TP53CM) gain the ability to interact with TAp63 isoforms and inhibit their antitumorigenic function, while indirectly promoting tumorigenic function of ΔN isoforms, but the exact mechanism of TP63-TP53CM interaction is unclear. The changes in the balance of TP63 isoform activity are crucial to understanding the transition between normal and tumor cells. Here, we modeled TP63-TP53CM complex using computational approaches. We then used our models to design peptides to disrupt the TP63-TP53CM interaction and restore antitumorigenic TAp63 function. In addition, we studied ΔN isoform oligomerization and designed peptides to inhibit its oligomerization and reduce their tumorigenic activity. We show that some of our peptides promoted cell death in a TP63 highly expressed cancer cell line, but not in a TP63 lowly expressed cancer cell line. Furthermore, we performed kinetic-binding assays to validate binding of our peptides to their targets. Our computational and experimental analyses present a detailed model for the TP63-TP53CM interaction and provide a framework for potential therapeutic peptides for the elimination of TP53CM cancer cells.

Relationships between RDW, NLR, CAR, and APACHE II scores in the context of predicting the prognosis and mortality in ICU patients.

OBJECTIVE: Intensive care units (ICU) are tasked with critical care and treatment with a view to improving prognosis. The Acute Physiology and Chronic Health Evaluation II (APACHE II) is one of the most commonly used scoring systems to predict prognosis. In this context, the objective of this study is to evaluate the prognostic value of Red Cell Distribution Width (RDW), Neutrophil-Lymphocyte ratio (NLR), and C-reactive protein to albumin ratio (CAR) in predicting the prognosis and mortality in patients admitted to the ICU. PATIENTS AND METHODS: The RDW, NLR, and CAR values and APACHE II scores of patients admitted into an ICU, where heterogeneous groups of patients are usually treated, were recorded, categorized based on survival status, and investigated for any correlation between surviving patients' mortality and length of stay (LoS) in ICU and the said parameters. RESULTS: The ICU mortality among the 2,147 patients included in the study was 43.2%. The most common diagnosis of the patients admitted to the ICU was sepsis. The RDW, NLR, and CAR values and APACHE II scores of the deceased patients were significantly higher than those of the survived patients. There was a significant correlation between LoS in ICU and the said parameters in the positive direction in the survived group only. The APACHE II score had the highest prognostic value in predicting mortality, followed by RDW, CAR, and NLR values in descending order. CONCLUSIONS: Among the parameters investigated in this study, RDW had the highest prognostic value in predicting the prognosis and mortality. Hence, it may be incorporated into or used alongside the APACHE II scoring system to predict patient outcomes with higher accuracy. However, further randomized controlled studies are needed to determine the cut-off values in predicting the prognosis and mortality.

In Silico Screening and Testing of FDA-Approved Small Molecules to Block SARS-CoV-2 Entry to the Host Cell by Inhibiting Spike Protein Cleavage.

The COVID-19 pandemic began in 2019, but it is still active. The development of an effective vaccine reduced the number of deaths; however, a treatment is still needed. Here, we aimed to inhibit viral entry to the host cell by inhibiting spike (S) protein cleavage by several proteases. We developed a computational pipeline to repurpose FDA-approved drugs to inhibit protease activity and thus prevent S protein cleavage. We tested some of our drug candidates and demonstrated a decrease in protease activity. We believe our pipeline will be beneficial in identifying a drug regimen for COVID-19 patients.

Ras Multimers on the Membrane: Many Ways for a Heart-to-Heart Conversation.

Formation of Ras multimers, including dimers and nanoclusters, has emerged as an exciting, new front of research in the 'old' field of Ras biomedicine. With significant advances made in the past few years, we are beginning to understand the structure of Ras multimers and, albeit preliminary, mechanisms that regulate their formation in vitro and in cells. Here we aim to synthesize the knowledge accrued thus far on Ras multimers, particularly the presence of multiple globular (G-) domain interfaces, and discuss how membrane nanodomain composition and structure would influence Ras multimer formation. We end with some general thoughts on the potential implications of Ras multimers in basic and translational biology.

THE EFFECTS OF CHRONIC PERIODONTITIS AND OBESITY ON TOTAL ANTIOXIDANT/OXIDANT STATUS AND OXIDATIVE STRESS INDEX.

Objective: Both obesity and periodontal diseases are significant diseases that affect the quality of life. Recent studies have focused on the relationship between obesity and periodontal disease. The aim of this study is to determine the pathophysiological relationship between obesity and periodontal disease by evaluating the clinical periodontal parameters and oxidative status. Subjects and Methods: The study included 80 individuals divided into four groups including 20 individuals in each group as following; periodontally healthy patients with normal weight, (NH), patients with chronic periodontitis and normal weight (NCP), periodontally healthy patients with obesity (OH) and patients with chronic periodontitis and obesity (OCP). Clinical periodontal parameters were recorded, and serum, saliva and gingival crevicular fluid (GCF) samples were obtained. Local and systemic levels of total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) were assessed biochemically. Results: No statistically significant difference was found among the groups regarding TAS, TOS and OSI values in serum and saliva samples (p>0.05). GCF-TAS values in NH group were statistically significantly higher compared with other groups (p<0,05) . GCF TOS values increased in obese groups (OH, OCP) compared with non-obese groups (NH, NCP) (p<0.05). Our results suggest that obesity and chronic periodontitis do not effect oxidant/antioxidant levels in serum and saliva. Conclusions: Many factors such as daily living conditions of the individual, stress and nutritional habits TAS and TOS levels of the individual may affect oxidative stress parameters. However, these factors could not be standardized in the study.

Can Carpobrotus edulis, heal incisional and excisional wounds on the skin?

OBJECTIVES: This study aimed to investigate the wound healing activity of liposomal Carpobrotus edulis powder extract (CEPE) formulation on incisional and excisional wounds in rat. BACKGROUND: In the event of any damage, the damaged tissue undergoes a process of regenerating itself, which is called wound healing. METHODS: Centella asiatica extract (CAE) was used as the reference molecule in the study. The wound healing process was tested by using the excisional and incisional wound model. On the 12th day of the study, maximum stress, stress, % of elongation values were evaluated in the incisional wound. Also; histological parameters and macroscopic photographic analyses were evaluated in the excisional wound. RESULTS: In the photo evaluations, the improvement was more prominent in both CAE and CEPE groups than in the control group. Histological evaluation showed that CEPE group had significant wound healing activity compared to the control and CAE groups. Axial tensile-elongation experiments in incisional wound tissue show that there was no significant difference between CAE and CEPE groups. CONCLUSION: Liposomal formulations of C.edulis extract were found to have positive effects on the healing process, both on excisional and incisional wound tissues (Tab. 2, Fig. 3, Ref. 30).

Molecular modelling of the FOXO4-TP53 interaction to design senolytic peptides for the elimination of senescent cancer cells.

BACKGROUND: Senescent cells accumulate in tissues over time as part of the natural ageing process and the removal of senescent cells has shown promise for alleviating many different age-related diseases in mice. Cancer is an age-associated disease and there are numerous mechanisms driving cellular senescence in cancer that can be detrimental to recovery. Thus, it would be beneficial to develop a senolytic that acts not only on ageing cells but also senescent cancer cells to prevent cancer recurrence or progression. METHODS: We used molecular modelling to develop a series of rationally designed peptides to mimic and target FOXO4 disrupting the FOXO4-TP53 interaction and releasing TP53 to induce apoptosis. We then tested these peptides as senolytic agents for the elimination of senescent cells both in cell culture and in vivo. FINDINGS: Here we show that these peptides can act as senolytics for eliminating senescent human cancer cells both in cell culture and in orthotopic mouse models. We then further characterized one peptide, ES2, showing that it disrupts FOXO4-TP53 foci, activates TP53 mediated apoptosis and preferentially binds FOXO4 compared to TP53. Next, we show that intratumoural delivery of ES2 plus a BRAF inhibitor results in a significant increase in apoptosis and a survival advantage in mouse models of melanoma. Finally, we show that repeated systemic delivery of ES2 to older mice results in reduced senescent cell numbers in the liver with minimal toxicity. INTERPRETATION: Taken together, our results reveal that peptides can be generated to specifically target and eliminate FOXO4+ senescent cancer cells, which has implications for eradicating residual disease and as a combination therapy for frontline treatment of cancer. FUNDING: This work was supported by the Cancer Early Detection Advanced Research Center at Oregon Health & Science University.

Optical coherence tomography angiography findings in patients with ocular and non-ocular Behcet disease / Achados de angiografia por tomografia de coerência óptica em pacientes com doença de Behçet com e sem acometimento ocular

ABSTRACT Purposes: To evaluate the optical coherence tomography angiography findings in patients with Behçet disease with and without ocular involvement. Methods: A total of 40 patients with Behçet disease and 30 healthy controls were enrolled in the study. Retinal vessel density in the superficial capillary plexus and deep capillary plexus, foveal avascular zone area and perimeter, acirculatory index, foveal density, and nonflow area in the superficial retina were automatically measured using the optical coherence tomography angiography software AngioVue and compared between the groups. Results: The mean parafoveal and perifoveal vessel densities in the superficial capillary plexus and deep capillary plexus and foveal density were significantly lower in the eyes with Behçet uveitis compared to the eyes without Behçet uveitis and eyes of the healthy controls. In the eyes with Behçet uveitis, logMAR visual acuity showed a moderate correlation with parafoveal and perifoveal vessel densities and foveal density (r=-0.43, p=0.006; r=-0.62, p<0.001; r=-0.42, p=0.008; respectively). Conclusion: Behçet disease with posterior uveitis was associated with significant perifoveal and parafoveal vascular decrements in the superficial and deep retina.(AU)

RESUMO Objetivo: Avaliar achados de angiografia por tomografia de coerência óptica em pacientes com doença de Behçet com e sem acometimento ocular. Métodos: Foram incluídos 40 pacientes com doença de Behçet e 30 controles saudáveis. A densidade vascular retiniana nos plexos capilares superficial e profundo, a zona avascular foveal, o índice de circularidade, a densidade foveal e a área sem fluxo da retina superficial foram medidos automaticamente, através do software AngioVue para angiografia por tomografia de coerência óptica, e comparados entre os grupos. Resultados: A densidade vascular parafoveal e perifoveal média nos plexos capilares superficial e profundo, bem como a densidade foveal, foram significativamente menores nos olhos com uveíte de Behçet em comparação com os olhos sem uveíte de Behçet e os olhos dos controles saudáveis. Nos olhos com uveíte de Behçet, a acuidade visual logMAR mostrou correlação moderada com a densidade vascular parafoveal e perifoveal e com a densidade foveal (respectivamente, r=-0,43, p=0,006; r=-0,62, p<0,001; e r=-0,42, p = 0,008). Conclusão: A doença de Behçet com uveíte posterior foi associada a decréscimos significativos da vascularização perifoveal e parafoveal na retina superficial e profunda.(AU)

Optical coherence tomography angiography findings in patients with ocular and non-ocular Behcet disease.

PURPOSES: To evaluate the optical coherence tomography angiography findings in patients with Behçet disease with and without ocular involvement. METHODS: A total of 40 patients with Behçet disease and 30 healthy controls were enrolled in the study. Retinal vessel density in the superficial capillary plexus and deep capillary plexus, foveal avascular zone area and perimeter, acirculatory index, foveal density, and nonflow area in the superficial retina were automatically measured using the optical coherence tomography angiography software AngioVue and compared between the groups. RESULTS: The mean parafoveal and perifoveal vessel densities in the superficial capillary plexus and deep capillary plexus and foveal density were significantly lower in the eyes with Behçet uveitis compared to the eyes without Behçet uveitis and eyes of the healthy controls. In the eyes with Behçet uveitis, logMAR visual acuity showed a moderate correlation with parafoveal and perifoveal vessel densities and foveal density (r=-0.43, p=0.006; r=-0.62, p<0.001; r=-0.42, p=0.008; respectively). CONCLUSION: Behçet disease with posterior uveitis was associated with significant perifoveal and parafoveal vascular decrements in the superficial and deep retina.

Expression of Serum Vascular Endothelial Growth Factor and Angiopoietin Receptor Tie-2 in Essential Hypertension

ABSTRACT Objective: To investigate the serum levels of a vascular endothelial growth factor (VEGF), an angiogenic factor and a soluble angiopoietin receptor Tie-2 (sTie-2) in patients with essential hypertension. Methods: In the present study 90 individuals (56 males and 34 females, mean age 48 ± 7 years) have been divided into 3 groups: 30 patients with hypertension, 30 healthy individuals with a family history of hypertension and 30 healthy individuals with no family history of hypertension. All individuals have been evaluated in terms of blood pressure and biochemical parameters. The levels of VEGF and Tie-2 receptor have been evaluated by using the enzyme-linked immunosorbent assay method. Results: The findings suggested that the serum VEGF, sTie-2 receptor, low-density lipoprotein and triglycerides levels in the hypertensive patients were significantly higher than those in the control group (p < 0.05). However, the level of high-density lipoprotein cholesterol in the patients was significantly lower than in those in the control group (p < 0.05). In correlation analysis, a positive correlation was found statistically significant between the values of VEGF and sTie-2 (r = 0.405, p = 0.026). Conclusion: As a result of this study, our data indicate that serum levels of VEGF and Tie-2 receptor may be related to the primary hypertension. This study could inspire to further studies to explore the roles of VEGF and Tie-2 receptor in essential hypertension.

Oncogenic K-Ras4B Dimerization Enhances Downstream Mitogen-activated Protein Kinase Signaling.

Ras recruits and activates effectors that transmit receptor-initiated signals. Monomeric Ras can bind Raf; however, Raf's activation requires dimerization, which can be facilitated by Ras dimerization. Previously, we showed that active K-Ras4B dimerizes in silico and in vitro through two major interfaces: (i) ß-interface, mapped to Switch I and effector-binding regions, (ii) α-interface at the allosteric lobe. Here, we chose constitutively active K-Ras4B as our control and two double mutants (K101D and R102E; and R41E and K42D) in the α- and ß-interfaces. Two of the mutations are from The Cancer Genome Atlas (TCGA) and the Catalogue Of Somatic Mutations In Cancer (COSMIC) data sets. R41 and R102 are found in several adenocarcinomas in Ras isoforms. We performed site-directed mutagenesis, cellular localization experiments, and molecular dynamics (MD) simulations to assess the impact of the mutations on K-Ras4B dimerization and function. α-interface K101D/R102E double mutations reduced dimerization but only slightly reduced downstream phosphorylated extracellular signal-regulated kinase (ERK) (pERK) levels. While ß-interface R41E/K42D double mutations did not interfere with dimerization, they almost completely blocked K-Ras4B-mediated ERK phosphorylation. Both double mutations increased downstream phosphorylated Akt (pAkt) levels in cells. Changes in pERK and pAkt levels altered ERK- and Akt-regulated gene expressions, such as EGR1, JUN, and BCL2L11. These results underscore the role of the α-interface in K-Ras4B homodimerization and the ß-surface in effector binding. MD simulations highlight that the membrane and hypervariable region (HVR) interact with both α- and ß-interfaces of K-Ras4B mutants, respectively, inhibiting homodimerization and probably effector binding. Mutations at both interfaces interfered with mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase signaling but in different forms and extents. We conclude that dimerization is not necessary but enhances downstream MAPK signaling.

Evaluation of serum ischaemia-modified albumin levels in patients with Bell's palsy.

OBJECTIVE: This prospective study aimed to evaluate the relationship between serum ischaemia-modified albumin levels and Bell's palsy severity. METHODS: The study included 30 patients diagnosed with Bell's palsy and 30 healthy individuals. The patients were separated into three disease severity groups (grades 2, 3 and 4) according to House-Brackmann classification. Blood samples were collected from all participants and the results compared between groups. RESULTS: Significant differences in serum ischaemia-modified albumin were found between the study and control groups (p < 0.001); values were significantly higher in the study group than in the control group. CONCLUSION: The significantly higher levels of serum ischaemia-modified albumin in the study group suggest that Bell's palsy pathogenesis is associated with oxidative stress.

Geographic Distribution of Multiple Arteries and Veins of 878 Kidney Donors From a Transplant Center in Turkey.

AIM: The diagnosis and management of multiple renal arteries and veins have gained importance with the increasing number of kidney transplantations and improved techniques in interventional radiology and vascular reconstructions. The aim of this study is to define and to detect the rate of multiple renal arteries and veins in our living kidney transplant donors coming from all parts of our country. METHODS: Abdominal computed tomography angiogram findings of 878 kidney transplant donors were analyzed. The presence and the distribution of multiple renal arteries and veins in donors coming from 7 geographic regions in Turkey were noted. RESULTS: The presence of multiple renal arteries was observed in 34% (48/141) of patients in the Marmara Region, 36.7% (79/215) of patients in the Black Sea Region, 37.2% (64/172) of patients in the Central Anatolia Region and 36.1% (30/83) of patients in the Southeastern Anatolia Region. The highest incidences of multiple renal arteries were observed in the Mediterranean and Aegean regions, affecting 40% (32/80) and 41.9% (26/62) of patients, respectively, while East Anatolia was found to have the lowest incidence, affecting 28% (35/125) of patients. The incidence of multiple renal veins also varied across regions. The highest incidence was observed in the Central Anatolia Region, where 23.3% (40/172) of patients were affected; the lowest was seen in the Aegean Region, where 11.3% (7/62) of patients were affected. In Turkey as a whole, 35.8% (314/878) of patients presented with multiple renal arteries, while the rate of multiple renal veins was found to be 19% (167/878) among our donors. CONCLUSIONS: As 80% of the kidney transplantations performed in Turkey involve living donors, we think it will be useful to have knowledge of not only the presence of multiple renal arteries and veins, but also the distribution of this feature throughout the different regions of the country.