Glucagon-like peptide-1 receptor expression in the human eye.

Semaglutide is a human glucagon-like peptide-1 (GLP-1) analogue that is in development for the treatment of type 2 diabetes. In the pre-approval cardiovascular outcomes trial SUSTAIN 6, semaglutide was associated with a significant increase in the risk of diabetic retinopathy (DR) complications vs placebo. GLP-1 receptor (GLP-1R) expression has previously been demonstrated in the retina in animals and humans; however, antibodies used to detect expression have been documented to be non-specific and fail to detect the GLP-1R using immunohistochemistry (IHC), a problem common for many G-protein coupled receptors. Using a validated GLP-1R antibody for IHC and in situ hybridization for GLP-1R mRNA in normal human eyes, GLP-1Rs were detected in a small fraction of neurons in the ganglion cell layer. In advanced stages of DR, GLP-1R expression was not detected at the protein or mRNA level. Specifically, no GLP-1R expression was found in the eyes of people with long-standing proliferative DR (PDR). In conclusion, GLP-1R expression is low in normal human eyes and was not detected in eyes exhibiting advanced stages of PDR.

Evaluation of prognostic factors and treatment in advanced small bowel adenocarcinoma: report of a multi-institutional experience of Anatolian Society of Medical Oncology (ASMO).

PURPOSE: Small bowel adenocarcinoma (SBA) is a rare tumor of the gastrointestinal system with poor prognosis. Since these are rarely encountered tumors, there are limited numbers of studies investigating systemic treatment in advanced SBA. The purpose of this study was to evaluate the prognostic factors and systemic treatments in patients with advance SBA. METHODS: Seventy-one patients from 18 Centers with advanced SBA were included in the study. Fifty-six patients received one of the four different chemotherapy regimens as first-line therapy and 15 patients were treated with best supportive care (BSC). RESULTS: Of the 71 patients, 42 (59%) were male and 29 (41%) female with a median age of 56 years. Median follow- up duration was 14.3 months. The median progression free survival (PFS) and overall survival (OS) were 7 and 13 months, respectively (N=71). In patients treated with FOLFOX (N=18), FOLFIRI (N=11), cisplatin-5-fluorouracil/ 5-FU (N=17) and gemcitabine alone (N=10), median PFS was 7, 8, 8 and 5 months, respectively, while median OS was 15, 16, 15 and 11 months, respectively. No significant differences between chemotherapy groups were noticed in terms of PFS and OS. Univariate analysis revealed that chemotherapy administration, de novo metastatic disease, ECOG PS 0 and 1, and overall response to therapy were significantly related to improved outcome. Only overall response to treatment was found to be significantly prognostic in multivariate analysis (p=0.001). CONCLUSIONS: In this study, overall response to chemotherapy emerged as the single significant prognostic factor for advanced SBAs. Platin and irinotecan based regimens achieved similar survival outcomes in advanced SBA patients.

ABT-089, but not ABT-107, ameliorates nicotine withdrawal-induced cognitive deficits in C57BL6/J mice.

Nicotine withdrawal produces cognitive deficits that can predict relapse. Amelioration of these cognitive deficits emerges as a target in current smoking cessation therapies. In rodents, withdrawal from chronic nicotine disrupts contextual fear conditioning (CFC), whereas acute nicotine enhances this hippocampus-specific learning and memory. These modifications are mediated by ß2-subunit-containing (ß2*) nicotinic acetylcholine receptors in the hippocampus. We aimed to test ABT-089, a partial agonist of α4ß2*, and ABT-107, an α7 nicotinic acetylcholine receptor agonist, for amelioration of cognitive deficits induced by withdrawal from chronic nicotine in mice. Mice underwent chronic nicotine administration (12.6 mg/kg/day or saline for 12 days), followed by 24 h of withdrawal. At the end of withdrawal, mice received 0.3 or 0.6 mg/kg ABT-089 or 0.3 mg/kg ABT-107 (doses were determined through initial dose-response experiments and prior studies) and were trained and tested for CFC. Nicotine withdrawal produced deficits in CFC that were reversed by acute ABT-089, but not ABT-107. Cued conditioning was not affected. Taken together, our results suggest that modulation of hippocampal learning and memory using ABT-089 may be an effective component of novel therapeutic strategies for nicotine addiction.

Nicotine shifts the temporal activation of hippocampal protein kinase A and extracellular signal-regulated kinase 1/2 to enhance long-term, but not short-term, hippocampus-dependent memory.

Acute nicotine enhances hippocampus-dependent learning through nicotine binding to ß2-containing nicotinic acetylcholine receptors (nAChRs), but it is unclear if nicotine is targeting processes involved in short-term memory (STM) leading to a strong long-term memory (LTM) or directly targeting LTM. In addition, the molecular mechanisms involved in the effects of nicotine on learning are unknown. Previous research indicates that protein kinase A (PKA), extracellular signal-regulated kinase 1/2 (ERK1/2), and protein synthesis are crucial for LTM. Therefore, the present study examined the effects of nicotine on STM and LTM and the involvement of PKA, ERK1/2, and protein synthesis in the nicotine-induced enhancement of hippocampus-dependent contextual learning in C57BL/6J mice. The protein synthesis inhibitor anisomycin impaired contextual conditioning assessed at 4 h but not 2 h post-training, delineating time points for STM (2 h) and LTM (4 h and beyond). Nicotine enhanced contextual conditioning at 4, 8, and 24 h but not 2 h post-training, indicating nicotine specifically enhances LTM but not STM. Furthermore, nicotine did not rescue deficits in contextual conditioning produced by anisomycin, suggesting that the nicotine enhancement of contextual conditioning occurs through a protein synthesis-dependent mechanism. In addition, inhibition of dorsal hippocampal PKA activity blocked the effect of acute nicotine on learning, and nicotine shifted the timing of learning-related PKA and ERK1/2 activity in the dorsal and ventral hippocampus. Thus, the present results suggest that nicotine specifically enhances LTM through altering the timing of PKA and ERK1/2 signaling in the hippocampus, and suggests that the timing of PKA and ERK1/2 activity could contribute to the strength of memories.

The epigenetic effect of nicotine on dopamine D1 receptor expression in rat prefrontal cortex.

Nicotine is a highly addictive drug and exerts its effect partially through causing dopamine release, thereby increasing intrasynaptic dopamine levels in the brain reward systems. Dopaine D1 receptor (DRD1) mRNAs and receptors are localized in reward-related brain regions, which receive cholinergic input. The aim of this study is to evaluate whether nicotine administration affects the expression of DRD1s, and if so, whether epigenetic mechanisms, such as histone acetylation, are involved. Twenty Male Sprague Dawley rats received nicotine (0.4 mg/kg/day, s.c.) or saline injections for 15 days. After nicotine/saline treatment, rats were perfused with saline; prefrontal cortex (PFC), corpus striatum (STR), and ventral tegmental area (VTA) were dissected. Homogenates were divided into two parts for total RNA isolation and histone H4 acetylation studies. DRD1 mRNA expression was significantly higher in the PFC of the nicotine-treated group compared with controls; similar trends were observed in the VTA and STR. To study epigenetic regulation, the 2kb upstream region of the DRD1 gene promoter was investigated for histone H4 acetylation in PFC samples. After chromatin immunoprecipitation with anti-acetyl histone H4 antibody, we found an increase in histone acetylation by two different primer pairs which amplified the -1365 to -1202 (P < 0.005) and -170 to +12 (P < 0.05) upstream regions of the DRD1 promoter. Our results suggest that intermittent subcutaneous nicotine administration increases the expression of DRD1 mRNA in the PFC of rats, and this increase may be due to changes in histone H4 acetylation of the 2kb promoter of the DRD1 gene.

Fog-cloud architecture-driven Internet of Medical Things framework for healthcare monitoring.

The new coronavirus disease (COVID-19) has increased the need for new technologies such as the Internet of Medical Things (IoMT), Wireless Body Area Networks (WBANs), and cloud computing in the health sector as well as in many areas. These technologies have also made it possible for billions of devices to connect to the internet and communicate with each other. In this study, an Internet of Medical Things (IoMT) framework consisting of Wireless Body Area Networks (WBANs) has been designed and the health big data from WBANs have been analyzed using fog and cloud computing technologies. Fog computing is used for fast and easy analysis, and cloud computing is used for time-consuming and complex analysis. The proposed IoMT framework is presented with a diabetes prediction scenario. The diabetes prediction process is carried out on fog with fuzzy logic decision-making and is achieved on cloud with support vector machine (SVM), random forest (RF), and artificial neural network (ANN) as machine learning algorithms. The dataset produced in WBANs is used for big data analysis in the scenario for both fuzzy logic and machine learning algorithm. The fuzzy logic gives 64% accuracy performance in fog and SVM, RF, and ANN have 89.5%, 88.4%, and 87.2% accuracy performance respectively in the cloud for diabetes prediction. In addition, the throughput and delay results of heterogeneous nodes with different priorities in the WBAN scenario created using the IEEE 802.15.6 standard and AODV routing protocol have been also analyzed. Fog-Cloud architecture-driven for IoMT networks • An IoMT framework is designed with important components and functions such as fog and cloud node capabilities. •Real-time data has been obtained from WBANs in Riverbed Modeler for a more realistic performance analysis of IoMT. •Fuzzy logic and machine learning algorithms (RF, SVM, and ANN) are used for diabetes predictions. •Intra and Inter-WBAN communications (IEEE 802.15.6 standard) are modeled as essential components of the IoMT framework with all functions.

Real-time internet of medical things framework for early detection of Covid-19.

The Covid-19 pandemic is a deadly epidemic and continues to affect all world. This situation dragged the countries into a global crisis and caused the collapse of some health systems. Therefore, many technologies are needed to slow down the spread of the Covid-19 epidemic and produce solutions. In this context, some developments have been made with artificial intelligence, machine learning and deep learning support systems in order to alleviate the burden on the health system. In this study, a new Internet of Medical Things (IoMT) framework is proposed for the detection and early prevention of Covid-19 infection. In the proposed IoMT framework, a Covid-19 scenario consisting of various numbers of sensors is created in the Riverbed Modeler simulation software. The health data produced in this scenario are analyzed in real time with Apache Spark technology, and disease prediction is made. In order to provide more accurate results for Covid-19 disease prediction, Random Forest and Gradient Boosted Tree (GBT) Ensemble Learning classifiers, which are formed by Decision Tree classifiers, are compared for the performance evaluation. In addition, throughput, end-to-end delay results and Apache Spark data processing performance of heterogeneous nodes with different priorities are analyzed in the Covid-19 scenario. The MongoDB NoSQL database is used in the IoMT framework to store big health data produced in real time and use it in subsequent processes. The proposed IoMT framework experimental results show that the GBTs classifier has the best performance with 95.70% training, 95.30% test accuracy and 0.970 area under the curve (AUC) values. Moreover, the promising real-time performances of wireless body area network (WBAN) simulation scenario and Apache Spark show that they can be used for the early detection of Covid-19 disease.

Tissue and serum adiponectin levels in patients with gastric cancer: are there any correlations between adiponectin levels and histopathological variables?

BACKGROUND/AIMS: Adiponectin is secreted from adipose tissue and is characterized by hyperinsulinemia, which is related with obesity. Adiponectin levels are significantly lower in gastric cancer patients than in healthy controls. The aim of this study was to investigate the relationship between adiponectin levels in serum, tumor tissue and normal tissue with some other insulin resistance parameters. METHODOLOGY: A total of 35 patients with gastric cancer who had undergone curative gastrectomy by standard lymph node dissection were enrolled in this study. Their serum adiponectin levels, tumor tissue and normal breast tissue adiponectin levels were compared. RESULTS: The mean adiponectin levels of the tumor tissue, normal gastric tissue and serum were 48.6±2.9 (range, 39.7-50.6), 48.3±4.2 (range, 34.4-50.69) and 49.4±0.83 (range, 48.2-50.2), respectively. There was no relationship between the adiponectin levels in serum, normal tissue and tumor tissue (p=0.08). There was an inverse relationship between normal tissue adiponectin levels and insulin levels (p=0.002, r=-0.5), but this association was not detected with adiponectin levels in tumor and serum (p>0.05). CONCLUSIONS: Relationships between adiponectin levels in serum, normal tissue and tumor tissue for gastric cancer patients were not found. The small sample size in this study may have influenced the results. However, we believe that our results constitute a first in evaluating the tissue adiponectin levels in gastric cancer tissue.

Prognostic significance of perineural invasion in patients with gastric cancer who underwent curative resection.

BACKGROUND: The prognostic significance of perineural invasion (PNI) in gastric cancer has been previously investigated in a few studies, but had not reached a consensus. The aim of this study was to determine the prognostic value of PNI in patients with gastric cancer who underwent curative resection. MATERIALS AND METHODS: We retrospectively analyzed 238 patients who had undergone curative gastrectomy. Paraffin sections of surgical specimens from all patients were stained with hematoxylin and eosin. PNI was defined when carcinoma cells infiltrated into the perineurium or neural fascicles. PNI and the other prognostic factors were evaluated by univariate and multivariate analysis. RESULTS: PNI was detected as positive in 180 of the 238 patients (75.6%). pT stage, tumor size, lymph node metastasis, clinical stage, tumor differentiation, Borrmann classification, histological type, lymphatic vessel invasion, and blood vessel invasion were closely associated with the presence of PNI. The PNI-positive tumors had significantly larger size and more lymph node metastasis than the PNI-negative tumors (P = .001 and P < .001, respectively). The median survival of the PNI-positive patients was significantly worse than that of the PNI-negative patients (28.1 vs. 64.9 months, P = .001). Multivariate analysis indicated that the positivity of PNI was an independent prognostic factor (P = .02, hazard ratio [HR]: 2.75; 95% confidence interval [95% CI]:1.12-3.13) as were classical clinicopathological features. CONCLUSION: Our results showed that the frequency of PNI was high in patients with gastric cancer who underwent curative gastrectomy and the proportion of PNI positivity increased with progression and clinical stage of disease. PNI may be useful in detecting patients who had poor prognosis after curative resection in gastric cancer.

Does the metastatic lymph node ratio influence the disease-free survival of patients with breast cancer: single-center experiences.

BACKGROUND: Axillary lymph nodes (ALNs) are the most important prognostic factor for survival in breast cancer. Pathological evaluation can affect the number of involved lymph nodes. In the current study, we evaluated whether the metastatic lymph node ratio (n ratio) is important in predicting disease-free survival (DFS) for breast cancer patients. MATERIAL AND METHODS: From 802 breast cancer cases, 427 patients with ALN metastasis were analyzed retrospectively. The n ratio was categorized as n ratio 1 (1-10%), n ratio 2 (10.01-50%) and n ratio 3 (>50%). DFS was established according to the Kaplan-Meier method. Predicting risk factors for relapse were analyzed using the Cox proportional hazards model. RESULTS: The n ratio was significantly higher in breast cancer patients with advanced pathologic pT, pN and clinical stage, undifferentiated histology, lymphovascular and extracapsular invasion, more resected ALNs and positive progesterone receptor. In the univariate analysis, multicentricity, necrosis, grade, pN stage, estrogen receptor and progesterone receptor positivity, trastuzumab and neoadjuvant chemotherapy usage, the presence of inflammatory breast cancer and n ratio were found to be important factors in predicting DFS. Multivariate analysis indicated that multicentricity, neoadjuvant chemotherapy, trastuzumab usage and n ratio were significantly associated with prognosis. CONCLUSIONS: The n ratio is inexpensive, easily available and a simple prognostic factor for breast cancer patients with positive ALNs.

Is metastatic lymph node ratio superior to the number of metastatic lymph nodes to assess outcome and survival of gastric cancer?

BACKGROUND: The aim of this study was to determine the prognostic value of metastatic lymph node ratio (n ratio). PATIENTS AND METHODS: We retrospectively analyzed 202 patients who had undergone curative gastrectomy. The prognostic factors including UICC/AJCC TNM classification and n ratio were evaluated by univariate and multivariate analysis. RESULTS: The n ratio was significantly higher in patients with gastric tumors with undifferentiated histology, greater size, lymphatic vessel, blood vessel and perineural invasion (PNI), and advanced stage. Multivariate analysis indicated that n ratio and pN classification were independent prognostic factors, as were age, tumor size, Borrmann classification, PNI, and tumor differentiation. The receiver operating characteristics (ROC) analysis showed that the sensitivity and the specificity of the presence of lymph node metastasis with 16 lymph nodes resected - which was required to assess the presence of lymph node involvement - were 67.1 and 66.6%, respectively. Three-year overall survival (OS) rates and the median OS time were lower in patients with <16 lymph nodes resected compared to the patients who had >16 lymph nodes resected (p = 0.04). CONCLUSIONS: Our results showed that n ratio and pN classification were independent prognostic indicators for OS of patients with radically resected gastric cancer, but the superiority of n ratio to pN stage could not be proved.

Impact of patient characteristics on efficacy and safety of once-weekly semaglutide versus dulaglutide: SUSTAIN 7 post hoc analyses.

OBJECTIVE: In SUSTAIN 7, once-weekly semaglutide demonstrated superior glycated haemoglobin (HbA1c) and body weight (BW) reductions versus once-weekly dulaglutide in subjects with type 2 diabetes (T2D). This post hoc analysis investigated the impact of clinically relevant subject characteristics on treatment effects of semaglutide versus dulaglutide. DESIGN: Analyses by baseline age (<65, ≥65 years), sex (male, female), diabetes duration (≤5, >5-10, >10 years), HbA1c (≤7.5, >7.5-8.5, >8.5% (≤58, >58-69, >69 mmol/mol)) and body mass index (BMI) (<30, 30-<35, ≥35 kg/m2). SETTING: 194 sites; 16 countries. PARTICIPANTS: Subjects with T2D (n=1199) exposed to treatment. INTERVENTIONS: Semaglutide 0.5 mg versus dulaglutide 0.75 mg (low-dose comparison); semaglutide 1.0 mg versus dulaglutide 1.5 mg (high-dose comparison), all subcutaneously once weekly. PRIMARY AND SECONDARY OUTCOME MEASURES: Change in HbA1c (primary endpoint) and BW (confirmatory secondary endpoint) from baseline to week 40; proportion of subjects achieving HbA1c targets (<7%, ≤6.5% (<53, ≤48 mmol/mol)) and weight-loss responses (≥5%, ≥10%) at week 40; and safety. RESULTS: HbA1c and BW reductions (estimated treatment difference ranges: -0.22 to -0.70%-point; -1.76 to -3.84 kg) and proportion of subjects achieving HbA1c targets and weight-loss responses were statistically significantly greater for the majority of comparisons of semaglutide versus dulaglutide within each subgroup category and, excepting glycaemic control within the low-dose comparison in HbA1c subgroups, this was irrespective of subgroup or dose comparison. Gastrointestinal adverse events, the most common with both treatments, were reported by more women than men and, with semaglutide, decreased with increasing BMI. CONCLUSIONS: Consistently greater improvements in HbA1c and BW with semaglutide versus dulaglutide, regardless of age, sex, diabetes duration, glycaemic control and BMI, support the efficacy of semaglutide across the continuum of care in a heterogeneous population with T2D. TRIAL REGISTRATION NUMBER: NCT02648204.

Superior weight loss with once-weekly semaglutide versus other glucagon-like peptide-1 receptor agonists is independent of gastrointestinal adverse events.

INTRODUCTION: Gastrointestinal (GI) adverse events (AEs) are the most common AEs with glucagon-like peptide-1 receptor agonists (GLP-1RAs). Weight loss (WL) is slightly greater in people who experience GI AEs than those who do not. A previous mediation analysis of the SUSTAIN 1-5 trials indicated minor contribution of nausea/vomiting to the greater WL with once-weekly semaglutide versus comparators. Semaglutide demonstrated superior glycated hemoglobin and body weight (BW) reductions versus other GLP-1RAs in SUSTAIN 3 (versus exenatide extended release 2.0 mg), SUSTAIN 7 (versus dulaglutide) and SUSTAIN 10 (liraglutide 1.2 mg). The objective of this analysis was to assess if significantly greater WL with semaglutide versus other GLP-1RAs is mediated by nausea/vomiting and other GI AEs (diarrhea, constipation, dyspepsia) during dose escalation (baseline to week 12, when GI AEs are generally most prevalent) and from baseline to end of treatment (EOT: week 56 (SUSTAIN 3), 40 (SUSTAIN 7) or 30 (SUSTAIN 10)). RESEARCH DESIGN AND METHODS: Subjects within trials were subdivided into those who reported (yes/no) nausea/vomiting or any other GI AE. Change from baseline in BW was assessed within each trial and subgroup. A mediation analysis separated WL into direct or indirect (mediated by GI AEs) effects. RESULTS: From baseline to week 12 or EOT, the nausea/vomiting-mediated difference in WL was, respectively: 0.05 or 0.09 kg of 3.78 kg at EOT (SUSTAIN 3); 0.06 or 0.03 kg of 2.26 kg at EOT (low-dose comparison) and 0.08 or 0.04 kg of 3.55 kg at EOT (high-dose comparison) (SUSTAIN 7) and 0.05 or 0.09 kg of 3.82 kg at EOT (SUSTAIN 10). CONCLUSIONS: In SUSTAIN 3, 7 and 10, nausea/vomiting by week 12 (end of dose escalation) or throughout treatment contributed minimally (<0.1 kg) to the superior WL with semaglutide versus GLP-1RA comparators at EOT.

Real-world efficacy and safety of Ledipasvir + Sofosbuvir and Ombitasvir/Paritaprevir/Ritonavir ± Dasabuvir combination therapies for chronic hepatitis C: A Turkish experience.

BACKGROUND/AIMS: This study aimed to evaluate the real-life efficacy and tolerability of direct-acting antiviral treatments for patients with chronic hepatitis C (CHC) with/without cirrhosis in the Turkish population. MATERIAL AND METHODS: A total of 4,352 patients with CHC from 36 different institutions in Turkey were enrolled. They received ledipasvir (LDV) and sofosbuvir (SOF)±ribavirin (RBV) orombitasvir/paritaprevir/ritonavir±dasabuvir (PrOD)±RBV for 12 or 24 weeks. Sustained virologic response (SVR) rates, factors affecting SVR, safety profile, and hepatocellular cancer (HCC) occurrence were analyzed. RESULTS: SVR12 was achieved in 92.8% of the patients (4,040/4,352) according to intention-to-treat and in 98.3% of the patients (4,040/4,108) according to per-protocol analysis. The SVR12 rates were similar between the treatment regimens (97.2%-100%) and genotypes (95.6%-100%). Patients achieving SVR showed a significant decrease in the mean serum alanine transaminase (ALT) levels (50.90±54.60 U/L to 17.00±14.50 U/L) and model for end-stage liver disease (MELD) scores (7.51±4.54 to 7.32±3.40) (p<0.05). Of the patients, 2 were diagnosed with HCC during the treatment and 14 were diagnosed with HCC 37.0±16.0 weeks post-treatment. Higher initial MELD score (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.22-2.38; p=0.023]), higher hepatitis C virus (HCV) RNA levels (OR: 1.44, 95% CI: 1.31-2.28; p=0.038), and higher serum ALT levels (OR: 1.38, 95% CI: 1.21-1.83; p=0.042) were associated with poor SVR12. The most common adverse events were fatigue (12.6%), pruritis (7.3%), increased serum ALT (4.7%) and bilirubin (3.8%) levels, and anemia (3.1%). CONCLUSION: LDV/SOF or PrOD±RBV were effective and tolerable treatments for patients with CHC and with or without advanced liver disease before and after liver transplantation. Although HCV eradication improves the liver function, there is a risk of developing HCC.

The role of BDNF and HPA axis in the neurobiology of burnout syndrome.

Chronic stress is known to affect the HPA axis. The few clinical studies which have been conducted on HPA-axis function in burnout have produced inconsistent results. The etiological relationship between sBDNF and burnout has not yet been studied. The aim of the current study was to investigate the role of BDNF and HPA axis in the neurobiology of burnout. In the current study 37 clinically diagnosed burnout participants were compared with 35 healthy controls in terms of BDNF, HPA axis, burnout symptoms, depression, anxiety and psychosomatic complaints. Basal serum cortisol, sBDNF and cortisol level after 1 mg DST was sampled. We found no significant differences in terms of HPA-axis function (for basal serum cortisol, p=0.592; for cortisol level after 1 mg DST, p=0.921), but we did find lowered sBDNF levels in burnout group (88.66+/-18.15 pg/ml) as compared to healthy controls (102.18+/-20.92 pg/ml) and the difference was statistically significant (p=0.005). Logistic Regression Analysis revealed that emotional exhaustion (p=0.05), depersonalization (p=0.005) and depression (p=0.025) were significantly associated with burnout. sBDNF levels correlated negatively with emotional exhaustion (r=-,268, p=0.026), depersonalization (r=-,333, p=0.005) and correlated positively with competence (r=0.293, p=0.015) sub-scales of burnout inventory. However, there were no significant relationships between cortisol levels and sBDNF levels (r=0.80, p=0.51), depression, anxiety, psychosomatic complaints and burnout inventory. Our results suggest that low BDNF might contribute to the neurobiology of burnout syndrome and it seems to be associated with burnout symptoms including altered mood and cognitive functions.

Extraction and preconcentration of trace Al and Cr from vegetable samples by vortex-assisted ionic liquid-based dispersive liquid-liquid microextraction prior to atomic absorption spectrometric determination.

In the study, a simple, and efficient microextraction approach, which is termed as vortex-assisted ionic liquid-based dispersive liquid-liquid microextraction (VA-IL-DLLME), was developed for flame atomic absorption spectrometric analysis of aluminum (Al) and chromium (Cr) in vegetables. The method is based on the formation of anionic chelate complexes of Al(III) and Cr(VI) with o-hydroxy azo dye, at pH 6.5, and then extraction of the hydrophobic ternary complexes formed in presence of cetyltrimethylammonium bromide (CTAB) into a 125 µL volume of 1-butyl-3-methylimidazolium bis(trifluorosulfonyl)imide [C4mim][Tf2N]) as extraction solvent. Under optimum conditions, the detection limits were 0.02 µg L-1 in linear working range of 0.07-100 µg L-1 for Al(III), and 0.05 µg L-1 in linear working range of 0.2-80 µg L-1 for Cr(VI). After the validation by analysis of a certified reference material (CRM), the method was successfully applied to the determination of Al and Cr in vegetables using standard addition method.

Serum adenosine deaminase levels in pancreatic diseases.

BACKGROUND: Adenosine deaminase (ADA) is found in most tissues including the pancreas. Its role in inflammation and malignancy has been studied experimentally. To date, serum ADA levels in pancreatic diseases have not been studied before. AIM: To assess the levels of ADA in patients with pancreatitis and cancer of the pancreas. METHODOLOGY: Serum levels of ADA were investigated in 14 cases with acute pancreatitis (mean age 46 years; male/female 5/9), 38 with chronic pancreatitis (mean age 46 years; male/female 25/13), 21 with cancer of the pancreas (mean age 67 years; male/female 11/10), and 21 healthy controls (mean age 40 years; male/female 11/10). The ADA levels were also compared among patients with pancreatic cancer with regard to tumor size and localization and the presence of metastases. Correlation analysis between ADA and CA 19.9 was also performed. RESULTS: Serum ADA levels were 12.66 (9.54-20.72), 12.51 (8.88-26.64), 15.36 (10.20-21.05) and 9.39 (6.58-11.84) U/l in patients with acute pancreatitis, chronic pancreatitis, pancreatic cancer, and healthy controls, respectively. Serum ADA levels were significantly higher in acute and chronic pancreatitis, and pancreatic cancer patients compared to the control group (p < 0.05). Pancreatic cancer patients had significantly higher serum ADA levels when compared with acute and chronic pancreatitis cases (p < 0.05). The serum ADA levels were comparable according to tumor size and location and the presence of metastases. There was a linear correlation between serum ADA and CA 19-9 levels (p = 0.027, r = 0.552). CONCLUSIONS: Our data suggest that the ADA enzyme may play a role in inflammatory diseases of the pancreas. Serum ADA levels increase in pancreatic disorders especially in pancreatic cancer. It may be a serum marker for the diagnosis of pancreatic cancer.

Evaluation of Bevacizumab in Advanced Small Bowel Adenocarcinoma.

BACKGROUND: Small bowel adenocarcinomas (SBAs) are rarely seen tumors. Data regarding the use of chemotherapy together with bevacizumab in patients with advanced SBA are lacking. The aim of this study was the evaluation of treatment with bevacizumab in advanced SBA. MATERIALS AND METHODS: Twenty-eight patients from 5 centers with a diagnosis of advanced SBA who received first-line treatments with modified FOLFOX6 (mFOLFOX6; oxaliplatin, leucovorin, and 5-fluorouracil) and FOLFIRI (leucovorin, 5-fluorouracil, and irinotecan) chemotherapy regimens were involved in the study. All patients were divided into 2 groups; those who received bevacizumab together with these chemotherapy regimens (Chemo+Bev group) and those who did not receive bevacizumab (Chemo group). RESULTS: The median progression-free survival (PFS) and overall survival (OS) times of all population were 8.7 months and 16.9 months, respectively. The overall response rate was 43.7% in the Chemo group and 58.3% in the Chemo+Bev group. The median PFSs in the Chemo and Chemo+Bev groups were found to be 7.7 months and 9.6 months, respectively, and the median OSs were 14.8 months and 18.5 months, respectively. There was not a significant difference between the groups in terms of overall response rate, PFS, and OS. CONCLUSION: Although there was no significant difference in any of the outcomes, use of bevacizumab together with chemotherapy is a more effective treatment approach compared with chemotherapy alone, and it does not cause an excess of significant toxicity.

Evaluation of Prognostic Factors and Adjuvant Chemotherapy in Patients With Small Bowel Adenocarcinoma Who Underwent Curative Resection.

BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare tumor of the gastrointestinal system with poor prognosis. Because these are rarely encountered tumors, the aim of this multicenter study was evaluation of prognostic factors and adjuvant chemotherapy in patients with curatively resected SBA. MATERIALS AND METHODS: A total of 78 patients diagnosed with curatively resected SBA were involved in the retrospective study. Forty-eight patients received 1 of 3 different chemotherapy regimens, whereas 30 patients did not receive any adjuvant treatment. No adjuvant and adjuvant chemotherapy cohorts were matched (1:1) by propensity scores based on the likelihood of receiving chemotherapy or the survival hazard from Cox modeling. Overall survival (OS) was compared with Kaplan-Meier estimates. RESULTS: Median age of 78 patients with curatively resected SBA was 58, and 59% of these were men. According to TNM classification, 8 (10%) of the patients were at stage I, 26 (34%) were at stage II, and 44 (56%) were at stage III. Median follow-up duration was 29 months. Three-year median disease-free survival (DFS) and OS were 62.5% and 67.0%, respectively. In univariate analysis, presence of vascular invasion, perineural invasion, lymph node involvement, and presence of positive surgical margin were significant predictors of poor survival. Multivariate analysis showed that the only adverse prognostic factor independently related with OS was the presence of positive surgical margin (hazard ratio, 0.37; 95% confidence interval, 0.11-1.26; P = .01). Neither DFS nor OS was found to be significantly improved by the adjuvant chemotherapy in both matched and unmatched cohorts. CONCLUSIONS: Only status of surgical margin was determined to be an independent prognostic factor in patients with SBA who underwent curative resection.

Glucagon like peptide-1 receptor agonists may ameliorate the metabolic adverse effect associated with antiretroviral therapy.

The number of people living with HIV and AIDS (PLWHA) reached to almost 40 million, half of which are under antiretroviral treatment (ART). Although the introduction of this therapy significantly improved the life span and quality of PLWHA, metabolic complications of these people remains to be an important issue. These metabolic complications include hyperlipidemia, abnormal fat redistribution and diabetes mellitus, which are defined as lipodystrophy syndrome. Glucagon-like peptide-1 (GLP-1) is a neuropeptide secreted from intestinal L cells and recently developed GLP-1 receptor agonists (GLP-1RAs) stimulate insulin secretion, improve weight control and reduce cardiovascular outcomes. This class of drugs may be a valuable medication in the treatment of HIV-associated metabolic adverse effects and extend the life expectancy of patients infected with HIV.