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Background: Choledochal cysts are seen commonly in Asian populations, but rarely in Western populations. The pathogenesis of these premalignant lesions is not fully understood yet and the risk of malignant transformation increases with age. The overall malignancy risk is 10%-15% in East Asian countries. In this study, we aimed to present our surgical experience as a hepatobiliary center to the literature., Methods: We retrospectively analyzed the data from the medical records of 70 patients operated for choledochal cyst between 2008-2019., Results: Sixty-two of the 70 (89%) patients were female and 8 (11%) were male, the mean age was 45.89 ± 15.32 years. Overall, 44 (63%) patients had type I (a+b+c), 20 (28%) type V (Caroli), 2 (3%) type II, 2 (3%) type III and 2 (3%) type IVb cysts. The most common operation was cyst excision combined with hepaticojejunostomy (n: 26, 37%). The median diameter of the resected cysts was 3 cm (min- max: 1-11 cm). Malignancy was observed only in three (4%) patients with type III, type Ib, and type V cyts, who were 19, 38, and 72 years old, respectively. Mortality was not observed, morbidity was determined totally in 30 (43%) cases during early and late postoperative periods., Conclusion: Type of surgery in choledochal cysts differs according to the type of the cyst. Malignancy was observed at a rate of 4% in all age groups. Although the frequency of malignancy varies, the main treatment of choice should be surgery because malignancy can be seen at a young age., (© 2021 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background and Aim: Although anyone can be affected by the COVID-19 pandemic, it may cause additional concern for people with chronic conditions. Epilepsy is the most common neurological disease in childhood and adolescence. The aim of this study was to determine anxiety levels among the mothers of children under follow-up for epilepsy in our clinic during the COVID-19 pandemic., Methods: The study group consisted of the mothers of epilepsy patients who were under follow-up in the pediatric neurology outpatient clinic of the tertiary care center and were scheduled for a routine examination during the COVID-19 pandemic. The mothers' anxiety levels according to the Beck Anxiety Inventory and their opinions about COVID-19 in relation to their child were assessed and compared based on whether the mother/patient attended their appointments in person and whether the child had frequent or infrequent seizures., Results: There was no statistically significant difference in anxiety level between the mothers of 64 children with epilepsy who attended their appointment during the pandemic and those of the mothers of 52 who did not attend their appointment. However, the mothers of children with frequent seizures had significantly higher anxiety levels., Conclusion: Anxiety level of mothers whose children have frequent seizures was significantly higher compared to mothers whose children have infrequent seizures. It is important to be aware about this point and using telemedicine approach in suitable population and postpone routine outpatient follow-up appointments as much as possible., (© 2021 S. Karger AG, Basel.)

BRAT1-related neurodevelopmental disorders are characterized by heterogeneous phenotypes with varying levels of clinical severity. Since the discovery of BRAT1 variants as the molecular etiology of lethal neonatal rigidity and multifocal seizure syndrome (RMFSL, OMIM 614498), these variants have also been identified in patients with milder clinical forms including neurodevelopmental disorder with cerebellar atrophy and with or without seizures (NEDCAS, OMIM 618056), epilepsy of infancy with migrating focal seizures (EIMFS), and congenital ataxia (CA). This study aims to examine the consequences and pathogenicity of a novel homozygous splice site variant in BRAT1 in a patient presenting with migrating focal seizures since birth without prominent rigidity. The patient was born from a consanguineous marriage and has had seizures since the neonatal period. He presented with dysmorphic features, pontocerebellar hypoplasia, and migrating focal seizures. Despite supportive treatment, his symptoms rapidly progressed to intractable myoclonic seizures, bouts of apnea and bradycardia, and arrest of head growth, with no acquisition of developmental milestones. Clinical exome sequencing yielded a novel homozygous splice variant in BRAT1. Genetic analysis based on reverse transcription of the patient's RNA followed by PCR amplifications performed on synthesized cDNA and Sanger sequencing was undertaken, and the functional effect of a BRAT1 variant on splicing machinery was demonstrated for the first time. The severe clinical presentation of migrating focal seizures and pontocerebellar hypoplasia in the absence of rigidity further expands the genotypic and phenotypic spectrum of BRAT1-related neurodevelopmental disorders.

Background-Aim: Noninvasive mechanical ventilation (NIV) failure rate is reported to be 5%-60% of intensive care unit (ICU) patients. Despite all precautions and well-known reasons, the risk factors of NIV failure are unclear for chronic obstructive pulmonary disease (COPD) with acute respiratory failure (ARF). The aim of this study was to examine risk factors for NIV failure in COPD patients with ARF, other than well defined., Methods: The retrospective cohort study was done in ICU of a chest disease hospital. All consecutive COPD patients with hypercapnic ARF were enrolled in study. Demographics, comorbidities, arterial blood gases, reasons of ARF and length of ICU stay were recorded. NIV success was defined as discharge from ICU and NIV failure was defined as need for intubation or died during NIV. Patients were grouped into; NIV failure and success. The groups were compared and NIV failure risk factors were analyzed., Results: About 265 NIV success and 142 NIV failure patients were enrolled into the study. Logistic regression test showed the risk factors for NIV failure; higher APACHE-II (≥ 29) (OR:11.71, CI95%4.39-31.18, P < 0.001), culture positivity (OR:7.59, CI95%3.21-17.92, P < 0.001), sepsis (OR:6.53 CI95%3.59-11.85, P < 0.001) and pneumonia (OR:3.71 CI95%0.60-2.02, P < 0.043) significantly. COPD patients using home-based NIV had less risk for NIV failure (OR: 0.49 CI95%0.28-0.87, P < 0.014)., Conclusions: APACHE II ≥ 29 score, culture positivity, sepsis and pneumonia are the risk factors for NIV failure in COPD patients with ARF. COPD patients previously on home-based NIV showed half times less risk for NIV failure., (© 2020 John Wiley & Sons Ltd.)

The health of mammals depends on a complex interplay with their microbial ecosystems. Compartments exposed to external environments such as the mucosal surfaces of the gastrointestinal tract accommodate the gut microbiota, composed by a wide range of bacteria. The gut microbiome confers benefits to the host, including expansion of metabolic potential and the development of an immune system that can robustly protect from external and internal insults. The cooperation between gut microbiome and host is enabled in part by the formation of partitioned niches that harbor diverse bacterial phyla. Bacterial secretion systems are commonly employed to manipulate the composition of these local environments. Here, we explore the roles of the bacterial type VI secretion system (T6SS), present in ~25% of gram-negative bacteria, including many symbionts, in the establishment and perturbation of bacterial commensalism, and symbiosis in host mucosal sites. This versatile apparatus drives bacterial competition, although in some cases can also interfere directly with host cells and facilitate nutrient acquisition. In addition, some bacterial pathogens cause disease when their T6SS leads to dysbiosis and subverts host immune responses in defined animal models. This review explores our knowledge of the T6SS in the context of the "host-microbiota-pathogen" triumvirate and examines contexts in which the importance of this secretion system may be underappreciated., (Copyright © 2020 Wood, Aksoy and Hachani.)

Schmallenberg virus (SBV), discovered in Germany in 2011, causes congenital malformations in ruminants. Reverse-transcription real-time PCR (RT-rtPCR) assays based on various segments of SBV have been developed for molecular detection. We developed alternative RT-rtPCR assays for SBV detection to avoid earlier reported mutations and hypervariable regions of the S and M segments of the viral genome. For SYBR Green-based detection of the S segment, the R 2 value and efficiency of the developed assay were 0.99 and 99%, respectively. For probe-based S segment detection, 2 assays were developed; the first had an R 2 value of 0.99 and 102% efficiency, and the second had a R 2 value of 0.98 and 86% efficiency. The probe-based M segment assay had an R 2 value of 1.00 and 103% efficiency. Detection limits of the RT-rtPCR assays with new primer sets were 10 2 and 10 1 copies/µL for the S and M segments, respectively. Field samples from cattle and sheep were also used for primary validation of the developed assays. Our assays should be suitable for SBV detection in ruminants and for in vitro studies of various SBV strains.

Objective: To investigate the effects of haemodynamic indices on colour Doppler ultrasound in differential diagnosis in patients with postpartum thyroiditis and with Graves' disease., Methods: The cross-sectional study was conducted at the Endocrinology Polyclinic of Medical Park Hospital, Ordu, Turkey, from March 2017 to May 2018 and comprised patients referred from the Gynaecology Department for routine check-up after parturition within the first 6 months. The patients were divided into two groups. Group 1 had postpartum thyroiditis patients and Group 2 had those of Graves' disease. In both groups, parameters measured were peak systolic velocity, end-diastolic velocity and resistive index of the inferior thyroid artery with proper angle (45-60⁰) on colour Doppler ultrasound. Data was analysed using SPSS 20., Results: Of the 42 subjects,18(42.85%) were in Group 1 and 24(57.14%) were in Group 2. Peak systolic velocity and end-diastolic velocity values of the inferior thyroid artery were higher in Group 2 compared to Group 1 (p<005). (p<0.05), while the resistive index value was significantly higher in Group 1 compared to Group 2., Conclusions: Due to its wide availability, the use of colour Doppler ultrasound parameters indicating parenchymal perfusion were found to be broadly useful in distinguishing between postpartum thyroiditis and Graves' disease.

Tumor-targeting oncolytic viruses such as vaccinia virus (VV) are attractive cancer therapeutic agents that act through multiple mechanisms to provoke both tumor lysis and anti-tumor immune responses. However, delivery of these agents remains restricted to intra-tumoral administration, which prevents effective targeting of inaccessible and disseminated tumor cells. In the present study we have identified transient pharmacological inhibition of the leukocyte-enriched phosphoinositide 3-kinase δ (PI3Kδ) as a novel mechanism to potentiate intravenous delivery of oncolytic VV to tumors. Pre-treatment of immunocompetent mice with the PI3Kδ-selective inhibitor IC87114 or the clinically approved idelalisib (CAL-101), prior to intravenous delivery of a tumor-tropic VV, dramatically improved viral delivery to tumors. This occurred via an inhibition of viral attachment to, but not internalization by, systemic macrophages through perturbation of signaling pathways involving RhoA/ROCK, AKT, and Rac. Pre-treatment using PI3Kδ-selective inhibitors prior to intravenous delivery of VV resulted in enhanced anti-tumor efficacy and significantly prolonged survival compared to delivery without PI3Kδ inhibition. These results indicate that effective intravenous delivery of oncolytic VV may be clinically achievable and could be useful in improving anti-tumor efficacy of oncolytic virotherapy., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Pancreatic cancer is one of the deadliest cancer types urgently requiring effective therapeutic strategies. Autophagy occurs in several compartments of pancreatic cancer tissue including cancer cells, cancer associated fibroblasts, and immune cells where it can be subjected to a multitude of stimulatory and inhibitory signals fine-tuning its activity. Therefore, the effects of autophagy on pancreatic carcinogenesis and progression differ in a stage and context dependent manner. In the initiation stage autophagy hinders development of preneoplastic lesions; in the progression stage however, autophagy promotes tumor growth. This double-edged action of autophagy makes it a hard therapeutic target. Indeed, autophagy inhibitors have not yet shown survival improvements in clinical trials, indicating a need for better evaluation of existing results and smarter targeting techniques. Clearly, the role of autophagy in pancreatic cancer is complex and many aspects have to be considered when moving from the bench to the bedside.

Our aim was to explore the existence of a possible relationship of sperm motility with serum 25-hydroxyvitamin D3 (25-OH VD) levels and with ischaemia-modified albumin (IMA) levels in infertile Turkish men. A total of 30 men with nonobstructive azoospermia (no spermatozoa in ejaculate), 30 men with oligospermia (total progressive motile sperm count (TPMSC) <15 × 10 6 /ml) and 33 fertile men with normospermia (with at least one child, as the control group) were enrolled in the study. The mean 25-OH VD levels for groups 1, 2 and 3 were 9.31 ± 6.46, 19.71 ± 12.80 and 30.52 ± 12.49 respectively (p < .05). There was a statistically significant difference in serum IMA levels among the groups (479.32 ± 307.56 vs. 296.37 ± 127.27 vs. 150.04 ± 81.05, respectively; p < .05). A positive correlation between serum 25-OH VD levels and TPMSC, and a negative correlation between TPMSC and serum IMA levels were determined. Infertile men had lower serum 25-OH VD and higher IMA levels than fertile men, with a positive correlation between serum 25-OH VD levels and TPMSC, and a negative correlation between TPMSC and serum IMA levels. Vitamin D supplementation may increase the sperm motility., (© 2020 Blackwell Verlag GmbH.)

Potato production is often constrained by abiotic stresses such as drought and high temperatures which are often present in combination. In the present work, we aimed to identify key mechanisms and processes underlying single and combined abiotic stress tolerance by comparative analysis of tolerant and susceptible cultivars. Physiological data indicated that the cultivars Desiree and Unica were stress tolerant while Agria and Russett Burbank were stress susceptible. Abiotic stress caused a greater reduction of photosynthetic carbon assimilation in the susceptible cultivars which was associated with a lower leaf transpiration rate. Oxidative stress, as estimated by the accumulation of malondialdehyde was not induced by stress treatments in any of the genotypes with the exception of drought stress in Russett Burbank. Stress treatment resulted in increases in ascorbate peroxidase activity in all cultivars except Agria which increased catalase activity in response to stress. Transcript profiling highlighted a decrease in the abundance of transcripts encoding proteins associated with PSII light harvesting complex in stress tolerant cultivars. Furthermore, stress tolerant cultivars accumulated fewer transcripts encoding a type-1 metacaspase implicated in programmed cell death. Stress tolerant cultivars exhibited stronger expression of genes associated with plant growth and development, hormone metabolism and primary and secondary metabolism than stress susceptible cultivars. Metabolite profiling revealed accumulation of proline in all genotypes following drought stress that was partially suppressed in combined heat and drought. On the contrary, the sugar alcohols inositol and mannitol were strongly accumulated under heat and combined heat and drought stress while galactinol was most strongly accumulated under drought. Combined heat and drought also resulted in the accumulation of Valine, isoleucine, and lysine in all genotypes. These data indicate that single and multiple abiotic stress tolerance in potato is associated with a maintenance of CO 2 assimilation and protection of PSII by a reduction of light harvesting capacity. The data further suggests that stress tolerant cultivars suppress cell death and maintain growth and development via fine tuning of hormone signaling, and primary and secondary metabolism. This study highlights potential targets for the development of stress tolerant potato cultivars., (Copyright © 2020 Demirel, Morris, Ducreux, Yavuz, Asim, Tindas, Campbell, Morris, Verrall, Hedley, Gokce, Caliskan, Aksoy, Caliskan, Taylor and Hancock.)

Colorado potato beetle, Leptinotarsa decemlineata Say (coleoptera: chrysomelidae), is the important pest of potato all over the world. This insect pest is resistant to more than 50 active compounds belonging to various chemical groups. Potential of RNA interference (RNAi) was explored to knock down transcript levels of imidacloprid resistant genes in Colorado potato beetle (CPB) under laboratory conditions. Three important genes belonging to cuticular protein (CP), cytochrome P450 monoxygenases (P450) and glutathione synthetase (GSS) families encoding imidacloprid resistance were targeted. Feeding bio-assays were conducted on various stages of imidacloprid resistant CPB lab population by applying HT115 expressing dsRNA on potato leaflets. Survival rate of insects exposed to CP-dsRNA decreased to 4.23%, 15.32% and 47.35% in 2nd, 3rd and 4th instar larvae respectively. Larval weight and pre-adult duration were also affected due to dsRNAs feeding. Synergism of RNAi with imidacloprid conducted on the 2nd instar larvae, exhibited 100% mortality of larvae when subjected to reduced doses of GSS and CP dsRNAs along with imidacloprid. Utilization of three different dsRNAs against imidacloprid resistant CPB population reveal that dsRNAs targeting CP, P450 and GSS enzymes could be useful tool in management of imidacloprid resistant CPB populations., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to determine changes in thyroid hormones and morphology with weight loss after bariatric surgery in obese patients., Methods: This prospective study was performed in our endocrinology and surgery clinic. Pre- and post-bariatric surgery thyroid function tests and thyroid ultrasonography parameters were compared., Results: Four hundred seventy-two patients were included in the study. Mean weight loss after surgery was 30.7 ± 5.1 kg. TSH levels decreased statistically significantly parallel with weight loss and decreased BMI (p = 0.025) after bariatric surgery. However, no statistically significant change was observed in fT4 or fT3 levels (p > 0.05). A significant increase in thyroid parenchyma echogenicity, correlated with weight loss and time elapsed since surgery, was detected at ultrasonography (US) grayscale histogram analysis compared with muscle echogenicity (p = 0.032). An increase in echogenicity was even detected in patients with isoechoic thyroid parenchyma before surgery. Fasting insulin and HOMA-IR levels decreased after surgery (p = 0.010 and p = 0.001, respectively). Patients were divided into three groups based on weight loss. In group 3, preoperative TSH of 4.1 ± 0.7 decreased to 1.6 ± 0.7 postoperatively (p = 0.001), while preoperative HOMA-IR of 4.9 ± 1.9 decreased to 2.4 ± 0.8 postoperatively (p = 0.001)., Conclusions: Obesity causes thyroid hormone resistance through a mechanism similar to insulin resistance and leads to an increase in TSH similar to hyperinsulinemia. Our findings show that echogenicity at thyroid US increases in line with weight loss following bariatric surgery.

The use of serious game tools in training of medical professions is steadily growing. However, there is a lack of reliable performance assessment methods to evaluate learner's outcome. The aim of this study is to determine whether functional near infrared spectroscopy (fNIRS) can be used as an additional tool for assessing the learning outcome of virtual reality (VR) based learning modules. The hypothesis is that together with an improvement in learning outcome there would be a decrease in the participants' cerebral oxygenation levels measured from the prefrontal cortex (PFC) region and an increase of participants' serious gaming results. To test this hypothesis, the subjects were recruited and divided into four groups with different combinations of prior virtual reality experience and prior Basic Life Support (BLS) knowledge levels. A VR based serious gaming module for teaching BLS and 16-Channel fNIRS system were used to collect data from the participants. Results of the participants' scores acquired from the serious gaming module were compared with fNIRS measures on the initial and final training sessions. Kruskal Wallis test was run to determine any significant statistical difference between the groups and Mann-Whitney U test was utilized to obtain pairwise comparisons. BLS training scores of the participants acquired from VR based serious game's the learning management system and fNIRS measurements revealed decrease in use of resources from the PFC, but increase in behavioral performance. Importantly, brain-based measures can provide an additional quantitative metric for trainee's expertise development and can assist the medical simulation instructors., (Copyright © 2019 Aksoy, Izzetoglu, Baysoy, Agrali, Kitapcioglu and Onaral.)

Objectives: Psychiatric comorbidities may intensify peripheral vertigo and increase the number of repositioning maneuvers required. This study was designed to examine the relationship between benign paroxysmal positional vertigo (BPPV) and anxiety and assess its association with somatic amplification and health anxiety., Materials and Methods: Sixty patients with BPPV (43 women, 17 men; age range: 24-81 years, mean age 40.4±13.3), and 60 healthy participants (29 women, 31 men; age range: 18-71, mean age 38.2±11.43) were prospectively enrolled. The participants completed the Beck Anxiety Inventory (BAI), Short Health Anxiety Inventory (SHAI), and Somatosensory Amplification Scale (SSAS) questionnaires., Results: The BAI scores of the patients with BPPV were higher than those of the control group participants and were as follows: (16.4 vs. 12.7; p=0.01). The SHAI (p=0.44) and SSAS (p=0.60) scores were not significantly different between the two groups. The BAI scores were positively correlated with the SHAI (rho: 0.273, p=0.035) and SSAS (rho: 0.357, p=0.005) scores. Neither the number of BPPV attacks nor the number of Epley maneuvers required showed any correlation with the BAI [(rho: 0.208, p=0.11); (rho: -0.007, p=0.96)], SHAI [(rho: 0.068, p=0.06); (rho: 0.021, p=0.87)], and SSAS [(rho: -0.081, p=0.53); (rho: -0.012, p=0.92)] scores., Conclusion: Our findings indicate that patients with BPPV had higher anxiety scores than healthy participants. Although our findings indicated normal health anxiety and somatic amplification levels in patients with BPPV, regular evaluation of psychological status would be a good strategy to prevent chronic dizziness.

Ibuprofen is a non-steroidal anti-inflammatory drug for the treatment of Rheumatoid Arthritis and osteoarthritis. In this study, we prepared topical gel network for enhancement of ibuprofen penetration, maintenance of controlled release and increased patient compliance. Nanoparticles containing ibuprofen were prepared by means of emulsion formation/solvent diffusion method using synthesized copolymer. Nanoparticles were then conjugated with aminoethylmethacrylate, resulting in ibuprofen-loaded nanoparticles in PLGA- b -PEG-MA structure. Ibuprofen-loaded gel networks were developed by crosslinking nanoparticles via UV exposure. Suitability for topical application has been assessed through characterization of particle size, zeta potential, morphology, encapsulation efficiency, in vitro release, cytotoxicity and enhancement of in vitro wound healing. The mean diameter of nanoparticles was measured as 230 ± 20 nm. Gel network formulations with higher particle size (2800 ± 350 nm) and zeta potential (39.8 ± 9.2 mV), depending on conjugation of methacrylate within copolymeric structure, and having encapsulation efficacy of 73.6 ± 2.8% were prepared. The in vitro release of ibuprofen was sustained for more than 7 hours. Gel network improved collagen synthesis, type I collagen mRNA expression and fibrosis in dose dependent manner. Based on this, we can conclude that PLGA- b -PEG gel network might be a promising systems for the local delivery of ibuprofen in RA patients.

Objectives: A continuous-flow centrifugal blood pump system has been recently developed as an implantable left ventricular assist device for patients with endstage heart failure. The objective of this study was to evaluate the initial in vivo performance of a newly developed left ventricular assist device (iHeart or Istanbul heart; Manufacturing and Automation Research Center, Koc University, Istanbul, Turkey) in an acute setting using a pig model., Materials and Methods: Three pigs (77, 83, 92 kg) received implants via a median sternotomy, with animals supported for up to 6 hours. An outflow cannula was anastomosed to the ascending aorta. Anticoagulation was applied by intravenous heparin administration. During the support period, pump performance was evaluated under several flow and operating conditions. All pigs were humanely sacrificied after the experiments, and organs were examined macroscopically and histopathologically., Results: Flow rate ranged between 1.5 and 3.6 L/min with pump speeds of 1500 to 2800 revolutions/min and motor current of 0.6 to 1.3 A. Initial findings confirmed thatthe iHeart ventricular assist device had sufficient hydraulic performance to support the circulation. During the experimental period, plasma free hemoglobin levels were found to be within normalranges.Thrombus formation was not observed inside the pump in all experiments., Conclusions: The iHeart ventricular assist device demonstrated encouraging hemodynamic performance and good biocompatibility in the pig model for use as an implantable left ventricular assist device. Further acute in vivo studies will evaluate the short-term pump performance prior to chronic studies for long-term evaluation.

Thymic stromal lymphopoietin (TSLP) is a cytokine produced by epithelial cells in the lungs, skin, and intestinal mucosa and is involved in several physiological and pathological processes. In this study, we evaluated serum TSLP levels in patients with celiac disease (CD). The prospective study was conducted at a gastroenterology outpatient clinic between March 2018 and August 2018. Eighty-nine participants aged between 18 and 75 years were classified into following groups: 22 patients with newly diagnosed CD; 20 patients with CD who were compliant with a gluten-free diet (GFD); 32 patients with CD who were not compliant with a GFD; and 15 healthy controls. Demographic characteristics, disease duration, and selected biochemical and hematologic parameters were recorded and compared between groups. Median serum TSLP levels were 1193.65 pg/mL (range: 480.1-1547.1) in newly diagnosed CD patients, 110.25 pg/mL (range: 60.3-216.7) in CD patients who were compliant with a GFD, 113.1 pg/mL (range: 76.3-303.4) in CD patients who were not compliant with a GFD, and 57 pg/mL (range: 49-67.8) in healthy controls. Overall, there was a significant difference in serum TSLP levels between groups (p = 0.001). Patients with newly diagnosed CD had the highest serum TSLP levels. There was no significant difference in serum TSLP levels between patients with CD who were and were not compliant with a GFD. TSLP appears to be involved in the pathogenesis of CD. Further studies are required to determine if the TSLP signaling pathway can be used in the treatment of CD.

Rehabilitation and mobility training of post-stroke patients is crucial for their functional recovery. While traditional methods can still help patients, new rehabilitation and mobility training methods are necessary to facilitate better recovery at lower costs. In this work, our objective was to design and develop a rehabilitation training system targeting the functional recovery of post-stroke users with high efficiency. To accomplish this goal, we applied a bilateral training method, which proved to be effective in enhancing motor recovery using tactile feedback for the training. One participant with hemiparesis underwent six weeks of training. Two protocols, "contralateral arm matching" and "both arms moving together", were carried out by the participant. Each of the protocols consisted of "shoulder abduction" and "shoulder flexion" at angles close to 30 and 60 degrees. The participant carried out 15 repetitions at each angle for each task. For example, in the "contralateral arm matching" protocol, the unaffected arm of the participant was set to an angle close to 30 degrees. He was then requested to keep the unaffected arm at the specified angle while trying to match the position with the affected arm. Whenever the two arms matched, a vibration was given on both brachialis muscles. For the "both arms moving together" protocol, the two arms were first set approximately to an angle of either 30 or 60 degrees. The participant was asked to return both arms to a relaxed position before moving both arms back to the remembered specified angle. The arm that was slower in moving to the specified angle received a vibration. We performed clinical assessments before, midway through, and after the training period using a Fugl-Meyer assessment (FMA), a Wolf motor function test (WMFT), and a proprioceptive assessment. For the assessments, two ipsilateral and contralateral arm matching tasks, each consisting of three movements (shoulder abduction, shoulder flexion, and elbow flexion), were used. Movements were performed at two angles, 30 and 60 degrees. For both tasks, the same procedure was used. For example, in the case of the ipsilateral arm matching task, an experimenter positioned the affected arm of the participant at 30 degrees of shoulder abduction. The participant was requested to keep the arm in that position for ~5 s before returning to a relaxed initial position. Then, after another ~5-s delay, the participant moved the affected arm back to the remembered position. An experimenter measured this shoulder abduction angle manually using a goniometer. The same procedure was repeated for the 60 degree angle and for the other two movements. We applied a low-cost Kinect to extract the participant's body joint position data. Tactile feedback was given based on the arm position detected by the Kinect sensor. By using a Kinect sensor, we demonstrated the feasibility of the system for the training of a post-stroke user. The proposed system can further be employed for self-training of patients at home. The results of the FMA, WMFT, and goniometer angle measurements showed improvements in several tasks, suggesting a positive effect of the training system and its feasibility for further application for stroke survivors' rehabilitation.

Objectives: In this study, we aimed to determine whether the prostate-specific antigen level is a reliable marker of prostate cancer in patients with hepatic insufficiency, based on evaluation of alterations in serum prostate-specific antigen levels after liver transplant in patients with hepatic insufficiency., Materials and Methods: Medical records of all patients who underwent liver transplant at our hospital between January 2003 and June 2017 were retrospectively reviewed. Male patients who were > 40 years old with available pre- and posttransplant serum total prostate-specific antigen levels were included in the study., Results: Our study included 36 male patients with a mean age of 54.6 ± 5.3 years (range, 45-73 y) at the time of liver transplant. The mean pretransplant serum total prostate-specific antigen level was 0.75 ± 0.77 ng/mL, which was significantly lower than the mean posttransplant level of 1.29 ± 1.57 ng/mL (P < .05). The pretransplant serum total prostate-specific antigen level was measured a mean of 4.9 ± 5.4 months before liver transplant versus a mean 27.6 ± 16.3 months after transplant. Prostate-specific antigen velocity was 0.2 ng/mL/year. Biochemical tests of liver function, including the mean serum levels of bilirubin, international normalized ratio, and albumin, were normal after liver transplant at 1.37 ± 2.33 mg/dL, 1.22 ± 0.36, and 4.16 ± 0.69 g/dL, respectively., Conclusions: Serum prostate-specific antigen levels may decrease in patients with hepatic insufficiency/cirrhosis; therefore, a low serum prostate-specific antigen level may not be a reliable marker for excluding prostate cancer in such patients. Transplant surgeons and clinicians must be aware of this so that all male transplant candidates > 40 years old are evaluated via digital rectal examination, regardless of the serum prostate-specific antigen level.

Objectives: The aim of this study is to investigate the factors affecting cost in patients with severe community-acquired pneumonia (CAP) who were admitted to the intensive care unit (ICU)., Materials and Methods: This retrospective cohort study was conducted between January 2013 and December 2016. A total of 291 sequential patients with severe CAP were included in the study. Patients' demographic and clinical data; the need for invasive mechanical ventilation or non-invasive mechanical ventilation; intensive care severity (ICU) scores, including Acute Physiology and Chronic Health Evaluation (APACHE II), Sepsis-related Organ Failure Assessment, Quick SOFA, pneumonia severity index (PSI); and Confusion, Urea, Respiratory Rate, and Blood Pressure-65 (CURB-65) scores were obtained from medical records and recorded for all cases., Results: The mean age of 291 patients was 68.4±16.8 years, and 61% were female. The median length of ICU stay was 7 days. Forty-six percent of patients had chronic obstructive pulmonary disease (COPD), and 42% had hypertension. The mean cost of each hospitalization was US$ 2722 (TL 5578). The highest cost was found in the group of patients aged 50-59 years, and the lowest cost was found in the patients aged <50 years. A statistically significant relationship was found between ICU severity scores and health cost. The cost of patients in PSI class V, APACHE II (>20 points), and CURB-65 score were higher. The presence of COPD, atrial fibrillation, congestive heart failure, hypoalbuminemia, mental state deterioration, in-hospital mortality, severe sepsis, septic shock, mechanical ventilation requirement, and haloperidol and vasopressor usage were associated with higher cost, while the use of florokinolon was associated with lower cost., Conclusion: The presence of certain comorbidities and high disease severity in patients with severe CAP hospitalized in ICU increase the cost of inpatient treatment. The need for mechanical ventilation during treatment and the presence of sepsis/septic shock are additional factors that increase the cost.

Background: Serious gaming is recognized as a training tool due its potential for a risk-free educational environment. There is still limited research about using serious gaming modules for emergency skills training., Objective: The aim of this study is to compare the effects on the knowledge level of participants after using a tablet-based serious game and a virtual reality (VR)-based serious game for Basic Life Support using a pretest/posttest method., Methods: The study was designed as a randomized trial comparing pretest and posttest results. A tablet-based and VR-based serious game with identical content was used for 40 participants. Over half of them (22/40, 55%) were included in the VR group and just under half (18/40, 45%) were in the tablet group. Student t test and Wilcoxon signed rank tests were used to determine the relation between the dependent and independent variables. In order to determine the effect size of the results, the effect size calculator (Cohen d) for t test was used. There is a significant difference between pre- and posttest results in both groups (P=.001; Wilcoxon)., Results: Mean posttest results were significantly higher in both groups. The posttest results were significantly higher in the VR group in terms of pre- and posttest changes (P=.021; Student t test)., Conclusions: Past research studies have shown that serious gaming presents a favorable additional tool for medical education. The results indicate that both serious gaming modules are effective and that VR-based serious gaming is more efficient in terms of learning outcome than tablet-based gaming., (©Emin Aksoy. Originally published in JMIR Serious Games (http://games.jmir.org), 01.05.2019.)

B cell lymphoma-6 (BCL6) is highly expressed in germinal center B cells, but how its expression is maintained is still not completely clear. Aryl hydrocarbon receptor interacting protein (AIP) is a co-chaperone of heat shock protein 90. Deletion of Aip in B cells decreased BCL6 expression, reducing germinal center B cells and diminishing adaptive immune responses. AIP was required for optimal AKT signaling in response to B cell receptor stimulation, and AIP protected BCL6 from ubiquitin-mediated proteasomal degradation by the E3-ubiquitin ligase FBXO11 by binding to the deubiquitinase UCHL1, thus helping to maintain the expression of BCL6. AIP was highly expressed in primary diffuse large B cell lymphomas compared to healthy tissue and other tumors. Our findings describe AIP as a positive regulator of BCL6 expression with implications for the pathobiology of diffuse large B cell lymphoma., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Tracheostomy is a method of separating a patient from the mechanical ventilator in the intensive care unit (ICU). The long-term survivors among patients followed up with tracheostomy and ventilator in the respiratory ICU (RICU) outpatient clinic due to different diseases were investigated., Materials and Methods: This was a retrospectively designed cohort study between January 2004 and July 2018. Patients with chronic respiratory failure followed up with tracheostomy and/or ventilator at the RICU outpatient clinic were included in the study. Age, gender, indications and date of tracheostomy, use of domestic mechanical ventilation, and mortality were recorded. The groups were compared according to age, gender, and tracheostomy indication diseases, and the 1-3-year long-term mortality rates were analyzed by the Kaplan-Meier survival analysis, and the Cox regression test was performed., Results: A total of 134 (64% male) patients with a median age of 66 (54-73) years were included in the study. The indications for tracheostomy were heart failure (HF) and cerebrovascular diseases (38.1%), chronic obstructive pulmonary disease (COPD) (23.1%), neuromuscular diseases (22.4%), obesity hypoventilation (9.7%), and kyphoscoliosis (6.7%). Mortality was higher in patients >75 years old in the 3-year follow-up (p=0.022). The 3-year mortality hazard ratio (HR) factors and 95% confidence interval (CI) were as follows: age >75 years HR=1.71 (95% CI, 1.03-2.82; p<0.036) and HF and cerebrovascular disease diseases sequela HR=1.84 (95% CI, 1.03-3.29; p<0.041) significantly increased the 3-year mortality, and having COPD decreased mortality in 46% (p<0.041)., Conclusion: Patients with neuromuscular disorders, kyphoscoliosis, and COPD who have undergone tracheostomy were the luckiest group according to the 3-year survival rates, whereas patients with HF and cerebrovascular diseases were the unluckiest ones. The most important decision triangle is the patient's acceptance (A), family support (B), and tracheostomy indication (C), and this may vary from country to country depending on the beliefs of subjects.

Schmallenberg virus (SBV), discovered in 2011 in Germany, is associated with clinical manifestations of fever, diarrhea, reduced milk yield, abortions and congenital malformations in ruminants. Despite many studies performed for SBV, there is no detailed research on in vitro apoptotic effect of SBV. This study is aimed to determine apoptosis pathways and role of pro-apoptotic and anti-apoptotic molecules in Vero cells infected with SBV. The study results showed that SBV induced apoptosis via both extrinsic and intrinsic pathways by activating both caspase-8 and caspase-9, respectively. Expression analyses of pro-apoptotic (Bax, Bak and Puma) and anti-apoptotic (Bcl-2 and Bcl-XL) genes revealed that SBV-induced apoptosis causes upregulation of pro-apoptotic genes, dominantly via Puma gene, whereas Bcl-2 and Bcl-XL genes were downregulated. In conclusion, this is the first detailed report about SBV induced apoptosis in the Vero cells via both extrinsic and intrinsic cascades and apoptosis induction is seem to be regulated by Puma.

Harakiri (HRK) is a BH3-only protein of the Bcl-2 family and regulates apoptosis by interfering with anti-apoptotic Bcl-2 and Bcl-xL proteins. While its function is mainly characterized in the nervous system, its role in tumors is ill-defined with few studies demonstrating HRK silencing in tumors. In this study, we investigated the role of HRK in the most aggressive primary brain tumor, glioblastoma multiforme (GBM). We showed that HRK is differentially expressed among established GBM cell lines and that HRK overexpression can induce apoptosis in GBM cells at different levels. This phenotype can be blocked by forced expression of Bcl-2 and Bcl-xL, suggesting the functional interaction of Bcl-2/Bcl-xL and HRK in tumor cells. Moreover, HRK overexpression cooperates with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a known tumor-specific pro-apoptotic agent. Besides, secondary agents that augment TRAIL response, such as the histone deacetylase inhibitor MS-275, significantly increases HRK expression. In addition, GBM cell response to TRAIL and MS-275 can be partly abolished by HRK silencing. Finally, we showed that HRK induction suppresses tumor growth in orthotopic GBM models in vivo, leading to increased survival. Taken together, our results suggest that HRK expression is associated with GBM cell apoptosis and increasing HRK activity in GBM tumors might offer new therapeutic approaches., Competing Interests: The authors declare that they have no conflict of interest.

Most of the commercialized insect resistant transgenic crops express cry gene(s) isolated from Bacillus thuringiensis; however, intensive cultivation of Bt crops over almost two decades has been questioned regarding its sustainability and durability in pest management. The present study focused on silencing of highly specific molting-associated Ecdysone receptor (EcR) gene of Colorado potato beetle (CPB) using RNA interference (RNAi) approach. The partial cDNA of EcR gene of CPB was amplified using specific primers in sense and anti-sense orientations, and cloned in pRNAi-GG vector flanked by an intronic sequence (pdk). Leaf and internodal explants of Agria and Lady Olympia potato cultivars were infected with Agrobacterium strain LBA4404 harboring constructs under the control of CaMV 35S promoter. Standard molecular analysis of primary transformants showed proper integration of T-DNA in plant genome. The transgenic plants of both cultivars were evaluated for their efficacy against first, second and third instar CPB larvae. The leaf biotoxicity assays revealed 15-80% of CPB mortality. A significantly lower fold-change (0.87-4.14×) in larval weight was observed in insects fed on transgenic plants compared to the ones fed on control plants (1.87-6.53×). Furthermore, CPB larvae fed on transgenic plants exhibited reduced EcR transcripts, indicating the functionality of dsRNA EcR in silencing EcR gene expression. This study is an excellent example of the integration of an alternative, effective and reliable method to cope with potato insect pests that incur significant losses to potato production in the world.

Background: Epilepsy is a serious clinical condition characterized by recurrent seizures. Oxidative stress plays an important role in the etio-pathogenesis of epilepsy. Measurements of serum thiol and disulfide levels were used to evaluate the antioxidant status of the body., Objective: The aim of this study was to determine serum levels of thiol and disulfide in epileptic pediatric patients., Methods: Ninety patients, 54 epilepsy and 36 controls were included in the study. Serum levels of native thiol total thiol and disulfide were measured and disulfide/native, disulfide / total thiol and native thiol/ total thiol ratios were calculated. Hence, the ratios of disulfide/ native thiol, disulfide / total thiol and native thiol/ total thiol were calculated., Results: Serum levels of native thiol, total thiol and disulfide were significantly lower in the epilepsy group than the control group. The ratio of disulfide/native thiol and disulfide / total thiol were significantly higher in the study group than the control group. As well as, the native thiol / total thiol ratio was lower in the epilepsy group than the control group. Native thiol, total thiol and disulfide were significantly lower in the epilepsy group who were taking anti-epileptic drugs than those who were not taking anti-epileptic drugs., Conclusion: We demonstrated a meaningful relationship between oxidative stress markers and epilepsy in pediatric patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Aims: Cells in pancreatic ductal adenocarcinoma (PDAC) undergo autophagy, but its effects vary with tumor stage and genetic factors. We investigated the consequences of varying levels of the autophagy related 5 (Atg5) protein on pancreatic tumor formation and progression., Methods: We generated mice that express oncogenic Kras in primary pancreatic cancer cells and have homozygous disruption of Atg5 (A5;Kras) or heterozygous disruption of Atg5 (A5 +/- ;Kras), and compared them with mice with only oncogenic Kras (controls). Pancreata were analyzed by histology and immunohistochemistry. Primary tumor cells were isolated and used to perform transcriptome, metabolome, intracellular calcium, extracellular cathepsin activity, and cell migration and invasion analyses. The cells were injected into wild-type littermates, and orthotopic tumor growth and metastasis were monitored. Atg5 was knocked down in pancreatic cancer cell lines using small hairpin RNAs; cell migration and invasion were measured, and cells were injected into wild-type littermates. PDAC samples were obtained from independent cohorts of patients and protein levels were measured on immunoblot and immunohistochemistry; we tested the correlation of protein levels with metastasis and patient survival times., Results: A5 +/- ;Kras mice, with reduced Atg5 levels, developed more tumors and metastases, than control mice, whereas A5;Kras mice did not develop any tumors. Cultured A5 +/- ;Kras primary tumor cells were resistant to induction and inhibition of autophagy, had altered mitochondrial morphology, compromised mitochondrial function, changes in intracellular Ca 2+ oscillations, and increased activity of extracellular cathepsin L and D. The tumors that formed in A5 +/- ;Kras mice contained greater numbers of type 2 macrophages than control mice, and primary A5 +/- ;Kras tumor cells had up-regulated expression of cytokines that regulate macrophage chemoattraction and differentiation into M2 macrophage. Knockdown of Atg5 in pancreatic cancer cell lines increased their migratory and invasive capabilities, and formation of metastases following injection into mice. In human PDAC samples, lower levels of ATG5 associated with tumor metastasis and shorter survival time., Conclusions: In mice that express oncogenic Kras in pancreatic cells, heterozygous disruption of Atg5 and reduced protein levels promotes tumor development, whereas homozygous disruption of Atg5 blocks tumorigenesis. Therapeutic strategies to alter autophagy in PDAC should consider the effects of ATG5 levels to avoid the expansion of resistant and highly aggressive cells., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Schmallenberg virus (SBV), a neurotropic member of the genus Orthobunyavirus, infects ruminants and causes neurological lesions and fetal malformations including cerebellar hypoplasia, hydranencephaly, and porencephaly. The aim of this study is to establish intracerebral (i.c.) infection of SBV in newborn BALB/c mice and to investigate some of the transcription factors in brain. For this aim, brain samples of newborn BALB/c mice which were infected with SBV i.c. were analyzed by plaque titration and real-time RT-PCR for T-bet, Gata3, RoRγt, Foxp3 and Eomes mRNA levels. Study results showed that SBV can replicate in BALB/c mice brain and cause death of newborn mice with generation of infectious viral particles. Analyses of transcription factor mRNA levels indicated up-regulation of T-bet, Gata3, RoRγt, Foxp3 and down-regulation of Eomes. In this report, we introduce preliminary data of T cell transcription factors affected by SBV infection of BALB/c mice. Keywords: Eomes; Foxp3; Gata3; RoRγt; Schmallenberg virus; T-bet.

Objective: Recent studies have demonstrated that angiogenesis is impaired in patients with celiac disease (CD). In this study, we evaluated the levels of the novel antiangiogenic factor pigment epithelium-derived factor (PEDF) in CD patients., Methods: Eighty-four patients were included in the study; 71 patients with CD and 13 healthy controls. In the CD patient cohort, there were 21 newly diagnosed patients, 19 with adherence to a gluten-free diet and 31 practicing no adherence to this diet. The PEDF levels were measured using enzyme-linked immunosorbent assays., Results: The data revealed that celiac patients had higher levels of PEDF than did healthy controls. PEDF levels were not significantly different among the three CD groups. Additionally, the PEDF levels were not correlated with tissue transglutaminase IgA or IgG., Conclusions: Our data indicate that PEDF levels are significantly higher in CD patients than those in the healthy controls. This result suggests that PEDF negatively affects angiogenesis in CD. Although we did not observe any differences of PEDF levels among celiac patients, additional studies including more patients could clarify this issue., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Results of measurements of radon around of the Black Sea are shown. Radon stations in zones of active faults were placed. Simultaneous hourly measurements of soil radon in 2005 were carried out in the Sivrice Fault Zone that is a segment of East Anatolian Fault System, in the town of Tbilisi (Georgia) and in the South Russia. In 2008 simultaneously hourly measurements of soil radon were carried out in the Western Caucasus (Russia) and in the Mytilene Island (Greece). In 2013 radon in underground waters simultaneously in midday was measuring in Crete (Greece), in the Pamukkale geothermal region (Southwest Turkey) and in the Western Caucasus. Measurements of radon concentration in the points located around of the Black Sea have shown identical regularities in changes of the data. Influence of meteorological, tidal and solar factors on changes of water radon concentrations and soil radon concentrations was observed in all researches points. But this influence was insignificant. Seismological application of observed results also was considered. Various mathematical methods of definition of anomaly in the radon data during earthquakes were considered. During researches in the Black Sea region basically earthquakes with M from 2.0 up to 5.0 and in a depth about 10 km were occurred. For these earthquakes method of daily subtraction of the data of the next and previous day was used. This method has allowed solving a problem with a choice of average value. Probability up to 0.69 (number of earthquakes with radon anomalies/total number of earthquakes) of detection of radon anomalies before earthquakes was achieved applying this method. Changes of radon maps before regional earthquakes were also observed. The frequency analysis of variations of the radon data on the basis of the Wavelet analysis was carried out. Occurrence of the short periods (about 2 days) was observed during regional earthquakes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The tsetse fly (Glossina sp.) midgut is colonized by maternally transmitted and environmentally acquired bacteria. Additionally, the midgut serves as a niche in which pathogenic African trypanosomes reside within infected flies. Tsetse's bacterial microbiota impacts many aspects of the fly's physiology. However, little is known about the structure of tsetse's midgut-associated bacterial communities as they relate to geographically distinct fly habitats in east Africa and their contributions to parasite infection outcomes. We utilized culture dependent and independent methods to characterize the taxonomic structure and density of bacterial communities that reside within the midgut of tsetse flies collected at geographically distinct locations in Kenya and Uganda., Results: Using culture dependent methods, we isolated 34 strains of bacteria from four different tsetse species (G. pallidipes, G. brevipalpis, G. fuscipes and G. fuscipleuris) captured at three distinct locations in Kenya. To increase the depth of this study, we deep sequenced midguts from individual uninfected and trypanosome infected G. pallidipes captured at two distinct locations in Kenya and one in Uganda. We found that tsetse's obligate endosymbiont, Wigglesworthia, was the most abundant bacterium present in the midgut of G. pallidipes, and the density of this bacterium remained largely consistent regardless of whether or not its tsetse host was infected with trypanosomes. These fly populations also housed the commensal symbiont Sodalis, which was found at significantly higher densities in trypanosome infected compared to uninfected flies. Finally, midguts of field-captured G. pallidipes were colonized with distinct, low density communities of environmentally acquired microbes that differed in taxonomic structure depending on parasite infection status and the geographic location from which the flies were collected., Conclusions: The results of this study will enhance our understanding of the tripartite relationship between tsetse, its microbiota and trypanosome vector competence. This information may be useful for developing novel disease control strategies or enhancing the efficacy of those already in use.

Background: Tsetse flies (Diptera, Glossinidae) display unique reproductive biology traits. Females reproduce through adenotrophic viviparity, nourishing the growing larva into their modified uterus until parturition. Males transfer their sperm and seminal fluid, produced by both testes and male accessory glands, in a spermatophore capsule transiently formed within the female reproductive tract upon mating. Both sexes are obligate blood feeders and have evolved tight relationships with endosymbionts, already shown to provide essential nutrients lacking in their diet. However, the partnership between tsetse and its symbionts has so far been investigated, at the molecular, genomic and metabolomics level, only in females, whereas the roles of microbiota in male reproduction are still unexplored., Results: Here we begin unravelling the impact of microbiota on Glossina m. morsitans (G. morsitans) male reproductive biology by generating transcriptomes from the reproductive tissues of males deprived of their endosymbionts (aposymbiotic) via maternal antibiotic treatment and dietary supplementation. We then compared the transcriptional profiles of genes expressed in the male reproductive tract of normal and these aposymbiotic flies. We showed that microbiota removal impacts several male reproductive genes by depressing the activity of genes in the male accessory glands (MAGs), including sequences encoding seminal fluid proteins, and increasing expression of genes in the testes. In the MAGs, in particular, the expression of genes related to mating, immunity and seminal fluid components' synthesis is reduced. In the testes, the absence of symbionts activates genes involved in the metabolic apparatus at the basis of male reproduction, including sperm production, motility and function., Conclusions: Our findings mirrored the complementary roles male accessory glands and testes play in supporting male reproduction and open new avenues for disentangling the interplay between male insects and endosymbionts. From an applied perspective, unravelling the metabolic and functional relationships between tsetse symbionts and male reproductive physiology will provide fundamental information useful to understanding the biology underlying improved male reproductive success in tsetse. This information is of particular importance in the context of tsetse population control via Sterile Insect Technique (SIT) and its impact on trypanosomiasis transmission.

Phosphoinositide-3 kinases (PI3Ks) generate 3-phosphorylated phosphoinositide lipids that are implicated in many biological processes in homeostatic states and pathologies such as cancer, inflammation and autoimmunity. Eight isoforms of PI3K exist in mammals and among them the class I PI3K, p110γ, and PI3Kδ, and class III Vps34 being the most expressed and well characterized in immune cells. Following engagement of pathogen recognition receptors (PRRs), PI3Ks coordinate vital cellular processes of signaling and vesicular trafficking in innate phagocytes such as macrophages and professional antigen presenting dendritic cells (DCs). Although previous studies demonstrated the involvement of PI3K isoforms in innate and adaptive immune cell types, the role of PI3Ks with respect to DC biology has been enigmatic. Thus, this review, based on studies involving PI3K isoforms, highlight how the different PI3Ks isoforms could regulate DC functions such as antigen processing and presentation including PRR responses.

Argininemia is a rare hereditary disease due to a deficiency of hepatic arginase, which is the last enzyme of the urea cycle and hydrolyzes arginine to ornithine and urea. Herein we report a patient with arginase I (ARG1) deficiency who presented with recurrent nonconvulsive status epilepticus and liver failure. A novel homozygous frameshift mutation c.703&#95;707delGGACTinsAGACTGGACC (p.G235Rfs*20) was detected.

Background and Study Aims: Although several factors are thought to be responsible for the development of colonic diverticulosis (CD), the underlying pathogenesis is still obscure and needs clarification. The aim of this study was to determine the prevalence, location and clinical features of CD and especially to detect whether there is an association between CD and postures during defecation., Patients and Methods: This prospective study enrolled 757 patients. The subjects were divided into two groups as a diverticulosis group (D group, n:95) and non-diverticulosis group (non-D group, n:662)., Results: The median patient age was 54.9±13.2 years. CD frequency was 12.5% (n:95). The most commonly involved part of the colon was the sigmoid colon (56.8%). Diverticula location was on the left in 45.3% (n:43), on the right in 24.2% (n:23) and on both sides of the colon in 30.5% (n:29). Patients in the D group were older (p<0.001) and were predominantly female (p:0.04). The frequency of sitting during defecation (Western type toilet) was higher in the D group compared to the non-D group (72.2% vs 53.5%; p:0.007). The use-time of a Western-type toilet was longer in the D group compared to the non-D group (p:0.04). In multivariable logistic regression analysis, age and toilet type were independent risk factors for the development of diverticulosis., Conclusion: Sitting during defecation seems to increase the risk of CD., (© Acta Gastro-Enterologica Belgica.)

Objectives: Chronic respiratory diseases exert a global health burden with high health care costs, morbidity, and mortality. The aim of the present study was to investigate the effect of pulmonary rehabilitation (PR) on emergency admission and hospitalization rates of patients with chronic respiratory disease., Materials and Methods: In this retrospective cohort study, hospitalization rates and emergency admissions of patients before (December 2014-December 2015) and after PR (January 2015-December 2016) were investigated. Patients with chronic respiratory diseases were included. Chronic obstructive pulmonary disease (COPD) patients were classified based on the Global Initiative Chronic Obstructive Pulmonary Disease assessment scheme. PR was applied by three physiotherapists over 8 weeks (2 days/week). Data on patient demographics, clinical and anthropometric data, spirometry, exercise capacity, and quality of life before and after PR were acquired., Results: This study evaluated 51 patients, of whom 76% were men. A total of 37 (73%) COPD patients and 14 (27%) non-COPD patients (7 bronchiectasis, 4 interstitial lung disease, and 3 kyphoscoliosis) were included. The patients exhibited significantly improved incremental shuttle walk test (ISWT) and endurance test scores (p<0.05) after PR. Similar to exercise capacity, the patients exhibited significantly improved Modified Medical Research Council (mMRC) score, St. George's Respiratory Questionnaire (SGRQ), anxiety and depression scores (p<0.05) after PR. In COPD patients, differences in pre- and post-PR ISWT, COPD assessment test, mMRC, and SGRQ scores were statistically significant (p=0.001). The number of emergency admissions and hospitalizations significantly decreased after PR (p=0.001; p=0.001). The post-PR FEV 1 % of COPD significantly increased (p=0.029)., Conclusion: Pulmonary rehabilitation leads to an increase in exercise capacity as well as improved quality of life, resulting in a decrease in emergency admissions and hospitalization rates. Considering the cost of hospitalization, it is important to add PR to the management of patients with chronic respiratory diseases, in addition to medical therapy.

Objectives: The choice of treatment according to the inflammation type in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has been of recent interest. This study investigated the role of novel biomarkers, hospital outcomes, and readmission rates in the first month in patients with eosinophilic or neutrophilic AECOPD., Materials and Methods: We conducted a retrospective observational cohort study in a Chest Teaching Hospital with hospitalized AECOPD patients. Subjects' characteristics, hemogram results, C-reactive protein (CRP), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), platelet/mean platelet volume (PLT/MPV), length of hospital stay, mortality, and steroid use were recorded. Eosinophilic AECOPD defined as peripheral blood eosinophilia (PBE) was >2% and neutrophilic AECOPD as PBE ≤2%. Readmission within 28 days of discharge was recorded., Results: Of 2727(31.5% females) patients, eosinophilic AECOPD was found in 510 (18.7%) patients. Leucocytes, CRP, NLR, and PLR were significantly higher in neutrophilic AECOPD than in eosinophilic AECOPD (p<0.001). Steroid use and mortality rate were 45% and 0.6% in eosinophilic AECOPD and 71%, and 1.4% in neutrophilic AECOPD, respectively (p=0.001, p=0.19). Age >75 years, albumin <2.5 g/dL, CRP >50 mg/dL, and PLT/MPV <20×103 were found to be risks factors for hospital mortality (p<0.05 each). Readmission rates within 28 days of discharge were 5% (n=136), and this rate was higher in eosinophilic AECOPD patients not taking steroids (p<0.001)., Conclusion: NLR, PLR, and CRP levels were higher in neutrophilic AECOPD compared with eosinophilic AECOPD. These markers decreased with treatment in neutrophilic AECOPD. A PLT/MPV ratio of <20×103 resulted in an increased mortality rate. Thus, appropriate steroid therapy may reduce readmission rates in the first 28 days after discharge in eosinophilic AECOPD.

Aim: Early identification and treatment of infections in patients using domiciliary non-invasive mechanical ventilation (NIMV) due to chronic respiratory failure (CRF) can reduce hospital admissions. We assessed C-reactive protein (CRP), procalcitonin, and neutrophil lymphocyte ratio (NLR) as indicators of infection/inflammation. Methods: The study was designed as a retrospective, observational, cross-sectional study, and was performed in 2016 in an intensive care unit outpatient clinic in patients using NIMV. Patients who came to the outpatient clinic with dyspnea, increased sputum, increased prothrombin, and who had hemogram, procalcitonin, and serum CRP, NLR, and PLT/MPV levels assessed, were enrolled into the study. Demographic characteristics, co-morbid diseases, respiratory symptoms, hemogram, biochemistry, CRP, and procalcitonin values in stable and acute attack patients were recorded from patient files. The descriptive statistics and CRP, NLR, and procalcitonin values were assessed. Results: During the study period, 49 patients (24 female) with chronic obstructive pulmonary disease (COPD, n = 24), obesity hypoventilation syndrome (OHS, n = 15), or interstitial lung disease, n = 10), and having had three inflammatory markers assessed, were included in the study. Their mean age was 67 (SD ± 12). Stable patients vs. those who had an acute attack was 41 vs. eight, and within 7 days of outpatient admission four patients were hospitalized. CRP, NLR, and PLT/MPV values were similar in patients' who had sputum purulence, and an increase in dyspnea and sputum, but procalcitonin was significantly higher in patients who had an acute attack. Procalcitonin was not correlated with CRP, NLR, and PLT/MPV. Conclusions: Patients with CRF had similar levels of CRP and NLR during a stable and acute attack state. Procalcitonin may be a better marker for therapeutic decisions in advanced chronic inflammatory diseases.

Background: Complete blood count parameters provide novel inflammatory markers, namely neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR). We aimed to assess any differences in these novel inflammatory markers according to exacerbation severity in patients with COPD in both eosinophilic and neutrophilic endotypes., Method: This retrospective cross-sectional study was conducted at a tertiary education hospital. Previously diagnosed COPD patients admitted to the hospital with acute COPD exacerbation (AECOPD) were enrolled into the study. Patients were grouped according to COPD endotype, eosinophilic (peripheral blood eosinophil rate ≥2%) and neutrophilic (peripheral blood eosinophil rate <2%), and further subdivided according to place of admission (outpatient clinic, ward, or intensive care unit [ICU]) as an indicator of disease severity. Complete blood count, biochemistry, C-reactive protein (CRP), NLR, PLR, and platelet to mean platelet volume values were recorded from an electronic hospital database system and compared among all groups., Results: Of the 10,592 patients included in the study, 7,864 were admitted as outpatients, 2,233 to the wards, and 495 to ICU. Neutrophilic COPD patients (n=6,536, 62%) had increased inflammatory markers compared with eosinophilic COPD patients (n=4,056, 38%); median NLR was 5.11 vs 2.62 ( P <0.001), PLR was 175.66 vs 130.00 ( P <0.001), and CRP was 11.6 vs 7.7 ( P <0.001). All values increased relative to admission to the outpatient clinic, ward, or ICU: median NLR was 3.20, 6.33, and 5.94, respectively, median PLR was 140.43, 208.46, and 207.39, respectively, and median CRP was 6.4, 15.0, and 22.8, respectively. The median NLR values of patients in outpatients/ward/ICU increased in neutrophilic and eosinophilic endotypes: 4.21/7.57/8.60 ( P <0.001) and 2.50/3.43/3.42 ( P =0.81), respectively. CRP showed a similar increased pattern according to severity of AECOPD endotypes., Conclusion: In COPD exacerbation, the inflammatory markers show different increases in each COPD endotypes. These findings may be crucial for defining exacerbation endotypes, the severity of exacerbation, and treatment response during follow-up in COPD patients., Competing Interests: Disclosure All the authors who have contributed to the study design do not have any industry relationships for the past 2 years. The manuscript has been read and approved by all the authors, and each author believes that the manuscript represents honest work. The authors report no conflicts of interest in this work.

Amberlite XAD-4 resin (AXAD-4) was chemically modified to an aminated Amberlite XAD-4 (AAXAD-4) resin and characterized by infrared spectroscopy. AAXAD-4 resin was used as an efficient solid phase for the preconcentration and speciation of Cr(III) and Cr(VI) ions by column technique. The concentration of chromium species was determined by microsample injection system-flame atomic absorption spectrometer (MIS-FAAS). Selective retention of Cr(III) ions was achieved at pH 8.0 and eluted using 1.0 mL of 3.0 mol L-1 HCl and 1.0 mL of 2.0 mol L-1 NaOH, successively, at the flow rate of 5.0 mL min-1. The maximal sorption capacity of AAXAD-4 resin for Cr(III) ions was found to be 67.0 mg g-1. The limit of detection (LOD) and limit of quantitation (LOQ) for Cr(III) ions were found to be 0.041 and 0.131 ∆g L-1, respectively, with preconcentration factor (PF) of 375 and relative standard deviation (RSD) of 3.75% (n = 11). The method was validated using certified reference materials (CRMs) and successfully applied to the real samples, spiked with Cr(III) and Cr(VI) ions.

Background: Parenchymal transection(PT) still remains a challenge in liver resection. The outcomes of the first experience of a novel vessel-sealer for hepatic transection were assessed., Methods: A bipolar articulating vessel-sealer (Caiman ® , Aesculap Inc., Center Valley, PA) was used in 100 liver resections through both open (OLR) and laparoscopic (LLR) approaches. All data were prospectively collected into an IRB-approved department database, and clinical, surgical and perioperative parameters were analyzed., Results: Fifty patients underwent OLR and 50 patients underwent LLR. Eighty hepatectomies were performed for malignancy. Median number of tumors was 1, with the largest focus measuring an average of 5.1 cm. Forty-nine of the procedures were major liver resections. Parenchymal transection time was 29.9 ± 3.1 min in OLR and 29.9 ± 3.6 min in LLR. Median estimated blood loss was 300 cc (Inter-quartile range (IQR) 100-575 cc). Median hospital stay was 6 days for open and 3 days for laparoscopic procedures. Ninety-day complication rate was 8% without any mortality. Bile leak rate was 4%. Staplers were used for parenchymal transection in 16 cases., Conclusion: This study introduces a new multifunctional device into the armamentarium of the liver surgeon. In our experience, this device facilitated the parenchymal transection by adding speed and consolidating the amount of instrumentation used in liver resection without increasing complications., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Introduction: An increased risk of cardiovascular complications has been defined in community-acquired pneumonia (CAP), but limited data is available for patients with severe CAP., Objective: The aim of the present study was to define the prevalence, characteristics, risk factors and impact on mortality of acute cardiac events in patients with severe CAP during short and long term., Method: This investigation was a multicenter, retrospective cohort sudy of patients with severe CAP. Cardiac events were defined as cardiac arrhytmia, congestive heart failure and myocardial infarction. A logistic regression analysis was performed to identify predictors for acute cardiac events and mortality., Results: Of 373 patients (mean age 68 ± 16, 61.4% male), 56 (15%) developed a cardiac event (43 arrhythmia, 11 congestive heart failure and 2 myocardial infarction). Patients who developed an acute cardiac event were older, had more severe disease, pleural effusion, hypoalbuminemia, hyponatremia and more acidosis. Also, beta-blocker and diuretic use were more significant in these patients. In-hospital mortality was significantly higher in patients who developed cardiac events (29.6% vs 11%, P < .001). According to the logistic regression analysis, haloperidol, vasopressor or diuretic use, hypoalbuminemia and age were the predictors for acute cardiac events. Acute cardiac events were significantly associated with in-hospital mortality (OR 2.1; 95%CI 1.03-4.61, P = .04), but not associated with 90-day mortality., Conclusion: Our findings demonstrated that acute cardiac events are seen in a substantial proportion of patients with severe CAP and their occurence significantly associated with in-hospital mortality., (© 2018 John Wiley & Sons Ltd.)

The ubiquitously expressed non-receptor protein tyrosine phosphatase SHP2, encoded by PTPN11, is involved in signal transduction downstream of multiple growth factor, cytokine and integrin receptors 1 . Its requirement for complete RAS-MAPK activation and its role as a negative regulator of JAK-STAT signaling have established SHP2 as an essential player in oncogenic signaling pathways 1-7 . Recently, a novel potent allosteric SHP2 inhibitor was presented as a viable therapeutic option for receptor tyrosine kinase-driven cancers, but was shown to be ineffective in KRAS-mutant tumor cell lines in vitro 8 . Here, we report a central and indispensable role for SHP2 in oncogenic KRAS-driven tumors. Genetic deletion of Ptpn11 profoundly inhibited tumor development in mutant KRAS-driven murine models of pancreatic ductal adenocarcinoma and non-small-cell lung cancer. We provide evidence for a critical dependence of mutant KRAS on SHP2 during carcinogenesis. Deletion or inhibition of SHP2 in established tumors delayed tumor progression but was not sufficient to achieve tumor regression. However, SHP2 was necessary for resistance mechanisms upon blockade of MEK. Synergy was observed when both SHP2 and MEK were targeted, resulting in sustained tumor growth control in murine and human patient-derived organoids and xenograft models of pancreatic ductal adenocarcinoma and non-small-cell lung cancer. Our data indicate the clinical utility of dual SHP2/MEK inhibition as a targeted therapy approach for KRAS-mutant cancers.