ZAP70 Activation Compensates for Loss of Class IA PI3K Isoforms Through Activation of the JAK-STAT3 Pathway.

BACKGROUND/AIM: Tyrosine kinases have crucial functions in cell signaling and proliferation. The phosphatidylinositol 3-kinase (PI3K) pathway is frequently deregulated in human cancer and is an essential regulator of cellular proliferation. We aimed to determine which tyrosine kinases contribute to resistance elicited by PI3K silencing and inhibition. MATERIALS AND METHODS: To mimic catalytic inactivation of p110α/ß, specific p110α (BYL719) and p110ß (KIN193) inhibitors were used in addition to genetic knock-out in in vitro assays. Cell viability was assessed using crystal violet staining, whereas cellular transformation ability was analyzed by soft-agar growth assays. RESULTS: Activated zeta chain of T-cell receptor-associated protein kinase 70 (ZAP70) generated resistance to PI3K inhibition. This resistance was via activation of the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) axis. We demonstrated that activated ZAP70 has a high transforming capability associated with the formation of malignant phenotype in untransformed cells and has the potential to be a tumor-initiating factor in cancer cells. CONCLUSION: ZAP70 may be a potent driver of proliferation and transformation in untransformed cells and is implicated in resistance to PI3K inhibitors in cancer cells.

Carbapenem-resistant Gram-negative pathogens associated with septic shock: a review of 120 cases.

This study aimed to evaluate the influencing variables for outcomes in patients with septic shock having culture-proven carbapenem-resistant Gram-negative pathogens. It included 120 patients (mean age 64.29 ± 1.35 years and 58.3% female). The mean Sequential Organ Failure Assessment score during septic shock diagnosis was found to be 11.22 ± 0.43 and 9 ± 0.79 among the patients with mortality and among the survivors, respectively (P = 0.017). The logistic regression analysis showed that empirical treatment as mono Gram-negative bacteria-oriented antibiotic therapy (P = 0.016, odds ratio (OR) = 17.730, 95% confidence interval (CI): 1.728-182.691), Charlson Comorbidity Index >2 (P = 0.032, OR = 7.312, 95% CI: 5.7-18.3), and systemic inflammatory response syndrome score 3 or 4 during septic shock diagnosis (P = 0.014, OR = 5.675, 95% CI: 1.424-22.619) were found as independent risk factors for day 30 mortality. Despite early diagnosis and effective management of patients with septic shock, the mortality rates are quite high in CRGNP-infected patients.

Analysis of YouTube as a source of information for restless leg syndrome.

BACKGROUND: YouTube is one of the major resources for health related videos around the world. OBJECTIVE: The aim of this study was to evaluate the quality of information available on YouTube about restless leg syndrome (RLS). METHODS: A YouTube search was carried out on https://www.youtube.com for videos pertaining to "restless leg syndrome" by using the keyword "restless leg syndrome". The first 100 relevant videos were included in the study. The videos were accepted as "useful" if they provided scientifically correct information about any aspect of RLS. The videos containing scientifically unproven information are defined as "misleading". The overall quality of all videos was subjectively graded using the global quality scale (GQS), a 5-point Likert scale. RESULTS: The median video length for the included videos was 3.39 (0.11-85) minutes, and the median views were 6,055 (32-2351490). The median GQS of useful videos was 3 (1-5). The median number of likes and the median number of comments of personal experience videos were significantly higher than that of the useful and misleading videos. Videos uploaded by the university hospitals frequently issued pharmacological treatment of the RLS; however, those uploaded by practitioners, individual users, and TV or social media accounts were about the non-pharmacological treatment of the RLS. CONCLUSIONS: This study demonstrates that 77% of the videos uploaded on YouTube regarding RLS are in the useful category, whereas only 16 videos were providing misleading information. However, even videos in the useful category do not provide a full and complete description of the RLS.

Analysis of YouTube as a source of information for restless leg syndrome / Análise do YouTube como fonte de informação para a síndrome das pernas inquietas

ABSTRACT Background: YouTube is one of the major resources for health related videos around the world. Objective: The aim of this study was to evaluate the quality of information available on YouTube about restless leg syndrome (RLS). Methods: A YouTube search was carried out on https://www.youtube.com for videos pertaining to "restless leg syndrome" by using the keyword "restless leg syndrome". The first 100 relevant videos were included in the study. The videos were accepted as "useful" if they provided scientifically correct information about any aspect of RLS. The videos containing scientifically unproven information are defined as "misleading". The overall quality of all videos was subjectively graded using the global quality scale (GQS), a 5-point Likert scale. Results: The median video length for the included videos was 3.39 (0.11-85) minutes, and the median views were 6,055 (32-2351490). The median GQS of useful videos was 3 (1-5). The median number of likes and the median number of comments of personal experience videos were significantly higher than that of the useful and misleading videos. Videos uploaded by the university hospitals frequently issued pharmacological treatment of the RLS; however, those uploaded by practitioners, individual users, and TV or social media accounts were about the non-pharmacological treatment of the RLS. Conclusions: This study demonstrates that 77% of the videos uploaded on YouTube regarding RLS are in the useful category, whereas only 16 videos were providing misleading information. However, even videos in the useful category do not provide a full and complete description of the RLS.

RESUMO Introdução: O YouTube é um dos principais recursos no mundo para vídeos relacionados à saúde. Objetivo: O objetivo deste estudo foi avaliar a qualidade das informações disponíveis no YouTube sobre a síndrome das pernas inquietas (SPI). Métodos: Realizou-se uma busca no YouTube (https://www.youtube.com) para vídeos pertencentes à 'síndrome das pernas inquietas' usando a palavra-chave 'síndrome das pernas inquietas'. Os primeiros 100 vídeos relevantes foram incluídos no estudo. Foram aceitos como 'úteis' vídeos que fornecessem informações cientificamente corretas sobre qualquer aspecto da SPI. Os vídeos que contêm informações não comprovadas cientificamente são definidos como 'enganosos'. A qualidade geral de todos os vídeos foi avaliada subjetivamente usando a escala de qualidade global (GQS), uma escala Likert de 5 pontos. Resultados: A duração média dos vídeos incluídos foi de 3,39 (0,11-85) minutos e as visualizações médias foram de 6.055 (32-2.351.490). A GQS média dos vídeos úteis foi 3 (1-5). O número médio de curtidas e o número médio de comentários de vídeos de experiências pessoais foram significativamente maiores do que os de vídeos úteis e enganosos. Vídeos enviados por hospitais universitários frequentemente divulgam tratamento farmacológico da SPI; no entanto, aqueles carregados por profissionais, usuários individuais e contas de TV ou mídia social eram sobre o tratamento não farmacológico da SPI. Conclusões: Este estudo demonstrou que 77% dos vídeos carregados no YouTube sobre a SPI estão na categoria útil, enquanto apenas 16 vídeos forneceram informações enganosas. No entanto, mesmo os vídeos na categoria útil não fornecem uma descrição extensa e completa da SPI.

Serum bicarbonate level improves specificity of Berlin Sleep Questionnaire for obstructive sleep apnea.

Several questionnaires have been developed to assist the diagnostic process in obstructive sleep apnea syndrome (OSAS). Berlin Sleep Questionnaire (BSQ) represents a validated screening tool for OSAS. Totally 450 patients admitted to the Sleep Center at Dicle University Medical Faculty were included prospectively. A risk analysis was performed for presence of OSAS using the BSQ. Arterial blood gas measurements were performed including bicarbonate (HCO3) level. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of BSQ for presence of OSAS and severe OSAS were determined. In patients with arterial HCO3 >24.94 mEq/L; sensitivity, specificity, PPV and NPV, of the BSQ were 93.04, 57.1, 98.3, and 23.5%, respectively. The addition of arterial HCO3 value increased the sensitivity of the BSQ in detecting OSAS patients. Although the cost of sleep studies is high for false positives from the BSQ plus arterial HCO3 level, this cost should be compared with the loss of work efficiency and severe healthcare costs of undiagnosed cases in the future. Therefore, finding possible OSAS cases in primary care health centers is important and adding serum HCO3 value to BSQ questionnaire may contribute to this topic.

Clinical value of anti-DFS70 antibodies in a cohort of patients undergoing routine antinuclear antibodies testing.

BACKGROUND: It is has been proposed that the presence of anti-DFS70 antibodies could be used to eliminate a SARD diagnosis. However, anti-DFS70 antibodies were also observed at relatively high frequency in patients with SARD. The clinical significance of these antibodies is therefore not yet clear. In this study, we assessed the clinical significance of the presence of anti-DFS70 antibodies. METHODS: A total of 3432 sera samples were obtained from patients who underwent routinely requested ANA screening in the clinical laboratory of a University Hospital, between June 2017 and June 2019. Antinuclear antibody testing was performed by indirect immunofluorescence (IIF) on Hep-2 cell substrates (Euroimmun, Germany), and anti-ENA were measured by LIA (Euroimmun, Germany). RESULTS: Among 3432 serum samples tested for ANA, 57.3% were ANA positive by IIF. Participants had mean age of 46.4 and 74.8% of the participants were female. Only 11.4% of the study population had SARD. The frequency of DFS pattern by IIF was 8.1%. Analysis of the DFS pattern positive samples by LIA revealed the presence of anti-DFS70 autoantibodies in 67.5% of all DFS, AC-2 pattern ANAs. When using the results of the ANA IIF HEp-2 DFS pattern/Anti-DFS70 LIA, likelihood ratio (LR) for SARD was 0.33. When comparing the ANA IIF HEp-2 DFS pattern with anti-DFS70 LIA, the ANA IIF HEp-2 DFS pattern's LR was lower (0.63 vs 0.85). CONCLUSIONS: Although the DFS pattern cannot exclude the presence of SARD, the likelihood is lower than with other patterns. Therefore, anti-DFS70 antibodies represent an important biomarker that can aid in the interpretation of positive ANA patients and, therefore, should be included in test algorithms for ANA testing. The optimal test algorithm might be laboratory specific being dependent on referral patterns for ANA testing.

Alterations of the neutrophil-lymphocyte ratio during the period of stable and acute exacerbation of chronic obstructive pulmonary disease patients.

OBJECTIVES: We aimed to investigate the importance of neutrophil-lymphocyte ratio (NLR) in patients with chronic obstructive pulmonary disease (COPD) for identifying the severity of inflammation and recognition of acute exacerbation. METHODS: We retrospectively enrolled 100 patients with a diagnosis of COPD exacerbation who were admitted to our clinic. Complete blood count (CBC), measurement of C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were determined within 2 h of hospital admission. Three months after an acute exacerbation, these measurements were obtained from the same patients during the stable period of COPD. The control group included 80 healthy subjects. NLR was calculated from CBC. RESULTS: NLR and other inflammatory markers, such as WBC, CRP and ESR were found to be significantly elevated in exacerbated COPD compared to stable COPD and control participants. There was a significant correlation of NLR with CRP (r = 0.415, P < 0.001), WBC (r = 0.304, P = 0.002) and ESR (r = 0.275, P = 0.035). For an NLR cutoff of 3.29, sensitivity for detecting exacerbation of COPD was 80.8% and specificity was 77.7% (AUC 0.894, P = 0.001). Some patients presenting with acute exacerbation of COPD and CRP, WBC or ESR levels lower than the optimal cut-off value had high NLR values. CONCLUSIONS: Elevated NLR can be used as a marker similar to CRP, WBC and ESR, in the determination of increased inflammation in acutely exacerbated COPD. NLR could be beneficial for the early detection of potential acute exacerbations in patients with COPD who have normal levels of traditional markers.

Effect of human development index parameters on tuberculosis incidence in Turkish provinces.

INTRODUCTION: A country's development level is measured with a quantitative parameter called the human development index (HDI). The present study researched the effects of HDI parameters (such as healthcare standards, income, and education level) on the incidence of tuberculosis. METHODOLOGY: HDI data of 36 provinces of Turkey and the tuberculosis surveillance data were obtained from the Ministry of Development and the Ministry of Health, respectively. The associations between the incidence of tuberculosis and other HDI parameters were analyzed. RESULTS: Higher population density (n/km2) (CI = 0.05 to 0.40) and higher relapse rate of tuberculosis (CI = 0.36 to 1.48) were identified to be independent predicting factors that increased the incidence of tuberculosis, whereas higher gross national product (CI = -0.06 to 0.00), the population that holds a green Medicare card (CI=-0.58 to -0.04), increased general practitioners per 100,000 people (CI=-0.66 to -0.01), female population (CI = -0.70 to -0.06), married population (CI = -1.34 to -0.03), were found to be significant negative predicting factors that were relevant to the incidence (protective against tuberculosis). CONCLUSIONS: Tuberculosis is a disease that is affected by multiple factors, including the components of HDI. Improvement of income level, facilitation of access to health services via health insurance, urbanization with lower population density strategy, and provision of enough general practitioners may be useful in reducing the incidence of TB' in provinces of developing countries such as Turkey.

Quality of Life, Psychological Burden, and Sleep Quality in Patients With Brain Metastasis Undergoing Whole Brain Radiation Therapy.

BACKGROUND: Patients with brain metastasis (BM) usually suffer from poor quality of life (QOL), anxiety, depression, and sleep disorders in their reduced lifespan. OBJECTIVES: The aim of this study was to evaluate QOL, anxiety, depression, and sleep characteristics in patients with BM at the beginning and end of whole brain radiation therapy (WBRT) and three months after treatment. METHODS: Thirty-three patients undergoing WBRT for BM were featured in this study. The authors used the Karnofsky Performance Status (KPS) scale to measure performance status, the Hospital Anxiety and Depression Scale (HADS) to evaluate anxiety and depression, the SF-36® to evaluate health-related QOL, and the Pittsburgh Sleep Quality Index to evaluate sleep disorders at the start of WBRT, the end of WBRT, and three months after WBRT. FINDINGS: Statistically significant improvements were noted in KPS scores from baseline evaluation to the end of WBRT and to three months after WBRT. No significant differences were observed in SF-36 and HADS scores between the start and the end of WBRT. Anxiety scores were negatively correlated with survival at the end of WBRT. Overall survival was better in those who reported better sleep. WBRT improves KPS scores and does not worsen sleep quality or mood, even in patients with poor performance status. When changes in mood and sleep quality are observed, survival and QOL may improve in patients with BM; consequently, nurses should be responsive to these changes.

Evaluation of Tpeak-Tend interval and Tpeak-end/QT ratio in patients with Sarcoidosis.

UNLABELLED: rdiogram (ECG), can be used as a marker of transmural dispersion of repolarization. Also, Tp-e/QT and Tp-e/QTc ratios are used as an index of arrhythmogenesis. Prolonged Tp-e interval and Tp-e/QT ratio was found associated with sudden cardiac death in different clinical conditions. Novel ventricular repolarization parameters, Tp-e interval, Tp-e/QT and Tp-e/QTc ratios have not been evaluated in patients with sarcoidosis without cardiac symptoms previously.Therefore, we investigated Tp-e interval in patients with pulmonary sarcoidosis. METHODS: Sixty-one consecutive patients diagnosed with biopsy-proven pulmonary sarcoidosis were retrospectively reviewed. The 12-lead ECG examinations were performed at speed of 25 mm/s while the patients were in supine position.  QT dispersion, Tp-e intervals and Tp-e/QT ratio were measured. RESULTS: Comparison of ECG parameters between two groups showed a significantly higher average heart rate (p< 0.05) in the patients with sarcoidosis than controls. QT dispersion was higher in patients group. Tp-e interval was significantly prolonged in the study group compared to the control group (92±21 ms and 85±14 ms, respectively; p< 0.05). Tp-e/QT and Tp-e/QTc ratios were significantly higher in patients with sarcoidosis compared to control subjects (all p values < 0.05). CONCLUSIONS: The novel repolarization parameters Tp-e interval, Tp-e/QT and Tp-e/QTc ratios are increased in patients with sarcoidosis without any cardiac symptoms. These parameters might be used as a marker for predicting the ventricular arrhythmias and sudden cardiac death in patients with sarcoidosis.

Pulmonary Function in Patients with End-Stage Renal Disease: Effects of Hemodialysis and Fluid Overload.

BACKGROUND Respiratory system disorders are one of the most prevalent complications in end-stage renal disease patients on hemodialysis. However, the pathogenesis of impaired pulmonary functions has not been completely elucidated in these patients. We designed a study to investigate acute effects of hemodialysis treatment on spirometry parameters, focusing on the relationship between pulmonary function and fluid status in hemodialysis patients. MATERIAL AND METHODS We enrolled 54 hemodialysis patients in this study. Multifrequency bioimpedance analysis (BIA) was used to assess fluid status before and 30 min after the midweek of hemodialysis (HD). Overhydration (OH)/extracellular water (ECW)% ratio was used as an indicator of fluid status. Fluid overload was defined as OH/ECW ≥7%. Spirometry was performed before and after hemodialysis. RESULTS Forced vital capacity (FVC), FVC%, and forced expiratory volume in the first second (FEV1) levels were significantly increased after hemodialysis. FVC, FVC%, FEV1, FEV1%, mean forced expiratory flow between 25% and 75% of the FVC (FEF25-75), FEF25-75%, peak expiratory flow rate (PEFR), and PEFR% were significantly lower in patients with fluid overload than in those without. OH/ECW ratio was negatively correlated with FVC, FVC%, FEV1, FEV1%, FEF25-75, FEF25-75%, PEFR, and PEFR%. Stepwise multiple regression analysis revealed that male sex and increased ultrafiltration volume were independently associated with higher FVC, whereas increased age and OH/ECW ratio were independently associated with lower FVC. CONCLUSIONS Fluid overload is closely associated with restrictive and obstructive respiratory abnormalities in HD patients. In addition, hemodialysis has a beneficial effect on pulmonary function tests, which may be due to reduction of volume overload.

Predictive value of platelet-to-lymphocyte ratio in exacerbation of chronic obstructive pulmonary disease.

AIM: We aimed to assess the platelet-to-lymphocyte ratio (PLR) and platelet parameters in patients with chronic obstructive pulmonary disease (COPD). METHODS: A total of 60 stable COPD patients, 50 acute exacerbation COPD patients and 50 healthy controls were enrolled in this study. RESULTS: The platelet distribution width and PLR were higher and the mean platelet volume was lower in the COPD patients during acute exacerbation compared with the stable patients and controls. The PLR was negatively correlated with the forced expiratory volume in 1 s. CONCLUSION: The PLR may be used as a useful and easily accessible tool for evaluating the ongoing inflammation during stable period and the disease severity during acute exacerbations in COPD patients.

Evaluation of New Biomarkers in the Prediction of Malignant Mesothelioma in Subjects with Environmental Asbestos Exposure.

INTRODUCTION: The purpose of this study was to investigate the potential value of certain biomarkers in predicting the presence of malignant pleural mesothelioma (MPM) in individuals environmentally exposed to asbestos. METHODS: This prospective study investigated three groups; a control group composed of 41 healthy subjects, an asbestos exposure group consisting of 48 individuals, and a MPM group consisting of 42 patients. Serum levels of soluble mesothelin-related peptide (SMRP), thioredoxin-1 (TRX), epidermal growth factor receptor (EGFR), fibulin-3, syndecan-1 (SDC-1), and mesothelin were determined. RESULTS: Benign pleural plaques were present in 27 (58.3 %) of the individuals in the asbestos exposure group. The asbestos exposure group had significantly higher mean TRX, SMRP, and mesothelin levels compared to the control group (p = 0.023, p = 0.011, and p < 0.001, respectively). Compared to the asbestos exposure group, the MPM group had significantly higher mean EGFR, TRX, SMRP, and fibulin-3 levels (p = 0.041, p = 0.023, p = 0.002, and p = 0.001, respectively), and significantly lower mean SDC-1 levels (p = 0.002). Unlike the other biomarkers, SMRP and TRX levels increased in a graded fashion among the control, asbestos exposure, and MPM groups, respectively. Area under the curve values for SMRP and TRX were 0.86 and 0.72, respectively (95 % CI 0.79-0.92 and p < 0.001 for SMRP, and 95 % CI 0.62-0.81 and p < 0.001 for TRX). The cut-off value for SMRP was 0.62 nmol/l (sensitivity: 97.6 %, specificity: 68.9 %, positive predictive value (PPV): 56.2 %, and negative predictive value (NPV): 98.3 %) and for TRX was 156.67 ng/ml (sensitivity: 92.9 %, specificity: 77.6 %, PPV: 41.4 %, and NPV: 92.1 %). The combination of the biomarkers reached a sensitivity of 100 %, but had lower specificity (as high as 27.7 %). CONCLUSIONS: Serum biomarkers may be helpful for early diagnosis of MPM in asbestos-exposed cases. SMRP and TRX increased in a graded fashion from the controls to asbestos exposure and MPM groups. These two seem to be the most valuable biomarkers for the diagnosis of MPM, both individually and in combination.

Relationship between metabolic syndrome and epicardial fat tissue thickness in patients with chronic obstructive pulmonary disease.

OBJECTIVE: An increase in epicardial fat tissue (EFT) thickness was found to be associated with metabolic syndrome (MS) and ischemic heart disease. MS is a comorbidity of chronic obstructive pulmonary disease (COPD) resulting from the accompanying systemic inflammation. The aim of our study was to investigate the usefulness of EFT thickness to predict MS in COPD patients. METHODS: COPD patients admitted to our clinic during January-December 2014 and healthy controls were included in this prospective case control study. Patients with comorbidities, COPD exacerbation, and malignancies were excluded. Patients and controls were compared in terms of anthropometric measurements, MS-related examination and laboratory findings, pulmonary function tests, and EFT thickness. The correlations between EFT thickness and markers of MS in COPD were evaluated using the Student's t-test and logistic regression analysis. RESULTS: COPD patients and controls were composed of 82 and 84 individuals, respectively. MS was diagnosed in 31 (37.8%) COPD patients. The EFT thickness was significantly higher in COPD patients than in the controls and was also higher in COPD patients with MS than in those without MS (all p<0.001). Each 1-mm increment of EFT raised the risk of MS two-fold (p=0.011, OR=2.08, 95% CI: 1.18-3.68). Increase in triglyceride level (p=0.004, OR=1.02, 95% CI: 1.01-1.03) and reduction in forced vital capacity (p=0.025, OR=0.26, 95% CI: 0.08-0.84) were found to be associated with increased MS risk. The cut-off value for EFT thickness in the prediction of MS in COPD patients was 6.75 mm (sensitivity: 83%, specificity: 65%). CONCLUSION: EFT thickness is a non-invasive and easily available parameter, which is valuable in the prediction of increased MS risk in COPD patients. Early diagnosis of patients at risk of MS may help to prevent ischemic heart disease in these patients.

The Protective Effects of Caffeic Acid Phenethyl Ester on Acetylsalicylic Acid-induced Lung Injury in Rats.

AIM: We aimed to investigate the protective effect of caffeic acid phenethyl ester (CAPE) on acetylsalicylic acid (ASA)-induced lung damage in rats in the present study. METHODS: A total of 40 rats were randomly divided into five groups, with eight rats in each group-group 1: control, not receiving any medication; group 2: ASA (50 mg/kg/day); group 3: ASA (50 mg/kg/day) plus CAPE (20 µg/kg/day); group 4: ASA (100 mg/kg/day); and group 5: ASA (100 mg/kg/day) plus CAPE (20 µg/kg/day). ASA and CAPE were given via orogastric gavage for 5 days. The total oxidant status (TOS), total antioxidant capacity (TAC), oxidant stress index (OSI), and paraoxonase-1 (PON-1) activity of the blood samples and lung tissues were determined. Histopathological examinations of the lung tissues were performed by using light microscopic methods. RESULTS: CAPE treatment significantly increased antioxidant PON-1 level both in the lung tissue and plasma (p < .05). Plasma antioxidant marker (TAC, PON-1) levels significantly increased and oxidant marker (TOS, OSI) levels significantly decreased in CAPE-treated rats (groups 3,5) compared to ASA given no-CAPE groups (group 2,4) (p < .05). Treatment with CAPE improved pulmonary interstitial inflammation and eosinophil accumulation due to ASA histopathologically. CONCLUSION: Eosinophil-rich inflammation and oxidative stress play important roles in ASA-induced lung toxicity, and CAPE may protect against ASA-induced lung toxicity by reduction of oxidative damage and inflammation in rats.