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Internet of Things (IoT) networks are becoming a part of our daily lives, as the number of IoT devices around us are surging. The authentication of millions of connected things and the distribution and management of secret keys between these devices pose challenging research problems. Current one-to-one authentication schemes do not take the resource limitations of IoT devices into consideration. Nor do they address the scalability problem of massive machine type communication (mMTC) networks. Group authentication schemes (GAS), on the other hand, have emerged as novel approaches for many-to-many authentication problems. They can be used to simultaneously authenticate numerous resource-constrained devices. However, existing GAS are not energy efficient, and they do not provide enough security for widespread use. In this paper, we propose a lightweight GAS that significantly reduces energy consumption on devices, providing almost 80% energy savings when compared to the state-of-the-art solutions. Our approach is also resistant to the replay and man-in-the-middle attacks. The proposed approach also includes a solution for key agreement and key distribution problems in mMTC environments. Moreover, this approach can be used in both centralized and decentralized group authentication scenarios. The proposed approach has the potential to address the fast authentication requirements of the envisioned agile 6G networks, supported through aerial networking nodes., Comment: Published in IEEE Internet of Things Journal

Hepatitis C virus (HCV) infection is the major risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). The mechanisms of HCC initiation, growth, and metastasis appear to be highly complex due to the decade-long interactions between the virus, immune system, and overlapping bystander effects of host metabolic liver disease. The lack of a readily accessible animal model system for HCV is a significant obstacle to understand the mechanisms of viral carcinogenesis. Traditionally, the primary prevention strategy of HCC has been to eliminate infection by antiviral therapy. The success of virus elimination by antiviral treatment is determined by the SVR when the HCV is no longer detectable in serum. Interferon-alpha (IFN-α) and its analogs, pegylated IFN-α (PEG-IFN-α) alone with ribavirin (RBV), have been the primary antiviral treatment of HCV for many years with a low cure rate. The cloning and sequencing of HCV have allowed the development of cell culture models, which accelerated antiviral drug discovery. It resulted in the selection of highly effective direct-acting antiviral (DAA)-based combination therapy that now offers incredible success in curing HCV infection in more than 95% of all patients, including those with cirrhosis. However, several emerging recent publications claim that patients who have liver cirrhosis at the time of DAAs treatment face the risk of HCC occurrence and recurrence after viral cure. This remains a substantial challenge while addressing the long-term benefit of antiviral medicine. The host-related mechanisms that drive the risk of HCC in the absence of the virus are unknown. This review describes the multifaceted mechanisms that create a tumorigenic environment during chronic HCV infection. In addition to the potential oncogenic programming that drives HCC after viral clearance by DAAs, the current status of a biomarker development for early prediction of cirrhosis regression and HCC detection post viral treatment is discussed. Since DAAs treatment does not provide full protection against reinfection or viral transmission to other individuals, the recent studies for a vaccine development are also reviewed.

In parallel with the advances of aerial networks, the use of drones is quickly included in daily activities. According to the characteristics of the operations to be carried out using the drones, the need for simultaneous use of one or more drones has arisen. The use of a drone swarm is preferred rather than the use of a single drone to complete activities such as secure crowd monitoring systems, cargo delivery. Due to the limited airtime of the drones, new members may be included in the swarm, or there may be a unification of two or more drone swarms when needed. Authentication of the new drone that will take its place in the drone swarm and the rapid mutual-verification of two different swarms of drones are some of the security issues in the swarm structures. In this study, group authentication-based solutions have been put forward to solve the identified security issues. The proposed methods and 5G new radio (NR) authentication methods were compared in terms of time and a significant time difference was obtained. According to the 5G NR standard, it takes 22 ms for a user equipment (UE) to be verified by unified data management (UDM), while in the proposed method, this time varies according to the threshold value of the polynomial used and it is substantially lower than 22 ms for most threshold values., Published in IEEE International Conference on Wireless for Space and Extreme Environments (WiSEE)

Chronic hepatitis C virus (HCV) infection causes hepatocellular carcinoma (HCC). Although HCV clearance has been improved by the advent of direct-acting antiviral agents (DAA), retrospective studies have shown that the risk of subsequent HCC, while considerably decreased compared with active HCV infection, persists after DAA regimens. However, either the mechanisms of how chronic HCV infection causes HCC or the factors responsible for HCC development after viral eradication in patients with DAA treatments remain elusive. We reported an in vitro model of chronic HCV infection and determined Wnt/β-catenin signaling activation due to the inhibition of GSK-3β activity via serine 9 phosphorylation (p-ser9-GSK-3β) leading to stable non-phosphorylated β-catenin. Immunohistochemical staining demonstrated the upregulation of both β-catenin and p-Ser9-GSK-3β in HCV-induced HCC tissues. Chronic HCV infection increased proliferation and colony-forming ability, but knockdown of β-catenin decreased proliferation and increased apoptosis. Unexpectedly, Wnt/β-catenin signaling remained activated in chronic HCV-infected cells after HCV eradication by DAA, but metformin reversed it through PKA/GSK-3β-mediated β-catenin degradation, inhibited colony-forming ability and proliferation, and increased apoptosis, suggesting that DAA therapy in combination with metformin may be a novel therapy to treat HCV-associated HCC where metformin suppresses Wnt/β-catenin signaling for HCV-infected patients.

The widespread use of new technologies such as the Internet of things (IoT) and machine type communication(MTC) forces an increase on the number of user equipments(UEs) and MTC devices that are connecting to mobile networks. Inherently, as the number of UEs inside a base station's (BS) coverage area surges, the quality of service (QoS) tends to decline. The use of drone-mounted BS (UxNB) is a solution in places where UEs are densely populated, such as stadiums. UxNB emerges as a promising technology that can be used for capacity injection purposes in the future due to its fast deployment. However, this emerging technology introduces a new security issue. Mutual authentication, creating a communication channel between terrestrial BS and UxNB, and fast handover operations may cause security issues in the use of UxNB for capacity injection. This new protocol also suggests performing UE handover from terrestrial to UxNB as a group. To the best of the authors' knowledge, there is no authentication solution between BSs according to LTE and 5G standards. The proposed scheme provides a solution for the authentication of UxNB by the terrestrial BS. Additionally, a credential sharing phase for each UE in handover is not required in the proposed method. The absence of a credential sharing step saves resources by reducing the number of communications between BSs. Moreover, many UE handover operations are completed in concise time within the proposed group handover method., Published in IEEE Internet of Things Journal 2021

Barrett's esophagus (BE) is one of the major complications of gastroesophageal reflux disease (GERD) commonly encountered in gastroenterology clinics. A consensus has not been achieved yet with respect to the definition of BE in published guidelines. It is advised to use the Prague classification and not to use the definition of short and long segments for the endoscopic standardization of BE. Undertaking biopsies with white-light endoscopy from each of the 4 quadrants at 2-cm intervals is the standard method for the diagnosis of BE. Because of the ability to perform targeted biopsies, the available data indicate that advanced endoscopic techniques may reduce the number of biopsies needed for diagnoses. In the presence of severe esophagitis along with BE, the biopsies should be taken after 8 weeks of PPI therapy. The evidence values of the suggestions about the surveillance requirements and surveillance frequencies are low because the available data mostly rely on retrospective studies. We suggest that all the patients with BE should be referred to specialized centers for surveillance in Turkey. Considering the additional risk factors of the patient, endoscopy surveillance intervals of the patients with BE without dysplasia should be in a range of 3-5 years and annual surveillance should be made in BE with low-grade dysplasia. In the presence of BE with high-grade dysplasia (HGD), the patients should be referred to specialized centers for treatment within 3 months at the latest.

This paper presents a study on optimized control for a magnetically levitated (MAGLEV) suspension system. Unstable magnetically levitated system is modelled and integer order PID (IOPID) and fractional order PID (FOPID) controller parameters are evaluated by using both Genetic Algorithm (GA) and Big Bang Big Crunch (BBBC) algorithm. Comparison between BBBC and GA based controllers are done. Responses for variable reference inputs are obtained. Results show that the performance of the BBBC based FOPID controller is better than GA optimized FOPID controller.

The mechanism why hepatitis C virus (HCV) clearance by direct-acting antivirals (DAAs) does not eliminate the risk of hepatocellular carcinoma (HCC) among patients with advanced cirrhosis is unclear. Many viral and bacterial infections degrade p53 in favor of cell survival to adapt an endoplasmic reticulum (ER)-stress response. In this study, we examined whether HCV clearance by interferon-alpha or DAAs normalizes the ER stress and restores the expression of p53 tumor suppressor in cell culture. We found that HCV infection induces chronic ER stress and unfolded protein response in untransformed primary human hepatocytes. The unfolded protein response induces chaperone-mediated autophagy (CMA) in infected primary human hepatocytes and Huh-7.5 cells that results in degradation of p53 and induced expression of mouse double minute 2 (Mdm2). Inhibition of p53/Mdm2 interactions by small molecule (nutlin-3) or silencing Mdm2 did not rescue the p53 degradation, indicating that HCV infection induces degradation of p53 independent of the Mdm2 pathway. Interestingly, we found that HCV infection degrades p53 in a lysosome-dependent mechanism because lysosome-associated membrane protein 2A silencing restored p53 degradation. Our results show that HCV clearance induced by interferon-alpha-based antiviral therapies normalizes the ER-stress response and restores p53, whereas HCV clearance by DAAs does neither. We show that decreased expression of p53 in HCV-infected cirrhotic liver is associated with expression of chaperones associated with ER stress and the CMA response. Conclusion: HCV-induced ER stress and CMA promote p53 degradation in advanced liver cirrhosis. HCV clearance by DAAs does not restore p53, which provides a potential explanation for why a viral cure by DAAs does not eliminate the HCC risk among patients with advanced liver disease. We propose that resolving the ER-stress response is an alternative approach to reducing HCC risk among patients with cirrhosis after viral cure. (Hepatology Communications 2017;1:256-269).

Hepatitis C virus (HCV) infection compromises the natural defense mechanisms of the liver leading to a progressive end stage disease such as cirrhosis and hepatocellular carcinoma (HCC). The hepatic stress response generated due to viral replication in the endoplasmic reticulum (ER) undergoes a stepwise transition from adaptive to pro-survival signaling to improve host cell survival and liver disease progression. The minute details of hepatic pro-survival unfolded protein response (UPR) signaling that contribute to HCC development in cirrhosis are unknown. This study shows that the UPR sensor, the protein kinase RNA-like ER kinase (PERK), mediates the pro-survival signaling through nuclear factor erythroid 2-related factor 2 (NRF2)-mediated signal transducer and activator of transcription 3 (STAT3) activation in a persistent HCV infection model of Huh-7.5 liver cells. The NRF2-mediated STAT3 activation in persistently infected HCV cell culture model resulted in the decreased expression of hepatocyte nuclear factor 4 alpha (HNF4A), a major liver-specific transcription factor. The stress-induced inhibition of HNF4A expression resulted in a significant reduction of liver-specific microRNA-122 (miR-122) transcription. It was found that the reversal of hepatic adaptive pro-survival signaling and restoration of miR-122 level was more efficient by interferon (IFN)-based antiviral treatment than direct-acting antivirals (DAAs). To test whether miR-122 levels could be utilized as a biomarker of hepatic adaptive stress response in HCV infection, serum miR-122 level was measured among healthy controls, and chronic HCV patients with or without cirrhosis. Our data show that serum miR-122 expression level remained undetectable in most of the patients with cirrhosis (stage IV fibrosis), suggesting that the pro-survival UPR signaling increases the risk of HCC through STAT3-mediated suppression of miR-122. In conclusion, our data indicate that hepatic pro-survival UPR signaling suppresses the liver-specific HNF4A and its downstream target miR-122 in cirrhosis. These results provide an explanation as to why cirrhosis is a risk factor for the development of HCC in chronic HCV infection.

Hepatitis C virus (HCV) infection is frequently associated with the development of chronic liver disease, liver cirrhosis, and hepatocellular cancer. While antiviral therapies, such as interferon (IFN) and ribavirin (RBV), were initially widely accepted, these agents are not very effective against HCV, resulting in numerous deaths due to liver failure secondary to advanced cirrhosis and liver cancer. The recent development of IFN-free, direct-acting antiviral (DAA) drugs has drastically improved patient outcomes, clearing the infection in more than 90% of patients. Of the newly developed DAA drugs, the NS5B polymerase inhibitor sofosbuvir has become an integral part of an effective anti-HCV therapy regimen due to its broad spectrum of antiviral activity against all HCV genotypes and high genetic barrier to resistance. This review will summarize recent progress made in understanding the structure and function of NS5B polymerase and the development of targeted NS5B inhibitors widely used in the treatment of chronic HCV infection.

In this paper we will present on two methods for high performance active magnetic bearings (AMBs). These methods based on robust Variable Structure Control (VSC) with sliding mode in non-adaptive and adaptive cases. Our approach combines two simple architectures often referred to as Dynamic Feedback Linearization (DFL) and recent advances in robust control design techniques to form a new approach for AMB for two cases. The procedure enables the designer to explicitly define the desired closed loop dynamics and enables the design of a robust stabilizing controller that forces the system dynamics to the specified desired dynamics, despite gravitational and centrifugal disturbances, modeling uncertainties, and variations in mass, moments of inertia, radii of eccentricities and center of mass of the rotor. Our design hangs the magnetic bearing on gravitational parabolic sliding surface by switching electronics and sliding mode control components. Thus, electromagnets do not constitute cross forces on rotor shaft that affects against each other. This operation guarantees the lowest power losses, by considering low bias currents method that the currents affects against. The methods also guarante both stability and performance robustness and enable the design for other unstable magnetic levitation systems. When the methods are compared with each other, the results in adaptive case are more efficient about high speed and wide range of parameter uncertainties.

Disability is utmost important on an aging population's health. Obesity is associated with increased risk for disability. On-the-other-hand, higher-BMI is reported as associated with better functionality in older people in some reports defined as "obesity paradox". There is some evidence on differential relationship between body weight status and functionality by living setting gender, and different populations. We studied the relation between body mass index and functionality in Turkish community dwelling older males accounting for the most confounding factors: age, multimorbidity, polypharmacy and nutritional status. This is a cross-sectional study in a geriatric outpatient clinic of a university hospital. Functionality was assessed with evaluation of activities of daily living (ADL) and instrumental activities of daily living (IADL) scales. Nutrition was assessed by mini-nutritional assessment test. Two hundred seventy-four subjects comprised our study cohort. Mean age was 74.4 ± 7.1 years, BMI was 25.8 ± 4.4 kg/m(2). Linear regression analysis revealed significant and independent association of lower BMI with higher ADL and IADL scores (B = 0.047 and B = 0.128, respectively) (p 0.05) and better nutritional status (B = 1.94 and B = 3.05, respectively) (p 0.001) but not with the total number of medications. Higher IADL score was associated with younger age and lower total number of diseases (B = 0.121, B = 0.595, respectively) (p 0.05) while ADL was not. We suggest that lower BMI is associated with better functional status in Turkish community-dwelling male older people. Our study recommends longitudinal studies with higher participants from different populations, genders and living settings are needed to comment more.

Background Transient elastography (TE) has recently emerged as an accurate noninvasive imaging method for the diagnosis of liver fibrosis in nonalcoholic fatty liver disease (NAFLD). Here, we tested whether adding serum measures of serum procollagen-III peptide (PIIIP) and caspase-cleaved cytokeratin 18 fragment (M30) to TE could improve its diagnostic accuracy in patients with biopsy-proven NAFLD. Patients and methods TE was performed in 87 patients with NAFLD. Serum PIIIP and M30 levels were determined by enzyme-linked immunosorbent assay. Liver histology was considered the gold standard. The diagnostic accuracies were assessed by measuring the area under the receiver operating curve. Results At histopathological examination, 34 patients (39.1%) had significant fibrosis (F2-F4) and 19 patients (21.8%) had advanced fibrosis (F3-F4). Both TE and serum M30 levels were independent predictors of fibrosis, whereas no association was found with PIIIP. No significant differences in terms of sensitivity and specificity for both significant and advanced fibrosis were evident for TE, serum M30, or their combination. Moreover, the area under the receiver operating curves of serum M30 combined with TE did not differ significantly from those of either test alone. Conclusion Both TE and serum M30 levels are accurate for the noninvasive diagnosis of fibrosis in NAFLD. However, their combination did not improve the overall diagnostic accuracy.

A novel zero tail OFDM (ZT OFDM) method based on Walsh Hadamard transform (ZT WHT OFDM) has been proposed to improve the performance of ZT OFDM systems, from 5G candidate waveforms in this paper. Computer simulations have been performed to show the performance of the proposed method in stationary and non-stationary frequency selective Rayleigh fading channels. The obtained simulation results using HIPERLAN/2 physical layer specifications have demonstrated that the proposed ZT WHT OFDM method has considerably better performance and Doppler shift tracking than conventional OFDM and ZT OFDM.

This paper presents a study on comparison between integer order PID (IOPID) and fractional order PID (FOPID) control of a magnetic bearing system. First, a magnetic levitation system model is derived. Genetic algorithm is used for the controller design to compensate derived model. Different fitness functions are used to determine controller parameters. System responses are compared for two controllers. Also, controller performances are tested both when the operation point is varied and controller parameters are changed. Moreover, a comparison between IOPID and FOPID is done.

In this paper, a contactless magnetic radial shaft bearing adaptive control algorithm has been developed for high speed five degrees of freedom rigid rotors with external asymmetrical loads. The developed control algorithm keeps the rotor on rotating through its geometric axis while keeping on the radial air gap in stator housing to be constant at maximum value in every direction to compensate the mass imbalance due to asymmetrical loading. In this method, the radial air gap lengths along the direct and quadrature axis of bearings are measured and then, from these measurements, the radial position errors and the angular position displacements around the direct and quadrature axes on the radial plane through the stator geometric center are estimated. In this paper we will present the method for high performance active magnetic bearings (AMBs). The method based on robust Variable Structure Control (VSC) with sliding mode in adaptive case. Dynamic Feedback Linearization (DFL) and recent advances in robust control design techniques is to form a new approach for AMB. A robust stabilizing controller forces the system dynamics to the specified desired dynamics, despite gravitational and centrifugal disturbances, modeling uncertainties, and variations in mass, moments of inertia, radii of eccentricities and center of mass of the rotor. The method gives both stability and performance robustness and enable the design for other unstable magnetic levitation systems. The results are very efficient about high speed and wide range of parameter uncertainties.

// Srinivas Chava 1 , Christine Lee 1 , Yucel Aydin 2 , Partha K. Chandra 1 , Asha Dash 1 , Milad Chedid 1 , Swan N. Thung 3 , Krzysztof Moroz 1 , Tong Wu 1 , Nabeen C. Nayak 4 and Srikanta Dash 1 1 Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana, USA 2 Department of Medicine, Division of Gastroenterology and Hepatology, Tulane University Health Sciences Center, New Orleans, Louisiana, USA 3 The Lillian and Henry M. Stratton-Hans Popper Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA 4 Senior Consultant and Advisor, Sir Ganga Ram Hospital, Department of Pathology, New Delhi, India Correspondence to: Srikanta Dash, email: // Keywords : liver cirrhosis, hepatocellular carcinoma, macroautophagy, chaperone-mediated autophagy, endoplasmic reticulum, Pathology Section Received : January 12, 2017 Accepted : March 19, 2017 Published : March 29, 2017 Abstract Macroautophagy and chaperone-mediated autophagy (CMA) represent two major lysosomal degradation processes and often compensate for one another to facilitate cell survival. The aim of this study was to determine whether these autophagy pathways could compensate for one another to promote HCC cell survival in the cirrhotic liver. Analysis of normal liver tissue showed no expression of glypican-3 or p62 proteins, suggesting that macroautophagy is the major contributor to autophagic flux under non-pathological conditions. Of 46 cirrhotic livers with HCC examined, 39 (84%) of HCCs showed increased expression of p62, and 36 (78%) showed increased expression of glypican-3, while adjacent non-tumorous hepatocytes were negative for expression of p62 and glypican-3, similar to normal liver tissue. These results suggest that macroautophagy flux is impaired in HCC. Furthermore, more than 95% of HCCs showed altered expression of LAMP-2A compared to the surrounding non-tumorous cirrhotic liver, consistent with induction of CMA in HCC. Elevated expression of glucose-regulated protein 78 (GRP78) and heat shock cognate protein (Hsc70) were detected in 100% of HCC and adjacent non-tumorous cirrhotic livers, suggesting that unresolved ER-stress is associated with HCC risk in liver cirrhosis. Interestingly, inhibition of lysosomal degradation using hydroxychloroquine (HCQ) induced expression of the tumor suppressor p53, promoted apoptosis, and inhibited HCC growth, whereas activation of autophagy using an mTOR inhibitor (Torin1) promoted HCC growth. Results of this study suggest that induction of CMA compensates for the impairment of macroautophagy to promote HCC survival in the cirrhotic liver.

Aim To analyze correlates of mortality with admission features/factors in older community-dwelling outpatients. Method This is an observational cohort study including 608 patients aged >60 years admitted to the geriatrics outpatient clinics of a university hospital. On admission, demographic characteristics, history of smoking-alcohol consumption, individual comorbidities, individual drugs, number of comorbidities, number of drugs and the components of comprehensive geriatric assessment (functional status, nutritional status, depression and cognition screening) of the patients were recorded. Survival status was assessed through the related official website. The relationship between mortality and recorded parameters were analyzed individually by univariate analyses. Consequently, stepwise forward Cox regression analysis was carried out to detect independent correlates for mortality (for those variables statistically significantly related to mortality.) Results The mean age was 73.8 ± 6.9 years. 66.6% of participants were female. The mean follow-up time was 40.4 ± 25.3 months. The mortality rate was 17.8%. Correlates of mortality were calculated using univariate analysis. They were age, sex, nutritional status, activities of daily living (ADL), instrumental ADL, diabetes mellitus (P

The relationship of body mass index (BMI) with functional status differs in diversified geriatric population and various settings. In this study, we aimed to investigate whether BMI is related to functional status independent of age, nutritional status, multimorbidity, and polypharmacy in a group of Turkish community-dwelling female elderly. This study was conducted using a cross-sectional study design. Geriatric outpatient clinic of a university hospital. There were 438 female patients aged 60 years or older included in the analysis. Body mass indexes were calculated from weight (kg) divided by the square of height (m). Functional status was assessed with the evaluation of activities of daily living (ADL) and instrumental activities of daily living (IADL) scales. Diseases and drugs were determined after the evaluation of the patients with comprehensive geriatric assessment, physical examination, first-line biochemical tests, and using the patients’ self-report and current medication lists. In total, 438 subjects comprised our study cohort. Mean age was 73.3 ± 6.9 years. Mean BMI was 27.8 ± 5.2 kg/m2. Linear regression analysis revealed significant and independent association of lower BMI with higher ADL and IADL scores (p = 0.02, B = −0.10; p

Objective: Non-alcoholic fatty liver disease (NAFLD) is associated with atherosclerosis and reduced vascular compliance. The purpose of this study was to examine the relationships between arterial stiffness measures, the histological severity of NAFLD, and epicardial fat thickness (EFT). Methods: A total of 100 patients with biopsy-proven NAFLD and 50 age- and sex-matched controls were enrolled. The histological severity was assessed in all NAFLD patients. Measurements of arterial stiffness [pulse-wave velocity (PWV) and augmentation index (AIx)] were carried out using a Mobil-O-Graph arteriograph system. EFT was assessed by means of echocardiography. Results: Compared with controls, NAFLD patients had significantly higher PWV and AIx values. Stepwise linear regression analysis demonstrated that the liver fibrosis score and EFT were independent predictors of both PWV and AIx values in NAFLD patients. Conclusions: Patients with NAFLD have an increased arterial stiffness, which reflects both the severity of liver fibrosis and increased EFT values.

Most elderly persons live in developing countries where current geriatric epidemiological data are scarce. We aimed to study major comorbidities, polypharmacy, functional and nutritional status in a Turkish community-dwelling female elderly clinic population. Female geriatrics outpatient clinic patients were assessed cross-sectionally. Patients underwent comprehensive geriatric cassessment, including identification of chronic diseases, drugs, functionality, and nutrition. Comorbidities and drugs were defined by the review of patients’ self-reports and current medications. Geriatric depression and cognition were assessed by 30-item geriatric depression scale and Folstein mini-mental-state-examination. Functional status was assessed by the evaluation of activities of daily living (ADL) and instrumental activities of daily living (IADL) scales. Nutritional assessment was performed by mini-nutritional-assessment-short form. Five-hundred and fifteen patients were included in this study over an 8-year period. Mean age was 73.4 ± 6.9 years. Mean number of chronic diseases was 2.8. 61.1 % had >3 chronic diseases. Most common 3 diagnoses were hypertension (75.3 %), depression (45.5 %) and dementia (39.4 %). Mean number of drugs was 4.8. Polypharmacy was noted as 63.2 and 47.6 % by definitions as >4 or >5 chronic drug use, respectively. Subjects with at least one dependency of ADL and IADL were 23.4 and 64.0 %. Prevalence of poor nutrition was 39.1 %. In patients with at least one ADL or IADL dependency, undernutrition (p

Hepatitis C virus (HCV) infection triggers autophagy processes, which help clear out the dysfunctional viral and cellular components that would otherwise inhibit the virus replication. Increased cellular autophagy may kill the infected cell and terminate the infection without proper regulation. The mechanism of autophagy regulation during liver disease progression in HCV infection is unclear. The autophagy research has gained a lot of attention recently since autophagy impairment is associated with the development of hepatocellular carcinoma (HCC). Macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA) are three autophagy processes involved in the lysosomal degradation and extracellular release of cytosolic cargoes under excessive stress. Autophagy processes compensate for each other during extreme endoplasmic reticulum (ER) stress to promote host and microbe survival as well as HCC development in the highly stressed microenvironment of the cirrhotic liver. This review describes the molecular details of how excessive cellular stress generated during HCV infection activates CMA to improve cell survival. The pathological implications of stress-related CMA activation resulting in the loss of hepatic innate immunity and tumor suppressors, which are most often observed among cirrhotic patients with HCC, are discussed. The oncogenic cell programming through autophagy regulation initiated by a cytoplasmic virus may facilitate our understanding of HCC mechanisms related to non-viral etiologies and metabolic conditions such as uncontrolled type II diabetes. We propose that a better understanding of how excessive cellular stress leads to cancer through autophagy modulation may allow therapeutic development and early detection of HCC.

Autophagy is an intracellular lysosomal degradation process performed by the cells to maintain energy balance. The autophagy response plays an important role in the progression of liver disease due to hepatitis virus infection, alcoholic liver disease, nonalcoholic fatty liver disease, liver cirrhosis, and hepatocellular carcinoma (HCC). An increased autophagy response also contributes to the pathogenesis of liver disease through modulation of innate and adaptive immune responses; a defective cellular autophagy response leads to the development of HCC. Recent progress in the field indicates that autophagy modulation provides a novel targeted therapy for human liver cancer. The purpose of this review is to update our understanding of how the cellular autophagy response impacts the pathophysiology of liver disease and HCC treatment.

WOS: 000389516600014 PubMed ID: 27619844 Objectives: Serum alanine aminotransferase (ALT) is a controversial marker for disease monitoring in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. The aim of this study was to determine the fibrosis stage and histological activity index (HAI) in HBeAg-negative CHB patients with persistently normal ALT (PNALT) and high serum HBV DNA (>= 2000 IU/ml) and to investigate clinical risk factors for the requirement of treatment through the examination of liver biopsy specimens. Methods: HBeAg-negative CHB patients with PNALT (= 2000 IU/ml) were included. HBV fibrosis stage and HAI were scored according to the Ishak system. Multivariate logistic regression analysis was used to estimate the independent risk factors for fibrosis stage >= 2 and/or HAI >= 6. Receiver operating characteristic curve analysis was used to determine an optimal age cut-off for liver biopsy. Results: A total 120 patients were enrolled. These patients had a mean HBV DNA level of 123 680 +/- 494 500 IU/ml; the HBV DNA load was 2000-20 000 IU/ml in 68 patients (56.6%) and >= 20 000 IU/ml in 52 (43.4%). Eighteen patients (15%) had moderate-to-severe histological activity (HAI >= 6). Forty-three patients (35.9%) had a fibrosis stage >= 2. Forty-eight patients (40%) had a fibrosis stage >= 2 and/or HAI >= 6. On multivariate logistic regression analysis, independent variables associated with fibrosis stage >= 2 and/or HAI >= 6 included age and HBV DNA viral load. Patients with HBV DNA 2000-20 000 IU/ml were more likely to require treatment compared to those with a viral load >= 20 000 IU/ml. The optimal age cut-off to predict fibrosis stage >= 2 and/or HAI >= 6 was 46 years. Conclusions: Significant liver damage was detected in 40% of CHB patients with PNALT and high HBV DNA upon biopsy. Age and HBV DNA viral load were independent predictors of significant liver damage. A biopsy to determine the degree of liver damage is advisable for CHB patients older than 46 years.

Besides reducing the reflux symptoms, the benefit of proton pump inhibitors (PPI) in the treatment of Barrett's esophagus (BE) is not exactly known. The data in the literature show that although the PPI treatment does not reduce the Barrett's segment length, it can reduce dysplasia or the development of early-stage adenocarcinoma (odds ratio (OR): 0.46). Therefore, treatments with PPI may be considered in patients with a diagnosis of BE and at a high risk of adenocarcinoma, even though they are not symptomatic.

Objective. To evaluate the clinicopathological prognostic factors and outcome of chemotherapy in ovarian carcinosarcomas. Methods. We reviewed the records of 26 patients treated from 1990 to 2006 at the Oncology Institute of Istanbul University. Clinical data including demographics, stage, surgery, chemotherapy, and survival were collected from patients' charts. Results. All patients underwent initial debulking surgery. Optimal debulking was achieved in 21 (81%) patients. The most striking clinicopathological finding was the high incidence of hemorrhagic ascites ( n : 6) which was observed in 60% of the patients with ascites ( n : 10). The overall median survival of the patients was 26 months. Residual disease was associated with a decreased overall survival, P =0.04. Median survival (50 months vs 9.7 months, P =0.042) of the patients with early stage disease were longer than the patients with advanced stage. Twenty-two patients received platinum-based combination chemotherapy. There was a trend for increased median survival in the patients who were treated with carboplatin/paclitaxel combination ( P =0.066). Although the numbers were insufficient for statistical evaluation, the patients treated with ifosfamide combinations had improved survival (36 months vs 26 months). However, when the patients treated with ifosfamide and carboplatin/paclitaxel combinations were combined, survival was statistically improved compared to the other regimens (36 months vs 9.7 months, P =0.04). Chemotherapy regimens containing doxorubicin or cyclophosphamide were not encouraging. Stage ( P =0.02) and adjuvant platinum-based chemotherapy containing either paclitaxel or ifosfamide ( P =0.024) remained predictive of outcome in the multivariate analysis. Conclusions. Hemorrhagic ascites can be used in the initial differential diagnosis of ovarian carcinosarcomas. Stage, optimal debulking and type of adjuvant therapy were statistically significant prognostic predictors of ovarian carcinosarcomas. We advise that patients with ovarian carcinosarcomas should be treated by optimal cytoreduction followed by adjuvant platinum/taxan or platinum/ifosfamide combinations.

Summary Objective Nonalcoholic fatty liver disease (NAFLD) is associated with increased risk of cardiovascular disease and impaired left ventricular (LV) function, yet the impact of NAFLD on right ventricular (RV) function remains unclear. We investigate the RV functional properties in patients with NAFLD. Methods Ninety consecutive patients with the diagnosis of biopsy-proven NAFLD and 45 age- and sex-matched controls were included. All patients underwent an echocardiographic examination. RV function was evaluated by two-dimensional (2D) speckle-tracking echocardiography (STE). Results Mean fibrosis stage and nonalcoholic steatohepatitis (NASH) scores were 1.3 ± 1.1 and 5.2 ± 1.6, respectively. NAFLD patients displayed decreased RV function compared to controls. NAFLD patients with liver fibrosis (67 patients) had significantly lower RV function assessed by GLS (global longitudinal strain) compared to patients without liver fibrosis (18.9 ± 3.4% vs. 21.6 ± 2.3%, P

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Functionality, comorbidities, polypharmacy, nutritional status and sarcopenia affect the prognosis of elderly excessively. These parameters are influenced by the population, living settings and age. We aimed to study these parameters in Turkish community-dwelling male elderly. We studied 274 male elderly ≥60 years of age admitted to our Geriatrics outpatient clinics. Mean age was 74.4 ± 7.1 years; 47.4% of the subjects were ≥75 years, 24.1% were ≥80 years. Mean activities-of-daily-living (ADL) and instrumental ADL (IADL) scores were 9.4 and 11.1, respectively. Patients with at least one-dependence at ADL-IADL were 22.6%-47.2%, and more than half-dependence at ADL-IADL were 2.8%-17.9%, respectively. Mean number of comorbidities were 2.6. Most common diagnosis was hypertension with 65%; mean number of drugs were 4.5; 55.3% were using ≥4 chronic drugs. Prevalences of malnutrition were 3.7%-6.9%, malnutrition risk were 23.5%-26.7% by the mini nutritional assessment test-long form and short form, respectively. Calf circumference was measured31 cm in 10.5%. Our findings suggest that Turkish community-dwelling male elderly may have greater prevalences of functional dependence, sarcopenia but lower rates of malnutrition and similar rates of polypharmacy compared with the western developing countries and developed countries. This study emphasized the geographical differences in and/or between the individual countries highlighting the need for studies both country- and world-wide.