Current and future treatment options in non-alcoholic steatohepatitis (NASH)

INTRODUCTION: Non-alcoholic steatohepatitis (NASH) is a chronic liver disease that can progress to cirrhosis and hepatocellular carcinoma. Diagnosis of NASH requires a liver biopsy and is defined as presence of hepatic steatosis, ballooning and lobular inflammation with or without fibrosis. Although NASH is the most common cause of liver disease in the west world and among the top three indications for liver transplantation, there are no universally accepted pharmacological therapies and therapeutic advances have been slow. AREAS COVERED: Current evidence about lifestyle interventions, bariatric surgery and pharmacotherapy is reviewed. Dietary recommendations and lifestyle interventions have shown promising results but are difficult to maintain. At the moment, there is no universally approved medical treatment for NASH. Pioglitazone and vitamin E are recommended by guidelines in selected patients. An increasing number of phase II and III trials in non-cirrhotic NASH are currently recruiting and their preliminary results discussed. EXPERT COMMENTARY: As NASH is classified as a medical condition of an unmet therapeutic need, it has gained an accelerated access pathway for drug approval based on surrogate endpoints. It is therefore expected that within the next five years, there will be at least one approved agent for the pharmacological treatment of pre-cirrhotic NASH

Investigation of the styloid process length in a Greek population

Background: The styloid process (SP) is a slender cylindrical bony projection of the temporal bone with 2 ligaments and 3 muscles attached to it. Symptomatic SP elongation is also referred to, as Eagle’s syndrome. The aim of the present study is to investigate the distribution of the SP length in a young adult Greek population.  Materials and methods: Moreover, we provide a comparison of the results by using two different methods for assessing SP elongation, as described in the lite- rature. Finally, we explore the possibility of using orthopantomograms (OPGs), as a diagnostic aid by investigating inter-examiner, intra-examiner and inter-exami- nation variability and we propose a limit for SP elongation measurable in OPGs.  Results: The sample comprised 805 digital OPGs, taken from student pilots and engineers entering the Hellenic Air Force Academy, from 2008 onwards. Two measuring approaches were selected, one using the temporal bone, as a cranial landmark and the other, using the external auditory meatus. The end tip of the process was always the caudal landmark. The mean SP length was 28.42 ± ± 8.48 mm in males and 26.04 ± 7.69 mm in females, when measured from the temporal bone. The mean SP length was 38.35 ± 8.90 mm in males and 34.24 ± ± 8.63 mm in females, when measured from the external auditory meatus. The length of 30 mm is most commonly used as a starting point for SP elongation. In the total sample, 30.6% of the measured SPs exceeded the length of 30 mm. In males, 33.12% of the SPs were elongated; while in females the corresponding incidence was 20%. One hundred and nineteen (14.8%) SPs were not traceable.  Conclusions: The SP is typically detectable and measurable in OPGs. An elonga- ted SP should be kept in mind, since symptoms of elongation may overlap with clinical manifestations of temporomandibular joint disorders.

Abdominoperineal Resection for Rectal Cancer: Is the Pelvic Drain Externalization Site an Independent Risk Factor for Perineal Wound Healing?

Aim. The aim of this paper is to investigate if the insertion of the pelvic drainage tube via the perineal wound could be considered as an independent risk factor for perineal healing disorders, after abdominoperineal resection for rectal malignancy. Patients and Methods. The last two decades, 75 patients underwent elective abdominoperineal resection for malignancy. In 42 patients (56%), the pelvic drain catheter was inserted through the perineal wound (PW group), while in the remaining 33 (44%) through a puncture skin wound of the perineum (SW group). Patients' data with respect to age (P = 0.136), stage (P > 0.05), sex (P = 0.188) and comorbidity (P = 0.128) were similar in both groups. 25 patients (PW versus SW: 8 versus 17, P = 0.0026) underwent neoadjuvant radio/chemotherapy. Results. The overall morbidity rate was 36%, but a significant increase was revealed in PW group (52.4% versus 9%, P = 0.0007). In 33.3% of the patients in the PW group, perineal healing was delayed, while in the SW group, no delay was noted. Perineal healing disorders were revealed as the main source of increased morbidity in this group. Conclusion. The insertion of the pelvic drain tube through the perineal wound should be considered as an independent risk factor predisposing to perineal healing disorders

Common denominators in the immunobiology of IgG4 autoimmune diseases: What do glomerulonephritis, pemphigus vulgaris, myasthenia gravis, thrombotic thrombocytopenic purpura and autoimmune encephalitis have in common?

IgG4 autoimmune diseases (IgG4-AID) are an emerging group of autoimmune diseases that are caused by pathogenic autoantibodies of the IgG4 subclass. It has only recently been appreciated, that members of this group share relevant immunobiological and therapeutic aspects even though different antigens, tissues and organs are affected: glomerulonephritis (kidney), pemphigus vulgaris (skin), thrombotic thrombocytopenic purpura (hematologic system) muscle-specific kinase (MuSK) in myasthenia gravis (peripheral nervous system) and autoimmune encephalitis (central nervous system) to give some examples. In all these diseases, patients’ IgG4 subclass autoantibodies block protein-protein interactions instead of causing complement mediated tissue injury, patients respond favorably to rituximab and share a genetic predisposition: at least five HLA class II genes have been reported in individual studies to be associated with several different IgG4-AID. This suggests a role for the HLA class II region and specifically the DRβ1 chain for aberrant priming of autoreactive T-cells toward a chronic immune response skewed toward the production of IgG4 subclass autoantibodies. The aim of this review is to provide an update on findings arguing for a common pathogenic mechanism in IgG4-AID in general and to provide hypotheses about the role of distinct HLA haplotypes, T-cells and cytokines in IgG4-AID

GEOCHEMICAL INVESTIGATION OF AQUIFER POLLUTION FROM WASTE MANAGEMENT. THE CASE OF KOMOTINI LANDFILL (GREECE)

According to European legislation, environmental control and monitoring of landfills has become of crucial importance. This study includes a thorough geochemical approach aiming to evaluate the environmental impact of the landfill of Komotini, N. Greece. Samples of waters were taken from inside the working landfill as well as from the area of the neighbouring old landfill. The waters were analyzed chemically (major elements and heavy metals) and isotopically (D and 18O). Also, biogas flow was measured and the ratio CH4/CO2. Based on the geomorphological, hydrogeological and land use data of the area, we proceeded to analyses of waters both from the area of the landfill and from the wider region (drainage basin). The obtained results were used to construct digital maps (GIS) in order to determine the special dispersion of the polluted aquifers. The biogas flow in the old and new garbage burial sites was measured by accumulation chamber device for methane and carbon dioxide ratio determination. The obtained results show an important agent of pollution in the water samples downstream from the landfill and in a distance more than 2km, along the dispersion of the leachate. The land use of the area was taken into account to evaluate the importance and the criticality of the situation

Isomorphs in model molecular liquids

Isomorphs are curves in the phase diagram along which a number of static and dynamic quantities are invariant in reduced units. A liquid has good isomorphs if and only if it is strongly correlating, i.e., the equilibrium virial/potential energy fluctuations are more than 90% correlated in the NVT ensemble. This paper generalizes isomorphs to liquids composed of rigid molecules and study the isomorphs of two systems of small rigid molecules, the asymmetric dumbbell model and the Lewis-Wahnstrom OTP model. In particular, for both systems we find that the isochoric heat capacity, the excess entropy, the reduced molecular center-of-mass self part of the intermediate scattering function, the reduced molecular center-of-mass radial distribution function to a good approximation are invariant along an isomorph. In agreement with theory, we also find that an instantaneous change of temperature and density from an equilibrated state point to another isomorphic state point leads to no relaxation. The isomorphs of the Lewis-Wahnstrom OTP model were found to be more approximative than those of the asymmetric dumbbell model, which is consistent with the OTP model being less strongly correlating. For both models we find "master isomorphs", i.e., isomorphs have identical shape in the virial/potential energy phase diagram.Comment: 20 page

Diagnostic Potential of Free-Space Radiometric Partial Discharge Measurements

The work reported in this paper addresses the calibration of four types of partial discharge (PD) emulator required for the development of a PD Wireless Sensor Network (WSN). Three partial discharge (PD) emulators have been constructed: a floating-electrode emulator, and two internal PD emulators. Both DC and AC HV power supplies are used to initiate PD which is measured using concurrent free-space radiometry (FSR) and a galvanic contact method based on the IEC 60270 standard. A new method of estimating absolute PD activity level from a radiometric measurement is proposed

Protein structures and optimal folding emerging from a geometrical variational principle

Novel numerical techniques, validated by an analysis of barnase and chymotrypsin inhibitor, are used to elucidate the paramount role played by the geometry of the protein backbone in steering the folding to the correct native state. It is found that, irrespective of the sequence, the native state of a protein has exceedingly large number of conformations with a given amount of structural overlap compared to other compact artificial backbones; moreover the conformational entropies of unrelated proteins of the same length are nearly equal at any given stage of folding. These results are suggestive of an extremality principle underlying protein evolution, which, in turn, is shown to be associated with the emergence of secondary structures.Comment: Revtex, 5 pages, 5 postscript figure