Combined Experimental and Numerical Modelling of the Electrical Behaviour of Laser-Soldered Steel Sheets.

The electric vehicle (EV) industry challenges battery joining technologies by requiring higher energy density both by mass and volume. Improving the energy density via new battery chemistry would be the holy grail but is seriously hindered and progresses slowly. In the meantime, alternative ways, such as implementing more efficient cell packaging by minimising the electrical resistance of joints, are of primary focus. In this paper, we discuss the challenges associated with the electrical characterisation of laser-soldered joints in general, and the minimisation of their resistive losses, in particular. In order to assess the impact of joint resistance on the overall resistance of the sample, the alteration in resistance was monitored as a function of voltage probe distance and modelled by finite element simulation. The experimental measurements showed two different regimes: one far from the joint area and another in its vicinity and within the joint cross-section. The presented results confirm the importance of the thickness of the filler material, the effective and total soldered area, and the area and position of the voids within the total soldered area in determining the electrical resistance of joints.

Effect of using Austrian pine cones powder as an additive on oil well cement properties.

There have been many investigations to improve both the physical and mechanical properties of oil well cement using a wide range of materials. Most of these additives are expensive and practically ineffective. In this article, a comprehensive evaluation was conducted for using Austrian pinecones powder (APCP) as an inexpensive supplementary cementing material (SCM) for well cement. Firstly, Portland cement class G was characterized based on X-Ray Fluorescence (XRF), X-Ray Diffraction (XRD). In this paper, the properties of the cement systems include rheological parameters, density, slurry stability (free water test, and sedimentation test), water absorption, porosity, permeability, the volume of fluid loss, pH value, thermogravimetric analysis, and the mechanical characteristics (in terms of compressive strength, tensile strength, flexural strength, and shear strength bond) were investigated in details. The cement sample containing the APCP was also examined using scanning electron microscopy (SEM). According to the experimental results, adding APCP led to increasing in rheological parameters. Also, led to decreasing in fluid loss, free water, sedimentation effect, and density which positively affects the preservation of the original properties of cement slurry. The results also showed a decrease in the permeability of cement samples and an increase in the porosity and the ability to absorb water. The addition of APCP did not significantly affect the pH values. The addition of APCP also deteriorated the mechanical properties of the cement samples. The addition of the APCP has contributed to an increase in total weight loss at high temperatures. So, the APCP can be considered as a new filler for well cement due to its ability to fill the pores in the cement matrix and at the same time improve some properties of the well cement such as density, free water, sedimentation, and fluid loss.

Hepatitis C Screening and Treatment Program in Hungarian Prisons in the Era of Direct Acting Antiviral Agents.

A hepatitis C virus (HCV) screening and treatment program was conducted in Hungarian prisons on a voluntary basis. After HCV-RNA testing and genotyping for anti-HCV positives, treatments with direct-acting antiviral agents were commenced by hepatologists who visited the institutions monthly. Patients were supervised by the prisons' medical staff. Data were retrospectively collected from the Hungarian Hepatitis Treatment Registry, from the Health Registry of Prisons, and from participating hepatologists. Eighty-four percent of Hungarian prisons participated, meaning a total of 5779 individuals (28% of the inmate population) underwent screening. HCV-RNA positivity was confirmed in 317/5779 cases (5.49%); 261/317 (82.3%) started treatment. Ninety-nine percent of them admitted previous intravenous drug use. So far, 220 patients received full treatment and 41 patients are still on treatment. Based on the available end of treatment (EOT) + 24 weeks timepoint data, per protocol sustained virologic response rate was 96.8%. In conclusion, the Hungarian prison screening and treatment program, with the active participation of hepatologists and the prisons' medical staff, is a well-functioning model. Through the Hungarian experience, we emphasize that the "test-and-treat" principle is feasible and effective at micro-eliminating HCV in prisons, where infection rate, as well as history of intravenous drug usage, are high.

Onset Symptom Clusters in Multiple Sclerosis: Characteristics, Comorbidities, and Risk Factors.

Background: Multiple sclerosis (MS) symptoms are expected to aggregate in specific patterns across different stages of the disease. Here, we studied the clustering of onset symptoms and examined their characteristics, comorbidity patterns and associations with potential risk factors. Methods: Data stem from the Swiss Multiple Sclerosis Registry, a prospective study including 2,063 participants by November 2019. MS onset symptoms were clustered using latent class analysis (LCA). The latent classes were further examined using information on socio-demographic characteristics, MS-related features, potential risk factors, and comorbid diseases. Results: The LCA model with six classes (frequencies ranging from 12 to 24%) was selected for further analyses. The latent classes comprised a multiple symptoms class with high probabilities across several symptoms, contrasting with two classes with solitary onset symptoms: vision problems and paresthesia. Two gait classes emerged between these extremes: the gait-balance class and the gait-paralysis class. The last class was the fatigue-weakness-class, also accompanied by depression symptoms, memory, and gastro-intestinal problems. There was a moderate variation by sex and by MS types. The multiple symptoms class yielded increased comorbidity with other autoimmune disorders. Similar to the fatigue-weakness class, the multiple symptoms class showed associations with angina, skin diseases, migraine, and lifetime prevalence of smoking. Mononucleosis was more frequently reported in the fatigue-weakness and the paresthesia class. Familial aggregation did not differ among the classes. Conclusions: Clustering of MS onset symptoms provides new perspectives on the heterogeneity of MS. The clusters comprise different potential risk factors and comorbidities. They point toward different risk mechanisms.

Alterations of Nigral Dopamine Levels in Parkinson's Disease after Environmental Enrichment and PACAP Treatment in Aging Rats.

The neuroprotective effects of environmental enrichment and PACAP (pituitary adenylate cyclase-activating polypeptide) are well-described in Parkinson's disease. The aim of our study is to investigate the beneficial effects of these factors in aging parkinsonian rats. Newborn Wistar rats were divided into standard and enriched groups according to their environmental conditions. Standard animals were raised under regular conditions. During the first five postnatal weeks, enriched pups were placed in larger cages with different objects. Aging animals received (1) saline, (2) 6-hydroxidopamine (6-OHDA), or (3) 6-OHDA + PACAP injections into the left substantia nigra (s.n.). On the seventh postoperative day, the left and right s.n. were collected. The s.n. of young and aging unoperated animals were also examined in our experiment. We determined the dopamine (DA) levels by the HPLC-MS technique, while the sandwich ELISA method was used to measure the Parkinson disease protein 7 (PARK7) protein levels. In healthy animals, we found an age-related decrease of DA levels. In aging parkinsonian-enriched rats, the operation did not result in a significant DA loss. PACAP treatment could prevent the DA loss in both the standard and enriched groups. All injured PACAP-treated rats showed remarkably higher protective PARK7 levels. The protective effect of PACAP correlated with the increase of the DA and PARK7 levels.

Macrophage frequency in the bone marrow correlates with morphologic subtype of myeloproliferative neoplasm.

Bone marrow (BM) fibrosis in myeloproliferative neoplasms (MPNs) is associated with a poor prognosis. The development of myelofibrosis and differentiation of mesenchymal stromal cells to profibrotic myofibroblasts depends on macrophages. Here, we compared macrophage frequencies in BM biopsies of MPN patients and controls (patients with non-neoplastic processes), including primary myelofibrosis (PMF, n = 18), essential thrombocythemia (ET, n = 14), polycythemia vera (PV, n = 12), and Philadelphia chromosome-positive chronic myeloid leukemia (CML, n = 9). In PMF, CD68-positive macrophages were greatly increased compared to CML (p = 0.017) and control BM (p < 0.001). Similar findings were observed by CD163 staining (PMF vs. CML: p = 0.017; PMF vs. control: p < 0.001). Moreover, CD68-positive macrophages were increased in PV compared with ET (p = 0.009) and reactive cases (p < 0.001). PMF had higher frequencies of macrophages than PV (CD68: p < 0.001; CD163: p < 0.001) and ET (CD68: p < 0.001; CD163: p < 0.001). CD163 and CD68 were often co-expressed in macrophages with stellate morphology in Philadelphia chromosome-negative MPN, resulting in a sponge-like reticular network that may be a key regulator of unbalanced hematopoiesis in the BM space and may explain differences in cellularity and clinical course.

Real-life efficacy of vedolizumab on endoscopic healing in inflammatory bowel disease - A nationwide Hungarian cohort study.

Background: GEMINI trials demonstrated the therapeutic efficacy of vedolizumab (VDZ) in Crohn's disease (CD) and ulcerative colitis (UC).Research design and methods: Aim of this study was to determine the real-life effectiveness of VDZ on endoscopic healing in the Hungarian nationwide cohort of inflammatory bowel disease (IBD) patients based on the changes on clinical and endoscopic scores. Every adult IBD patient in the country (121 UC and 83 CD) who completed the short-term VDZ therapy was enrolled, of which 72 UC and 52 CD patients could complete the long-term therapy.Results: The rates of endoscopic healing were substantially higher in UC compared with CD patients during the short- and long-term therapy (52.9% vs. 21.7%, p < 0.0001, and 51.4% vs. 21.2%, p = 0.015, respectively). In CD, the rate of endoscopic healing was lower at week 14 compared with week 22 (14.5% vs. 37.0%, p = 0.026). Prior anti-TNF-α therapy (88.73%) was not associated with a significant decrease in therapeutic response. The average disease duration was significantly lower in CD patients achieving endoscopic healing at week 52 (11.75 vs. 5.27 years, p = 0.007).Conclusions: VDZ therapy is an effective therapeutic option in anti-TNF-α refractory IBD. However, the endoscopic healing rate was substantially lower and showed a significant delay in CD compared with UC.

E2FA and E2FB transcription factors coordinate cell proliferation with seed maturation.

The E2F transcription factors and the RETINOBLASTOMA-RELATED repressor protein are principal regulators coordinating cell proliferation with differentiation, but their role during seed development is little understood. We show that in fully developed Arabidopsis thaliana embryos, cell number was not affected either in single or double mutants for the activator-type E2FA and E2FB Accordingly, these E2Fs are only partially required for the expression of cell cycle genes. In contrast, the expression of key seed maturation genes LEAFY COTYLEDON 1/2 (LEC1/2), ABSCISIC ACID INSENSITIVE 3, FUSCA 3 and WRINKLED 1 is upregulated in the e2fab double mutant embryo. In accordance, E2FA directly regulates LEC2, and mutation at the consensus E2F-binding site in the LEC2 promoter de-represses its activity during the proliferative stage of seed development. In addition, the major seed storage reserve proteins, 12S globulin and 2S albumin, became prematurely accumulated at the proliferating phase of seed development in the e2fab double mutant. Our findings reveal a repressor function of the activator E2Fs to restrict the seed maturation programme until the cell proliferation phase is completed.

Worse lung cancer outcome in patients with lower respiratory tract infection confirmed at time of diagnosis.

BACKGROUND: Pulmonary malignancy is one of the most frequent and fatal cancers in older patients. As data on lower respiratory tract infection (LRTI) and the outcome of lung cancer are scarce, our objective was to determine the impact of LRTI on therapeutic possibilities and one-year mortality. METHODS: Patients undergoing bronchoscopy in 2017 who had bronchial microbial sampling at the time of the lung cancer diagnosis (n = 143) were included. Group 1 (LRTI+) included patients with confirmed infection (n = 74) while Group 2 (LRTI-) included patients without infection (n = 69). Clinical characteristics, pathogen profile and one-year survival were analyzed. RESULTS: Age, gender, TNM stage, histology type, comorbidities or underlying lung disease did not differ among groups. The most common LRTI pathogens included aerobic (n = 49), anaerobic (n = 14) and fungal (n = 26) infections. Chemo/immune/target therapy alone, or in combination with radiotherapy were significantly less frequently used, whilst palliative care was more common in Group 1 (LRTI+). Multiple pathogen LRTI patients were significantly older, less frequently diagnosed with adenocarcinoma and had worse performance status compared to solitary pathogen LRTI patients. One-year median survival was 274 days (235 vs. 305 days Group 1 vs. Group 2). Risk factors for increased one-year mortality included performance status ≥2 (OR 30.00, CI 95% 5.23-313.00), performance status 1 (OR 11.87, CI 95% 4.12-33.78), male gender (OR 4.04, CI 2.03-8.04), LRTI with multiple pathogens (OR 2.72, CI 1.01-6.81) and nonadenocarcinoma histology (OR 2.26, CI 1.15-4.56). CONCLUSION: LRTIs in lung cancer patients, especially multiple pathogen infections, are associated with less oncotherapeutic possibilities and significant risk for lower one-year median survival.

NLRP3 inflammasome-activating arginine-based liposomes promote antigen presentations in dendritic cells.

Purpose: The NLRP3 inflammasome activation has been proposed as a common mechanism for some adjuvants to boost the immune system, and cationic liposomes were reported to potentially activate the NLRP3 inflammasome. Herein, we questioned whether the NLRP3 inflammasome-activating cationic liposomes could promote antigen presentation and be applied as an immune adjuvant. In addition, we aimed to investigate the structure effect of lipid on triggering these immune responses. Materials and methods: A series of structurally similar lipids, consisting of arginine (Arg) head group and varied lengths of alkyl chains or spacers in between were used to prepare cationic liposomes. Lipopolysaccharide-primed human or murine macrophages or phorbol 12-myristate 13-acetate-primed THP-1 cells were treated with these liposomes, and interleukin (IL)-1ß secretion was measured to quantify the NLRP3 inflammasome activation. Lysosome rupture was examined in THP-1 cells by the fluorescence loss of acridine orange, a lysosome dye. Further, chicken ovalbumin (OVA) was loaded on the liposome surface and applied to murine bone marrow-derived dendritic cells (BMDCs), which activate OT-I and OT-II lymphocytes upon major histocompatibility complex (MHC) class I- and class II-mediated antigen presentation, respectively. OT-I and OT-II cell division and IL-2 secretion were measured to evaluate the antigen presentation efficiency. The expressions of MHC molecules and co-stimulatory molecules ie, CD80, CD86, and CD40 on BMDCs were investigated by flow cytometry. Results: All the liposomes showed size distributions of 80-200 nm and zeta potentials of around 50 mV. A3C14 liposomes, consisting of Arg-C3-Glu2C14 lipids induced the most potent lysosome rupture and NLRP3 inflammasome activation. OVA-A3C14 also exhibited the most potent MHC class I- and class II-mediated antigen presentation in BMDCs without interfering MHC and co-stimulatory molecules. Conclusion: The hydrophobic moieties of arginine-based liposomes are crucial in stimulating innate immune cells. A3C14 liposomes were non-immunogenic but strongly activated innate immune cells and promoted antigen presentation, and therefore can be applied as immune adjuvants.

[Modern management of otologic consequences of Wegener's granulomatosis - a case report and review of the literature]. / Wegener-granulomatosis talaján kialakult krónikus gennyes középfülgyulladás komplex kezelése.

Wegener's granulomatosis - or, in other words, granulomatosis with polyangiitis - is an anti-neutrophil cytoplasmic antibody associated granuloma forming vasculitis, mainly affecting the respiratory tract and the renal system. Otologic manifestations of Wegener's disease can be otitis media with effusion or chronic silent mastoiditis with conductive hearing loss, but sensorineural hearing loss can also evolve. The diagnosis is based on the clinical appearance as well as the immunoserological and histopathological results. It is of paramount importance to begin a combined immunosuppressive treatment immediately, besides eradicating the otologic manifestations. The intractable cases of chronic otitis media due to Wegener's granulomatosis are challenging any ear surgeons. Subtotal petrosectomy has proved to be an effective solution in such cases to create a dry ear and to provide a safe surgical field for hearing restoration. The authors reviewed the literature and report a case history to present the modern management of Wegener's granulomatosis with otologic manifestation. Orv Hetil. 2019; 160(4): 151-157.

Ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin in HCV genotype 1 infected patients who failed previous protease inhibitor therapy.

AIM OF THE STUDY: Combination of ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (3DDA±RBV) therapy is shown to be effective in HCV genotype 1 (GT1) infected patients. However, sparse data exist in patients who failed previous boceprevir or telaprevir based therapies. Real life efficacy and safety of this combination were evaluated in HCV GT1b infected patients (mostly cirrhotics) with compensated liver disease who failed previous boceprevir or telaprevir based therapies more than a year before. MATERIAL AND METHODS: Data of previous protease inhibitor failure patients, treated with 3DAA+RBV for 12 weeks (GT1b and/or non-cirrhotics) or 24 weeks (non-GT1b cirrhotics), were retrospectively collected. RESULTS: Population characteristics: boceprevir/telaprevir-failure: 82/45, GT1b: 117, cirrhotic: 111 (87.4%). SVR12/24 was observed in 103/105 patients (98.1%) of those who reached either time point. Four SAEs reported: one death due to myocardial infarction, another due to recurrent hepatocellular carcinoma after achieving SVR12, two hospitalizations (elevation of transaminases, pneumonia). Grade ≥ 3 AEs or laboratory abnormalities were reported in < 10% of patients; they were transient in all patients. No early discontinuation of drugs due to SAE has been reported. CONCLUSIONS: One year after previous failure of boceprevir or telaprevir based therapy, 12 weeks of 3DAA+RBV combination in HCV GT1b infected patients is similarly effective and safe as in those with no previous HCV therapy, even in the presence of cirrhosis. These findings might be of particular interest in settings where alternative therapies for such patients are not available or not affordable.

[Screening, diagnosis, treatment, and follow up of hepatitis C virus related liver disease. National consensus guideline in Hungary from 22 September 2017]. / A hepatitis C-vírus-fertozés szurése, diagnosztikája, antivirális terápiája, kezelés utáni gondozása. Magyar konszenzusajánlás. Érvényes: 2017. szeptember 22-tol.

The treatment of hepatitis C is based on a national consensus guideline updated six-monthly according to local availability and affordability of approved therapies through a transparent allocation system in Hungary. This updated guideline incorporates some special new aspects, including recommendations for screening, diagnostics, use and allocation of novel direct acting antiviral agents. The indication of therapy in patients with no contraindication is based on the demonstration of viral replication with consequent inflammation and/or fibrosis in the liver. Non-invasive methods (elastographies and biochemical methods) are preferred for liver fibrosis staging. The budget allocated for these patients is limited. Interferon-based or interferon-free therapies are available for the treatment. Due to their limited success rate as well as to their (sometimes severe) side-effects, the mandatory use of interferon-based therapies as first line treatment can not be accepted from the professional point of view. However, they can be used as optional therapy in treatment-naïve patients with mild disease. As of interferon-free therapies, priority is given to those with urgent need based on a pre-defined scoring system reflecting mainly the stage of the liver disease, but considering also additional factors, i.e., hepatic decompensation, other complications, activity and progression of liver disease, risk of transmission and other special issues. Approved treatments are restricted to the most cost-effective combinations based on the cost per sustained virological response value in different patient categories with consensus amongst treating physicians, the National Health Insurance Fund of Hungary and patients' organizations. Interferon-free treatments and shorter therapy durations are preferred. Orv Hetil. 2018; 159(Suppl 1): 3-23.

[Diagnosis and treatment of chronic hepatitis B and D. National consensus guideline in Hungary from 22 September 2017]. / A hepatitis B- és D-vírus-fertozés diagnosztikája, antivirális kezelése. Magyar konszenzusajánlás. Érvényes: 2017. szeptember 22-tol.

Diagnosis and treatment of hepatitis B virus (HBV) and hepatitis D virus infection mean for the patient to be able to maintain working capacity, to increase quality of life, to prevent cancer, and to prolong life expectancy, while the society benefits from eliminating the chances of further transmission of the viruses, and decreasing the overall costs of serious complications. The guideline delineates the treatment algorithms from 22 September 2017 set by a consensus meeting of physicians involved in the treatment of these diseases. The prevalence of HBV infection in the Hungarian general population is 0,5-0,7%. The indications of treatment are based upon viral examinations (including viral nucleic acid determination), determinations of disease activity and stage (including biochemical, pathologic, and/or non-invasive methods), and excluding contraindications. To avoid unnecessary side effects and for a cost-effective approach, the guideline stresses the importance of quick and detailed virologic evaluations, the applicability of transient elastography as an acceptable alternative of liver biopsy in this regard as well as the relevance of appropriate consistent follow-up schedule for viral response during therapy. The first choice of therapy in chronic HBV infection can be pegylated interferon for 48 weeks or continuous entecavir or tenofovir therapy. The latter two must be continued for at least 12 months after hepatitis B surface antigen seroconversion. Lamivudine is no longer the first choice; patients currently taking lamivudine must switch if the response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection. Orv Hetil. 2018; 159(Suppl 1): 24-37.

Lysine-containing cationic liposomes activate the NLRP3 inflammasome: Effect of a spacer between the head group and the hydrophobic moieties of the lipids.

Cationic lipids containing lysine head groups and ditetradecyl, dihexadecyl or dioctadecyl glutamate hydrophobic moieties with/without propyl, pentyl or heptyl spacers were applied for the preparation of cationic liposomes using a simple bath type-sonicator. The size distribution, zeta potential, cellular internalization, and cytotoxicity of the liposomes were characterized, and the innate immune stimulation, e.g., the NLRP3 inflammasome activation of human macrophages and THP-1 cells, was evaluated by the detection of IL-1ß release. Comparatively, L3C14 and L5C14 liposomes, made from the lipids bearing lysine head groups, ditetradecyl hydrophobic chains and propyl or pentyl spacers, respectively, were the most potent to activate the NLRP3 inflammasome. The possible mechanism includes endocytosis of the cationic liposomes and subsequent lysosome rupture without significant inducement of reactive oxygen species production. In summary, we first disclosed the structural effect of cationic liposomes on the NLRP3 inflammasome activation, which gives an insight into the application of nanoparticles for improved immune response.

[Screening, diagnosis, treatment, and follow up of hepatitis C virus related liver disease. National consensus guideline in Hungary from 15 October 2016]. / A hepatitis C-vírus-fertozés szurése, diagnosztikája, antivirális terápiája, kezelés utáni gondozása. Magyar konszenzusajánlás. Érvényes: 2016. október 15-tol.

Treatment of hepatitis C is based on a national consensus guideline updated six-monthly according to local availability and affordability of approved therapies through a transparent allocation system in Hungary. This updated guideline incorporates some special new aspects, including recommendations for screening, diagnostics, use and allocation of novel direct acting antiviral agents. Indication of therapy in patients with no contraindication is based on demonstration of viral replication with consequent inflammation and/or fibrosis in the liver. Non-invasive methods (elastographies and biochemical methods) are preferred for liver fibrosis staging. The budget allocated for these patients is limited. Therefore, expensive novel direct acting antiviral combinations as first line treatment are reimbursed only, if the freely available, but less effective and more toxic pegylated interferon plus ribavirin dual therapy deemed to prone high chance of adverse events and/or low chance of cure. Priority is given to those with urgent need based on a pre-defined scoring system reflecting mainly the stage of the liver disease, but considering also additional factors, i.e., hepatic decompensation, other complications, activity and progression of liver disease, risk of transmission and other special issues. Approved treatments are restricted to the most cost-effective combinations based on the cost per sustained virological response value in different patient categories with consensus amongst treating physicians, the National Health Insurance Fund and patient's organizations. Interferon-free treatments and shorter therapy durations are preferred. Orv. Hetil., 2017, 158(Suppl. 1), 3-22.

[Diagnosis and treatment of chronic hepatitis B and D. National consensus guideline in Hungary from 15 October 2016]. / A hepatitis B- és D-vírus-fertozés diagnosztikája, antivirális kezelése. Magyar konszenzusajánlás. Érvényes: 2016. október 15-tol.

Diagnosis and treatment of HBV/HDV infection means for the patient to be able to maintain working capacity, to increase quality of life, to prevent cancer, and to prolong life expectancy, while society benefits from eliminating the chances of further transmission of the viruses, and decreasing the overall costs of serious complications. The guideline delineates the treatment algorithms for 2017 set by a consensus meeting of physicians involved in the treatment of these diseases. The prevalence of HBV infection in the Hungarian general population is 0.5-0.7%. The indications of treatment is based upon viral examinations (including viral nucleic acid determination), determinations of disease activity and stage (including biochemical, pathologic, and/or non-invasive methods), and excluding contraindications. To avoid unnecessary side effects and for cost-effective approach the guideline stresses the importance of quick and detailed virologic evaluations, the applicability of elastography as an acceptable alternative of liver biopsy in this regard, as well as the relevance of appropriate consistent follow up schedule for viral response during therapy. The first choice of therapy in chronic hepatitis B infection can be pegylated interferon for 48 weeks or continuous entecavir or tenofovir therapy. The latter two must be continued for at least 12 months after hepatitis B surface antigen seroconversion. Adefovir dipivoxil is recommended mainly in combination therapy. Lamivudine is no longer a first choice; patients currently taking lamivudine must switch if response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection. Orv. Hetil., 2017, 158(Suppl. 1) 23-35.

Detection of Changes in the Medicago sativa Retinoblastoma-Related Protein (MsRBR1) Phosphorylation During Cell Cycle Progression in Synchronized Cell Suspension Culture.

Deepening our knowledge on the regulation of the plant cell division cycle depends on techniques that allow for the enrichment of cell populations in defined cell cycle phases. Synchronization of cell division can be achieved using different plant tissues; however, well-established cell suspension cultures provide large amount of biological sample for further analyses. Here, we describe the methodology of the establishment, propagation, and analysis of a Medicago sativa suspension culture that can be used for efficient synchronization of the cell division. A novel 5-ethynyl-2'-deoxyuridine (EdU)-based method is used for the estimation of cell fraction that enters DNA synthesis phase of the cell cycle and we also demonstrate the changes in the phosphorylation level of Medicago sativa retinoblastoma-related protein (MsRBR1) during cell cycle progression.

[Efficacy and safety of boceprevir based triple therapy in Hungarian patients with hepatitis C genotype 1 infection, advanced stage fibrosis and prior treatment failure]. / Bocepreviralapú hármas kezelés hatékonyságának és biztonságosságának retrospektív elemzése elorehaladott fibrosisstádiumú, hepatitis C-vírus 1-es genotípussal fertozött, korábban sikertelenül kezelt magyar betegeknél.

INTRODUCTION: During 2011 and 2013, 155 Hungarian hepatitis C genotype 1 infected patients, mostly with advanced liver fibrosis, who did not respond to prior peginterferon + ribavirin dual therapy, started boceprevir based triple therapy in an early access program. AIM AND METHOD: Efficacy and safety of the therapy was retrospectively assessed based on sustained virologic responses, as well as on frequency and type of serious adverse events and of those leading to therapy discontinuation. RESULTS: In an intent-to-treat analysis 39.4% patients (61/155) reached sustained virologic response. Amongst pervious relapsers, partial responders and null-responders 59.5%, 41.4 % and 22.9% (p<0.05 compared to the other two categories) reached sustained virologic response, respectively, while amongst non-cirrhotics and cirrhotics 52.5% and 31.3% (p<0.05 compared to the non-cirrhotics) achieved sutained virologic response, respectively. Six out of the 33 most difficult to cure patients (previous null responder and cirrhotic) have reached sustained virologic response (18.2%). Frequency of early discontinuations due to insufficient virologic response was 31.1%, while due to adverse event 10.3%. Reported frequency of serious adverse event was 9.8%. These events represented anemia, diarrhoea, depression, agranulocytosis, elevated aminotransferases, generalized dermatitis and severe gingivitis with loss of teeth, prolonged QT interval on ECG, generalized oedema and severe dyspnoea, uroinfection, exacerbation of Crohn's disease, Campylobacter pylori infection and unacceptable weakness and fatigue. Eight patients received transfusion, 4 patients erythropoietin and 1 granulocyte colony stimulating factor during therapy. No death has been reported. CONCLUSIONS: With boceprevir based triple therapy, one of the bests available in 2011-2013 in Hungary, a relevant proportion of hepatitis C infected patients with advanced liver fibrosis achieved sustained viral response. In this cohort, side-effects resembled those reported in registration studies, and resulted in therapy discontinuation with consequent treatment failure in a relevant number of patients. Efficacy and tolerability of boceprevir-based triple therapy are suboptimal, particularly in the most difficult to cure patient population. Orv. Hetil., 2016, 157(34), 1366-1374.

Evaluation of hepatic fibrosis - access to non-invasive methods, national practice/guidelines in Central Europe.

Noninvasive methods have improved diagnostic tools of liver fibrosis. Although liver biopsy is the gold standard for diagnosis of hepatis fibrosis, the noninvasive tests are usually much less expensive than liver biopsy, better tolerated, and can be repeated without any risk for the patient. Two groups of these noninvasive tests are included in clinical practice: serum biomarkers and elastography. In our paper we summarize noninvasive diagnostic options for liver fibrosis in the Czech Republic, Hungary, Poland and Slovakia. Noninvasive diagnostic methods, especially elastography, are widely accessible in all countries.