Origin Of The Far Off-Axis GRB171205A

We show that observed properties of the low luminosity GRB171205A and its afterglow, like those of most other low-luminosity (LL) gamma ray bursts (GRBs) associate with a supernova (SN), indicate that it is an ordinary SN-GRB, which was produced by inverse Compton scattering of glory light by a highly relativistic narrowly collimated jet ejected in a supernova explosion and viewed from a far off-axis angle. As such, VLA/VLBI follow-up radio observations of a superluminal displacement of its bright radio afterglow from its parent supernova, will be able to test clearly whether it is an ordinary SN-GRB viewed from far off-axis or it belongs to a distinct class of GRBs, which are different from ordinary GRBs, and cannot be explained by standard fireball models of GRBs as ordinary GRBsComment: 5 pages, 6 figures, updated data in Fig. 3, Corrected GRB angular distance used in Fig.

Новое в развитии пластической хирургии носа

Рассмотрены проблемы, возникающие при реконструктивных вмешательствах на структурах наружного носа и его внутренних полостях, характеристики трансплантатов и условия, способствующие возникновению осложнений. На основании собственных наблюдений сделан вывод о практической целесообразности использования гомо− и гетеротрансплантатов с учетом конкретных медико−социальных показаний.The problems arising at reconstructive surgery on the external structures of the nose and its inner cavities as well as characteristics of the implants and the conditions promoting complication development are featured. Basing on the original research the authors conclude about practical expediency of application of homo− and heterotransplants with the account of definite medical−social parameters

Adherence to nucleos(t)ide analogue therapies for chronic Hepatitis B infection: A systematic review and meta-analysis

Successful treatment outcomes for chronic hepatitis B virus (HBV) infection requires high levels of adherence to treatment. We searched three databases and abstracts from two conferences up to January 2018 for studies reporting the proportion of patients who were adherent to HBV antiviral therapy and pooled data using random effects meta‐analysis. We included 30 studies, providing data for 23,823 patients. Overall, adherence to treatment was 74.6% (95% confidence interval [CI] 67.1%‐82.1%). Adherence was similar in high‐income settings (75.1%; 95% CI, 65.4%‐85.0%) and in low‐income and middle‐income settings (72.9%; 95% CI, 57.8%‐88.0%). Reported barriers to adherence included forgetting, limited understanding of the importance of adherence, and change to routine. Conclusion: There is a need to reinforce assessment and reporting of adherence as a routine part of HBV care and to assess the extent to which evidence‐based interventions to improve adherence to medication for human immunodeficiency virus [HIV] and other chronic diseases are effective for HBV infection

A lower global lung ultrasound score is associated with higher likelihood of successful extubation in invasively ventilated COVID-19 patients

Lung ultrasound (LUS) can be used to assess loss of aeration, which is associated with outcome in patients with coronavirus disease 2019 (COVID-19) presenting to the emergency department. We hypothesized that LUS scores are associated with outcome in critically ill COVID-19 patients receiving invasive ventilation. This retrospective international multicenter study evaluated patients with COVID-19-related acute respiratory distress syndrome (ARDS) with at least one LUS study within 5 days after invasive mechanical ventilation initiation. The global LUS score was calculated by summing the 12 regional scores (range 0-36). Pleural line abnormalities and subpleural consolidations were also scored. The outcomes were successful liberation from the ventilator and intensive care mortality within 28 days, analyzed with multistate, competing risk proportional hazard models. One hundred thirty-seven patients with COVID-19-related ARDS were included in our study. The global LUS score was associated with successful liberation from mechanical ventilation (hazard ratio [HR]: 0.91 95% confidence interval [CI] 0.87-0.96; P = 0.0007) independently of the ARDS severity, but not with 28 days mortality (HR: 1.03; 95% CI 0.97-1.08; P = 0.36). Subpleural consolidation and pleural line abnormalities did not add to the prognostic value of the global LUS score. Examinations within 24 hours of intubation showed no prognostic value. To conclude, a lower global LUS score 24 hours after invasive ventilation initiation is associated with increased probability of liberation from the mechanical ventilator COVID-19 ARDS patients, independently of the ARDS severity.Pathogenesis and treatment of chronic pulmonary disease

Keratan sulphate in the tumour environment

Keratan sulphate (KS) is a bioactive glycosaminoglycan (GAG) of some complexity composed of the repeat disaccharide D-galactose β1→4 glycosidically linked to N-acetyl glucosamine. During the biosynthesis of KS, a family of glycosyltransferase and sulphotransferase enzymes act sequentially and in a coordinated fashion to add D-galactose (D-Gal) then N-acetyl glucosamine (GlcNAc) to a GlcNAc acceptor residue at the reducing terminus of a nascent KS chain to effect chain elongation. D-Gal and GlcNAc can both undergo sulphation at C6 but this occurs more frequently on GlcNAc than D-Gal. Sulphation along the developing KS chain is not uniform and contains regions of variable length where no sulphation occurs, regions which are monosulphated mainly on GlcNAc and further regions of high sulphation where both of the repeat disaccharides are sulphated. Each of these respective regions in the KS chain can be of variable length leading to KS complexity in terms of chain length and charge localization along the KS chain. Like other GAGs, it is these variably sulphated regions in KS which define its interactive properties with ligands such as growth factors, morphogens and cytokines and which determine the functional properties of tissues containing KS. Further adding to KS complexity is the identification of three different linkage structures in KS to asparagine (N-linked) or to threonine or serine residues (O-linked) in proteoglycan core proteins which has allowed the categorization of KS into three types, namely KS-I (corneal KS, N-linked), KS-II (skeletal KS, O-linked) or KS-III (brain KS, O-linked). KS-I to -III are also subject to variable addition of L-fucose and sialic acid groups. Furthermore, the GlcNAc residues of some members of the mucin-like glycoprotein family can also act as acceptor molecules for the addition of D-Gal and GlcNAc residues which can also be sulphated leading to small low sulphation glycoforms of KS. These differ from the more heavily sulphated KS chains found on proteoglycans. Like other GAGs, KS has evolved molecular recognition and information transfer properties over hundreds of millions of years of vertebrate and invertebrate evolution which equips them with cell mediatory properties in normal cellular processes and in aberrant pathological situations such as in tumourogenesis. Two KS-proteoglycans in particular, podocalyxin and lumican, are cell membrane, intracellular or stromal tissue–associated components with roles in the promotion or regulation of tumour development, mucin-like KS glycoproteins may also contribute to tumourogenesis. A greater understanding of the biology of KS may allow better methodology to be developed to more effectively combat tumourogenic processes

Viral hepatitis B and C related outcomes: Unraveling the impact of HIV coinfection and treatment compliance

In chapter 2 and 3 hepatitis C virus (HCV) NS3 amino acids 1-181 were sequenced by the Sanger method and analyzed for resistance associated substitutions (RASs). RASs and their distribution between HCV genotype 1a clade I and II viruses were compared between HIV-infected versus HIV-uninfected patients. We found that prevalence of clade I viruses and Q80K was significantly higher in HCV genotype 1a infected patients with HIV coinfection than in those without HIV coinfection. We found that Q80K is a highly stable and transmissible RAS and was present in a large part of Dutch HIV-coinfected men-who-have-sex-with men. The introduction and expansion of Q80K variants in this key population suggests a founder effect. Prevalence of N174 and S122 RASs was significantly higher in clade II than clade I viruses. In chapter 4 and 5 data were compared between HIV/hepatitis B virus (HBV) coinfected patients in the Dutch HIV Monitoring database and HBV mono-infected patients from two medical centers. We found that HIV/HBV coinfected patients no longer seem to be at increased risk for progression to end-stage liver disease (portal hypertension, decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, and liver-related mortality) compared to HBV mono-infected patients, likely due to widespread use of highly effective cART with dual HBV and HIV activity. Moreover, we found that HIV/HBV coinfected patients have a similar incidence of HBsAg seroconversion, but a decreased incidence of HBeAg seroconversion compared to their HBV mono-infected counterparts. Lastly, HBV mono-infected patients had a higher prevalence of advanced fibrosis at their first presentation compared to their HIV coinfected counterparts. In chapter 6 a systematic review was conducted to give an overview of studies exploring adherence to combination treatment (PEG-interferon plus ribavirin) for HCV and nucleos(t)ide analogues for HBV. We found that non-adherence to treatment in chronic viral hepatitis is not a frequent phenomenon. In chapter 7 we investigated the effect of real-time medication monitoring on adherence to ribavirin in a randomized controlled trial during 24 weeks PEG-interferon/ribavirin±boceprevir or telaprevir. We found that adherence to ribavirin is high and that real-time medication monitoring did not influence this. In chapter 8 we assessed the association between ribavirin steady-state plasma levels and sustained virological response (SVR) in HCV infected patients treated with direct-acting antivirals (DAAs) plus RBV. 85% of these patients had one or more difficult-to-cure characteristics (i.e. treatment-experienced, HCV genotype 3, cirrhosis). We found that higher RBV steady-state plasma level was an independent predictor of SVR. In chapter 9 we provided 100 hepatitis B patients with a medication dispenser that monitored entecavir intake during 16 weeks therapy in a prospective study. We found that 70% of chronic hepatitis B patients exhibited good adherence to entecavir. Lastly, in chapter 10, data from all HBV-infected patients in a Dutch center were reviewed for outpatient loss to follow up. A total of 47% had ever been lost to follow-up. Main reasons for outpatient compliance and loss to follow-up were doctor’s advice and physicians presuming inactive disease respectively. In a questionnaire, the patients also affirmed to have relatively little insight into what the disease entailed. Thus, properly educating patients might increase understanding of the disease, help increase compliance, and improve treatment outcomes

Viral hepatitis B and C related outcomes: Unraveling the impact of HIV coinfection and treatment compliance

In chapter 2 and 3 hepatitis C virus (HCV) NS3 amino acids 1-181 were sequenced by the Sanger method and analyzed for resistance associated substitutions (RASs). RASs and their distribution between HCV genotype 1a clade I and II viruses were compared between HIV-infected versus HIV-uninfected patients. We found that prevalence of clade I viruses and Q80K was significantly higher in HCV genotype 1a infected patients with HIV coinfection than in those without HIV coinfection. We found that Q80K is a highly stable and transmissible RAS and was present in a large part of Dutch HIV-coinfected men-who-have-sex-with men. The introduction and expansion of Q80K variants in this key population suggests a founder effect. Prevalence of N174 and S122 RASs was significantly higher in clade II than clade I viruses. In chapter 4 and 5 data were compared between HIV/hepatitis B virus (HBV) coinfected patients in the Dutch HIV Monitoring database and HBV mono-infected patients from two medical centers. We found that HIV/HBV coinfected patients no longer seem to be at increased risk for progression to end-stage liver disease (portal hypertension, decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, and liver-related mortality) compared to HBV mono-infected patients, likely due to widespread use of highly effective cART with dual HBV and HIV activity. Moreover, we found that HIV/HBV coinfected patients have a similar incidence of HBsAg seroconversion, but a decreased incidence of HBeAg seroconversion compared to their HBV mono-infected counterparts. Lastly, HBV mono-infected patients had a higher prevalence of advanced fibrosis at their first presentation compared to their HIV coinfected counterparts. In chapter 6 a systematic review was conducted to give an overview of studies exploring adherence to combination treatment (PEG-interferon plus ribavirin) for HCV and nucleos(t)ide analogues for HBV. We found that non-adherence to treatment in chronic viral hepatitis is not a frequent phenomenon. In chapter 7 we investigated the effect of real-time medication monitoring on adherence to ribavirin in a randomized controlled trial during 24 weeks PEG-interferon/ribavirin±boceprevir or telaprevir. We found that adherence to ribavirin is high and that real-time medication monitoring did not influence this. In chapter 8 we assessed the association between ribavirin steady-state plasma levels and sustained virological response (SVR) in HCV infected patients treated with direct-acting antivirals (DAAs) plus RBV. 85% of these patients had one or more difficult-to-cure characteristics (i.e. treatment-experienced, HCV genotype 3, cirrhosis). We found that higher RBV steady-state plasma level was an independent predictor of SVR. In chapter 9 we provided 100 hepatitis B patients with a medication dispenser that monitored entecavir intake during 16 weeks therapy in a prospective study. We found that 70% of chronic hepatitis B patients exhibited good adherence to entecavir. Lastly, in chapter 10, data from all HBV-infected patients in a Dutch center were reviewed for outpatient loss to follow up. A total of 47% had ever been lost to follow-up. Main reasons for outpatient compliance and loss to follow-up were doctor’s advice and physicians presuming inactive disease respectively. In a questionnaire, the patients also affirmed to have relatively little insight into what the disease entailed. Thus, properly educating patients might increase understanding of the disease, help increase compliance, and improve treatment outcomes