Interferon free antiviral treatment of chronic hepatitis C in patients affected by β-thalassemia major

Chronic hepatitis C (CHC) significantly affects the prognosis of liver disease [1] and health related quality of life (HRQOL) in patients with β-thalassemia major [2, 3]. CHC cure is a crucial event in the prognosis of the disease, since prevents fibrosis progression, decreases the risk of hepatocellular carcinoma (HCC), and improves survival. Standard antiviral therapy with Pegylated Interferon (PEG-IFN) and Ribavirin (RBV) has long been the standard of care, despite its limited efficacy and increased ribavirin induced hematological adverse events in thalassemic patients [4]. Recently, several novel highly effective direct antiviral agents (DAAs) have been approved for HCV treatment, with impressive cure rates, higher than 90%, after 8–12 weeks of therapy and mild adverse events [5], but there are no published reports documenting the efficacy, safety and impact on QOL of available interferon-free antiviral regimens in patients with βthalassemia majo

Temperature profile in a reverse flow reactor for catalytic partial oxidation of methane by fast IR imaging

Catalytic partial oxidation of methane with air was investigated in a reverse flow reactor with commercial Rh/A1(2)O(3) catalyst in pellets. Temperature profile of the catalyst bed was measured by fast IR thermography and product composition was measured with a continuous gas analyzer. The effect of internal heat recovery on reactor performance and catalyst thermal stress is presented and compared with steady state operation. Feed direction switching time, total flow rate, and methane to oxygen ratio were investigated as process operating parameters. Data of catalyst bed temperature evolution during the flow cycle are presented and discussed. Comparison of dynamic heat integration with external feed preheating in terms of product composition and catalyst temperature profile is also presented. (C) 2008 American Institute of Chemical Engineers

Gut-seeded α-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice

Parkinson’s disease is a synucleinopathy that is characterized by motor dysfunction, death of midbrain dopaminergic neurons and accumulation of α-synuclein (α-Syn) aggregates. Evidence suggests that α-Syn aggregation can originate in peripheral tissues and progress to the brain via autonomic fibers. We tested this by inoculating the duodenal wall of mice with α-Syn preformed fibrils. Following inoculation, we observed gastrointestinal deficits and physiological changes to the enteric nervous system. Using the AAV-PHP.S capsid to target the lysosomal enzyme glucocerebrosidase for peripheral gene transfer, we found that α-Syn pathology is reduced due to the increased expression of this protein. Lastly, inoculation of α-Syn fibrils in aged mice, but not younger mice, resulted in progression of α-Syn histopathology to the midbrain and subsequent motor defects. Our results characterize peripheral synucleinopathy in prodromal Parkinson’s disease and explore cellular mechanisms for the gut-to-brain progression of α-Syn pathology

Stereoselective Solvolysis in the Synthesis of Dorzolamide Intermediates

The key intermediate in the synthesis of dorzolamide,(4S,6S)-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-4-ol-7,7-dioxide,can beobtained in the diastereoisomerically pure form in two straightforwardsteps starting from diastereoisomeric mixtures of cis/trans-(6S)-6-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-4-yl acetate,regardless of their ratio. The reaction of crucial importance in thisscheme is a remarkably stereoselective solvolysis of the acetate esterin an acetone/phosphate buffer mixture as the solvent system. Investigationof this so far unrecognized stereoselective reaction reveals thatit proceeds via an S(N)1-like pathway as indicated by thecorrelation of the solvolysis rate constants with the Y (OTs) values of different solvent mixtures and by trappingof the reaction intermediate with sodium azide. The structure of (4S,6S)-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-4-ol-7,7-dioxide was confirmedby single-crystal X-ray analysis

Could the use of bedside lung ultrasound reduce the number of chest x-rays in the intensive care unit?

Background: Lung ultrasound can be used as an alternative to chest radiography (CXR) for the diagnosis and follow-up of various lung diseases in the intensive care unit (ICU). Our aim was to evaluate the influence that introducing a routine daily use of lung ultrasound in critically ill patients may have on the number of CXRs and as a consequence, on medical costs and radiation exposure. Methods: Data were collected by conducting a retrospective evaluation of the medical records of adult patients who needed thoracic imaging and were admitted to our academic polyvalent ICU. We compared the number of CXRs and relative costs before and after the introduction of lung ultrasound in our ICU. Results: A total of 4134 medical records were collected from January 2010 to December 2014. We divided our population into two groups, before (Group A, 1869 patients) and after (Group B, 2265 patients) the introduction of a routine use of LUS in July 2012. Group A performed a higher number of CXRs compared to Group B (1810 vs 961, P = 0.012), at an average of 0.97 vs 0.42 exams per patient. The estimated reduction of costs between Groups A and B obtained after the introduction of LUS, was 57%. No statistically significant difference between the outcome parameters of the two groups was observed. Conclusions: Lung ultrasound was effective in reducing the number of CXRs and relative medical costs and radiation exposure in ICU, without affecting patient outcome

Oral Ethanol-Reinforced Responding in Rhesus Monkeys: Effects of Opioid Antagonists Selective for the Μ-,Κ-, or Δ-Receptor

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65904/1/j.1530-0277.1998.tb03960.x.pd

Discontinuation of alpha-interferon treatment in patients with chronic myeloid leukemia in long-lasting complete molecular response

To evaluate follow-up after α-interferon (IFN) discontinuation, 23 patients with chronic myeloid leukemia (CML) in stable complete molecular response (CMolR) with IFN were revisited. After a median IFN treatment of 105.8 months (IR 56.1 - 127.3), all patients discontinued IFN for prolonged CMolR (12), intolerance (8) or planned ABMT (3). After 12.5 months, one patient developed an extramedullar blast crisis. Four patients needed to start imatinib, all achieving again molecular response. Eighteen patients are still off-therapy (median time from IFN discontinuation 125.5 months, IR 86.9-205.3); among these, five are BCR-ABL negative, six present with a sporadic positivity (BCR-ABL ratio < 0.1) and seven show a stable and long-lasting mild positivity (BCR-ABL ratio < 0.5). Patients in prolonged CMolR with IFN have low risk of recurrence after discontinuation; the reappearance of a BCR-ABL positivity < 0.5 did not always precede a relapse, suggesting mechanisms of immunological control induced by IFN