CRISPR-based strategies in infectious disease diagnosis and therapy

CRISPR gene-editing technology has the potential to transform the diagnosis and treatment of infectious diseases, but most clinicians are unaware of its broad applicability. Derived from an ancient microbial defence system, these so-called "molecular scissors" enable precise gene editing with a low error rate. However, CRISPR systems can also be targeted against pathogenic DNA or RNA sequences. This potential is being combined with innovative delivery systems to develop new therapeutic approaches to infectious diseases.info:eu-repo/semantics/publishedVersio

Autoimmune responses to amyloid structures of A beta(25-35) peptide and human lysozyme in the serum of patients with progressive Alzheimer's disease

We have found an increased level of serum antibodies to the prefibrillar structures of both Abeta(25-35) peptide and human lysozyme in Alzheimer's disease (AD) patients compared to age-matched controls, indicating that autoimmunity is implicated in AD. In the serum of AD patients with a long-term duration (>15 years) the titer of serum antibodies to aggregates of Abeta(25-35) peptide increased by approximately 5-fold, whilst the antibody titer to lysozyme protofilaments decreased by approximately 8-fold compared to patients with AD duration of 15 years. An increase in the concentration of immune complexes and higher lysozyme activity was detected in the serum of all patients and this was suggestive of an inflammatory reaction. We propose that the autoimmune response to different amyloid structures in AD can be viewed as a clearance pathway targeting amyloid development. Autoimmune response can be exploited as a marker of ongoing protein aggregation and hence be used as a diagnostic feature of AD

Allogeneic Hematopoietic Stem Cell Transplantation in Myelofibrosis

Background & Aims. At present, the allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment option with curative potential in patients with myelofibrosis (MF), especially in intermediate and high risk categories. The aim of the study is to perform a retrospective analysis of allo-HSCT outcomes in MF patients. Materials & Methods. Outcomes of allo-HSCT in 11 intermediate-2 (n = 3) and high (n = 6) risk patients (based on Dynamic International Prognostic Scoring Scale, DIPSSplus) performed in the R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation over the period from 2005 till 2015 were analyzed in the study. Two more patients underwent allo-HSCT in MF blast phase. Two patients received ruxolitinib before allo-HSCT and 1 patient before and after allo-HSCT. Reduced intensity conditioning regimen was used in all cases. Results. Primary engraftment was documented in 8 patients. 72 % of patients achieved complete hematological remission. Molecular remission and myelofibrosis regression were confirmed in 5 patients. 5 of 11 patients were still with remission and followed-up by the date of the paper submission. The overall two-year survival was 46 %. Conclusion. Allo-HSCT is an effective treatment option for MF patients. Further trials are required to evaluate an optimal timing for allo-HSCT in MF patients and efficacy of Janus kinase (JAK) inhibitors as pre- and posttransplant therapy in MF

New Сytogenetic Approaches in Patients with Primary Myelofibrosis

Aim. To evaluate the potential of a new cytogenetic technique in patients with primary myelofibrosis (PMF). Materials and methods. 48-hour blood cell cultures (according to Singh et al., 2013) were used for cytogenetic study in 11 PMF patients (5 female, 6 men, aged 32–60 years; median 48.6 years). GTG-banding and different types of fluorescence in situ hybridization (FISH) techniques were used for identification of chromosomal aberrations. Results. The incidence of abnormal karyotypes in blood cultures was significantly higher than that in standard bone marrow cultures (82 vs 27 %; p < 0.01). The polyploid clones were found in blood cultures of 45 % of patients. Structural chromosomal aberrations were found in chromosomes 6, 1, 3, as well as 16 and 17 (in 2 and 1 patients with each aberration, respectively). In all but one patients these abnormalities in diploid and polyploid metaphases were identical. Partial 1q trisomy resulted from adding of additional (1q21–1q44) material translocated to the short arm of chromosome 5 to the material of 2 normal homologue of chromosome 1. It seems that 1q+, i(17q) and some others chromosomal abnormalities were secondary, whereas 6p21 locus involvement may be a primary defect in PMF. The t(3;6)(q25;p21) translocation described for the first time and confirmed by FISH should be considered a variant of well-known translocation t(1;6). Allo-HSCT in 2 patients with 1q+ was successful, whereas there were problems with engraftment in a female patient with prognostically unfavorable t(3;3)(q21;q26) translocation associated with the EVI1 gene overexpression. Conclusion. Cytogenetic examinations in blood cultures provide important additional information about PMF patients

Phagetherapy: Clinical Applications – Critical Appraisal of Randomized Controlled Trials

Phagotherapy, defined as the use of bacteriophage to treat bacterial infections, was initially proposed by Felix d’Herelle, a French-Canadian who did a lot of research on this topic in Paris, but also travelled the world to treat patients in different settings and conditions. While the literature on this topic is quite extensive, the number of randomized controlled trials is rather limited. Large studies were performed and published in the former USSR republics more than 50 years ago. Since then, there were few trials performed, enrolling a limited number of patients and assessing potential phage efficacy in different settings such as chronic otitis or infected burn wounds. In this chapter, we review and discuss these different randomized trials. While the results might look disappointing at first sight, they all confirm safety of phage used for treatment of difficult clinical situations. Those trials should help define further studies in order to obtain the best possible results and hopefully confirm that phages could be used as an alternative to treat difficult to treat multi-drug-resistant bacterial infections