Diagnosis, prevention and treatment of central nervous system involvement in peripheral t-cell lymphomas

Non-Hodgkin lymphomas with T-cell immunophenotype encompass a heterogeneous group of infrequent neoplasms that follow variable clinical courses but prevalently include aggressive behavior and high mortality rates. The involvement of the central nervous system (CNS) is an uncommon event in T-cell lymphomas, with wide variability among the different disease entities. CNS can be affected either at initial diagnosis or at recurrence, and both forms are considered “secondary CNS T-cell lymphoma”. Given the low incidence of secondary CNS T-cell lymphoma, related literature is sparse, contradictory, and primarily constituted by small case series and single case reports. However, reported studies uniformly suggest high mortality rates related to this event. Therefore, to improve our ability to identify high-risk patients and offer them successful CNS prophylaxis or timely and effective treatment once the event has occurred may prevent CNS-related T-cell lymphomas deaths. For example, some entities like aggressive adult T-cell leukemia/lymphoma, extranodal natural killer/T-cell lymphoma, and other peripheral T-cell lymphomas with involvement of two or more extranodal organs are prone to CNS dissemination and should be considered for personalized CNS prophylaxis. The level of evidence suggesting an increased risk of CNS recurrence for other T-cell lymphomas and for other risk factors is lower. Published case series show that, following the example of aggressive B-cell lymphomas, patients with T-cell lymphomas and putative increased CNS risk receive different forms of prophylaxis, mostly methotrexate and cytarabine delivered by intrathecal and/or intravenous routes, with varied success. To date, achievements in the treatment of CNS involvement in patients with aggressive B-cell lymphoma were not replicated in secondary CNS T-cell lymphomas, and identification of effective therapies remains an urgent research target. This review is focused on clinical findings, diagnosis, treatment, and prognosis of patients with T-cell lymphoma experiencing CNS dissemination either at presentation or relapse. It aims to provide logical and, oftentimes, evidence-based answers to the most common questions on the most probable risk factors to CNS involvement in patients with T-cell lymphoma, the indications and strategies to prevent this life-threating event, and the management of patients with CNS disease

High Rates of Human Fecal Carriage of mcr-1–Positive Multidrug-Resistant Enterobacteriaceae Emerge in China in Association With Successful Plasmid Families

Background: mcr-1–mediated colistin resistance in Enterobacteriaceae is concerning, as colistin is used in treating multidrug-resistant Enterobacteriaceae infections. We identified trends in human fecal mcr-1-positivity rates and colonization with mcr-1–positive, third-generation cephalosporin-resistant (3GC-R) Enterobacteriaceae in Guangzhou, China, and investigated the genetic contexts of mcr-1 in mcr-1–positive 3GC-R strains. / Methods: Fecal samples were collected from in-/out-patients submitting specimens to 3 hospitals (2011–2016). mcr-1 carriage trends were assessed using iterative sequential regression. A subset of mcr-1–positive isolates was sequenced (whole-genome sequencing [WGS], Illumina), and genetic contexts (flanking regions, plasmids) of mcr-1 were characterized. / Results: Of 8022 fecal samples collected, 497 (6.2%) were mcr-1 positive, and 182 (2.3%) harbored mcr-1–positive 3GC-R Enterobacteriaceae. We observed marked increases in mcr-1 (0% [April 2011] to 31% [March 2016]) and more recent (since January 2014; 0% [April 2011] to 15% [March 2016]) increases in human colonization with mcr-1–positive 3GC-R Enterobacteriaceae (P < .001). mcr-1–positive 3GC-R isolates were commonly multidrug resistant. WGS of mcr-1–positive 3GC-R isolates (70 Escherichia coli, 3 Klebsiella pneumoniae) demonstrated bacterial strain diversity; mcr-1 in association with common plasmid backbones (IncI, IncHI2/HI2A, IncX4) and sometimes in multiple plasmids; frequent mcr-1 chromosomal integration; and high mobility of the mcr-1–associated insertion sequence ISApl1. Sequence data were consistent with plasmid spread among animal/human reservoirs. / Conclusions: The high prevalence of mcr-1 in multidrug-resistant E. coli colonizing humans is a clinical threat; diverse genetic mechanisms (strains/plasmids/insertion sequences) have contributed to the dissemination of mcr-1, and will facilitate its persistence

Somatic expression of piRNA and associated machinery in the mouse identifies short, tissue-specific piRNA

Piwi-interacting RNAs (piRNAs) are small non-coding RNAs that associate with PIWI proteins for transposon silencing via DNA methylation and are highly expressed and extensively studied in the germline. Mature germline piRNAs typically consist of 24–32 nucleotides, with a strong preference for a 5ʹ uridine signature, an adenosine signature at position 10, and a 2ʹ-O-methylation signature at the 3ʹ end. piRNA presence in somatic tissues, however, is not well characterized and requires further systematic evaluation. In the current study, we identified piRNAs and associated machinery from mouse somatic tissues representing the three germ layers. piRNA specificity was improved by combining small RNA size selection, sodium periodate treatment enrichment for piRNA over other small RNA, and small RNA next-generation sequencing. We identify PIWIL1, PIWIL2, and PIWIL4 expression in brain, liver, kidney, and heart. Of note, somatic piRNAs are shorter in length and tissue-specific, with increased occurrence of unique piRNAs in hippocampus and liver, compared to the germline. Hippocampus contains 5,494 piRNA-like peaks, the highest expression among all tested somatic tissues, followed by cortex (1,963), kidney (580), and liver (406). The study identifies 26 piRNA sequence species and 40 piRNA locations exclusive to all examined somatic tissues. Although piRNA expression has long been considered exclusive to the germline, our results support that piRNAs are expressed in several somatic tissues that may influence piRNA functions in the soma. Once confirmed, the PIWI/piRNA system may serve as a potential tool for future research in epigenome editing to improve human health by manipulating DNA methylation

Reclassification of Wolbachia persica as Francisella persica comb. nov and emended description of the family Francisellaceae

The taxonomic status of the bacterium Wolbachia persica is described, and based on the evidence presented, transfer of this species to the genus Francisella as Francisella persica comb. nov. is proposed. This reclassification is supported by data generated from genomic comparisons of W. persica ATCC VR-331(T) (=FSC845(T)=DSM 101678(T)) to other near neighbours, including Francisella tularensis subsp. novicida. The full-length 16S rRNA gene sequence of strain ATCC VR-331(T) had 98.5 % nucleotide identity to the cognate gene in F. tularensis, with the highest similarity to subspecies novicida. Phylogenetic trees of full-length 16S rRNA gene, gyrA and recA sequences from species of the genera Wolbachia (class Alphaproteobacteria) and Francisella (class Gammaproteobacteria) indicated that W. persica ATCC VR-331(T) was most closely related to members of the genus Francisella and not Wolbachia. Local collinear blocks within the chromosome of strain ATCC VR-331(T) had considerable similarity with F. tularensis subsp. novicida, but not with any Wolbachia strain. The genomes of strain ATCC VR-331(T) and F. tularensis subsp. novicida Utah 112(T) (=ATCC 15482(T)) contained an average nucleotide identity mean of 88.72 % and median of 89.18 %. Importantly, the genome of strain ATCC VR-331(T) contained one Francisella Pathogenicity Island, similar to F. tularensis subsp. novicida, as well as the Francisella-specific gene fopA1 and F. tularensis-specific genes fopA2 and lpnA (also referred to as tul4). In contrast to the obligate intracellular genus Wolbachia, strain ATCC VR-331(T) and facultative intracellular Francisella can replicate in specialized cell-free media. Collectively, these results demonstrate that Wolbachia persica should be reclassified in the genus Francisella as Francisella persica comb. nov. The type strain of Francisella persica comb. nov. is ATCC VR-331(T) (=FSC845(T)=DSM 101678(T)). An emended description of the family Francisellaceae is also provided

Recovery of synthetic dye red 3BS from simulated wastewater using supported liquid membrane process containing immobilized kerosene-tridodecylamine liquid membrane

The discharge of reactive dyes into the environment has led to the toxicity problems especially to the aquatic organism. Therefore, there is a necessity for treatment of the reactive dyes from wastewater. In this work, Red 3BS reactive dye was separated using supported liquid membrane process. Commercial polypropylene (PP) membrane was used as a support of kerosene-tridodecylamine liquid membrane. Several important parameters such as flow rate, pH of feed phase, initial concentration of feed phase and stripping agent concentration were investigated. The result shows that for 50 ppm Red 3BS solution containing 0.00001M Na2SiO3 almost 100 and 89% of Red 3BS was removed and recovered respectively at the favorable condition of 0.1 M NaOH as a stripping agent, pH 3 of feed phase and 100 ml/min of flow rate

T-cell Brazil project : preliminary results after 2 years of T-cell lymphoma registry

sem informação85S31S3210th Eurasian hematology oncology congres