GntR is involved in the expression of virulence in strain Streptococcus suis P1/7

Abstract

Streptococcus suis is a severe zoonotic pathogen, responsible for acute diseases in pigs and human. GntR proteins widely distribute in various bacteria species. In previous study, GntR proteins were reported to be involved in virulence in many pathogens. To investigate the relationship between GntR and S. suis serotype 2, we constructed an isogenic deletion mutant P1/7ΔgntR and an isogenic single-nucleotide substitution mutant P1/7gntR^(SC070731), which took strain P1/7 as parent. The results show that the mutants P1/7ΔgntR and P1/7gntR^(SC070731) have a stronger ability to tolerate the oxidative stress and reproduce in blood. Moreover, higher fatality rate observed in mice when challenged with P1/7ΔgntR or P1/7gntR^(SC070731) compared with that of P1/7. Overall, all results suggest that GntR greatly impacts the virulence of S. suis serotype 2 strain P1/7 and give a new perspective of virulence generation in S. suis.

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Neisseria meningitidis disease-associated clones in Amazonas State, Brazil

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Cancers, Vol. 10, Pages 110: New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by NGS Approaches: An Update

Cancers, Vol. 10, Pages 110: New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by NGS Approaches: An Update

Cancers doi: 10.3390/cancers10040110

Authors: Adrián Montaño Maribel Forero-Castro Darnel Marchena-Mendoza Rocío Benito Jesús María Hernández-Rivas

The identification and study of genetic alterations involved in various signaling pathways associated with the pathogenesis of acute lymphoblastic leukemia (ALL) and the application of recent next-generation sequencing (NGS) in the identification of these lesions not only broaden our understanding of the involvement of various genetic alterations in the pathogenesis of the disease but also identify new therapeutic targets for future clinical trials. The present review describes the main deletions, amplifications, sequence mutations, epigenetic lesions, and new structural DNA rearrangements detected by NGS in B-ALL and T-ALL and their clinical importance for therapeutic procedures. We reviewed the molecular basis of pathways including transcriptional regulation, lymphoid differentiation and development, TP53 and the cell cycle, RAS signaling, JAK/STAT, NOTCH, PI3K/AKT/mTOR, Wnt/β-catenin signaling, chromatin structure modifiers, and epigenetic regulators. The implementation of NGS strategies has enabled important mutated genes in each pathway, their associations with the genetic subtypes of ALL, and their outcomes, which will be described further. We also discuss classic and new cryptic DNA rearrangements in ALL identified by mRNA-seq strategies. Novel cooperative abnormalities in ALL could be key prognostic and/or predictive biomarkers for selecting the best frontline treatment and for developing therapies after the first relapse or refractory disease.

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Retinal detachment in albinism

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Disease-Modifying Treatment in Progressive Multiple Sclerosis

Abstract

Purpose of review

Multiple sclerosis (MS) is an immune-mediated disorder that affects the central nervous system (CNS), often first affecting people in early adulthood. Although most MS patients have a relapsing-remitting course (RRMS) at disease onset, a substantial proportion later develop chronic progression, termed secondary progressive MS (SPMS). Approximately 10% of MS patients experience chronic progression from disease onset, termed primary progressive multiple sclerosis (PPMS). Although several disease-modifying treatment (DMT) options exist for relapsing forms of this disease, DMT options are few for progressive MS (PPMS and SPMS). Herein, we strive to define progressive MS, review major clinical trials aimed at progressive MS, and delineate potential strategies in the management of progressive MS.

Recent findings

In 2017, the first DMT for PPMS, the B lymphocyte-depleting monoclonal antibody, ocrelizumab, came to market. Ocrelizumab reduced 12-week confirmed disability progression (CDP) by 24% versus placebo. Siponimod, a selective sphingosine-1-phosphate receptor modulator, reduced 3-month CDP by 21% versus placebo in SPMS. Ibudilast slowed brain atrophy in PPMS and SPMS patients in a multicenter phase 2b study. Smaller early phase studies of alpha-lipoic acid and simvastatin each found slowing of rate of whole brain atrophy in SPMS patients.

Summary

Reasons now exist for optimism in the search for DMTs for progressive MS. It remains a challenge to identify outcome measures that accurately reflect the underlying pathology in progressive MS, which is less inflammatory and more degenerative than RRMS.

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Development of a blunt chest injury care bundle: an integrative review

Publication date: Available online 7 April 2018
Source:Injury
Author(s): Sarah Kourouche, Thomas Buckley, Belinda Munroe, Kate Curtis
BackgroundBlunt chest injuries (BCI) are associated with high rates of morbidity and mortality. There are many interventions for BCI which may be able to be combined as a care bundle for improved and more consistent outcomes.ObjectiveTo review and integrate the BCI management interventions to inform the development of a BCI care bundle.MethodsA structured search of the literature was conducted to identify studies evaluating interventions for patients with BCI. Databases MEDLINE, CINAHL, PubMed and Scopus were searched from 1990–April 2017. A two-step data extraction process was conducted using pre-defined data fields, including research quality indicators. Each study was appraised using a quality assessment tool, scored for level of evidence, then data collated into categories. Interventions were also assessed using the APEASE criteria then integrated to develop a BCI care bundle.ResultsEighty-one articles were included in the final analysis. Interventions that improved BCI outcomes were grouped into three categories; respiratory intervention, analgesia and surgical intervention. Respiratory interventions included continuous positive airway pressure and high flow nasal oxygen. Analgesia interventions included regular multi-modal analgesia and paravertebral or epidural analgesia. Surgical fixation was supported for use in moderate to severe rib fractures/BCI. Interventions supported by evidence and that met APEASE criteria were combined into a BCI care bundle with four components: respiratory adjuncts, analgesia, complication prevention, and surgical fixation.ConclusionsThe key components of a BCI care bundle are respiratory support, analgesia, complication prevention including chest physiotherapy and surgical fixation.



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Loss of histone H3K27me3 identifies a subset of meningiomas with increased risk of recurrence

Abstract

Epigenetic patterns on the level of DNA methylation have already been shown to separate clinically relevant subgroups of meningiomas. We here set out to identify potential prognostic implications of epigenetic modification on the level of histones with focus on H3K27 trimethylation (H3K27me3). H3K27me3 was assessed by immunohistochemistry on 232 meningiomas from 232 patients. In 194 cases, trimethylation was detected in tumor cells. In 25 cases, staining was limited to vessels while all tumor cells were negative. Finally, 13 cases yielded equivocal staining patterns. Reduced abundance of H3K27me3 in cases with staining limited to vessels was confirmed by mass spectrometry on a subset of cases. Lack of staining for H3K27me3 in all tumor cells was significantly associated with more rapid progression (p = 0.009). In line, H3K27me3-negative cases were associated with a DNA methylation pattern of the more aggressive types among the recently introduced DNA methylation groups. Also, NF2 and SUFU mutations were enriched among cases with complete lack of H3K27me3 staining in tumor cells (p < 0.0001 and p = 0.029, respectively). H3K27me3 staining pattern added significant prognostic insight into WHO grade II cases and in the compound subset of WHO grade I and II cases (p = 0.04 and p = 0.007, respectively). However, it did not further stratify within WHO grade III cases. Collectively, these data indicate that epigenetic modifications beyond DNA methylation are involved in the aggressiveness of meningioma. It also suggests that H3K27me3 immunohistochemistry might be a useful adjunct in meningioma diagnostics, particularly for cases with WHO grade II histology or at the borderline between WHO grade I and II.

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