Vacuolating cytotoxin (vacA) alleles of Helicobacter pylori comprise two geographically widespread types, m1 and m2, and have evolved through limited recombination

Vacuolating cytotoxin (vacA) alleles of Helicobacter pylori vary, particularly in their mid region (which may be type m1 or m2) and their signal peptide coding region (type s1 or s2). We investigated nucleotide diversity among vacA alleles in strains from several locales in Asia, South America, and the USA. Phylogenetic analysis of vacA mid region sequences from 18 strains validated the division into two main groups (m1 and m2) and showed further significant divisions within these groups. Informative site analysis demonstrated one example of recombination between m1 and m2 alleles, and several examples of recombination among alleles within these groups. Recombination was not sufficiently extensive to destroy phylogenetic structure entirely. Synonymous nucleotide substitution rates were markedly different between regions of vacA, suggesting different evolutionary divergence times and implying horizontal transfer of genetic elements within vacA. Non-synonymous/synonymous rate ratios were greater between m1 and m2 sequences than among m1 sequences, consistent with m1 and m2 alleles encoding functions fitting strains for slightly different ecological niches

Altered expression of glutamate signaling, growth factor, and glia genes in the locus coeruleus of patients with major depression.

Several studies have proposed that brain glutamate signaling abnormalities and glial pathology have a role in the etiology of major depressive disorder (MDD). These conclusions were primarily drawn from post-mortem studies in which forebrain brain regions were examined. The locus coeruleus (LC) is the primary source of extensive noradrenergic innervation of the forebrain and as such exerts a powerful regulatory role over cognitive and affective functions, which are dysregulated in MDD. Furthermore, altered noradrenergic neurotransmission is associated with depressive symptoms and is thought to have a role in the pathophysiology of MDD. In the present study we used laser-capture microdissection (LCM) to selectively harvest LC tissue from post-mortem brains of MDD patients, patients with bipolar disorder (BPD) and from psychiatrically normal subjects. Using microarray technology we examined global patterns of gene expression. Differential mRNA expression of select candidate genes was then interrogated using quantitative real-time PCR (qPCR) and in situ hybridization (ISH). Our findings reveal multiple signaling pathway alterations in the LC of MDD but not BPD subjects. These include glutamate signaling genes, SLC1A2, SLC1A3 and GLUL, growth factor genes FGFR3 and TrkB, and several genes exclusively expressed in astroglia. Our data extend previous findings of altered glutamate, astroglial and growth factor functions in MDD for the first time to the brainstem. These findings indicate that such alterations: (1) are unique to MDD and distinguishable from BPD, and (2) affect multiple brain regions, suggesting a whole-brain dysregulation of such functions

Draft genome sequences of two <em>Micromonospora </em>strains isolated from the root nodules of <em>Alnus glutinosa</em>

\ua9 2024 American Society for Microbiology. All rights reserved.In this paper, the draft genomes of Micromonospora RTGN7 and RTP1Z1, derived from Alnus glutinosa root nodules, are reported. The assembly of RTGN7 is 6.6 Mbp, composed of 59 contigs, with an N50 of 321,872. RTP1Z1’s assembly is 6.3 Mbp, composed of 151 contigs, with an N50 of 76,442 bp

Oropharyngeal mucositis-specific quality-of-life measure in patients with cancer therapy.

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Submillimeter Studies of Prestellar Cores and Protostars: Probing the Initial Conditions for Protostellar Collapse

Improving our understanding of the initial conditions and earliest stages of protostellar collapse is crucial to gain insight into the origin of stellar masses, multiple systems, and protoplanetary disks. Observationally, there are two complementary approaches to this problem: (1) studying the structure and kinematics of prestellar cores observed prior to protostar formation, and (2) studying the structure of young (e.g. Class 0) accreting protostars observed soon after point mass formation. We discuss recent advances made in this area thanks to (sub)millimeter mapping observations with large single-dish telescopes and interferometers. In particular, we argue that the beginning of protostellar collapse is much more violent in cluster-forming clouds than in regions of distributed star formation. Major breakthroughs are expected in this field from future large submillimeter instruments such as Herschel and ALMA.Comment: 12 pages, 9 figures, to appear in the proceedings of the conference "Chemistry as a Diagnostic of Star Formation" (C.L. Curry & M. Fich eds.

The effects of climatic fluctuations and extreme events on running water ecosystems

Most research on the effects of environmental change in freshwaters has focused on incremental changes in average conditions, rather than fluctuations or extreme events such as heatwaves, cold snaps, droughts, floods or wildfires, which may have even more profound consequences. Such events are commonly predicted to increase in frequency, intensity and duration with global climate change, with many systems being exposed to conditions with no recent historical precedent. We propose a mechanistic framework for predicting potential impacts of environmental fluctuations on running water ecosystems by scaling up effects of fluctuations from individuals to entire ecosystems. This framework requires integration of four key components: effects of the environment on individual metabolism, metabolic and biomechanical constraints on fluctuating species interactions, assembly dynamics of local food webs and mapping the dynamics of the meta-community onto ecosystem function. We illustrate the framework by developing a mathematical model of environmental fluctuations on dynamically assembling food webs. We highlight (currently limited) empirical evidence for emerging insights and theoretical predictions. For example, widely supported predictions about the effects of environmental fluctuations are: high vulnerability of species with high per capita metabolic demands such as large-bodied ones at the top of food webs; simplification of food web network structure and impaired energetic transfer efficiency; reduced resilience and top-down relative to bottom-up regulation of food web and ecosystem processes. We conclude by identifying key questions and challenges that need to be addressed to develop more accurate and predictive bio-assessments of the effects of fluctuations, and implications of fluctuations for management practices in an increasingly uncertain world

Endovascular or open repair strategy for ruptured abdominal aortic aneurysm: 30 day outcomes from IMPROVE randomised trial

Objective To assess whether a strategy of endovascular repair (if aortic morphology is suitable, open repair if not) versus open repair reduces early mortality for patients with suspected ruptured abdominal aortic aneurysm. Design Randomised controlled trial. Setting 30 vascular centres (29 UK, 1 Canadian), 2009-13. Participants 613 eligible patients (480 men) with a clinical diagnosis of ruptured aneurysm. Interventions 316 patients were randomised to the endovascular strategy (275 confirmed ruptures, 174 anatomically suitable for endovascular repair) and 297 to open repair (261 confirmed ruptures). Main outcome measures 30 day mortality, with 24 hour and in-hospital mortality, costs, and time and place of discharge as secondary outcomes. Results 30 day mortality was 35.4% (112/316) in the endovascular strategy group and 37.4% (111/297) in the open repair group: odds ratio 0.92 (95% confidence interval 0.66 to 1.28; P=0.62); odds ratio after adjustment for age, sex, and Hardman index 0.94 (0.67 to 1.33). Women may benefit more than men (interaction test P=0.02) from the endovascular strategy: odds ratio 0.44 (0.22 to 0.91) versus 1.18 (0.80 to 1.75). 30 day mortality for patients with confirmed rupture was 36.4% (100/275) in the endovascular strategy group and 40.6% (106/261) in the open repair group (P=0.31). More patients in the endovascular strategy than in the open repair group were discharged directly to home (189/201 (94%) v 141/183 (77%); P<0.001). Average 30 day costs were similar between the randomised groups, with an incremental cost saving for the endovascular strategy versus open repair of £1186 (€1420; $1939) (95% confidence interval −£625 to £2997). Conclusions A strategy of endovascular repair was not associated with significant reduction in either 30 day mortality or cost. Longer term cost effectiveness evaluations are needed to assess the full effects of the endovascular strategy in both men and women

Single-cycle viral gene expression, rather than progressive replication and oncolysis, is required for VSV therapy of B16 melanoma

A fully intact immune system would be expected to hinder the efficacy of oncolytic virotherapy by inhibiting viral replication. Simultaneously, however, it may also enhance antitumor therapy through initiation of proinflammatory, antiviral cytokine responses at the tumor site. The aim of this study was to investigate the role of a fully intact immune system on the antitumor efficacy of an oncolytic virus. In this respect, injection of oncolytic vesicular stomatitis virus (VSV) into subcutaneous B16ova melanomas in C57Bl/6 mice leads to tumor regression, but it is not associated with viral replicative burst in the tumor. In contrast, intratumoral delivery of VSV induces an acute proinflammatory reaction, which quickly resolves concomitantly with virus clearance. Consistent with the hypothesis that therapy may not be dependent on the ability of VSV to undergo progressive rounds of replication, a single-cycle VSV is equally effective as a fully replication-competent VSV, whereas inactivated viruses do not generate therapy. Even though therapy is dependent on host CD8+ and natural killer cells, these effects are not associated with interferon-γ-dependent responses against either the virus or tumor. There is, however, a strong correlation between viral gene expression, induction of proinflammatory reaction in the tumor and in vivo therapy. Overall, our results suggest that acute innate antiviral immune response, which rapidly clears VSV from B16ova tumors, is associated with the therapy observed in this model. Therefore, the antiviral immune response to an oncolytic virus mediates an intricate balance between safety, restriction of oncolysis and, potentially, significant immune-mediated antitumor therapy

Observations from the IMPROVE trial concerning the clinical care of patients with ruptured abdominal aortic aneurysm.

BACKGROUND: Single-centre series of the management of patients with ruptured abdominal aortic aneurysm (AAA) are usually too small to identify clinical factors that could improve patient outcomes. METHODS: IMPROVE is a pragmatic, multicentre randomized clinical trial in which eligible patients with a clinical diagnosis of ruptured aneurysm were allocated to a strategy of endovascular aneurysm repair (EVAR) or to open repair. The influences of time and manner of hospital presentation, fluid volume status, type of anaesthesia, type of endovascular repair and time to aneurysm repair on 30-day mortality were investigated according to a prespecified plan, for the subgroup of patients with a proven diagnosis of ruptured or symptomatic AAA. Adjustment was made for potential confounding factors. RESULTS: Some 558 of 613 randomized patients had a symptomatic or ruptured aneurysm: diagnostic accuracy was 91·0 per cent. Patients randomized outside routine working hours had higher operative mortality (adjusted odds ratio (OR) 1·47, 95 per cent confidence interval 1·00 to 2·17). Mortality rates after primary and secondary presentation were similar. Lowest systolic blood pressure was strongly and independently associated with 30-day mortality (51 per cent among those with pressure below 70 mmHg). Patients who received EVAR under local anaesthesia alone had greatly reduced 30-day mortality compared with those who had general anaesthesia (adjusted OR 0·27, 0·10 to 0·70). CONCLUSION: These findings suggest that the outcome of ruptured AAA might be improved by wider use of local anaesthesia for EVAR and that a minimum blood pressure of 70 mmHg is too low a threshold for permissive hypotension

The impact of surgery for vulval cancer upon health-related quality of life and pelvic floor outcomes during the first year of treatment: A longitudinal, mixed methods study

© 2015 The Authors.Objective: To measure the long-term impact of surgical treatment for vulval cancer upon health-related quality of life and pelvic floor outcomes during the first year of therapy. Methods: Prospective, longitudinal, mixed-methods study. Twenty-three women aged >18 years with a new diagnosis of vulval cancer were recruited. The EORTC QLQ C30, SF-36 and an electronic pelvic floor assessment questionnaire (ePAQ-PF) were administered at baseline (pre-treatment) and 3, 6, 9 and 12 months post-treatment. Mixed effects repeated measures models (all adjusted for age and BMI) were used to investigate changes over time and differences between cancer stage. Qualitative interviews were carried out with 11 of the women and analysed using a thematic approach. Results: Mean age was 59.9 years (SD=15.3; range=23.8-86.6 yrs). Mean BMI was 30.0 (SD=4.5; range=24.4-38.2). Sixteen women had early (Stage 1 to 2B), and seven women had advanced stage disease (Stage 3 to 4B). Questionnaire scores revealed that physical and social functioning, fatigue, pain and general sex life were significantly worse at 12 months than pre-treatment (p=< 0.05). Qualitative analysis revealed multiple treatment side effects which were perceived as severe and enduring. Women with advanced vulval cancer had significantly worse SF-36 mental health scores at 12 months compared to women with early stage disease (p=0.037). Conclusions: Surgery for vulval cancer has long-term implications which can be persistent 12 months post-treatment. High rates of morbidity relating to lymphoedema and sexual function re-enforce the need for specialist clinics to support women who suffer these complications