Metabolic reconfigurations aimed at the detoxification of a multi-metal stress in Pseudomonas fluorescens: implications for the bioremediation of metal pollutants.

Although the ability of microbial systems to adapt to the toxic challenge posed by numerous metal pollutants individually has been well documented, there is little detailed information on how bacteria survive in a multiple-metal environment. Here we describe the metabolic reconfiguration invoked by the soil microbe Pseudomonas fluorescens in a medium with millimolar amounts of aluminum (Al), iron (Fe), gallium (Ga), calcium (Ca), and zinc (Zn). While enzymes involved in the production of NADH were decreased, there was a marked increase in enzymatic activities dedicated to NADPH formation.

[Progressive multifocal leukoencephalopathy associated to natalizumab: the importance of magnetic resonance imaging in its early diagnosis].

Introduction: Natalizumab is a drug used in multiple sclerosis (MS) and its main side effect is the development of progressive multifocal leukoencephalopathy (PML). Since this is potentially fatal or disabling, treatment must be stopped immediately if it is suspected, taking into account the possible later development of immune reconstitution syndrome or renewed exacerbation of MS.

Case Report: We report a case of initially asymptomatic PML within the context of treatment with natalizumab in a female patient with MS.

Tetrahydrocannabinol induces brain mitochondrial respiratory chain dysfunction and increases oxidative stress: a potential mechanism involved in cannabis-related stroke.

Cannabis has potential therapeutic use but tetrahydrocannabinol (THC), its main psychoactive component, appears as a risk factor for ischemic stroke in young adults. We therefore evaluate the effects of THC on brain mitochondrial function and oxidative stress, key factors involved in stroke. Maximal oxidative capacities V max (complexes I, III, and IV activities), V succ (complexes II, III, and IV activities), V tmpd (complex IV activity), together with mitochondrial coupling (V max/V 0), were determined in control conditions and after exposure to THC in isolated mitochondria extracted from rat brain, using differential centrifugations.

Glycine metabolism and anti-oxidative defence mechanisms in Pseudomonas fluorescens.

The role of metabolism in anti-oxidative defence is only now beginning to emerge. Here, we show that the nutritionally-versatile microbe, Pseudomonas fluorescens, reconfigures its metabolism in an effort to generate NADPH, ATP and glyoxylate in order to fend off oxidative stress. Glyoxylate was produced predominantly via the enhanced activities of glycine dehydrogenase-NADP(+) (GDH), glycine transaminase (GTA) and isocitrate lyase (ICL) in a medium exposed to hydrogen peroxide (H₂O₂).

Pixel-by-Pixel Comparison of Volume Transfer Constant and Estimates of Cerebral Blood Volume from Dynamic Contrast-Enhanced and Dynamic Susceptibility Contrast-Enhanced MR Imaging in High-Grade Gliomas.

Background And Purpose: Estimates of blood volume and volume transfer constant are parameters commonly used to characterize hemodynamic properties of brain lesions. The purposes of this study were to compare values of volume transfer constant and estimates of blood volume in high-grade gliomas on a pixel-by-pixel basis to comprehend whether they provide different information and to compare estimates of blood volume obtained by dynamic contrast-enhanced MR imaging and dynamic susceptibility contrast-enhanced MR imaging.

Materials And Methods: Thirty-two patients with biopsy-proved grade IV gliomas underwent dynamic contrast-enhanced MR imaging and dynamic susceptibility contrast-enhanced MR imaging, and parametric maps of volume transfer constant, plasma volume, and CBV maps were calculated.

Effectiveness of a computerized drug-monitoring program to detect and prevent adverse drug events and medication non-adherence in outpatient ambulatory care: study protocol of a randomized controlled trial.

Background: Medications are an effective intervention for managing and preventing health problems but their benefit can be undermined by non-adherence or adverse drug events (ADEs). Since these issues may be interconnected, efforts to improve non-adherence should also include reduction of ADEs. We have developed the ISTOP-ADE system (Information Systems-enabled Outreach for Preventing Adverse Drug Events), which enables timely monitoring and managing of ADEs.

Brain metabolism and Alzheimer's disease: the prospect of a metabolite-based therapy.

The brain is one of the most energy-demanding organs in the body. It has evolved intricate metabolic networks to fulfill this need and utilizes a variety of substrates to generate ATP, the universal energy currency. Any disruption in the supply of energy results in various abnormalities including Alzheimer's disease (AD), a condition with markedly diminished cognitive ability.

Mobile applications for participation at the shopping mall: content analysis and usability for persons with physical disabilities and communication or cognitive limitations.

The aim of this exploratory study was to determine the important features in content and usability of existing mobile applications evaluating environmental barriers and facilitators (EBF) to participation for persons with physical disabilities presenting mild communication or cognitive limitations. A rigorous process based on a user-centered design approach led to the identification of two relevant mobile applications to evaluate the EBF. An accessibility expert, the research team as well as five users then tested the mobile applications in a shopping mall.

Nuclear lactate dehydrogenase modulates histone modification in human hepatocytes.

It is becoming increasingly apparent that the nucleus harbors metabolic enzymes that affect genetic transforming events. Here, we describe a nuclear isoform of lactate dehydrogenase (nLDH) and its ability to orchestrate histone deacetylation by controlling the availability of nicotinamide adenine dinucleotide (NAD(+)), a key ingredient of the sirtuin-1 (SIRT1) deacetylase system. There was an increase in the expression of nLDH concomitant with the presence of hydrogen peroxide (H2O2) in the culture medium.

Brain atrophy in natalizumab-treated patients: A 3-year follow-up.

Background: A pseudoatrophy effect has been held responsible for the lack of net impact of natalizumab on brain volume outcomes in 2-year trials, but no data are available beyond 24 months.

Objective: We aimed to investigate brain volume dynamics in natalizumab-treated patients in up to 3 years after therapy initiation with clinical correlations.

Methods: Patients on natalizumab for at least 3 years were clinically assessed 3-monthly.

Significant clinical worsening after natalizumab withdrawal: Predictive factors.

We aimed to single out multiple sclerosis (MS) cases with poor outcome after natalizumab withdrawal and to identify predictive variables. We ascertained 47 withdrawals, and compared their pre- and post-natalizumab periods. We objectively defined significant clinical worsening after natalizumab withdrawal as a 2-step increase in Expanded Disability Status Scale (EDSS).

A novel ATP-generating machinery to counter nitrosative stress is mediated by substrate-level phosphorylation.

Background: It is well-known that elevated amounts of nitric oxide and other reactive nitrogen species (RNS) impact negatively on the tricarboxylic acid (TCA) cycle and oxidative phosphorylation. These perturbations severely compromise O2-dependent energy production. While bacteria are known to adapt to RNS, a key tool employed by macrophages to combat infections, the exact mechanisms are unknown.

Redox-sensitive induction of Src/PI3-kinase/Akt and MAPKs pathways activate eNOS in response to EPA:DHA 6:1.

Aims: Omega-3 fatty acid products containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have vasoprotective effects, in part, by stimulating the endothelial formation of nitric oxide (NO). This study determined the role of the EPA:DHA ratio and amount, and characterized the mechanism leading to endothelial NO synthase (eNOS) activation.

Methods And Results: EPA:DHA 6∶1 and 9∶1 caused significantly greater endothelium-dependent relaxations in porcine coronary artery rings than EPA:DHA 3∶1, 1∶1, 1∶3, 1∶6, 1∶9, EPA and DHA alone, and EPA:DHA 6∶1 with a reduced EPA + DHA amount, which were inhibited by an eNOS inhibitor.

Collapsin response-mediator protein 5 (CRMP5) phosphorylation at threonine 516 regulates neurite outgrowth inhibition.

The collapsin response-mediator proteins (CRMPs) are multifunctional proteins highly expressed during brain development but down-regulated in the adult brain. They are involved in axon guidance and neurite outgrowth signalling. Among these, the intensively studied CRMP2 has been identified as an important actor in axon outgrowth, this activity being correlated with the reorganisation of cytoskeletal proteins via the phosphorylation state of CRMP2.

French-Canadian translation of the WheelCon-M (WheelCon-M-F) and evaluation of its validity evidence using telephone administration.

Purpose: The objectives of this study were to: (1) translate the Wheelchair Use Confidence Scale for Manual Wheelchair Users (WheelCon-M) into a French-Canadian version (WheelCon-M-F); and (2) evaluate the WheelCon-M-F validity evidence based on response processes, internal structure, and relations with other variables.

Methods: The WheelCon-M was translated from English to French using the Translation and Cultural Adaptation of Patient Reported Outcomes Measures - Principles of Good Practice guidelines. We used a test-retest design to examine the validity of the WheelCon-M-F with 24 community dwelling, experienced manual wheelchair users who had a variety of musculoskeletal and neurological diagnoses.

Great heterogeneity of commercial fruit juices to induce endothelium-dependent relaxations in isolated porcine coronary arteries: role of the phenolic content and composition.

Since polyphenol-rich products such as red wine, grape juice, and grape extracts have been shown to induce potent endothelium-dependent relaxations, we have evaluated whether commercial fruit juices such as those from berries are also able to induce endothelium-dependent relaxations of isolated coronary arteries and, if so, to determine whether this effect is related to their phenolic content. Among the 51 fruit juices tested, 2/12 grape juices, 3/7 blackcurrant juices, 4/5 cranberry juices, 1/6 apple juices, 0/5 orange juices, 2/6 red fruit and berry juices, 3/6 blends of red fruit juices, and 0/4 non-red fruit juices were able to induce relaxations achieving more than 50% at a volume of 1%. The active fruit juices had phenolic contents ranging from 0.

Reproducibility of qualitative assessments of temporal lobe atrophy in MRI studies.

Objective: To determine the reproducibility of the Scheltens visual rating scale in establishing atrophy of the medial temporal lobe.

Material And Methods: We used coronal T1-weighted inversion recovery sequences on a 1.5 Tesla MRI scanner to study 25 patients with clinically diagnosed Alzheimer's disease or mild cognitive decline and 25 subjects without cognitive decline.

Age modulates Fe3O4 nanoparticles liver toxicity: dose-dependent decrease in mitochondrial respiratory chain complexes activities and coupling in middle-aged as compared to young rats.

We examined the effects of iron oxide nanoparticles (IONPs) on mitochondrial respiratory chain complexes activities and mitochondrial coupling in young (3 months) and middle-aged (18 months) rat liver, organ largely involved in body iron detoxification. Isolated liver mitochondria were extracted using differential centrifugations. Maximal oxidative capacities (V(max), complexes I, III, and IV activities), V(succ) (complexes II, III, and IV activities), and V tmpd, (complex IV activity), together with mitochondrial coupling (V(max)/V0) were determined in controls conditions and after exposure to 250, 300, and 350 μ g/ml Fe3O4 in young and middle-aged rats.

Fumarate metabolism and ATP production in Pseudomonas fluorescens exposed to nitrosative stress.

Although nitrosative stress is known to severely impede the ability of living systems to generate adenosine triphosphate (ATP) via oxidative phosphorylation, there is limited information on how microorganisms fulfill their energy needs in order to survive reactive nitrogen species (RNS). In this study we demonstrate an elaborate strategy involving substrate-level phosphorylation that enables the soil microbe Pseudomonas fluorescens to synthesize ATP in a defined medium with fumarate as the sole carbon source. The enhanced activities of such enzymes as phosphoenolpyruvate carboxylase and pyruvate phosphate dikinase coupled with the increased activities of phospho-transfer enzymes like adenylate kinase and nucleoside diphophate kinase provide an effective strategy to produce high energy nucleosides in an O2-independent manner.

Early predictors of multiple sclerosis after a typical clinically isolated syndrome.

Background: The 2010 McDonald criteria allow diagnosing multiple sclerosis (MS) with one magnetic resonance imaging (MRI) scan. Nevertheless, not all patients at risk fulfil criteria at baseline. Other predictive factors (PFs) are: age ≤40 years, positive oligoclonal bands (OBs), and ≥3 periventricular lesions.

Probiotics (VSL#3) prevent endothelial dysfunction in rats with portal hypertension: role of the angiotensin system.

Aims: Portal hypertension characterized by generalized vasodilatation with endothelial dysfunction affecting nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) has been suggested to involve bacterial translocation and/or the angiotensin system. The possibility that ingestion of probiotics prevents endothelial dysfunction in rats following common bile duct ligation (CBDL) was evaluated.

Methods: Rats received either control drinking water or the probiotic VSL#3 solution (50 billion bacteria.

Neuroimaging in status epilepticus secondary to paraneoplastic autoimmune encephalitis.

Aim: To describe the characteristic magnetic resonance imaging (MRI) findings of paraneoplastic autoimmune encephalitis in patients with new-onset status epilepticus.

Materials And Methods: The neuroimaging and clinical data of five patients with paraneoplastic autoimmune encephalitis debuting as status epilepticus were retrospectively reviewed. All patients met the criteria for definite paraneoplastic syndrome and all underwent brain MRI during the status epilepticus episode or immediately after recovery.

Zinc toxicity and ATP production in Pseudomonas fluorescens.

Aims: To identify the molecular networks in Pseudomonas fluorescens that convey resistance to toxic concentrations of Zn, a common pollutant and hazard to biological systems.

Methods And Results: Pseudomonas fluorescens strain ATCC 13525 was cultured in growth medium with millimolar concentrations of Zn. Enzymatic activities and metabolite levels were monitored with the aid of in-gel activity assays and high-performance liquid chromatography, respectively.