Integrated Place-Based Primary Interventions: Levers and Tensions Related to Multilevel Governance for Community Integrated Pathways, A Multiple Case Study.

Integrated Place-Based Primary Interventions (IPPIs) are considered an innovative response to the challenges and complex issues faced in disadvantaged areas where traditional institutional services have difficulty reaching people in vulnerable situations. IPPIs are an innovative approach to the delivery of in services, conceived as an original community-based local care and service pathways. However, these intervention practices require adaptive modes of governance.

Distribution of metals and radionuclides in the lichens and from the past uranium mining region of Elliot Lake, Ontario, Canada.

The present study was performed in the Elliot Lake area (Ontario, Canada), a site of uranium mining and milling for nearly 40 years between 1950's and 1990's. Although mining activities ceased in the mid-1990's, the site hosts several tailings management areas (TMAs) which are under ongoing rehabilitation and monitoring. Several surveys using lichens as a biomonitoring tool were completed in the 1980s and the 1990s to assess the levels of contaminants.

A balancing act: interactions within NuA4/TIP60 regulate picNuA4 function in Saccharomyces cerevisiae and humans.

The NuA4 lysine acetyltransferase complex acetylates histone and nonhistone proteins and functions in transcription regulation, cell cycle progression, and DNA repair. NuA4 harbors an interesting duality in that its catalytic module can function independently and distinctly as picNuA4. At the molecular level, picNuA4 anchors to its bigger brother via physical interactions between the C-terminus of Epl1 and the HSA domain of Eaf1, the NuA4 central scaffolding subunit.

A review on the use of lichens as a biomonitoring tool for environmental radioactivity.

Lichens have been widely used as a biomonitoring tool to record the distribution and concentration of airborne radioactivity and pollutants such as metals. There are limitations, however: although pollutants can be preserved in lichen tissues for long periods of time, not all radioactive and inert elements behave similarly. The chemical species of elements at the source, once captured, and the mode of storage within lichens play a role in this biomonitoring tool.

Canadian French Translation and Preliminary Validation of the Conformity to Masculine Norms Inventory: A Pilot Study.

Conformity to masculine norms has been linked to poor mental and physical health outcomes. Its valid assessment among subgroups of the population is therefore a crucial step in the investigation of intercultural variability in the enactment of masculinity, as well as its causes, costs, and benefits. The present pilot study aimed to adapt and conduct a preliminary validation of a French version of the Conformity to Masculine Norms Inventory (CMNI-22), a self-report questionnaire designed to assess overall conformity to male gender standards.

Sinapic acid phenethyl ester as a potent selective 5-lipoxygenase inhibitor: Synthesis and structure-activity relationship.

Given the hepatotoxicity and an unfavorable pharmacokinetic profile of zileuton (Zyflo ), currently the only approved and clinically used 5-Lipoxygenase (5-LO) inhibitor, the search for potent and safe 5-LO inhibitors is highly demanded. The action of several phenolic acid phenethyl esters as potential 5-Lipoxygenase (5-LO) inhibitors has been investigated. For this purpose, a series of 14 phenethyl esters was synthesized and their impact on 5-LO inhibition was evaluated.

Oncogenic role of PDK4 in human colon cancer cells.

Background: Cancer cells maintain high rates of glycolysis. Pyruvate dehydrogenase kinases (PDK) contribute to this phenomenon, which favours apoptosis resistance and cellular transformation. We previously reported upregulation of PDK4 in normal mucosa of colorectal cancer (CRC) patients compared with controls and in preneoplastic intestine of our mouse model.

Murine MTHFD1-synthetase deficiency, a model for the human MTHFD1 R653Q polymorphism, decreases growth of colorectal tumors.

The common R653Q variant (∼20% homozygosity in Caucasians) in the synthetase domain of the folate-metabolizing enzyme MTHFD1 reduces purine synthesis. Although this variant does not appear to affect risk for colorectal cancer, we questioned whether it would affect growth of colorectal tumors. We induced tumor formation in a mouse model for MTHFD1-synthetase deficiency (Mthfd1S ) using combined administration of azoxymethane (AOM) and dextran sodium sulfate (DSS) in male and female wild-type and Mthfd1S mice.

Structure-activity relationship of caffeic acid phenethyl ester analogs as new 5-lipoxygenase inhibitors.

Leukotrienes (LTs) are a class of lipid mediators implicated in numerous inflammatory disorders. Caffeic acid phenethyl ester (CAPE) possesses potent anti-LTs activity through the inhibition of 5-lipoxygenase (5-LO), the key enzyme in the biosynthesis of LTs. In this study, we describe the design and synthesis of CAPE analogs as radical scavengers and 5-LO inhibitors.

The Psychometric Properties of a Modified Sit-to-Stand Test With Use of the Upper Extremities in Institutionalized Older Adults.

Current sit-to-stand protocols do not permit use of upper extremities, limiting the protocols' utility for institutionalized older adults with diminished physical function. The objective of this study was to modify a 30-s sit-to-stand protocol to allow for arm use and to examine test-retest reliability and convergent validity; 54 institutionalized older adult men (age = 91 ± 3 year) performed the 30-s sit-to-stand twice within a span of 3 to 7 days. Results suggest good test-retest reliability (intraclass correlation coefficient = .

Deep brain stimulator implantation in a diagnostic MRI suite: infection history over a 10-year period.

OBJECTIVE The objective of this study was to assess the incidence of postoperative hardware infection following interventional (i)MRI-guided implantation of deep brain stimulation (DBS) electrodes in a diagnostic MRI scanner. METHODS A diagnostic 1.5-T MRI scanner was used over a 10-year period to implant DBS electrodes for movement disorders.

Murine diet/tissue and human brain tumorigenesis alter Mthfr/MTHFR 5'-end methylation.

Polymorphisms and decreased activity of methylenetetrahydrofolate reductase (MTHFR) are linked to disease, including cancer. However, epigenetic regulation has not been thoroughly studied. Our goal was to generate DNA methylation profiles of murine/human MTHFR gene regions and examine methylation in brain and liver tumors.

Synthesis and biological activity of arylspiroborate salts derived from caffeic Acid phenethyl ester.

Two novel boron compounds containing caffeic acid phenethyl ester (CAPE) derivatives have been prepared and characterized fully. These new compounds and CAPE have been investigated for potential antioxidant and antimicrobial properties and their ability to inhibit 5-lipoxygenase and whether chelation to boron improves their biological activity. Sodium salt 4 was generally more active than ammonium salt 5 in the biological assays and surpassed the radical scavenging ability of CAPE.

High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice.

Background: Increased consumption of folic acid is prevalent, leading to concerns about negative consequences. The effects of folic acid on the liver, the primary organ for folate metabolism, are largely unknown. Methylenetetrahydrofolate reductase (MTHFR) provides methyl donors for S-adenosylmethionine (SAM) synthesis and methylation reactions.

Clicked cinnamic/caffeic esters and amides as radical scavengers and 5-lipoxygenase inhibitors.

5-Lipoxygenase (5-LO) is the key enzyme responsible for the conversion of arachidonic acid to leukotrienes, a class of lipid mediators implicated in inflammatory disorders. In this paper, we describe the design, synthesis, and preliminary activity studies of novel clicked caffeic esters and amides as radical scavengers and 5-LO inhibitors. From known 5-LO inhibitor 3 as a lead, cinnamic esters 8a-h and amides 9a-h as well as caffeic esters 15a-h and amides 16a-h were synthesized by Cu(I)-catalyzed [1,3]-dipolar cycloaddition with the appropriate azide precursors and terminal alkynes.

Genes with aberrant expression in murine preneoplastic intestine show epigenetic and expression changes in normal mucosa of colon cancer patients.

An understanding of early genetic/epigenetic changes in colorectal cancer would aid in diagnosis and prognosis. To identify these changes in human preneoplastic tissue, we first studied our mouse model in which Mthfr⁺/⁻ BALB/c mice fed folate-deficient diets develop intestinal tumors in contrast to Mthfr⁺/⁺ BALB/c mice fed control diets. Transcriptome profiling was performed in normal intestine from mice with low or high tumor susceptibility.

β,β-carotene 15,15'-monooxygenase and its substrate β-carotene modulate migration and invasion in colorectal carcinoma cells.

Background: β,β-Carotene 15,15'-monooxygenase (BCMO1) converts β-carotene to retinaldehyde. Increased β-carotene consumption is linked to antitumor effects. Retinoic acid reduces the invasiveness in cancer, through inhibition of matrix metalloproteinases (MMPs).

Loss of H3 K79 trimethylation leads to suppression of Rtt107-dependent DNA damage sensitivity through the translesion synthesis pathway.

Genomic integrity is maintained by the coordinated interaction of many DNA damage response pathways, including checkpoints, DNA repair processes, and cell cycle restart. In Saccharomyces cerevisiae, the BRCA1 C-terminal domain-containing protein Rtt107/Esc4 is required for restart of DNA replication after successful repair of DNA damage and for cellular resistance to DNA-damaging agents. Rtt107 and its interaction partner Slx4 are phosphorylated during the initial phase of DNA damage response by the checkpoint kinases Mec1 and Tel1.

NuA4 and SWR1-C: two chromatin-modifying complexes with overlapping functions and components.

Chromatin structure is important for the compaction of eukaryotic genomes, thus chromatin modifications play a fundamental role in regulating many cellular processes. The coordinated activities of various chromatin-remodelling and -modifying complexes are crucial in maintaining distinct chromatin neighbourhoods, which in turn ensure appropriate gene expression, as well as DNA replication, repair, and recombination. SWR1-C is an ATP-dependent histone deposition complex for the histone variant H2A.

Subthalamic nucleus deep brain stimulator placement using high-field interventional magnetic resonance imaging and a skull-mounted aiming device: technique and application accuracy.

Object: The authors discuss their method for placement of deep brain stimulation (DBS) electrodes using interventional MR (iMR) imaging and report on the accuracy of the technique, its initial clinical efficacy, and associated complications in a consecutive series of subthalamic nucleus (STN) DBS implants to treat Parkinson disease (PD).

Methods: A skull-mounted aiming device (Medtronic NexFrame) was used in conjunction with real-time MR imaging (Philips Intera 1.5T).

Microelectrode recording in the posterior hypothalamic region in humans.

Introduction: Deep brain stimulation of the posterior hypothalamic region (PHR) is an emerging technique for the treatment of medically intractable cluster headache. Few reports have analyzed single unit neuronal recordings in the human PHR. We report properties of spontaneous neuronal discharge in PHR for 6 patients who underwent DBS for cluster headaches.

Single unit "pauser" characteristics of the globus pallidus pars externa distinguish primary dystonia from secondary dystonia and Parkinson's disease.

The presence of high frequency discharge neurons with long periods of silence or "pauses" in the globus pallidus pars externa (GPe) is a unique identifying feature of this nucleus. Prior studies have demonstrated that pause characteristics reflect synaptic inputs into GPe. We hypothesized that GPe pause characteristics should distinguish movement disorders whose basal ganglia network abnormalities are different.

Health management program: factors influencing completion of therapy with high-dose interferon alfa-2b for high-risk melanoma.

The goal of the 1-year observational, multicentre, open-label study reported here was to identify factors influencing adherence to high-dose interferon alfa-2b adjuvant therapy in patients at high risk of recurrence following surgical excision of malignant melanoma. The study was carried out in 23 tertiary-care centres across Canada.The 225 patients enrolled in the study all had malignant melanoma that was surgically excised and that required adjuvant treatment with interferon alfa-2b.

Placement of deep brain stimulator electrodes using real-time high-field interventional magnetic resonance imaging.

A methodology is presented for placing deep brain stimulator electrodes under direct MR image guidance. The technique utilized a small, skull-mounted trajectory guide that is optimized for accurate alignment under MR fluoroscopy. Iterative confirmation scans are used to monitor device alignment and brain penetration.

A phylogenetically based secondary structure for the yeast telomerase RNA.

Background: Telomerase is a ribonucleoprotein complex whose RNA moiety dictates the addition of specific simple sequences onto chromosomes ends. While relevant for certain human genetic diseases, the contribution of the essential telomerase RNA to RNP assembly still remains unclear. Phylogenetic analyses of vertebrate and ciliate telomerase RNAs revealed conserved elements that potentially organize protein subunits for RNP function.