Alien Registration- Perreault, Mary A. (Caribou, Aroostook County)

https://digitalmaine.com/alien_docs/26081/thumbnail.jp

Le pouvoir médical et le défi de la collaboration interprofessionnelle. Trois cas de figure

Dans la foulée de la loi 90 adoptée au Québec en 2002, l’article analyse l’évolution du statut professionnel des médecins dans le cadre spécifique de leurs relations avec trois groupes de professionnels : les infirmières, les chiropraticiens et les techniciens ambulanciers. Tirées d’entrevues et de sources documentaires, nos données montrent que les médecins n’ont pas renoncé à une part significative de leur pouvoir dans leurs rapports avec ces groupes professionnels : en refusant de déléguer le droit au diagnostic et à la détermination du traitement médical, ils continuent d’exercer un contrôle réel sur les pratiques des autres groupes professionnels.Following the adoption of Bill 90 in Québec in 2002, this paper analyses the changes in the professional status of physicians in the specific context of their relations with three professional groups: nurses, chiropractors and ambulance technicians. Our data, drawn from interviews and from documentary sources, indicate that physicians have not given up a significant portion of their power in their relations with these professional groups: by refusing to delegate the right to perform diagnosis and to prescribe medical treatment, they continue to exercise significant control over the practices of other professional groups

G-quadruplex located in the 5’UTR of the BAG-1 mRNA affects both its cap-dependent and cap-independent translation through global secondary structure maintenance

Abstract: The anti-apoptotic BAG-1 protein isoforms are known to be overexpressed in colorectal tumors and are considered to be potential therapeutic targets. The isoforms are derived fromalternative translation initiations occuring at four in-frame start codons of a single mRNA transcript. Its 5'UTR also contains an internal ribosome entry site (IRES) regulating the capindependent translation of the transcript. An RNA Gquadruplex (rG4) is located at the 5'end of the BAG- 1 5'UTR, upstream of the known cis-regulatory elements. Herein, we observed that the expression of BAG-1 isoforms is post-transcriptionally regulated in colorectal cancer cells and tumors, and that stabilisation of the rG4 by small molecules ligands reduces the expression of endogenous BAG-1 isoforms. We demonstrated a critical role for the rG4 in the control of both cap-dependent and independent translation of the BAG-1 mRNA in colorectal cancer cells. Additionally, we found an upstream ORF that also represses BAG-1 mRNA translation. The structural probing of the complete 5'UTR showed that the rG4 acts as a steric block which controls the initiation of translation at each start codon of the transcript and also maintains the global 5'UTR secondary structure required for IRES-dependent translation

Dissecting the expression landscape of cytochromes P450 in hepatocellular carcinoma: towards novel molecular biomarkers

Abstract: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths around the world. Recent advances in genomic technologies have allowed the identification of various molecular signatures in HCC tissues. For instance, differential gene expression levels of various cytochrome P450 genes (CYP450) have been reported in studies performed on limited numbers of HCC tissue samples, or focused on a small subset on CYP450s. In the present study, we monitored the expression landscape of all the members of the CYP450 family (57 genes) in more than 200 HCC tissues using RNA-Seq data from The Cancer Genome Atlas. Using stringent statistical filters and data from paired tissues, we identified significantly dysregulated CYP450 genes in HCC. Moreover, the expression level of selected CYP450s was validated by qPCR on cDNA samples from an independent cohort. Threshold values (sensitivity and specificity) based on dysregulated gene expression were also determined to allow for confident identification of HCC tissues. Finally, a global look at expression levels of the 57 members of the CYP450 family across ten different cancer types revealed specific expression signatures. Overall, this study provides useful information on the transcriptomic landscape of CYP450 genes in HCC and on new potential HCC biomarkers

3′ UTR G-quadruplexes regulate miRNA binding

Abstract : MicroRNAs (miRNAs) are small noncoding RNAs that repress the translation of their target genes. It has previously been shown that a target’s availability to miRNA can be affected by its structure. G-quadruplexes (G4) are noncanonical structures adopted by G-rich nucleic acids that have been shown to have multiple biological functions. In this study, whether or not G4 structures’ presence in the 3′ UTRs of mRNAs can hinder miRNA binding was investigated. Putative G4 overlapping with predicted miRNAs’ binding sites was searched for, and 44,294 hits were found in humans. The FADS2 mRNA/mir331-3p pair was selected as a model example. In-line probing and G4-specific fluorescent ligand experiments binding were performed and confirmed the presence of a G4 near the predicted miRNA binding site. Subsequent luciferase assays showed that the presence of the G4 prevents the binding of mir331-3p in cellulo. Together, these results served as proof of concept that a G4 structure present in a 3′ UTR sequence should be taken into consideration when predicting miRNA binding sites

Role of glucuronidation for hepatic detoxification and urinary elimination of toxic bile acids during biliary obstruction

Biliary obstruction, a severe cholestatic condition, results in a huge accumulation of toxic bile acids (BA) in the liver. Glucuronidation, a conjugation reaction, is thought to protect the liver by both reducing hepatic BA toxicity and increasing their urinary elimination. The present study evaluates the contribution of each process in the overall BA detoxification by glucuronidation. Glucuronide (G), glycine, taurine conjugates, and unconjugated BAs were quantified in pre- and post-biliary stenting urine samples from 12 patients with biliary obstruction, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The same LC-MS/MS procedure was used to quantify intra- and extracellular BA-G in Hepatoma HepG2 cells. Bile acid-induced toxicity in HepG2 cells was evaluated using MTS reduction, caspase-3 and flow cytometry assays. When compared to post-treatment samples, pre-stenting urines were enriched in glucuronide-, taurine- and glycine-conjugated BAs. Biliary stenting increased the relative BA-G abundance in the urinary BA pool, and reduced the proportion of taurine- and glycine-conjugates. Lithocholic, deoxycholic and chenodeoxycholic acids were the most cytotoxic and pro-apoptotic/necrotic BAs for HepG2 cells. Other species, such as the cholic, hyocholic and hyodeoxycholic acids were nontoxic. All BA-G assayed were less toxic and displayed lower pro-apoptotic/necrotic effects than their unconjugated precursors, even if they were able to penetrate into HepG2 cells. Under severe cholestatic conditions, urinary excretion favors the elimination of amidated BAs, while glucuronidation allows the conversion of cytotoxic BAs into nontoxic derivatives

Reovirus μ2 protein modulates host cell alternative splicing by reducing protein levels of U5 snRNP core components

Abstract : Mammalian orthoreovirus (MRV) is a doublestranded RNA virus from the Reoviridae family presenting a promising activity as an oncolytic virus. Recent studies have underlined MRV’s ability to alter cellular alternative splicing (AS) during infection, with a limited understanding of the mechanisms at play. In this study, we investigated how MRV modulates AS. Using a combination of cell biology and reverse genetics experiments, we demonstrated that theM1 gene segment, encoding the μ2 protein, is the primary determinant of MRV’s ability to alter AS, and that the amino acid at position 208 in μ2 is critical to induce these changes. Moreover, we showed that the expression of μ2 by itself is sufficient to trigger AS changes, and its ability to enter the nucleus is not required for all these changes. Moreover, we identified core components of the U5 snRNP (i.e. EFTUD2, PRPF8, and SNRNP200) as interactors of μ2 that are required for MRV modulation of AS. Finally, these U5 snRNP components are reduced at the protein level by both MRV infection and μ2 expression. Our findings identify the reduction of U5 snRNP components levels as a new mechanism by which viruses alter cellular AS

A Novel Ribozyme-Based Prophylaxis Inhibits Influenza A Virus Replication and Protects from Severe Disease

Influenza A virus seasonal outbreaks and occasional pandemics represent a global health threat. The high genetic instability of this virus permits rapid escape from the host immune system and emergence of resistance to antivirals. There is thus an urgent need to develop novel approaches for efficient treatment of newly emerging strains. Based on a sequence alignment of representatives from every subtype known to infect humans, we identified nucleic acid regions that are conserved amongst these influenza A populations. We then engineered SOFA-HDV-Ribozymes as therapeutic tools recognizing these conserved regions to catalytically cleave the corresponding viral mRNA targets. The most promising ribozymes were chosen based on an initial in silico screening, and their efficacy was assessed using in vitro cleavage assays. Further characterization of their antiviral effect in cell culture and in mice led to the gradual identification of prophylactic SOFA-HDV-Ribozyme combinations, providing proof-of-principle for the potential of this novel strategy to develop antivirals against genetically highly variable viruses

Priority interventions to improve the management of chronic non-cancer pain in primary care: a participatory research of the ACCORD program

Purpose: There is evidence that the management of chronic non-cancer pain (CNCP) in primary care is far from being optimal. A 1-day workshop was held to explore the perceptions of key actors regarding the challenges and priority interventions to improve CNCP management in primary care. Methods: Using the Chronic Care Model as a conceptual framework, physicians (n=6), pharmacists (n=6), nurses (n=6), physiotherapists (n=6), psychologists (n=6), pain specialists (n=6), patients (n=3), family members (n=3), decision makers and managers (n=4), and pain researchers (n=7) took part in seven focus groups and five nominal groups. Results: Challenges identified in focus group discussions were related to five dimensions: knowledge gap, “work in silos”, lack of awareness that CNCP represents an important clinical problem, difficulties in access to health professionals and services, and patient empowerment needs. Based on the nominal group discussions, the following priority interventions were identified: interdisciplinary continuing education, interdisciplinary treatment approach, regional expert leadership, creation and definition of care paths, and patient education programs. Conclusion: Barriers to optimal management of CNCP in primary care are numerous. Improving its management cannot be envisioned without considering multifaceted interventions targeting several dimensions of the Chronic Care Model and focusing on both clinicians and patients

Portable point-of-use photoelectrocatalytic device provides rapid water disinfection

Portable water purification devices are needed to provide safe drinking water in rural communities, developing communities with low quality centralized water distribution, and military or recreational applications. Filtration, ultraviolet light, or chemical additives provide a spectrum of alternatives to remove pathogens from water. For the first time, we design, fabricate and demonstrate the performance of a small portable photoelectric point-of-use device, and document its performance on pathogen inactivation. The device utilizes a commercial teacup from which TiO2 nanotube photoanodes were produced in-situ and, with a small rechargeable battery powered 365 nm light emitting diode, was able to achieve 5-log inactivation of Escherichia coli in 10 s and 2.6-log of Legionella in 60 s of treatment in model water samples. Treatment of natural water achieved a 1-log bacteria inactivation after 30 s due to matrix effects. The electro-photocatalytic disinfection reactor in a kup (e-DRINK) can provide a feasible and affordable solution to ensure access to clean water. More broadly, this work demonstrates the potential for illumination to improve the efficiency of electrocatalytic surfaces