Survey of northern informal and formal mental health practitioners.

Background: This survey is part of a multi-year research study on informal and formal mental health support in northern Canada involving the use of qualitative and quantitative data collection and analysis methods in an effort to better understand mental health in a northern context.

Objective: The main objective of the 3-year study was to document the situation of formal and informal helpers in providing mental health support in isolated northern communities in northern British Columbia, northern Alberta, Yukon, Northwest Territories and Nunavut. The intent of developing a survey was to include more participants in the research and access those working in small communities who would be concerned regarding confidentiality and anonymity due to their high profile within smaller populations.

Mal, more than a bridge to MyD88.

The family of type 1 transmembrane proteins known as Toll-like receptors (TLRs) provide early immune system recognition and response to infection. In order to transmit their signal to the nucleus and initiate activation of pro-inflammatory and anti-microbial genes, TLRs must initiate a cytoplasmic signalling cascade, which is alternately controlled by 6 known signalling adaptors. These signaling adaptors are crucial for activating the correct immune response to any given TLR / pathogen interaction.

Informal and formal mental health: preliminary qualitative findings.

Background: Northern-based research on mental health support, no matter the specific profession, helps to inform instruction of new practitioners and practitioners already working in rural or isolated conditions. Understanding the complexities of northern mental health support not only benefits clients and practitioners living in the North, but also helps prepare psychologists and counsellors preparing to work in other countries with large rural and isolated populations. The qualitative phase is part of a multi-year research study on informal and formal mental health support in northern Canada involving the use of qualitative and quantitative data collection and analysis methods.

Caring for oneself to care for others: physicians and their self-care.

It is well known that clinicians experience distress and grief in response to their patients' suffering. Oncologists and palliative care specialists are no exception since they commonly experience patient loss and are often affected by unprocessed grief. These emotions can compromise clinicians' personal well-being, since unexamined emotions may lead to burnout, moral distress, compassion fatigue, and poor clinical decisions which adversely affect patient care.

Bruton's tyrosine kinase mediates the synergistic signalling between TLR9 and the B cell receptor by regulating calcium and calmodulin.

B cells signal through both the B cell receptor (BCR) which binds antigens and Toll-like receptors (TLRs) including TLR9 which recognises CpG DNA. Activation of TLR9 synergises with BCR signalling when the BCR and TLR9 co-localise within an auto-phagosome-like compartment. Here we report that Bruton's tyrosine kinase (BTK) is required for synergistic IL6 production and up-regulation of surface expression of MHC-class-II, CD69 and CD86 in primary murine and human B cells.

Distinct mechanisms for induction and tolerance regulate the immediate early genes encoding interleukin 1β and tumor necrosis factor α.

Interleukin-1β and Tumor Necrosis Factor α play related, but distinct, roles in immunity and disease. Our study revealed major mechanistic distinctions in the Toll-like receptor (TLR) signaling-dependent induction for the rapidly expressed genes (IL1B and TNF) coding for these two cytokines. Prior to induction, TNF exhibited pre-bound TATA Binding Protein (TBP) and paused RNA Polymerase II (Pol II), hallmarks of poised immediate-early (IE) genes.

A long noncoding RNA mediates both activation and repression of immune response genes.

An inducible program of inflammatory gene expression is central to antimicrobial defenses. This response is controlled by a collaboration involving signal-dependent activation of transcription factors, transcriptional co-regulators, and chromatin-modifying factors. We have identified a long noncoding RNA (lncRNA) that acts as a key regulator of this inflammatory response.

Nuclear factor κB2 p52 protein has a role in antiviral immunity through IκB kinase epsilon-dependent induction of Sp1 protein and interleukin 15.

In this study we describe a previously unreported function for NFκB2, an NFκB family transcription factor, in antiviral immunity. NFκB2 is induced in response to poly(I:C), a mimic of viral dsRNA. Poly(I:C), acting via TLR3, induces p52-dependent transactivation of a reporter gene in a manner that requires the kinase activity of IκB kinase ε (IKKε) and the transactivating potential of RelA/p65.

How metabolism generates signals during innate immunity and inflammation.

The interplay between immunity, inflammation, and metabolic changes is a growing field of research. Toll-like receptors and NOD-like receptors are families of innate immune receptors, and their role in the human immune response is well documented. Exciting new evidence is emerging with regard to their role in the regulation of metabolism and the activation of inflammatory pathways during the progression of metabolic disorders such as type 2 diabetes and atherosclerosis.

Building unique bonds to fight misplaced DNA.

A cyclic dinucleotide comprised of GMP and AMP was previously shown to be a key intermediate during activation of innate immune responses to cytosolic DNA. A report by Patel and Tuschl groups published in Cell reveals the structure of the enzyme involved in the synthesis of this second messenger and identifies this cyclic dinucleotide as a unique compound in metazoan cell signaling.

miR-223: infection, inflammation and cancer.

Expression of the microRNA miR-223 is deregulated during influenza or hepatitis B infection and in inflammatory bowel disease, type 2 diabetes, leukaemia and lymphoma. Although this may also be the result of the disease per se, increasing evidence suggests a role for miR-223 in limiting inflammation to prevent collateral damage during infection and in preventing oncogenic myeloid transformation. Validated targets for miR-223 that have effects on inflammation and infection include granzyme B, IKKα, Roquin and STAT3.

The history of Toll-like receptors - redefining innate immunity.

The discovery of Toll-like receptors (TLRs) was an important event for immunology research and was recognized as such with the awarding of the 2011 Nobel Prize in Physiology or Medicine to Jules Hoffmann and Bruce Beutler, who, together with Ralph Steinman, the third winner of the 2011 Nobel Prize and the person who discovered the dendritic cell, were pioneers in the field of innate immunity. TLRs have a central role in immunity - in this Timeline article, we describe the landmark findings that gave rise to this important field of research.

Admission criteria and diversity in medical school.

Context: The under-representation in medical education of students from lower socio-economic backgrounds is an important social issue. There is currently little evidence about whether changes in admission strategies might increase the diversity of the medical student population. Denmark introduced an 'attribute-based' admission track to make it easier for students who may not be eligible for admission on the 'grade-based' track to be admitted on the basis of attributes other than academic performance.

Nurse-led Early Triage (NET) study of chest pain patients: a long term evaluation study of a service development aimed at improving the management of patients with non-ST-elevation acute coronary syndromes.

Background: Patients presenting with non-ST-elevation acute coronary syndrome (NSTE-ACS) are at risk of early death. This may be reduced by timely assessment and treatment.

Objectives: The purpose of this study was to evaluate if Nurse-led Early Triage (NET) in the coronary care unit (CCU) can improve time to assessment and management of NSTE-ACS patients.

The histone deacetylase inhibitor sodium valproate causes limited transcriptional change in mouse embryonic stem cells but selectively overrides Polycomb-mediated Hoxb silencing.

Background: Histone deacetylase inhibitors (HDACi) cause histone hyperacetylation and H3K4 hypermethylation in various cell types. They find clinical application as anti-epileptics and chemotherapeutic agents, but the pathways through which they operate remain unclear. Surprisingly, changes in gene expression caused by HDACi are often limited in extent and can be positive or negative.

MyD88 adaptor-like (Mal) functions in the epithelial barrier and contributes to intestinal integrity via protein kinase C.

MyD88 adapter-like (Mal)-deficient mice displayed increased susceptibility to oral but not intraperitoneal infection with Salmonella Typhimurium. Bone marrow chimeras demonstrated that mice with Mal-deficient non-hematopoietic cells were more susceptible to infection, indicating a role for Mal in non-myeloid cells. We observed perturbed barrier function in Mal(-/-) mice, as indicated by reduced electrical resistance and increased mucosa blood permeability following infection.

Succinate is an inflammatory signal that induces IL-1β through HIF-1α.

Macrophages activated by the Gram-negative bacterial product lipopolysaccharide switch their core metabolism from oxidative phosphorylation to glycolysis. Here we show that inhibition of glycolysis with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1β but not tumour-necrosis factor-α in mouse macrophages. A comprehensive metabolic map of lipopolysaccharide-activated macrophages shows upregulation of glycolytic and downregulation of mitochondrial genes, which correlates directly with the expression profiles of altered metabolites.

Co-blasting of titanium surfaces with an abrasive and hydroxyapatite to produce bioactive coatings: substrate and coating characterisation.

The aim of this work is to assess the influence of two blast media on the deposition of hydroxyapatite onto a titanium substrate using a novel ambient temperature coating technique named CoBlast. CoBlast was developed to address the problems with high temperature coating techniques. The blasting media used in this study were Al2O3 and a sintered apatite powder.

An investigation of the biochemical properties of tetrazines as potential coating additives.

1,2,4,5-Tetrazine and its 3,6-disubstituted derivatives are currently used for a range of industrial and medical applications as they exhibit particular coordination chemistries, characterised by electron and charge transfer phenomena. The aim of the present work is to synthesise two tetrazine derivatives, namely 3,6-dihydrazino-1,2,4,5-tetrazine (DHDTZ) and 1,2,4,5-tetrazine dicarboxylic acid (DCTZ), and determine their antibacterial, antioxidant and anticorrosion characteristics as additives in a sol-gel coating on SS316L steel. The structure of the tetrazines was confirmed by NMR and FTIR while the surface morphology of bacterial cells in their presence was observed by AFM.

C/EBPα and MYB regulate FLT3 expression in AML.

The interaction between the receptor FLT3 (FMS-like tyrosine kinase-3) and its ligand FL leads to crucial signalling during the early stages of the commitment of haematopoietic stem cells. Mutation or over-expression of the FLT3 gene, leading to constitutive signalling, enhances the survival and expansion of a variety of leukaemias and is associated with an unfavourable clinical outcome for acute myeloid leukaemia (AML) patients. In this study, we used a murine cellular model for AML and primary leukaemic cells from AML patients to investigate the molecular mechanisms underlying the regulation of FLT3 gene expression and identify its key cis- and trans-regulators.

Metabolism of inflammation limited by AMPK and pseudo-starvation.

Metabolic changes in cells that participate in inflammation, such as activated macrophages and T-helper 17 cells, include a shift towards enhanced glucose uptake, glycolysis and increased activity of the pentose phosphate pathway. Opposing roles in these changes for hypoxia-inducible factor 1α and AMP-activated protein kinase have been proposed. By contrast, anti-inflammatory cells, such as M2 macrophages, regulatory T cells and quiescent memory T cells, have lower glycolytic rates and higher levels of oxidative metabolism.

The GOLD domain-containing protein TMED1 is involved in interleukin-33 signaling.

The proinflammatory danger signal IL-33, which is released from damaged or dying cells, achieves its effects via the IL-1R family member ST2L. The detection of IL-33 by ST2L initiates downstream signaling pathways that result in the activation of MAPKs and NF-κB. Here, we show that TMED1 associates with ST2L.

Modulatory mechanisms controlling the NLRP3 inflammasome in inflammation: recent developments.

The protein NLRP3 has emerged as a central regulator in the inflammatory process, being implicated directly in hereditary cryopyrinopathies, and indirectly in diseases such as gout, Type 2 diabetes and atherosclerosis. NLRP3 is an important regulator of caspase-1, the enzyme that processes the immature form of IL-1β into the active protein. The control of NLRP3 has therefore become a focus of research with evidence for redox regulation, ubiquitination and regulation by miRNA-223, kinases and calcium all emerging as controllers of NLRP3.

"Transflammation": when innate immunity meets induced pluripotency.

A surprising link between innate immunity and nuclear reprogramming is reported by Lee et al.; this discovery may boost the efficiency of stem cell production.