"Head of the Class": equity discourses related to department head appointments at one Canadian medical school.

Purpose: Equitable appointments of departmental leaders in medical schools have lagged behind other Equity, Diversity, and Inclusion (EDI) advancements. The purpose of this research was to 1) analyze how policy documents communicate changing ideas of EDI, employment equity, and departmental leadership; and 2) investigate department heads' (DH) perspectives on EDI policies and practices.

Methods: We conducted a critical discourse analysis to examine underlying assumptions shaping EDI and departmental leadership in one Canadian medical school.

Improving comprehensive emergency obstetric and newborn care in Tanzania: A qualitative study.

Aim: The purpose of this qualitative study was to explore how health care professionals, managers and community members experienced the implementation of a training program in comprehensive emergency obstetric and neonatal care training in rural Tanzania.

Background: Given the high rates of maternal and newborn mortality in Tanzania, the government committed to improving maternal health by increasing access to health care; improving reproductive, maternal, newborn health; reducing maternal and neonate mortality; and increasing the number of public health centers with emergency obstetric and neonatal care. To address the gap in emergency obstetric and neonatal care amongst the health workforce, five health care facilities in rural Tanzania participated in a 3-month specialized training program.

Healthcare providers and caregivers' perspectives on factors responsible for persistent malnutrition of under 5 children in Buhweju district, South Western Uganda; a phenomenological qualitative study.

Background: Unacceptably high levels of childhood malnutrition have been registered in all regions of Uganda over the years. Buhweju district alone contributed 46% prevalence of childhood malnutrition to the 47.8% estimated national prevalence for the whole of western Uganda in 2014.

Human Pharmacokinetic Parameters of Orally Administered Δ-Tetrahydrocannabinol Capsules Are Altered by Fed Versus Fasted Conditions and Sex Differences.

There is variability in the reported Δ-tetrahydrocannabinol (THC) and 11-hydroxy-tetrahydrocannabinol (11-OH-THC) pharmacokinetic (PK) and pharmacodynamic (PD) parameters between studies and there is limited investigation into how the presence of food or sex affect these parameters. In this study, we examined the PK and PD parameters of an encapsulated THC extract and its major active metabolite, 11-OH-THC, under different fed states. The study was a single-dose, randomized, double-blinded, four-way crossover investigation.

Providing postpartum care with limited resources: Experiences of nurse-midwives and obstetricians in urban Tanzania.

Background: Tanzania has high maternal and neonatal mortality rates. Comprehensive guidelines for postpartum care have been developed by the government as a means to improve health outcomes during the perinatal period. Despite the creation of these guidelines and the government's commitment to universal perinatal care for women and neonates, there is concern that the delivery of postpartum services may not be meeting the needs of mothers and neonates.

Modulating the endocannabinoid pathway as treatment for peripheral neuropathic pain: a selected review of preclinical studies.

Chemotherapy-induced neuropathic pain is a distressing and commonly occurring side effect of many commonly used chemotherapeutic agents, which in some cases may prevent cancer patients from being able to complete their treatment. Cannabinoid based therapies have the potential to manage or even prevent pain associated with this syndrome. Pre-clinical animal studies that investigate the modulation of the endocannabinoid system (endogenous cannabinoid pathway) are being conducted to better understand the mechanisms behind this phenomenon.

Paced monophasic and biphasic waveforms alter transmembrane potentials and metabolism of human fibroblasts.

Resting transmembrane potential (TMP) of primary human fibroblast cells was altered in predictable directions by subjecting cell cultures to specific monophasic and biphasic waveforms. Cells electrically stimulated with an anodal pulse resulted in hyperpolarization while a cathodal waveform depolarized the TMP to below that of non-paced control cells. The biphasic waveform, consisting of an anodal pulse followed immediately by an inverse symmetric cathodal pulse, also lessened the TMP similar to that of the cathodal pulse.

A selective review of medical cannabis in cancer pain management.

Insufficient management of cancer-associated chronic and neuropathic pain adversely affects patient quality of life. Patients who do not respond well to opioid analgesics, or have severe side effects from the use of traditional analgesics are in need of alternative therapeutic op-tions. Anecdotal evidence suggests that medical cannabis has potential to effectively manage pain in this patient population.

The Challenges of Providing Postpartum Education in Dar es Salaam, Tanzania: Narratives of Nurse-Midwives and Obstetricians.

Postpartum education can save lives of mothers and babies in developing countries, and the World Health Organization recommends all mothers receive three postpartum consultations. More information is needed to better understand how postpartum education is delivered and ultimately improves postpartum health outcomes. The purpose of this qualitative study was to examine how postpartum care was delivered in three postnatal hospital clinics in Dar es Salaam, Tanzania.

Support infrastructure available to Canadian residents completing post-graduate global health electives: current state and future directions.

Background: Global health electives offer medical trainees the opportunity to broaden their clinical horizons. Canadian universities have been encouraged by regulatory bodies to offer institutional support to medical students going abroad; however, the extent to which such support is available to residents has not been extensively studied.

Methods: We conducted a survey study of Canadian universities examining the institutional support available to post-graduate medical trainees before, during, and after global health electives.

Strengthening systems and scholarship for global health - and public health.

No abstract available.

Progressive increase in mtDNA 3243A>G heteroplasmy causes abrupt transcriptional reprogramming.

Variation in the intracellular percentage of normal and mutant mitochondrial DNAs (mtDNA) (heteroplasmy) can be associated with phenotypic heterogeneity in mtDNA diseases. Individuals that inherit the common disease-causing mtDNA tRNA(Leu(UUR)) 3243A>G mutation and harbor ∼10-30% 3243G mutant mtDNAs manifest diabetes and occasionally autism; individuals with ∼50-90% mutant mtDNAs manifest encephalomyopathies; and individuals with ∼90-100% mutant mtDNAs face perinatal lethality. To determine the basis of these abrupt phenotypic changes, we generated somatic cell cybrids harboring increasing levels of the 3243G mutant and analyzed the associated cellular phenotypes and nuclear DNA (nDNA) and mtDNA transcriptional profiles by RNA sequencing.

An inherited heteroplasmic mutation in mitochondrial gene COI in a patient with prostate cancer alters reactive oxygen, reactive nitrogen and proliferation.

Mitochondrial DNA (mtDNA) mutations have been found in many cancers but the physiological derangements caused by such mutations have remained elusive. Prostate cancer is associated with both inherited and somatic mutations in the cytochrome c oxidase (COI) gene. We present a prostate cancer patient-derived rare heteroplasmic mutation of this gene, part of mitochondrial respiratory complex IV.

Role of high mobility group box 1 (HMGB1) in wound healing.

Background: HMGB1, a non-histone chromosomal protein, can bind to the receptor for advanced glycation end products (RAGE) and act as an inflammatory mediator. We examined the role of HMGB1 in incisional wound healing and its possible mechanism of action through receptor for advanced glycation end products (RAGE).

Methods: Male Sprague-Dawley rats undergoing full-thickness incisional wounding with subcutaneous implantation of PVA sponges were given daily injections of ethyl pyruvate (EP) (40 mg/kg, i.

A neonatal polyvisceral failure linked to a de novo homoplasmic mutation in the mitochondrially encoded cytochrome b gene.

Mutations within the mitochondrially encoded cytochrome b (MTCYB) gene are heteroplasmic and lead to severe exercise intolerance. We describe an unusual clinical presentation secondary to a novel homoplasmic mutation within MTCYB. The m.

A novel NDUFA1 mutation leads to a progressive mitochondrial complex I-specific neurodegenerative disease.

Mitochondrial diseases have been shown to result from mutations in mitochondrial genes located in either the nuclear DNA (nDNA) or mitochondrial DNA (mtDNA). Mitochondrial OXPHOS complex I has 45 subunits encoded by 38 nuclear and 7 mitochondrial genes. Two male patients in a putative X-linked pedigree exhibiting a progressive neurodegenerative disorder and a severe muscle complex I enzyme defect were analyzed for mutations in the 38 nDNA and seven mtDNA encoded complex I subunits.

Trypanosoma brucei RNA editing protein TbMP42 (band VI) is crucial for the endonucleolytic cleavages but not the subsequent steps of U-deletion and U-insertion.

Trypanosome mitochondrial mRNAs achieve their coding sequences through RNA editing. This process, catalyzed by approximately 20S protein complexes, involves large numbers of uridylate (U) insertions and deletions within mRNA precursors. Here we analyze the role of the essential TbMP42 protein (band VI/KREPA2) by individually examining each step of the U-deletional and U-insertional editing cycles, using reactions in the approximately linear range.

In Trypanosoma brucei RNA editing, TbMP18 (band VII) is critical for editosome integrity and for both insertional and deletional cleavages.

In trypanosome RNA editing, uridylate (U) residues are inserted and deleted at numerous sites within mitochondrial pre-mRNAs by an approximately 20S protein complex that catalyzes cycles of cleavage, U addition/U removal, and ligation. We used RNA interference to deplete TbMP18 (band VII), the last unexamined major protein of our purified editing complex, showing it is essential. TbMP18 is critical for the U-deletional and U-insertional cleavages and for integrity of the approximately 20S editing complex, whose other major components, TbMP99, TbMP81, TbMP63, TbMP52, TbMP48, TbMP42 (bands I through VI), and TbMP57, instead sediment as approximately 10S associations.

T. brucei RNA editing: action of the U-insertional TUTase within a U-deletion cycle.

Trypanosome RNA editing is massive post-transcriptional U-insertion and U-deletion, which generates mature mRNA coding regions through cycles of endonuclease, terminal U transferase (TUTase) or 3'-U-exo, and ligase action. Both types of editing are thought to be catalyzed by distinct sets of proteins of a multiprotein complex, and no enzymatic activity of wild-type editing complex had been shown to function in both forms of editing. By examining the individual steps of the U-deletion cycle using purified editing complex, traditional mitochondrial extract, and rapidly prepared cell lysate, we here demonstrate that TbMP57 TUTase of U-insertion can act efficiently within a U-deletion cycle.

Molecular research technologies in mitochondrial diseases: the microarray approach.

Mitochondria are ubiquitous in eukaryotic cells where they generate much of the cellular energy by the process of oxidative phosphorylation (OXPHOS). The approximately 1500 genes of the mitochondrial genome are distributed between the cytoplasmic, maternally-inherited, mitochondrial DNA (mtDNA) which encodes 37 genes and the nuclear DNA (nDNA) which encompasses the remaining mitochondrial genes. The interplay between the mtDNA and nDNA encoded mitochondrial genes and their role in mitochondrial disorders is still largely unclear.

In Trypanosoma brucei RNA editing, band II enables recognition specifically at each step of the U insertion cycle.

Trypanosome RNA editing is the posttranscriptional insertion and deletion of uridylate (U) residues, often to a massive extent, through cycles of cleavage, U addition or U removal, and ligation. These editing cycles are catalyzed by a complex that we purified to seven major proteins (bands I through VII). Here we analyze the role of band II using extracts of clonal band II RNA interference (RNAi) cell lines prepared by a rapid protocol that enables retention of activities that are lost during traditional extract preparation.

Trypanosoma brucei RNA editing complex: band II is structurally critical and maintains band V ligase, which is nonessential.

Maturation of Trypanosoma brucei mitochondrial mRNA involves massive posttranscriptional insertion and deletion of uridine residues. This RNA editing utilizes an enzymatic complex with seven major proteins, band I through band VII. We here use RNA interference (RNAi) to examine the band II and band V proteins.

MolCom: a method to compare protein molecules based on 3-D structural and chemical similarity.

This paper describes an improved method for conducting global feature comparisons of protein molecules in three dimensions and for producing a new form of multiple structure alignment. Our automated MolCom method incorporates an octtree strategy to partition and examine molecular properties in three-dimensional space at multiple levels of analysis. The MolCom method's multiple alignment is in the form of an octtree which locates regions in three-dimensional space where correspondence between molecules is identified based on a dynamic set of molecular features.

Assembly and function of the RNA editing complex in Trypanosoma brucei requires band III protein.

Trypanosome RNA editing, the posttranscriptional insertion and deletion of U residues in mitochondrial transcripts, is catalyzed by a protein complex containing seven distinct proteins. In this study, we cloned the gene for band III, a 555-amino-acid protein with two separate zinc finger motifs. We prepared antibodies that showed band III protein cofractionates with the previously characterized band IV protein throughout the purification of the editing complex and is not found free or in other protein associations; therefore, it is a true constituent of the editing complex.

Roles for ligases in the RNA editing complex of Trypanosoma brucei: band IV is needed for U-deletion and RNA repair.

Trypanosome RNA editing utilizes a seven polypeptide complex that includes two RNA ligases, band IV and band V. We now find that band IV protein contributes to the structural stability of the editing complex, so its lethal genetic knock-out could reflect structural or catalytic requirements. To assess the catalytic role in editing, we generated cell lines which inducibly replaced band IV protein with an enzymatically inactive but structurally conserved version.