Healing journeys: Indigenous Men's reflections on resources and barriers to mental wellness.

Indigenous peoples in Canada and other settler colonial nations experience barriers to healing in the health care system and their communities. Drawing on four sequential sharing circles and indepth interviews with 11 Indigenous men, this article shares the stories of Indigenous men and their healing journeys with the aim of improving culturally safe support in the community. In sharing their stories, these men identified coping with colonialism, as well as trauma and grief, as barriers in their healing journey. They also described finding strength in cultural role models, fathering, as well as ceremony and connecting to the land. We discuss the implications of these findings for service provision and decolonizing community health services.

Human and Pathogen Factors Associated with Chlamydia trachomatis-Related Infertility in Women.

Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen worldwide. Infection can result in serious reproductive pathologies, including pelvic inflammatory disease, ectopic pregnancy, and infertility, in women. However, the processes that result in these reproductive pathologies have not been well defined. Here we review the evidence for the human disease burden of these chlamydial reproductive pathologies. We then review human-based evidence that links Chlamydia with reproductive pathologies in women. We present data supporting the idea that host, immunological, epidemiological, and pathogen factors may all contribute to the development of infertility. Specifically, we review the existing evidence that host and pathogen genotypes, host hormone status, age of sexual debut, sexual behavior, coinfections, and repeat infections are all likely to be contributory factors in development of infertility. Pathogen factors such as infectious burden, treatment failure, and tissue tropisms or ascension capacity are also potential contributory factors. We present four possible processes of pathology development and how these processes are supported by the published data. We highlight the limitations of the evidence and propose future studies that could improve our understanding of how chlamydial infertility in women occurs and possible future interventions to reduce this disease burden.

A new method for freezing testicular biopsy sperm: three pregnancies with sperm extracted from cryopreserved sections of seminiferous tubule.

OBJECTIVE: To determine whether spermatozoa, located in the seminiferous tubules obtained by needle puncture testicular biopsy, could be cryopreserved successfully within the tubules and subsequently be used for in oocyte fertilization via intracytoplasmic sperm injection (ICSI) after the spermatozoa were removed from the thawed tubules. DESIGN: Clinical case series. SETTING: Private IVF unit. PATIENT(S): Six azoospermic patients (four obstructive, two maturation arrest). MAIN OUTCOME MEASURE(S): Survival rate of thawed spermatozoa, fertilization rate of oocytes after ICSI with spermatozoa extracted from thawed tubules and pregnancies. RESULT(S): All six patients had adequate motile spermatozoa extracted from the thawed tubule sections, and all patients achieved fertilization via ICSI with their partner's eggs. The fertilization rate was 46%, compared with 56% obtained in other previous patient cycles using fresh testicular spermatozoa. Three pregnancies resulted from five ETs. CONCLUSION(S): Cryopreservation and subsequent thawing of seminiferous tubules proved to be a simple and successful method for storage of testicular spermatozoa, reducing the need for repetitive testicular biopsies and increasing the likelihood of sperm availability on the day of oocyte retrieval.

Binding of gelatinases A and B to type-I collagen and other matrix components.

Matrix sequestration of matrix metalloproteinases may be important for the facilitation of remodelling events and the migration of cells through the extracellular matrix. Using an ELISA technique we studied the ability of pro and active forms of gelatinases A and B (GLA and GLB) to bind to matrix components and the contribution made by the different enzyme domains. Pro and active forms of GLA and GLB bound to type-I and type-IV collagens, gelatin and laminin films. Binding to collagens occurred exclusively via the N-terminal portion of the molecule in both of the gelatinases; deletion of the fibronectin-like domain in GLA abolished binding. Fibronectin was shown to compete with GLA, confirming that binding occurs through this domain. GLA and GLB competed for binding to collagen type I, whereas collagenase and stromelysin bound to different sites and could be co-localized with the gelatinases. We conclude that gelatinases have different binding specificities from those previously documented for stromelysin and collagenase, which bind through their C-terminal domains to collagen fibrils.

Assessment of the role of the fibronectin-like domain of gelatinase A by analysis of a deletion mutant.

The properties of a deletion mutant delta V191-Q364 of gelatinase A, which represents the removal of the fibronectin-like type II repeats defined by exons 5-7, were compared with those of full-length gelatinase A. Both enzymes underwent self-activation over a similar time course in the presence of 4-aminophenylmercuric acetate. The fully active enzymes had similar kcat/Km values for the cleavage of an octapeptide substrate, but the deletion mutant had 50% of the activity of wild type gelatinase A against beta-casein and 10% of the activity against gelatin. The cleavage pattern for gelatin was similar for both enzymes but differed for type IV collagen. Comparison of the rates of association of the tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 and their N-terminal domains to both forms of gelatinase indicated that the fibronectin-like domain plays little role in TIMP binding. The deletion mutant failed to bind to collagen, while the wild type gelatinase bound tightly, indicating that the fibronectin-like domain is the sole site of collagen binding. Both gelatinases could be activated by concanavalin A-activated fibroblasts, suggesting that the fibronectin-like domain is not required for the membrane-mediated activation process.

The challenges of educational program evaluation.

The demand for fiscal restraint and accountability has forced health care facilities to carefully evaluate the benefits of new programs. Some time ago, the Long Term Care Nursing Department of Sunnybrook Health Science Centre in Toronto, Ontario, collaborated with Centennial College to provide a Gerontology Certificate Program to registered nurses. While originally conceived as a retention and recruitment strategy, it became obvious that such a program could and should have additional benefits to staff and long term care residents alike. This article describes the changes as indicated by three scales, and the benefits described by the registered nurses. It also illustrates, rather humorously, that even the more educated and experienced among us can make mistakes and learn from them!

Dreams of anorexic and bulimic women. A research study.

The research paradigms used in this study fit with the content analysis paradigms of Hall and Van de Castle (1966) and Dippel et al. (1987), but differ in the use of descriptive scenarios specific to eating disorders. Anorexic and bulimic patients are often able to share their dreams with their therapists, and this process is sometimes the start of building an analytical relationship. This study compared the dreams of twelve eating-disordered women with eleven 'normal' women. A total of 275 dreams was collected over a four-week period and rated on a 91-item scale (Brink 1991) by eight raters. Significant differences were found between the two groups, with eating-disordered women having more dream scenarios depicting themes of: impending doom at the end of the dream, attitudes of 'whatever I do I won't succeed', and images of the dreamer being attacked, and being watched. Significant differences were also found in dream content portraying the psychological traits of: ineffectiveness, self-hate, negative emotions, an inability to self-nourish, obsession with weight, and anger. The discussion centres around the role of 'inordinate oral rage', the nature of ego defences, how these defences manifest themselves in dream images and in daily living, and how they severely impair positive transformative processes. The implications for clinical practice are that dreams are an amenable way of working with eating-disordered women, and that the therapist is more likely to promote positive transformation through focusing on their dreams than trying to change their behaviour.

The role of the C-terminal domain in collagenase and stromelysin specificity.

Recombinant human interstitial collagenase, an N-terminal truncated form, delta 243-450 collagenase, recombinant human stromelysin-1, and an N-terminal truncated form, delta 248-460 stromelysin, have been stably expressed in myeloma cells and purified. The truncated enzymes were similar in properties to their wild-type counterparts with respect to activation requirements and the ability to degrade casein, gelatin, and a peptide substrate, but truncated collagenase failed to cleave native collagen. Removal of the C-terminal domain from collagenase also modified its interaction with tissue inhibitor of metalloproteinases-1. Hybrid enzymes consisting of N-terminal (1-242) collagenase.C-terminal (248-460) stromelysin and N-terminal (1-233) stromelysin.C-terminal (229-450) collagenase, representing an exchange of the complete catalytic and C-terminal domains of the two enzymes, were expressed in a transient system using Chinese hamster ovary cells and purified. Both proteins showed similar activity to their N-terminal parent and neither was able to degrade collagen. Analysis of the ability of the different forms of recombinant enzyme to bind to collagen by ELISA showed that both pro and active stromelysin and N-terminal collagenase.C-terminal stromelysin bound to collagen equally well. In contrast, only the active forms of collagenase and N-terminal stromelysin.C-terminal collagenase bound well to collagen, as compared with their pro forms.

Sexual differentiation and regulation of cytochrome P-450 CYP2C7.

The multigene family of proteins known as the cytochrome P-450-dependent monooxygenases play a central role in the metabolism of hormones and foreign compounds. As part of our studies into the function and regulation of these proteins we have isolated a little studied constitutively expressed isozyme CYP2C7 and have investigated its substrate specificity and mode of regulation. Interestingly the haem of this enzyme in its isolated form is almost 100% in the high spin state. The enzyme was active in the metabolism of a range of model resorufin substrates, but exhibits highest activity towards benzyloxyresorufin. Indeed, this isozyme appears to play a significant role in the metabolism of this substrate in microsomal samples from untreated male rats. Tissue distribution studies indicated that CYP2C7 was expressed in liver, kidney and possibly muscle tissue. Cytochrome P-450 CYP2C7 could not be significantly induced by any of a wide range of known modulators of cytochrome P-450 expression at the mRNA level, however some significant changes in protein expression were observed. Some of the agents used (e.g., diethylnitrosamine and carbon tetrachloride) caused a significant reduction in the expression of this protein. In agreement with other reports where mRNA levels were measured we found that the level of CYP2C7 protein expression was sexually differentiated. Female rats express two to three times the level found in males, the sex difference being reversible by hypophysectomy.

Binding of latent and high Mr active forms of stromelysin to collagen is mediated by the C-terminal domain.

A specific high-titre polyclonal antiserum to recombinant human prostromelysin was raised in a sheep and shown by immunoblotting to detect latent prostromelysin, high and low Mr active forms and the C-terminal domain. This antiserum was used to demonstrate by indirect immunofluorescence that latent and active high Mr prostromelysin bind to reconstituted collagen fibrils, and to other extracellular matrix components in tissues ex vivo but that active low Mr stromelysin does not. Isolation of the C-terminal domain was carried out to demonstrate that stromelysin binding was through this domain. By use of an antiserum to the tissue inhibitor of metalloproteinases (TIMP) it was shown that TIMP is unable to bind to reconstituted collagen fibrils. TIMP, however, will bind when active high Mr stromelysin is present but not if latent prostromelysin is bound. We conclude that stromelysin has different binding specificities from those previously documented for collagenase; only active collagenase binds to reconstituted collagen fibrils. However, TIMP binds to the active forms of both stromelysin and collagenase when these are bound to the collagen fibrils. These results have important implications for the interpretation of immunolocalization data in establishing the roles of metalloproteinases and their inhibitors in vivo.

Sex differences in the phenomenology of schizophrenic disorder.

The content and structure of delusions were compared in 30 women and 30 age-matched men with Schizophrenic Disorder. Men showed an excess of homosexual persecutory delusions and of grandiose delusions involving social status and personal power. Women showed an excess of delusions of fertility and of jealousy, and were more often than men objects rather than subjects in their grandiose delusions. There was an excess of women who reported co-objects of persecution, and who personally knew their persecutors, nearly always men. These differences mirrored aspects of the social environment, especially with regard to sex-role stereotyping.

A group method for learning about psychiatric research.

Psychiatric trainees in their final year of training met fortnightly with an experienced psychiatric researcher. A group format was used to facilitate the development of skills employed in psychiatric research. Various exercises, including conducting a research project during the group sessions, were undertaken. This report highlights certain issues that may inhibit clinicians from undertaking research projects. It is presented from both the group leader's and the participants' perspectives.

Summary of the toxicologic profile of iopentol.

Repeat dose toxicity studies, reproductive studies and mutagenicity studies were performed to assess the safety of iopentol. It is concluded that iopentol, a non-ionic contrast medium, is free from significant toxic effects.

Control of obesity in Avy/a mice by 5alpha-androstan-17-one.

Treating VY/WfL-Avy/a mice with 5 alpha-androston-17-one, a mammalian glucose-6-phosphate dehydrogenase inhibitor, prevented the mice from becoming obese. The weight difference between treated and control Avy/a mice was mainly due to a decreased accumulation of triacylglycerol. The compound did not suppress appetite, had no detectable toxicity and did not affect the lipogenesis rates in the liver and carcass. The weight-controlling effect of 5alpha-androstan-17-one in Avy/a mice was reversible upon withdrawal of treatment.

Dissociation of obesity, hypercholesterolemia and diabetes from atherosclerosis in ob/ob mice.

Genetically obese, diabetic and hypercholesterolemic C57BL/6J-ob/ob mice were placed on Purina Laboratory Chow containing 2% cholesterol for up to 4 months. They developed higher plasma cholesterol levels and accumulated an increased quantity of cholesterol in the liver but failed to develop atherosclerotic lesions in the aorta as would be expected in an obese, diabetic and hypercholesterolemic human adult.

Prevention of obesity in Avy/a mice by dehydroepiandrosterone.

Dehydroepiandrosterone, a mammalian glucose-6-phosphate dehydrogenase inhibitor, prevented Avy/a mice from becoming obese. Decreased accumulation of triacylglycerol accounted for a large portion of the weight difference between treated and control Avy/a mice. Hepatic lipogenesis as measured by 3H2O incorporation into total lipid was less in the dehydroepiandrosterone-treated mice. Dehydroepiandrosterone did not suppress appetite and had no apparent toxic effects at the doses used, and its weight controlling effects were reversible upon withdrawal of treatment.