Scope of coverage of medical genetics and genomics in pre-clerkship programs of Canadian faculties of medicine: A curriculum analysis.

We appraised the scope of medical genetics and genomics concepts covered in the pre-clerkship programs of Canadian faculties of medicine through an analysis of course objectives. All course objectives linked to medical genetics and genomics in pre-clerkship programs of Canadian faculties of medicine were compiled. From this, the fraction of objectives dedicated to medical genetics and genomics was calculated. Course objectives were also categorized according to a curriculum and a competency classification. Of the 17 Canadian faculties of medicine, the complete set of course syllabi (5 faculties) or the listing of learning objectives (4 faculties) were obtained and reviewed. The fraction of learning objectives dedicated to medical genetics and genomics varied between 0.65% and 5.05%. From the objectives classification, "foundational knowledge" was most frequently covered (64% of the compiled objectives), while topics such as: "ethics and professionalism," "communicate genetics information," and "obtain specialist help" were covered by less than 5%. Coverage of medical genetics and genomics in pre-clerkship programs of Canadian faculties of medicine appears to be low. Genetics and genomics are playing a rapidly expanding role in healthcare and clinical practice and educational programs should consider this new reality.

Maternal Metabolic Complications in Pregnancy and Offspring Behavior Problems at 2 Years of Age.

Objectives Prenatal maternal metabolic problems such as pre-pregnancy adiposity, excess gestational weight gain, and gestational diabetes mellitus (GDM) are associated with an increased risk of psychopathology in offspring. We examined whether these exposures were linked to symptoms of emotional and behavioral problems in offspring at 2 years of age, or if associations were due to confounding variables. Methods Data from 815 mother-child pairs enrolled at the Edmonton site of the Canadian Healthy Infant Longitudinal Development cohort were used to examine associations between gestational metabolic complications and scores on the externalizing and internalizing scales of the Child Behavior Checklist (CBCL-1½ to 5) at age two. Associations between maternal metabolic complications and offspring psychopathology were assessed before and after adjustment for gestational diet, socioeconomic status (SES), postpartum depression (PPD), prenatal smoking and breastfeeding. Results Pre-pregnancy body mass index and GDM, but not gestational weight gain, predicted more offspring externalizing and internalizing problems. However, after adjustment for confounding variables, these associations were no longer statistically significant. Post-hoc analyses revealed that gestational diet accounted for unique variance in both externalizing (semi-partial rdiet = - 0.20, p < 0.001) and internalizing (semi-partial rdiet = - 0.16, p = 0.01) problems. PPD and SES also accounted for a similar amount of variance for both externalizing (semi-partial rPPD = 0.17, p < 0.001; rses = - 0.11, p = 0.03) and internalizing problems (semi-partial rPPD = 0.21, p < 0.001; rses = - 0.14, p = 0.004). Conclusions for Practice Since the confounding effect of gestational diet persisted after adjustment for, and was similar in magnitude to, SES and PPD, future research should consider the impact of unhealthy prenatal diets on offspring neurodevelopment.

Genetic Counselors' and Genetic Counseling Students' Attitudes Around the Clinical Doctorate and Other Advanced Educational Options for Genetic Counselors: A Report from the Genetic Counseling Advanced Degree Task Force.

Since its establishment over 40 years ago, the genetic counseling profession has grown to an estimated ~4,000 professionals in North America. While the profession has maintained the Master's degree as the entry-level and terminal degree, many other allied health professions have added advanced training pathways, such as the clinical doctorate (ClinD) either as an optional post-professional degree or required entry-level degree. Discussions regarding advanced degrees have also occurred within the genetic counseling profession, dating back to as early as the 1980s. In 2011, the Genetic Counseling Advanced Degree Task Force (GCADTF) was convened to explore the issue again, with the goal of "[engaging] all of the professional leadership organizations in the field of genetic counseling in a decision-making process about whether the profession should move to a Clinical Doctorate". As part of their work, the GCADTF surveyed practicing genetic counselors (n = 4,321) and genetic counseling students (n = 522) in the US and Canada regarding their interest in moving to the ClinD as the entry-level degree. This survey also included questions about other options for advanced training to generate data to inform future discussions around this very important professional issue. Herein, we describe the results of the survey, with particular attention to genetic counselor preferences for additional advanced education/certification opportunities and recommendations for future discussion.

Zipime-Weka-Schista study protocol: a longitudinal cohort study and economic evaluation of an integrated home-based approach for genital multipathogen screening in women, including female genital schistosomiasis, human papillomavirus, Trichomonas and HIV in Zambia.

INTRODUCTION: Multiplathogen home-based self-sampling offers an opportunity to increase access to screening and treatment in endemic settings with high coinfection prevalence of sexually transmitted (HIV, Trichomonas vaginalis (Tv), human papillomavirus (HPV)) and non-sexually transmitted pathogens (Schistosoma haematobium (Sh)). Chronic coinfections may lead to disability (female genital schistosomiasis) and death (cervical cancer). The Zipime-Weka-Schista (Do self-testing sister!) study aims to evaluate the validity, acceptability, uptake, impact and cost-effectiveness of multipathogen self-sampling for genital infections among women in Zambia. METHODS AND ANALYSIS: This is a longitudinal cohort study aiming to enrol 2500 non-pregnant, sexually active and non-menstruating women aged 15-50 years from two districts in Zambia with 2-year follow-up. During home visits, community health workers offer HIV and Tv self-testing and cervicovaginal self-swabs for (1) HPV by GeneXpert and, (2) Sh DNA detection by conventional (PCR)and isothermal (recombinase polymerase assay) molecular methods. Schistosoma ova and circulating anodic antigen are detected in urine. At a clinic follow-up, midwives perform the same procedures and obtain hand-held colposcopic images. High-risk HPV positive women are referred for a two-quadrant cervical biopsy according to age and HIV status. A cost-effectiveness analysis is conducted in parallel. ETHICS AND DISSEMINATION: The University of Zambia Biomedical Research Ethics Committee (UNZABREC) (reference: 1858-2021), the London School of Hygiene and Tropical Medicine (reference: 25258), Ministry of Health and local superintendents approved the study in September 2021.Written informed consent was obtained from all participants prior to enrolment. Identifiable data collected are stored securely and their confidentiality is protected in accordance with the Data Protection Act 1998.

Effects of second language usage on genetic counseling training and supervision.

We conducted an exploratory study of the experiences of genetic counselors who have either trained or supervised in a second language to assess the relevance of this issue to genetic counseling training and supervision. Two hundred-thirty NSGC members, CAGC members and genetic counseling students completed the online questionnaire. Many of the respondents reported that training and supervision differed when another language was involved. Supervisors reported difficulty in assessing students' counseling skills and discomfort with an incomplete understanding of session content. Students described a greater focus on vocabulary at the expense of psychosocial dimensions. Despite this, most felt that using another language enhanced their training experience. As such, training programs might consider increasing support to these learners and supervisors by explicitly acknowledging the challenges they face, providing students with language tools to aid in their acquisition of basic skills and providing supervisors with new methods for assessing student counseling skills when using other languages.

The establishment of core competencies for canadian genetic counsellors: validation of practice based competencies.

Numerous groups of health professionals have undertaken the task of defining core competencies for their profession. The goal of establishing core competencies is to have a defined standard for such professional needs as practice guidelines, training curricula, certification, continuing competency and re-entry to practice. In 2006, the Canadian Association of Genetic Counsellors (CAGC) recognized the need for uniform practice standards for the profession in Canada, given the rapid progress of genetic knowledge and technologies, the expanding practice of genetic counsellors and the increasing demand for services. We report here the process by which the CAGC Practice Based Competencies were developed and then validated via two survey cycles, the first within the CAGC membership, and the second with feedback from external stakeholders. These competencies were formally approved in 2012 and describe the integrated skills, attitudes and judgment that genetic counsellors in Canada require in order to perform the services and duties that fall within the practice of the profession responsibly, safely, effectively and ethically.

Extensor tendon repair with and without central slip reattachment to bone: a biomechanical study.

PURPOSE: Swanson's technique for repair of the extensor tendon of the proximal interphalangeal (PIP) joint, entailing bony reattachment of the extensor tendon to the base of the middle phalanx, is a common procedure. We introduce a repair technique that is less complicated and that may be equally appropriate for approach to the PIP joint. The extensor tendon is incised longitudinally directly over the PIP joint. The insertion of the central slip and capsule are elevated off of the base of the middle phalanx. This allows excellent visualization of the PIP joint. The extensor tendon is then repaired by side-to-side approximation using Ethibond suture. The purpose of this study was to test and compare the strength of this proposed technique with that of Swanson in a cadaver model. METHODS: The index, long, and ring fingers from 4 pairs of fresh-frozen cadaver hands were harvested (24 digits total). One technique was performed and tested in all digits of the 3-digit contralateral pairings from 2 pairs of hands (3 digits x 4 hands; 12 digits total per technique). Twelve control digits were used to measure the fixation strength and stiffness of the Swanson approach, and the other 12 digits were used to measure the fixation strength and stiffness of the new procedure. RESULTS: All tendon repairs tolerated physiologic loading of 25 N. There was no statistically significant difference in stiffness between the control and experimental groups (mean +/- SD, 4.74 N/mm +/- 0.46 and 4.62 N/mm +/- 0.30, respectively; p >.05). CONCLUSIONS: Simple repair of the central slip without reattachment to bone preserves the function of the extensor mechanism at the PIP joint and provides excellent exposure to the joint.

Spinal hamartoma with severe kyphoscoliosis--a rare case of spinal mass in a fetus.

Spinal hamartomas are rare lesions consisting of disorganized ecto- and mesodermal tissues of the spinal region. While postnatal identification of spinal hamartomas has been reported, a literature search did not reveal any published reports of prenatal identification of spinal hamartomas. Here we report a 46,XX fetus who presented at 20 weeks' gestation with a lower thoracic and lumbar kyphoscoliosis, suspected spina bifida, and amniotic fluid alpha-fetoprotein (AFP) levels within the normal range. Interestingly, autopsy at 22 weeks revealed a lumbosacral spinal hamartoma with kyphoscoliosis. We discuss the differential diagnosis for such spinal masses which includes congenital tumors and spinal dysraphism. This case illustrates that spinal hamartomas should be considered as part of the prenatal differential diagnosis of spinal dysraphisms, especially in the presence of normal AFP levels.

Biomphalaria glabrata transcriptome: cDNA microarray profiling identifies resistant- and susceptible-specific gene expression in haemocytes from snail strains exposed to Schistosoma mansoni.

BACKGROUND: Biomphalaria glabrata is an intermediate snail host for Schistosoma mansoni, one of the important schistosomes infecting man. B. glabrata/S. mansoni provides a useful model system for investigating the intimate interactions between host and parasite. Examining differential gene expression between S. mansoni-exposed schistosome-resistant and susceptible snail lines will identify genes and pathways that may be involved in snail defences. RESULTS: We have developed a 2053 element cDNA microarray for B. glabrata containing clones from ORESTES (Open Reading frame ESTs) libraries, suppression subtractive hybridization (SSH) libraries and clones identified in previous expression studies. Snail haemocyte RNA, extracted from parasite-challenged resistant and susceptible snails, 2 to 24 h post-exposure to S. mansoni, was hybridized to the custom made cDNA microarray and 98 differentially expressed genes or gene clusters were identified, 94 resistant-associated and 4 susceptible-associated. Quantitative PCR analysis verified the cDNA microarray results for representative transcripts. Differentially expressed genes were annotated and clustered using gene ontology (GO) terminology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. 61% of the identified differentially expressed genes have no known function including the 4 susceptible strain-specific transcripts. Resistant strain-specific expression of genes implicated in innate immunity of invertebrates was identified, including hydrolytic enzymes such as cathepsin L, a cysteine proteinase involved in lysis of phagocytosed particles; metabolic enzymes such as ornithine decarboxylase, the rate-limiting enzyme in the production of polyamines, important in inflammation and infection processes, as well as scavenging damaging free radicals produced during production of reactive oxygen species; stress response genes such as HSP70; proteins involved in signalling, such as importin 7 and copine 1, cytoplasmic intermediate filament (IF) protein and transcription enzymes such as elongation factor 1alpha and EF-2. CONCLUSION: Production of the first cDNA microarray for profiling gene expression in B. glabrata provides a foundation for expanding our understanding of pathways and genes involved in the snail internal defence system (IDS). We demonstrate resistant strain-specific expression of genes potentially associated with the snail IDS, ranging from signalling and inflammation responses through to lysis of proteinacous products (encapsulated sporocysts or phagocytosed parasite components) and processing/degradation of these targeted products by ubiquitination.

Schistosome egg production is dependent upon the activities of two developmentally regulated tyrosinases.

Egg production is responsible for life cycle progression and host immunopathology during schistosomiasis, with the associated parasite molecules being investigated as potential novel chemotherapeutic targets. Here, we characterize two Schistosoma mansoni products, tyrosinase 1 and tyrosinase 2 (SmTYR1/SmTYR2) and show that their diphenol oxidase enzyme activities are critical for eggshell formation and production. The genes encoding these bifunctional enzymes (monophenol and diphenol oxidases) result from a duplication event that likely occurred before speciation and exist in the parasite's genome as multiple copies, which are linked and localized to chromosomes 4 and W. SmTYR1/SmTYR2 transcription and diphenol oxidase action are developmentally regulated with most enzyme activity localized to the eggshell-producing cells contained within the vitellaria of adult female worms. Importantly, kojic-acid mediated inhibition (IC50=0.5 microM) of SmTYR1/SmTYR2's diphenol oxidase activity during in vitro culture of sexually mature adult worms resulted in a significant decrease in the production of phenotypically normal eggs. Therefore our data suggest that SmTYR1/2 inhibition represents a novel and potentially effective strategy for combating schistosomiasis and furthermore, it may point to new methods for combinatorial control of immunopathology and egg transmission during platyhelminth infection.

Integrating transcriptome, proteome and glycome analyses of Schistosoma biology.

Publication of the transcriptomes of Schistosoma mansoni and Schistosoma japonicum, in conjunction with the sequencing and assembly of their genomes, has generated a comprehensive picture of Schistosoma transcriptional and genomic diversity. Subsequently, researchers who study conjugal and developmental biology, tegumental composition and larval or egg, secretory and excretory products have used these data, in combination with the latest '-omics' technologies, to extend large-scale screens of the schistosome transcriptome, proteome and glycome. In this article, we review these postgenomic investigations and contend that the generated datasets provide a plethora of novel drug, vaccine and immunomodulatory targets that might be useful for developing new antischistosome agents.

Schistosoma mansoni: DNA microarray gene expression profiling during the miracidium-to-mother sporocyst transformation.

For the human blood fluke, Schistosoma mansoni, the developmental period that constitutes the transition from miracidium to sporocyst within the molluscan host involves major alterations in morphology and physiology. Although the genetic basis for this transformation process is not well understood, it is likely to be accompanied by changes in gene expression. In an effort to reveal genes involved in this process, we performed a DNA microarray analysis of expressed mRNAs between miracidial and 4 d old in vitro-cultured mother sporocyst stages of S. mansoni. Fluorescently labeled, dsDNA targets were synthesized from miracidia and sporocyst total RNA and hybridized to oligonucleotide DNA microarrays containing 7335 S. mansoni sequences. Fluorescence intensity ratios were statistically compared between five biologically replicated experiments to identify particular transcripts that displayed stage-associated expression within miracidial and sporocyst mRNA populations. A total of 361 sequences showed stage-associated expression in miracidia, while 273 probes displayed sporocyst-associated expression. Differentially expressed mRNAs were annotated with gene ontology terminology based on BLAST homology using high throughput gene ontology functional annotation toolkit (HT-GO-FAT) and clustered using the GOblet GO browser software. A subset of genes displaying stage-associated expression by microarray analyses was verified utilizing real-time quantitative PCR. The use of DNA microarrays for the profiling of gene expression in early-developing S. mansoni larvae provides a starting point for expanding our understanding of the genes that may be involved in the establishment of parasitism and maintenance of infection in these important life cycle stages.

Dioecious Schistosoma mansoni express divergent gene repertoires regulated by pairing.

Pairing of adult Schistosoma mansoni parasites initiates a cascade of events including mating and egg production that ultimately leads to immuno-pathological lesions during schistosomiasis. To identify genes associated with this important biological process, we studied parasites isolated from single- versus mixed-sex cercariae-infected mice using DNA microarray analysis to uncover pair-regulated transcriptional profiles. We report that: (i) transcriptomes of parasites isolated from single-sex infections are significantly more complex than their mixed-sex counterparts; (ii) transcriptomes of single-sex males are distinct from mixed-sex males; and (iii) not all transcripts, previously hypothesized to be critical in female egg production, are regulated by pairing.

An oligonucleotide microarray for transcriptome analysis of Schistosoma mansoni and its application/use to investigate gender-associated gene expression.

Global profiling transcriptomes of parasitic helminths offers the potential to simultaneously identify co-ordinately expressed genes, novel genetic programs and uniquely utilized metabolic pathways, which together provide an extensive and new resource for vaccine and drug discovery. We have exploited this post-genomic approach to fabricate the first oligonucleotide DNA microarray for gene expression analysis of the parasitic trematode Schistosoma mansoni. A total of 17,329 S. mansoni DNA sequences were used to design a microarray consisting of 7335 parasite elements or approximately 50% of this parasite's transcriptome. Here, we describe the design of this new microarray resource and its evaluation by extending studies into gender-associated gene expression in adult schistosomes. We demonstrate a high degree of reproducibility in detecting transcriptional differences among biologically replicated experiments and the ability of the microarray to distinguish between the expression of closely related gene family members. Importantly, for issues related to sexual dimorphism, labour division, gamete production and drug target discovery, 197 transcripts demonstrated a gender-biased pattern of gene expression in the adult schistosome, greatly extending the number of sex-associated genes. These data demonstrate the power of this new resource to facilitate a greater understanding into the biological complexities of schistosome development and maturation useful for identifying novel intervention strategies.

Biceps Tenotomy Versus Tenodesis in Active Patients Younger Than 55 Years: Is There a Difference in Strength and Outcomes?

BACKGROUND: Proximal biceps pathology is a significant factor in shoulder pain. Surgical treatment options include biceps tenotomy and subpectoral biceps tenodesis. Tenotomy is a simple procedure, but it may produce visible deformity, subjective cramping, or loss of supination strength. Tenodesis is a comparatively technical procedure involving a longer recovery, but it has been hypothesized to achieve better outcomes in younger active patients (<55 years). HYPOTHESIS: This study investigated the outcomes of younger patients who underwent either a biceps tenotomy or tenodesis as part of treatment for shoulder pain. The hypothesis was that, apart from cosmetic deformity, there will be no difference in outcome between the 2 treatment options. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Isometric strength and endurance testing of operative and nonoperative shoulders for forearm supination (FS) and elbow flexion (EF) were tested utilizing an isometric dynamometer. Objective physical assessment was also performed. Subjective outcomes using the modified American Shoulder and Elbow Surgeons score (ASES); Disability of the Arm, Shoulder, and Hand (DASH); visual analog scale (VAS); and perceived biceps symptoms were collected. RESULTS: A total of 42 patients (22 tenotomy, 20 tenodesis) with an average follow-up of 3.3 years were studied. The average age at follow-up was 49.9 years. Thirty-five percent (7/20) of tenotomy patients exhibited a "Popeye" deformity, compared with 18.2% (4/22) of tenodesis patients. Strength prior to fatiguing exercise was similar between tenodesis and tenotomy for FS (6.9 vs 7.3 lbs; P < .05), EF in neutral (35.4 vs 35.4 lbs), and EF in supination (33.8 vs 34.2 lbs). Strength was not significantly different between groups for isometric strength and endurance measures. Subjective functional outcome measured by the DASH, ASES, and VAS scores were similar between groups. Frequency of complaints of cramping was higher in the tenotomy group (4/20 vs 1/22), and complaints of pain were higher in the tenodesis group (11/22 vs 5/20). CONCLUSION: Despite increased demands and activity placed on biceps function in a younger population, this study showed no differences in functional and subjective outcome measurements. The choice between biceps tenotomy and tenodesis for pathology of the proximal biceps tendon can continue to be based on surgeon and patient preference.

Gender-associated gene expression in two related strains of Schistosoma japonicum.

Host inflammatory responses directed against eggs laid by sexually-mature Schistosoma japonicum female worms instigate lesion formation and associated clinical pathologies during infection. To identify parasite gene transcripts that associate with egg production and to characterise sexually-mature adult gene expression profiles of two related Chinese strains, S. japonicum cDNA microarrays were fabricated using 457 ESTs originating from three parasite developmental stages. Twenty-two female-associated and 8 male-associated gene transcripts were identified in the adult Anhui strain whereas 21 female-associated and 7 male-associated gene transcripts were revealed in the adult Zhejiang strain. RT-PCR analysis, in situ enzyme localisation studies and enzymatic assays confirmed the cDNA microarray results, and importantly, provided information previously unappreciated in schistosome conjugal biology. Specifically, our novel findings include the female-specific expression of genes putatively involved in haemoglobin digestion and eggshell formation including extracellular superoxide dismutase, two histidine-rich proteins, a large blood-brain barrier amino acid transporter and two tyrosinase orthologues. In contrast, transcripts involved in mechanical support (actin), cytoskeletal infrastructure (e.g. dynein light chain 3 and myosin regulatory light chain) and tegumental biology (e.g. TM4SF and Sj25) were more highly represented in adult male schistosomes. Together these data establish a transcriptional basis for adult schistosome labour division and expands the list of novel S. japonicum gender-associated gene transcripts that may be considered targets for improved intervention strategies.

Gene expression studies using self-fabricated parasite cDNA microarrays.

DNA microarray platforms represent a functional genomics technology that uses structured information obtained from genomic sequencing efforts as a means to study transcriptional processes in a systematic and high-throughput manner. Specifically in this chapter, we outline the ordered processes involved in large-scale parasite gene expression studies including complementary (cDNA) microarray fabrication, total RNA isolation, cDNA labeling using fluorochromes, and DNA:DNA hybridization. Methods described herein were adapted for the study of schistosome sexual maturation and developmental biology but could be easily modified for the study of any additional parasitological system.

The use of the Tsuge procedure for pedal macrodactyly: relevance in pediatric orthopedics.

Pedal macrodactyly is a rare clinical entity that poses a challenge to practicing pediatric orthopedic surgeons. Many treatment options have been proposed. In 1967, Kenya Tsuge proposed a method to decrease the length, width, and circumference of a macrodactylous digit, while maintaining the cosmetic benefit of keeping the nail. We retrospectively reviewed our experience with using this technique in four children (six toes) over a 4-year period. The surgery is described and our results reviewed. We believe that the Tsuge procedure is a technically feasible, effective, single-stage reconstructive technique for pedal macrodactyly that pediatric orthopedic surgeons should have in their armamentarium.