Exome Sequencing in a Family with Luminal-Type Breast Cancer Underpinned by Variation in the Methylation Pathway.

Panel-based next generation sequencing (NGS) is currently preferred over whole exome sequencing (WES) for diagnosis of familial breast cancer, due to interpretation challenges caused by variants of uncertain clinical significance (VUS). There is also no consensus on the selection criteria for WES. In this study, a pathology-supported genetic testing (PSGT) approach was used to select two mutation-negative breast cancer patients from the same family for WES.

The impact of a faculty development programme for health professions educators in sub-Saharan Africa: an archival study.

Background: In 2008 the sub-Saharan FAIMER Regional Institute launched a faculty development programme aimed at enhancing the academic and research capacity of health professions educators working in sub-Saharan Africa. This two-year programme, a combination of residential and distance learning activities, focuses on developing the leadership, project management and programme evaluation skills of participants as well as teaching the key principles of health professions education-curriculum design, teaching and learning and assessment. Participants also gain first-hand research experience by designing and conducting an education innovation project in their home institutions.

Genomic medicine and risk prediction across the disease spectrum.

Genomic medicine is based on the knowledge that virtually every medical condition, disease susceptibility or response to treatment is caused, regulated or influenced by genes. Genetic testing may therefore add value across the disease spectrum, ranging from single-gene disorders with a Mendelian inheritance pattern to complex multi-factorial diseases. The critical factors for genomic risk prediction are to determine: (1) where the genomic footprint of a particular susceptibility or dysfunction resides within this continuum, and (2) to what extent the genetic determinants are modified by environmental exposures.

Understanding rural clinical learning spaces: Being and becoming a doctor.

Context: Calls for health professions education that can foster transformative educational experiences have been voiced. Studies suggest that extended clinical training at rural sites potentially provides transformative learning spaces. This article explores 'being and becoming' as a construct for understanding the student experience at a rural clinical school (RCS).

Minimal supervision out-patient clinical teaching.

Background: Minimal faculty member supervision of students refers to a method of instruction in which the patient-student encounter is not directly supervised by a faculty member, and presents a feasible solution in clinical teaching. It is unclear, however, how such practices are perceived by patients and how they affect student learning.

Context: We aimed to assess patient and medical student perceptions of clinical teaching with minimal faculty member supervision.

Necrotizing enterocolitis in HIV-exposed and nonexposed infants: clinical presentation and histopathological features.

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in neonates and is associated with significant morbidity and mortality. An association between HIV-positive maternal status and increased risk of NEC in preterm infants has been described, and antiretroviral therapy has been proposed as an independent risk factor. Our aim was to compare the clinical presentation and histopathological features of necrotizing enterocolitis in HIV-exposed and unexposed infants.

Microscopic colitis as a missed cause of chronic diarrhea.

Aim: To determine the prevalence of increased intraepithelial lymphocytes, using immunohistochemistry in patients with normal colonoscopy and near normal biopsy.

Methods: We retrospectively reviewed all non-malignant colon mucosal biopsies between 2005 and 2007, reported as normal, chronic inflammation or melanosis coli in patients who were undergoing routine colonoscopy. Immunohistochemistry using CD3 was performed on all mucosal biopsies and an intraepithelial lymphocyte count (IEL) was determined.

Alienation and engagement in postgraduate training at a South African medical school.

Background: The importance of contextual factors, such as the learning environment and sociocultural characteristics of the student, are becoming increasingly evident. Mann [2001. Alternative perspectives on the student experience: Alienation and engagement.

Pleural tuberculosis in patients with early HIV infection is associated with increased TNF-alpha expression and necrosis in granulomas.

Although granulomas may be an essential host response against persistent antigens, they are also associated with immunopathology. We investigated whether HIV co-infection affects histopathological appearance and cytokine profiles of pleural granulomas in patients with active pleural tuberculosis (TB). Granulomas were investigated in pleural biopsies from HIV positive and negative TB pleuritis patients.

Associations between toll-like receptors and interleukin-4 in the lungs of patients with tuberculosis.

Toll-like receptors (TLRs) are implicated in the intracellular killing of Mycobacterium tuberculosis, and their expression is modulated by interleukin-4 (IL-4) in vitro. Our aim was to examine the expression of TLRs at the site of pathology in tuberculous lung granulomas and to explore the effect of the immune response on TLR expression. Immunohistochemistry was performed on lung granulomas from nine patients with tuberculosis undergoing lobectomy for haemoptysis.

In situ detection of Mycobacterium tuberculosis transcripts in human lung granulomas reveals differential gene expression in necrotic lesions.

We have used RNA-RNA in situ hybridization to detect the expression of several Mycobacterium tuberculosis genes in tuberculous granulomas in lung tissue sections from tuberculosis patients. The M. tuberculosis genes chosen fall into two classes.

Localisation of mycobacterial DNA and mRNA in human tuberculous granulomas.

In situ hybridisation was used to detect the presence of Mycobacterium tuberculosis in paraffin-embedded lung tissue of nine patients diagnosed with tuberculosis (TB). Mycobacterial DNA was found in all nine patients and in 175 out of 191 granulomas examined. A combination of in situ hybridisation and immunohistochemistry techniques demonstrated that mycobacterial DNA was associated with CD68-positive cells with the morphology of macrophages and giant cells.

Distribution of IFN-gamma, IL-4 and TNF-alpha protein and CD8 T cells producing IL-12p40 mRNA in human lung tuberculous granulomas.

In order to examine the immune response at the site of pathology in tuberculosis, we analysed cytokines present in lung granulomas, their associations with each other and with caseous necrosis as well as the phenotype of the cellular infiltrate. Paraffin-embedded tissue from the lungs of seven patients with pulmonary tuberculosis was analysed by immunohistochemistry and in situ hybridization to detect interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and interleukin-4 (IL-4) proteins and IL-12p40 mRNA. All seven patients had granulomas staining positive for IFN-gamma, TNF-alpha and IL-12p40, but only four stained positive for IL-4.