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Flipped learning has become a popular blended learning approach in higher education and is now being adopted in medical schools across Australia and internationally. There are a number of principal educational justifications for the introduction of this approach, primarily, that it fosters deeper student learning through active engagement in the classroom. As a pedagogical intervention however, what do the various stakeholders think about its introduction? This paper explores reactions to implementation of a flipped learning approach to pre-clinical medical education in a regional Victorian medical course, via a mixed method approach. A range of quantitative and qualitative data was collected concerning the implementation, including a student survey, student focus groups, a staff survey for both academic and professional staff members involved in the implementation of the approach, and an independent student-driven social media questionnaire conducted in the second year post implementation survey. These data provide critical feedback for refinement of the flipped learning approach, including more robust student and faculty development and support during implementation of this pedagogy. Taken together, our results provide a unique perspective of the introduction of the flipped approach through different stakeholder lenses, and over time.

Background Female subjects with X-linked Alport syndrome have a single COL4A5 mutation, germ cell mosaicism in affected tissues and typically develop renal failure later or less often than male subjects. Women with two mutations are exceedingly rare, and usually have consanguineous parents or uniparental disomy. We describe here a 20-year-old woman who inherited two different COL4A5 variants, one from her father (c.2677G>C) and one from her mother (c.384+1 G>A). Case-diagnosis/treatment The index case had normal renal function, proteinuria and no clinically detectable hearing loss, or ocular abnormalities. Her father and paternal uncle developed end-stage renal disease at 37 and 28 years respectively, together with hearing loss, but not lenticonus or central retinopathy. Her mother had mildly impaired renal function, proteinuria, hearing loss, but no ocular abnormalities. Her maternal grandfather and 22-year-old brother, both with this mutation, developed renal failure by 28 years with hearing loss, or had proteinuria and hearing loss respectively. Conclusion The index case has clinical features consistent with germ cell mosaicism of two COL45A mutations associated with adult-onset renal failure, but no ocular abnormalities. Her risk of renal failure is high, but the rate of progression to end-stage disease depends on the underlying mutations, and disease modification with renin-angiotensin blockade. Keywords X-linked Alport syndrome * Female * COL4A5 mutation, Introduction Alport syndrome affects 1 in 10,000 individuals, and 85% of patients have X-linked disease due to mutations in the COL4A5 gene. Clinical features include hematuria, proteinuria, renal failure, hearing [...]

Background This study determined the family history and clinical features that suggested autosomal recessive rather than X-linked Alport syndrome. Methods All patients had the diagnosis of Alport syndrome and the mode of inheritance confirmed by genetic testing, and underwent examination at a single centre. Results Patients comprised 9 males and 6 females with autosomal recessive Alport syndrome, and 18 males and 22 females with X-linked disease. Fourteen (93%) individuals with autosomal recessive Alport syndrome developed early end-stage renal failure, all 15 had hearing loss, and most had lenticonus (12, 80%), and a central (13, 87%) or peripheral (13, 87%) retinopathy. These features occurred as often as in males with X-linked disease. Females with autosomal recessive inheritance were less likely to have an affected family member in another generation (p =0.01) than females with X-linked disease. They were more likely to have renal failure (p = 0.003), hearing loss (p =0.02) and lenticonus (p < 0.001). Fifty percent had a central retinopathy compared with 18% with X-linked disease (p = 0.14), but peripheral retinopathy prevalence was not different (p = 0.64). Nonsense mutations accounted for 67% (8/12) of these disease-causing mutations. Conclusions Autosomal recessive inheritance is increased in females with Alport syndrome and early onset renal failure, hearing loss, lenticonus, and, possibly, central retinopathy. Keywords Alport syndrome * Retinopathy * Nonsense mutations, Introduction Alport syndrome is characterised by hematuria, progressive renal failure, hearing loss, lenticonus, perimacular flecks and a peripheral coalescing retinopathy [1, 2]. X-linked inheritance accounts for 85% of patients [3] [...]

Scalp-Ear-Nipple syndrome is caused by pathogenic KCTD1 variants and characterised by a scalp defect, prominent ears, and rudimentary breasts. We describe here further clinical associations in the eye and kidney. Fifteen affected members from two unrelated families with p.(Ala30Glu) or p.(Pro31Leu) in KCTD1 were examined for ocular and renal abnormalities. The relevant proteins were studied in the eye and kidney, and the mutation consequences determined from mouse knockout models. Five males and 10 females with a median age of 40 years (range 1–70) with pathogenic variants p.(Ala30Glu) (n = 12) or p.(Pro31Leu) (n = 3) in KCTD1 were studied. Of the 6 who underwent detailed ophthalmic examination, 5 (83%) had low myopic astigmatism, the mean spherical equivalent of 10 eyes was 2.38D, and one (17%) had hypermetropic astigmatism. One female had a divergent strabismus. Five individuals had renal cysts (5/15, 33%), with renal biopsy in one demonstrating a thinned glomerular basement membrane identical to that seen in Thin basement membrane nephropathy (AD Alport syndrome). In the eye, KCTD1 and its downstream targets, TFAP2, and the collagen IV α3 and α4 chains localised to the cornea and near the retinal amacrine cells. In the kidney, all these proteins except TFAP2 were expressed in the podocytes and distal tubules. TFAP2B and COL4A4 knockout mice also had kidney cysts, and COL4A3 and COL4A4 knockout mice had myopia. Individuals with a pathogenic KCTD1 variant may have low myopic astigmatism and represent a further rare genetic cause for a thinned glomerular basement membrane. [ABSTRACT FROM AUTHOR]

Background and objectives: Alport syndrome is an inherited disease characterized by renal failure, hearing loss, and ocular abnormalities, including temporal retinal thinning. This study compared retinal thinning in Alport syndrome and other renal diseases. Methods: Alport syndrome was diagnosed on renal biopsy and genetic testing. Subjects underwent optical coherence tomography (OCT) (Spectralis OCT, Heidelberg Instruments). Retinal thinning was determined from horizontal macular OCT scans through the foveal center using the formula: Temporal thickness index (TTI) = (nasal – temporal thickness) ÷ nasal thickness × 100%, and compared with the normal range for each age group. Statistical analysis was performed using Student’s t test, Mann–Whitney U test, and ROC analysis (SPPS, IBM). Results: The mean temporal retinal thickness index was 12.4 ± 5.2% in men (n = 19) and 7.4 ± 1.4% in women (n = 28) with X-linked Alport syndrome; 13.1 ± 4.5% (n = 4) in recessive disease; 6.4 ± 2.2% (n = 5) in Thin basement membrane nephropathy; and 6.3 ± 3.3% (n = 14) in other renal diseases. Thinning was worse in men than women with X-linked disease (p < 0.01), and worse in men who developed early onset renal failure (R2 = 0.75). Temporal retinal thinning was 84% sensitive for men with X-linked Alport syndrome and 67% specific (AUC = 0.83) compared with other renal diseases. Conclusions: Retinal temporal thinning is diagnostic for X-linked Alport syndrome in men and distinguishes them this condition from Thin basement membrane nephropathy, but only in men (p = 0.002). Temporal retinal thinning may also identify men and women with the rarer autosomal recessive disease. [ABSTRACT FROM AUTHOR]

Background and Objectives: The retinal features of Alport syndrome include a central and peripheral fleck retinopathy, temporal retinal thinning, and a macular hole. Here we describe further retinal abnormalities. Methods: We identified a case of bull's eye maculopathy 20 years previously in a 68-year-old female, and reviewed archived retinal images from our cohort of X-linked (28 males, 28 females) or autosomal recessive (n = 13) Alport syndrome. All individuals had Alport syndrome confirmed on genetic testing or renal biopsy, were examined by an ophthalmologist, and underwent retinal imaging (KOWA non-mydriatic camera, Japan). Results: The index case had the p.Q379X variant in COL4A5 and currently had renal impairment, (eGFR = 45ml/min/1.73 m²), bilateral hearing loss, and central and peripheral retinopathies. Her maculopathy had deteriorated, and she had a bilateral central visual field loss. Optical coherence tomography (Heidelberg Spectralis) demonstrated a disrupted retinal pigment epithelium and retinal atrophy. We identified a further early bull's eye maculopathy (1/69, 1.4%) from a female with autosomal recessive disease and normal renal function. We also noted a subtle pigment maculopathy associated with an abnormal retinal pigment epithelium in 27 (27/69, 39%) subjects with Alport syndrome, in both males (8/28, 29%) and females (13/28, 46%) with X-linked disease, and in autosomal recessive disease (6/13, 38%). Conclusions: The bull's eye and pigment maculopathies in Alport syndrome result mainly from the damaged Bruch's membrane and overlying retinal pigment epithelium. Bull's eye maculopathy affects vision and patients should undergo regular monitoring for retinal complications. [ABSTRACT FROM AUTHOR]