A critical question in Alzheimer's disease (AD) research is the cause of memory loss that leads to dementia. The amyloid precursor protein + presenilin-1 (APP+PS1) transgenic mouse is a model for amyloid deposition, and like AD, the mice develop memory deficits as amyloid deposits accumulate. We profiled gene expression in these transgenic mice by microarray and quantitative RT-PCR (qRT-PCR). At the age when these animals developed cognitive dysfunction, they had reduced mRNA expression of several genes essential for long-term potentiation and memory formation (Arc, Zif268, NR2B, GluR1, Homer-1a, Nur77/TR3). These changes appeared to be related to amyloid deposition, because mRNA expression was unchanged in the regions that did not accumulate amyloid. Transgene expression was similar in both amyloid-containing and amyloid-free regions of the brain. Interestingly, these changes occurred without apparent changes in synaptic structure, because a number of presynaptic marker mRNAs (growth-associated protein-43, synapsin, synaptophysin, synaptopodin, synaptotagmin, syntaxin) remained stable. Additionally, a number of genes related to inflammation were elevated in transgenic mice, primarily in the regions containing amyloid. In AD cortical tissue, the same memory-associated genes were downregulated. However, all synaptic and neuronal transcripts were reduced, implying that the loss of neurons and synapses contributed to these changes. We conclude that reduced expression of selected genes associated with memory consolidation are linked to memory loss in both circumstances. This suggests that the memory loss in APP+PS1 transgenic mice may model the early memory dysfunction in AD before the degeneration of synapses and neurons.

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Summary. The thigh skin collagen content and the metacarpal index were measured in 69 untreated postmenopausal women and in 37 postmenopausal women who had been receiving oestradiol and testos terone implants for 2–10 years. There was a significant positive correlation between the skin collagen content and the metacarpal index in both groups of patients. In the untreated group, there was a statistically significant decrease both in the thigh skin collagen content and in the metacarpal index with the years since the menopause. This decrease was preventable in women who were on sex hormone replacement therapy.

BackgroundPortfolios are increasingly used in undergraduate and postgraduate medical education. Four medical schools have collaborated with an established NHS electronic portfolio provider to develop and implement an authentic professional electronic portfolio for undergraduate students. We hypothesized that using an authentic portfolio would have significant advantages for students, particularly in familiarizing them with the tool many will continue to use for years after graduation. This paper describes the early evaluation of this undergraduate portfolio at two participating medical schools.MethodsTo gather data, a questionnaire survey with extensive free text comments was used at School 1, and three focus groups were held at School 2. This paper reports thematic analysis of students’ opinions expressed in the free text comments and focus groups.ResultsFive main themes, common across both schools were identified. These concerned the purpose, use and acceptability of the portfolio, advantages of and barriers to the use of the portfolio, and the impacts on both learning and professional identity.ConclusionsAn authentic portfolio mitigated some of the negative aspects of using a portfolio, and had a positive effect on students’ perception of themselves as becoming past of the profession. However, significant barriers to portfolio use remained, including a lack of understanding of the purpose of a portfolio and a perceived damaging effect on feedback.Electronic supplementary materialThe online version of this article (doi:10.1186/s12909-014-0265-2) contains supplementary material, which is available to authorized users.

Objectives: The number of doctors directly entering UK specialty training after their foundation year 2 (F2) has steadily declined from 83% in 2010 to 42.6% in 2017. The year following F2, outside the UK training pathway, is informally termed an 'F3' year. There is a paucity of qualitative research exploring why increasingly doctors are taking F3s. The aim of this study is to explore the reasons why F2 doctors are choosing to take a year out of training and the impact upon future career choices. Design: This is an exploratory qualitative study, using indepth interviews and content analysis. Setting: UK. Participants: Fourteen participants were interviewed from one foundation school. Participants included five doctors who commenced their F3 in 2015, five who started in 2016 and finally four recently starting this in 2017. Main outcome measures: Content analysis was conducted to distill the themes which exemplified the totality of the experience of the three groups. Results: There were four predominant themes arising within the data set which can be framed as 'unmet needs' arising within foundation years, sought to be fulfilled by the F3 year. First, doctors describe exhaustion and stress resulting in a need for a 'break'. Second, doctors required more time to make decisions surrounding specialty applications and prepare competitive portfolios. Third, participants felt a loss of control which was (partially) regained during their F3s. The final theme was the impact of taking time out upon return to training (for those participants who had completed their F3 year). When doctors returned to NHS posts they brought valuable experience. Conclusions:This study provides evidence to support the important ongoing initiatives from Health Education England and other postgraduate bodies, exploring approaches to further engage, retain and support the junior doctor workforce.

Summary. Connective tissue collagen is thought to contribute to the generation of urethral pressure. It has been previously shown that skin collagen and urethral pressure are oestrogen dependent. This study demonstrates a correlation between urethral pressure measurements and skin collagen content. It is suggested that the beneficial effect of oestrogens on urethral function may be mediated by collagen.

Study objective-To compare oral and implanted oestrogens for their effects in preventing postmenopausal osteoporosis.Design-Non-randomised cohort study of postmenopausal women treated with oral or depot oestrogens and postmenopausal controls.Setting-Gynaecological endocrine clinic in tertiary referral centre.Patients-Oral treatment group of 37 postmenopausal women (mean age 57*5 years, median 8-75 years from last menstrual period), compared with 41 women given oestrogen implants (mean age 56-2 years, median 9-5 years from last menstrual period) and 36 controls (mean age 51-8 years, median 2.0 years from last menstrual period). Weight was not significantly different among the groups.Interventions-Oral treatment group was given continuous treatment with cyclic oestrogen and progesterone preparations (Prempak C or Cycloprogynova) for a median of 8-0 years. Implant group was given subcutaneous implants of oestradiol 50 mg combined with testosterone 100 mg, on average six monthly for a median of 8 5 years. Controls were not treated.End point-Significant increase in bone density. Measurements and main results-Bone density measured by dual beam photon absorptiometry was 1*02 (SD 0-13) g hydroxyapatite/cm2 in implant group versus 0-89 (0-11) in oral group (p<001) and 0-87 (0-14) in controls (p<0.01). Serum oestradiol concentration in implant group was (median) 725 pmolIl versus 170 pmolIl in oral group (p<001) and 99 pmol/l in controls (p<0-01). Serum follicular stimulating hormone was median 1 IU/I (range 1-11) in implant group (equivalent to premenopausal values) versus 43 (4-94) IU/I in oral group (p<0-01) and 72 (28-99) IU/I in controls (p<0-01).Conclusions-Subcutaneous oestrogen is more effective than oral oestrogen in preventing osteoporosis, probably owing to the more physiological (premenopausal) serum oestradiol concentrations achieved. It also avoids problems of compliance that occur with oral treatment. IntroductionPeak bone mass is achieved in the fourth decade of life in both men and women, after which it decreases with age. The rate at which bone is lost accelerates in women after the menopause to the extent that they have lost half of their skeletal calcium by the age of 70. This leads to the excess of osteoporotic fractures in

Respect for patient wishes expressed in advance directives is reassuringly high. The findings suggest significant misunderstanding by medical practitioners of terminologies and systems around substitute decision-making for incompetent persons. Further education and standardisation of terminologies and systems across different jurisdictions would assist in addressing these issues. Low response rate, relating to only one legal jurisdiction, means results may not be generalisable.