Protein synthesis is required for the enhancement of long-term potentiation and long-term memory by spaced training

Spaced training is generally more effective than massed training for learning and memory, but the molecular mechanisms underlying this trial spacing effect remain poorly characterized. One potential molecular basis for the trial spacing effect is the differential modulation, by distinct temporal patterns of neuronal activity, of protein synthesis-dependent processes that contribute to the expression of specific forms of synaptic plasticity in the mammalian brain. Long-term potentiation (LTP) is a type of synaptic modification that may be important for certain forms of memory storage in the mammalian brain. To explore the role of protein synthesis in the trial spacing effect, we assessed the protein synthesis dependence of hippocampal LTP induced by 100-Hz tetraburst stimulation delivered to mouse hippocampal slices in either a temporally massed (20-s interburst interval) or spaced (5-min interburst interval) fashion. To extend our studies to the behavioral level, we trained mice in fear conditioning using either a massed or spaced training protocol and examined the sensitivity of long-term memory to protein synthesis inhibition. Larger LTP was induced by spaced stimulation in hippocampal slices. This improvement of synaptic potentiation following temporally spaced synaptic stimulation in slices was attenuated by bath application of an inhibitor of protein synthesis. Further, the maintenance of LTP induced by spaced synaptic stimulation was more sensitive to disruption by anisomycin than the maintenance of LTP elicited following massed stimulation. Temporally spaced behavioral training improved long-term memory for contextual but not for cued fear conditioning, and this enhancement of memory for contextual fear was also protein synthesis dependent. Our data reveal that altering the temporal spacing of synaptic stimulation and behavioral training improved hippocampal LTP and enhanced contextual long-term memory. From a broad perspective, these results suggest that the recruitment of protein synthesis-dependent processes important for long-term memory and for long-lasting forms of LTP can be modulated by the temporal profiles of behavioral training and synaptic stimulation.     

UK food and nutrition security during and after the COVID‐19 pandemic

The COVID‐19 pandemic is a major shock to society in terms of health and economy that is affecting both UK and global food and nutrition security. It is adding to the ‘perfect storm’ of threats to society from climate change, biodiversity loss and ecosystem degradation, at a time of considerable change, rising nationalism and breakdown in international collaboration. In the UK, the situation is further complicated due to Brexit. The UK COVID‐19 Food and Nutrition Security project, lasting one year, is funded by the Economic and Social Research Council and is assessing the ongoing impact of COVID‐19 on the four pillars of food and nutrition security: access, availability, utilisation and stability. It examines the food system, how it is responding, and potential knock on effects on the UK’s food and nutrition security, both in terms of the cascading risks from the pandemic and other threats. The study provides an opportunity to place the initial lessons being learnt from the on‐going responses to the pandemic in respect of food and nutrition security in the context of other long‐term challenges such as climate change and biodiversity loss.     

Hospital image based on quality, fact, perception

Quality "in fact"--appropriate clinical outcomes--and quality in "perception"--consumer evaluation--are two important parts of the "image equation" for a hospital. But, how do administrators use either to promote their institutions? The authors explain how to use both to give your institution the competitive edge.     

An overview of Canadian physician work force databases

Physician-resource planning activities have increased dramatically in Canada since the release of the Barer-Stoddart report, "Toward Integrated Medical Resource Policies for Canada" in 1991. One of the key concepts of the Barer-Stoddart report is the "medical career life cycle," beginning with entry to medical school and ending with exit from practice. To apply this concept in a planning context, it is essential to have a current information base that will contain data on numbers of physicians, where they are, what they do, and how active they are. In addition, a longitudinal capability is important for understanding issues such as retention and attrition. The objective of this article is to review and assess recent initiatives in the establishment of physician-resource databases in Canada by medical associations, governments, licensing bodies, certifying colleges, and other groups with a respect to comprehensiveness and comparability of key data elements and their ability to address key policy questions in physician-resource planning and to identify opportunities for collaboration and links.     

Critical success in management development

Details the results of an attempt to identify the impact of a comprehensive management development programme on organizational effectiveness within the health service public sector. Concludes that management development programmes must have a prespecified set of strategically linked outcomes, identifying the benefits to the organization, and a set of critical success factor measures to determine their achievement or otherwise. Programmes which do not result in managers feeling empowered will be criticized in not impacting positively on the organization.     

Depo Provera. Position paper on clinical use, effectiveness and side effects.

Depo Provera (medroxyprogesterone acetate, DMPA) when given as 150 mg by deep intramuscular injection every 12 calendar weeks (84 days+5 days), is a highly effective contraceptive with a very low failure rate comparable to modern copper IUDs and lower than many other methods. It should be available as a first line method to all who wish to make an informed choice about reversible methods of contraception. Pre-use counselling is essential to minimise the effect of menstrual change which occurs in most patients. However there is great patient variability. Use of DMPA is independent of intercourse and also independent of the user's memory (and thus of continuing motivation), other than remembering the 12 weekly appointments. For many women this is a great advantage. Oral contraceptive methods involve remembering to take a pill each day, in the case of the progestogen only pill within the same three hours each day. This places considerable strain on women who lead irregular lifestyles, who are very busy or travel frequently. Such women often describe a constant 'fear of forgetting', especially with the POP. The main potential disadvantage of DMPA in this country are likely to be menstrual disturbance and weight gain. The combined oral contraceptive pill gives the appearance of excellent cycle control because it removes the natural cycle altogether and replaces it with an artificial one. All progestogen-only methods, whether low or high dose, lead to menstrual disturbances, so in this respect DMPA is not unique. Although troublesome, the menstrual disturbances which occur in DMPA users very rarely require operative medical intervention, and can often be improved simply by short courses of oestrogen or shorter injection intervals. Again, women need to know what can be done so that they are aware that they should seek advice early, rather than miserably waiting.for their 12 week appointment. DMPA has no appreciable effects on blood pressure or thrombosis risk. In this it has an advantage over the combined oral contraceptive pill, and provides a simple, effective alternative for women who cannot use the pill for these reasons. Similarly, it has been suggested that women who suffer from focal migraine and are therefore advised against use of the combined oral contraceptive pill can still use progestogen-only contraceptives. Although the POP is medically safe in these circumstances, in young women it is less effective, and involves strict time keeping, which will be disadvantageous for some women. Side effects, long term use and schedules of administration are also discussed. The use of local protocols to allow nurse administration is to be supported both in general practice and the clinic situation. Perhaps the most important issue surrounding the use of DMPA is that of patient information. The method has had a particularly bad public image, which naturally makes potential users anxious and subject to misinformation from poorly informed or biased sources. Also, it is temporarily irreversible during its three months duration, so the duration of any problems or anxieties resulting from side effects may be longer than for other methods. It is of paramount importance that easily understood, accurate patient information leaflets are available, since biased and inaccurate information is readily available from women's magazines, perpetuating the myths surrounding the method.     

The management of women with breast symptoms referred to secondary care clinics in Sheffield: implications for improving local services

Information was collected about 302 women referred for breast symptoms and seen in surgical outpatient or outreach clinics during one month at two hospitals in Sheffield. Three-quarters of the women (n = 244) were referred to specialist breast clinics, 22% (n = 70) were referred to general surgical clinics and 3% (n = 6) were referred to outreach clinics. The ages of the women ranged from 16 to 85 years with a mean and median age of 45 years. Some 200 women (66%) presented with a lump or lumpiness, 42 women (14%) presented with pain, 29 women (10%) had a skin and/or nipple problem, and the remaining 31 women (10%) were concerned about their family history or reported other symptoms. A total of 23 women (8%) were diagnosed as having cancer, 180 (60%) were diagnosed as having benign breast disease, and 99 (33%) were diagnosed as normal. Of the 23 women with cancer, 22 were over 40 years of age; 21 women presented with a lump, one presented with pain, and one presented with metastatic disease. The time required to reach a final clinical diagnosis varied from the same day as the clinic visit to 35 weeks, with a median time of 3 weeks. Surgeons assessed the appropriateness of GPs' referrals for 257 cases and judged that 122 (47%) could have been managed by a GP. The implications of the findings for the organisation of specialist outpatient clinics are discussed, and a categorisation of women as either urgent or routine cases is suggested.     

Community care. Flexible friends

A scheme that trains students to become part-time community support workers to people with mental health problems has proved popular with clients. A third of the carers had felt unsafe on at least one occasion and the service requires a high level of supervision. Professionals considered the service particularly useful for clients who felt isolated, and those at risk of self-neglect.