Amyloid-β acts as a regulator of neurotransmitter release disrupting the interaction between synaptophysin and VAMP2.

BACKGROUND: It is becoming increasingly evident that deficits in the cortex and hippocampus at early stages of dementia in Alzheimer's disease (AD) are associated with synaptic damage caused by oligomers of the toxic amyloid-β peptide (Aβ42). However, the underlying molecular and cellular mechanisms behind these deficits are not fully understood. Here we provide evidence of a mechanism by which Aβ42 affects synaptic transmission regulating neurotransmitter release. METHODOLOGY/FINDINGS: We first showed that application of 50 nM Aβ42 in cultured neurones is followed by its internalisation and translocation to synaptic contacts. Interestingly, our results demonstrate that with time, Aβ42 can be detected at the presynaptic terminals where it interacts with Synaptophysin. Furthermore, data from dissociated hippocampal neurons as well as biochemical data provide evidence that Aβ42 disrupts the complex formed between Synaptophysin and VAMP2 increasing the amount of primed vesicles and exocytosis. Finally, electrophysiology recordings in brain slices confirmed that Aβ42 affects baseline transmission. CONCLUSIONS/SIGNIFICANCE: Our observations provide a necessary and timely insight into cellular mechanisms that underlie the initial pathological events that lead to synaptic dysfunction in Alzheimer's disease. Our results demonstrate a new mechanism by which Aβ42 affects synaptic activity

Case studies on the socio-economic characteristics and lifestyles subsistence and informal fisheries in South Africa

To develop a management strategy for informal fishers, a necessary first step is information about the nature of these fishers, their numbers and their socio-economic status. To accomplish this, a survey of socio-economic conditions and use of marine resources was undertaken in 1999 at 20 localities where fishing occurs around the coast of South Africa, concentrating on subsistence or small- to micro-scale artisanal commercial fishers. In each locality, 16–31 “fisher households” were surveyed by questionnaires, focus-group discussions and interviews with key informants. Demographic analyses revealed a low level of migrancy (~5%), an average of 5.3 persons per household and a mean age of 27. Only ~20% of fishers were women and ~15% were children. Poverty was prevalent: unemployment averaged 40.3% (much higher than the national norm of 29.3%). Mean adult equivalent income per month spanned R193–R735 among regions, and was not correlated with size of settlement. Education levels were low, only ~33% of people >20 years old having completed primary school. Migrancy was highest in rural areas (but still much less than the national norm), intermediate in towns and least in metropolitan areas. Household size, participation of women and poverty all followed similar trends. Comparing regions, the East Coast and the province of KwaZulu-Natal had higher migrancy rates, larger household sizes, greater poverty, and greater participation by women in fishing, than on the South and West coasts. Household expenditure on food was ~R450 per month on the South-East and KwaZulu-Natal coasts and ~R750 on the West Coast, and exceeded 60% of income (a measure of “food security”) in about half the households surveyed. Harvested resources were sold, consumed or used as bait. In all regions, the two most frequently harvested resources were fish (mostly sold, predominantly fished by men) and intertidal rocky-shore invertebrates (largely consumed, and involving women to a greater degree). On the West Coast, rock lobster Jasus lalandii was the third-most important resource, but on the South and KwaZulu-Natal coasts this species was replaced by estuarine invertebrates. Abalone Haliotis midae, oysters, sandy-beach invertebrates and kelp or seaweeds made up the balance. Diversity of harvested resources increased west to east, following biogeographic trends. The resources could be divided into those of high value (rock lobsters, abalone and, to a lesser extent, fish) and those of lower value (such as limpets, mussels and bait organisms). It is argued that high-value resources are best used to create micro- and small-scale commercial enterprises that can serve to uplift poor fishers. Lowvalue resources constitute subsistence resources, for which preferential rights should be established for subsistence fishers, including development of exclusive-use zones where necessary. Emerging characteristics of fishing communities that were helpful in defining subsistence fishers in the South African context were poverty, harvest for self-use (whether by consumption or sale to meet basic needs of food security), use of low-technology gear, and concentration of effort on or from shores or in estuaries. At least portions of the catches of all resources are sold, and the majority of equipment is purchased, so any definition of subsistence fishers cannot exclude those who sell part of their catch or do not use hand-made equipment. Some success was evident with co-management, encouraging further exploration of this style of management for subsistence fishers. Keywords: informal fishers, socio-economics of fishers, subsistence fishersAfrican Journal of Marine Science 2002, 24: 439–46

Perceptions of subsistence and informal fishers in South Africa regarding the management of living marine resources

Following the legal recognition of subsistence fishers in 1998 through the promulgation of the Marine Living Resources Act, a Subsistence Fisheries Task Group (SFTG) was appointed by national government to provide recommendations on the management of subsistence fishing in South Africa. To achieve effective management, the SFTG recognized that fishers' needs, perceptions and concerns must be understood and incorporated into future management strategies. As a result, information from fishers was gathered through a five-month research programme that included questionnaire surveys, focus-group meetings, a “roadshow” and a national workshop. Research findings indicated that the fishers' responses centred on four key themes related to (1) the criteria for defining a subsistence fisher, (2) current management practices, (3) resource use and (4) livelihood strategies. Feedback from fishers revealed several issues that have led to uncertainty and dissatisfaction among informal and subsistence fishers. However, these perceptions need to be contextualized within the historical circumstances of fisheries management in South Africa, and it must be recognized that attitudes will only change when management approaches embrace the needs, perceptions and concerns of the users. The information outlined in this paper was instrumental in guiding the formulation of the SFTG recommendations regarding the definition of subsistence fishers and their future management in South Africa.Keywords: fisheries management, perceptions about fisheries, subsistence fishersAfrican Journal of Marine Science 2002, 24: 463–47

Could Public Restrooms Be an Environment for Bacterial Resistomes?

PMCID: PMC3547874This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

An affordable, quality-assured community-based system for high-resolution entomological surveillance of vector mosquitoes that reflects human malaria infection risk patterns.

ABSTRACT: BACKGROUND: More sensitive and scalable entomological surveillance tools are required to monitor low levels of transmission that are increasingly common across the tropics, particularly where vector control has been successful. A large-scale larviciding programme in urban Dar es Salaam, Tanzania is supported by a community-based (CB) system for trapping adult mosquito densities to monitor programme performance. Methodology An intensive and extensive CB system for routine, longitudinal, programmatic surveillance of malaria vectors and other mosquitoes using the Ifakara Tent Trap (ITT-C) was developed in Urban Dar es Salaam, Tanzania, and validated by comparison with quality assurance (QA) surveys using either ITT-C or human landing catches (HLC), as well as a cross-sectional survey of malaria parasite prevalence in the same housing compounds. RESULTS: Community-based ITT-C had much lower sensitivity per person-night of sampling than HLC (Relative Rate (RR) [95% Confidence Interval (CI)] = 0.079 [0.051, 0.121], P < 0.001 for Anopheles gambiae s.l. and 0.153 [0.137, 0.171], P < 0.001 for Culicines) but only moderately differed from QA surveys with the same trap (0.536 [0.406,0.617], P = 0.001 and 0.747 [0.677,0.824], P < 0.001, for An. gambiae or Culex respectively). Despite the poor sensitivity of the ITT per night of sampling, when CB-ITT was compared with QA-HLC, it proved at least comparably sensitive in absolute terms (171 versus 169 primary vectors caught) and cost-effective (153US$versus 187US$ per An. gambiae caught) because it allowed more spatially extensive and temporally intensive sampling (4284 versus 335 trap nights distributed over 615 versus 240 locations with a mean number of samples per year of 143 versus 141). Despite the very low vectors densities (Annual estimate of about 170 An gambiae s.l bites per person per year), CB-ITT was the only entomological predictor of parasite infection risk (Odds Ratio [95% CI] = 4.43[3.027,7. 454] per An. gambiae or Anopheles funestus caught per night, P =0.0373). Discussion and conclusion CB trapping approaches could be improved with more sensitive traps, but already offer a practical, safe and affordable system for routine programmatic mosquito surveillance and clusters could be distributed across entire countries by adapting the sample submission and quality assurance procedures accordingly

Training teachers in classroom management to improve mental health in primary school children: the STARS cluster RCT

This is the final version. Available from NIHR Journals Library via the DOI in this record.Background Poor mental health in childhood is common, persistent and associated with a range of adverse outcomes that include persistent psychopathology, as well as risk-taking behaviour, criminality and educational failure, all of which may also compromise health. There is a growing policy focus on children’s mental health and the role of schools in particular in addressing this. Objectives To evaluate whether or not the Incredible Years® (IY) Teacher Classroom Management (TCM) training improved children’s mental health, behaviour, educational attainment and enjoyment of school, improved teachers’ mental health and relationship with work, and was cost-effective in relation to potential improvements. Design A two-arm, pragmatic, parallel-group, superiority, cluster randomised controlled trial. Setting A total of 80 UK schools (clusters) were recruited in three distinct cohorts between 2012 and 2014 and randomised to TCM (intervention) or teaching as usual [(TAU) control] with follow-ups at 9, 18 and 30 months. Schools and teachers were not masked to allocation. Participants Eighty schools (n = 2075 children) were randomised: 40 (n = 1037 children) to TCM and 40 (n = 1038 children) to TAU. Interventions TCM was delivered to teachers in six whole-day sessions, spread over 6 months. The explicit goals of TCM are to enhance classroom management skills and improve teacher–student relationships. Main outcome measures The primary planned outcome was the teacher-reported Strengths and Difficulties Questionnaire Total Difficulties (SDQ-TD) score. Random-effects linear regression and marginal logistic regression models using generalized estimating equations were used to analyse outcomes. Results The intervention reduced the SDQ-TD score at 9 months [adjusted mean difference (AMD) –1.0, 95% confidence interval (CI) –1.9 to –0.1; p = 0.03] but there was little evidence of effects at 18 months (AMD –0.1, 95% CI –1.5 to 1.2; p = 0.85) and 30 months (AMD –0.7, 95% CI –1.9 to 0.4; p = 0.23). Planned subgroup analyses suggested that TCM is more effective than TAU for children with poor mental health. Cost-effectiveness analysis using the SDQ-TD suggested that the probability of TCM being cost-effective compared with TAU was associated with some uncertainty (range of 40% to 80% depending on the willingness to pay for a unit improvement in SDQ-TD score). In terms of quality-adjusted life-years (QALYs), there was evidence to suggest that TCM was cost-effective compared with TAU at the National Institute for Health and Care Excellence thresholds of £20,000–30,000 per QALY at 9- and 18-month follow-up, but not at 30-month follow-up. There was evidence of reduced disruptive behaviour (p = 0.04) and reductions in inattention and overactivity (p = 0.02) at the 30-month follow-up. Despite no main effect on educational attainment, subgroup analysis indicated that the intervention’s effect differed between those who did and those who did not have poor mental health for both literacy (interaction p = 0.04) and numeracy (interaction p = 0.03). Independent blind observations and qualitative feedback from teachers suggested that teachers’ behaviour in the classroom changed as a result of attending TCM training. Limitations Teachers were not masked to allocation and attrition was marked for parent-reported data. Conclusions Our findings provide tentative evidence that TCM may be an effective universal child mental health intervention in the short term, particularly for primary school children who are identified as struggling, and it may be a cost-effective intervention in the short term. Future work Further research should explore TCM as a whole-school approach by training all school staff and should evaluate the impact of TCM on academic progress in a more thorough and systematic manner.National Institute for Health Research (NIHR