Dysregulated ADAM10-Mediated Processing of APP during a Critical Time Window Leads to Synaptic Deficits in Fragile X Syndrome.

The Fragile X mental retardation protein (FMRP) regulates neuronal RNA metabolism, and its absence or mutations leads to the Fragile X syndrome (FXS). The β-amyloid precursor protein (APP) is involved in Alzheimer's disease, plays a role in synapse formation, and is upregulated in intellectual disabilities. Here, we show that during mouse synaptogenesis and in human FXS fibroblasts, a dual dysregulation of APP and the α-secretase ADAM10 leads to the production of an excess of soluble APPα (sAPPα). In FXS, sAPPα signals through the metabotropic receptor that, activating the MAP kinase pathway, leads to synaptic and behavioral deficits. Modulation of ADAM10 activity in FXS reduces sAPPα levels, restoring translational control, synaptic morphology, and behavioral plasticity. Thus, proper control of ADAM10-mediated APP processing during a specific developmental postnatal stage is crucial for healthy spine formation and function(s). Downregulation of ADAM10 activity at synapses may be an effective strategy for ameliorating FXS phenotypes.

Variation in treatment strategies of Swiss general practitioners for subclinical hypothyroidism in older adults.

QUESTIONS UNDER STUDY: As the best management of subclinical hypothyroidism is controversial, we aimed to assess variations in treatment strategies depending on different Swiss regions, physician and patient characteristics. METHODS: We performed a case-based survey among general practitioners (GPs) in different Swiss regions, which consisted of eight hypothetical cases presenting a female patient with subclinical hypothyroidism and nonspecific complaints differing by age, vitality status and thyroid-stimulating hormone (TSH) concentration. RESULTS: A total of 262 GPs participated in the survey. There was considerable variation in the levothyroxine starting dose chosen by GPs, ranging from 25 µg to 100 µg. Across the Swiss regions, GPs in the Bern region were significantly more inclined to treat, with a higher probability of initiating treatment (60%, p = 0.01) and higher mean starting doses (45 µg, p <0.01) compared with the French-speaking region (44%, 36 µg); the Zurich region had intermediate values (52%, 39 µg). We found no association between treatment rate and other physician characteristics. GPs were more reluctant to initiate treatment in 85-year-old than in 70-year-old women (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.63-0.94), and more likely to treat women with a TSH of 15 mU/l than those with a TSH of 6mU/l (OR 8.71, 95% CI 6.21-12.20). CONCLUSIONS: There are strong variations in treatment strategies for elderly patients with subclinical hypothyroidism across different Swiss regions, including use of higher starting doses than the recommended 25 µg in the Swiss guidelines, which recommend a starting dose of 25 µg. These variations likely reflect the current uncertainty about the benefits of treatment, which arise from the current lack of evidence from adequately powered clinical trials.

The origins of exercise adherence in the Canadian seniors population

This research identified and examined the responses of 19 physically active seniors to determine why they were physically active. The participants were physically active seniors, from the Niagara region who participated in physical activity 2, or more times per week. The purpose to this research was to determine what specific experiences or characteristics those seniors' possessed which motivated them to follow an exercise regime in later life. Three focus group interviews were conducted and participants responded to a set of predetermined questions. Responses to the interview questions were transcribed and analysed by comparing words and participant responses. This method of analysis is known as ethnographic summary. Themes, concepts, and experiences that emerged from the focus group interviews were also recorded according to systematic coding by way of content analysis. From this study, factors that predispose, enable, reinforce and prevent seniors from participating in exercise have been identified. Nine recommendations for improving seniors quality of life have also emerged from the study. Additionally, the findings from the study illustrate that those responsible for planning programs for seniors need to consider senior's wants and needs. Finally, the study also has educational implications. All participants in the study experienced a positive introduction to daily phyiscal activity through their school setting. Participants of the study believed, that their positive experiences at school, directly influenced their lifelong involvement in exercise.

Electrocortical indices of cognitive control in working memory : exploring the effects of proactive interference, cognitive load, and aging

Cognitive control involves the ability to flexibly adjust cognitive processing in order to resist interference and promote goal-directed behaviour. Although frontal cortex is considered to be broadly involved in cognitive control, the mechanisms by which frontal brain areas implement control functions are unclear. Furthermore, aging is associated with reductions in the ability to implement control functions and questions remain as to whether unique cortical responses serve a compensatory role in maintaining maximal performance in later years. Described here are three studies in which electrophysiological data were recorded while participants performed modified versions of the standard Sternberg task. The goal was to determine how top-down control is implemented in younger adults and altered in aging. In study I, the effects of frequent stimulus repetition on the interference-related N450 were investigated in a Sternberg task with a small stimulus set (requiring extensive stimulus resampling) and a task with a large stimulus set (requiring no stimulus resampling).The data indicated that constant stimulus res amp ling required by employing small stimulus sets can undercut the effect of proactive interference on the N450. In study 2, younger and older adults were tested in a standard version of the Sternberg task to determine whether the unique frontal positivity, previously shown to predict memory impairment in older adults during a proactive interference task, would be associated with the improved performance when memory recognition could be aided by unambiguous stimulus familiarity. Here, results indicated that the frontal positivity was associated with poorer memory performance, replicating the effect observed in a more cognitively demanding task, and showing that stimulus familiarity does not mediate compensatory cortical activations in older adults. Although the frontal positivity could be interpreted to reflect maladaptive cortical activation, it may also reflect attempts at compensation that fail to fully ameliorate agerelated decline. Furthermore, the frontal positivity may be the result of older adults' reliance on late occurring, controlled processing in contrast to younger adults' ability to identify stimuli at very early stages of processing. In the final study, working memory load was manipulated in the proactive interference Sternberg task in order to investigate whether the N450 reflects simple interference detection, with little need for cognitive resources, or an active conflict resolution mechanism that requires executive resources to implement. Independent component analysis was used to isolate the effect of interference revealing that the canonical N450 was based on two dissociable cognitive control mechanisms: a left frontal negativity that reflects active interference resolution, , but requires executive resources to implement, and a right frontal negativity that reflects global response inhibition that can be relied on when executive resources are minimal but at the cost of a slowed response. Collectively, these studies advance understanding of the factors that influence younger and older adults' ability to satisfy goal-directed behavioural requirements in the face of interference and the effects of age-related cognitive decline.

Propriedades mecânicas do músculo de ratos adultos e idosos, exercitado pós-imobilização

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Morphology and incidence of torus palatinus and mandibularis in Brazilian Indians

The incidence and morphology of torus platinus and mandibularis was verified in 200 Indians, residents of two Brazilian Indian Reserves in Sao Paulo State, Brazil. A low incidence of both types of exostoses was observed, with torus palatinus occurring more frequently than mandibularis. These structures did not occur in individuals less than 10 years of age. Flattened torus palatinus predominated in relation to the other forms.

Anatomic data of the human coronary sinus

The authors studied the formation, tributaries, lenght and the ostium of the coronary sinus, as well as the relationship of the venous walls to the myocardium and to the epicardium. The observations were made out of 143 hearts of subjects of different ages, and it was found that the most frequent display of the coronary sinus valve was a semilunar form (52 adults, 15 youngsters, 2 children, 3 newborn); it was also found valves in a cribiform or septal form. The absence of the valve of coronary sinus was noted in 53 cases (42 adults, 9 youngsters, 2 newborn). The valve of Vieussens was found, in some cases, at the level of the transition between the great cardiac vein and the coronary sinus, as well as others single or double parietal venous valves. The action of the valve of coronary sinus is also discussed by the authors.

Anemia em crianças menores de dois anos atendidas nas unidades básicas de saúde no Estado de São Paulo, Brasil

The present study sought to determine the prevalence of anemia in 2,992 children, aged between 6 and 23 months, who voluntarily attended 160 Basis Health Care Units, located in 63 cities of the 5 Regional Health Coordinating areas of the State of S. Paulo, Brazil. Blood samples were collected by venous puncture and hemoglobin was measured by the cianometahemoglobin method. The WHO criteria for the diagnosis of anemia (Hb < 11.0 g/dl) were used: 59.1% of the children were shown to be anemic, with prevalence varying from 47.8% to 68.7% in the 5 RHCs. RHC 1, which comprises the Greater S. Paulo Region, presented a prevalence of anemia significantly lower than the other 4 RHCs, which cover the rest of the State. Hemoglobin levels 9.5 g/dl were found in 25.1% of the children. Anemia was more frequent in male children in male children, in those born, with a weight of less than 3,000 gr, in those who were breastfed for less than 2 months and in those that who presented some degree of energy deficient proteic malnutrition, according to Gomez's criteria. This is the first of a series of 4 articles whose purpose is the determining the prevalence of anemia in the State of S. Paulo and of testing the intervention alternatives with a view to curtailing the incidence of this pathology which today is the most prevalent nutritional disturbance in the world.

Indices de atividade da doença inflamatória do intestino: indicadores clínicos e laboratoriais.

The quantification of the degree of activity of inflammatory bowel disease is assuming growing importance nowadays. The activity index of the disease can be attained by clinical and laboratorial indicators. For ulcerative colitis the mostly used clinical parameters are daily bowel movements and presence of bloody diarrhea whereas albumin, hemoglobin, ESR and positive acute phase protein measurements are the laboratory parameters. For Crohn's disease activity besides the daily bowel movements the presence of abdominal pain and discomfort sensation are also frequently used whereas the C-reactive protein is the most used laboratory test which is able to detect the disease reactivation even before the appearance of any clinical sign. The combinations of clinical signs with the laboratory tests earned the sympathy of the specialists and the set of ensembled indicators has been recognized by the author's name. In this sense, the classification of the ulcerative colitis activity originally proposed by Truelove and Witts deserves presently a wide acceptance whereas such agreement is still lacking for Crohn's disease activity. In the mean time, the Bristol index is clinically the most feasible, once the Crohn's disease activity index and the Van Hees index are considered too complex. However the latter indexes are still useful mainly for comparisons among multicentric data. It seems that the currently existing clinical signs used for Crohn's disease activity would be quantitatively improved by adding some easily made laboratory tests such as C-reactive protein.

Implicações da agregação espacial de parasitas para a dinâmica populacional na interação hospedeiro-parasita

Some aspects of the widely observed over-dispersed pattern of the distribution of parasites within the host population are examined. It has been established in the parasitological literature that most hosts usually harbour few parasites, while only few hosts harbour a large proportion of the parasite population. Factors that may influence the pattern of distribution of parasites, the relation between the level of parasite aggregation and the prevalence of infection, and changes in this level of aggregation as a function of host age are analysed. Factors which determine the diversity of species in parasite communities are presented, and aspects of exploitative and interference competition among parasites and their relations with biological control procedures are also considered. Attention is also focused on the regulatory and destabilizing processes influencing the dynamic behaviour of host-parasite population interactions.

Prevalence and severity of caries in 3-12-year-old children from three districts with different fluoridation histories in Araraquara, SP, Brazil

Objective: To determine the prevalence and severity of caries in 3-12-year-old children in three districts of the city of Araraquara, Design: An epidemiological survey was carried out by trained and calibrated examiners in 1995 and 1996, using the WHO diagnostic criteria. Setting: Two districts, Araraquara and Vila Xavier had been fluoridated since 1963 and one, Gavião Peixoto, since 1994. Subjects: The study included 1,191 children from Araraquara, 653 from Vila Xavier and 652 from Gavião Peixoto. Outcome measures: Prevalence of caries, dmft, dmfs, DMFT and DMFS indices. Results: Results showed moderate caries experience in all three districts. Differences between districts in relation to fluoridation history were particularly obvious in primary teeth. In 3-4-year-old children, one third of those in Araraquara and Vila Xavier had some caries experience compared to 58% in Gavião Peixoto. In permanent teeth, 20% or less of the mean DMFT was made up of untreated decay in Araraquara and Vila Xavier whereas in Gaviao Peixoto it made up between 50 and 57% of values in 7-12-year-old children. Conclusions: The prevalence and severity of caries was lower in dentitions of children from the districts fluoridated since 1963. Improvements are likely in the future in Gaviao Peixoto as the benefit of fluoridation continues but additional means of promoting oral health are needed in all three districts.