Toll-like receptor 2 (TLR2) polymorphisms are associated with reversal reaction in leprosy.

BACKGROUND: Leprosy is characterized by a spectrum of clinical manifestations that depend on the type of immune response against the pathogen. Patients may undergo immunological changes known as "reactional states" (reversal reaction and erythema nodosum leprosum) that result in major clinical deterioration. The goal of the present study was to assess the effect of Toll-like receptor 2 (TLR2) polymorphisms on susceptibility to and clinical presentation of leprosy. METHODS: Three polymorphisms in TLR2 (597C-->T, 1350T-->C, and a microsatellite marker) were analyzed in 431 Ethiopian patients with leprosy and 187 control subjects. The polymorphism-associated risk of developing leprosy, lepromatous (vs. tuberculoid) leprosy, and leprosy reactions was assessed by multivariate logistic regression models. RESULTS: The microsatellite and the 597C-->T polymorphisms both influenced susceptibility to reversal reaction. Although the 597T allele had a protective effect (odds ratio [OR], 0.34 [95% confidence interval {CI}, 0.17-0.68]; P= .002 under the dominant model), homozygosity for the 280-bp allelic length of the microsatellite strongly increased the risk of reversal reaction (OR, 5.83 [95% CI, 1.98-17.15]; P= .001 under the recessive model). These associations were consistent among 3 different ethnic groups. CONCLUSIONS: These data suggest a significant role for TLR-2 in the occurrence of leprosy reversal reaction and provide new insights into the immunogenetics of the disease.

Prevalence, pathophysiology, health consequences and treatment options of obesity in the elderly: a guideline.

The prevalence of obesity is rising progressively, even among older age groups. By the year 2030-2035 over 20% of the adult US population and over 25% of the Europeans will be aged 65 years and older. The predicted prevalence of obesity in Americans, 60 years and older was 37% in 2010. The predicted prevalence of obesity in Europe in 2015 varies between 20 and 30% dependent on the model used. This means 20.9 million obese 60+ people in the USA in 2010 and 32 million obese elders in 2015 in the EU. Although cut-off values of BMI, waist circumference and percentages of fat mass have not been defined for the elderly (nor for the elderly of different ethnicity), it is clear from several meta-analyses that mortality and morbidity associated with overweight and obesity only increases at a BMI above 30 kg/m(2). Thus, treatment should only be offered to patients who are obese rather than overweight and who also have functional impairments, metabolic complications or obesity-related diseases, that can benefit from weight loss. The weight loss therapy should aim to minimize muscle and bone loss but also vigilance as regards the development of sarcopenic obesity - a combination of an unhealthy excess of body fat with a detrimental loss of muscle and fat-free mass including bone - is important in the elderly, who are vulnerable to this outcome. Life-style intervention should be the first step and consists of a diet with a 500 kcal (2.1 MJ) energy deficit and an adequate intake of protein of high biological quality together with calcium and vitamin D, behavioural therapy and multi-component exercise. Multi-component exercise includes flexibility training, balance training, aerobic exercise and resistance training. The adherence rate in most studies is around 75%. Knowledge of constraints and modulators of physical inactivity should be of help to engage the elderly in physical activity. The role of pharmacotherapy and bariatric surgery in the elderly is largely unknown as in most studies people aged 65 years and older have been excluded.

Spontaneous pre-stimulus fluctuations in the activity of right fronto-parietal areas influence inhibitory control performance.

Inhibitory control refers to the ability to suppress planned or ongoing cognitive or motor processes. Electrophysiological indices of inhibitory control failure have been found to manifest even before the presentation of the stimuli triggering the inhibition, suggesting that pre-stimulus brain-states modulate inhibition performance. However, previous electrophysiological investigations on the state-dependency of inhibitory control were based on averaged event-related potentials (ERPs), a method eliminating the variability in the ongoing brain activity not time-locked to the event of interest. These studies thus left unresolved whether spontaneous variations in the brain-state immediately preceding unpredictable inhibition-triggering stimuli also influence inhibitory control performance. To address this question, we applied single-trial EEG topographic analyses on the time interval immediately preceding NoGo stimuli in conditions where the responses to NoGo trials were correctly inhibited [correct rejection (CR)] vs. committed [false alarms (FAs)] during an auditory spatial Go/NoGo task. We found a specific configuration of the EEG voltage field manifesting more frequently before correctly inhibited responses to NoGo stimuli than before FAs. There was no evidence for an EEG topography occurring more frequently before FAs than before CR. The visualization of distributed electrical source estimations of the EEG topography preceding successful response inhibition suggested that it resulted from the activity of a right fronto-parietal brain network. Our results suggest that the fluctuations in the ongoing brain activity immediately preceding stimulus presentation contribute to the behavioral outcomes during an inhibitory control task. Our results further suggest that the state-dependency of sensory-cognitive processing might not only concern perceptual processes, but also high-order, top-down inhibitory control mechanisms.

Polymorphisms in Toll-like receptor 4 (TLR4) are associated with protection against leprosy.

Accumulating evidence suggests that polymorphisms in Toll-like receptors (TLRs) influence the pathogenesis of mycobacterial infections, including leprosy, a disease whose manifestations depend on host immune responses. Polymorphisms in TLR2 are associated with an increased risk of reversal reaction, but not susceptibility to leprosy itself. We examined whether polymorphisms in TLR4 are associated with susceptibility to leprosy in a cohort of 441 Ethiopian leprosy patients and 197 healthy controls. We found that two single nucleotide polymorphisms (SNPs) in TLR4 (896G>A [D299G] and 1196C>T [T399I]) were associated with a protective effect against the disease. The 896GG, GA and AA genotypes were found in 91.7, 7.8 and 0.5% of leprosy cases versus 79.9, 19.1 and 1.0% of controls, respectively (odds ratio [OR] = 0.34, 95% confidence interval [CI] 0.20-0.57, P < 0.001, additive model). Similarly, the 1196CC, CT and TT genotypes were found in 98.1, 1.9 and 0% of leprosy cases versus 91.8, 7.7 and 0.5% of controls, respectively (OR = 0.16, 95% CI 0.06--.40, P < 0.001, dominant model). We found that Mycobacterium leprae stimulation of monocytes partially inhibited their subsequent response to lipopolysaccharide (LPS) stimulation. Our data suggest that TLR4 polymorphisms are associated with susceptibility to leprosy and that this effect may be mediated at the cellular level by the modulation of TLR4 signalling by M. leprae.

Effects of pro-cholinergic treatment in patients suffering from spatial neglect.

Spatial neglect is a neurological condition characterized by a breakdown of spatial cognition contralateral to hemispheric damage. Deficits in spatial attention toward the contralesional side are considered to be central to this syndrome. Brain lesions typically involve right fronto-parietal cortices mediating attentional functions and subcortical connections in underlying white matter. Convergent findings from neuroimaging and behavioral studies in both animals and humans suggest that the cholinergic system might also be critically implicated in selective attention by modulating cortical function via widespread projections from the basal forebrain. Here we asked whether deficits in spatial attention associated with neglect could partly result from a cholinergic deafferentation of cortical areas subserving attentional functions, and whether such disturbances could be alleviated by pro-cholinergic therapy. We examined the effect of a single-dose transdermal nicotine treatment on spatial neglect in 10 stroke patients in a double-blind placebo-controlled protocol, using a standardized battery of neglect tests. Nicotine-induced systematic improvement on cancellation tasks and facilitated orienting to single visual targets, but had no significant effect on other tests. These results support a global effect of nicotine on attention and arousal, but no effect on other spatial mechanisms impaired in neglect.

Análise Económica de quatro explorações Agrícolas na Ilha de Santiago – Cabo Verde

Cabo verde é um País pobre do ponto de vista agrícola, pois as condições edafo-climáticas condicionam o desenvolvimento desse sector. Apesar desses constrangimentos, o sector agrícola desempenha um papel socioeconómico muito importante para o mundo rural, pois contribui significativamente para a melhoraria das condições de vida dos camponeses, diminuir o desemprego rural e estimula a actividade pecuária. Pratica-se em Cabo Verde dois tipos de agricultura: A de sequeiro praticadas sobretudo na época das as águas, e a agricultura de regadio, praticadas na época seca. Apesar das suas limitações sobretudo no que toca a produção de sequeiro, elas são actividades importantes para a população rural cabo-verdiana, pois são através delas que a população rural na sua maioria garante a sua sobrevivência (53,9% das explorações agrícolas, na Ilha de Santiago tem como fonte de rendimento o sector agro-pecuário RGA, 2004). Essa actividade é rotina tanto na época das chuvas com as culturas pluviais como na época seca com as culturas irrigadas, aproveitando as águas subterrâneas. São actividades praticadas por toda a população do meio rural, mas, sem uma análise em termos numéricos dos custos e benefícios que uma exploração agrícola possa trazer para uma família camponesa. Tendo em conta essa situação, a partir de Julho 2009 iniciou-se os trabalhos de inquérito à exploração agrícola privada nas diferentes zonas da Ilha de Santiago com o objectivo de recolher dados que nos permitem: i) caracterizar a exploração agrícola; ii) determinar em termos percentuais a participação de cada sector de actividade no rendimento dos agricultores e analisar a rentabilidade da exploração agrícola cabo-verdiana durante o exercício, 2009/2010. Para isso Foram elaborados os orçamentos anuais de actividades para cada sector, para análise da rentabilidade das actividades agro-pecuária, realizadas durante o período referido.

Criteria for EASO-collaborating centres for obesity management.

Obesity is recognised as a global epidemic and the most prevalent metabolic disease world-wide. Specialised obesity services, however, are not widely available in Europe, and obesity care can vary enormously across European regions. The European Association for the Study of Obesity (EASO, www.easo.org) has developed these criteria to form a pan-European network of accredited EASO-Collaborating Centres for Obesity Management (EASO-COMs) in accordance with accepted European and academic guidelines. This network will include university, public and private clinics and will ensure that the obese and overweight patient is managed by a holistic team of specialists and receives comprehensive state-ofthe-art clinical care. Furthermore, the participating centres, under the umbrella of EASO, will work closely for quality control, data collection, and analysis as well as for education and research for the advancement of obesity care and obesity science.