Cost-Effectiveness of Inpatient Continuous Glucose Monitoring.

Introduction Our department conducted a retrospective cohort study to compare the efficacy of continuous glucose monitoring devices versus capillary blood glucose in the glycemic control of inpatient type 2 diabetes on intensive insulin therapy in a Portuguese hospital. The use of continuous glucose monitoring devices was associated with improved glycemic control, including an increased number of glucose readings within target range and reduced hyperglycemic events, being safe concerning hypoglycemias. This is the cost-effectiveness analysis associated with these results. Aim The primary objective was to compare the cost-effectiveness of achieving glycemic control, defined as the number of patients within glycemic goals, between groups. Secondary endpoints included cost-effectiveness analyses of each time in range goal, and each percentual increment in time in range. Methods We defined each glycemic goal as: "readings within range (70-180 mg/dL) >70%", "readings below range (below 70 mg/dL) <4%", "severe hypoglycemia (below 54 mg/dL) <1%", "readings above range (above 180 mg/dL) <25%", "very high glycemic readings (above 250 mg/dL) <5%". Results Continuous glucose monitoring showed lower median cost per effect for the primary outcome (€11.1 vs. €34.9/patient), with lower cost for readings in range (€7.8 vs. €11.6/patient) and for both readings above range goals ("above 180mg/dL": €7.4 vs. €9.9/patient, and "above 250mg/dL": €6.9 vs. €17.4/patient). Conclusions There are no published data regarding the cost-effectiveness of continuous glucose monitoring devices in inpatient settings. Our results show that continuous glucose monitoring devices were associated with an improved glycemic control, at a lower cost, and endorse the feasibility of incorporating these devices into hospital settings, presenting a favorable cost-effective option compared to capillary blood glucose.

Physicochemical variables influencing the abundance of Atlantic goliath grouper juveniles (Epinephelus itajara) in a tropical Brazilian mangrove habitat.

The purpose of this study was to investigate the relationships between the abundance and occurrence of juvenile Atlantic goliath grouper and physicochemical variables in a tropical mangrove ecosystem, employing a non-lethal methodology. Juvenile Atlantic goliath grouper individuals were captured biweekly, using blue crab traps, across three locations within the São Mateus estuary (18°36'S, 39°44'W), from August 2021 to July 2022. Simultaneously, the physicochemical water variables were assessed during each trap inspection. The physicochemical water variables influence on the abundance and occurrence of Atlantic goliath grouper juveniles were assessed using the Zero-Inflated Binomial (ZIB) and the Poisson (ZIP) generalized linear mixed-effects models (GLMMs). A total of 66 Atlantic goliath grouper juveniles were sampled (Pontal do Sul = 50, Lagoa Creek = 13, and Pitangueiras Creek = 3), ranging from 32 to 319 mm in total length. The best model fitted to presence-absence data (AIC = 278.6) consisted of location, depth, and salinity, with only location having a significant influence on the likelihood of species occurrence. Regarding abundance data, the best model (AIC = 336.4) included location, depth, and turbidity, with only location and depth showing a significant impact on abundance variation, with lower abundance at deeper areas. Although our results indicate a weak significant influence of physicochemical variables on juvenile Atlantic goliath grouper distribution, it is imperative to continue this monitoring effort, considering that additional data may be required to gain a deeper understanding of these patterns.

Are perceptions of climate change in Amazonian coastal communities influenced by socioeconomic and cultural factors?

Climate changes have become undisputed, as have their consequences for global ecosystems and mankind. The coastal areas are among the most affected areas on the planet due to their geographical location. The effects suffered by coastal areas can render the residing populations homeless, as well as compromise the continuity of the history and culture of these environments. The Marine Extractive Reserve of the city of Soure (coastal area of eastern Amazonia) stands out for housing populations that have developed an intimate relationship with nature and have knowledge that can explain people's perception of climate changes. In this context, this study investigated how local residents perceive climate change and its consequences considering different temporal and spatial scales. To this end, questionnaires were developed and applied using a 5-point Likert scale. Our results indicate that perception is shaped by socioeconomic and demographic factors, and that they are perceived on different time scales and geographic space. These findings reflect the awareness-raising efforts of the management body of this Conservation Unit and the local knowledge, derived from the relationship of the residents with the natural environment, which, together, provided the population with assertive information that favor a better understanding of this phenomenon.

Local perceptions do not follow rainfall trends: A case study in traditional Marajo island communities (eastern para state, BR).

The great current challenge for the conservation and use of natural resources refers to global climate change, because of its impacts felt in different intensities at global, regional, and local spatial scales. Within the system of environmental protection areas in Brazil, the extractive reserves ensure the sustainable use of natural resources by traditional populations, thus maintaining the cultural and biological aspects of a region. Such populations, being in close management of the surrounding environments, tend to perceive changes in ecological processes that many need for their livelihoods. The use of this perception of local populations in conjunction with academic research evidence has a high potential to allow a whole and systemic view of possible changes in natural phenomena. This study developed an integrated analysis of scientific evidence and local perceptions to understand the variation of precipitation in a community inserted in an extractive reserve in the eastern Amazon. We used 30 years of precipitation data from the Brazilian National Institute of Meteorology - INMET, the Southern Oscillation Index - SOI, and the Atlantic Meridional Mode Index - AMM. Furthermore, we applied a form to measure the population's perception of possible changes in rainfall cycles in the region. The meteorological data indicate that the region of the community has been presenting a rainfall reduction; however, people in the community do not perceive this trend. Although it is public knowledge that the global climate is undergoing changes, a fact noted after the integrating analysis of scientific evidence with local knowledge in Resexmar Soure is that the perceptions of traditional populations often focus on smaller temporal and spatial scale visions.

Gut Dysbiosis: A Target for Protective Interventions against Parkinson's Disease.

Sub-chronic inflammation, caused by age-related dysbiosis, primes the brain to neuroinflammation and neurodegenerative diseases. Evidence revealed that Parkinson's disease (PD) might originate in the gut, demonstrating gastro-intestinal disturbances, as reported by PD patients long before developing motor symptoms. In this study, we conducted comparative analyses in relatively young and old mice maintained in conventional or gnotobiotic conditions. We aimed to confirm that the effects induced by age-related dysbiosis, rather than aging itself, sensitize to PD onset. This hypothesis was confirmed in germ-free (GF) mice, which proved resistant to the pharmacological induction of PD, regardless of their age. Contrary to conventional animals, old GF mice did not develop an inflammatory phenotype or an accumulation of iron in the brain, two catalysts sensitizing to disease onset. The resistance of GF mice to PD is reverted when colonized with stool collected from conventional old animals, but not if receiving bacterial content from young mice. Hence, changes in gut microbiota composition are a risk factor for PD development and can be targeted preventively by iron chelators, shown to protect the brain from pro-inflammatory intestinal priming that sensitizes to neuroinflammation and the development of severe PD.

Baseline Characteristics of Subjects with Chronic Obstructive Pulmonary Disease Associated to the Improvement in Activities of Daily Living after Exercise Training.

This study aimed to identify baseline variables predicting improvement in ADLs following an exercise training program in subjects with COPD. Sixty-seven patients with COPD underwent assessment of spirometry, modified Medical Research Council scale, COPD Assesment Test (CAT), Six Minute Walk Test (6MWT), London Chest Activity of Daily Living (LCADL) scale and Glittre-ADL test (TGlittre). After 24 sessions, they were reassessed for limitation in ADLs (LCADL and TGlittre). The main outcome was the achieving of minimal important difference (MID) of TGlittre, LCADL and both (ADLs). The cut-off points to discriminate the subjects who achieved the MID of TGlittre, LCADL and ADLs were established using the ROC curve. A cut-off point of 3.7 min in baseline TGlittre was able to discriminate subjects who achieved the MID of TGlittre (AUC = 0.77). Subjects with baseline TGlittre ≥3.7 min were 6.92 (95%CI 2.2-20.9) times more likely to achieve the MID of TGlittre post-exercise training. A cut-off point of 32% in LCADL was able to discriminate subjects who achieved the MID of LCADL (AUC = 0.81) and in ADLs (AUC = 0.78). Subjects with baseline LCADL ≥32% were 12.3 (95% CI 2.50 - 60.7) times more likely to achieve the MID of LCADL. In conclusion, the baseline variables that best predict the improvement of individuals after exercise training are TGlittre and LCADL, showing that subjects with significant functional impairment are more likely to clinically significantly improve their ADLs.

Obesity-related genes are expressed in human Sertoli cells and modulated by energy homeostasis regulating hormones.

The strong hormonal dysregulation associated with obesity is responsible for the disruption of several reproductive events. Sertoli cells (SCs) function is dependent on energetic homeostasis and thus, directly associated with energy homeostasis regulating hormones. To further understand the influence of those hormones with SCs function and obesity, we hypothesize that human SCs express obesity-related genes (ORG; MC4R, GNPDA2, TMEM18, and FTO) and that they respond to energy homeostasis regulating hormones (leptin, ghrelin, and glucagon-like protein 1 [GLP-1]) stimuli. To test our hypothesis, SCs were cultured with increasing doses of leptin (0, 5, 25, or 50 ng/ml, for 24 h), ghrelin (0, 20, 100, and 500 pM, for 24 h), and GLP-1 (10, 1000, or 1 × 105 pM, for 6 h). The presence and abundance of ORG transcripts and proteins in SCs were accessed by polymerase chain reaction techniques, Western blot analysis, and immunofluorescence staining. Our results show that human SCs express MC4R, GNPDA2, TMEM18, and FTO in specific cellular locations. MC4R and FTO expression in human SCs was not responsive to the treatments. However, GNPDA2 and TMEM18 expression increased after exposure to the highest concentration of leptin and ghrelin, respectively. We highlight for the first time that human SCs express ORG and that these are responsive to energy homeostasis hormonal stimuli. GNPDA2 and TMEM18 expression respond in opposite directions according to overall energy status, mediated by energy homeostasis regulating hormones. Leptin and ghrelin control of ORG expression by human SCs can be associated with overweight-related infertility and subfertility in males.

Checklist of mammals from Goiás, central Brazil / Lista de Mamíferos de Goiás, Brasil central

Abstract: The state of Goiás, in central Brazil, is covered mainly by the Cerrado domain, with the Alto Paraná Atlantic Forest occupying its central-southern portion. Goiás is one of the 20 Brazilian federative units without a mammal checklist. In this study, we provide the first checklist of mammals from Goiás state. We recorded mammal species based primarily on the analysis of specimens housed in scientific collections as well as on literature with associated voucher material. We listed 191 mammalian species belonging to 125 genera, 31 families and 10 orders, which represents 25.2% of the mammal species occurring in Brazil. The most speciose orders were Chiroptera (90 spp.), followed by Rodentia (43 spp.), Carnivora (19 spp.) and Didelphimorphia (17 spp.). The following orders accounted for a smaller portion of the state diversity: Cetartiodactyla (7 spp.), Cingulata (7 spp.), Primates (4 spp.), Pilosa (2 spp.), Lagomorpha (1 sp.), and Perissodactyla (1 sp.). A total of 28 species (14.7%), mainly represented by medium and large-sized mammals, are nationally threatened while 12 (6.3%) are globally threatened. Our results indicate great portions of the state lacking a proper survey of mammals, especially the northwestern portion. We discuss species richness, distribution and conservation status of the mammals of Goiás state in national and regional scenarios. We highlight the need for mammal inventories based on complementary survey techniques with the collection of vouchers in order to provide karyologic, molecular, morphologic, parasitologic, and ecological data. These informations are the basis for integrative studies that lead to the understanding of current mammalian richness and diversity. Indeed, knowledge on species richness distribution in the state will guide conservation strategies, especially in areas undergoing habitat loss and fragmentation, such as the central-southern portion of Goiás.

Resumo: O estado de Goiás, no Brasil central, é coberto principalmente pelo domínio do Cerrado, com a Mata Atlântica do Alto Paraná ocupando sua porção centro-sul. Goiás é uma das 20 unidades federativas brasileiras que ainda não possui uma lista de espécies de mamíferos. Neste estudo, apresentamos a primeira lista de mamíferos para o estado. Registramos as espécies de mamíferos com base principalmente na análise de espécimes depositados em coleções científicas, bem como na literatura apresentando material testemunho associado. Listamos 191 espécies pertencentes a 125 gêneros, 31 famílias e 10 ordens, as quais representam 25,2% das espécies de mamíferos que ocorrem no Brasil. As ordens mais especiosas foram Chiroptera (90 spp.), seguida pelas ordens Rodentia (43 spp.), Carnivora (19 spp.) e Didelphimorphia (17 spp.), com as demais ordens respondendo por uma porção menor da diversidade: Cetartiodactyla (7 spp.), Cingulata (7 spp.), Primates (4 spp.), Pilosa (2 spp.), Lagomorpha (1 sp.) e Perissodactyla (1 sp.). Um total de 28 espécies (14,7%), principalmente representadas por mamíferos de médio e grande porte, estão ameaçadas nacionalmente e 12 (6,3%) encontram-se globalmente ameaçadas. Nossos resultados indicaram grandes porções do estado ainda não devidamente pesquisadas em relação aos seus mamíferos, com informações escassas e fragmentadas, principalmente no que diz respeito à sua porção noroeste. Discutimos a riqueza de espécies, a distribuição e o estado de conservação dos mamíferos do estado de Goiás nos cenários nacional e regional. Ressaltamos a importância da realização de inventários que utilizem técnicas complementares de amostragem, incluindo a coleta de material testemunho, proporcionando a obtenção de dados cariotípicos, moleculares, morfológicos, parasitológicos e ecológicos. Estas informações são a base de estudos integrativos, os quais aumentam nossa compreensão a respeito da riqueza e diversidade atual dos mamíferos. O conhecimento a respeito da distribuição da riqueza de espécies em Goiás é essencial para embasar estratégias de conservação, tão necessárias em áreas que vem sofrendo com a perda e fragmentação de seus hábitats naturais, como a porção centro-sul do estado.

Validation of a tool to evaluate women's satisfaction with breastfeeding for the Brazilian population / Validação de instrumento para avaliação da satisfação da mulher com a amamentaçãopara a população brasileira

Abstract Objective To perform the construct validity and the internal consistency of the Maternal Breastfeeding Evaluation Scale tool, aiming at its application in the Brazilian population. Methods Cross-sectional study that applied the tool to 287 Brazilian women 30 days after childbirth. Main component analysis with varimax rotation was used for the factor analysis, verifying the number of subscales and the maintenance or extraction of the components. Four hypotheses were tested using the unpaired Student's t-test for construct validation. The reliability analysis was performed using Cronbach's alpha coefficient. Results The exploratory factor analysis identified the need to exclude an item and to reformulate the subscales. The results of the construct validity showed that all hypotheses proposed were confirmed: women who were breastfeeding, those who were exclusively breastfeeding, those who did not have problems related to breastfeeding, and those who intended to breastfeed for at least 12 months achieved significantly higher mean values in the scale. The tool showed adequate internal consistency (Cronbach's alpha = 0.88, 95% CI: 0.86-0.90), as did the pleasure and fulfillment of the maternal role subscales (0.92, 95% CI: 0.91-0.93%); child growth, development, and satisfaction (0.70; 95% CI: 0.65-0.75); and maternal physical, social, and emotional aspects (0.75, 95% CI: 0.70-0.79). Conclusions The validation process of the Brazilian version of the Maternal Breastfeeding Evaluation Scale tool showed that it is valid and reliable tool to be applied to the Brazilian population.

Resumo Objetivo Realizar a validação de constructo e avaliar a consistência interna do instrumento Maternal Breastfeeding Evaluation Scale, visando à sua aplicação na população brasileira. Métodos Estudo transversal com aplicação do instrumento a 287 mulheres brasileiras após 30 dias do nascimento da criança. Para a análise fatorial utilizou-se a análise de componentes principais com rotação varimax, verificando o número de subescalas e a manutenção ou extração dos componentes. Para a validação de constructo quatro hipóteses foram testadas pelo teste T-student não pareado. A análise de confiabilidade foi realizada utilizando o coeficiente de alfa de Cronbach. Resultados A análise fatorial exploratória identificou a necessidade de exclusão de um item e a reformulação das subescalas. Os resultados da validade de constructo mostraram que todas as hipóteses propostas foram confirmadas: as mulheres que estavam amamentando, as que estavam em amamentação exclusiva, as que não apresentavam problemas relacionados à amamentação e aquelas com intenção de amamentar por pelo menos 12 meses apresentaram valores médios significativamente superiores na escala. O instrumento apresentou consistência interna adequada (alfa de Cronbach = 0,88; IC95%: 0,86-0,90), assim como as subescalas prazer e realização do papel materno (0,92; IC95%: 0,91-0,93), crescimento, desenvolvimento e satisfação infantil (0,70; IC95%: 0,65-0,75) e aspectos físico, social e emocional materno (0,75; IC95%: 0,70-0,79). Conclusões O processo de validação do instrumento Maternal Breastfeeding Evaluation Scale/BRASIL constatou que ele é válido e confiável para ser aplicado à população brasileira.

Validation of a tool to evaluate women's satisfaction with breastfeeding for the Brazilian population.

OBJECTIVE: To perform the construct validity and the internal consistency of the Maternal Breastfeeding Evaluation Scale tool, aiming at its application in the Brazilian population. METHODS: Cross-sectional study that applied the tool to 287 Brazilian women 30 days after childbirth. Main component analysis with varimax rotation was used for the factor analysis, verifying the number of subscales and the maintenance or extraction of the components. Four hypotheses were tested using the unpaired Student's t-test for construct validation. The reliability analysis was performed using Cronbach's alpha coefficient. RESULTS: The exploratory factor analysis identified the need to exclude an item and to reformulate the subscales. The results of the construct validity showed that all hypotheses proposed were confirmed: women who were breastfeeding, those who were exclusively breastfeeding, those who did not have problems related to breastfeeding, and those who intended to breastfeed for at least 12 months achieved significantly higher mean values in the scale. The tool showed adequate internal consistency (Cronbach's alpha=0.88, 95% CI: 0.86-0.90), as did the pleasure and fulfillment of the maternal role subscales (0.92, 95% CI: 0.91-0.93%); child growth, development, and satisfaction (0.70; 95% CI: 0.65-0.75); and maternal physical, social, and emotional aspects (0.75, 95% CI: 0.70-0.79). CONCLUSIONS: The validation process of the Brazilian version of the Maternal Breastfeeding Evaluation Scale tool showed that it is valid and reliable tool to be applied to the Brazilian population.

iRAGu: A Novel Inducible and Reversible Mouse Model for Ubiquitous Recombinase Activity.

Developing lymphocytes express the recombination activating genes (RAGs) 1 and 2 products that form a site specific recombinase complex (RAG), introducing double strand DNA breaks (DSBs) at recombination signal sequences (RSSs) flanking the V, D, and J gene segments in the antigen receptor loci. The subsequent steps in the reaction consist in the ligation of DSBs by ubiquitous enzymes of the non-homologous end joining DNA repair pathway. This mutagenesis process is responsible for the generation of the very large clonal diversity of T and B lymphocytes, itself allowing the recognition of a virtually open-ended antigenic universe. Sequences resembling RSS are found at high frequency all over the genome, and involved in RAG mediated illegitimate recombination and translocations. Hence, natural and induced ectopic activity of RAG is a threat to the genome only recently underscored. Here, we report and characterize a novel mouse transgenic system for which ubiquitous expression of the recombinase is inducible. In this system, the RAG1 protein is constitutively expressed and functional, while the RAG2 protein, coupled to the estrogen receptor, becomes functionally active upon 4-hydroxytamoxifen (TAM) administration. We describe two transgenic lines. The first one, when introgressed into an endogenous Rag2-/- genetic background is faithfully recapitulating lymphocyte development, repertoire dynamics and cryptic rearrangements, in a TAM-dependent manner. In this model, deprivation of TAM is followed by lymphocyte development arrest, evidencing the reversibility of the system. The second transgenic line is leaky, as the transgenes promote lymphocyte differentiation in absence of TAM treatment. Upon TAM-induction defects in lymphocytes composition and global health reveals the deleterious effect of uncontrolled RAG activity. Overall, this novel transgenic model provides a tool where RAG activity can be specifically manipulated to assess the dynamics of lymphocyte differentiation and the challenges imposed by the recombinase on the vertebrate genome.

Iron Metabolism and the Inflammatory Response.

Iron (Fe) is essential to almost all organisms, as required by cells to satisfy metabolic needs and accomplish specialized functions. Its ability to exchange electrons between different substrates, however, renders it potentially toxic. Fine tune-mechanisms are necessary to maintain Fe homeostasis and, as such, to prevent its participation into the Fenton reaction and generation of oxidative stress. These are particularly important in the context of inflammation/infection, where restricting Fe availability to invading pathogens is one, if not, the main host defense strategy against microbial growth. The ability of Fe to modulate several aspects of the immune response is associated with a number of "costs" and "benefits", some of which have been described in this review. © 2017 IUBMB Life, 69(6):442-450, 2017.

Assessing a novel polymer-wick based electrode for EEG neurophysiological research.

BACKGROUND: The EEG technique has decades of valid applications in clinical and experimental neurophysiology. EEG equipment and data analysis methods have been characterized by remarkable developments, but the skin-to-electrode signal transfer remains a challenge for EEG recording. NEW METHOD: A novel quasi-dry system - the polymer wick-based electrode - was developed to overcome the limitations of conventional dry and wet silver/silver-chloride (Ag/AgCl) electrodes for EEG recording. RESULTS: Nine participants completed an auditory oddball protocol with simultaneous EEG acquisition using both the conventional Ag/AgCl and the wick electrodes. Wick system successfully recorded the expected P300 modulation. COMPARISON WITH EXISTING METHOD(S): Standard ERP analysis, residual random noise analysis, and single-trial analysis of the P300 wave were performed in order to compare signal acquired by both electrodes. It was found that the novel wick electrode performed similarly to the conventional Ag/AgCl electrodes. CONCLUSIONS: The developed wick electrode appears to be a reliable alternative for EEG research, representing a promising halfway alternative between wet and dry electrodes.

Modeling of laccase inhibition by formetanate pesticide using theoretical approaches.

The inhibition of laccase enzymatic catalytic activity by formetanate hydrochloride (FMT) was investigated by cyclic voltammetry and by quantum chemical calculations based on density functional theory with a protein fragmentation approach. The cyclic voltammograms were obtained using a biosensor prepared by enzyme immobilization on gold electrodes modified with gold nanoparticles and 4-aminophenol as the target molecule. The decrease in the peak current in the presence of FMT was used to characterize the inhibition process. The calculations identified Asp206 as the most relevant moiety in the interaction of FMT with the laccase enzymatic ligand binding domain. The amino acid residue Cys453 was important, because the Cys453-FMT interaction energy was not affected by the dielectric constant, although it was not a very close residue. This study provides an overview of how FMT inhibits laccase catalytic activity.

Prevalence of Cognitive Impairment Without Dementia and Dementia in Tremembé, Brazil.

BACKGROUND: The prevalence of cognitive impairment is insufficiently determined in developing countries. The aim of this study was to ascertain the prevalence of cognitive impairment without dementia and dementia in community-dwelling elderly in Brazil. METHODS: This was a single-phase cross-sectional survey of the elderly (aged 60 years and above) living in the municipality of Tremembé, Brazil. Twenty percent of the households with elderly persons were randomly selected from urban and rural areas, to obtain a homogenous representation of all socioeconomic and cultural levels. RESULTS: We assessed 630 individuals [mean age, 71.3 y (±7.99); mean years of education, 4.9 (±4.54)] and found prevalence rates of 17.5% (95% confidence interval, 14.6-20.6) for dementia and 19.5% (95% confidence interval, 16.6-22.8) for cognitive impairment without dementia. These prevalence rates were influenced by age (P<0.001) and by educational level (P<0.001). There was no significant sex difference among diagnostic groups (P=0.166). The prevalence of dementia was higher in relatively younger individuals (below 70 y) when compared with other studies. Besides, dementia was associated with low socioeconomic status, stroke, previous psychiatric disorder, alcoholism, and epilepsy. CONCLUSIONS: The prevalence of dementia in this study was higher than in other studies, particularly among younger elderly.

Development of polymer wicks for the fabrication of bio-medical sensors.

Polymer based wicking structures were fabricated by sintering powders of polycarbonate (PC), ultra-high molecular weight polyethylene and polyamide 12, aiming at selecting a suitable material for an innovative electroencephalography (EEG) bio-electrode. Preliminary experiments showed that PC based wicks displayed the best mechanical properties, therefore more detailed studies were carried out with PC to evaluate the influence of powder granulometry and processing parameters (pressure, temperature and time) on the mechanical properties, porosity, mean pore radius and permeability of the wicks. It was concluded that the mechanical properties are significantly enhanced by increasing the processing time and pressure, although at the expense of a significant decrease of porosity and mean pore diameter (and thus permeability), particularly for the highest applied pressures (74kPa). However, a good compromise between porosity/permeability and mechanical properties could be obtained by sintering PC powders of particle sizes below 500µm at 165°C for 5min, upon an applied pressure of 56kPa. Moreover, PC proved to be chemically stable in contact with an EEG common used disinfectant. Thus, wicking structures with appropriate properties for the fabrication of reusable bio-electrodes could be fabricated from the sintering of PC powders.

Differential shift in spatial bias over time depends on observers׳ initial bias: Observer subtypes, or regression to the mean?

Healthy subjects typically exhibit a subtle bias of visuospatial attention favouring left space that is commonly termed 'pseudoneglect'. This bias is attenuated, or shifted rightwards, with decreasing alertness over time, consistent with theoretical models proposing that pseudoneglect is a result of the right hemisphere׳s dominance in regulating attention. Although this 'time-on-task effect' for spatial bias is observed when averaging across whole samples of healthy participants, Benwell, C. S. Y., Thut, G., Learmonth, G., & Harvey, M. (2013b). Spatial attention: differential shifts in pseudoneglect direction with time-on-task and initial bias support the idea of observer subtypes. Neuropsychologia, 51(13), 2747-2756 recently presented evidence that the direction and magnitude of bias exhibited by the participant early in the task (left biased, no bias, or right biased) were stable traits that predicted the direction of the subsequent time-on-task shift in spatial bias. That is, the spatial bias of participants who were initially left biased shifted in a rightward direction with time, whereas that of participants who were initially right biased shifted in a leftward direction. If valid, the data of Benwell et al. are potentially important and may demand a re-evaluation of current models of the neural networks governing spatial attention. Here we use two novel spatial attention tasks in an attempt to confirm the results of Benwell et al. We show that rather than being indicative of true participant subtypes, these data patterns are likely driven, at least in part, by 'regression towards the mean' arising from the analysis method employed. Although evidence supports the contention that trait-like individual differences in spatial bias exist within the healthy population, no clear evidence is yet available for participant/observer subtypes in the direction of time-on-task shift in spatial biases.

Cutting edge: Intrathymic differentiation of adaptive Foxp3+ regulatory T cells upon peripheral proinflammatory immunization.

Thymocytes differentiate into CD4(+) Foxp3(+) regulatory T cells (T(R)) upon interaction between their TCR and peptide-MHC II complexes locally expressed in the thymus. Conversion of naive CD4(+) T cells into T(R) can additionally take place in the periphery under noninflammatory conditions of Ag encounter. In this study, making use of TCR transgenic models naturally devoid of Foxp3(+) cells, we report de novo generation of T(R) upon a single footpad injection of Ag mixed with a classic proinflammatory adjuvant. Abrupt T(R) differentiation upon immunization occurred intrathymically and was essential for robust tolerance induction in a mouse model of spontaneous encephalomyelitis. This phenomenon could be attributed to a specific feature of thymocytes, which, in contrast to mature peripheral CD4(+) T cells, were insensitive to the inhibitory effects of IL-6 on the induction of Foxp3 expression. Our findings uncover a pathway for T(R) generation with major implications for immunity and tolerance induction.

Natural Treg cells spontaneously differentiate into pathogenic helper cells in lymphopenic conditions.

Induction of Forkhead-box p3 (Foxp3) expression in developing T cells upon peptide-MHC encountering has been proposed to define a lineage of committed Treg cells. However, sustained expression of Foxp3 is required for Treg function and what maintains Foxp3 expression in peripheral Treg remains obscure. To address this issue, we monitored natural Treg phenotype and function upon adoptive transfer into lymphocyte-deficient mice. We first show that about 50% of Foxp3-GFP(+) Treg isolated from Foxp3(gfp) KI animals loose Foxp3 expression in severe lymphopenic conditions. We next evidence that the cytokine IL-2, either produced by co-transferred conventional T cells or administrated i.v. prevents Foxp3 downregulation. Moreover, we document that Treg that lost Foxp3 expression upon adoptive transfer produce IL-2 are not suppressive and promote tissue infiltration and damage upon secondary transfer into alymphoid mice. Our findings that Treg convert into pathogenic Th cells in absence of IL-2 provide new clues to the success of Treg-based immune therapies.