Chebyshev-type quadrature formulas for new weight classes

We give Chebyshev-type quadrature formulas for certain new weight classes. These formulas are of highest possible degree when the number of nodes is a power of 2. We also describe the nodes in a constructive way, which is important for applications. One of our motivations to consider these type of problems is the Faraday cage phenomenon for discrete charges as discussed by J. Korevaar and his colleagues.

Wellposedness of a nonlinear, logarithmic Schrödinger equation of Doebner-Goldin type modeling quantum dissipation

This paper is concerned with the modeling and analysis of quantum dissipation phenomena in the Schrödinger picture. More precisely, we do investigate in detail a dissipative, nonlinear Schrödinger equation somehow accounting for quantum Fokker–Planck effects, and how it is drastically reduced to a simpler logarithmic equation via a nonlinear gauge transformation in such a way that the physics underlying both problems keeps unaltered. From a mathematical viewpoint, this allows for a more achievable analysis regarding the local wellposedness of the initial–boundary value problem. This simplification requires the performance of the polar (modulus–argument) decomposition of the wavefunction, which is rigorously attained (for the first time to the best of our knowledge) under quite reasonable assumptions.

Molecular mechanisms for the transcriptional regulation of the Connexin36 gene expression in insulin-secreting cells

Résumé Régulation de l'expression de la Connexin36 dans les cellules sécrétrices d'insuline La communication intercellulaire est en partie assurée via des jonctions communicantes de type "gap". Dans la cellule ß pancréatique, plusieurs observations indiquent que le couplage assuré par des jonctions gap formées parla Connexine36 (Cx36) est impliqué dans le contrôle de la sécrétion de l'insuline. De plus, nous avons récemment démontré qu'un niveau précis d'expression de la Cx36 est nécessaire pour maintenir une bonne coordination de l'ensemble des cellules ß, et permettre ainsi une sécrétion synchrone et contrôlée d'insuline. Le développement du diabète et du syndrome métabolique est partiellement dû à une altération de la capacité des cellules ß à sécréter de l'insuline en réponse à une augmentation de la glycémie. Cette altération est en partie causée par l'augmentation prolongée des taux circulant de glucose, mais aussi de lipides, sous la forme d'acides gras libres, et de LDL (Low Density Lipoproteins), particules assurant le transport des acides gras et du cholestérol dans le sang. Nous avons étudié la régulation de l'expression de la Cx36 dans différentes conditions reflétant la physiopathologie du diabète de type 2 et du syndrome métabolique et démontré qu'une exposition prolongée à des concentrations élevées de glucose, de LDL, ainsi que de palmitate (acide gras saturé le plus abondant dans l'organisme), inhibent l'expression de la Cx36 dans les cellules ß. Cette inhibition implique l'activation de la PKA (Proteine Kinase A), qui stimule à son tour l'expression du facteur de transcription ICER-1 (Inductible cAMP Early Repressor-1). Ce puissant répresseur se fixe spécifiquement sur un motif CRE (cAMP Response Element), situé dans le promoteur du gène de la Cx36, inhibant ainsi son expression. Nous avons de plus démontré que des cytokines pro-inflammatoires, qui pourraient contribuer au développement du diabète, inhibent également l'expression de la Cx36. Cependant, les cytokines agissent indépendamment du répresseur ICER-1, mais selon un mécanisme requérant l'activation de l'AMPK (AMP dependant protein kinase). Sachant qu'un contrôle précis des niveaux d'expression de la Cx36 est un élément déterminant pour une sécrétion optimale de l'insuline, nos résultats suggèrent que la Cx36 pourrait être impliquée dans l'altération de la sécrétion de l'insuline contribuant à l'apparition du diabète de type 2. Summary A particular way by which cells communicate with each other is mediated by gap junctions, transmembrane structures providing a direct pathway for the diffusion of small molecules between adjacent cells. Gap junctional communication is required to maintain a proper functioning of insulin-secreting ß-cells. Moreover, the expression levels of connexin36 (Cx36), the sole gap junction protein expressed in ß-cells, are critical in maintaining glucose-stimulated insulin secretion. Chronic hyperglycemia and hyperlipidemia exert deleterious effects on insulin secretion and may contribute to the progressive ß-cell failure linked to the development of type 2 diabetes and metabolic syndrome. Since modulations of the Cx36 levels might impair ß-cell function, the general aim of this work was to elucidate wether elevated levels of glucose and lipids affect Cx36 expression. The first part of this work was dedicated to the study of the effect of high glucose concentrations on Cx36 expression. We demonstrated that glucose transcriptionally down-regulates the expression of Cx36 in insulin-secreting cells through activation of the protein kinase A (PKA), which in turn stimulates the expression of the inducible cAMP early repressor-1 (ICER-1). This repressor binds to a highly conserved cAMP response element (CRE) located in the Cx36 promoter, thereby inhibiting Cx36 expression. The second part of this thesis consisted in studying the effects of sustained exposure to free fatty acids (FFA) and human lipoproteins on Cx36 levels. The experiments revealed that the most abundant FFA, palmitate, as well as the atherogenic low density lipoproteins (LDL), also stimulate ICER-1 expression, resulting in Cx36 down-regulation. Finally, the third part of the work focused on the consequences of long-term exposure to proinflammatory cytokines on Cx36 content. Interleukin-1 ß (IL-1 ß) inhibits Cx36 expression and its effect is potentialized by tumor necrosis factor α (TNFα) and interferon γ (IFNγ). We further unveiled that the cytokines effect on Cx36 levels requires activation of the AMP dependent protein kinase (AMPK). Prolonged exposures to glucose, palmitate, LDL, and pro-inflammatory cytokines have all been proposed to contribute to the development of diabetes and metabolic syndrome. Since Cx36 expression levels are critical to maintain ß-cell function, Cx36 down-regulation by glucose, lipids, and cytokines might participate to the ß-cell failure associated with diabetes development.

Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa.

Autosomal recessive cutis laxa type I (ARCL type I) is characterized by generalized cutis laxa with pulmonary emphysema and/or vascular complications. Rarely, mutations can be identified in FBLN4 or FBLN5. Recently, LTBP4 mutations have been implicated in a similar phenotype. Studying FBLN4, FBLN5, and LTBP4 in 12 families with ARCL type I, we found bi-allelic FBLN5 mutations in two probands, whereas nine probands harbored biallelic mutations in LTBP4. FBLN5 and LTBP4 mutations cause a very similar phenotype associated with severe pulmonary emphysema, in the absence of vascular tortuosity or aneurysms. Gastrointestinal and genitourinary tract involvement seems to be more severe in patients with LTBP4 mutations. Functional studies showed that most premature termination mutations in LTBP4 result in severely reduced mRNA and protein levels. This correlated with increased transforming growth factor-beta (TGFβ) activity. However, one mutation, c.4127dupC, escaped nonsense-mediated decay. The corresponding mutant protein (p.Arg1377Alafs(*) 27) showed reduced colocalization with fibronectin, leading to an abnormal morphology of microfibrils in fibroblast cultures, while retaining normal TGFβ activity. We conclude that LTBP4 mutations cause disease through both loss of function and gain of function mechanisms.

The type specimens of chewing lice (Insecta, Mallophaga) deposited in the entomological collection of Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil

This paper presents a list of 131 Mallophaga type specimens deposited in the Werneck Collection of Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil. It includes 69 holotypes, 62 allotypes, 683 paratypes, 1 syntype and 2 neoparatypes, distributed among 6 families and 35 genera. The types are listed with their respective data and literature.

Comparative immunological recognition of proteins from New Guinea "C" dengue virus type 2 prototype and from a dengue virus type 2 strain isolated in the State of Rio de Janeiro, Brazil

The protein profiles of the New Guinea "C" dengue virus type 2 (DENV-2)prototype and those of a Brazilian DENV-2 isolated in the State of Rio de Janeiro in 1995 were compared. SDS-PAGE analysis showed that the virus from Rio de Janeiro expresses NS5 (93.0 kDa), NS3 (66.8 kDa) E (62.4 kDa) and NS1 (41.2 kDa) proteins differently from the New Guinea "C" virus. The immunoblot revealed specificity and antigenicity for the NS3 protein from DENV-2 Rio de Janeiro mainly in primary infections, convalescent cases, and in secondary infections in both cases and only antigenicity for E and NS1 proteins for both viruses in primary and secondary infections.

Role of genetic and social factors in modulating the efficiency of division of labour in social insects

Summary : Division of labour is one of the most fascinating aspects of social insects. The efficient allocation of individuals to a multitude of different tasks requires a dynamic adjustment in response to the demands of a changing environment. A considerable number of theoretical models have focussed on identifying the mechanisms allowing colonies to perform efficient task allocation. The large majority of these models are built on the observation that individuals in a colony vary in their propensity (response threshold) to perform different tasks. Since individuals with a low threshold for a given task stimulus are more likely to perform that task than individuals with a high threshold, infra-colony variation in individual thresholds results in colony division of labour. These theoretical models suggest that variation in individual thresholds is affected by the within-colony genetic diversity. However, the models have not considered the genetic architecture underlying the individual response thresholds. This is important because a better understanding of division of labour requires determining how genotypic variation relates to differences in infra-colony response threshold distributions. In this thesis, we investigated the combined influence on task allocation efficiency of both, the within-colony genetic variability (stemming from variation in the number of matings by queens) and the number of genes underlying the response thresholds. We used an agent-based simulator to model a situation where workers in a colony had to perform either a regulatory task (where the amount of a given food item in the colony had to be maintained within predefined bounds) or a foraging task (where the quantity of a second type of food item collected had to be the highest possible). The performance of colonies was a function of workers being able to perform both tasks efficiently. To study the effect of within-colony genetic diversity, we compared the performance of colonies with queens mated with varying number of males. On the other hand, the influence of genetic architecture was investigated by varying the number of loci underlying the response threshold of the foraging and regulatory tasks. Artificial evolution was used to evolve the allelic values underlying the tasks thresholds. The results revealed that multiple matings always translated into higher colony performance, whatever the number of loci encoding the thresholds of the regulatory and foraging tasks. However, the beneficial effect of additional matings was particularly important when the genetic architecture of queens comprised one or few genes for the foraging task's threshold. By contrast, higher number of genes encoding the foraging task reduced colony performance with the detrimental effect being stronger when queens had mated with several males. Finally, the number of genes determining the threshold for the regulatory task only had a minor but incremental effect on colony performance. Overall, our numerical experiments indicate the importance of considering the effects of queen mating frequency, genetic architecture underlying task thresholds and the type of task performed when investigating the factors regulating the efficiency of division of labour in social insects. In this thesis we also investigate the task allocation efficiency of response threshold models and compare them with neural networks. While response threshold models are widely used amongst theoretical biologists interested in division of labour in social insects, our simulation reveals that they perform poorly compared to a neural network model. A major shortcoming of response thresholds is that they fail at one of the most crucial requirement of division of labour, the ability of individuals in a colony to efficiently switch between tasks under varying environmental conditions. Moreover, the intrinsic properties of the threshold models are that they lead to a large proportion of idle workers. Our results highlight these limitations of the response threshold models and provide an adequate substitute. Altogether, the experiments presented in this thesis provide novel contributions to the understanding of how division of labour in social insects is influenced by queen mating frequency and genetic architecture underlying worker task thresholds. Moreover, the thesis also provides a novel model of the mechanisms underlying worker task allocation that maybe more generally applicable than the widely used response threshold models. Resumé : La répartition du travail est l'un des aspects les plus fascinants des insectes vivant en société. Une allocation efficace de la multitude de différentes tâches entre individus demande un ajustement dynamique afin de répondre aux exigences d'un environnement en constant changement. Un nombre considérable de modèles théoriques se sont attachés à identifier les mécanismes permettant aux colonies d'effectuer une allocation efficace des tâches. La grande majorité des ces modèles sont basés sur le constat que les individus d'une même colonie diffèrent dans leur propension (inclination à répondre) à effectuer différentes tâches. Etant donné que les individus possédant un faible seuil de réponse à un stimulus associé à une tâche donnée sont plus disposés à effectuer cette dernière que les individus possédant un seuil élevé, les différences de seuils parmi les individus vivant au sein d'une même colonie mènent à une certaine répartition du travail. Ces modèles théoriques suggèrent que la variation des seuils des individus est affectée par la diversité génétique propre à la colonie. Cependant, ces modèles ne considèrent pas la structure génétique qui est à la base des seuils de réponse individuels. Ceci est très important car une meilleure compréhension de la répartition du travail requière de déterminer de quelle manière les variations génotypiques sont associées aux différentes distributions de seuils de réponse à l'intérieur d'une même colonie. Dans le cadre de cette thèse, nous étudions l'influence combinée de la variabilité génétique d'une colonie (qui prend son origine dans la variation du nombre d'accouplements des reines) avec le nombre de gènes supportant les seuils de réponse, vis-à-vis de la performance de l'allocation des tâches. Nous avons utilisé un simulateur basé sur des agents pour modéliser une situation où les travailleurs d'une colonie devaient accomplir une tâche de régulation (1a quantité d'une nourriture donnée doit être maintenue à l'intérieur d'un certain intervalle) ou une tâche de recherche de nourriture (la quantité d'une certaine nourriture doit être accumulée autant que possible). Dans ce contexte, 'efficacité des colonies tient en partie des travailleurs qui sont capable d'effectuer les deux tâches de manière efficace. Pour étudier l'effet de la diversité génétique d'une colonie, nous comparons l'efficacité des colonies possédant des reines qui s'accouplent avec un nombre variant de mâles. D'autre part, l'influence de la structure génétique a été étudiée en variant le nombre de loci à la base du seuil de réponse des deux tâches de régulation et de recherche de nourriture. Une évolution artificielle a été réalisée pour évoluer les valeurs alléliques qui sont à l'origine de ces seuils de réponse. Les résultats ont révélé que de nombreux accouplements se traduisaient toujours en une plus grande performance de la colonie, quelque soit le nombre de loci encodant les seuils des tâches de régulation et de recherche de nourriture. Cependant, les effets bénéfiques d'accouplements additionnels ont été particulièrement important lorsque la structure génétique des reines comprenait un ou quelques gènes pour le seuil de réponse pour la tâche de recherche de nourriture. D'autre part, un nombre plus élevé de gènes encodant la tâche de recherche de nourriture a diminué la performance de la colonie avec un effet nuisible d'autant plus fort lorsque les reines s'accouplent avec plusieurs mâles. Finalement, le nombre de gènes déterminant le seuil pour la tâche de régulation eu seulement un effet mineur mais incrémental sur la performance de la colonie. Pour conclure, nos expériences numériques révèlent l'importance de considérer les effets associés à la fréquence d'accouplement des reines, à la structure génétique qui est à l'origine des seuils de réponse pour les tâches ainsi qu'au type de tâche effectué au moment d'étudier les facteurs qui régulent l'efficacité de la répartition du travail chez les insectes vivant en communauté. Dans cette thèse, nous étudions l'efficacité de l'allocation des tâches des modèles prenant en compte des seuils de réponses, et les comparons à des réseaux de neurones. Alors que les modèles basés sur des seuils de réponse sont couramment utilisés parmi les biologistes intéressés par la répartition des tâches chez les insectes vivant en société, notre simulation montre qu'ils se révèlent peu efficace comparé à un modèle faisant usage de réseaux de neurones. Un point faible majeur des seuils de réponse est qu'ils échouent sur un point crucial nécessaire à la répartition des tâches, la capacité des individus d'une colonie à commuter efficacement entre des tâches soumises à des conditions environnementales changeantes. De plus, les propriétés intrinsèques des modèles basés sur l'utilisation de seuils conduisent à de larges populations de travailleurs inactifs. Nos résultats mettent en évidence les limites de ces modèles basés sur l'utilisation de seuils et fournissent un substitut adéquat. Ensemble, les expériences présentées dans cette thèse fournissent de nouvelles contributions pour comprendre comment la répartition du travail chez les insectes vivant en société est influencée par la fréquence d'accouplements des reines ainsi que par la structure génétique qui est à l'origine, pour un travailleur, du seuil de réponse pour une tâche. De plus, cette thèse fournit également un nouveau modèle décrivant les mécanismes qui sont à l'origine de l'allocation des tâches entre travailleurs, mécanismes qui peuvent être appliqué de manière plus générale que ceux couramment utilisés et basés sur des seuils de réponse.

Sequence and phylogenetic analysis of human T cell lymphotropic virus type 1 from Tumaco, Colombia

Human T cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes leukemia and the neurological disorder HTLV-1 associated myelopathy or tropical spastic paraparesis (HAM/TSP). Infection with this virus - although it is distributed worldwide - is limited to certain endemic areas of the world. Despite its specific distribution and slow mutation rate, molecular epidemiology on this virus has been useful to follow the movements of human populations and routes of virus spread to different continents. In the present study, we analyzed the genetic variability of a region of the env gene of isolates obtained from individuals of African origin that live on the Pacific coast of Colombia. Sequencing and comparison of the fragment with the same fragment from different HTLV-1 isolates showed a variability ranging from 0.8% to 1.2%. Phylogenetic studies permit us to include these isolates in the transcontinental subgroup A in which samples isolated from Brazil and Chile are also found. Further analyses will be necessary to determine if these isolates were recently introduced into the American continent or if they rather correspond to isolates introduced during the Paleolithic period.

Human immunodeficiency virus type 1: drug resistance in treated and untreated Brazilian children

Twenty-two vertically human immunodeficiency virus type 1 (HIV-1) infected Brazilian children were studied for antiretroviral drug resistance. They were separated into 2 groups according to the administration of antiretroviral therapy into those who presented disease symptoms or without symptoms and no therapy. Viral genome sequencing reactions were loaded on an automated DNA sampler (TruGene, Visible Genetics) and compared to a database of wild type HIV-1. In the former group 8 of 12 children presented isolates with mutations conferring resistance to protease inhibitors (PIs), 7 presented isolates resistant to nucleoside reverse transcriptase inhibitors (NRTIs) and 2 presented isolates resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Ten children were included in the antiretroviral naïve group. Eight were susceptible to NRTIs and all of them were susceptible to PIs; one presented the V108I mutation, which confers low-level resistance to NNRTIs. The data report HIV mutant isolates both in treated and untreated infants. However, the frequency and the level of drug resistance were more frequent in the group receiving antiretroviral therapy, corroborating the concept of selective pressure acting on the emergence of resistant viral strains. The children who presented alterations at polymorphism sites should be monitored for the development of additional mutations occurring at relevant resistance codons.

Identification of small RNAs in Pseudomonas species

Summary: Bacterial small RNAs (sRNAs) are transcripts most of which have regulatory functions. Sequence and secondary structure elements enable numerous sRNAs to interact with mRNAs or with regulatory proteins resulting in diverse regulatory effects on virulence, iron storage, organization of cell envelope proteins or stress response. sRNAs having high affinity for RsmA-like RNA-binding proteins are important for posttranscriptional regulation in various Gram-negative bacteria. In Pseudomonas spp., the GacS/GacA two component system positively controls the production of such sRNAs. They titrate RsmA-like proteins and thus overcome translational repression due to these proteins. As a consequence, secondary metabolites can be produced that are implicated in the biocontrol capacity of P. fluorescens or in the virulence of P. aeruginosa. A genome-wide search carried out in P. aeruginosa PAO1 and in closely related Pseudomonas spp. resulted in the identification of 15 genes coding for sRNAs. Eight of these are novel, the remaining seven have previously been observed. Among them, the 1698 sRNA gene was expressed under GacA control, whereas the transcription of 1887 sRNA gene was transcribed under the control of the anaerobic regulator Anr in an oxygen-limited environment. Overexpression of 1698 sRNA in P. fluorescens strain CHAO did not affect the expression of the GacA-regulated hcnA gene (first gene of the operon coding for HCN synthase), indicating that 1698 sRNA is probably not part of the secondary metabolite regulation pathway. The expression of 1698 sRNA was positively regulated by RpoS in both P. aeruginosa PAO 1 and P. ,fluorescens CHAO and appeared to be modulated temporarily by oxidative stress conditions. However, the effect of 1698 sRNA on oxidative stress survival has not yet been established. Hfq protein interacted with 1698 sRNA in vitro and improved 1698 sRNA expression in vivo in P. aeruginosa. In P. fluorescens, GacA and Hfq were both required for expression of rpoS and GacA showed a positively control on the hfq expression; therefore, at least in this organism, GacA control of 1698 sRNA expression may act indirectly via Hfq and RpoS. Different methods were employed to find abase-pairing target for 1698 sRNA. In a proteomic analysis carried out in P. aeruginosa, positive regulation by 1698 sRNA was observed for Soda, the iron-associated superoxide dismutase, an enzyme involved in oxidative stress resistance. A sequence complementary with 1698 sRNA was predicted to be located in the 5' leader of soda mRNA. However, base-pairing between soda mRNA and 1698 sRNA remains to be proven. In conclusion, this work has revealed eight novel sRNAs and novel functions of two sRNAs in Pseudomonas spp. Résumé Les petits ARNs non-codants (sRNAs) produits par les bactéries sont des transcrits ayant pour la plupart des activités régulatrices importantes. Leurs séquences nucléotidiques ainsi que leurs structures secondaires permettent aux sRNAs d'interagir soit avec des RNA messagers (mRNAs), de sorte à modifier l'expression des protéines pour lesquelles ils codent, soit avec des protéines régulatrices liant des rnRNAs, ce qui a pour effet de modifier l'expression de ces mRNAs. Des sRNAs sont impliqués dans diverses voies de régulation, telles que celles qui régissent la virulence, le stockage du fer, l'organisation des protéines de l'enveloppe bactérienne ou la réponse au stress. Chez les Pseudomonas spp., le système à deux composantes GacS/GacA contrôle la production de métabolites secondaires. Ceux-ci sont engagés dans l'établissement du biocontrôle, chez P. fluorescens, ou. de la virulence, chez P. aeruginosa. La régulation génique dirigée par le système GacS/GacA fait intervenir les sRNAs du type RsmZ, capables de contrecarrer l'action au niveau traductionnel exercée par les protéines régulatrices du type RsmA. Une recherche au niveau du génome a été menée chez P. aeruginosa PAO1 de même que chez des espèces qui lui sont étroitement apparentées, débouchant sur la mise en évidence de 15 gènes codant pour des sRNAs. Parmi ceux-ci, huit ont été découverts pour la première fois et sept confirment des travaux publiés. L'expression du gène du sRNAs 1698 s'avère être régulée par GacA, vraisemblablement de manière indirecte. La transcription du gène du sRNA 1887 montre une dépendance envers Anr, régulateur de l'anaérobiose, et envers une carence en oxygène. La surexpression du sRNA 1698 chez P. fluorescens CHAO n'affecte pas l'expression de hcnA, un gène du régulon GacA, laissant supposer que le sRNA n'intervient pas dans la régulation des métabolites secondaires. Chez P. aeruginosa PAOI et chez P. fluorescens CHAO, RpoS, le facteur sigma du stress, est nécessaire à l'expression du sRNA 1698, et la concentration de ce dernier est modulée par des conditions de stress oxydatif. Toutefois, un effet du sRNA 1698 quant à la survie suite au stress oxydatif n'a pas été établi. Par ailleurs, l'interaction entre le sRNA 1698 et Hfq, la protéine chaperone de RNAs, in vitro ainsi qu'un rôle positif de Hfq pour l'expression du sRNA 1698 in vivo ont été démontrés chez P. aeruginosa. L'induction de l'expression par GacA de rpoS et de hfq a été confirmée chez P. fluorescens CHAO, suggérant que la régulation par GacA du sRNA 1698 pourrait se faire par l'intermédiaire de RpoS et Hfq. Diverses méthodes ont été employées pour identifier un transcrit qui puisse être apparié par le sRNA 1698. Une analyse de protéome chez P. aeruginosa montre que l'expression de Soda, la superoxyde dismutase associée au fer, est positivement régulée par le sRNA 1698. Soda est une enzyme impliquée dans la résistance au stress oxydatif. Une séquence de complémentarité avec le sRNA 1698 a bien été prédite sur le leader 5' du mRNA de soda. Cependant, l'appariement entre le sRNA et son transcrit cible est encore à prouver. En conclusion, ce travail a dévoilé huit nouveaux sRNAs et de nouvelles fonctions pour deux sRNAs chez les Pseudomonas.

CD4+ T cell count recovery in HIV type 1-infected patients is independent of class of antiretroviral therapy.

BACKGROUND: In recent years, treatment options for human immunodeficiency virus type 1 (HIV-1) infection have changed from nonboosted protease inhibitors (PIs) to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) and boosted PI-based antiretroviral drug regimens, but the impact on immunological recovery remains uncertain. METHODS: During January 1996 through December 2004 [corrected] all patients in the Swiss HIV Cohort were included if they received the first combination antiretroviral therapy (cART) and had known baseline CD4(+) T cell counts and HIV-1 RNA values (n = 3293). For follow-up, we used the Swiss HIV Cohort Study database update of May 2007 [corrected] The mean (+/-SD) duration of follow-up was 26.8 +/- 20.5 months. The follow-up time was limited to the duration of the first cART. CD4(+) T cell recovery was analyzed in 3 different treatment groups: nonboosted PI, NNRTI, or boosted PI. The end point was the absolute increase of CD4(+) T cell count in the 3 treatment groups after the initiation of cART. RESULTS: Two thousand five hundred ninety individuals (78.7%) initiated a nonboosted-PI regimen, 452 (13.7%) initiated an NNRTI regimen, and 251 (7.6%) initiated a boosted-PI regimen. Absolute CD4(+) T cell count increases at 48 months were as follows: in the nonboosted-PI group, from 210 to 520 cells/muL; in the NNRTI group, from 220 to 475 cells/muL; and in the boosted-PI group, from 168 to 511 cells/muL. In a multivariate analysis, the treatment group did not affect the response of CD4(+) T cells; however, increased age, pretreatment with nucleoside reverse-transcriptase inhibitors, serological tests positive for hepatitis C virus, Centers for Disease Control and Prevention stage C infection, lower baseline CD4(+) T cell count, and lower baseline HIV-1 RNA level were risk factors for smaller increases in CD4(+) T cell count. CONCLUSION: CD4(+) T cell recovery was similar in patients receiving nonboosted PI-, NNRTI-, and boosted PI-based cART.

Vibration training elicits a mixed aerobic and resistance-type exercise in sedentary subjects.

Objective. Vibration training (VT) is a new exercise method, with good acceptance among sedentary subjects, due to its passive principle: the machine moves the subject, not the opposite. We hypothesize that untrained subjects can benefit from a greater cardiovascular and metabolic stimulation than trained athletes, resembling classical aerobic-type activity, in addition of eliciting strength gains shown in diverse studies. Methods. 3 group of male subjects, inactive (SED), endurance trained athletes (END) and strength trained athletes (STR) underwent fitness (VO2max) and lower-body strength tests (isokinetic). Subjects were submitted to a session of oscillating VT, composed of 3 exercises (isometric half-squat, dynamic squat, dynamic squat with added load), each of 3 minutes duration, and repeated at 3 frequencies. VO2, heart rate and Borg scale were monitored. Results. 27 healthy subjects (10 SED, 9 END and 8 STR), mean age 24.5 (SED), 25.0 (STR) and 29.8 (END) were included. VO2max was significantly different as expected (47.9 vs. 52.9 vs. 63.9 ml/kg/min, resp. for SED, STR and END). Isokinetic dominant leg extensors strength was higher in STR (3.32 Nm/kg vs. 2.60 and 2.74 in SED and END). During VT, peak oxygen consumption (% of VO2max) attained was 59.3 in SED, 50.8 in STR and 48.0 in END (P<0.001 between SED and other subjects). Peak heart rate (% of heart rate max) was 82.7 in SED, 80.4 in STR and 72.4 in END. In SED, dynamic exercises without extra load elicited 51.0% of VO2max and 72.1% of heart rate max, and perceived effort reached 15.1/20. Conclusions. VT is an unconventional type of exercise, which has been shown to enhance strength, bone density, balance and flexibility. Users are attracted by the relative passivity. In SED, we show that VT elicits sufficient cardiovascular response to benefit overall fitness in addition to the known strength effects. VT's higher acceptance as an exercise in sedentary people, compared to jogging or cycling for example, can lead to better adherence to physical activity. Although long-term effects of VT on health are not avalaible, we believe this type of combination of aerobic and resistance-type exercise can be beneficial on multiple health parameters, especially cardiovascular health.

Human immunodeficiency virus type 1 Brazilian subtype B variant showed an increasing avidity of the anti-V3 antibodies over time compared to the subtype B US/European strain in São Paulo, Brazil

The Brazilian variant of human immunodeficiency virus type 1 (HIV-1) subtype B, (serotype B"-GWGR), has a tryptophan replacing the proline in position 328 the HIV-1 envelope. A longer median time period from infection to acquired immunodeficiency syndrome (AIDS) for serotype B (B"-GWGR) infected subjects compared to the B-GPGR US/European strain was reported. In a cohort study, in São Paulo city, 10 B"-GWGR patients had a statistically significant increased avidity of the anti-V3 antibodies, from 79% ± 33% to 85% ± 75%, versus from 48% ± 59% to 32% ± 17% for the 10 B-GPGR subjects (p = 0.02). The T CD4+ cells showed a mean increase of + 0.45 cells/month for the B-GPGR subjects and for B"-GWGR the slope was + 1.24 cells/month (p = 0.06), for 62 and 55 months of follow up, respectively. RNA plasma viral load decreased from 3.98 ± 1.75 to 2.16 ± 1.54 log10 in the B"-GWGR group while B-GPGR patients showed one log10 reduction in viral load from 4.09 ± 0.38 to 3.17 ± 1.47 log10 over time (p = 0.23), with a decreasing slope of 0.0042 ± log10,/month and 0.0080 ± log10/month, for B-GPGR and B"-GWGR patients, respectively (p = 0.53). Neither group presented any AIDS defining events during the study, according to Center for Diseases Control criteria. Although the sample size is small, these results may indicate that differences in the pathogenicity of the 2 HIV-1 B serotypes which co-circulate in Brazil may be correlated to the avidity of anti-V3 antibodies.

Prevent type 2 diabetes by preventing obesity

In 2011 nearly 73,000 adults in Northern Ireland are registered as having diabetes. Many cases of diabetes are preventable and are the result of obesity. With this in mind, on World Diabetes Day, 14 November 2011, the Public Health Agency is encouraging everyone across Northern Ireland to be aware of how Type 2 diabetes can be prevented, the dangers it can cause to your health and what the signs and symptoms of diabetes are to ensure early diagnosis.The links between type 2 diabetes and obesity are firmly established. Without the intervention of a healthy diet and appropriate exercise, obesity may develop into diabetes over a relatively short period of time. According to the International Diabetes Federation (IDF), worldwide 80 per cent of people with Type 2 diabetes are overweight or obese at the time of diagnosis.If you are overweight, or obese the key step to preventing or delaying the onset of Type 2 diabetes is to lose a small amount of weight by making healthy food choices and being physically active 30 minutes a day, 5 days a week.Diabetes, if left untreated can cause serious long term health complications such as heart disease, kidney damage, eye problems, which can affect vision, and foot problems leading to amputation.Dr Brid Farrell, Consultant in Public Health Medicine, PHA, said: "The increase of diabetes occurring in the population can be explained by rising levels of obesity, people living longer and improved detection and diagnosis of diabetes in primary care."Having a family history of Type 2 diabetes increases your chances of developing diabetes. Take the first step today toward lowering your risk for Type 2 diabetes and improving your health and the health of future generations." The symptoms of diabetes can include increased thirst, passing urine more, frequently (bedwetting in children), extreme tiredness, slow healing infections, blurred vision and significant or unexplained weight loss. Symptoms of diabetes can develop quickly over days or weeks, and sometimes with Type 2 diabetes, a person may have no symptoms. Early diagnosis is important. If you think you have diabetes speak to your GP or pharmacist.Dr Farrell continued: "Diabetes is a lifelong condition, but complications can be prevented or delayed by controlling your blood sugar, and treating high blood pressure and high cholesterol. If you have diabetes, a healthy diet and regular exercise is very important."Health Minister Edwin Poots said:"Diabetes is a serious condition, which affects many thousands of people across Northern Ireland. While not all diabetes is preventable, we all have a responsibility to look after our own health. "By making healthier lifestyle choices such as eating a healthy, well-balanced diet and taking regular exercise, we can reduce our risk of developing potentially life threatening conditions such as type 2 diabetes. I would urge everyone to take every possible step to improve their health and avoid developing preventable illnesses