Comparison of the clinical effectiveness of a single and a triple-headed toothbrushes in a population of mentally retarded patients

Tooth brushing is a very simple and effective method for removing daily dental deposits and for preventing dental and periodontal diseases. However, it can cause considerable manipulative difficulties among some populations, e.g., young children, physically handicapped and mentally retarded patients. In order to test and compare the efficiency of a newly designed toothbrush (Superbrush® 1 ), we have performed a pilot study on patients staying at the «Reine Fabiola Village N° 1», an institution for patients who are followed for mental retardation at different levels. 30 patients were included in the study, aged between 18 to 40 years. Among these 30, five had to be eliminated for their incapacity to follow the initial training in how to brush their teeth. The comparison was made with a normal single headed tooth brush, in a double blind trial, based on bleeding and plaque indexes, performed on 6 different teeth on day 0,7 and 21. The results of this study indicate that there is no significant difference between the two types of toothbrushes with respect to the ability of plaque removing and gingivitis prevention, during the period of time of this study. However, the easiness of manipulating this newly designed toothbrush renders it a useful tool for the dental hygiene for this special part of the dental compromised population.Le brossage des dents constitue une méthode simple et efficace pour ôter le dépôt dentaire journalier, et pour empêcher les maladies dentaires et parodontales. Cependant, le brossage peut engendrer des difficultés de manipulation au sein de certaines populations, chez les jeunes enfants par exemple, ou chez les handicapés physiques ou encore chez les retardés mentaux. En vue de tester et de comparer l’efficacité d’une nouvelle brosse à dents avec un nouveau design (Superbrush ® 1), nous avons réalisé une étude pilote sur des patients résidant au «village Reine Fabiola n° 1», une institution pour personnes retardées mentalement à différents niveaux. Notre échantillon s’est composé de 30 patients âgés de 18 à 40 ans. Parmi ceuxci, cinq ont été éliminé suite à leur incapacité de suivre les explications initiales concernant les méthodes de brossage. Nous avons vérifié l’efficacité de la nouvelle brosse en comparant le saignement et les index de plaque dentaire par rapport à ceux obtenus avec une brosse à tête unique. Ces tests ont été réalisés sur 6 dents différentes, au jour 0, 7 et 21. Les résultats de cette étude indiquent qu’il n’y a pas de différences significatives entre les deux types de brosses à dents quant à leur efficacité d’ôter la plaque et d’empêcher les gingivites pendant la période étudiée. Cependant, vu la facilité de manipulation de la nouvelle brosse à dents, celle-ci peut s’avérer être très utile pour l’hygiène dentaire de certaines catégories de population.

Adaptive model-driven user interface development systems

Adaptive user interfaces (UIs) were introduced to address some of the usability problems that plague many software applications. Model-driven engineering formed the basis for most of the systems targeting the development of such UIs. An overview of these systems is presented and a set of criteria is established to evaluate the strengths and shortcomings of the state-of-the-art, which is categorized under architectures, techniques, and tools. A summary of the evaluation is presented in tables that visually illustrate the fulfillment of each criterion by each system. The evaluation identified several gaps in the existing art and highlighted the areas of promising improvement

Imaging of Bubonic Plague Dynamics by In Vivo Tracking of Bioluminescent Yersinia pestis

Yersinia pestis dissemination in a host is usually studied by enumerating bacteria in the tissues of animals sacrificed at different times. This laborious methodology gives only snapshots of the infection, as the infectious process is not synchronized. In this work we used in vivo bioluminescence imaging (BLI) to follow Y. pestis dissemination during bubonic plague. We first demonstrated that Y. pestis CO92 transformed with pGEN-luxCDABE stably emitted bioluminescence in vitro and in vivo, while retaining full virulence. The light produced from live animals allowed to delineate the infected organs and correlated with bacterial loads, thus validating the BLI tool. We then showed that the first step of the infectious process is a bacterial multiplication at the injection site (linea alba), followed by a colonization of the draining inguinal lymph node(s), and subsequently of the ipsilateral axillary lymph node through a direct connection between the two nodes. A mild bacteremia and an effective filtering of the blood stream by the liver and spleen probably accounted for the early bacterial blood clearance and the simultaneous development of bacterial foci within these organs. The saturation of the filtering capacity of the spleen and liver subsequently led to terminal septicemia. Our results also indicate that secondary lymphoid tissues are the main targets of Y. pestis multiplication and that colonization of other organs occurs essentially at the terminal phase of the disease. Finally, our analysis reveals that the high variability in the kinetics of infection is attributable to the time the bacteria remain confined at the injection site. However, once Y. pestis has reached the draining lymph nodes, the disease progresses extremely rapidly, leading to the invasion of the entire body within two days and to death of the animals. This highlights the extraordinary capacity of Y. pestis to annihilate the host innate immune response

Proportions of CD4+ memory T cells are altered in individuals chronically infected with Schistosoma haematobium

Characterisation of protective helminth acquired immunity in humans or experimental models has focused on effector responses with little work conducted on memory responses. Here we show for the first time, that human helminth infection is associated with altered proportions of the CD4+ memory T cells, with an associated alteration of TH1 responses. The reduced CD4+ memory T cell proportions are associated with a significantly lower ratio of schistosome-specific IgE/IgG4 (marker for resistance to infection/re-infection) in uninfected older people. Helminth infection does not affect the CD8+ memory T cell pool. Furthermore, we show for the first time in a helminth infection that the CD4+ memory T cell proportions decline following curative anti-helminthic treatment despite increased CD4+ memory cell replication. Reduced accumulation of the CD4+ memory T cells in schistosome-infected people has implications for the development of natural or vaccine induced schistosome-specific protective immunity as well as for unrelated pathogens

Stimulation of lymphocyte anti-melanoma activity by co-cultured macrophages activated by complex homeopathic medication

<p>Abstract</p> <p>Background</p> <p>Melanoma is the most aggressive form of skin cancer, and the most rapidly expanding cancer in terms of worldwide incidence. Chemotherapeutic approaches to treat melanoma have been uniformly disappointing. A Brazilian complex homeopathic medication (CHM), used as an immune modulator, has been recommended for patients with depressed immune systems. Previous studies in mice have demonstrated that the CHM activates macrophages, induces an increase in the number of leukocytes and improves the murine response against Sarcoma-180.</p> <p>Methods</p> <p>Here we studied the interaction of mouse lymph node lymphocytes, co-cultured <it>in vitro </it>with macrophages in the presence or absence of the CHM, with B16F10 melanoma cells.</p> <p>Results</p> <p>Lymphocytes co-cultured with macrophages in the presence of the CHM had greater anti-melanoma activity, reducing melanoma cell density and increasing the number of lysed tumor cells. There was also a higher proportion of activated (CD25⁺) lymphocytes with increased viability. Overall, lymphocytes activated by treatment destroyed growing cancer cells more effectively than control lymphocytes.</p> <p>Conclusion</p> <p>Co-culture of macrophages with lymphocytes in the presence of the CHM enhanced the anti-cancer performance of lymphocytes against a very aggressive lineage of melanoma cells. These results suggest that non-toxic therapies using CHMs are a promising alternative approach to the treatment of melanomas. In addition, they are attractive combination-therapy candidates, which may enhance the efficacy of conventional medicines by improving the immune response against tumor cells.</p

Identification and Phylogenetic Analysis of Tityus pachyurus and Tityus obscurus Novel Putative Na+-Channel Scorpion Toxins

Background: Colombia and Brazil are affected by severe cases of scorpionism. In Colombia the most dangerous accidents are caused by Tityus pachyurus that is widely distributed around this country. In the Brazilian Amazonian region scorpion stings are a common event caused by Tityus obscurus. The main objective of this work was to perform the molecular cloning of the putative Na+-channel scorpion toxins (NaScTxs) from T. pachyurus and T. obscurus venom glands and to analyze their phylogenetic relationship with other known NaScTxs from Tityus species. Methodology/Principal Findings: cDNA libraries from venom glands of these two species were constructed and five nucleotide sequences from T. pachyurus were identified as putative modulators of Na+-channels, and were named Tpa4, Tpa5, Tpa6, Tpa7 and Tpa8; the latter being the first anti-insect excitatory b-class NaScTx in Tityus scorpion venom to be described. Fifteen sequences from T. obscurus were identified as putative NaScTxs, among which three had been previously described, and the others were named To4 to To15. The peptides Tpa4, Tpa5, Tpa6, To6, To7, To9, To10 and To14 are closely related to the a-class NaScTxs, whereas Tpa7, Tpa8, To4, To8, To12 and To15 sequences are more related to the b-class NaScTxs. To5 is possibly an arthropod specific toxin. To11 and To13 share sequence similarities with both a and b NaScTxs. By means of phylogenetic analysis using the Maximum Parsimony method and the known NaScTxs from Tityus species, these toxins were clustered into 14 distinct groups. Conclusions/Significance: This communication describes new putative NaScTxs from T. pachyurus and T. obscurus and their phylogenetic analysis. The results indicate clear geographic separation between scorpions of Tityus genus inhabiting the Amazonian and Mountain Andes regions and those distributed over the Southern of the Amazonian rainforest. Based on the consensus sequences for the different clusters, a new nomenclature for the NaScTxs is proposed

CD4+ Regulatory and Effector/Memory T Cell Subsets Profile Motor Dysfunction in Parkinson’s Disease

Animal models and clinical studies have linked the innate and adaptive immune system to the pathology of Parkinson’s disease (PD). Despite such progress, the specific immune responses that influence disease progression have eluded investigators. Herein, we assessed relationships between T cell phenotype and function with PD progression. Peripheral blood lymphocytes from two separate cohorts, a discovery cohort and a validation cohort, totaling 113 PD patients and 96 age- and environment-matched caregivers were examined by flow cytometric analysis and T cell proliferation assays. Increased effector/memory T cells (Tem), defined as CD45RO+ and FAS+ CD4+ T cells and decreased CD31+ and α4β7+ CD4+ T cells were associated with progressive Unified Parkinson’s Disease Rating Scale III scores. However, no associations were seen between immune biomarkers and increased age or disease duration. Impaired abilities of regulatory T cells (Treg) from PD patients to suppress effector T cell function was observed. These data support the concept that chronic immune stimulation, notably Tem activation and Treg dysfunction is linked to PD pathobiology and disease severity, but not disease duration. The association of T cell phenotypes with motor symptoms provides fresh avenues for novel biomarkers and therapeutic designs

IL-10 Blocks the Development of Resistance to Re-Infection with Schistosoma mansoni

Despite effective chemotherapy to treat schistosome infections, re-infection rates are extremely high. Resistance to reinfection can develop, however it typically takes several years following numerous rounds of treatment and re-infection, and often develops in only a small cohort of individuals. Using a well-established and highly permissive mouse model, we investigated whether immunoregulatory mechanisms influence the development of resistance. Following Praziquantel (PZQ) treatment of S. mansoni infected mice we observed a significant and mixed anti-worm response, characterized by Th1, Th2 and Th17 responses. Despite the elevated anti-worm response in PBMC's, liver, spleen and mesenteric lymph nodes, this did not confer any protection from a secondary challenge infection. Because a significant increase in IL-10-producing CD4+CD44+CD25+GITR+ lymphocytes was observed, we hypothesised that IL-10 was obstructing the development of resistance. Blockade of IL-10 combined with PZQ treatment afforded a greater than 50% reduction in parasite establishment during reinfection, compared to PZQ treatment alone, indicating that IL-10 obstructs the development of acquired resistance. Markedly enhanced Th1, Th2 and Th17 responses, worm-specific IgG1, IgG2b and IgE and circulating eosinophils characterized the protection. This study demonstrates that blocking IL-10 signalling during PZQ treatment can facilitate the development of protective immunity and provide a highly effective strategy to protect against reinfection with S. mansoni

Association of the Gene Polymorphisms IFN-γ +874, IL-13 −1055 and IL-4 −590 with Patterns of Reinfection with Schistosoma mansoni

Approximately 200 million people have schistosomiasis in parts of Africa, South America, the Middle East, the Caribbean and Asia. Several studies of multiple treatments and reinfections indicate that some people develop resistance to reinfection. Of all the immunologic findings associated with such studies, the most consistent observation is that resistance (usually defined as lower levels of infection upon reinfection) correlates with high IgE and low IgG4 antibodies against schistosome antigens. Our studies test whether single nucleotide polymorphisms residing in the gene or promoter regions of cytokines pivotal in controlling production of these antibody isotypes are different amongst those that develop resistance to reinfection as opposed to those that do not. Through genotyping of these polymorphisms in a cohort of occupationally exposed car washers, we found that men with certain genotypic patterns of polymorphisms in IL-4, IFN-γ, and IL-13 were significantly more likely to be resistant to reinfection than those with different patterns. These data provide initial insights into the potential genetic foundation of propensities of people to develop resistance to reinfection by schistosomes, and offer a basis for further molecular studies of how these polymorphisms might work at the transcriptional and gene product level in cells stimulated by schistosome antigens

Strategies to Target Tumor Immunosuppression

The tumor microenvironment is currently in the spotlight of cancer immunology research as a key factor impacting tumor development and progression. While antigen-specific immune responses play a crucial role in tumor rejection, the tumor hampers these immune responses by creating an immunosuppressive microenvironment. Recently, major progress has been achieved in the field of cancer immunotherapy, and several groundbreaking clinical trials demonstrated the potency of such therapeutic interventions in patients. Yet, the responses greatly vary among individuals. This calls for the rational design of more efficacious cancer immunotherapeutic interventions that take into consideration the “immune signature” of the tumor. Multimodality treatment regimens that aim to enhance intratumoral homing and activation of antigen-specific immune effector cells, while simultaneously targeting tumor immunosuppression, are pivotal for potent antitumor immunity