CD19 LYMPHOCYTE PROLIFERATION INDUCED BY Bifidobacterium animalis subsp. lactis IN C57BL/6 MICE EXPERIMENTALLY INFECTED WITH Toxoplasma gondii

Toxoplasmosis is frequently acquired through the oral route by the ingestion of cysts or oocysts of Toxoplasma gondii. Once ingested, the parasites penetrate the intestinal epithelial cells and rapidly disseminate to all organs in the host. During T. gondii infection, the intestinal microbiota plays an important role in stimulating a protective immune response against the parasite. In this sense the use of probiotics is worthy of note since they are live microorganisms that have beneficial effects on the host through stimulation of the immune response that can be important in the control of T. gondii proliferation and dissemination in the host. In the present study, the action of the probiotic Bifidobacterium animalis subsp. lactis was investigated in C57BL/6 mice infected with oocysts of ME49 strain of T. gondii. The probiotic had an immunomodulatory action, inducing CD19 lymphocyte proliferation and consequently increasing anti-T. gondii antibody level.Bifidobacterium animalis subsp. lactisprovided protection in supplemented mice, compared to the control group. In addition, supplemented animals had milder inflammatory process in the small intestine, indicating that the probiotic protects the intestinal mucosa during infection with T. gondii. It was concluded that the probioticB. animalis subsp. lactis induces humoral immune response capable of providing protection against T. gondii infection

Heterozygous <em>COL17A1 </em>variants are a frequent cause of amelogenesis imperfecta

\ua9 Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.Background: Collagen XVII is most typically associated with human disease when biallelic COL17A1 variants (&gt;230) cause junctional epidermolysis bullosa (JEB), a rare, genetically heterogeneous, mucocutaneous blistering disease with amelogenesis imperfecta (AI), a developmental enamel defect. Despite recognition that heterozygous carriers in JEB families can have AI, and that heterozygous COL17A1 variants also cause dominant corneal epithelial recurrent erosion dystrophy (ERED), the importance of heterozygous COL17A1 variants causing dominant non-syndromic AI is not widely recognised. Methods: Probands from an AI cohort were screened by single molecule molecular inversion probes or targeted hybridisation capture (both a custom panel and whole exome sequencing) for COL17A1 variants. Patient phenotypes were assessed by clinical examination and analyses of affected teeth. Results: Nineteen unrelated probands with isolated AI (no co-segregating features) had 17 heterozygous, potentially pathogenic COL17A1 variants, including missense, premature termination codons, frameshift and splice site variants in both the endo-domains and the ecto-domains of the protein. The AI phenotype was consistent with enamel of near normal thickness and variable focal hypoplasia with surface irregularities including pitting. Conclusion: These results indicate that COL17A1 variants are a frequent cause of dominantly inherited non-syndromic AI. Comparison of variants implicated in AI and JEB identifies similarities in type and distribution, with five identified in both conditions, one of which may also cause ERED. Increased availability of genetic testing means that more individuals will receive reports of heterozygous COL17A1 variants. We propose that patients with isolated AI or ERED, due to COL17A1 variants, should be considered as potential carriers for JEB and counselled accordingly, reflecting the importance of multidisciplinary care

Dynasore, a Dynamin Inhibitor, Inhibits Trypanosoma cruzi Entry into Peritoneal Macrophages

BACKGROUND: Trypanosoma cruzi is an intracellular parasite that, like some other intracellular pathogens, targets specific proteins of the host cell vesicular transport machinery, leading to a modulation of host cell processes that results in the generation of unique phagosomes. In mammalian cells, several molecules have been identified that selectively regulate the formation of endocytic transport vesicles and the fusion of such vesicles with appropriate acceptor membranes. Among these, the GTPase dynamin plays an important role in clathrin-mediated endocytosis, and it was recently found that dynamin can participate in a phagocytic process. METHODOLOGY/PRINCIPAL FINDINGS: We used a compound called dynasore that has the ability to block the GTPase activity of dynamin. Dynasore acts as a potent inhibitor of endocytic pathways by blocking coated vesicle formation within seconds of its addition. Here, we investigated whether dynamin is involved in the entry process of T. cruzi in phagocytic and non-phagocytic cells by using dynasore. In this aim, peritoneal macrophages and LLC-MK2 cells were treated with increasing concentrations of dynasore before interaction with trypomastigotes, amastigotes or epimastigotes. We observed that, in both cell lines, the parasite internalization was drastically diminished (by greater than 90% in LLC-MK2 cells and 70% in peritoneal macrophages) when we used 100 microM dynasore. The T. cruzi adhesion index, however, was unaffected in either cell line. Analyzing these interactions by scanning electron microscopy and comparing peritoneal macrophages to LLC-MK2 cells revealed differences in the stage at which cell entry was blocked. In LLC-MK2 cells, this blockade is observed earlier than it is in peritoneal macrophages. In LLC-MK2 cells, the parasites were only associated with cellular microvilli, whereas in peritoneal macrophages, trypomastigotes were not completely engulfed by a host cell plasma membrane. CONCLUSIONS/SIGNIFICANCE: Taken together our results demonstrate that dynamin is an essential molecule necessary for cell invasion and specifically parasitophorous vacuole formation by host cells during interaction with Trypanosoma cruzi

Acurácia do relacionamento probabilístico na avaliação da alta complexidade em cardiologia

OBJETIVO: Evaluar la viabilidad de estrategia de relación probabilística en la identificación de pacientes sometidos a procedimientos de alta complejidad en cardiología. MÉTODOS: El costo de procesamiento fue calculado con base en 1.672 registros de pacientes sometidos a cirugía de revascularización del miocardio, relacionados con todos los registros de óbito en Brasil en 2005. La precisión de la relación se basó en linkage probabilística de 99 registros de autorización de internación hospitalaria de pacientes sometidos a cirugías cardíacas en instituto de referencia en cardiología, con status vital conocido, con todos los registros de óbito del estado de Rio de Janeiro en 2005. El linkage fue realizado en cuatro etapas: estandarización de las bases, blocaje, pareamiento y clasificación de los pares. Se utilizó blocaje en cinco pasos, con claves de blocaje con combinación de variables como soundex del primero y último nombre, sexo y año de nacimiento. Las variables utilizadas en el pareamiento fueron "nombre completo", con la utilización de la distancia de Levenshtein y "fecha de nacimiento". RESULTADOS: El segundo y el quinto pasos de blocaje tuvieron los mayores números de pares formados y los mayores tiempos de procesamiento para el pareamiento. El cuarto paso demandó menor costo de procesamiento. En el estudio de precisión, posterior a cinco pasos de blocaje, la sensibilidad del linkage fue de 90,6% y la especificidad fue de 100%. CONCLUSIONES: La estrategia de relación probabilística utilizada presenta buena precisión y podrá ser utilizada en estudios sobre la efectividad de los procedimientos de alta complejidad y alto costo en cardiología.OBJECTIVE: To evaluate the viability of a probabilistic record linkage strategy to identify patients who underwent complex cardiology procedures among the total deceased population. METHODS: The processing cost was estimated based on 1,672 records of patients undergoing coronary artery bypass grafting that were compared with all death records in Brazil in 2005. The accuracy of the linkage strategy was based on the probabilistic linkage of 99 hospital admissions records of patients, with known vital status, who underwent cardiac surgery at a single cardiology institute, with the death records of the state of Rio de Janeiro, Southeastern Brazil, in 2005. Linkage was conducted in four stages: standardizing the databases, blocking, matching, and rating peers. Blocking in five steps was used, with blocking keys formed by a combination of variables such as soundex codes for the first and last names, sex, and year of birth. The variables used for matching were "full name" with the use of Levenshtein distance and "birth date". RESULTS: The second and fifth blocking steps resulted in the largest number of formed pairs and the largest processing times for the matching. The fourth step required a lower processing cost. In the accuracy study, after five blocking steps, the sensitivity of the linkage was 90.6%, and the specificity was 100%. CONCLUSIONS: The probabilistic strategy used has high accuracy and can be used in studies of the effectiveness of high-complexity, high-cost cardiology procedures.OBJETIVO: Avaliar a viabilidade de estratégia de relacionamento probabilístico de bases de dados na identificação de óbitos de pacientes submetidos a procedimentos de alta complexidade em cardiologia. MÉTODOS: O custo de processamento foi estimado com base em 1.672 registros de pacientes submetidos à cirurgia de revascularização do miocárdio, relacionados com todos os registros de óbito no Brasil em 2005. A acurácia do relacionamento baseou-se em linkage probabilístico entre 99 registros de autorização de internação hospitalar de pacientes submetidos a cirurgias cardíacas em instituto de referência em cardiologia, com status vital conhecido, e todos os registros de óbito do estado do Rio de Janeiro em 2005. O linkage foi realizado em quatro etapas: padronização das bases, blocagem, pareamento e classificação dos pares. Utilizou-se a blocagem em cinco passos, com chaves de blocagem com combinação de variáveis como soundex do primeiro e último nome, sexo e ano de nascimento. As variáveis utilizadas no pareamento foram "nome completo", com a utilização da distância de Levenshtein, e "data de nascimento". RESULTADOS: O segundo e o quinto passos de blocagem tiveram os maiores números de pares formados e os maiores tempos de processamento para o pareamento. O quarto passo demandou menor custo de processamento. No estudo de acurácia, após os cinco passos de blocagem, a sensibilidade do linkage foi de 90,6% e a especificidade foi de 100%. CONCLUSÕES: A estratégia de relacionamento probabilístico utilizada apresenta boa acurácia e poderá ser utilizada em estudos sobre a efetividade dos procedimentos de alta complexidade e alto custo em cardiologia

Brazilian network for the surveillance of maternal potentially life threatening morbidity and maternal near-miss and a multidimensional evaluation of their long term consequences

<p>Abstract</p> <p>Background</p> <p>It has been suggested that the study of women who survive life-threatening complications related to pregnancy (maternal near-miss cases) may represent a practical alternative to surveillance of maternal morbidity/mortality since the number of cases is higher and the woman herself is able to provide information on the difficulties she faced and the long-term repercussions of the event. These repercussions, which may include sexual dysfunction, postpartum depression and posttraumatic stress disorder, may persist for prolonged periods of time, affecting women's quality of life and resulting in adverse effects to them and their babies.</p> <p>Objective</p> <p>The aims of the present study are to create a nationwide network of scientific cooperation to carry out surveillance and estimate the frequency of maternal near-miss cases, to perform a multicenter investigation into the quality of care for women with severe complications of pregnancy, and to carry out a multidimensional evaluation of these women up to six months.</p> <p>Methods/Design</p> <p>This project has two components: a multicenter, cross-sectional study to be implemented in 27 referral obstetric units in different geographical regions of Brazil, and a concurrent cohort study of multidimensional analysis. Over 12 months, investigators will perform prospective surveillance to identify all maternal complications. The population of the cross-sectional component will consist of all women surviving potentially life-threatening conditions (severe maternal complications) or life-threatening conditions (the maternal near miss criteria) and maternal deaths according to the new WHO definition and criteria. Data analysis will be performed in case subgroups according to the moment of occurrence and determining cause. Frequencies of near-miss and other severe maternal morbidity and the association between organ dysfunction and maternal death will be estimated. A proportion of cases identified in the cross-sectional study will comprise the cohort of women for the multidimensional analysis. Various aspects of the lives of women surviving severe maternal complications will be evaluated 3 and 6 months after the event and compared to a group of women who suffered no severe complications in pregnancy. Previously validated questionnaires will be used in the interviews to assess reproductive function, posttraumatic stress, functional capacity, quality of life, sexual function, postpartum depression and infant development.</p