Analysis of immunoglobulin/T-cell receptor repertoires by high-throughput RNA sequencing reveals a continuous dynamic of positive clonal selection in follicular lymphoma.

Follicular lymphoma (FL) course is highly variable, making its clinical management challenging. In this incurable and recurring pathology, the interval between relapses tends to decrease while aggressiveness increases, sometimes resulting in the transformation to higher-grade lymphoma. These evolutions are particularly difficult to anticipate, resulting from complex clonal evolutions where multiple subclones compete and thrive due to their capacity to proliferate and resist therapies. Here, to apprehend further these processes, we used a high-throughput RNA sequencing approach to address simultaneously the B-cell immunoglobulin repertoires and T-cell immunoglobulin repertoires repertoires of lymphoma cells and their lymphoid microenvironment in a large cohort of 131 FL1/2-3A patients. Our data confirm the existence of a high degree of intra-clonal heterogeneity in this pathology, resulting from ongoing somatic hyper-mutation and class switch recombination. Through the evaluation of the Simpson ecological-diversity index, we show that the contribution of the cancerous cells increases during the course of the disease to the detriment of the reactive compartment, a phenomenon accompanied by a concomitant decrease in the diversity of the tumoral population. Clonal evolution in FL thus contrasts with many tumors, where clonal heterogeneity steadily increases over time and participates in treatment evasion. In this pathology, the selection of lymphoma subclones with proliferative advantages progressively outweighs clonal diversification, ultimately leading in extreme cases to transformation to high-grade lymphoma resulting from the rapid emergence of homogeneous subpopulations.

Compound heterozygous mutations in the kinase domain of IKKα lead to immunodeficiency and immune dysregulation.

IKKα, encoded by CHUK , is crucial in the non-canonical NF-κB pathway and part of the IKK complex activating the canonical pathway alongside IKKß. Absence of IKKα cause fetal encasement syndrome in human, fatal in utero, while an impaired IKKα-NIK interaction was reported in a single patient and cause combined immunodeficiency. Here, we describe compound heterozygous variants in the kinase domain of IKKα in a female patient with hypogammaglobulinemia, recurrent lung infections, and Hay-Wells syndrome-like features. We showed that both variants were loss-of-function. Non-canonical NF-κB activation was profoundly diminished in stromal and immune cells while the canonical pathway was partially impaired. Reintroducing wild-type CHUK restored non-canonical NF-κB activation. The patient had neutralizing autoantibodies against type I IFN, akin to non-canonical NF-κB pathway deficiencies. Thus, this is the first case of bi-allelic CHUK mutations disrupting IKKα kinase function, broadening non-canonical NF-κB defect understanding and suggesting IKKα's role in canonical NF-κB target gene expression in human.

Mechanical properties and characteristics of developmental copolymers incorporating catechin or chlorhexidine.

OBJECTIVES: This study evaluated catechin and chlorhexidine release from copolymers based on bis-GMA diluted with TEGDMA (R1), propoxylated bis-GMA-CH(3)bis-GMA (R2) or fluorinated bis-GMA-CF(3)bis-GMA (R3). Mechanical properties, degree of conversion, water sorption and solubility were also tested. METHODS: Experimental comonomers (R1, R2, R3) were prepared combining bis-GMA with the diluents (70/30 mol%). Each comonomer had either catechin or chlorhexidine incorporated in the following ratios: 0, 0.2, 1.0, 2.0 wt%. The degree of conversion (%DC) of resins was evaluated by FT-IR spectrophotometry (n=3). Flexural strength and elastic modulus were tested on a universal testing machine at a crosshead speed of 0.5mm/min (n=6). Resin disks (7 mm in diameter × 2 mm high) were immersed in deionized water and mass changes recorded daily. Spectral measurements were made to follow any changes in optical densities of deionized water in order to examine catechin and chlorhexidine release rates (n=6). After a 28-day period, water sorption and solubility were calculated using appropriate equations (n=6). Data within the tests were evaluated by one- and three-way ANOVA and Tukey-Kramer's test (α=0.05). RESULTS: Except for R1 with 2.0% drug none of the groups had changes in degree of conversion and water sorption. Solubility increased with increased drug ratios. Changes in flexural strength and elastic modulus were shown to be variable and material-dependent. All resins presented a ∼24 h burst of drug release. Release rates were drug-ratio dependent and significantly higher for chlorhexidine than for catechin. SIGNIFICANCE: Monomer type, %DC, drug ratio and type lead to different interactions between resins and chlorhexidine/catechin drug particles. It should be possible to develop different resins based on clinical needs.

Amyand's hernia.

We present vermiform appendix finding within an inguinal hernia sac, rare pathology, well-known as Amyand's hernia. We relate the incidence in the literature and the recommended conducts.

Hérnia de Amyand / Amyand's hernia

We present vermiform appendix finding within an inguinal hernia sac, rare pathology, well-known as Amyand's hernia. We relate the incidence in the literature and the recommended conducts.

Abordagem sobre saúde bucal pelo material bibliográfico da área médica / Contents on oral health in the medical literature

A interação Médico pediatra-Odontopediatra se faz muito importante no sentido de promover a saúde, assim também, como fornecer aos mesmos informações e condições necessárias a um trabalho multiprofissional bem sucedido. Desta forma, o objetivo desse trabalho foi avaliar a literatura médica com relação aos conteúdos concernentes à saúde bucal, vinculando-a com a necessidade de uma efetiva interação Médico-pediatra-Odontopediatra. Foram pesquisados todos os livros (29) e 14 periódicos (730 fascículos), nacionais e internacionais, de Pediatria Médica da Biblioteca da Faculdade de Medicina da UFMG. Além de 9 livos do acervo de Pedriatria da Biblioteca da Faculdade de Medicina da Faculdade de Ciências Médicas de Minas Gerais. Para a análise dos livros, foram considerados os últimos 20 anos de publicação, enquanto que para a análise dos periódicos, os últimos 7 anos. Analisou-se: o período e o local das publicações, o espaço dedicado ao tema, a formação acadêmica dos autores e os conteúdos odontológicos abordados pelo material bibliográfico. Dos livros que continham citações sobre Odontologia grande parte foi publicada de 1985 a 1989 (31,9%); 39,5% do total de livros (o que corresponde a 68,2% do material com citações odontológicas) continha, no máximo, 1% do seu conteúdo dedicado à Odontologia. Quanto à formação dos autores dos capítulos dedicados à saúde bucal, 92,5% são Médicos e 7,5% Dentistas. A erupção dentária (31,3%) e características da boca (25%) foram os conteúdos com maior índice de abordagem. Cinquenta e oito por cento do material que continha citações representou parte do capítulo e 41,7% representou capítulo específico. Com relação aos periódicos, 0,11% (88 páginas em um total de 80.608) continham citações odontológicas; os temas mais abordados foram cárie e patologais bucais.