CXCL16/CXCR6 axis drives microglia/macrophages phenotype in physiological conditions and plays a crucial role in glioma

Microglia are patrolling cells that sense changes in the brain microenvironment and respond acquiring distinct phenotypes that can be either beneficial or detrimental for brain homeostasis. Anti-inflammatory microglia release soluble factors that might promote brain repair; however, in glioma, anti-inflammatory microglia dampen immune response and promote a brain microenvironment that foster tumor growth and invasion. The chemokine CXCL16 is expressed in the brain, where it is neuroprotective against brain ischemia, and it has been found to be over-expressed in glioblastoma (GBM). Considering that CXCL16 specific receptor CXCR6 is diffusely expressed in the brain including in microglia cells, we wanted to investigate the role of CXCL16 in the modulation of microglia cell activity and phenotype, and in the progression of glioma. Here we report that CXCL16 drives microglia polarization toward an anti-inflammatory phenotype, also restraining microglia polarization toward an inflammatory phenotype upon LPS and IFN? stimulation. In the context of glioma, we demonstrate that CXCL16 released by tumor cells is determinant in promoting glioma associated microglia/macrophages (GAMs) modulation toward an anti-inflammatory/pro-tumor phenotype, and that cxcr6ko mice, orthotopically implanted into the brain with GL261 glioma cells,survive longer compared to wild-type mice. We also describe that CXCL16/CXCR6 signaling acts directly on mouse glioma cells, as well as human primary GBM cells, promoting tumor cell growth, migration and invasion. All together these data suggest that CXCL16 signaling could represent a good target to modulate microglia phenotype in order to restrain inflammation or to limit glioma progression

Repeated successful use of eltrombopag in chronic primary immune thrombocytopenia: description of an intriguing case.

Thrombopoietin receptor agonists (TPO-RAs) are used as effective alternative treatments in ITP patients unresponsive to first-/second-line therapies. TPO- RAs can also be used to normalize platelet count to safely perform invasive pro- cedures and chemotherapy, in case of malignancies. In few responsive patients, TPO-RAs can be suspended maintaining a sustained respons

Os múltiplos rastos da literatura, de textos e traduções, ou uma alegoria da violência: uma Argentina em pedaços

Resumo: A arte e suas múltiplas expressões são testemunho dos sucessos e processos políticos e sociais acontecidos no mundo — e segundo o meu interesse, aqueles acontecidos em terras latino-americanas —, e perpassam toda a história do ser humano na terra. Observa-se assim que a literatura latino-americana não é indiferente à realidade histórica e social da qual emana. Percebe-se que nas últimas décadas estão se elaborando literariamente as distintas experiências da violência política vividas no continente a partir dos anos sessenta e setenta até hoje, e ao longo de toda a América Latina, desde o México até o Cone Sul. Impõe-se uma reflexão sobre o conhecimento das representações literárias das violências políticas no continente, e especificamente quanto à Argentina, sob o império das ditaduras, do horror.Palavras-chave: literatura, linguagem, violência, representação, tradução

Os múltiplos rastos da literatura, de textos e traduções, ou uma alegoria da violência: uma Argentina em pedaços

Resumo: A arte e suas múltiplas expressões são testemunho dos sucessos e processos políticos e sociais acontecidos no mundo — e segundo o meu interesse, aqueles acontecidos em terras latino-americanas —, e perpassam toda a história do ser humano na terra. Observa-se assim que a literatura latino-americana não é indiferente à realidade histórica e social da qual emana. Percebe-se que nas últimas décadas estão se elaborando literariamente as distintas experiências da violência política vividas no continente a partir dos anos sessenta e setenta até hoje, e ao longo de toda a América Latina, desde o México até o Cone Sul. Impõe-se uma reflexão sobre o conhecimento das representações literárias das violências políticas no continente, e especificamente quanto à Argentina, sob o império das ditaduras, do horror.Palavras-chave: literatura, linguagem, violência, representação, tradução

Addressing some challenges of congenital fibrinogen disorders in 2023 and beyond

Congenital fibrinogen disorders (CFD) include several types and subtypes of fibrinogen deficiency, resulting from monoallelic or biallelic mutations in one of the three fibrinogen genes. While it is relatively easy to make an accurate diagnosis based on activity and antigen levels of fibrinogen and genotype, prediction of the clinical phenotype is challenging. Even among patients with the same genotype, the clinical features are heterogeneous and unpredictable. The development of next-generation sequencing rises the possibility to integrate genetic modifiers to explain the subtle relationship between genotype and clinical phenotype. A recent development in integrative hemostasis assays can also help in the determination of patients at risk of bleeding or thrombosis. In this short review, we go through these topics and explain why CFD could be considered an oligogenic rather than a monogenic disease

Desempenho das tecnicas de fertilização in vitro convencional e injeção intracitoplasmatica, segundo a qualidade do semen

Orientador: Luis BahamondesTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: Este foi um estudo de coorte retrospectivo, que teve como objetivo comparar as técnicas de fertilização in vitro (FIV) convencional e injeção intracitoplasmática (ICSI), tendo como base algumas características do sêmen. Foram analisados 4.016 procedimentos de reprodução assistida, sendo 1.832 de fertilização in vitro convencional e 2.184 de injeção intracitoplasmática. A avaliação dos gametas e as técnicas de FIV foram realizadas no Laboratório de Reprodução Humana da Clínica Saint-Antoine na cidade de Bois Guillaume ¿ França. Para análise dos dados foram consideradas variáveis independentes o ano de realização dos procedimentos de FIV convencional e ICSI, a idade das mulheres submetidas à FIV, a concentração de espermatozóides, a porcentagem de espermatozóides progressivos rápidos, a porcentagem de espermatozóides normais, a qualidade espermática, o número de óvulos e a técnica de fertilização in vitro. A variável dependente foi a taxa de fertilização. Para avaliação estatística utilizou-se a análise de regressão logística múltipla. A única variável que teve influência na taxa de fertilização foi a técnica utilizada. As variáveis espermáticas estudadas não tiveram influência na taxa de fertilização quando se considerou a amostra de sêmen normal. Concluindo, em mulheres até 38 anos de idade, cujos companheiros tinham sêmen normal ou anormal leve e moderado, a técnica de FIV foi superior à técnica de ICSI, considerando-se a taxa de fertilizaçãoAbstract: This was a retrospective cohort study, which compared the conventional in vitro fertilization technique (IVF) and intracytoplasmic sperm injection (ICSI) according to some characteristic of the semen. A total of 4,016 procedures of assisted reproductive procedures, included 1,832 conventional IVF and 2,184 ICSI. The evaluation of gametes and the IVF¿s techniques were performed at the Laboratory of Human Reproduction of the Clínica Saint-Antoine Bois Guillaume, France. For the analysis of the data, it considered as independent variables the year when the procedures (conventional IVF and ICSI) was done, the women's age, the concentration of spermatozoa, the percentage of fast progressive spermatozoa, the percentage of normal spermatozoa, the sperm quality, number of the oocytes and the technique of IVF. The dependent variable was the fertilization rate. For statistical analysis it was use the multiple logistic regression. It was observed that the variable with high association to the fertilization rate was the technique (conventional IVF and ICSI) used. The sperm variables did not have influence in the fertilization rate when it considered sample of normal semen. In conclusion, in women up to 38 years old, whose partners had norm al semen or some anormality, the conventional IVF technique was superior than ICSI, taking into account the fertilization rateDoutoradoTocoginecologiaDoutor em Tocoginecologi

Effects of dietary level of pantothenic acid and sex on carcass, meat quality traits and fatty acid composition of thigh subcutaneous adipose tissue in Italian heavy pigs.

Two trials were carried out to evaluate the effects of i) supranutritional doses of pantothenic acid (PA) and ii) sex on carcass, meat quality and fatty acid (FA) composition of subcutaneous adipose tissue in Italian heavy pig. In trial 1, 59 Duroc x (LxLW) pigs were fed the same diet containing either 10 [in the control (C) group] or 110 ppm [in the treatment (T) group] PA, from 107 to 168 kg live weight. At slaughtering, forty carcasses were sampled randomly. The T carcasses had lower backfat thickness (P<0.05), lower incidence of adipose cuts (P<0.05), higher lean cuts percentage (63.09 vs 60.64%; P<0.01) and lean meat yield (P<0.07). In trial 2, 42 pigs [Dumeco Cofok x (LxLW)], evenly divided into three groups, were fed the same feed containing respectively 10 (C), 60 (T1) and 110 ppm (T2) PA, from 95 to 165 kg live weight. The treatment lowered total adipose cuts yield (P<0.05) and increased lean/adipose cuts ratio (P<0.07). In the outer layer of thighs subcutaneous adipose tissue, the treatment raised polyunsaturated FA content (P<0.01), unsaturation coefficient (P<0.01) and polyunsaturated/saturated (P/S) FA ratio (P<0.05). In the inner layer, the treatment led to a lower saturated FA (P<0.05) and higher polyunsaturated FA content (P<0.01). In both trials, females generally provided leaner carcasses. In neither trials, vitamin level affected meat quality. Thus, feeding high levels of PA to heavy pigs can yield more valuable carcasses without affecting meat quality. However, effects on FA composition suggest caution in adopting this practice in the Italian heavy pig production

KCa3.1 channel inhibition sensitizes malignant gliomas to temozolomide treatment

Malignant gliomas are among the most frequent and aggressive cerebral tumors, characterized by high proliferative and invasive indexes. Standard therapy for patients, after surgery and radiotherapy, consists of temozolomide (TMZ), a methylating agent that blocks tumor cell proliferation. Currently, there are no therapies aimed at reducing tumor cell invasion. Ion channels are candidate molecular targets involved in glioma cell migration and infiltration into the brain parenchyma. In this paper we demonstrate that: i) blockade of the calcium-activated potassium channel KCa3.1 with TRAM-34 has co-adjuvant effects with TMZ, reducing GL261 glioma cell migration, invasion and colony forming activity, increasing apoptosis, and forcing cells to pass the G2/M cell cycle phase, likely through cdc2 de-phosphorylation; ii) KCa3.1 silencing potentiates the inhibitory effect of TMZ on glioma cell viability; iii) the combination of TMZ/TRAM-34 attenuates the toxic effects of glioma conditioned medium on neuronal cultures, through a microglia dependent mechanism since the effect is abolished by clodronate-induced microglia killing; iv) TMZ/TRAM-34 co-treatment increases the number of apoptotic tumor cells, and the mean survival time in a syngeneic mouse glioma model (C57BL6 mice implanted with GL261 cells); v) TMZ/TRAM-34 co-treatment reduces cell viability of GBM cells and cancer stem cells (CSC) freshly isolated from patients.Taken together, these data suggest a new therapeutic approach for malignant glioma, targeting both glioma cell proliferating and migration, and demonstrate that TMZ/TRAM-34 co-treatment affects both glioma cells and infiltrating microglia, resulting in an overall reduction of tumor cell progression

Prevalence of nursing diagnosis of decreased cardiac output and the predictive value of defining characteristics in patients under evaluation for heart transplant

Este estudo teve como propósito identificar a prevalência das características definidoras do débito cardíaco diminuído (DCD), em indivíduos com insuficiência cardíaca em avaliação para transplante cardíaco, e verificar a chance de as características definidoras serem fatores preditivos para a existência de diminuição no débito cardíaco. Os dados foram obtidos por análise documental retrospectiva de registros clínicos de cateterismo cardíaco direito em 38 pacientes, entre 2004 e 2009. Os resultados mostraram que 71,1% dos pacientes tiveram redução do débito cardíaco (medida pelo índice cardíaco). A maioria das características definidoras da NANDA-International para DCD foi mais frequente em indivíduos com redução do índice cardíaco. Destacam-se como razões de chances (odds ratio/OR) a resistência vascular sistêmica aumentada OR=4,533, a terceira bulha OR=3,429 e a fração de ejeção diminuída OR=2,850. Com a obtenção do valor preditivo das características definidoras, o estudo aponta as mesmas como indicativas do diagnóstico de débito cardíaco diminuído.El estudio tiene como objetivos identificar la prevalencia de las características definitorias de la disminución del gasto cardíaco (DGC) en pacientes con insuficiencia cardíaca (IC) en evaluación para el trasplante de corazón y ver la probabilidad de las características definitorias sean factores predictivos de la existencia de una disminución del gasto cardíaco. Los datos se obtuvieron mediante el análisis documental retrospectivo de historias clínicas de cateterismo cordiaco derecho en 38 pacientes con insuficiencia cardíaca en la evaluación para el trasplante de corazón entre 2004 y 2009. Los resultados mostraron que el 71% de los pacientes habían reducido el gasto cardíaco (medido por el índice cardíaco). La mayoría de las características definitorias de la NANDA-International para el DGC fueron más frecuentes en individuos con índice cardíaco reducido. Los aspectos más destacados son la razón de probabilidad (odds ratio / OR) RVS mayor OR=4,533, el tercer sonido OR=3,429 y la disminución de la fracción de eyección OR=2,850. Al obtener el valor predictivo de las características definitorias de estudio indica la importancia de las características para el diagnóstico de la disminución del gasto cardíaco.The purposes of the study were to identify the prevalence of defining characteristics (DC) of decreased cardiac output (DCO) in patients with cardiac insufficiency under evaluation for heart transplantation, and to ascertain the likelihood of defining characteristics being predictive factors for the existence of reduction in cardiac output. Data was obtained by retrospective documental analysis of the clinical records of right-sided heart catheterizations in 38 patients between 2004 and 2009. The results showed that 71.1% of the patients had decreased cardiac output (measured by cardiac index). The majority of the NANDA-International defining characteristics for DCO were more frequent in individuals with reduced cardiac index levels. The study emphasizes the odds ratio (OR) for increased Systemic Vascular Resistance of OR=4.533, of the third heart sound with OR=3.429 and the reduced ejection fraction with OR=2.850. By obtaining the predictive values for the defining characteristics the study identifies them as diagnostic indicators of decreased cardiac output