Evaluation of blood cell count using an automatic hematology analyzer to optimize collection of peripheral blood progenitor cells by leukapheresis.

BACKGROUND: Autologous stem cell transplantation is a treatment modality for several diseases. Prediction of successful mobilization may be useful to optimize hematopoietic stem cell collection. STUDY DESIGN AND METHODS: This was a retrospective study with data from transplantation candidates between September 2015 and December 2021 being analyzed. The medical record of each patient was reviewed to mine mobilization information. The laboratory data analyzed were CD34+ cell enumeration and pre-collection peripheral blood cell count. The primary outcome, good mobilization, was defined as a CD34+ cell count ≥20/µL. RESULTS: This study included 807 patients. Increased patient weight, low mean corpuscular volume, high nucleated red blood cells, peripheral blood mononuclear cell and immature granulocyte counts were significantly associated with good mobilization. In addition, patients diagnosed with multiple myeloma were two times more likely to be good mobilizers than patients with lymphoma. The model was applied to a validation set to identify patients who underwent apheresis (CD34+ cell count ≥10 µL), resulting in a sensitivity of 69 %, a specificity of 95 %, positive predictive value of 98 %, and a negative predictive value of 50 %. CONCLUSION: Success in mobilization was greater in patients who underwent the first mobilization cycle and who had a diagnosis of multiple myeloma. Furthermore, higher body weight, and nucleated red blood cells, immature granulocytes and mononuclear cell counts, as well as low mean corpuscular volumes, were associated with successful mobilization.

Inflammasome-Mediated Cytokines: A Key Connection between Obesity-Associated NASH and Liver Cancer Progression.

Liver cancer is one of the most lethal malignancies and is commonly diagnosed as hepatocellular carcinoma (HCC), a tumor type that affects about 90% of patients. Non-alcoholic steatohepatitis (NASH) and obesity are both risk factors for this disease. HCC initiation and progression are deeply linked with changes in the hepatic microenvironment, with cytokines playing key roles. The understanding of the pathogenic pathways that connect these disorders to liver cancer remains poor. However, the inflammasome-mediated cytokines associated with both diseases are central actors in liver cancer progression. The release of the pro-inflammatory cytokines IL-1ß and IL-18 during inflammasome activation leads to several detrimental effects on the liver microenvironment. Considering the critical crosstalk between obesity, NASH, and HCC, this review will present the connections of IL-1ß and IL-18 from obesity-associated NASH with HCC and will discuss approaches to using these cytokines as therapeutic targets against HCC.

Influence of laboratory procedures on postthawing cell viability and hematopoietic engraftment after autologous peripheral blood stem cell transplantation.

BACKGROUND: The kinetics of hematopoietic recovery after autologous stem cell transplantation (ASCT) may be affected by laboratory procedures. The aim of this study was to evaluate the influence of characteristics of the cryopreserved units of peripheral blood stem cells (PBSC) on postthawing cell viability and engraftment outcomes after ASCT. STUDY DESIGN AND METHODS: This was a retrospective cohort study including individuals referred for ASCT. Cryopreservation was conducted at a single processing facility between 2014 and 2019, and patients received clinical care at six transplant centers. Covariates and outcome data were retrieved from participants' records. RESULTS: The study population comprised 619 patients (345 [55.7%] male). Median age was 53 years. Multiple myeloma was the most common diagnosis (62.7%). Higher preapheresis CD34+ cell count, lower nucleated cell (NC) concentration per cryobag, and composition of the cryoprotectant solution (5% dimethyl sulfoxide [DMSO] and 6% hydroxyethyl starch) were statistically significantly associated with higher postthawing cell viability. The linear regression model for time to neutrophil and platelet engraftment included the infused CD34+ cell dose and the composition of the cryoprotectant solution. Patients who had PBSC cryopreserved using 10% DMSO solution presented six times higher odds (odds ratio [OR] = 6.9; 95% confidence interval [CI]: 2.2-21.1; p = .001) of delayed neutrophil engraftment (>14 days) and two times higher odds (OR = 2.3, 95%CI: 1.4-3.7; p = .001) of prolonged hospitalization (>18 days). DISCUSSION: The study showed that mobilization efficacy, NC concentration, and the composition of the cryoprotectant solution significantly affected postthawing cell viability. In addition, the composition of the cryoprotectant solution significantly impacted engraftment outcomes and time of hospitalization after ASCT.

EGFR-Pak Signaling Selectively Regulates Glutamine Deprivation-Induced Macropinocytosis.

Macropinocytosis has emerged as an important nutrient-scavenging pathway that supports tumor cell fitness. By internalizing extracellular protein and targeting it for lysosomal degradation, this endocytic pathway functions as an amino acid supply route, permitting tumor cell growth and survival despite the nutrient-poor conditions of the tumor microenvironment. Here, we provide evidence that a subset of pancreatic ductal adenocarcinoma (PDAC) tumors are wired to integrate contextual metabolic inputs to regulate macropinocytosis, dialing up or down this uptake pathway depending on nutrient availability. We find that regional depletion of amino acids coincides with increased levels of macropinocytosis and that the scarcity of glutamine uniquely drives this process. Mechanistically, this stimulation of macropinocytosis depends on the nutrient stress-induced potentiation of epidermal growth factor receptor signaling that, through the activation of Pak, controls the extent of macropinocytosis in these cells. These results provide a mechanistic understanding of how nutritional cues can control protein scavenging in PDAC tumors.

Copying the development: mirror neurons in child development. / Copiando el desarrollo: neuronas espejo en el desarrollo infantil.

Since intrauterine life, our brain is exposed to diverse internal and external factors that generate epigenetic changes affecting the neural networks and thus modifying the properties of the mirror neurons of the developing infant. We consider that changes on the mirror neurons may play a role on the neuro-developmental pathologies of an infant where no structural brain lesion is observed.

Desde la vida intrauterina nuestro cerebro está siendo expuesto a factores internos y externos que generan cambios epigenéticos que afectan las redes neuronales y por tanto modifican las propiedades de las neuronas espejo del infante en desarrollo. Consideramos que cambios en las neuronas espejo pueden jugar un papel en las patologías del neuro-desarrollo del infante donde no es observada una lesión estructural cerebral.

Sodium trimetaphosphate enhances the effect of 250 p.p.m. fluoride toothpaste against enamel demineralization in vitro.

This in vitro study investigated the effect of sodium trimetaphosphate (TMP), added to toothpaste containing 250 p.p.m. fluoride, on enamel demineralization. Bovine enamel blocks (n = 96) were subjected to five pH cycles over a 7-d period and treatment with suspensions of toothpastes containing 0, 250, 500, and 1,100 p.p.m. fluoride (as sodium fluoride), as well as with 250 p.p.m. fluoride containing TMP at 0.25, 0.5, 1.0, and 3.0%. Treatment with toothpaste suspensions was performed under agitation twice a day, for 1 min. Surface and cross-sectional hardness, and fluoride firmly bound to enamel, were quantified. Data were subjected to one-way anova, followed by Tukey's test. Low-fluoride toothpastes containing TMP at 0.25-1.0% resulted in enamel mineral loss similar to that seen for the toothpaste containing 1,100 p.p.m. fluoride. Also, the addition of TMP to the toothpaste containing 250 p.p.m. fluoride promoted enamel fluoride concentrations similar to those obtained for the 500 p.p.m. fluoride group. The toothpaste containing 250 p.p.m. fluoride and 0.25% TMP led to the lowest mineral loss among all groups. It was concluded that the addition of as little as 0.25% TMP to a toothpaste containing 250 p.p.m. fluoride can reduce enamel demineralization to levels similar to those seen for a conventional toothpaste containing 1,100 p.p.m. fluoride, in vitro.

Talin1 has unique expression versus talin 2 in the heart and modifies the hypertrophic response to pressure overload.

Integrins are adhesive, signaling, and mechanotransduction proteins. Talin (Tln) activates integrins and links it to the actin cytoskeleton. Vertebrates contain two talin genes, tln1 and tln2. How Tln1 and Tln2 function in cardiac myocytes (CMs) is unknown. Tln1 and Tln2 expression were evaluated in the normal embryonic and adult mouse heart as well as in control and failing human adult myocardium. Tln1 function was then tested in the basal and mechanically stressed myocardium after cardiomyocyte-specific excision of the Tln1 gene. During embryogenesis, both Tln forms are highly expressed in CMs, but in the mature heart Tln2 becomes the main Tln isoform, localizing to the costameres. Tln1 expression is minimal in the adult CM. With pharmacological and mechanical stress causing hypertrophy, Tln1 is up-regulated in CMs and is specifically detected at costameres, suggesting its importance in the compensatory response to CM stress. In human failing heart, CM Tln1 also increases compared with control samples from normal functioning myocardium. To directly test Tln1 function in CMs, we generated CM-specific Tln1 knock-out mice (Tln1cKO). Tln1cKO mice showed normal basal cardiac structure and function but when subjected to pressure overload showed blunted hypertrophy, less fibrosis, and improved cardiac function versus controls. Acute responses of ERK1/2, p38, Akt, and glycogen synthase kinase 3 after mechanical stress were strongly blunted in Tln1cKO mice. Given these results, we conclude that Tln1 and Tln2 have distinct functions in the myocardium. Our data show that reduction of CM Tln1 expression can lead to improved cardiac remodeling following pressure overload.

The linkage between inflammation and Type 2 diabetes mellitus.

The Type 2 diabetes mellitus (DM2) is considered nowadays as one of the most important chronic disturbances because of the significant number of people with diabetes and its severe complications, responsible for elevated indexes of morbidity and mortality. DM2 is characterized by several degrees of insulin resistance and relative deficiency in its secretion. Genetic and environmental factors have been described as of major importance in the DM2 development as obesity, which is directly correlated with development of resistance in peripheral tissues and inflammatory state in metabolic activated adipose tissue. Inflammatory responses may have a dual role in DM2, since it may have either a causal relationship leading to resistance to insulin or may be intensified by the hyperglycemic state, resulting in DM2 complications. In this review, we discuss the association of polymorphisms in genes encoding inflammatory cytokines and the increased level of these pro-inflammatory markers, associated to chronic pathologic conditions in DM2.

Efeito de dentifrícios com concentração reduzida de fluoreto associado ao trimetafosfato de sódio sobre a erosão do esmalte dentário / Effect of low-fluoride toothpaste combined with sodium trimetaphosphate on enamel erosion

O objetivo deste estudo foi avaliar in vitro o efeito de dentifrícios com baixa concentração de fluoreto (250 ppm), combinado com trimetafosfato de sódio (TMP) sobre a erosão do esmalte. Cento e quarenta e quatro blocos de esmalte bovino foram selecionados pela dureza de superfície inicial e submetidos a desafios erosivos (2 e 5 dias). Os tratamentos foram realizados com slurry de dentifrício (5 mL / bloco por 15 s): Sem Fluoreto e TMP (controle negativo), 250 ppm de F, 250 ppm F com 0,25, 0,5 e 1,0% de TMP e controle positivo (1425 ppm F) . O desafio erosivo foi produzido por imersão em Sprite (pH 2,8) 4 vezes / dia por 5 minutos, seguido por 1 hora em saliva artificial. A dureza de superfície, dureza transversal e desgaste da superfície foram analisados como variáveis de resposta. Os dados foram submetidos à análise de variância (2-way), seguido pelo teste de Student-Newman-Keuls. O aumento do tempo do desafio erosivo resultou em maior desgaste do esmalte (p <0,001). Grupos com TMP apresentaram menor desgaste do esmalte do que os grupos com apenas flúor e o controle negativo (p <0,001). A presença de maior quantidade de fluoreto (controle positivo), levou a uma superfície mais dura do esmalte (p <0,001) em comparação com o controle negativo e o dentifrício de 250 ppm F. A adição de TMP ao dentifrício com 250 ppm de F teve um efeito direto sobre a dureza. O trimetafosfato de sódio (0,25%) pode aumentar o efeito contra a erosão do dentifrício de baixa concentração de fluoreto (250 ppm). Este efeito foi melhor do que o observado com a pasta de dente comercial.

The purpose of this study was to evaluate in vitro the effect of low-F toothpastes (250 ppm) combined with sodium trimetaphosphate (TMP) on enamel erosion, one hundred forty four bovine enamel blocks were selected by their initial surface hardness and subjected to a erosion challenges (2- and 5-days). Treatments were carried out using slurry toothpastes (5 mL/block for 15 s): non fluoride and TMP (negative control), 250 ppm F, 250 ppm F plus 0.25, 0.5 and 1.0% TMP toothpastes and positive control (1,425 ppm F). The erosive challenge was produced by immersion in soda (pH 2.8) 4 times/day, 5 minutes each time, followed by 1 hour in artificial saliva. The surface and cross-sectional hardness and surface wear were analyzed as response variables. The data were submitted to analysis of variance (2-way) followed by Student-Newman-Keuls’s test.The rise in the time of erosive challenge resulted in a larger enamel wear (p < 0.001). TMP groups showed lower enamel wear than fluoride-only and negative control (p < 0.001). The presence of higher amounts of fluoride (positive control) led to a harder enamel surface (p < 0.001) compared to the negative control and 250 ppm F toothpaste. The addition of TMP to toothpaste with 250 ppm F had a direct effect on hardness.The results suggest that the sodium trimetaphosphate (0.25%) can enhance the effect against erosion of low fluoride toothpaste (250 ppm). This effect it was in higher level than the observed with the commercial toothpaste.

Efeito de dentifrícios com concentração reduzida de fluoreto associado ao trimetafosfato de sódio sobre a erosão do esmalte dentário / Effect of low-fluoride toothpaste combined with sodium trimetaphosphate on enamel erosion

O objetivo deste estudo foi avaliar in vitro o efeito de dentifrícios com baixa concentração de fluoreto (250 ppm), combinado com trimetafosfato de sódio (TMP) sobre a erosão do esmalte. Cento e quarenta e quatro blocos de esmalte bovino foram selecionados pela dureza de superfície inicial e submetidos a desafios erosivos (2 e 5 dias). Os tratamentos foram realizados com slurry de dentifrício (5 mL / bloco por 15 s): Sem Fluoreto e TMP (controle negativo), 250 ppm de F, 250 ppm F com 0,25, 0,5 e 1,0% de TMP e controle positivo (1425 ppm F) . O desafio erosivo foi produzido por imersão em Sprite (pH 2,8) 4 vezes / dia por 5 minutos, seguido por 1 hora em saliva artificial. A dureza de superfície, dureza transversal e desgaste da superfície foram analisados como variáveis de resposta. Os dados foram submetidos à análise de variância (2-way), seguido pelo teste de Student-Newman-Keuls. O aumento do tempo do desafio erosivo resultou em maior desgaste do esmalte (p <0,001). Grupos com TMP apresentaram menor desgaste do esmalte do que os grupos com apenas flúor e o controle negativo (p <0,001). A presença de maior quantidade de fluoreto (controle positivo), levou a uma superfície mais dura do esmalte (p <0,001) em comparação com o controle negativo e o dentifrício de 250 ppm F. A adição de TMP ao dentifrício com 250 ppm de F teve um efeito direto sobre a dureza. O trimetafosfato de sódio (0,25%) pode aumentar o efeito contra a erosão do dentifrício de baixa concentração de fluoreto (250 ppm). Este efeito foi melhor do que o observado com a pasta de dente comercial

The purpose of this study was to evaluate in vitro the effect of low-F toothpastes (250 ppm) combined with sodium trimetaphosphate (TMP) on enamel erosion, one hundred forty four bovine enamel blocks were selected by their initial surface hardness and subjected to a erosion challenges (2- and 5-days). Treatments were carried out using slurry toothpastes (5 mL/block for 15 s): non fluoride and TMP (negative control), 250 ppm F, 250 ppm F plus 0.25, 0.5 and 1.0% TMP toothpastes and positive control (1,425 ppm F). The erosive challenge was produced by immersion in soda (pH 2.8) 4 times/day, 5 minutes each time, followed by 1 hour in artificial saliva. The surface and cross-sectional hardness and surface wear were analyzed as response variables. The data were submitted to analysis of variance (2-way) followed by Student-Newman-Keuls’s test.The rise in the time of erosive challenge resulted in a larger enamel wear (p < 0.001). TMP groups showed lower enamel wear than fluoride-only and negative control (p < 0.001). The presence of higher amounts of fluoride (positive control) led to a harder enamel surface (p < 0.001) compared to the negative control and 250 ppm F toothpaste. The addition of TMP to toothpaste with 250 ppm F had a direct effect on hardness.The results suggest that the sodium trimetaphosphate (0.25%) can enhance the effect against erosion of low fluoride toothpaste (250 ppm). This effect it was in higher level than the observed with the commercial toothpaste

A competência técnica em informática de alunos de enfermagem / Nursing undergraduates' technical competence in informatics / La competencia tecnica en informática de estudiantes de enfermería

Os enfermeiros na era da informação precisam desenvolver seus conhecimentos e habilidades para que se tornem competentes nessa área. O objetivo deste estudo foi verificar o conhecimento dos alunos matriculados no primeiro e no oitavo semestres do curso de graduação em enfermagem dos anos de 2008 e 2007, respectivamente, no que se refere à utilização de recursos da informática. Trata-se de uma pesquisa não experimental do tipo estudo survey descritivo exploratório usado para a coleta dos dados em um questionário baseado em um conjunto de competências em informática. Os resultados mostraram o baixo índice de conhecimentos em informática dos alunos que estão ingressando no curso de graduação. Contudo, na comparação dos aplicativos que os alunos têm maior dificuldade, entre os dois períodos avaliados, a maior porcentagem foi de alunos do oitavo semestre, demonstrando a necessidade da introdução do uso do computador na formação desses novos profissionais para sua posterior adaptação ao mercado de trabalho.

Nurses in the information age need to build their knowledge and abilities in order to be competent in this area. The objective of this study was to verify the knowledge of nursing freshmen (1st semester) and seniors (8th semester) registered in 2008 and 2007, respectively, regarding their ability to use informatics resources. This is a non-experimental, descriptive, exploratory survey. Data collection was performed using a questionnaire based on a set of competences in informatics. The results revealed a low rate of informatics knowledge among the freshmen. However, regarding the applications that students had the most difficulty to operate, between the two periods, seniors had the worst performance, which shows it is necessary to include computer classes in the preparation of these new professional, in order to prepare them for the work market.

Los enfermeros en la era informática necesitan construir conocimientos y habilidades con el objeto de ser competentes en dicha área. Este estudio objetivó verificar el conocimiento de alumnos matriculados en primer y octavo semestres del curso de graduación en enfermería de los años 2008 y 2007, respectivamente, en referencia a utilización de recursos informáticos. Investigación no experimental del tipo estudio survey, descriptivo, exploratorio, utilizándose para recolección de datos un cuestionario basado en un conjunto de competencias en informática. Los resultados demostraron el bajo índice de conocimientos informáticos de los alumnos que están ingresando al curso de graduación. Así y todo, en la comparación de las aplicaciones en que los alumnos tienen mayor dificultad, entre ambos períodos, el mayor porcentaje fue de alumnos de octavo semestre, demostrándose la necesidad de introducción de uso del computador en la formación de los nuevos profesionales para su posterior adaptación al mercado laboral.

HFE, MTHFR, and FGFR4 genes polymorphisms and breast cancer in Brazilian women.

Genetic factors related to cancer have been extensively studied and several polymorphisms have been associated to breast cancer. The FGFR4, MTHFR, and HFE genes have been associated with neoplastic diseases development. The current report outlines the analysis of the polymorphisms G388A (FGFR4), C677T (MTHFR), C282Y, and H63D (HFE) in Brazilian breast cancer patients. We studied 68 patients with invasive ductal and operable breast carcinoma and 85 women as a control group. The polymorphism frequencies in the breast cancer and control groups were analyzed, but no significant difference was observed by comparing the two groups. The presence of each polymorphism was analyzed according to the clinical features and markers already established as prognostic in the breast cancer group. The C677T, H63D, and G388A polymorphisms were not associated to histological grade, age of diagnosis, expression of HER2 receptor, or estrogen and progesterone receptor. The H63D polymorphism showed a significant association (P = 0.02) with the presence of p53 mutations, and C667T showed association to lymph node involvement (P = 0.05). Lymph node involvement, G388A polymorphism, and histological grade were independently associated to metastasis/death. Our data suggests that the polymorphisms G388A, C677T, and H63D are not useful in breast cancer diagnosis, but they may be significant additional prognostic markers related to breast cancer survival.

Nursing undergraduates' technical competence in informatics. / A competência técnica em informática de alunos de enfermagem.

Nurses in the information age need to build their knowledge and abilities in order to be competent in this area. The objective of this study was to verify the knowledge of nursing freshmen (1st semester) and seniors (8th semester) registered in 2008 and 2007, respectively, regarding their ability to use informatics resources. This is a non-experimental, descriptive, exploratory survey. Data collection was performed using a questionnaire based on a set of competences in informatics. The results revealed a low rate of informatics knowledge among the freshmen. However, regarding the applications that students had the most difficulty to operate, between the two periods, seniors had the worst performance, which shows it is necessary to include computer classes in the preparation of these new professional, in order to prepare them for the work market.