hbg2 and hbg1 nucleotide substitutions and hbf production in thalassemia patients

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Intradermal DNA Electroporation Induces Cellular and Humoral Immune Response and Confers Protection against HER2/neu Tumor

Skin represents an attractive target for DNA vaccine delivery because of its natural richness in APCs, whose targeting may potentiate the effect of vaccination. Nevertheless, intramuscular electroporation is the most common delivery method for ECTM vaccination. In this study we assessed whether intradermal administration could deliver the vaccine into different cell types and we analyzed the evolution of tissue infiltrate elicited by the vaccination protocol. Intradermal electroporation (EP) vaccination resulted in transfection of different skin layers, as well as mononuclear cells. Additionally, we observed a marked recruitment of reactive infiltrates mainly 6–24 hours after treatment and inflammatory cells included CD11c+. Moreover, we tested the efficacy of intradermal vaccination against Her2/neu antigen in cellular and humoral response induction and consequent protection from a Her2/neu tumor challenge in Her2/neu nontolerant and tolerant mice. A significant delay in transplantable tumor onset was observed in both BALB/c ( ≤ 0,0003) and BALB-neuT mice ( = 0,003). Moreover, BALB-neuT mice displayed slow tumor growth as compared to control group ( < 0,0016). In addition, while in vivo cytotoxic response was observed only in BALB/c mice, a significant antibody response was achieved in both mouse models. Our results identify intradermal EP vaccination as a promising method for delivering Her2/neu DNA vaccine

Peptide-nucleic acid-mediated enriched polymerase chain reaction as a key point for non-invasive prenatal diagnosis of β-thalassemia

The presence of fetal DNA in maternal plasma can be exploited to develop new procedures for non-invasive prenatal diagnosis. Tests to detect 7 frequent beta-globin gene mutations in people of Mediterranean origin were applied to the analysis of maternal plasma in couples where parents carried different mutations. A mutant enrichment amplification protocol was optimized by using peptide nucleic acids (PNAs) to clamp maternal wild-type alleles. By this approach, 41 prenatal diagnoses were performed by microelectronic microchip analysis, with total concordance of results obtained on fetal DNA extracted from chorionic villi. Among these, 27/28 were also confirmed by direct sequencing and 4 by pyrosequencing

Identification of Relevant Conformational Epitopes on the HER2 Oncoprotein by Using Large Fragment Phage Display (LFPD)

We developed a new phage-display based approach, the Large Fragment Phage Display (LFPD), that can be used for mapping conformational epitopes on target molecules of immunological interest. LFPD uses a simplified and more effective phage-display approach in which only a limited set of larger fragments (about 100 aa in length) are expressed on the phage surface. Using the human HER2 oncoprotein as a target, we identified novel B-cell conformational epitopes. The same homologous epitopes were also detected in rat HER2 and all corresponded to the epitopes predicted by computational analysis (PEPITO software), showing that LFPD gives reproducible and accurate results. Interestingly, these newly identified HER2 epitopes seem to be crucial for an effective immune response against HER2-overexpressing breast cancers and might help discriminating between metastatic breast cancer and early breast cancer patients. Overall, the results obtained in this study demonstrated the utility of LFPD and its potential application to the detection of conformational epitopes on many other molecules of interest, as well as, the development of new and potentially more effective B-cell conformational epitopes based vaccines

El desprendimiento del tiempo como sedimentación de la conciencia de la vejez

En este texto nos inclinamos sobre una mirada del envejecimiento desde una concepción filosófica de la conciencia del tiempo ya que es uno de los elementos más relevantes que no solo ha emergido en el Proyecto de investigación SABE Colombia (Encuesta Salud, bienestar y Envejecimiento), sino de la estructura misma de la vida; es más la vejez en sí misma, como fenómeno temporal, es la acumulación de tiempo en un mismo cuerpo; además, la noción de tiempo está implícita en el estudio del envejecimiento. Este artículo tiene como objetivo revelar el sentido de la conciencia temporal de la vejez o la vejez a la luz de la conciencia temporal, en tanto el tiempo se va desprendiendo de la existencia humana poco a poco hasta agotar su contenido en el cuerpo como revelación del tiempo, como huella,  como rastro en donde se revela la vida misma. Para lograr este objetivo se proponen tres puntos nodales de reflexión, primero, entre la latencia y la presencia de la vejez; segundo, entre vejez y clandestinidad del futuro, y por último, el rostro de la vejez: el desprendimiento de cuerpo a través de la conciencia temporal del presente

The detachment of time as sedimentation of the consciousness of old age

En este texto nos inclinamos sobre una mirada del envejecimiento desde una concepción filosófica de la conciencia del tiempo ya que es uno de los elementos más relevantes que no solo ha emergido en el Proyecto de investigación SABE Colombia (Encuesta Salud, bienestar y Envejecimiento), sino de la estructura misma de la vida; es más la vejez en sí misma, como fenómeno temporal, es la acumulación de tiempo en un mismo cuerpo; además, la noción de tiempo está implícita en el estudio del envejecimiento. Este artículo tiene como objetivo revelar el sentido de la conciencia temporal de la vejez o la vejez a la luz de la conciencia temporal, en tanto el tiempo se va desprendiendo de la existencia humana poco a poco hasta agotar su contenido en el cuerpo como revelación del tiempo, como huella,&nbsp; como rastro en donde se revela la vida misma. Para lograr este objetivo se proponen tres puntos nodales de reflexión, primero, entre la latencia y la presencia de la vejez; segundo, entre vejez y clandestinidad del futuro, y por último, el rostro de la vejez: el desprendimiento de cuerpo a través de la conciencia temporal del presente.In this text we approach the process of aging from the philosophical view-point of the awareness of time. We consider this awareness of paramount importance not only in the course of the research project SABE Colombia (Survey of Health, Well-being and Aging, according to its initials in Spanish), but also because of the very structure of life. Moreover, old age in itself, as a time-related phenomenon, consists of the accumulation of time in a single body: therefore, the notion of time must be implicit in the study of aging. This article aims at revealing the sense of the time consciousness of old age or (in other words) at viewing old age in the light of time consciousness, insofar as time lets human existence come off gradually until its exhaustion reveals life as a time trace, as a time mark in the body. To achieve this goal, we propose three nodal points of reflection: first, between the latency and the presence of old age; second, between old age and the secrecy of future, and finally, the face of old age: the detachment of the body through the time consciousness of the present

Diagnóstico de tricomoníase em felino: características ultrassonográficas: Diagnosis of trichomoniasis in feline: sonographic findings

A tricomoníase é causa importante de enteropatia em gatos domésticos. Apesar de afetar felinos de todas as idades, sua ocorrência é mais comum nos animais jovens. O presente estudo tem como objetivo relatar um caso de colite associada a hematoquezia persistente em uma gata, através dos achados ultrassonográficos. As alterações visibilizadas incluíram diminuição no lúmen do cólon descendente, espessamento transmural acentuado, lesões hipoanecogênicas de aspecto oval e perda da estratificação parietal. Embora os exames específicos não possam ser substituídos, esses achados podem ser correlacionados a colite causada por tricomoníase felina, auxiliando no direcionamento do diagnóstico

Variações pedológicas influenciam a composição florístico-estrutural de florestas aluviais?

This study aimed to investigate if the floristic-structural composition of an alluvial forest is influenced by pedological variations and if there is low floristic diversity and similarity in these environments. Furthermore, it aimed to assess whether, independently of the type of soil, these forests have monodominance. The study was carried out in the Iguaçu River, in the municipality of Araucária, Paraná state, where two soil classes were mapped and demarcated: Gleysol and Fluvisol. To analyze the phytosociological structure, we installed 10 plots of 10 m x 10 m in each compartment and monitor the average depth of the water table. We sampled thirty-nine species, distributed in 21 botanical families. Of these, only six ones were similar to both compartments. The fluctuation of the water table differed between the compartments, being closer to the surface in the Gleysol. Gymnanthes klotzschiana showed the highest values of density, dominance, and importance in both compartments. The second most important species in Gleysol was Myrciaria tenella and in the Fluvisol Araucaria angustifolia stands out, due to the greater depth of the water table and the non-hydromorphic character of the soil. The riparian environments presented floristic-structural distinctions, highlighting the need for compartmentalization based on pedological parameters, thus obtaining a more detailed understanding of the plant community.Este estudo buscou investigar se a composição florístico-estrutural de uma floresta aluvial é influenciada pelas variações pedológicas e se há baixa diversidade e similaridade florística nesses ambientes. Ainda, objetivou avaliar se, independentemente do tipo de solo, essas florestas apresentam monodominância. O estudo foi realizado às margens do rio Iguaçu, no município de Araucária, Paraná, onde foram mapeadas e demarcadas a área de ocorrência de duas classes de solo: Gleissolo Háplico Ta Distrófico típico e Neossolo Flúvico Psamítico típico. Para a análise da estrutura fitossociológica, foram instaladas em cada compartimento 10 parcelas de 10 m x 10 m e monitorada a profundidade média do lençol freático. Foram amostradas 39 espécies, distribuídas em 21 famílias botânicas. Destas, somente seis espécies foram similares nos compartimentos analisados. A flutuação do lençol freático diferiu entre os compartimentos, sendo mais próximo da superfície no Gleissolo. Gymnanthes klotzschiana apresentou os maiores valores de densidade, dominância e importância em ambos os compartimentos. A segunda espécie de maior importância na área de Gleissolo foi Myrciaria tenella, e na área de Neossolo destaca-se Araucaria angustifolia, devido à maior profundidade do lençol freático e ao caráter não hidromórfico do solo. Os ambientes ripários apresentaram distinções florístico-estruturais, evidenciando a necessidade de compartimentação baseada em parâmetros pedológicos, obtendo-se assim um melhor entendimento da comunidade vegetal

Reduction of hospitalizations for myocardial infarction in Italy in the COVID-19 era

Aims: To evaluate the impact of the COVID-19 pandemic on patient admissions to Italian cardiac care units (CCUs). Methods and results: We conducted a multicentre, observational, nationwide survey to collect data on admissions for acute myocardial infarction (AMI) at Italian CCUs throughout a 1 week period during the COVID-19 outbreak, compared with the equivalent week in 2019. We observed a 48.4% reduction in admissions for AMI compared with the equivalent week in 2019 (P < 0.001). The reduction was significant for both ST-segment elevation myocardial infarction [STEMI; 26.5%, 95% confidence interval (CI) 21.7-32.3; P = 0.009] and non-STEMI (NSTEMI; 65.1%, 95% CI 60.3-70.3; P < 0.001). Among STEMIs, the reduction was higher for women (41.2%; P = 0.011) than men (17.8%; P = 0.191). A similar reduction in AMI admissions was registered in North Italy (52.1%), Central Italy (59.3%), and South Italy (52.1%). The STEMI case fatality rate during the pandemic was substantially increased compared with 2019 [risk ratio (RR) = 3.3, 95% CI 1.7-6.6; P < 0.001]. A parallel increase in complications was also registered (RR = 1.8, 95% CI 1.1-2.8; P = 0.009). Conclusion: Admissions for AMI were significantly reduced during the COVID-19 pandemic across Italy, with a parallel increase in fatality and complication rates. This constitutes a serious social issue, demanding attention by the scientific and healthcare communities and public regulatory agencies

The blood count as a compass to navigate in the ever-changing landscape of the carrier state of hemoglobinopathies: a single-center Italian experience

IntroductionApproximately 7% of the worldwide population exhibits variations in the globin genes. The recent migration of populations from countries where hemoglobin disorders are endemic has resulted in important epidemiological changes with the diffusion of newly discovered or poorly characterized genetic variants and new combinations and very heterogeneous clinical phenotypes. The aim of our study is to assess the parameters that are more significant in predicting a positive genetic testing outcome for hemoglobinopathies in a pediatric population of patients presenting with anemia or microcythemia, without a definite diagnosis.Methods and materialsThis study included patients evaluated in our hematological outpatient clinic for anemia and/or microcythemia despite normal ferritin levels. A screening of pathological hemoglobins using high-performance liquid chromatography (HPLC) was performed for the entire population of the study. Subsequently, patients with hemoglobin (Hb) S trait and patients with an HPLC profile compatible with beta thalassemia trait were excluded from the study. Genetic screening tests for hemoglobinopathies were performed on the remaining patients, which involved measuring the red blood cell (RBC) counts, red blood cells distribution width (RDW), reticulocyte count, and mean corpuscular volume of reticulocytes (MCVr).ResultsThis study evaluated a total of 65 patients, consisting of nine patients with negative genetic analysis results and 56 patients with positive genetic analysis results. The Hb and RDW values in these two groups did not demonstrate statistical significance. On the other hand, there were statistically significant differences observed in the mean corpuscular volume (MCV), RBC count, reticulocyte count, and MCVr between the two groups. Furthermore, in the group of patients with positive genetic test results, specific genetic findings associated with different HPLC results were observed. In particular, 13 patients with positive genetic test results had normal HPLC findings.DiscussionThis study has demonstrated that HPLC, while serving as a valuable first-level test, has some limitations. Specifically, it has been observed that some patients may exhibit a negative HPLC result despite a positive genetic analysis. In addition to the presence of low levels of Hb and HPLC alterations, other parameters could potentially indicate the underlying mutations in the globin genes. Therefore, we propose that the complete blood cell count be utilized as a widely available parameter for conducting targeted genetic analyses to avoid the risk of overlooking rare hemoglobinopathies