Hematological Neoplasms with Eosinophilia.

Eosinophils in peripheral blood account for 0.3-5% of leukocytes, which is equivalent to 0.05-0.5 × 109/L. A count above 0.5 × 109/L is considered to indicate eosinophilia, while a count equal to or above 1.5 × 109/L is defined as hypereosinophilia. In bone marrow aspirate, eosinophilia is considered when eosinophils make up more than 6% of the total nuclear cells. In daily clinical practice, the most common causes of reactive eosinophilia are non-hematologic, whether they are non-neoplastic (allergic diseases, drugs, infections, or immunological diseases) or neoplastic (solid tumors). Eosinophilia that is associated with a hematological malignancy may be reactive or secondary to the production of eosinophilopoietic cytokines, and this is mainly seen in lymphoid neoplasms (Hodgkin lymphoma, mature T-cell neoplasms, lymphocytic variant of hypereosinophilic syndrome, and B-acute lymphoblastic leukemia/lymphoma). Eosinophilia that is associated with a hematological malignancy may also be neoplastic or primary, derived from the malignant clone, usually in myeloid neoplasms or with its origin in stem cells (myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions, acute myeloid leukemia with core binding factor translocations, mastocytosis, myeloproliferative neoplasms, myelodysplastic/myeloproliferative neoplasms, and myelodysplastic neoplasms). There are no concrete data in standardized cytological and cytometric procedures that could predict whether eosinophilia is reactive or clonal. The verification is usually indirect, based on the categorization of the accompanying hematologic malignancy. This review focuses on the broad differential diagnosis of hematological malignancies with eosinophilia.

Importancia del conocimiento anatómico del espacio extraperitoneal y su utilidad en los abordajes quirúrgicos / Importance of anatomical knowledge of the extraperitoneal space and its usefulness in surgical approaches

Introducción. El espacio extraperitoneal, se define como el segmento topográfico ubicado entre el peritoneo parietal internamente y la fascia transversalis externamente. Como resultado del desarrollo y consolidación de la cirugía laparoscópica, en particular de la herniorrafia inguinal por esta vía, se ha presentado un renovado y creciente interés en esta área anatómica, debido a la importancia de su conocimiento detallado en la cirugía de mínima invasión. Métodos. Se hizo una revisión narrativa de la literatura para presentar una información actualizada y detallada sobre la anatomía del espacio extraperitoneal y su importancia en diferentes procedimientos quirúrgicos realizados actualmente. Resultados. Por fuera del espacio peritoneal, se encuentran las áreas anatómicas externas al peritoneo parietal, que incluyen la preperitoneal y la retroperitoneal. Mediante la laparoscopia, se pueden localizar en estos espacios cinco triángulos anatómicos, además de la corona mortis y el triángulo supra vesical. Conclusión. El conocimiento del espacio extraperitoneal es de gran importancia para el cirujano general, teniendo en cuenta los múltiples procedimientos que requieren el abordaje de esta área topográfica

Introduction. The extraperitoneal space is defined as the topographic segment located between the parietal peritoneum internally and the fascia transversalis externally. As a result of the development and consolidation of laparoscopic surgery, particularly inguinal herniorrhaphy by this route, there has been a renewed and growing interest in this anatomical area, due to the importance of its detailed knowledge in minimally invasive surgery. Methods. A narrative review of the literature was made to present updated and detailed information on the anatomy of the extraperitoneal space and its importance in different surgical procedures currently performed. Results. Outside the peritoneal space are the anatomical areas external to the parietal peritoneum, including the preperitoneal and extraperitoneal. Using laparoscopy, five anatomical triangles, in addition to the corona mortis and the supravesical triangle, can be located in these spaces. Conclusion. Knowledge of the extraperitoneal space is of great importance for the general surgeon, taking into account the multiple procedures that require the approach of this topographic area

Severe gastrointestinal injury associated with SARS-CoV-2 infection: Thrombosis or Inflammation?: A retrospective case series study.

OBJECTIVES: Acute gastrointestinal injury (AGI) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a low incidence of complications in patients admitted to the intensive care unit (ICU). Pathophysiological knowledge related to AGI is limited, as few studies have been published on this topic. Therefore, this study was carried out to identify the clinical and histopathological features of patients with SARS-CoV-2 infection and grade IV AGI. METHODS: This is a retrospective case study of fifteen patients with SARS-CoV-2 infection and grade IV AGI who underwent emergency surgery. RESULTS: This study revealed a mortality rate of 62.5%. The most frequent gastrointestinal symptoms were abdominal distension (100%) and increased gastric residual volume (93.3%). Distended bowel loops on plain abdominal radiography (90%) and intestinal pneumatosis on computed tomography (50%) were the most frequent imaging findings. Surgical exploration revealed intestinal ischemia (66.6%) and necrosis (46.6%), and histopathology showed ischemic and liquefactive necrosis with mixed inflammatory involvement and absence of thrombosis as the cause of AGI. CONCLUSIONS: AGI associated with severe SARS-CoV-2 infection has a high mortality rate and poses a diagnostic challenge in the ICU. The complex pathophysiology and histopathological findings indicate an associated inflammatory phenomenon as the main alteration in the absence of thrombosis, as per the intestinal biopsies of the cases studied. Further clinical studies are required to gain a better understanding of this pathology.

ASXL1 mutation as a surrogate marker in acute myeloid leukemia with myelodysplasia-related changes and normal karyotype.

Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) are poor outcome leukemias. Its diagnosis is based on clinical, cytogenetic, and cytomorphologic criteria, last criterion being sometimes difficult to assess. A high frequency of ASXL1 mutations have been described in this leukemia. We sequenced ASXL1 gene mutations in 61 patients with AML-MRC and 46 controls with acute myeloid leukemia without other specifications (AML-NOS) to identify clinical, cytomorphologic, and cytogenetic characteristics associated with ASXL1 mutational status. Mutated ASXL1 (ASXL1+) was observed in 31% of patients with AML-MRC compared to 4.3% in AML-NOS. Its presence in AML-MRC was associated with older age, a previous history of myelodysplastic syndrome (MDS) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN), leukocytosis, presence of micromegakaryocytes in bone marrow, lower number of blasts in bone marrow, myelomonocytic/monocytic morphological features and normal karyotype. ASXL1 mutation was not observed in patients with myelodysplastic syndrome-related cytogenetic abnormalities or TP53 mutations. Differences in terms of overall survival were found only in AML-MRC patients without prior MDS or MDS/MPN and with intermediate-risk karyotype, having ASXL1+ patients a worst outcome than ASXL1-. We conclude that the ASXL1 mutation frequency is high in AML-MRC patients being its presence associated with specific characteristics including morphological signs of dysplasia. This association raises the possible role of ASXL1 as a surrogate marker in AML-MRC, which could facilitate the diagnosis of patients within this group when the karyotype is normal, and especially when the assessment of multilineage dysplasia morphologically is difficult. This mutation could be used as a worst outcome marker in de novo AML-MRC with intermediate-risk karyotype.

Is Genetic Counseling a Form of Eugenics? / Asesoramiento genético: ¿una práctica que estimula la eugenesia? / Assessoria genética: uma prática que estimula a eugenia?

Abstract Introduction: Genetic counseling can be practiced under four scenarios: preconception, preimplantation, prenatal, and postnatal (which is similar to preconception). Some authors argue that it should be considered a form of eugenics. The aim of this article is to present different views expressed in the literature regarding the relation between genetic counseling and eugenics. Materials and methods: A search of articles was conducted in several academic databases using the MeSH/DeCS terms bioethics, medical genetics, genetic counseling, and eugenics. Articles were included if they discussed eugenics or genetic screening. Articles were excluded if they provided a technical description of procedures. The selection was made after examining titles, abstracts, and full texts. Results: Fifty-seven articles were selected for analysis. In preconception counseling, the "reproductive beneficence principle" can be based on eugenic practices of the early twentieth century. In pre-implantation consultation, the genetic selection of embryos can be considered eugenic when it is used to change the natural course of reproduction or used for non-medical purposes. Prenatal diagnosis, when linked to abortion as a response to congenital malformations, can be considered negative eugenics. Conclusion: At present, eugenics can be defined in multiple ways. By some definitions, genetic counseling can be framed as a eugenic practice. However, the design of health policies and the interests of society may influence the autonomy of individuals. The possibility of generating a genetic selection of individuals, on the other hand, can be constituted as positive eugenics.

Resumen Introducción: el asesoramiento genético es una práctica que puede enmarcarse en cuatro escenarios: preconcepcional, preimplantación, prenatal y posnatal (similar al preconcepcional). Para algunos autores este tipo de práctica se considera eugenesia. El objetivo del presente artículo es exponer los distintos puntos de vista, descritos en la literatura, sobre la relación del asesoramiento genético con la eugenesia. Materiales y métodos: se buscaron artículos en bases de datos académicas con los términos MeSH/DeCS bioética, genética médica, asesoramiento genético y eugenesia. Se incluyeron artículos que hablaran sobre eugenesia o sobre cribaje genético; se excluyeron artículos con la descripción técnica de procedimientos. La selección se realizó por título, resumen y texto completo. Resultados: se seleccionaron 57 artículos para el análisis. En el asesoramiento preconcepcional, el "principio de beneficencia procreativa" se considera que parte de posturas similares a las prácticas eugenésicas de principios del siglo XX. En la consulta preimplantación, la selección genética de embriones puede considerarse eugenesia cuando se usa para alterar el curso natural de la procreación o para fines no médicos. El diagnóstico prenatal, cuando se vincula con el aborto por malformaciones congénitas, puede considerarse eugenesia negativa. Conclusión: en la actualidad, la eugenesia abarca múltiples definiciones. Según la definición escogida, el asesoramiento genético puede enmarcarse como una práctica eugenésica. Sin embargo, el diseño de políticas de salud y el interés de la sociedad puede influir en la autonomía de los individuos. Por otro lado, la posibilidad de generar una selección genética de individuos puede constituirse como eugenesia positiva.

Resumo Introdução: a assessoria genética é uma prática que pode enquadrar-se em quatro cenários: pré-concepcional, pré-implantação, pré-natal e pós-natal (similar o pré-concepcional). Para alguns autores este tipo de prática considera-se eugenia. O objetivo do presente artigo é expor os distintos pontos de vista, descritos na literatura, sobre a relação da assessoria genética com a eugenia. Materiais e métodos: buscaram-se artigos em bases de dados acadêmicas com os termos eSH/DeCS bioética, genética médica, assessoria genética e eugenia. Incluíram-se artigos que falaram sobre eugenia ou sobre rastreio genético; excluíram-se artigos com a descrição técnica de procedimentos. A seleção se realizou por título, resumo e texto completo. Resultados: selecionaram-se 57 artigos para a análise. Na assessoria pré-concepcional, o "princípio d beneficência procriativa" se considera que parte de posturas similares às práticas eugénicas de começos do século XX. Na consulta pré-implantação, a seleção genética de embriões pode considerar-se eugenia quando se usa para alterar o curso natural da procriação ou para fins não médicos. O diagnóstico pré-natal, quando se vincula com o aborto por malformações congénitas, pode considerar-se eugenia negativa. Conclussão: na atualidade, a eugenia abarca múltiplas definições. Segundo a definição escolhida, a assessoria genética pode enquadrar-se como uma prática eugénica. No entanto, o desenho de políticas de saúde e o interesse da sociedade pode influir na autonomia dos indivíduos pode constituir-se como eugenia positiva.

MLL-rearranged acute myeloid leukemia: Influence of the genetic partner in allo-HSCT response and prognostic factor of MLL 3' region mRNA expression.

OBJECTIVE: MLL gene is involved in more than 80 known genetic fusions in acute leukemia. To study the relevance of MLL partner gene and selected gene's expression, in this work, we have studied a cohort of 20 MLL-rearranged acute myeloid leukemia (AML). METHODS: Twenty MLL-rearranged AML patients along with a control cohort of 138 AML patients are included in this work. By RT-PCR and sequencing, MLL genetic fusion was characterized, and relative gene expression quantification was carried out for EVI1, MEIS1, MLL-3', RUNX1, SETBP1, HOXA5, and FLT3 genes. Risk stratification and association of MLL genetic partner and gene expression to overall survival, in the context of received therapy, were performed. RESULTS: MLLr cohort showed to have an OS more similar to intermediate-risk AML. Type of MLL genetic partner showed to be relevant in allo-HSCT response; having MLLT1 and MLLT3, a better benefit from it. Expression of MLL-3' region, EVI1 and FLT3, showed association with OS in patients undergoing allo-HSCT. CONCLUSION: We show that the MLL genetic partner could have implications in allo-HSCT response, and we propose three genes whose expression could be useful for the prognosis of this leukemia in patients undergoing allo-HSCT: 3' region of MLL, EVI1, and FLT3.

Atomically Precise Au25(SG)18 Nanoclusters: Rapid Single-Step Synthesis and Application in Photothermal Therapy.

Remarkable recent advances on Au25(SR)18 nanoclusters have led to significant applications in catalysis, sensing, and magnetism. However, the existing synthetic routes are complicated, particularly for the water-soluble Au25(SG)18 nanoclusters. Here, we report a single-step concentration and temperature-controlled method for rapid synthesis of the Au25(SG)18 nanoclusters in as little as 2 h without the need for low-temperature reaction or even stirring. A systematic time-based investigation was carried out to study the effects of volume, concentration, and temperature on the synthesis of these nanoclusters. Further, we discovered for the first time that the Au25(SG)18 nanoclusters exhibit excellent photothermal activities in achieving 100% cell death for MDA-MB-231 breast cancer cells at a power of 10 W/cm2 using an 808 nm laser source, demonstrating applications toward photothermal therapy.

The human mitochondrial Hsp60 in the APO conformation forms a stable tetradecameric complex.

The human mitochondrial chaperonin is a macromolecular machine that catalyzes the proper folding of mitochondrial proteins and is of vital importance to all cells. This chaperonin is composed of 2 distinct proteins, Hsp60 and Hsp10, that assemble into large oligomeric complexes that mediate the folding of non-native polypeptides in an ATP dependent manner. Here, we report the bacterial expression and purification of fully assembled human Hsp60 and Hsp10 recombinant proteins and that Hsp60 forms a stable tetradecameric double-ring conformation in the absence of co-chaperonin and nucleotide. Evidence of the stable double-ring conformation is illustrated by the 15 Å resolution electron microscopy reconstruction presented here. Furthermore, our biochemical analyses reveal that the presence of a non-native substrate initiates ATP-hydrolysis within the Hsp60/10 chaperonin to commence protein folding. Collectively, these data provide insight into the architecture of the intermediates used by the human mitochondrial chaperonin along its protein folding pathway and lay a foundation for subsequent high resolution structural investigations into the conformational changes of the mitochondrial chaperonin.

Translocation of the papillomavirus L2/vDNA complex across the limiting membrane requires the onset of mitosis.

The human papillomavirus type 16 (HPV16) L2 protein acts as a chaperone to ensure that the viral genome (vDNA) traffics from endosomes to the trans-Golgi network (TGN) and eventually the nucleus, where HPV replication occurs. En route to the nucleus, the L2/vDNA complex must translocate across limiting intracellular membranes. The details of this critical process remain poorly characterized. We have developed a system based on subcellular compartmentalization of the enzyme BirA and its cognate substrate to detect membrane translocation of L2-BirA from incoming virions. We find that L2 translocation requires transport to the TGN and is strictly dependent on entry into mitosis, coinciding with mitotic entry in synchronized cells. Cell cycle arrest causes retention of L2/vDNA at the TGN; only release and progression past G2/M enables translocation across the limiting membrane and subsequent infection. Microscopy of EdU-labeled vDNA reveals a rapid and dramatic shift in vDNA localization during early mitosis. At late G2/early prophase vDNA egresses from the TGN to a pericentriolar location, accumulating there through prometaphase where it begins to associate with condensed chromosomes. By metaphase and throughout anaphase the vDNA is seen bound to the mitotic chromosomes, ensuring distribution into both daughter nuclei. Mutations in a newly defined chromatin binding region of L2 potently blocked translocation, suggesting that translocation is dependent on chromatin binding during prometaphase. This represents the first time a virus has been shown to functionally couple the penetration of limiting membranes to cellular mitosis, explaining in part the tropism of HPV for mitotic basal keratinocytes.

Disecando la crisis de la anatomía / Dissecting the Crisis of Anatomy / Dissecando a crise da anatomia

Introducción: la anatomía fue una de las primeras ciencias biomédicas en establecerse. Gozando de un gran crecimiento desde sus inicios como ciencia a principios del siglo XVI hasta su cúspide a principios del siglo XX. Posterior a lo cual, la anatomía comienza a perder influencia académica, tanto desde la perspectiva de la educación médica como en el impacto y número de sus investigaciones, a lo que en este documento se le denomina "Disecando la crisis de la anatomía". Desarrollo: este artículo de reflexión, intenta mostrar los diferentes elementos que configuran dicha crisis, como son la disminución del número de horas dentro del plan de estudios de medicina, la pérdida de influencia académica dentro del gremio médico, la disminución en el número de artículos, en la influencia de estos y en el bajo factor de impacto de las publicaciones dedicadas exclusivamente a la anatomía, así como la cada vez mayor resistencia a las técnicas clásicas de enseñanza de estas, específicamente la disección de cadáveres. Lo anterior evidencia cuáles son los elementos que han emergido y cómo están cambiando los paradigmas establecidos, lo que le está permitiendo reconfigurar su papel en el marco de las ciencias básicas médicas y en la formación de los nuevos profesionales de la salud. Conclusiones: aunque la forma de estudiar, investigar y enseñar la anatomía se encuentre en crisis, han surgido elementos que le han permitido redescubrir sus raíces humanistas, lo que le ha generado nuevos enfoques en los aspectos pedagógicos, éticos y de profesionalismo médico dentro de la misma anatomía.

Introduction: Anatomy was one of the first established biomedical sciences and enjoyed a tremendous growth since its inception as a science in the early sixteenth century until its peak in the early twentieth century. Then, anatomy begins to lose academic influence, both from the perspective of medical education, and the number and impact of research studies connected with it, hence the title "Dissecting the Crisis of Anatomy". Development: The reflection in this article tries to show the different elements that make up the crisis, such as the reduction of the number of hours of anatomy lectures within the curriculum of medicine, the loss of academic influence of anatomy within the medical profession, the decrease in the number of articles on this subject reflected in their diminished influence and the low impact factor of publications devoted exclusively to anatomy, as well as the growing resistance to conventional techniques for teaching it, specifically the subject of dissecting corpses. It is intended to evidence which elements have emerged and how the established paradigms are changing, thus allowing to reshape the role of anatomywithin the basic medical sciences and teaching new health professionals. Conclusions: Although the the way anatomy is being studied, researched and taught is in a crisis, elements have emerged that have led to rediscover the humanist roots of this science, producing new approaches in the pedagogical and ethical aspects and issues of medical professionalism within anatomy itself.

Introdução: A anatomia foi uma das primeiras ciências biomédicas em estabelecer-se. Gozando de um grande crescimento desde os seus inícios como ciência a começos do século XVI até a sua cúspide a começos do século XX. Posterior ao qual, a anatomia começa a perder influência acadêmica tanto desde a perspectiva da educação médica, quanto no impacto e número de suas investigações, ao que neste documento se denomina "Dissecando a crise da anatomia". Desenvolvimento: Este artigo de reflexão tenta mostrar os diferentes elementos que configuram dita crise, como são a diminuição do número de horas dentro do plano de estudos de medicina, a perda de influência acadêmica dentro do grêmio médico, a diminuição no número de artigos, na influência destes e no baixo fator de impacto das publicações dedicadas exclusivamente à anatomia, assim como a cada vez maior resistência às técnicas clássicas de ensino destas, especificamente a disseção de cadáveres. Evidenciando quais são os elementos que têm emergido e como estão mudando os paradigmas estabelecidos, o que lhe está permitindo reconfigurar seu papel no marco das ciências básicas médicas e na formação dos novos profissionais da saúde. Conclusões: Ainda que a forma de estudar, pesquisar e ensinar a anatomia encontra-se em crise, têm surgido elementos que lhe têm permitido redescobrir as suas raízes humanistas, o que lhe tem gerado novos enfoques nos aspetos pedagógicos, éticos e de profissionalismo médico dentro da mesma anatomia.