Microscopic and metabolomics analysis of the anti-Listeria activity of natural and engineered cruzioseptins.

Listeria monocytogenes is a human opportunistic foodborne pathogen that produces life-threatening infections with a high mortality rate. The control of Listeria in the food production environment and effective clinical management of human listeriosis are challenging due to the emergence of antibiotic resistance. Hence we evaluate the in vitro anti-Listeria activity of two synthetic cruzioseptins reproducing their natural sequences CZS-9, and CZS-12, and one engineered sequence based on CZS-1, named [K4K15]CZS-1. The assessment of the in vitro potential of cruzioseptins, highlighted the promising antibacterial effect of [K4K15]CZS-1 in very low concentrations (0.91 µM) and its thermal stability at high-temperature conditions, is compatible with the food industry. Microscopic and metabolomic analyses suggest cruzioseptin induces anti-Listeria bioactivity through membrane disruption and changes in the intracellular metabolome. We also report that [K4K15]CZS-1 is not resistant to peptidases/proteases emphasizing a key advantage for their use as a food preservative. However, there is a need for further structural and functional optimisations for the potential clinical application as an antibiotic. In conclusion, [K4K15]CZS-1 stand out as membrane-active peptides with the ability to induce shifts in the bacteria metabolome and inspire the development of strategies for the prevention of L. monocytogenes emergence and dissemination.

Probing the Antiplasmodial Properties of Plakortinic Acids C and D: An Uncommon Pair of Marine Peroxide-Polyketides Isolated from a Two-Sponge Association of Plakortis symbiotica and Xetospongia deweerdtae Collected near Puerto Rico.

Plakortinic acids C (1) and D (2), an unseparable pair of endoperoxide polyketides isolated and purified from the symbiotic association of Caribbean Sea sponges Plakortis symbiotica-Xestospongia deweerdtae, underwent in vitro evaluation for antiplasmodial activity against the malaria parasite Plasmodium berghei using a drug luminescence assay. Initial screening at 10 µM revealed 50% in vitro parasite growth inhibition. The title compounds displayed antiplasmodial activity with an EC50 of 5.3 µM toward P. berghei parasites. The lytic activity against erythrocytes was assessed through an erythrocyte cell lysis assay, which showed non-lytic activity at lower concentrations ranging from 1.95 to 3.91 µM. The antiplasmodial activity and the absence of hemolytic activity support the potential of plakortinic acids C (1) and D (2) as promising lead compounds. Moreover, drug-likeness (ADMET) properties assessed through the pkCSM server predicted high intestinal absorption, hepatic metabolism, and volume of distribution, indicating favorable pharmacokinetic profiles for oral administration. These findings suggest the potential suitability of these metabolites for further investigations of antiplasmodial activity in multiple parasitic stages in the mosquito and Plasmodium falciparum. Notably, this study represents the first report of a marine natural product exhibiting the unique 7,8-dioxatricyclo[4.2.2.02,5]dec-9-ene motif being evaluated against malaria.

Isolation of total DNA from Placenta Samples, both Fresh and following Formalin and Paraffin Treatment.

The isolation of DNA from placental tissue suspected of infection is an important tool for identifying microorganisms such as bacteria, fungi, and viruses associated with complications during and after pregnancy. While experts primarily process placental tissue, the preservation methods employed pose challenges to extracting complete DNA. Therefore, selecting the appropriate protocol is paramount to achieving greater efficiency in obtaining genetic material.

Humeral chondrosarcoma associated with lung metastases in a young dog - case report / [Condrossarcoma em úmero associado a metástases pulmonares em cão jovem - relato de caso]

ABSTRACT Chondrosarcoma, an unusual malignant neoplasm, develops in cartilaginous tissue and presents low rate of metastasis, mainly affecting the axial skeleton from the adult to senile dogs. In the face of unusual occurrence of chondrosarcoma in the long bones of young dogs, the present report aimed to describe it in the right humerus of a two-and-a-half-year-old Siberian Husky, attended at the Veterinary Hospital of the University of Franca, with limping of the right thoracic limb, for 20 days. The radiographic examination of the humerus showed bone lysis and periosteal proliferation. In the incisional biopsy, proliferation of atypical chondrocytes with diffuse distribution, interspersed with compact bone matrix, was observed. The amputation of the limb was performed, and the fragment histopathological analysis showed grade I chondrosarcoma. Periodic returns were made for neoplastic staging, and at 240 days after surgery lung metastases were detected, however, the tutor did not authorize chemotherapy and radiotherapy for financial reasons and due to the absence of respiratory symptoms so far (410 days after surgery). Although uncommon, chondrosarcoma can affect the long bones of young dogs, with clinical signs similar to other bone neoplasms, and, even with the radical limb amputation, can demonstrate systemic metastasis.

RESUMO O condrossarcoma, neoplasia maligna incomum, desenvolve-se em tecido cartilaginoso e apresenta baixo índice de metástases, acometendo principalmente o esqueleto axial de cães adultos a senis. Diante da ocorrência incomum de condrossarcoma em ossos longos de cães jovens, o presente relato teve como objetivo descrevê-lo no úmero direito de um Husky Siberiano de dois anos e meio de idade, atendido no Hospital Veterinário da Universidade de Franca, com claudicação do membro torácico direito, há 20 dias. O exame radiográfico do úmero mostrou lise óssea e proliferação periosteal. Na biópsia incisional, observou-se proliferação de condrócitos atípicos com distribuição difusa, intercalados com matriz óssea compacta. Foi realizada a amputação do membro, e a análise histopatológica do fragmento evidenciou condrossarcoma grau I. Foram feitos retornos periódicos para estadiamento neoplásico e, aos 240 dias após a cirurgia, foram detectadas metástases pulmonares. O tutor não autorizou quimioterapia e radioterapia por motivos financeiros e por ausência de sintomas respiratórios até o momento (410 dias após a cirurgia). Apesar de incomum, o condrossarcoma pode acometer os ossos longos de cães jovens, com sinais clínicos semelhantes a outras neoplasias ósseas, e, mesmo com a amputação radical do membro, pode demonstrar metástase sistêmica.

Who is in the emergency room matters when we talk about door-to-needle time: a single-center experience / Quien está en el servicio de emergencia importa al hablar de tiempo puerta-aguja: experiencia de un centro clínico

Abstract Background The efficacy of intravenous thrombolysis (IVT) is time-dependent. Objective To compare the door-to-needle (DTN) time of stroke neurologists (SNs) versus non-stroke neurologists (NSNs) and emergency room physicians (EPs). Additionally, we aimed to determine elements associated with DTN ≤ 20 minutes. Methods Prospective study of patients with IVT treated at Clínica Alemana between June 2016 and September 2021. Results A total of 301 patients underwent treatment for IVT. The mean DTN time was 43.3 ± 23.6 minutes. One hundred seventy-three (57.4%) patients were evaluated by SNs, 122 (40.5%) by NSNs, and 6 (2.1%) by EPs. The mean DTN times were 40.8 ± 23, 46 ± 24.7, and 58 ± 22.5 minutes, respectively. Door-to-needle time ≤ 20 minutes occurred more frequently when patients were treated by SNs compared to NSNs and EPs: 15%, 4%, and 0%, respectively (odds ratio [OR]: 4.3, 95% confidence interval [95%CI]: 1.66-11.5, p = 0.004). In univariate analysis DTN time ≤ 20 minutes was associated with treatment by a SN (p = 0.002), coronavirus disease 2019 pandemic period (p = 0.21), time to emergency room (ER) (p = 0.21), presence of diabetes (p = 0.142), hypercholesterolemia (p = 0.007), atrial fibrillation (p < 0.09), score on the National Institutes of Health Stroke Scale (NIHSS) (p = 0.001), lower systolic (p = 0.143) and diastolic (p = 0.21) blood pressures, the Alberta Stroke Program Early CT Score (ASPECTS; p = 0.09), vessel occlusion (p = 0.05), use of tenecteplase (p = 0.18), thrombectomy (p = 0.13), and years of experience of the physician (p < 0.001). After multivariate analysis, being treated by a SN (OR: 3.95; 95%CI: 1.44-10.8; p = 0.007), NIHSS (OR: 1.07; 95%CI: 1.02-1.12; p < 0.002) and lower systolic blood pressure (OR: 0.98; 95%CI: 0.96-0.99; p < 0.003) remained significant. Conclusions Treatment by a SN resulted in a higher probability of treating the patient in a DTN time within 20 minutes.

Resumen Antecedentes La respuesta a la trombólisis intravenosa (TIV) es dependiente del tiempo. Objetivo Comparar los tiempo puerta-aguja (TPAs) de neurólogos vasculares (NVs) contra los de neurólogos no vasculares (NNVs) y médicos emergencistas (MEs), y determinar los elementos asociados a un PTA ≤ 20 minutos. Métodos Análisis observacional prospectivo de pacientes con TIV tratados en Clínica Alemana entre junio de 2016 y septiembre de 2021. Resultados En total, 301 pacientes con TIV fueron tratados. El TPA promedio fue de 43,3 ± 23,6 minutos. Un total de 173 (57,4%) pacientes fueron evaluados por NVs, 122 (40,5%), por NNVs, y 6 (2,1%), por MEs; los TPAs promedios fueron de 40,8 ± 23; 46 ± 24,7 y 58 ± 22,5 minutos, respectivamente. Los TPAs ≤ 20 minutos fueron más frecuentes en pacientes tratados por NVs versus NNVs y MEs: 15%, 4% y 0%, respectivamente (odds ratio [OR]: 4,3; intervalo de confianza del 95% [IC95%]: 1,66-11,5; p = 0,004). El análisis univariado demostró que TPA ≤ 20 minutos se asoció con: tratamiento por NVs (p = 0,002), periodo de la pandemia de enfermedad por coronavirus 2019 (COVID-19; p = 0,21), tiempo a urgencia (p = 0,21), diabetes (p = 0,142), hipercolesterolemia (p = 0,007), fibrilación auricular (p < 0,09), puntaje en la National Institutes of Health Stroke Scale [NIHSS] (p = 0,001), presión arterial sistólica (p = 0,143) y diastólica menores (p = 0,21), Alberta Stroke Program Early CT Score (ASPECTS ; p = 0,09), oclusión de vasos cerebrales (p =0,05), uso de tecneteplase (p = 0,18), trombectomía (p = 0,13) y años de experiencia del médico (p < 0,001). El análisis multivariado demostró que ser tratado por NVs (OR: 3,95; IC95%: 1,44-10,8; p = 0,007), el puntaje en la NIHSS (OR: 1,07; IC95%: 1,02-1,12; p < 0,002) y la presión arterial sistólica (OR: 0,98; IC95%: 0,96-0,99; p < 0,003) se asociaron a TPA ≤ 20 minutos. Conclusões El tratamiento por NVs resultó en un TPA menor y en una mayor probabilidad de tratamiento ≤ 20 minutos.

Tumor lysis syndrome in hematological inpatients, experience from a university hospital in Brazil: A retrospective cohort study.

INTRODUCTION: The tumor lysis syndrome is a medical emergency. Its presentation can be spontaneous or secondary, as a consequence of the established treatment. The diagnosis and treatment of the tumor lysis syndrome (TLS) has become a crucial goal to the evolution and improvement of treatments and targeted therapies. METHODS: Between January 2014 and December 2019, we retrospectively reviewed inpatients aged over 18 years with hematological neoplasms from a tertiary hospital in Brazil. We identified 112 episodes of TLS in 97 patients. The incidence was 10.5% and the median OS was 13.0 months (95%CI 6.2 - 19.7). The median age was 56 years (IQR 39.5 - 64). The most frequent diagnoses were multiple myeloma (18.6%), acute myeloid leukemia (17.5%) and diffuse large B-cell lymphoma (17.5%). All patients received intravenous (IV) hydration. The management also included the administration of allopurinol in 76% of the cases and rasburicase in eight patients. Renal replacement therapy was necessary in 37% of the cases. In the multivariate analysis, age, HIV status and ICU treatment were significantly associated with OS. CONCLUSION: The TLS is a serious complication in the setting of hematological malignancies. The use of scores for risk stratification, as well as the inclusion of prophylactic measures and prompt treatment with frequent laboratory monitoring, is essential to reduce morbidity and mortality in the comprehensive treatment of these patients.

Assessment of fungal spores and spore-like diversity in environmental samples by targeted lysis.

At particular stages during their life cycles, fungi use multiple strategies to form specialized structures to survive unfavorable environmental conditions. These strategies encompass sporulation, as well as cell-wall melanization, multicellular tissue formation or even dimorphism. The resulting structures are not only used to disperse to other environments, but also to survive long periods of time awaiting favorable growth conditions. As a result, these specialized fungal structures are part of the microbial seed bank, which is known to influence the microbial community composition and contribute to the maintenance of diversity. Despite the importance of the microbial seed bank in the environment, methods to study the diversity of fungal structures with improved resistance only target spores dispersing in the air, omitting the high diversity of these structures in terms of morphology and environmental distribution. In this study, we applied a separation method based on cell lysis to enrich lysis-resistant fungal structures (for instance, spores, sclerotia, melanized yeast) to obtain a proxy of the composition of the fungal seed bank. This approach was first evaluated in-vitro in selected species. The results obtained showed that DNA from fungal spores and from yeast was only obtained after the application of the enrichment method, while mycelium was always lysed. After validation, we compared the diversity of the total and lysis-resistant fractions in the polyextreme environment of the Salar de Huasco, a high-altitude athalassohaline wetland in the Chilean Altiplano. Environmental samples were collected from the salt flat and from microbial mats in small surrounding ponds. Both the lake sediments and microbial mats were dominated by Ascomycota and Basidiomycota, however, the diversity and composition of each environment differed at lower taxonomic ranks. Members of the phylum Chytridiomycota were enriched in the lysis-resistant fraction, while members of the phylum Rozellomycota were never detected in this fraction. Moreover, we show that the community composition of the lysis-resistant fraction reflects the diversity of life cycles and survival strategies developed by fungi in the environment. To the best of our knowledge this is the first time that the fungal diversity is explored in the Salar de Huasco. In addition, the method presented here provides a simple and culture independent approach to assess the diversity of fungal lysis-resistant cells in the environment.

Características del síndrome de lisis tumoral en pacientes pediátricos oncológicos. Un estudio observacional de centro único / Characteristics of tumor lysis syndrome in pediatric oncology patients. A single-center observational study

Introducción:El síndrome de lisis tumoral (SLT) es una emergencia oncológica, que produce alteraciones en el metabolismo, causando manifestaciones clínicas y trastornos bioquímicos que ponen en peligro la vida del paciente.El objetivo del presente estudio fue identificar las características clínicas, de laboratorio y tratamiento del SLT, en pacientes pediátricos onco-lógicos, del Instituto del Cáncer SOLCA-Cuenca, en el periodo 2010 ­2020.Materiales y métodos:En este estudio se identificó las características del SLT, en pacientes pediátricos oncológicos, del Instituto del Cáncer SOLCA-Cuenca, en el periodo 2010 ­2020, a través de un estudio de tipo descriptivo-observacional.Resultados:Seincluyó 463 historias clínicas, en el cual se obtuvo que el SLT tuvo una frecuen-cia del 5.61 %, con predominio del sexo masculino (57.7%) y con una edad media de 7 ± 1.29 años. La presentación clínica más observada fue la deshidratación con náusea, vómito y dia-rrea (57.7%). Las alteraciones de laboratorio más frecuentes fueron la hiperuricemia y la hi-pocalcemia, con un 76.9 %y un 73.1 %respectivamente. La Leucemia linfoblástica aguda (LLA) fue el diagnósticooncológico con más casos (61.5 %). Los pilares del tratamiento fue-ron la hiperhidratación y el uso de alopurinol, utilizados en el 100% y un 80.8 %respectiva-mente.Conclusión:El SLT afectó más frecuentemente a varones, con diagnóstico de leucemia, ma-nifestaciones clínicas digestivas y alteraciones de laboratorio (hiperuricemia e hipocalcemia). El tratamiento empleado resultó eficaz y se basó en lo recomendado por la literatura médica

Introduction:Tumor lysis syndrome (TLS) is an oncological emergency that results in meta-bolic alterations, causing clinical manifestations and biochemical disorders that endanger pa-tients' lives. The objective of the present study was to identify the clinical, laboratory, and treat-ment characteristics of TLSsin pediatric oncology patients at the SOLCA-Cuenca Cancer Ins-titute from 2010­2020.Materials and methods: In this study, the characteristics of TLS were identified in pediatric oncology patients at the SOLCA-Cuenca Cancer Institute from 2010 to 2020 through a des-criptive observational study.Results: A total of463 medical records were included. TLSs were associated witha frequency of 5.61%, with a predominance of males(57.7%) and a mean age of 7 ± 1.29 years. The most commonclinical presentation was dehydration with nausea, vomiting, and diarrhea (57.7%). The most frequent laboratory alterations were hyperuricemia and hypocalcemia, with 76.9% and 73.1%,respectively. The oncological diagnosis was acutelymphoblastic leukemia (ALL) in most patients(61.5%). The pillars of treatment were hyperhydration and allopurinol, used in 100% and 80.8%, respectively.Conclusion: TLSsmore frequently affectmen with a diagnosis of leukemia, digestive clinical manifestations, orlaboratory alterations (hyperuricemia and hypocalcemia). The treatment used was effective and based on what the medical literature recommended

Eficácia da rasburicase para prevenção e tratamento da síndrome de lise tumoral: uma revisão sistemática de literatura / Efficacy of rasburicase for prevention and treatment of tumor lysis syndrome: a systematic literature review / Eficacia de la rasburicasa en la prevención y tratamiento del síndrome de lisis tumoral: una revisión sistemática de la literatura

A síndrome de lise tumoral (SLT) é uma emergência onco-hematológica, associada à alta mortalidade e morbidade, que pode ocorrer espontaneamente ou em resposta à quimioterapia ou bioterapia anticâncer. A rasburicase é uma droga urato oxidase recombinante, a qual reduz o ácido úrico sanguíneo liberado, prevenindo e tratando a lesão renal aguda, que representa a principal complicação da SLT. O objetivo deste artigo foi avaliar a eficácia da rasburicase na prevenção e no tratamento da SLT, contribuindo para melhor compreensão do manejo dessa frequente síndrome em pacientes oncológicos. Foi realizada uma revisão de literatura sistematizada por meio de busca no banco de dados do PubMed e uptodate, de novembro de 2021 a janeiro de 2022, utilizando-se os descritores: prevention [title/abstract] AND prophylaxis [title/abstract] AND tumor lysis syndrome [title/abstract]. Dos 212 artigos encontrados, após exclusão por título, abstract e leitura completa, apenas nove foram selecionados. Os estudos mostraram, em sua maioria, uma redução do ácido úrico plasmático com o uso da rasburicase em pacientes com alto risco para SLT. A rasburicase foi eficaz para prevenção e tratamento da hiperuricemia em pacientes com risco de SLT. Apesar dos estudos analisados serem positivos para eficácia da rasburicase na prevenção e no tratamento da síndrome, nenhum deles trouxe como desfecho principal a redução de mortalidade. Torna-se relevante, portanto, a realização de mais estudos multicêntricos, prospectivos e com emprego de instrumentos validados sobre o tema desta revisão sistemática.

Tumor lysis syndrome (TLS) is an onco-hematological emergency associated with high mortality and morbidity, of spontaneous onset or in response to chemotherapy or anticancer biotherapy. Rasburicase is a recombinant urate oxidase drug that reduces blood uric acid released, preventing and treating acute kidney injury, considered the main TLS complication. This systematic literature review sought to evaluate the rasburicase effectiveness in preventing and treating tumor lysis syndrome, to better understand how to manage this frequent syndrome in cancer patients. Bibliographic search was conducted on the PubMed database from November 2021 to January 2022, using the following descriptors: prevention [title/abstract] AND prophylaxis [title/abstract] AND tumor lysis syndrome [title/abstract]. After exclusion by title, abstract and full reading, only nine papers were selected from the 212 found. Most studies showed reduced plasma uric acid by rasburicase use in high-risk patients for TLS. Rasburicase effectively prevented and treated hyperuricemia in patients at risk for tumor lysis syndrome. Despite these positive outcomes, none of the studies showed reduced mortality as the main outcome. Thus, further multicenter prospective studies using validated instruments are needed on the subject.

El síndrome de lisis tumoral (SLT) es una urgencia oncohematológica, asociada a una alta mortalidad y morbilidad, que puede presentarse de forma espontánea o en respuesta a quimioterapia o bioterapia anticancerígena. La rasburicasa es un fármaco de urato oxidasa recombinante, que reduce el ácido úrico sanguíneo liberado mediante la prevención y el tratamiento de la lesión renal aguda, que representa la principal complicación del SLT. El objetivo de este artículo fue evaluar la efectividad de la rasburicasa en la prevención y tratamiento del SLT, lo que contribuye a una mejor comprensión del manejo de este síndrome frecuente en pacientes oncológicos. Se hizo una revisión sistemática de la literatura mediante búsqueda en la base de datos PubMed y actualizada de noviembre de 2021 a enero de 2022, utilizando los descriptores de PubMed: prevention [title/abstract] AND prophylaxis [title/abstract] AND tumor lysis syndrome [title/abstract]. De los 212 artículos encontrados, después de la exclusión por título, resumen y lectura completa, solo 9 fueron seleccionados. La mayoría de los estudios mostraron una reducción del ácido úrico plasmático con el uso de rasburicasa en pacientes con alto riesgo de SLT. La rasburicasa fue eficaz para la prevención y el tratamiento de la hiperuricemia en pacientes con riesgo de síndrome de lisis tumoral. A pesar de que los estudios analizados fueron positivos para la eficacia de la rasburicasa en la prevención y tratamiento del síndrome, ninguno de ellos trajo como desenlace principal la reducción de la mortalidad. Por lo tanto, es relevante realizar más estudios prospectivos multicéntricos utilizando instrumentos validados sobre el tema de esta revisión sistemática.

Más allá del diagnóstico de leucemia congénita neonatal / Beyond the Diagnosis of Neonatal Congenital Leukemia / Além do diagnóstico de leucemia congênita neonatal

Resumen: la leucemia congénita neonatal se presenta en los primeros 30 días de vida y es una enfermedad muy poco frecuente en este grupo etario, pero sí de mayor presencia entre los pacientes con síndrome de Down. Su etiología es principalmente genética, pero también se asocia con el consumo de alcohol, la marihuana y el tabaquismo. Se debe hacer diagnóstico diferencial con el desorden mieloproliferativo transitorio, que es una entidad benigna y se resuelve de forma espontánea. Se presenta un caso clínico de un paciente recién nacido a término, de 16 días, que inicialmente presenta sintomatología sugestiva de enterocolitis necrotizante. Sin embargo, al ingresar a unidad neonatal, se evidencia abdomen muy distendido con hepatoesplenomegalia severa con hemograma con hiperleucocitosis severa, anemia y trombocitopenia asociado a blastos del 100 % y paraclínicos de extensión, sugestivo de síndrome de lisis tumoral, por lo que se inicia manejo con hiperhidratación, alopurinol y rasburicasa, sin mejoría. Por esta razón se adiciona citarabina. La citometría de flujo reporta patrón megaloblástico, es decir, un patrón de leucemia mieloide. Requiere hospitalización por mes y medio; luego de este tiempo pueden presentarse complicaciones esperadas. No obstante, se consideró que el recién nacido cursó con trastorno mieloide transitorio, en razón a evolución clínica satisfactoria, con disminución de sintomatología y de leucocitosis severa.

Abstract: Neonatal congenital leukemia manifests within the first 30 days of life and is exceedingly rare in this age group, but more prevalent among patients with Down syndrome. Its etiology is primarily genetic but is also linked to alcohol consumption, marijuana, and smoking. Differential diagnosis should be made with transient myeloproliferative disorder, a benign condition that resolves spontaneously. We present a clinical case of a full-term newborn, 16 days old, initially displaying symptoms suggestive of necrotizing enterocolitis. However, upon admission to the neonatal unit, the patient exhibited a greatly distended abdomen with severe hepatosplenomegaly, severe leukocytosis, anemia, and thrombocytopenia, accompanied by 100% blasts and laboratory findings consistent with tumor lysis syndrome. Management was initiated with hyperhydration, allopurinol, and rasbu-ricase, but there was no improvement. Therefore, cytarabine was added. Flow cytometry indicated a megaloblastic pattern, indicative of myeloid leukemia. The patient required hospitalization for a month and a half, during which expected complications might arise. However, it was considered that the newborn experienced transient myeloid disorder, given the satisfactory clinical evolution, with reduced symptoms and severe leukocytosis.

Resumo: a leucemia congênita neonatal ocorre nos primeiros 30 dias de vida e é uma doença pouco frequente nesse grupo etário, no entanto, ela é mais comum entre pacientes com síndrome de Down. Sua etiologia é principalmente genética, mas também está associada ao consumo de álcool, maconha e tabagismo. Deve-se fazer um diagnóstico diferencial com o distúrbio mieloproliferativo transitório, que é uma condição benigna e se resolve espontaneamente. Apresentamos um caso clínico de um recém-nascido, com 16 dias de idade, que inicialmente apresentou sintomas sugestivos de enterocolite necrosante. No entanto, ao ser admitido na unidade neonatal, foi evidenciado um abdômen muito distendido com hepatosplenomegalia grave, com hemograma mostrando hiperleucocitose grave, anemia e trombocitopenia, associado a 100% de blastos e resultados de extensão sugestivos de síndrome de lise tumoral. Portanto, foi iniciado tratamento com hiperidratação, alopurinol e rasburicasa, sem melhora. Por esse motivo, a citarabina foi adicionada. A citometria de fluxo relatou um padrão megaloblástico, ou seja, um padrão de leucemia mieloide. O paciente necessita, então, de hospitalização por um mês e meio; após esse tempo, complicações esperadas podem ocorrer. No entanto, considerou-se que o recém-nascido teve um distúrbio mieloide transitório, devido à evolução clínica satisfatória, com diminuição dos sintomas e da hiperleucocitose.

Expanding the Database of Signal-Anchor-Release Domain Endolysins Through Metagenomics.

Endolysins are bacteriophage-derived lytic enzymes with antimicrobial activity. The action of endolysins against Gram-negative bacteria remains a challenge due to the physical protection of the outer membrane. However, recent research has demonstrated that signal-anchor-release (SAR) endolysins permeate the outer membrane of Gram-negative bacteria. This study investigates 2628 putative endolysin genes identified in 183,298 bacteriophage genomes. Previously, bioinformatic approaches resulted in a database of 66 SAR endolysins. This manuscript almost doubles the list with 53 additional SAR endolysin candidates. Forty-eight of the putative SAR endolysins described in this study contained one muramidase catalytic domain, and five included additional cell wall-binding domains at the C-terminus. For the moment, SAR domains are found in four protein families: glycoside hydrolase family 19 (GH19), glycoside hydrolase family 24 (GH24), glycoside hydrolase family 25 (GH25), and glycoside hydrolase family 108 (GH108). These SAR lysis are clustered in eight groups based on biochemical properties and domain presence/absence. Therefore, in this study, we expand the arsenal of endolysin candidates that might act against Gram-negative bacteria and develop a consult database for antimicrobial proteins derived from bacteriophages.

Trastornos mieloproliferativos y leucemia en síndrome de Down. Presentación de dos casos clínicos en el período neonatal / Myeloproliferative disorders and leukemia related to Down syndrome. Report of two clinical cases in neonatal period

ElsíndromedeDownpredisponeatrastornosmieloproliferativos. Se estima que del 5 % al 30 % de los neonatos con esta condición desarrollarán mielopoyesis anormal transitoria. El tratamiento no está estandarizado; la exanguinotransfusión y la citarabina podrían ser efectivos. Se describen dos casos de pacientes con síndrome de Down, quienes durante el período neonatal presentaron leucemia mieloide aguda y mielopoyesis anormal transitoria, los tratamientos utilizados y sus desenlaces. Se considera que la sospecha y el diagnóstico temprano de esta entidad son factores determinantes en el pronóstico.

Down syndrome predisposes to haematological disorders. It is estimated that 5-30% of neonates with this condition will develop transient abnormal myelopoiesis. Treatment is not standardized; exchange transfusion and the use of cytarabine could be effective. We present two clinical cases of patients with Down syndrome, who during the neonatal period showed acute myeloid leukemia and transient abnormal myelopoiesis, the treatments used and their outcomes. Suspicion and early diagnosis of this entity are considered determining factors in prognosis.

[Myeloproliferative disorders and leukemia related to Down syndrome. Report of two clinical cases in neonatal period]. / Trastornos mieloproliferativos y leucemia en síndrome de Down. Presentación de dos casos clínicos en el período neonatal.

Down syndrome predisposes to haematological disorders. It is estimated that 5-30% of neonates with this condition will develop transient abnormal myelopoiesis. Treatment is not standardized; exchange transfusion and the use of cytarabine could be effective. We present two clinical cases of patients with Down syndrome, who during the neonatal period showed acute myeloid leukemia and transient abnormal myelopoiesis, the treatments used and their outcomes. Suspicion and early diagnosis of this entity are considered determining factors in prognosis.

El síndrome de Down predispone a trastornos mieloproliferativos. Se estima que del 5 % al 30 % de los neonatos con esta condición desarrollarán mielopoyesis anormal transitoria. El tratamiento no está estandarizado; la exanguinotransfusión y la citarabina podrían ser efectivos. Se describen dos casos de pacientes con síndrome de Down, quienes durante el período neonatal presentaron leucemia mieloide aguda y mielopoyesis anormal transitoria, los tratamientos utilizados y sus desenlaces. Se considera que la sospecha y el diagnóstico temprano de esta entidad son factores determinantes en el pronóstico.

Generalidades de las principales urgencias en el paciente oncológico: revisión de tema / Overview of the main emergencies in cancer patients: Review / Generalidades das principais urgências no paciente oncológico: revisão de tema

Las urgencias oncológicas son complicaciones comunes de la evolución natural del tumor o de su manejo. Algunas pueden presentarse de manera sutil y ser pasadas por alto, lo que aumenta la morbimortalidad. El objetivo de esta revisión narrativa es recopilar información actualizada de las principales complicaciones oncológicas, para ello se realizó una revisión de artículos originales, revisiones sistemáticas y narrativas en bases de datos como Scopus, SciELO, PubMed, ScienceDirect y en el buscador Google Scholar. Se seleccionaron 63 referencias que mostraran información relevante acerca de las urgencias oncológicas planteadas para el desarrollo del artículo. En la revisión se discute que las complicaciones pueden clasificarse de acuerdo con su origen en infecciosas (neutropenia febril), metabólicas (síndrome de lisis tumoral e hipercalcemia maligna) y obstructivas (síndrome de vena cava superior, obstrucción intestinal, compresión medular y taponamiento cardiaco). El diagnóstico requiere un alto índice de sospecha, el médico debe tener la capacidad resolutiva y el conocimiento necesarios para el manejo y hacer uso racional de los recursos diagnósticos. Es necesario adoptar medidas terapéuticas que impacten positivamente en el pronóstico y que reduzcan la morbimortalidad.

Oncological emergencies are common complications resulting from the natural evolution of the tumor or its management; however, some of them may be subtle or even overlooked, which contributes to greater morbidity and mortality. Our aim was to gather updated information on the main oncological complications. A narrative literatura review was performed by searching for original articles, systematic reviews and narratives, in databases such as Scopus, SciELO, PubMed, ScienceDirect and in the Google Scholar search engine. 63 references were selected that addressed relevant information about the oncological emergencies raised for the development of the article. According to their origin, complications can be classified into infectious (febrile neutropenia), metabolic (tumor lysis syndrome and malignant hypercalcemia) and obstructive (superior vena cava syndrome, intestinal obstruction, spinal cord compression and cardiac tamponade). Facing these complications requires a high level of suspicion; the physician must be able to resolve each complication and have the necessary knowledge to approach each case, with a rational use of diagnostic resources. It is also necessary to adopt therapeutic measures that positively impact patients. patient prognosis, decreasing morbidity and death.

As urgências oncológicas são complicações comuns da evolução natural do tumor ou do seu manejo. Algumas podem apresentar-se de maneira sutil e ser passadaspor encima, o que aumenta a morbimortalidade. O objetivo desta revisão narrativa é recopilar informação atualizada das principais complicações oncológicas, para isso se realizou uma revisão de artigos originais, revisões sistemáticas e narrativas em bases de dados como Scopus, SciELO, PubMed, ScienceDirect e no buscador Google Scholar. Se selecionaram 63 referências que mostraram informação relevante sobre às urgências oncológicas apresentadas para o desenvolvimento do artigo. Na revisão se discuteque as complicações podem classificar-se de acordo com a sua origem em infecciosas (neutropenia febril), metabólicas (síndrome de lise tumoral e hipercalcemia maligna) e obstrutivas (síndrome de veia cava superior, obstrução intestinal, compressão medular e entupimento cardíaco). O diagnóstico requere um alto índice de suspeita, o médico deve ter a capacidade resolutiva e o conhecimento necessário para o manejo e fazer uso racional dos recursos diagnósticos. É necessário adotar medidas terapêuticas que impactem positivamente no prognóstico e que reduzam a morbimortalidade.

Síndrome de lisis tumoral secundario a la administración de corticoides en una adolescente sin enfermedad neoplásica confirmada: reporte de un caso / Tumor lysis syndrome after the administration of corticosteroids in an adolescent without confirmed neoplastic disease. Case report

El síndrome de lisis tumoral es una complicación potencialmente letal y constituye, junto con las infecciones, la emergencia oncológica más frecuente. En pediatría, este cuadro puede ser secundario a enfermedades neoplásicas, y los corticoides son un factor desencadenante. En este trabajo se presenta el caso de una paciente adolescente, sin neoplasias conocidas o evidentes, que desarrolló un síndrome de lisis tumoral luego de la administración de corticoides por sospecha de una infección respiratoria. Se discute la forma de presentación y los diagnósticos diferenciales del cuadro clínico inicial. Se hace especial foco en la administración de corticoides en cuadros clínicos en los que no existe evidencia científica que respalde fuertemente su indicación. El uso de corticosteroides sistémicos en infecciones respiratorias agudas debe ser evaluado en el contexto clínico y solo debe indicarse en situaciones con probada efectividad.

Tumor lysis syndrome is a potentially lethal complication and constitutes with infections the most frequent oncological emergency. In children, this condition can be secondary to neoplastic diseases, with corticosteroids being a triggering factor. This paper presents the case of an adolescent patient, without known or obvious neoplasms, who developed a tumor lysis syndrome after the administration of corticosteroids due to suspected respiratory infection.The clinical presentation and differential diagnoses are discussed. Special focus is placed on the administration of corticosteroids in clinical conditions with weak scientific evidence. The use of systemic corticosteroids in acute respiratory infections should be evaluated in the clinical context and only indicated in situations with proven effectiveness.

[Tumor lysis syndrome after the administration of corticosteroids in an adolescent without confirmed neoplastic disease. Case Reports]. / Síndrome de lisis tumoral secundario a la administración de corticoides en una adolescente sin enfermedad neoplásica confirmada: reporte de un caso.

Tumor lysis syndrome is a potentially lethal complication and constitutes with infections the most frequent oncological emergency. In children, this condition can be secondary to neoplastic diseases, with corticosteroids being a triggering factor. This paper presents the case of an adolescent patient, without known or obvious neoplasms, who developed a tumor lysis syndrome after the administration of corticosteroids due to suspected respiratory infection. The clinical presentation and differential diagnoses are discussed. Special focus is placed on the administration of corticosteroids in clinical conditions with weak scientific evidence. The use of systemic corticosteroids in acute respiratory infections should be evaluated in the clinical context and only indicated in situations with proven effectiveness.

El síndrome de lisis tumoral es una complicación potencialmente letal y constituye, junto con las infecciones, la emergencia oncológica más frecuente. En pediatría, este cuadro puede ser secundario a enfermedades neoplásicas, y los corticoides son un factor desencadenante. En este trabajo se presenta el caso de una paciente adolescente, sin neoplasias conocidas o evidentes, que desarrolló un síndrome de lisis tumoral luego de la administración de corticoides por sospecha de una infección respiratoria. Se discute la forma de presentación y los diagnósticos diferenciales del cuadro clínico inicial. Se hace especial foco en la administración de corticoides en cuadros clínicos en los que no existe evidencia científica que respalde fuertemente su indicación. El uso de corticosteroides sistémicos en infecciones respiratorias agudas debe ser evaluado en el contexto clínico y solo debe indicarse en situaciones con probada efectividad.

Oncolytic virus therapy in cancer: A current review.

In view of the advancement in the understanding about the most diverse types of cancer and consequently a relentless search for a cure and increased survival rates of cancer patients, finding a therapy that is able to combat the mechanism of aggression of this disease is extremely important. Thus, oncolytic viruses (OVs) have demonstrated great benefits in the treatment of cancer because it mediates antitumor effects in several ways. Viruses can be used to infect cancer cells, especially over normal cells, to present tumor-associated antigens, to activate "danger signals" that generate a less immune-tolerant tumor microenvironment, and to serve transduction vehicles for expression of inflammatory and immunomodulatory cytokines. The success of therapies using OVs was initially demonstrated by the use of the genetically modified herpes virus, talimogene laherparepvec, for the treatment of melanoma. At this time, several OVs are being studied as a potential treatment for cancer in clinical trials. However, it is necessary to be aware of the safety and possible adverse effects of this therapy; after all, an effective treatment for cancer should promote regression, attack the tumor, and in the meantime induce minimal systemic repercussions. In this manuscript, we will present a current review of the mechanism of action of OVs, main clinical uses, updates, and future perspectives on this treatment.

Fatal tumor lysis syndrome in a patient with metastatic gastric adenocarcinoma.

Tumor lysis syndrome is a well-characterized and potentially deadly complication of spontaneous or treatment-related tumor destruction, and it is most commonly associated with hematologic malignancies. Our case illustrates a rare example of fatal tumor lysis syndrome in the setting of metastatic gastric adenocarcinoma treated with radiation therapy. This case highlights the critical importance of identifying patients with solid organ malignancies at risk for tumor lysis syndrome and of early recognition and treatment of this syndrome.

Antimicrobial Polymer-Based Assemblies: A Review.

An antimicrobial supramolecular assembly (ASA) is conspicuous in biomedical applications. Among the alternatives to overcome microbial resistance to antibiotics and drugs, ASAs, including antimicrobial peptides (AMPs) and polymers (APs), provide formulations with optimal antimicrobial activity and acceptable toxicity. AMPs and APs have been delivered by a variety of carriers such as nanoparticles, coatings, multilayers, hydrogels, liposomes, nanodisks, lyotropic lipid phases, nanostructured lipid carriers, etc. They have similar mechanisms of action involving adsorption to the cell wall, penetration across the cell membrane, and microbe lysis. APs, however, offer the advantage of cheap synthetic procedures, chemical stability, and improved adsorption (due to multipoint attachment to microbes), as compared to the expensive synthetic routes, poor yield, and subpar in vivo stability seen in AMPs. We review recent advances in polymer-based antimicrobial assemblies involving AMPs and APs.

The Saccharomyces cerevisiae Ncw2 protein works on the chitin/ß-glucan organisation of the cell wall.

The NCW2 gene was recently described as encoding a GPI-bounded protein that assists in the re-modelling of the Saccharomyces cerevisiae cell wall (CW) and in the repair of damage caused by the polyhexamethylene biguanide (PHMB) polymer to the cell wall. Its absence produces a re-organization of the CW structure that result in resistance to lysis by glucanase. Hence, the present study aimed to extend the analysis of the Ncw2 protein (Ncw2p) to determine its physiological role in the yeast cell surface. The results showed that Ncw2p is transported to the cell surface upon O-mannosylation mediated by the Pmt1p-Pmt2p enzyme complex. It co-localises with the yeast bud scars, a region in cell surface formed by chitin deposition. Once there, Ncw2p enables correct chitin/ß-glucan structuring during the exponential growth. The increase in molecular mass by hyper-mannosylation coincides with the increasing in chitin deposition, and leads to glucanase resistance. Treatment of the yeast cells with PHMB produced the same biological effects observed for the passage from exponential to stationary growth phase. This might be a possible mechanism of yeast protection against cationic biocides. In conclusion, we propose that Ncw2p takes part in the mechanism involved in the control of cell surface rigidity by aiding on the linkage between chitin and glucan layers in the modelling of the cell wall during cell growth.