MAP kinase ERK5 modulates cancer cell sensitivity to extrinsic apoptosis induced by death-receptor agonists.

Death receptor ligand TRAIL is a promising cancer therapy due to its ability to selectively trigger extrinsic apoptosis in cancer cells. However, TRAIL-based therapies in humans have shown limitations, mainly due inherent or acquired resistance of tumor cells. To address this issue, current efforts are focussed on dissecting the intracellular signaling pathways involved in resistance to TRAIL, to identify strategies that sensitize cancer cells to TRAIL-induced cytotoxicity. In this work, we describe the oncogenic MEK5-ERK5 pathway as a critical regulator of cancer cell resistance to the apoptosis induced by death receptor ligands. Using 2D and 3D cell cultures and transcriptomic analyses, we show that ERK5 controls the proteostasis of TP53INP2, a protein necessary for full activation of caspase-8 in response to TNFα, FasL or TRAIL. Mechanistically, ERK5 phosphorylates and induces ubiquitylation and proteasomal degradation of TP53INP2, resulting in cancer cell resistance to TRAIL. Concordantly, ERK5 inhibition or genetic deletion, by stabilizing TP53INP2, sensitizes cancer cells to the apoptosis induced by recombinant TRAIL and TRAIL/FasL expressed by Natural Killer cells. The MEK5-ERK5 pathway regulates cancer cell proliferation and survival, and ERK5 inhibitors have shown anticancer activity in preclinical models of solid tumors. Using endometrial cancer patient-derived xenograft organoids, we propose ERK5 inhibition as an effective strategy to sensitize cancer cells to TRAIL-based therapies.

Machine learning combining multi-omics data and network algorithms identifies adrenocortical carcinoma prognostic biomarkers.

Background: Rare endocrine cancers such as Adrenocortical Carcinoma (ACC) present a serious diagnostic and prognostication challenge. The knowledge about ACC pathogenesis is incomplete, and patients have limited therapeutic options. Identification of molecular drivers and effective biomarkers is required for timely diagnosis of the disease and stratify patients to offer the most beneficial treatments. In this study we demonstrate how machine learning methods integrating multi-omics data, in combination with system biology tools, can contribute to the identification of new prognostic biomarkers for ACC. Methods: ACC gene expression and DNA methylation datasets were downloaded from the Xena Browser (GDC TCGA Adrenocortical Carcinoma cohort). A highly correlated multi-omics signature discriminating groups of samples was identified with the data integration analysis for biomarker discovery using latent components (DIABLO) method. Additional regulators of the identified signature were discovered using Clarivate CBDD (Computational Biology for Drug Discovery) network propagation and hidden nodes algorithms on a curated network of molecular interactions (MetaBase™). The discriminative power of the multi-omics signature and their regulators was delineated by training a random forest classifier using 55 samples, by employing a 10-fold cross validation with five iterations. The prognostic value of the identified biomarkers was further assessed on an external ACC dataset obtained from GEO (GSE49280) using the Kaplan-Meier estimator method. An optimal prognostic signature was finally derived using the stepwise Akaike Information Criterion (AIC) that allowed categorization of samples into high and low-risk groups. Results: A multi-omics signature including genes, micro RNA's and methylation sites was generated. Systems biology tools identified additional genes regulating the features included in the multi-omics signature. RNA-seq, miRNA-seq and DNA methylation sets of features revealed a high power to classify patients from stages I-II and stages III-IV, outperforming previously identified prognostic biomarkers. Using an independent dataset, associations of the genes included in the signature with Overall Survival (OS) data demonstrated that patients with differential expression levels of 8 genes and 4 micro RNA's showed a statistically significant decrease in OS. We also found an independent prognostic signature for ACC with potential use in clinical practice, combining 9-gene/micro RNA features, that successfully predicted high-risk ACC cancer patients. Conclusion: Machine learning and integrative analysis of multi-omics data, in combination with Clarivate CBDD systems biology tools, identified a set of biomarkers with high prognostic value for ACC disease. Multi-omics data is a promising resource for the identification of drivers and new prognostic biomarkers in rare diseases that could be used in clinical practice.

The ERK5/NF-κB signaling pathway targets endometrial cancer proliferation and survival.

Endometrial cancer (EC) is the most common type of gynecologic cancer in women of developed countries. Despite surgery combined with chemo-/radiotherapy regimens, overall survival of patients with high-risk EC tumors is poor, indicating a need for novel therapies. The MEK5-ERK5 pathway is activated in response to growth factors and to different stressors, including oxidative stress and cytokines. Previous evidence supports a role for the MEK5-ERK5 pathway in the pathology of several cancers. We investigated the role of ERK5 in EC. In silico analysis of the PanCancer Atlas dataset showed alterations in components of the MEK5-ERK5 pathway in 48% of EC patients. Here, we show that ERK5 inhibition or silencing decreased EGF-induced EC cell proliferation, and that genetic deletion of MEK5 resulted in EC impaired proliferation and reduced tumor growth capacity in nude mice. Pharmacologic inhibition or ERK5 silencing impaired NF-kB pathway in EC cells and xenografts. Furthermore, we found a positive correlation between ERK5 and p65/RELA protein levels in human EC tumor samples. Mechanistically, genetic or pharmacologic impairment of ERK5 resulted in downregulation of NEMO/IKKγ expression, leading to impaired p65/RELA activity and to apoptosis in EC cells and xenografts, which was rescued by NEMO/IKKγ overexpression. Notably, ERK5 inhibition, MEK5 deletion or NF-kB inhibition sensitized EC cells to standard EC chemotherapy (paclitaxel/carboplatin) toxicity, whereas ERK5 inhibition synergized with paclitaxel to reduce tumor xenograft growth in mice. Together, our results suggest that the ERK5-NEMO-NF-κB pathway mediates EC cell proliferation and survival. We propose the ERK5/NF-κB axis as new target for EC treatment.

ERK5 Inhibition Induces Autophagy-Mediated Cancer Cell Death by Activating ER Stress.

Autophagy is a highly conserved intracellular process that preserves cellular homeostasis by mediating the lysosomal degradation of virtually any component of the cytoplasm. Autophagy is a key instrument of cellular response to several stresses, including endoplasmic reticulum (ER) stress. Cancer cells have developed high dependency on autophagy to overcome the hostile tumor microenvironment. Thus, pharmacological activation or inhibition of autophagy is emerging as a novel antitumor strategy. ERK5 is a novel member of the MAP kinase family that is activated in response to growth factors and different forms of stress. Recent work has pointed ERK5 as a major player controlling cancer cell proliferation and survival. Therefore small-molecule inhibitors of ERK5 have shown promising therapeutic potential in different cancer models. Here, we report for the first time ERK5 as a negative regulator of autophagy. Thus, ERK5 inhibition or silencing induced autophagy in a panel of human cancer cell lines with different mutation patterns. As reported previously, ERK5 inhibitors (ERK5i) induced apoptotic cancer cell death. Importantly, we found that autophagy mediates the cytotoxic effect of ERK5i, since ATG5-/- autophagy-deficient cells viability was not affected by these compounds. Mechanistically, ERK5i stimulated autophagic flux independently of the canonical regulators AMPK or mTORC1. Moreover, ERK5 inhibition resulted in ER stress and activation of the Unfolded Protein Response (UPR) pathways. Specifically, ERK5i induced expression of the ER luminal chaperone BiP (a hallmark of ER stress), the UPR markers CHOP and ATF4, and the spliced form of XBP1. Pharmacological inhibition of UPR with chemical chaperone TUDC, or ATF4 silencing, resulted in impaired ERK5i-mediated UPR, autophagy and cytotoxicity. Overall, our results suggest that ERK5 inhibition induces autophagy-mediated cancer cell death by activating ER stress. Since ERK5 inhibition sensitizes cancer cells and tumors to chemotherapy, future work will determine the relevance of UPR and autophagy in the combined use of chemotherapy and ERK5i to tackle Cancer.

Distribución del género Tityus Koch, 1836 (Scorpiones: Buthidae) en la ciudad de La Plata (Argentina) / Distribution of the genus Tityus Koch, 1836 (Scorpiones: Buthidae) in the city of La Plata (Argentina)

Resumen En la ciudad de La Plata se encuentra el género Tityus con registros desde 1943. Se estudió la distribución territorial del género Tityus en esta ciudad y su expansión en los últimos 15 años a partir de las consultas recibidas en el Laboratorio de Aracnología del CEPAVE, provenientes de particulares e instituciones públicas y privadas. Se recibieron 189 consultas desde el año 2005 al 2020. Se utilizó el programa QGIS para geolocalizar cada escorpión con capas de trazado urbano y desagües pluviales. Para el análisis espacial de distribución se consideró un home range de una hectárea por individuo para el cálculo de área y en los casos de áreas de influencias solapadas durante el mismo año se consideró el área como la unión de las mismas. El género Tityus en la ciudad de La Plata está representado por las especies T. carrilloi y T. confluens ambas de interés sanitario y de hábitos sinantrópicos, que ocupan dos zonas diferentes bien definidas. El análisis de la dispersión independiente en las dos zonas indicaría que podrían usar los desagües para dispersarse, y al ser inconexos estos no habría flujo de escorpiones entre ambas zonas. La colonización de estas especies en la zona en estudio se vio afianzada para T. confluens a partir del año 2005 y para T. carrilloi a partir del 2011. Los mayores registros son en los meses cálidos, desde enero a abril, siendo este último el de mayor valor. Septiembre es el único mes sin denuncia. La tasa de expansión calculada fue de 4.42 ha/año.

Abstract In the city of La Plata occurs the genus Tityus with records dating back to 1943. The territorial distribution of the genus Tityus in this city and its expansion was studied based on inquiries received at the CEPAVE Arachnology Laboratory from individuals and public and private institutions. 189 inquiries were received from 2005 to 2020. The QGIS program was used to geolocate each scorpion with urban layout layers and storm drains. For the spatial analysis of distribution, a home range of one hectare per individual was considered to calculate the area and in the cases of areas of overlapping influences during the same year, the area was considered as their union. The genus Tityus in the city of La Plata is represented by the species T. carrilloi and T. confluens, both of health interest and of synanthropic habits, which occupy two different well-defined areas. The analysis of the independent dispersion in the two zones would indicate that they could use the drains to disperse, and since they are unconnected there would be no flow of scorpions between both zones. The colonization of these species in the study area was strengthened for T. confluens as of 2005 and for T. carrilloi as of 2011. The highest records are in the warm months, from January to April, the latter being of higher value. September is the only month without complaints. The expansion rate calculated was 4.42 ha/year.

[Predictors of complex urethral surgery in anterior urethral stricture disease.] / Predictores de cirugía uretral compleja en estenosis de la uretra anterior.

OBJECTIVE: To determine the clinical-surgical factors associated with Complex Urethral Surgery (CUC) in anterior urethral stenosis. MATERIAL AND METHOD: This is a cross-sectional study with retrospective data recording, including all male patients who under went anterior urethroplasty between 2011 and 2018. CUC included two or more grafts urethroplasty, excisional augmented anastomotic urethroplasty, combined flaps and grafts urethroplasty and stages surgery. The data were collected from the electronic medical record, recording the demographic data, background of previous treatments as well as the characteristics of the stenosis (etiology, anatomical location, length, number of strictures, among others). A univariate and multivariate analysis were conducted using the chi-squared test and logistic regression to identify the variables related to CUC. RESULTS: The data of 665 patients met the inclusion criteria were analyzed. The mean age was 56.1 years, 27.5% were smokers, 32.5% had received some previous treatment, and dilatations were the most common procedure. The most prevalent etiology was iatrogenic, followed by idiopathic in a 61.1 and 20.3% respectively. Bulbar urethral stricture were the most common location (56.2%) while the mean length of the stenosis was 4.8 cm. After univariate and multivariate analysis, previous dilations (HR 2.6), multifocality (2.51), lengthof stenosis (>4 cm) (HR 1.49) and the hypospadias etiology (HR 11.9) were independent predictors for CUC (p<0.05)CONCLUSIONS: Hypospadias was the only etiology factor that predicts the need for CUC. Regarding radiological findings, extensive and multifocal stenosis, were predictors of complex surgery. History of previous dilations were also predictors of CUC.

OBJETIVO: Determinar los factores predictores asociados a Cirugía Uretral Compleja (CUC) en los casos de estenosis de la uretra anterior.MATERIAL Y MÉTODO: Estudio transversal con registro de datos retrospectivo, incluye a todos los pacientes masculinos a quienes se les practicó una plastía de la uretra anterior entre 2011 y 2018. Como CUC se consideró a la Uretroplastia con dos o más injertos, la anastomosis término terminal ampliada, la uretroplastia combinada y la cirugía por estadíos. Los datos se recabaron de la historia clínica electrónica consignándose aquellos demográficos, antecedente de tratamientos previos, así como las características de la estenosis (etiología, ubicación anatómica, longitud, número de estenosis entre otras). Se realizó un análisis univariado y multivariado para identificar variables predictoras de CUC. RESULTADOS: Se analizaron los datos de 665 pacientes con criterios de inclusión válidos. La media de edad fue de 56,1 años, 27,5% eran fumadores crónicos, 32,5% habían recibido algún tratamiento previo, siendo las dilataciones el procedimiento más común (17,6%), la etiología más prevalente fue la iatrógena seguida por la idiopática en un 61,1 y un 20,3% respectivamente, la ubicación más común fue la uretra bulbar en 56,2% mientras que la media de longitud de la estenosis fue de 4,8 cm. En el análisis univariado y multivariable el antecedente de dilataciones (HR 2,6), la multifocalidad (HR 2,51), la longitud de la estenosis (>4 cm) (HR 1,49) y la etiología hipospadias (HR 11,9) resultaron ser factores predictores independientes para CUC (p<0,05). CONCLUSIONES: La hipospadia fue dentro de las etiologías analizadas la única que predice la necesidad de CUC. En lo que respecta a antecedentes y hallazgos radiológicos, las dilataciones y las estenosis extensas y multifocales respectivamente fueron predictores de CUC.

The anti-cancer drug ABTL0812 induces ER stress-mediated cytotoxic autophagy by increasing dihydroceramide levels in cancer cells.

ABTL0812 is a first-in-class small molecule with anti-cancer activity, which is currently in clinical evaluation in a phase 2 trial in patients with advanced endometrial and squamous non-small cell lung carcinoma (NCT03366480). Previously, we showed that ABTL0812 induces TRIB3 pseudokinase expression, resulting in the inhibition of the AKT-MTORC1 axis and macroautophagy/autophagy-mediated cancer cell death. However, the precise molecular determinants involved in the cytotoxic autophagy caused by ABTL0812 remained unclear. Using a wide range of biochemical and lipidomic analyses, we demonstrated that ABTL0812 increases cellular long-chain dihydroceramides by impairing DEGS1 (delta 4-desaturase, sphingolipid 1) activity, which resulted in sustained ER stress and activated unfolded protein response (UPR) via ATF4-DDIT3-TRIB3 that ultimately promotes cytotoxic autophagy in cancer cells. Accordingly, pharmacological manipulation to increase cellular dihydroceramides or incubation with exogenous dihydroceramides resulted in ER stress, UPR and autophagy-mediated cancer cell death. Importantly, we have optimized a method to quantify mRNAs in blood samples from patients enrolled in the ongoing clinical trial, who showed significant increased DDIT3 and TRIB3 mRNAs. This is the first time that UPR markers are reported to change in human blood in response to any drug treatment, supporting their use as pharmacodynamic biomarkers for compounds that activate ER stress in humans. Finally, we found that MTORC1 inhibition and dihydroceramide accumulation synergized to induce autophagy and cytotoxicity, phenocopying the effect of ABTL0812. Given the fact that ABTL0812 is under clinical development, our findings support the hypothesis that manipulation of dihydroceramide levels might represents a new therapeutic strategy to target cancer.Abbreviations: 4-PBA: 4-phenylbutyrate; AKT: AKT serine/threonine kinase; ATG: autophagy related; ATF4: activating transcription factor 4; Cer: ceramide; DDIT3: DNA damage inducible transcript 3; DEGS1: delta 4-desaturase, sphingolipid 1; dhCer: dihydroceramide; EIF2A: eukaryotic translation initiation factor 2 alpha; EIF2AK3: eukaryotic translation initiation factor 2 alpha kinase 3; ER: endoplasmic reticulum; HSPA5: heat shock protein family A (Hsp70) member 5; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MEF: mouse embryonic fibroblast; MTORC1: mechanistic target of rapamycin kinase complex 1; NSCLC: non-small cell lung cancer; THC: Δ9-tetrahydrocannabinol; TRIB3: tribbles pseudokinase 3; XBP1: X-box binding protein 1; UPR: unfolded protein response.

In vitro evaluation of the dissolving effect of carbonated beverages (Coca-Cola®) and enzyme-based solutions on enteroliths obtained from horses: pilot study / Avaliação in vitro do efeito dissolvente de bebidas carbonatadas (Coca-Cola®) e soluções à base de enzimas sobre enterólitos obtidos de cavalos: estudo piloto

Enteroliths are concretions of minerals that cause partial or total obstruction of the intestinal lumen, resulting in recurrent and chronic colic in horses. This pilot study aimed to evaluate the in vitro solvent effect of carbonated beverages (Coca-Cola® and Coca-Cola® Zero), and papain and cellulase enzymes (Robinson Pharma®, Santa Ana, CA, USA) on enteroliths obtained from horses. Six 51-grams-samples of six enteroliths were assigned to six treatments of immersion solutions: T1, Coca-Cola®; T2: Coca-Cola® Zero; T3: distilled water + papain (90 mg) and cellulase (120 mg); T4: Coca-Cola® + papain and cellulase; T5: Coca-Cola® Zero + papain and cellulase; and, CT: distilled water (control). The volume for immersion in the assigned solution was 150 mL, at a pH of 7.1, using an incubation shaker (Heidolph®, Germany) at 37ºC and 25 rpm, for 72 h. The evaluation periods of the dissolution percentage (difference between the initial weight and final weight of the samples), were 0, 3, 12, 24, 36, 48, 60, and 72 h. After 72 h of immersion, solutions T4, T5, and T1 presented 47, 38.8, and 14.9% of dissolution, respectively. The other solutions did not have major differences with CT (control). Under the in vitro conditions of this pilot study, papain and cellulase enzymes potentiated the dissolving effect of the carbonated solutions on the enteroliths obtained from horses. Further studies are suggested since the existing literature is on the dissolution of phytobezoars and not of enteroliths.(AU)

Enterólitos são concreções de minerais que causam obstrução parcial ou total do lume intestinal, resultando em cólica crônica e recorrente nos cavalos. Este estudo piloto teve como objetivo avaliar in vitro o efeito dissolvente sobre os enterólitos das bebidas carbonatadas (Coca-Cola® e Coca-Cola® Zero) e a solução à base das enzimas papaína e celulase (Robinson Pharma®, Santa Ana, CA, USA). Seis (6) amostras de seis (6) enterólitos de 51gramas de peso foram distribuídas em seis tratamentos de imersão: T1: Coca-Cola®; T2: Coca-Cola® Zero; T3: água destilada + papaína (90 mg) e celulase (120 mg); T4: Coca-Cola® + papaína e celulase; T5: Coca-Cola® Zero + papaína e celulase; e, CT: água destilada (controle). O volume das soluções de imersão foi de 150 mL, com pH de 7.1, usando um shaker de incubação (Heidolph®, Germany) com 37ºC e 25 rpm, durante 72 horas. A avaliação dos períodos da porcentagem de dissolução (diferenças entre o peso inicial e o peso final das amostras) foram 0, 3, 12, 24, 36, 48, 60 e 72 h. Depois de 72 h de imersão, as soluções T4, T5 e T1 apresentaram 47, 38,8 e 14,9% de dissolução, respectivamente. As outras soluções não tiveram diferenças com relação ao CT (controle). Nas condições in vitro deste estudo piloto, as enzimas papaína e celulase potenciam o efeito dissolvente das bebidas carbonatadas sobre os enterólitos obtidos de cavalos. Mais estudos são sugeridos, uma vez que só existe literatura sobre a dissolução de fitobezoares e não de enterólitos.(AU)

STK11 (LKB1) missense somatic mutant isoforms promote tumor growth, motility and inflammation.

Elucidating the contribution of somatic mutations to cancer is essential for personalized medicine. STK11 (LKB1) appears to be inactivated in human cancer. However, somatic missense mutations also occur, and the role/s of these alterations to this disease remain unknown. Here, we investigated the contribution of four missense LKB1 somatic mutations in tumor biology. Three out of the four mutants lost their tumor suppressor capabilities and showed deficient kinase activity. The remaining mutant retained the enzymatic activity of wild type LKB1, but induced increased cell motility. Mechanistically, LKB1 mutants resulted in differential gene expression of genes encoding vesicle trafficking regulating molecules, adhesion molecules and cytokines. The differentially regulated genes correlated with protein networks identified through comparative secretome analysis. Notably, three mutant isoforms promoted tumor growth, and one induced inflammation-like features together with dysregulated levels of cytokines. These findings uncover oncogenic roles of LKB1 somatic mutations, and will aid in further understanding their contributions to cancer development and progression.

SUMOylation Is Required for ERK5 Nuclear Translocation and ERK5-Mediated Cancer Cell Proliferation.

The MAP kinase ERK5 contains an N-terminal kinase domain and a unique C-terminal tail including a nuclear localization signal and a transcriptional activation domain. ERK5 is activated in response to growth factors and stresses and regulates transcription at the nucleus by either phosphorylation or interaction with transcription factors. MEK5-ERK5 pathway plays an important role regulating cancer cell proliferation and survival. Therefore, it is important to define the precise molecular mechanisms implicated in ERK5 nucleo-cytoplasmic shuttling. We previously described that the molecular chaperone Hsp90 stabilizes and anchors ERK5 at the cytosol and that ERK5 nuclear shuttling requires Hsp90 dissociation. Here, we show that MEK5 or overexpression of Cdc37-mechanisms that increase nuclear ERK5-induced ERK5 Small Ubiquitin-related Modifier (SUMO)-2 modification at residues Lys6/Lys22 in cancer cells. Furthermore, mutation of these SUMO sites abolished the ability of ERK5 to translocate to the nucleus and to promote prostatic cancer PC-3 cell proliferation. We also show that overexpression of the SUMO protease SENP2 completely abolished endogenous ERK5 nuclear localization in response to epidermal growth factor (EGF) stimulation. These results allow us to propose a more precise mechanism: in response to MEK5 activation, ERK5 SUMOylation favors the dissociation of Hsp90 from the complex, allowing ERK5 nuclear shuttling and activation of the transcription.

Caracterização epidemiológica de 4 anos dos pacientes grandes queimados no Hospital "Celia Sánchez Manduley", 2015 ­ 2018 / Four-year epidemiological characterization of large burn patients at Celia Sánchez Manduley Surgical Hospital, 2015­2018

Introdução: O paciente "grande queimado" é definido como um paciente que sofre uma queimadura de tal magnitude que carrega um importante risco vital, deFInido por diferentes parâmetros. As queimaduras são um problema de saúde pública mundial e nacional, devido à morbidade e mortalidade que produzem. O objetivo é descrever as características epidemiológicas e clínicas relacionadas ao paciente grande queimado hospitalizado. Métodos: Estudo descritivo, retrospectivo e longitudinal realizado no Serviço de Cirurgia Plástica e Queimadura do Hospital Estadual Clínico Cirúrgico "Celia Sánchez Manduley", Manzanillo ­ Granma, no período de janeiro de 2015 a dezembro de 2018, a FIm de conhecer as características epidemiológicas do paciente grande queimado hospitalizado. Resultados: O maior número de internações foi em 2018 com 45 pacientes (35,16%). Houve predomínio do sexo feminino com 74 pacientes (57,81%). Os acidentes como modo de produção de queimaduras foram os mais frequentes com 71 pacientes (55,47%). Grandes pacientes queimados relatados graves foram os mais frequentes com 48 (37,50%). O maior número de casos correspondeu aos municípios de Bayamo com 40 (31,25%) e Manzanillo 21 casos (16,41%). Conclusão: O ano de 2018 foi o que apresentou maior número de casos, predominantemente o sexo feminino e entre eles os grupos de idade entre 30 e 59 anos. Os acidentes foram o principal modo de produção, a sobrevivência foi acima das expectativas. Os municípios com mais casos foram Bayamo e Manzanillo.

Introduction: A "large burn" patient is defined as a patient who suffers a burn of such magnitude that it carries a major risk of life, defined by different parameters. Burns are a national and worldwide public health problem due to the morbidity and mortality they cause. The objective of this study is to describe the epidemiological and clinical characteristics of hospitalized patients with large burns. Methods: A descriptive, retrospective and longitudinal study was carried out at the Plastic Surgery and Burn Service of the Celia Sánchez Manduley Surgical Hospital, Manzanillo - Granma, from January 2015 to December 2018, to understand the epidemiological characteristics of hospitalized large burn patients. Results: The largest number of hospitalizations (45 patients [35.16%]) occurred in 2018. There was a predominance of females (74 patients [57.81%]). Accidents were the most frequent cause of burns (71 patients [55.47%]). Severe large burn patients were the most frequently treated (48 [37.50%]). The highest number of cases occurred in the municipalities of Bayamo (40 cases [31.25%]) and Manzanillo (21 cases [16.41%]). Conclusion: The highest number of cases occurred in 2018, with a predominance of females between the age of 30­59 years. Accidents were the primary cause for burns, and the survival rate exceeded expectations. The municipalities with the most cases were Bayamo and Manzanillo.

Evaluación del conocimiento de mitos y verdades sobre sobre arácnidos en Argentina y su posible incidencia en salud / Avaliação do conhecimento de mitos e verdades sobre aracnídeos na Argentina e sua possível incidência na saúde / Assessment of knowledge of myths and truths about arachnids in Argentina and their possible impact on health

Resumen Los arácnidos son un grupo megadiverso, en el cuál están las arañas y los escorpiones. Si bien todas las especies de ambos grupos tienen veneno, solo algunas son peligrosas para el ser humano, pudiendo causar hasta la muerte, y ocupan un lugar importante en las tradiciones de muchos pueblos. El objetivo del presente trabajo es conocer, mediante una encuesta, cuáles son los conocimientos de las personas sobre arañas y escorpiones y poner a prueba mitos y verdades mediante preguntas y repreguntas. Los resultados muestran un desconocimiento considerable en la población participante, especialmente con avanzado nivel educativo, que aceptan mitos por encima de los descubrimientos científicos verdaderos; además la respuesta entre varones y mujeres difiere de manera significativa en muchas preguntas. Estos resultados obligan a pensar políticas de educación que reviertan esos conocimientos erróneos basados en prejuicios o información de dudosa veracidad, por aquellos basados en la evidencia científica. Esto permitiría un manejo racional de estos grupos y así brindar medidas de prevención eficientes y pautas de acción si ocurriese un accidente.

Resumo Os aracnídeos são um grupo megadiverso, que inclui aranhas e escorpiões. Embora todas as espécies de ambos os grupos tenham veneno, só algumas são perigosas para o ser humano, podendo causar até a morte, e ocupam lugar importante nas tradições de muitas cidades. O objetivo do presente trabalho é conhecer, através de uma pesquisa, quais são os conhecimentos das pessoas sobre aranhas e escorpiões, e testar mitos e verdades por meio de perguntas e perguntas cruzadas. Os resultados mostram considerável desconhecimento por parte da população participante, em especial aquela com nível avançado de educação, que acredita em mitos mais frequentemente do que nas verdadeiras descobertas científicas; além disso, a resposta entre homens e mulheres difere significativamente em muitas questões. Esses resultados nos levam a pensar em políticas educacionais que revertam esses conhecimentos errôneos baseados em preconceitos ou informações de veracidade duvidosa, para aqueles baseados em evidências científicas. Isso permitiria um manejo racional dessas espécies, possibilitando medidas de prevenção eficientes e diretrizes para ação caso ocorra um acidente.

Abstract Arachnids are a megadiverse group, that include spiders and scorpions. Although the species of both groups are poisonous, only a few are dangerous to human beings, having the potential of causing death, and have an important place in the traditions of many cultures. This work aimed to evaluate, by means of a survey, the knowledge of the public about spiders and scorpions, and to test myths and truths through questions and cross-examinations. Results show a significant lack of awareness among the participants, especially those with higher level of education, who accept myths over true scientific discoveries; besides answers to many questions differ significantly between men and women. These results require the development of education policies that replace such erroneous knowledge based on prejudices or information of doubtful veracity, for scientific facts. This would allow a rational management of these species and thus provide efficient preventive measures and guidelines in case of accidents.

Morphological and cytogenetic description of a new species of Parasitylenchus Micoletzky, 1922 (Tylenchida, Allantonematidae) parasitizing Harmonia axyridis (Pallas, 1773) (Coleopera, Coccinellidae) in Argentina / Descripción morfológica y citogenética de una nueva especie de Parasitylenchus Micoletzky, 1922 (Tylenchida, Allantonematidae) parasitando Harmonia axyridis (Pallas, 1773) (Coleopera, Coccinellidae) en Argentina

Se cita y describe por primera vez para Argentina Parasitylenchus pseusobifurcatus sp.n. (Tylenchida, Allantonematidae), parásito de adultos de Harmonia axyridis (Pallas, 1773) (Coleopera, Coccinellidae). Esta nueva especie está muy cercana a P. bifurcatus Poinar Jr. y Steenberg, 2012, por la característica de tener todas las hembras vermiformes y los machos inmaduros la punta del apéndice caudal bifurcada, pero se diferencian entre otros por el tamaño del gubernáculo. Se describe su fórmula cariotípica.

Parasitylenchus pseusobifurcatus sp.n. (Tylenchida, Allantonematidae) is described for the first time for Argentina as a parasite of adults of Harmonia axyridis (Pallas, 1773) (Coleopera, Coccinellidae). The new species is closed to P. bifurcatus Poinar Jr. & Steenberg, 2012, by the characteristic of having the tail tip of all vermiform females and immature males bifurcated, but they differ by the size of the gubernaculum. Its karyotype formula is described.

Reconstrucción del cuero cabelludo después de una quemadura eléctrica de alto voltaje / Scalp Reconstruction after High-Voltage Electric Burn

Las quemaduras en el cuero cabelludo son raras. Cuando se producen suelen estar causadas por alta tensión eléctrica. La reconstrucción de los defectos del cuero cabelludo por quemaduras eléctricas se hace difícil, en parte por la extensión del defecto y la falta de determinados recursos. Se realizó una técnica con mínimo de secuelas. Se presenta un paciente masculino de 35 años, el cual llega al Cuerpo de Guardia de Caumatología por lesiones por quemaduras eléctricas de alto voltaje. Recibió el tratamiento médico quirúrgico correspondiente, injertos de piel, amputación del tercio distal del pie derecho y el 4to y 5to dedos del pie izquierdo. Solo quedó por resolver el defecto de tejido a nivel de cuero cabelludo. Se realizó rotación de un colgajo con lo cual se logró cubrir casi la totalidad del defecto, completando una pequeña zona con homoinjerto de piel. Se logró un resultado estético adecuado para el paciente con un nivel de satisfacción alto(AU)

Scalp burns are rare. When they occur, they are usually caused by high electrical voltage. The scalp reconstruction for defects caused by electrical burns is difficult, partly because of the defect area and the lack of certain resources. A technique was performed, with minimal sequelae. A 35-year-old male patient is presented with injuries due to high-voltage electricity burns, at the emergency room for caumatology attention. He received the corresponding surgical medical treatment, skin grafts, amputation of the distal third of the right foot and the fourth and fifth fingers of the left foot. Thus pending to solve the tissue defect at the level of the scalp. A flap rotation was performed, based on which almost the entire defect was covered, completing a small area with skin homograft. An adequate aesthetic result was achieved for the patient and with a high level of satisfaction(AU)

Mortalidade por queimaduras em pacientes hospitalizados em Manzanillo-Cuba em 2015-2017 / Mortality due to burns in hospitalized patients in Manzanillo-Cuba in 2015-2017 / Mortalidad por quemaduras en pacientes ingresados en Manzanillo-Cuba en 2015-2017

Objetivo: Descrever as características dos pacientes hospitalizadas por queimaduras e que foram a óbito. Método: Foi realizado um estudo descritivo, transversal e retrospectivo no Departamento de Cirurgia Plástica e Queimadura do Hospital Estadual Clínico Cirúrgico "Celia Sánchez Manduley", em Manzanillo, Granma, Cuba, no período de janeiro de 2015 a dezembro de 2017. Foram incluídos registros de 19 pacientes queimados falecidos hospitalizados. Resultados: De um total de 224 pacientes hospitalizados por queimaduras, receberam alta com evolução satisfatória 91,52% e morreram apenas 8,48%. O sexo feminino apresentou maior frequência de pacientes falecidos, com 78,98%, e entre eles a faixa etária de 60 a 74 anos, com 31,58%. A frequência de mortalidade foi maior no pacientes com queimaduras intencionais, com 63,16%. O maior número de mortes por queimaduras foi no grupo com 81-90% de superfície corporal queimada (SCQ), com 31,58%. As principais causas de óbito foram relacionadas ao choque por queimaduras, com 63,16%. Conclusões: Existe uma relação estritamente proporcional que a idade mais elevada (principalmente com 60 anos ou mais) e porcentagem de SCQ acima de 40 aumentam a possibilidade de complicações e morte em pacientes queimados, evidenciando-se a necessidade de campanhas preventivas e de promoção da saúde, o que pode ser feito por meio dos meios de comunicação de massa (televisão, rádio, internet), centros de trabalho e educação, comunidade e centros de saúde.

Objective: To identify the characteristics of patients admitted for burns and who died. Methods: A descriptive, cross and retrospective study was carried out in the Department of Plastic Surgery and Burns of the Provincial Clinical Surgical Hospital "Celia Sánchez Manduley", in Manzanillo, Granma, Cuba, from January 2015 to December 2017. Nineteen burned patients who died were included in the sample. Results: Of a total of 224 patients hospitalized for burns, 91.52% presented a satisfactory evolution and only 8.48% died. The female sex presented a greater frequency of deceased patients, with 78.98%, and includes the age group of 60 to 74 years, with 31.58%. The frequency of mortality was higher in patients with intentional burns, with 63.16%. The highest number of burn deaths was in the group of 81-90% burned body surface (BBS), with 31.58%. The main causes of death were related to the burn shock, with 63.16%. Conclusions: A strictly proportional relation exists than to higher ages (especially 60 years-old or more) and percent of BBS higher of 40, are the main possibilities of complications and death in burnt patients. The need for preventive campaigns and health promotion was evidenced, which can be done by the mass media (TV, radio, internet), work and education centers, community and health centers.

Objetivo: Describir las características de los pacientes ingresados por quemaduras y que egresaron fallecidas. Método: Se realizó un estudio descriptivo, transversal y retrospectivo en el Departamento de Cirugía Plástica y Quemaduras del Hospital Provincial Clínico Quirúrgico "Celia Sánchez Manduley", en Manzanillo, Granma, Cuba, en el período de enero de 2015 a diciembre de 2017. Se incluyeron registros de 19 pacientes quemados fallecidos hospitalizados Resultados: De un total de 224 pacientes internados por quemaduras fueron dados de alta con evolución satisfactoria el 91,52% y apenas murieron 8,48%. El sexo femenino presentó mayor frecuencia de pacientes falecidos, con 78,98%, y entre ellos el grupo de edad de 60 a 74 años, con 31,58%. La frecuencia de mortalidad fue mayor en los pacientes con quemaduras intencionales, con 63,16%. El mayor número de muertes por quemaduras fue en el grupo con 81- 90% superficie corporal quemada (SCQ), con 31,58%. Las principales causas de muerte fueron relacionadas con el choque por quemaduras, con el 63,16%. Conclusiones: Existe una relación estrictamente proporcional que a mayor edades (principalmente edades de 60 años o más) y porciento de superficie corporal quemada mayor de 40, mayor posibilidades de complicaciones y muerte en pacientes quemados, se evidenció la necesidad de campañas preventivas y de promoción de la salud, lo que puede ser realizado a través de los medios de comunicación masiva (televisión, radio, internet), centros de trabajo y educación, comunidad y centros de salud.

Hydatid cyst of the gallbaldder: A systematic review of the literature.

AIM: To evaluate all the references about primary gallbladder hidatidosis looking for best treatment evidence. METHODS: Search: 1966-2015 in MEDLINE, Cochrane Library, SciELO, and Tripdatabase. KEY WORDS: "gallabladder hydatid disease" and "gallbladder hydatid cyst". We found 124 papers in our searches but only 14 papers including 16 cases were about hydatid cyst of the gallbladder (GBHC). RESULTS: Eight cases of GBHC were women and seven men. One not mentioned. Median age was 48.3 years. The most frequent clinical symptom was abdominal pain (94%) usually in the right upper quadrant. Ultrasound was performed in ten patients (62.5%) but in most cases a combination of several techniques was performed. The location of the cysts was intravesicular in five patients. Five patients presented GBHC and liver hydatid cysts. Two patients presented cholelithiasis and one choledocholithiasis. The most frequent surgical technique was cholecystectomy by laparotomy (81.25%). Simultaneous surgery of liver cysts was carried out in five cases. Eleven patients did not present postoperative complications, but one died. The mean hospital stay was seven days. No recurrence of GBHC was recorded. CONCLUSION: In GBHC, the most frequent symptom is right hypocondrium pain (evidence level V). Best diagnostic methods are ultrasound and computed tomography (level V, grade D). Suggested treatment is open cholecystectomy and postoperative albendazole (level V, grade D) obtaining good clinical results and none relapses.

The effector AWR5 from the plant pathogen Ralstonia solanacearum is an inhibitor of the TOR signalling pathway.

Bacterial pathogens possess complex type III effector (T3E) repertoires that are translocated inside the host cells to cause disease. However, only a minor proportion of these effectors have been assigned a function. Here, we show that the T3E AWR5 from the phytopathogen Ralstonia solanacearum is an inhibitor of TOR, a central regulator in eukaryotes that controls the switch between cell growth and stress responses in response to nutrient availability. Heterologous expression of AWR5 in yeast caused growth inhibition and autophagy induction coupled to massive transcriptomic changes, unmistakably reminiscent of TOR inhibition by rapamycin or nitrogen starvation. Detailed genetic analysis of these phenotypes in yeast, including suppression of AWR5-induced toxicity by mutation of CDC55 and TPD3, encoding regulatory subunits of the PP2A phosphatase, indicated that AWR5 might exert its function by directly or indirectly inhibiting the TOR pathway upstream PP2A. We present evidence in planta that this T3E caused a decrease in TOR-regulated plant nitrate reductase activity and also that normal levels of TOR and the Cdc55 homologues in plants are required for R. solanacearum virulence. Our results suggest that the TOR pathway is a bona fide T3E target and further prove that yeast is a useful platform for T3E function characterisation.

Caracterización clínica epidemiológica de las quemaduras del adulto mayor ingresado en el Hospital Celia Sánchez / Clinical Epidemiological Description of Burns in the Elderly Admitted to the Celia Sánchez Hospital

Introducción: las quemaduras constituyen una causa frecuente de lesión en el adulto mayor, pues es una etapa de la vida del individuo en la cual se pierde progresivamente la capacidad de adaptación y la aptitud de reaccionar adecuadamente a los cambios. Objetivo: caracterizar el comportamiento clínico epidemiológico de las quemaduras en el adulto mayor ingresado en el Hospital Provincial Clínico Quirúrgico Docente Celia Sánchez Manduley de 2009 al 2011. Métodos: se realizó un estudio descriptivo transversal cuyo universo de estudio se conformó por 23 pacientes adultos mayores quemados, los cuales fueron atendidos de forma hospitalizada. Se evaluaron las variables: edad, sexo, modo de producción, agente etiológico, pronóstico de vida según clasificación cubana y el estado al egreso de los pacientes. Resultados: el sexo femenino con el 52,17 % y el grupo de edades de 60 a 69 años con 47,83 % predominaron en los ingresos, además fue más frecuente los accidentes con el 52,17 % principalmente el sexo masculino con 34,79 %. Los líquidos calientes o hirvientes e inflamados fueron los agentes etiológicos. Los clasificados como leves, menos graves, graves y muy graves tuvieron una supervivencia del 100 %. Conclusiones: los accidentes por líquidos calientes o inflamados constituyeron las principales causas de ingreso hospitalario por quemaduras en adultos mayores. Se logró una elevada supervivencia.

Introduction: burns are a common cause of injury in the elderly, as it is a stage of life in which the individual progressively loses resilience and ability to react adequately to changes. Objective: to describe the clinical epidemiologic behavior of burns in the elderly hospitalized at Celia Sánchez Hospital between 2009 -2011. Method: a cross-sectional study whose study universe was formed by 23 elderly burned patients, who were treated in a hospital was performed. The variables age, sex, way of production, etiologic agent, prognosis of Cuban life as classification and discharge status of patients were evaluated. Results: the female sex with the 52.17 % and the age group between 60 and 69 years with 47.83 % predominated in revenue for burns; besides the accidents was more frequent with 52.17 % mainly the male sex with 34.79 %. Hot liquids and or boiling (56.52 %) were the etiological agent. and those classified like slight, less severe, severe and very severe had a 100 % of survival. Conclusions: accidents by liquid hot or inflamed were the main causes of hospitalization for burns in older adults. High survival was achieved.

Cytogenetic studies of three Lycosidae species from Argentina (Arachnida, Araneae)

Cytogenetic studies of the family Lycosidae (Arachnida: Araneae) are scarce. Less than 4% of the described species have been analyzed and the male haploid chromosome numbers ranged from 8+X1 X 2 to 13+X1 X 2. Species formerly classified as Lycosa were the most studied ones. Our aim in this work was to perform a comparative analysis of the meiosis in "Lycosa" erythrognatha Lucas, "Lycosa" pampeana Holmberg and Schizocosa malitiosa (Tullgren). We also compared male and female karyotypes and characterized the heterochromatin of "L." erythrognatha. The males of the three species had 2n = 22, n = 10+X1X2, all the chromosomes were telocentric and there was generally a single chiasma per bivalent. In "Lycosa" pampeana, which is described cytogenetically for the first time herein, the bivalents and sex chromosomes showed a clustered arrangement at prometaphase I. The comparison of the male/female karyotypes (2n = 22/24) of "Lycosa" erythrognatha revealed that the sex chromosomes were the largest of the complement and that the autosomes decreased gradually in size. The analysis of the amount, composition and distribution of heterochromatin with C-banding and staining with DAPI- and CMA3 - showed that "Lycosa" erythrognatha had little GC-rich heterochromatin in the pericentromeric region of all chromosomes. In addition, the actual occurrence of the genus Lycosa in the Southern Hemisphere is discussed.

Cistadenoma de pâncreas / Pancreatic cystadenomes

Os autores apresentam dois casos de cistadenomas de pâncreas, considerados tumores raros, discutindo seus aspectos clínicos, diagnósticos e terapêuticos