NME1 and DCC variants are associated with susceptibility and tumor characteristics in Mexican patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) ranks third in cancer incidence globally and is the second leading cause of cancer-related mortality. The nucleoside diphosphate kinase 1 (NME1) and netrin 1 receptor (DCC) genes have been associated with resistance against tumorigenesis and tumor metastasis. This study investigates the potential association between NME1 (rs34214448 G > T and rs2302254 C > T) and DCC (rs2229080 G > C and rs714 A > G) variants and susceptibility to colorectal cancer development. METHODS: Samples from 232 colorectal cancer patients and 232 healthy blood donors underwent analysis. Variants were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Associations were assessed using odds ratios (OR), and the p values were adjusted with Bonferroni test. RESULTS: Individuals carrying the G/T and T/T genotypes for the NME1 rs34214448 variant exhibited a higher susceptibility for develop colorectal cancer (OR = 2.68, 95% CI: 1.76-4.09, P = 0.001 and OR = 2.47, 95% CI: 1.37-4.47, P = 0.001, respectively). These genotypes showed significant associations in patients over 50 years (OR = 2.87, 95% CI: 1.81-4.54, P = 0.001 and OR = 2.99, 95% CI: 1.54-5.79, P = 0.001 respectively) and with early Tumor-Nodule-Metastasis (TNM) stage (P = 0.001), and tumor location in the rectum (P = 0.001). Furthermore, the DCC rs2229080 variant revealed that carriers of the G/C genotype had an increased risk for develop colorectal cancer (OR = 2.00, 95% CI: 1.28-3.11, P = 0.002) and were associated with age over 50 years, sex, and advanced TNM stages (P = 0.001). CONCLUSIONS: These findings suggest that the NME1 rs34214448 and DCC rs2229080 variants play a significant role in colorectal cancer development.

Expression of ornithine decarboxylase in peripheral blood mononuclear cells from patients with pancreatic adenocarcinoma: A preliminary report.

Ductal adenocarcinoma represents 90-95% of pancreatic cancer (PC) cases and it is an aggressive disease with asymptomatic evolution at early stages, non-specific symptoms and a typical late diagnosis with a 5-year survival rate estimated to be 8%. A window of opportunity lies in early diagnosis as there are currently no reliable biomarkers. CA 19-9 is one of the most frequently used biomarkers of PC, with 75 and 77.6% sensitivity (Se) and specificity (Sp), respectively, and the carcinoembryonic antigen (CEA) shows 39.5 and 81.3% of Se and Sp, respectively. A case-control study was conducted including adult patients with a histological diagnosis of PC (n=11) without previous treatment at the Oncology Service of the CMNO-IMSS between 2019 and 2020, and a control group of adult volunteers (n=11) who were clinically healthy or with controlled disease including hypertension, hypothyroidism and diabetes. Clinical, laboratory and sociodemographic data as well as blood, urine and saliva samples were collected following patient consent. Polyamines were quantified using high-performance liquid chromatography with fluorescence detection, CA 19-9 and CEA were evaluated using enzyme-linked immunosorbent assay, and the protein expression of ornithine decarboxylase (ODC) was evaluated using western blotting. Polyamine metabolism and modulation by means of ODC were increased in the serum and saliva of patients with PC, and the expression of ODC alone was increased in peripheral blood mononuclear cells (PBMCs). The present study focused on the evaluation of putrescine, spermine, spermidine and ODC in PBMCs associated with CA 19-9 and CEA as an auxiliary tool in PC diagnosis.

Entrenamiento de Habilidades Sociales y estrese en la universidad: un estudio de caso / Treinamento de habilidades sociais e estresse na universidade: um estudo de caso / Social skills training and stress at the university: a case study

A aplicação do Treinamento de Habilidades Sociais no contexto universitário pode ser eficaz para a redução do estresse percebido pelos estudantes. Assim, o objetivo do presente artigo foi descrever, no formato de um estudo de caso único, o processo terapêutico de um Treinamento de Habilidades Sociais realizado com uma estudante de Psicologia, apresentando dados referentes à eficácia da intervenção. As avaliações pré e pós-teste foram feitas com os seguintes instrumentos: Inventário de Habilidades Sociais 2 (IHS2-Del-Prette), Escala de Estresse Percebido (PSS-14), entrevistas e diário de campo. Contatou-se o aprimoramento de habilidades sociais como recusar e fazer pedidos, lidar com críticas e expor desagrado e solicitar mudança de comportamento do outro, e redução dos níveis de estresse com base em dados qualitativos e quantitativos, com manutenção desses resultados no follow-up de seis semanas. Concluiu-se que o Treinamento de Habilidades Sociais realizado possibilitou a melhora da experiência na universidade para a participante.

La aplicación del entrenamiento de Habilidades Sociales en el contexto universitario puede ser eficaz para la disminución del estrese percibido por los estudiantes. Delante eso, el objetivo del presente artículo fue describir, en el molde de un estudio de caso único, el proceso terapéutico de un entrenamiento de Habilidades Sociales realizado con una estudiante de Psicología, que presentaba, también, datos referentes a la eficacia de la intervención. Las evaluaciones antes y e después de la prueba se hicieron con los siguientes instrumentos: Inventario de Habilidades Sociales 2 (IHS2-Del-Prette), Escala de Estrese Percibido (PSS-14), entrevistas y diario de campo. Fue posible constatar el perfeccionamiento de habilidades sociales como recusar y hacer pedidos, lidiar con críticas y exponer desagrado y solicitar cambio de comportamiento del otro, y reducción de los niveles de estrese con base en datos cualitativos y cuantitativos, con manutención de esos resultados en elfollow-upde seis semanas. Se concluye que el Entrenamiento de Habilidades Sociales realizado posibilitó la mejora de la experiencia en la universidad para la participante.

The application of Social Skills Training in the university context can be effective in reducing the stress perceived by students. Therefore, the objective of this article was to describe, in the format of a single case study, the therapeutic process of a Social Skills Training carried out with a Psychology student, also presenting data regarding the effectiveness of the intervention. Pre- and post-test assessments were performed using the following instruments: Social Skills Inventory 2 (IHS2-Del-Prette), Perceived Stress Scale (PSS-14), interviews and field diary. It was possible to verify the improvement of social skills such as refusing and making requests, dealing with criticism and exposing displeasure and requesting a change in the other's behavior, and reduction of stress levels based on qualitative and quantitative data, with maintenance of these results in the follow-up of six weeks. It was concluded that the Social Skills Training carried out enabled the participant to improve her university experience.

Extracellular Vesicles Contribute to the Difference in Lipid Composition between Ovarian Follicles of Different Size Revealed by Mass Spectrometry Imaging.

Follicular fluid (FF) ensures a safe environment for oocyte growth and maturation inside the ovarian follicle in mammals. In each cycle, the large dominant follicle (LF) contains the oocyte designated to be ovulated, whereas the small subordinate follicles (SFs) of the same wave will die through atresia. In cows, the oocytes from the SF, being 2 mm in size, are suitable for in vitro reproduction biotechnologies, and their competence in developing an embryo depends on the size of the follicles. FF contains proteins, metabolites, fatty acids, and a multitude of extracellular vesicles (ffEVs) of different origins, which may influence oocyte competence through bidirectional exchanges of specific molecular cargo between follicular cells and enclosed oocytes. FF composition evolves along with follicle growth, and the abundance of different lipids varies between the LF and SF. Here, significant differences in FF lipid content between the LFs and SFs within the same ovary were demonstrated by MALD-TOF mass spectrometry imaging on bovine ovarian sections. We then aimed to enlighten the lipid composition of FF, and MALDI-TOF lipid profiling was performed on cellular, vesicular, and liquid fractions of FF. Differential analyses on the abundance of detected lipid features revealed specific enrichment of phospholipids in different ffEV types, such as microvesicles (MVs) and exosomes (Exo), compared to depleted FF. MALDI-TOF lipid profiling on MVs and Exo from the LF and SF samples (n = 24) revealed that more than 40% of detected features were differentially abundant between the groups of MVs and Exo from the different follicles (p < 0.01, fold change > 2). Glycerophospholipid and sphingolipid features were more abundant in ffEVs from the SFs, whereas different lysophospholipids, including phosphatidylinositols, were more abundant in the LFs. As determined by functional analysis, the specific lipid composition of ffEVs suggested the involvement of vesicular lipids in cell signaling pathways and largely contributed to the differentiation of the dominant and subordinate follicles.

Validação do protocolo de terapia familiar aplicado à saúde mental (PTF-SM1) / Validation of the family therapy protocol applied to mental health (PTF-SM1) / Validación del protocolo de terapia familiar aplicado a la salud mental (PTF-SM1)

Objetivo: validar o conteúdo do PTF-SM1 por profissionais de saúde mental com experiência em terapia familiar. Método: estudo metodológico, descritivo e com abordagem quantitativa, que ocorreu de julho a agosto de 2019, com a participação de profissionais de saúde mental com experiência em terapia familiar. Verificou-se o grau de concordância entre os avaliadores pelo percentual de concordância (PC) e o Índice de Validade de Conteúdo (IVC). Resultados: obteve-se PC igual a 100,00% e IVC igual a 1,0, na avaliação do conteúdo e aparência do instrumento (PTF-SM1 e seu manual), quanto à representatividade, viabilidade, gramática, clareza, coerência, atualização, legibilidade, redação compatível aos profissionais, ao tamanho dos títulos e tópicos adequados, e operatividade para utilização nos serviços de saúde. Conclusão: o conteúdo do PTF-SM1 demonstrou-se adequado, conforme apontamentos dos avaliadores, tendo na versão final características de um instrumento possível de ser usado na prática clínica pelos profissionais de saúde mental.

Objective: to validate the content of the PTF-SM1 by mental health professionals with experience in family therapy. Method: methodological, quantitative, descriptive study carried out from July to August 2019, with the participation of mental health professionals with experience in family therapy. The degree of agreement between the evaluators was determined using the percentage of agreement (PC) and the Content Validity Index (CVI). Results: PC equal to 100.00% and CVI equal to 1.0 were obtained, in the evaluation of the content and appearance of the instrument (PTF-SM1 and its manual), regarding representativeness, feasibility, grammar, clarity, coherence, updating, readability, writing compatible with professionals, size of titles and appropriate topics, and operability for use in health services. Conclusion: the content of the PTF-SM1 proved to be adequate, according to the evaluators' scores, with the final version having characteristics of an instrument that can be used in clinical practice by mental health professionals.

The bovine uterine fluid proteome is more impacted by the stage of the estrous cycle than the proximity of the ovulating ovary in the periconception period.

Uterine secretions provide a suitable environment for sperm selective migration during a couple of days preceding ovulation and for early embryo development before implantation. Our goal was to identify and quantify proteins in the bovine uterine fluid during the periovulatory period of the estrous cycle. Genital tracts with normal morphology were collected from adult cyclic Bos taurus females in a local slaughterhouse and classified into pre-ovulatory or post-ovulatory stages of cycle (around days 19-21 and 0-5 of cycle, respectively; n = 8 cows per stage) based on ovarian morphology. Proteins from uterine fluid collected from the utero-tubal junction to the base of each horn (four pools of two cows per condition) were analyzed by nanoLiquid Chromatography coupled with tandem Mass Spectrometry (nanoLC-MS/MS). A total of 1214 proteins were identified, of which 91% were shared between all conditions. Overall, 57% of proteins were predicted to be secreted and 17% were previously reported in uterine extracellular vesicles. Paired comparisons between uterine horns ipsilateral and contralateral to ovulation evidenced 12 differentially abundant proteins, including five at pre-ovulatory stage. Furthermore, 35 proteins differed in abundance between pre- and post-ovulatory stages, including 21 in the ipsilateral side of ovulation. Functional analysis of identified proteins demonstrated roles in binding, metabolism, cellular detoxification and the immune response. This study provides a valuable database of uterine proteins for functional studies on sperm physiology and early embryo development.

Functional Variants in MicroRNAs (rs895819, rs11614913 and rs2910164) Are Associated with Susceptibility and Clinicopathological Features in Mexican Patients with Colorectal Cancer.

BACKGROUND: miRNAs are non-coding RNAs participating actively in the post-translational regulation of oncogenes, tumor suppressor, and DNA repair genes implicated in colorectal cancer (CRC). This study aims to examine the association of the variants miR-27a (rs895819 A>G), miR-196a2 (rs11614913 T>G) and miR-146a (rs2910164 C>G) in Mexican CRC patients. METHODS: DNA samples from 183 patients and 186 healthy Mexican subjects were analyzed. Variants were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) and adjusted by the Bonferroni test. RESULTS: Patients carrying the G/G genotype of the rs895819 variant in the miR-27a gene showed an increased risk of CRC (19% vs 12%, P=0.013). A similar tendency was noticed for patients younger than 50 years carrying A/G (48% vs 41%, P=0.014). The A/G genotype in TNM stages I+II (55.7% vs 40.8%, P=0.011) and tumor location in the colon (69.5 vs 40.8%, P=0.001) were also increased. For the variant rs11614913 of the miR-196a2 gene, carriers of the C/C genotype showed an increased risk of CRC (32% vs 22%, P=0.009). This genotype was more frequent in TNM stage III+IV (36.8% vs 22.5%, P=0.007) and the tumor had a more recurrent location in the rectum (31.6% vs 22.5%, P=0.013). The rs2910164 variant of the miR-146a gene was found to have no significant risk associations. CONCLUSION: Our results reveal that the rs895819 variant in miR-27a and rs11614913 in miR-196a2 have a substantial impact on the development of CRC.

Circulating cell-free-DNA concentration is a good biomarker for diagnosis of colorectal cancer in Mexican patients.

Colorectal cancer (CRC) is the third most common cancer in the world. Overall survival is related to clinical stage: more advanced stages show lower survival rates; therefore, they need to be monitored regularly with new, less invasive and more specific biomarkers. The concentration and integrity index of circulating cell-free DNA (ccfDNA) have been proposed as potential diagnostic and prognostic biomarkers for CRC, however, inconsistent results are still observed in different reports. Here we analyze these potential CRC biomarkers in a Mexican population. In this study, 124 patients with sporadic CRC and 37 healthy individuals were examined as a reference group. The ccfDNA was isolated from plasma samples of all included subjects. The ccfDNA concentration was determined by fluorometry and the integrity index (ALU247/ALU115 ratio) by quantitative PCR amplification (qPCR) of ALU sequences. The results show that ccfDNA concentration was higher in CRC patients than in the reference group (P=0.001). The integrity index showed no significant differences between these groups (P=0.258), except for histological type (P=0.012). A higher ccfDNA concentration was also associated with patients younger than 50 years (P=0.030). The ccfDNA concentration showed significant discriminatory power (AUC: 0.854, C.I.: 0.78-0.92, P=0.001) between patients and the reference group and between tumor-node-metastasis (TNM) stages. In conclusion, ccfDNA concentration proves to be a good diagnostic biomarker for CRC patients, whereas the integrity index did not show diagnostic utility.

Treinamento de habilidades sociais na promoção do Coping eficaz: um estudo piloto / Social skills training in the promotion of effective Coping: a pilot trial / Entrenamiento de habilidades sociais en la promoción del coping eficaz: un estudio piloto

Esta pesquisa teve como objetivo avaliar a eficácia de um Treinamento de Habilidades Sociais (THS) na ampliação das habilidades sociais, na redução do estresse e no desenvolvimento do coping eficaz de oito estudantes de Psicologia. As participantes foram recrutadas via link de um formulário enviado nas redes sociais e por contato telefônico, sendo voluntariamente submetidas à intervenção na universidade onde estudavam. A intervenção análoga a um quase experimento teve avaliações pré e pós-teste sem grupo controle, utilizando-se os instrumentos Inventário de Habilidades Sociais 2 (IHS2-Del-Prette), Escala de Estresse Percebido (PSS-14), Inventário de Estratégias de Coping de Folkman e Lazarus, entrevistas e diário de campo. Os resultados indicaram redução do estresse, aquisição de habilidades sociais e potencialização da estratégia de resolução de problemas. Sugere-se, para estudos futuros, a avaliação da eficácia do THS em amostras maiores e mais heterogêneas de estudantes universitários.

This research aimed to evaluate the efficacy of a Social Skills Training (SST) in increasing social skills, reducing stress levels, and developing effective coping of eight female undergraduate Psychology students. The participants were recruited through a form sent on social media and telephone contact and were voluntarily submitted to the intervention at the university in which they studied. The intervention, analogous to a quasi-experiment, had pre- and posttest evaluations without a control group, using the instruments Social Skills Inventory 2 (IHS2-Del-Prette), Perceived Stress Scale (PSS14), Folkman and Lazarus' Coping Strategies Inventory, interviews, and a field diary. The results indicated stress reduction, acquisition of social skills, and enhancement of problem-solving strategies. Further studies regarding the evaluation of the SST's efficacy in a larger and more heterogeneous sample of university students would be worthwhile.

El objetivo de la investigación fue evaluar la eficacia de un Entrenamiento de Habilidades Sociales (EHS) en la expansión de las habilidades sociales, reducción del estrés y desarrollo de un coping eficaz de ocho estudiantes de Psicología. Las participantes fueron reclutadas por medio de un link para un formulario enviado en redes sociales y contacto telefónico, siendo voluntariamente sometidos a la intervención en la universidad donde estudiaban. La intervención análoga a un casi-experimento tuvo evaluaciones previas y posteriores a la experiencia, sin un grupo de control, utilizando los instrumentos Inventario de Habilidades Sociales 2 (IHS2-Del-Prette), Escala de Estrés Percibido (PSS-14), Inventario de Estrategias de Coping de Folkman y Lazarus, entrevistas y diario de campo. Los resultados indicaron reducción del estrés, adquisición de habilidades sociales y potencialización de estrategias para resolución de problemas. Se sugiere, para futuros estudios, la evaluación de la eficacia del EHS en muestras mayores y más heterogéneas de estudiantes universitarios.

Multifaceted roles of the egg perivitelline layer in avian reproduction: Functional insights from the proteomes of chicken egg inner and outer sublayers.

The avian egg perivitelline layer (PL) is a proteinaceous structure that encloses the egg yolk. It consists of the inner and the outer perivitelline layers (IPL and OPL, respectively) that are assumed to play distinct roles in bird reproduction. To gain insight into their respective function, we analyzed the proteome of IPL and OPL in chicken unfertilized eggs after mechanical separation, using a GeLC-MS/MS strategy. Of the 412 proteins identified, 173 proteins were uniquely recovered in IPL and 98 proteins in OPL, while 141 proteins were identified in both sublayers. Genes coding the most abundant proteins were shown to be expressed either in the liver/ovary (IPL formation) or in the oviduct (OPL formation), but rarely in both. The presence of oviduct-specific proteins (including LYZ, VMO1, AvBD11, PTN, OVAL and LOC10175704) in IPL strongly suggests that they participate in the physical association of IPL to OPL, whose tight attachment was further evidenced by analyses of IPL/OPL interfaces (by scanning electron microscopy). Functional annotation of identified proteins revealed functions associated with fertilization and early development for IPL, while OPL would rather participate in egg defense and embryogenesis. Collectively, our data highlight the complementary functions of IPL and OPL that are major determinants of bird reproductive success. SIGNIFICANCE: The present study unveils for the first time the individual proteomes of the two sublayers composing the chicken egg perivitelline layer (PL), which allowed to assign their respective putative biological roles in avian reproduction. The combination of proteomics with gene expression and ultrastructural analyses provides insightful data on the structure and biochemistry of the avian PL. The functional annotation of PL proteins highlights the multifaceted biological functions of this structure in reproduction including fertilization, embryonic development, and antimicrobial protection. This work will stimulate further research to validate predicted functions and to compare the physiology and the functional specificities of PL in egg-laying species.

MKK4 variants rs3826392 and rs3809728 are associated with susceptibility and clinicopathological features in colorectal cancer patients.

OBJECTIVES: The mitogen-activated protein kinase kinase 4 (MKK4) plays a key role in several processes like inflammation, apoptosis, and tumorigenesis. Several authors have proposed that genetic variations in these genes may alter their expression with subsequent cancer risk. This study aimed to examine the possible association of MKK4 rs3826392 and rs3809728 variants in Mexican patients with colorectal cancer (CRC). These variants were also compared with clinical features as sex, age, TNM stage, and tumor location. MATERIALS AND METHODS: The study included genomic DNA from 218 control subjects and 250 patients. Genotyping of the MKK4 variants was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) procedure. RESULTS: Individuals with A/T and T/T genotypes for the rs3809728 (-1044 A>T) variant showed a significantly increased risk for CRC (P=0.012 and 0.007, respectively); while individuals with the G/G genotype for the rs3826392 (-1304 T>G) variant showed a decreased risk for CRC (P=0.012). Genotypes of the MKK4 rs3809728 variant were also significantly related to colon localization and advanced TNM stage in CRC patients. T-T haplotype (rs3826392 and rs3809728) of the MKK4 gene was associated with risk in patients with CRC. CONCLUSION: The rs3826392 variant in the MKK4 gene could be a cancer protective factor, while the rs3809728 variant could be a risk factor. These variants play a significant role in CRC risk.

Use of MALDI-TOF mass spectrometry to explore the peptidome and proteome of in-vitro produced bovine embryos pre-exposed to oviduct fluid.

In order to identify oviduct fluid (OF) peptides and proteins possibly uptaken by developing embryos, in-vitro produced bovine embryos exposed or not to OF were individually analyzed by MALDI-TOF mass spectrometry. Overall, 11 masses were overabundant in OF-treated embryos compared to controls, among which one at 8.9 kDa annotated as immediate early response 3-interacting protein 1 or a peptide of transitional endoplasmic reticulum ATPase met the criteria of an OF embryo-interacting protein or peptide.

Proteomic Changes Associated With Sperm Fertilizing Ability in Meat-Type Roosters.

The molecular basis of male fertility remains unclear, especially in chickens, where decades of genetic selection increased male fertility variability as a side effect. As transcription and translation are highly limited in sperm, proteins are key molecules defining their functionality, making proteomic approaches one of the most adequate methods to investigate sperm capacity. In this context, it is interesting to combine complementary proteomic approaches to maximize the identification of proteins related to sperm-fertilizing ability. In the present study, we aimed at identifying proteins related to fertility in meat-type roosters, showing fertility variability. Fertile roosters (fertility rates higher than 70% after artificial insemination) differed from subfertile roosters (fertility rates lower than 40%) in their sperm mass motility. Fertile and subfertile sperm protein contents were compared using two complementary label-free quantitative proteomic methods: Intact Cell MALDI-TOF-Mass Spectrometry and GeLC-MS/MS. Combining the two strategies, 57 proteins were identified as differentially abundant. Most of them were described for the first time as differentially abundant according to fertility in this species. These proteins were involved in various molecular pathways including flagellum integrity and movement, mitochondrial functions, sperm maturation, and storage in female tract as well as oocyte-sperm interaction. Collectively, our data improved our understanding of chicken sperm biology by revealing new actors involved in the complexity of male fertility that depends on multiple cell functions to reach optimal rates. This explains the inability of reductionist in vitro fertility testing in predicting male fertility and suggests that the use of a combination of markers is a promising approach.

Letalidade e características dos óbitos por COVID-19 em Rondônia: estudo observacional / Letalidad y características de los óbitos debidos a COVID-19 en Rondônia: un estudio observacional / Lethality and characteristics of deaths due to COVID-19 in Rondônia: an observational study

Objetivo: Descrever as características dos óbitos por COVID-19 no estado de Rondônia. Métodos: Estudo descritivo, com dados do Sistema Estratégia de Informatização do Sistema Único de Saúde Vigilância Epidemiológica (E-SUS-VE), notificados entre 1º de janeiro e 20 de agosto de 2020. Foram aplicados testes estatísticos (qui-quadrado e procedimento de Marascuilo), considerando-se como diferenças significantes quando os testes apresentaram p-valor <0,05. Resultados: Foram notificados 184.146 casos suspeitos, dos quais 49.804 foram confirmados como COVID-19, e 1.020 evoluíram para óbito (letalidade 2,1%). Observaram-se diferenças significantes estatisticamente entre as faixas etárias e a letalidade (p-valor <0,001); maior letalidade quanto maior a idade (procedimento de Marascuilo, significativo na comparação entre maiores de 60 anos com as demais faixas etárias); maior óbito no sexo masculino (letalidade de 2,7%); e maior letalidade entre as pessoas de cor preta (3,0%). Conclusão: Em Rondônia, observou-se maior letalidade entre idosos, homens e pessoas pardas e pretas.

Objetivo: Describir las características de los óbitos debidos a COVID-19 en Rondônia. Métodos: Estudio descriptivo, con datos del Sistema de Estrategia de Computación del Sistema Unificado de Salud de Vigilancia Epidemiológica (E-SUS-VE), notificados entre el 1 de enero y el 20 de agosto de 2020. Se aplicaron pruebas estadísticas (procedimiento Chi-cuadrado y Marascuilo), considerando significativas cuando las pruebas presentaron valor p<0,05. Resultados: se notificaron 184.146 casos sospechosos, con 49.804 confirmados como COVID-19 y 1.020 muertes (letalidad 2,1%). Se observaron diferencias estadísticamente significativas entre grupos de edad y letalidad (valor p <0,001); a mayor edad mayor letalidad (procedimiento de Marascuilo, significativo en la comparación entre mayores de 60 años con los otros grupos de edad); mayor óbito en el sexo masculino (letalidad del 2,7%); y mayor letalidad entre la raza negra (3,0%). Conclusión: En Rondônia, hubo una mayor letalidad entre los adultos mayores, hombres y pardos y negros.

Objective: To describe the characteristics of deaths due to COVID-19 in the state of Rondônia. Methods: This was a descriptive study, with data from the Brazilian National Health System Epidemiological Surveillance System Computerization Strategy (E-SUS-VE, notified between January 1 and August 20, 2020. Statistical tests (Chi-square and Marascuilo procedure) were applied, where differences were considered to be significant when p< 0.05. Results 184,146 suspected cases were reported, of which 49,804 were confirmed as COVID-19, and 1,020 died (lethality 2.1%). Statistically significant differences were observed between age groups and lethality (p-value <0.001); lethality was greater as age increased (Marascuilo procedure, significant in the comparison between the over 60s and the other age groups); death was higher among males (2.7% lethality); and lethality was higher among Black people (3.0%). Conclusion: Lethality was greater among the elderly, males and people of brown and black skin color in Rondônia.

Lethality and characteristics of deaths due to COVID-19 in Rondônia: an observational study. / Letalidade e características dos óbitos por COVID-19 em Rondônia: estudo observacional.

OBJECTIVE: To describe the characteristics of deaths due to COVID-19 in the state of Rondônia. METHODS: This was a descriptive study, with data from the Brazilian National Health System Epidemiological Surveillance System Computerization Strategy (E-SUS-VE, notified between January 1 and August 20, 2020. Statistical tests (Chi-square and Marascuilo procedure) were applied, where differences were considered to be significant when p< 0.05. RESULTS: 184,146 suspected cases were reported, of which 49,804 were confirmed as COVID-19, and 1,020 died (lethality 2.1%). Statistically significant differences were observed between age groups and lethality (p-value <0.001); lethality was greater as age increased (Marascuilo procedure, significant in the comparison between the over 60s and the other age groups); death was higher among males (2.7% lethality); and lethality was higher among Black people (3.0%). CONCLUSION: Lethality was greater among the elderly, males and people of brown and black skin color in Rondônia.

Acute pathophysiological myocardial changes following intra-cardiac electrical shocks using a proteomic approach in a sheep model.

Implantable cardioverter-defibrillators (ICD) are meant to fight life-threatening ventricular arrhythmias and reduce overall mortality. Ironically, life-saving shocks themselves have been shown to be independently associated with an increased mortality. We sought to identify myocardial changes at the protein level immediately after ICD electrical shocks using a proteomic approach. ICD were surgically implanted in 10 individuals of a healthy male sheep model: a control group (N = 5) without any shock delivery and a shock group (N = 5) with the delivery of 5 consecutive shocks at 41 J. Myocardial tissue samples were collected at the right-ventricle apex near to the lead coil and at the right ventricle basal free wall region. Global quantitative proteomics experiments on myocardial tissue samples were performed using mass spectrometry techniques. Proteome was significantly modified after electrical shock and several mechanisms were associated: protein, DNA and membrane damages due to extreme physical conditions induced by ICD-shock but also due to regulated cell death; metabolic remodeling; oxidative stress; calcium dysregulation; inflammation and fibrosis. These proteome modifications were seen in myocardium both "near" and "far" from electrical shock region. N-term acetylated troponin C was an interesting tissular biomarker, significantly decreased after electrical shock in the "far" region (AUC: 0.93). Our data support an acute shock-induced myocardial tissue injury which might be involved in acute paradoxical deleterious effects such as heart failure and ventricular arrhythmias.

Lethality and characteristics of deaths due to COVID-19 in Rondônia: an observational study / La letalidad y las características de las muertes debidas a COVID-19 en Rondônia: un estudio observacional / Letalidade e características dos óbitos por COVID-19 em Rondônia: estudo observacional

Objective: To describe the characteristics of deaths due to COVID-19 in the state of Rondônia. Methods: Descriptive study, with data from the Computerization Strategy System of the Unified Health System Epidemiological Surveillance (E-SUS-VE, notified between January 1 and August 20, 2020. Statistical tests (Chi-square and Marascuilo procedure) were applied, considering as significant differences when the tests presented p-value < 0.05. Results: 184,146 suspected cases were reported, of which 49,804 were confirmed as COVID-19, and 1,020 died (lethality 2.1%). Statistically significant differences were observed between age groups and lethality (p-value <0.001); higher lethality the older the age (Marascuilo procedure, significant in the comparison between over 60 years with the other age groups); higher death in males (lethality of 2.7%); and higher lethality among black people (3.0%). Conclusion: In Rondônia, there was greater lethality among the elderly, men and brown and black people.

Objetivo: Descrever as características dos óbitos por COVID-19 no estado de Rondônia. Métodos: Estudo descritivo, com dados do Sistema Estratégia de Informatização do Sistema Único de Saúde Vigilância Epidemiológica (E-SUS-VE), notificados entre 1º de janeiro e 20 de agosto de 2020. Foram aplicados testes estatísticos (Qui-Quadrado e procedimento de Marascuilo), considerando como diferenças significantes quando os testes apresentaram p-valor <0,05. Resultados: Foram notificados 184.146 casos suspeitos, dos quais 49.804 foram confirmados como COVID-19, e 1.020 evoluíram para óbito (letalidade 2,1%). Observou-se diferenças significantes estatisticamente entre as faixas etárias e letalidade (p-valor <0,001); maior letalidade quanto maior a idade (procedimento de Marascuilo, significativo na comparação entre maiores de 60 anos com as demais faixas etárias); maior óbito no sexo masculino (letalidade de 2,7%); e maior letalidade entre as pessoas de cor preta (3,0%).  Conclusão: Em Rondônia, observou-se maior letalidade entre idosos, homens e pessoas pardas e pretas.

Oviduct Fluid Extracellular Vesicles Change the Phospholipid Composition of Bovine Embryos Developed In Vitro.

Oviduct fluid extracellular vesicles (oEVs) have been proposed as bringing key molecules to the early developing embryo. In order to evaluate the changes induced by oEVs on embryo phospholipids, fresh bovine blastocysts developed in vitro in the presence or absence of oEVs were analyzed by intact cell MALDI-TOF (Matrix assisted laser desorption ionization-Time of flight) mass spectrometry (ICM-MS). The development rates, cryotolerance, and total cell number of blastocysts were also evaluated. The exposure to oEVs did not affect blastocyst yield or cryotolerance but modified the phospholipid content of blastocysts with specific changes before and after blastocoel expansion. The annotation of differential peaks due to oEV exposure evidenced a shift of embryo phospholipids toward more abundant phosphatidylcholines (PC), phosphatidylethanolamines (PE), and sphingomyelins (SM) with long-chain fatty acids. The lipidomic profiling of oEVs showed that 100% and 33% of the overabundant masses in blastocysts and expanded blastocysts, respectively, were also present in oEVs. In conclusion, this study provides the first analysis of the embryo lipidome regulated by oEVs. Exposure to oEVs induced significant changes in the phospholipid composition of resulting embryos, probably mediated by the incorporation of oEV-phospholipids into embryo membranes and by the modulation of the embryonic lipid metabolism by oEV molecular cargos.

CD44 Genotypes Are Associated with Susceptibility and Tumor Characteristics in Colorectal Cancer Patients.

Colorectal cancer is the third cause of cancer and the second leading cause of death worldwide. The CD44 gene plays a key role in malignant processes, including growth, survival, epithelial to mesenchymal transition and metastasis. It is also known that some variants as rs187116 (c.67+4883G>A) and rs7116432 (c.2024+779A>G) can modulate the function of the CD44 gene and malignant transformation in several neoplasms. This study aims to explore, for the first time, the association of the CD44 rs187116 and rs7116432 variants in patients with colorectal cancer. Genomic DNA from 250 patients and 250 healthy blood donors were analyzed. The identification of variants was made by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test and multivariate analysis. Individuals carrying the G/A and A/A genotypes for the rs187116 polymorphism showed an increased risk for colorectal cancer (OR = 3.11, 95% CI: 1.87-5.16, P = 0.001 and OR = 3.59, 95% CI: 2.06-6.25, P = 0.001, respectively). After adjusting for age and gender, these same genotypes and the G/G genotype of the rs7116432 polymorphism were associated with TNM stage and tumor location in the colon. Moreover, the A-G (rs187116 and rs7116432) haplotype was associated with increased risk; while, the haplotype G-A (rs187116 and rs7116432) was related with decreased risk. In conclusion, our results suggest that the here analyzed CD44 variants are involved with risk, TNM stage and tumor location in colorectal cancer.

Novel tacrine-benzofuran hybrids as potential multi-target drug candidates for the treatment of Alzheimer's Disease.

Pursuing the widespread interest on multi-target drugs to combat Alzheimer´s disease (AD), a new series of hybrids was designed and developed based on the repositioning of the well-known acetylcholinesterase (AChE) inhibitor, tacrine (TAC), by its coupling to benzofuran (BF) derivatives. The BF framework aims to endow the conjugate molecules with ability for inhibition of AChE (bimodal way) and of amyloid-beta peptide aggregation, besides providing metal (Fe, Cu) chelating ability and concomitant extra anti-oxidant activity, for the hybrids with hydroxyl substitution. The new TAC-BF conjugates showed very good activity for AChE inhibition (sub-micromolar range) and good capacity for the inhibition of self- and Cu-mediated Aß aggregation, with dependence on the linker size and substituent groups of each main moiety. Neuroprotective effects were also found for the compounds through viability assays of neuroblastoma cells, after Aß1-42 induced toxicity. Structure-activity relationship analysis provides insights on the best structural parameters, to take in consideration for future studies in view of potential applications in AD therapy.