Targeting Translation and the Cell Cycle Inversely Affects CTC Metabolism but Not Metastasis.

Melanoma brain metastasis (MBM) is significantly associated with poor prognosis and is diagnosed in 80% of patients at autopsy. Circulating tumor cells (CTCs) are "seeds" of metastasis and the smallest functional units of cancer. Our multilevel approach has previously identified a CTC RPL/RPS gene signature directly linked to MBM onset. We hypothesized that targeting ribogenesis prevents MBM/metastasis in CTC-derived xenografts. We treated parallel cohorts of MBM mice with FDA-approved protein translation inhibitor omacetaxine with or without CDK4/CDK6 inhibitor palbociclib, and monitored metastatic development and cell proliferation. Necropsies and IVIS imaging showed decreased MBM/extracranial metastasis in drug-treated mice, and RNA-Seq on mouse-blood-derived CTCs revealed downregulation of four RPL/RPS genes. However, mitochondrial stress tests and RT-qPCR showed that omacetaxine and palbociclib inversely affected glycolytic metabolism, demonstrating that dual targeting of cell translation/proliferation is critical to suppress plasticity in metastasis-competent CTCs. Equally relevant, we provide the first-ever functional metabolic characterization of patient-derived circulating neoplastic cells/CTCs.

Calidad de vida en pacientes con enfermedad de Pompe: estudio observacional / Quality of Life in Patients with Pompe Disease: Cross-Sectional Study

Introducción: La enfermedad de Pompe es una enfermedad genética multisistémica y rápidamente progresiva, que causa compromiso muscular (esquelético, cardíaco y liso), severa hipotonía y dificultad en la deglución. Debido a la naturaleza de la enfermedad, la calidad de vida de las personas que la padecen puede verse más afectada con respecto a la población general. Método: Se llevó a cabo un estudio descriptivo de corte transversal. Se diseñó un instrumento tipo encuesta con preguntas de caracterización sociodemográfica y referentes a la enfermedad. Para medir la calidad de vida se aplicó el Medical Outcomes Study 36-Item Short Form (SF-36) Questionnaire. Se hizo una comparación entre grupos, con nivel de significancia de 0,05. Resultados: Se obtuvieron encuestas de 27 pacientes de seis países. La edad media fue de 40,52 años, el 59 % fueron mujeres, el 51 % casados, el 63 % activos laboralmente, con edad media de diagnóstico de 30,3 años (SD = 15,557). La dimensión con menor media fue el rol físico (10,2; IC 95 % = 1,5-21,9), mientras que la de mayor media fue la salud mental (65,5; IC 95 % = 56,9-74,0). El 29,7 % (IC 95 % = 11,2-48,0) de los encuestados consideró sentirse en peores condiciones de salud que el año anterior. Discusión: Se evidencia una baja calidad de vida en pacientes con EP, en comparación con la población general, si se tienen en cuenta otros estudios que utilizan el mismo cuestionario. Conclusiones: Se evidencia una baja calidad de vida en los pacientes con enfermedad de Pompe participantes; las dimensiones asociadas con parámetros físicos fueron las de menores puntuaciones.

Introduction: Pompe disease is a rapidly progressive, multisystemic genetic disease that causes muscle involvement (skeletal, cardiac and smooth), severe hypotonia and difficulty in swallowing. Due to the nature of the disease, the quality of life may be more affected compared to the general population. Method: A descriptive cross-sectional study was carried out. A survey-type instrument was designed with questions of sociodemographic characterization and those referring to the disease. To measure Quality of Life, the Medical Outcomes Study 36-Item Short Form (SF-36) questionnaire was applied. A comparison was made between groups with a significance level of 0,05. Results: 27 surveys of patients from six countries were obtained. The mean age 40.52 years, women 59 %, married 51 %, 63 % active in employment, with a mean age of diagnosis of 30.3 years (SD = 15,557). The dimension with the lowest mean was the Physical Role (10.2; 95 % CI = 1.5 - 21.9), while the one with the highest mean was the Mental Health dimension (65.5; 95 % CI = 56.9 - 74.0). 29.7 % (95 % CI = 11.2 - 48.0) of those surveyed considered they felt in worse health conditions than the previous year. Discussion: Low quality of life is evidenced in patients with PD in comparison to the general population described in other studies using the same questionnaire. Conclusions: A low quality of life is evidenced in the study individuals where the dimensions related to the physical area were lower.

Clinical Efficacy of SARS-CoV-2 Vaccination in Hemodialysis Patients.

Introduction: The COVID-19 pandemic is a global public health problem. Patients with end-stage renal disease on hemodialysis are at a higher risk of infection and mortality than the general population. Worldwide, a vaccination campaign has been developed that has been shown to reduce severe infections and deaths in the general population. However, there are currently limited data on the clinical efficacy of vaccinations in the hemodialysis population. Methods: A national multicenter observational cohort was performed in Chile to evaluate the clinical efficacy of anti-SARS-CoV-2 vaccination in end-stage renal disease patients on chronic hemodialysis from February 2021 to August 2021. In addition, the BNT162b2 (Pfizer-BioNTech) and CoronaVac (Sinovac) vaccines were evaluated. The efficacy of vaccination in preventing SARS-CoV-2 infection, hospitalizations, and deaths associated with COVID-19 was determined. Results: A total of 12,301 patients were evaluated; 10,615 (86.3%) received a complete vaccination (2 doses), 490 (4.0%) received incomplete vaccination, and 1196 (9.7%) were not vaccinated. During follow-up, 1362 (11.0%) patients developed COVID-19, and 150 died (case fatality rate: 11.0%). The efficacy of the complete vaccination in preventing infection was 18.1% (95% confidence interval [CI]:11.8-23.8%), and prevention of death was 66.0% (95% CI:60.6-70.7%). When comparing both vaccines, BNT162b2 and CoronaVac were effective in reducing infection and deaths associated with COVID-19. Nevertheless, the BNT162b2 vaccine had higher efficacy in preventing infection (42.6% vs. 15.0%) and deaths (90.4% vs. 64.8%) compared to CoronaVac. Conclusion: The results of our study suggest that vaccination against SARS-CoV-2 in patients on chronic hemodialysis was effective in preventing infection and death associated with COVID-19.

Prevalencia y patrones de consumo de bebidas energizantes en estudiantes en una universidad colombiana / Prevalence and consumption patterns of energy drinks in students at a Colombian university / Prevalência e padrões de consumo de bebidas energéticas em estudantes, estudo de caso com uma universidade colombiana

Introducción. Las bebidas energizantes son preparaciones con contenido de sustancias estimulantes. En los últimos tiempos, la prevalencia de uso de estas bebidas entre adolescentes y adultos jóvenes ha ido en aumento Objetivo. Describir la prevalencia y los patrones de consumo de bebidas energizantes entre estudiantes universitarios de la Corporación Universitaria Rafael Núñez de Cartagena. Métodos. Se llevó a cabo un estudio observacional, descriptivo y de corte transversal. Se utilizó un instrumento previamente validado y sometido a una prueba piloto, para caracterizar la frecuencia y los patrones de consumo de bebidas energizantes en 558 estudiantes de 10 programas profesionales de la Corporación Universitaria Rafael Núñez. Resultados. La prevalencia del consumo de bebidas energizantes fue de 35 %. En los programas de Bacteriología e Instrumentación Quirúrgica se encontró la mayor prevalencia de consumo. Se encontró una diferencia estadísticamente significativa entre ser consumidor de bebidas energizantes y programa académico (p<0,001) y sexo (p<0,001). La marca de bebida más consumida fue Vive 100® y la principal motivación para el consumo fue el estudio, principalmente en tiempos de exámenes. El efecto indeseable más presentado entre los consumidores fue el aumento de la frecuencia cardiaca. El 100% de la población desconoce el marco legal en Colombia que cubre la producción de estas bebidas. Conclusiones. Existe una prevalencia moderada de consumo de bebidas energizantes con respecto a otros estudios en la población universitaria, con baja frecuencia en la ingestión. Hay poco conocimiento sobre los componentes y efectos que estas bebidas producen. Se presentan prácticas de consumo que aumentan los potenciales riesgos para la salud. Se recomienda a las autoridades universitarias la implementación de estrategias que permitan disminuir los riesgos derivados de los patrones de consumo que aumentan los potenciales efectos adversos de las bebidas energizantes.

Prevalencia y patrones de consumo de bebidas energizantes en estudiantes en una universidad colombianaTorres C, Angulo H, Rocha M, García K, Romero M, Polo M8 | Págs. 7-15 | Número 1 | Volumen 9 | ene. - jun. de 2019 | ISSN 2248-5759 (impresa) | ISSN 2322-9462 (digital) | Rev. salud. bosque.AbstractOverview: Energy drinks have amongst their ingredients stimu-lating substances. Nowadays the prevalence of these drinks amongst teens and young adults have been increasing.Objective: To estimate prevalence and consumption patterns of energy drinks in university students from Cartagena, Colombia Methods: This is an observational, descriptive, cross-section study. A tool previously validated and piloted, aimed at charac-terizing frequency and consumption patterns of energy drinks was administered to 558 students from 10 academic programs from the said university in Cartagena, Colombia.Results: The prevalence of consumption of energy drinks was 35%, being Bacteriology and Surgical Instrumentation the aca-demic programs with higher prevalence. Statistically significant difference was found between a regular consumer of energy drinks and academic program (p<0.001) and, sex (p<0.001). The beverage brand most consumed was Vive 100 and accor-ding to this study, the main reason for consumption was study. The most common undesirable effect amongst consumers was increased heart rate. 100% of the participants of this study are unaware of the regulations and currently in place in Colombia regarding the production of these drinks.Conclusions: There is a moderate prevalence of consumption of energy drinks, compared to other similar studies conducted on the subject. The general population is not knowledgeable about the ingredients or the effects of these drinks. It is recom-mended that university managers implement strategies aimed at decreasing the risks entailed in consumption patterns of energy drinks associated to potentially adverse effects.

Introducao. As bebidas energéticas são preparações com conteúdos de substâncias estimulantes, a prevalência do uso destas bebidas entre adolescentes e jovens tem aumentado.Objetivo. O artigo visa descrever a prevalência e padrões de consumo de bebidas energéticas em estudantes universitários em Cartagena.Materiais e métodos. O estudo é observacional descritivo e de corte transversal. Foi aplicado um instrumento validado e sometido a prova piloto, para caracterizar frequência e padrões de consumo de bebidas energéticas em 558 estudantes de 10 programas de graduação de uma Universidade.Resultados. A prevalência de consumo de bebidas energéticas foi de 35%, apresentando maior prevalência Bacteriologia e Instrumentação Quirurgica. Foi achada uma diferencia estatisticamente significativa entre consumir estas bebidas e o programa acadêmico e sexo. A marca mais consumida foi Vive 100, sendo usada para favorecimento dos estudos na época dos testes. O efeito indesejável mais mencionado foi aumento de frequência cardíaca, todos desconheciam o marco legal as-sociado a estas bebidas na Colômbia.Conclusoes. Existe uma prevalência de consumo de bebidas energéticas moderada e pouco conhecimento dos componentes e efeitos que produzem estas bebidas. Apresentamse praticas de consumo que aumentam potenciais riscos para a saúde e recomenda-se às autoridades universitárias desenvolver estratégias para diminuir riscos associados ao alto consumo destas bebidas.

The health system in Chile: the nephrologist perspective.

Chile is a country with 17 million inhabitants, 13% of them living in rural areas, and with a per capita income of approximately US $14,500. Three percent of national income is assigned to the health budget, with a mixed public and private system, with guaranteed medical benefits from the state to cover chronic kidney disease (CKD) and renal replacement therapy (RRT). Hemodialysis has reached in 2009 a prevalence of 857 patients per million population (pmp). Peritoneal dialysis is less developed, with a prevalence of 40 patients pmp. Both therapies show good quality indexes with a patient mortality rate close to 12% per year. A centralized national renal transplantation program registered 5,949 renal transplants performed up to 2009. Renal survival at 5 years is 86% for living and 76% for cadaveric donor transplants. Organ donation is relatively low with 7.1 cadaveric donors pmp in 2009, despite legal and educational strategies to increase it. Although the country demonstrates one of the highest standards for RRT indexes in Latin America, the proportion of resources invested makes it necessary to improve early diagnosis and renal prevention policies to avoid having the growing incidence of CKD constrain the national health budget.

Expression of gremlin, a bone morphogenetic protein antagonist,is associated with vascular calcification in uraemia.

BACKGROUND: Vascular calcification has been widely recognized as a significant contributor to cardiovascular risk in patients with chronic kidney disease. Recent evidence suggests that BMP-7 decreases the vascular calcification observed in uraemic rats, while BMP-2 could also be participating in this process. Gremlin, a bone morphogenetic protein antagonist, has been detected in rat aortic vascular smooth muscle cells (VSMCs), and since the role of the VSMCs into vascular calcification in uraemia is considered critical in this process, we hypothesized that gremlin could be participating in its pathogenesis. With this aim, we studied its expression in aorta from uraemic rats with calcitriol-induced vascular calcification and in 16-vessel biopsies of uraemic patients undergoing kidney transplantation. METHODS: Gremlin was detected by in situ hybridization (ISH) and immunohistochemistry (IMH). BMP-7, BMP-2 and BMP-2 receptor (BMPR2) were detected by IMH. Vascular calcification was assessed by the von Kossa staining method. Sham-operated and 5/6 nephrectomized rats (NFX) (1.2%P) were treated with vehicle or calcitriol (80 ng/kg, intraperitoneally every other day). Rats were killed after 4 weeks of treatment, and abdominal aorta was dissected for assessment of gremlin expression and vascular calcification. Epigastric arteries were obtained from dialysis patients during kidney transplantation procedure. Arteries from kidney donors were also studied. RESULTS: NFX rats developed a mild vascular calcification, whereas NFX-calcitriol rats developed a severe vascular and tissue calcification. A marked overexpression of gremlin was observed in the vascular media of aorta from NFX-calcitriol rats as compared with NFX and sham-calcitriol groups (4.8 +/- 1.3 versus 0.59 +/- 0.17 versus 0.19 +/- 0.07 percentage/mm(2), P < 0.01), and correlated with the BMP-2 and BMPR2 expression. Sham rats showed minimal or null gremlin expression. BMP-7 was not found in sham or calcified arteries. In human studies, we observed strong expression of gremlin mRNA and protein in the media layer of vessels from uraemic patients as compared with those from normal humans (staining score 3.72 +/- 0.95 versus 0.91 +/- 0.08 percentage/mm(2), P < 0.05). CONCLUSION: We observed a marked gremlin overexpression in the media layer of vessels in uraemic rats and patients in association with vascular calcification and BMP-2 expression. We postulate that gremlin may play a role in the vascular calcification process in uraemia, and its interaction with BMP-7 or BMP-2 remains to be elucidated.

Thrombocytopenia in Newcastle disease: haematological evaluation and histological study of bone marrow.

A Newcastle disease virus (NDV) isolated in Mexico and called Chimalhuacan strain was characterised by gene F restriction enzyme analysis and found to be a genotype II velogenic virus. Haematological evaluations and histological studies of bone marrow were conducted on chickens experimentally infected with the Chimalhuacan virus and on control chickens. Within 72 hours post infection (hpi), a 50% decrease in thrombocyte and monocyte counts and a complete cellular depletion in bone marrow islands were evident in the infected group. These findings suggest that the Chimalhuacan strain of NDV causes an early and severe damage of the haematopoietic cells including thrombocyte precursors, which might explain the marked thrombocytopenia detected in early stages of this disease.

On-line multidimensional liquid chromatography and capillary electrophoresis systems for peptides and proteins.

Peptides and proteins are gaining increasing attention in biosciences and, consequently, in analysis. This overview highlights the different approaches to couple on-line various separation techniques for the determination of proteins and peptides. The first section discusses the liquid chromatography (LC)-LC coupling, the second one reviews the on-line LC-capillary electrophoresis (CE) coupled systems and the third section summarizes the strategies for on-line CE-CE. The advantages, disadvantages, most relevant difficulties and particular systems for on-line coupling are discussed. Special attention is paid to the interface between the two dimensions. Applications are summarized in tables and a few typical examples are discussed. Many multidimensional separation methods are available, and it is demonstrated that peptide and protein mapping, or quantitation of proteins or peptides in various samples (aqueous solutions, cells, plasma) require different coupled systems. For mapping a semi-quantitative detection is often sufficient, while comprehensiveness is very important. For quantitation of a certain peptide or protein at a low concentration level a validated method should be used, while a heart-cut transport of the first dimension to the second one can offer sufficient selectivity. The combination with mass spectrometry as part of the total system is stressed and illustrated.