Pharmacotherapy and clinical outcomes of hospitalized COVID-19 patients in Chile during the first wave of pandemic / Farmacoterapia y desenlaces clínicos de pacientes de COVID-19 hospitalizados en Chile durante la primera ola de pandemia

BACKGROUND: The largest growth in cases of COVID-19 worldwide during 2020 was in the Americas, and Chile was one of the most affected countries. AIM: To describe, characterize, and evaluate the use of drugs as treatment for COVID-19 in hospitalized patients in Chile during the first wave of the pandemic. METHODS: We performed a multicenter, observational study that included 442 patients with confirmed SARS-CoV-2 infection admitted in Chilean hospitals between March 21 and September 22, 2020. The analysis included demographics, comorbidities, specific drug therapy, and outcomes over a 28-day follow-up period. RESULTS: The median age of patients was 68 years (IQR 55-73), and 38.9% were women. The most common comorbidities were hypertension (57.7%) and diabetes (36.9%). Fifty-seven (12.9%) patients died. Hypertension (HR 2.99; CI 95% 1.43-6.26) and age ≥; 65 (2.14; CI 95% 1.10- 4.17) were the main predictors of mortality. Primary drugs were azithromycin (58.8%) and corticosteroids (51.1%). In this sample, azithromycin was a protective factor regarding mortality (HR 0.53; CI 95% 0.31-0.90), increasing clinical improvement and avoiding progression. CONCLUSIONS: The patterns of use of drugs to treat COVID-19 in Chile during the first wave of the pandemic were very dynamic and followed the international, evidence-based guidelines. The low mortality rate indicates that the clinical management of hospitalized patients was adequate.

ANTECEDENTES: Durante 2020, el mayor incremento de casos de COVID-19 se observó en el continente americano, donde Chile fue uno de los países más afectados. Objetivos: Describir, caracterizar y evaluar el uso de fármacos indicados para tratar el COVID-19 en pacientes hospitalizados en Chile durante la primera ola de pandemia. PACIENTES Y MÉTODOS: Un estudio multicéntrico observacional incorporó a 442 pacientes con infección confirmada por SARS- CoV-2 admitidos en hospitales chilenos entre el 21 de marzo y el 22 de septiembre de 2020. Se analizaron variables demográficas, comorbilidades, terapia farmacológica específica y desenlaces clínicos para un período de seguimiento de 28 días. Resultados: La mediana de la edad fue de 68 años (RIC 55-73), y un 38,9% fueron mujeres. Las comorbilidades más comunes fueron hipertensión (57,7%) y diabetes (36,9%). Cincuenta y siete (12,9%) de los pacientes murieron. Los principales predictores de mortalidad fueron la hipertensión (HR 2,99; IC 95% 1,43-6,26) y la edad ≥ 65 años (2,14; IC 95% 1,10- 4,17). Los fármacos más utilizados fueron azitromicina (58,8%) y corticosteroides (51,1%). En esta muestra, la azitromicina fue un factor de protección respecto a la mortalidad (HR 0,53; IC 95% 0,31-0,90), incrementando igualmente la mejoría y evitando la progresión. CONCLUSIONES: Los patrones de uso de fármacos para tatar COVID-19 en Chile durante la primera ola de pandemia fueron muy dinámicos y siguieron las directrices internacionales basadas en la evidencia. La baja mortalidad sugiere que el manejo de los pacientes hospitalizados fue adecuado.

Adaptation by Men to the Nurse Role. "Being Craftsmen in the Construction of their Professional Trajectory" / La adaptación de los hombres al rol de enfermero. "Ser un artesano en la construcción de su trayectoria profesional" / A adaptação do homem ao papel de enfermeiro. "Ser artesão na construção da sua carreira profissional"

Objective. This work sought to describe the adaptation process by men to the nurse role. Methods.Secondary analysis of data from a collective case study that had as participants 12 male nurses working in the city of Medellín, with ages between 28 and 47 years and average time of professional experience of 11 years. Information collection was carried out through in-depth interviews. The analysis was conducted through Roy's Adaptation Model (RAM), reading of the interviews, identification of RAM's components, grouping of fragments, assignment of tags, construction of a matrix and classification. Results. The analysis performed accounts for the coping processes and adaptation by male nurses and the ineffective responses (control of emotions and emotional silencing) when practicing a role considered feminine. Conclusion.In this study, it was possible to establish that, to achieve adaptation within nursing, men use strategies related with changes in bodily appearance, management of physical strength, and management of emotions.

Objetivo. Describir el proceso de adaptación de los hombres al rol enfermero. Métodos. Análisis secundario de los datos de un estudio de casos colectivo que tuvo como participantes a 12 enfermeros que trabajan en la ciudad de Medellín, con edades entre los 28 y los 47 años y un tiempo de experiencia profesional promedio de 11 años. La recolección de la información se realizó mediante entrevistas en profundidad. El análisis se realizó a partir del Modelo de Adaptación de Roy (RAM), lectura de las entrevistas, identificación de los componentes del RAM, agrupación de fragmentos, asignación de etiquetas, construcción de una matriz y clasificación. Resultados. El análisis realizado da cuenta de los procesos de afrontamiento y adaptación de los enfermeros y las respuestas inefectivas (control de emociones y silenciamiento emocional) al ejercer un rol considerado femenino. Conclusión. En este estudio fue posible establecer que, para alcanzar una adaptación dentro de la enfermería, los hombres utilizan estrategias relacionadas con cambios en la apariencia corporal, el manejo de la fuerza física y el manejo de las emociones.

Objetivo. Descrever o processo de adaptação do homem à função de enfermagem. Métodos.Análise secundária de dados de um estudo de caso coletivo que teve como participantes 12 enfermeiros que atuam na cidade de Medellín, com idade entre 28 e 47 anos e tempo de experiência profissional média 11 anos. As informações foram coletadas por meio de entrevistas em profundidade. A análise foi realizada por meio do Modelo de Adaptação de Roy (RAM), leitura das entrevistas, identificação dos componentes do RAM, agrupamento de fragmentos, atribuição de rótulos, construção de matriz e classificação. Resultados. A análise realizada dá conta dos processos de enfrentamento e adaptação das enfermeiras e das respostas ineficazes (controle das emoções e silenciamento emocional) ao exercer um papel considerado feminino. Conclusão.Neste estudo foi possível constatar que, para conseguir uma adaptação dentro da enfermagem, os homens utilizam estratégias relacionadas a mudanças na aparência corporal, manejo da força física e manejo emocional

A highly-specific fully-human antibody and CAR-T cells targeting CD66e/CEACAM5 are cytotoxic for CD66e-expressing cancer cells in vitro and in vivo.

Neuro-endocrine prostate cancer (NEPC) accounts for about 20% of lethal metastatic castration-resistant prostate cancer (CRPC). NEPC has the most aggressive biologic behavior of all prostate cancers and is associated with poor patient outcome. Effective treatment for NEPC is not available because NEPC exhibit distinct cell-surface expression profiles compared to other types of prostate cancer. Recently, the carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) (known as CEA or CD66e) was suggested to be a specific surface protein marker for NEPC. Therefore, we identified a new, fully-human anti-CEACAM5 monoclonal antibody, 1G9, which bound to the most proximal membrane domains, A3 and B3, of CEACAM5 with high affinity and specificity. It shows no off-target binding to other CEACAM family members, membrane distal domains of CEACAM5, or 5800 human membrane proteins. IgG1 1G9 exhibited CEACAM5-specific ADCC activity toward CEACAM5-positive prostate cancer cells in vitro and in vivo. Chimeric antigen receptor T cells (CAR-T) based on scFv 1G9 induced specific and strong antitumor activity in a mouse model of prostate cancer. Our results suggest that IgG1 and CAR-T cells based on 1G9 are promising candidate therapeutics for CEACAM5-positive NEPC and other cancers.

El rol de los hombres en enfermería, el reconocimiento y las emociones que subyacen en la práctica profesional / The role of men in nursing, recognition and emotions underlying professional practice

Objetivo: comprender el rol de los hombres en enfermería, teniendo en cuenta su reconocimiento y las emociones que subyacen en el ejercicio de su práctica profesional. Metodología: esta tesis fue realizada desde la metodología de estudio de casos colectivo propuesta por Robert E. Stake. Se entrevistaron 12 enfermeros con desempeño en diferentes escenarios laborales empleando entrevistas en profundidad, notas de campo y memorando analíticos para registrar las experiencias emotivas de los participantes. El análisis se realizó por medio de agrupamiento y reducción de los fragmentos de las entrevistas y la construcción de un mapa conceptual. Resultados: los roles de género son producto de una construcción social, y en este sentido, se moldean y cambian con el devenir histórico y cultural, prueba de esto es el ingreso de los hombres a la enfermería. Sin embargo, a nivel social persiste una naturalización de la enfermería como un oficio femenino que se traduce en una imagen estereotipada del papel de los enfermeros que dificulta su reconocimiento. Conclusiones: los hombres desde el momento en que manifiestan su intención de convertirse en enfermeros, inician un proceso de adaptación en diferentes esferas, donde no solo deben negociar sus emociones, sino emprender una lucha permanente por el reconocimiento como un motor para el desarrollo y el cambio en diferentes aspectos de su vida. (Tomado del repositorio institucional)

Objective: to understand the role of men in nursing, taking into account their recognition and the emotions that underlie their professional practice. Methodology: This thesis was conducted using the collective case study methodology proposed by Robert E. Stake. Twelve nurses with performance in different work scenarios were interviewed using in-depth interviews, field notes, and analytical memorandum to record the emotional experiences of the participants. The analysis was carried out by grouping and reducing the fragments of the interviews and constructing a conceptual map. Results: gender roles are the product of a social construction, and in this sense, they are molded and change with historical and cultural evolution, proof of which is the entry of men into nursing. However, at the social level, a naturalization of nursing as a female profession persists, which translates into a stereotyped image of the role of female patients that hinders its recognition. Conclusions: men, from the moment they express their intention to become nurses, begin a process of adaptation in different areas, where they must, in addition to negotiating their emotions, constantly fight for recognition as the engine of change and development in different aspects of their lives. (Tomado del repositorio institucional)

A resource of high-quality and versatile nanobodies for drug delivery.

Therapeutic and diagnostic efficacies of small biomolecules and chemical compounds are hampered by suboptimal pharmacokinetics. Here, we developed a repertoire of robust and high-affinity antihuman serum albumin nanobodies (NbHSA) that can be readily fused to small biologics for half-life extension. We characterized the thermostability, binding kinetics, and cross-species reactivity of NbHSAs, mapped their epitopes, and structurally resolved a tetrameric HSA-Nb complex. We parallelly determined the half-lives of a cohort of selected NbHSAs in an HSA mouse model by quantitative proteomics. Compared to short-lived control nanobodies, the half-lives of NbHSAs were drastically prolonged by 771-fold. NbHSAs have distinct and diverse pharmacokinetics, positively correlating with their albumin binding affinities at the endosomal pH. We then generated stable and highly bioactive NbHSA-cytokine fusion constructs "Duraleukin" and demonstrated Duraleukin's high preclinical efficacy for cancer treatment in a melanoma model. This high-quality and versatile Nb toolkit will help tailor drug half-life to specific medical needs.

La educación en tiempo de pandemia COVID 19: ¿realidad o ficción? / Educação em tempos de pandemia COVID 19: fato ou ficção? / Education in a time of pandemic COVID 19: fact or fiction?

De manera sorpresiva el COVID-19 detuvo al mundo, o puntualmente frenó el acelerado ritmo en que confluía la actividad humana, pues los capullos siguen brotando en primavera, las ballenas continúan sus largas migraciones por el océano, la temporada de sequía volvió para quemar la tierra y el planeta continuó su incesante danza de rotación y traslación. Es decir, todos los seres vivos continuaron con normalidad su existencia, excepto los seres humanos, aterrados por una muerte invisible y un enemigo despiadado que hasta este momento parece infranqueable.

Transcription with a laser: Radiation-damage-free diffraction of RNA Polymerase II crystals.

Well-diffracting crystals are essential to obtain relevant structural data that will lead to understanding of RNA Polymerase II (Pol II) transcriptional processes at a molecular level. Here we present a strategy to study Pol II crystals using negative stain transmission electron microscopy (TEM) and a methodology to optimize radiation damage free data collection using free electron laser (FEL) at the Linac Coherent Light Source (LCLS). The use of negative stain TEM allowed visualization and optimization of crystal diffraction by monitoring the lattice quality of crystallization conditions. Nano crystals bearing perfect lattices were seeded and used to grow larger crystals for FEL data collection. Moreover, the use of in house designed crystal loops together with ultra-violet (UV) microscopy for crystal detection facilitated data collection. Such strategy permitted collection of multiple crystals of radiation-free-damage data, resulting in the highest resolution of wild type (WT) Pol II crystals ever observed.

Phosphorylation and Proteasome Recognition of the mRNA-Binding Protein Cth2 Facilitates Yeast Adaptation to Iron Deficiency.

Iron is an indispensable micronutrient for all eukaryotic organisms due to its participation as a redox cofactor in many metabolic pathways. Iron imbalance leads to the most frequent human nutritional deficiency in the world. Adaptation to iron limitation requires a global reorganization of the cellular metabolism directed to prioritize iron utilization for essential processes. In response to iron scarcity, the conserved Saccharomyces cerevisiae mRNA-binding protein Cth2, which belongs to the tristetraprolin family of tandem zinc finger proteins, coordinates a global remodeling of the cellular metabolism by promoting the degradation of multiple mRNAs encoding highly iron-consuming proteins. In this work, we identify a critical mechanism for the degradation of Cth2 protein during the adaptation to iron deficiency. Phosphorylation of a patch of Cth2 serine residues within its amino-terminal region facilitates recognition by the SCFGrr1 ubiquitin ligase complex, accelerating Cth2 turnover by the proteasome. When Cth2 degradation is impaired by either mutagenesis of the Cth2 serine residues or deletion of GRR1, the levels of Cth2 rise and abrogate growth in iron-depleted conditions. Finally, we uncover that the casein kinase Hrr25 phosphorylates and promotes Cth2 destabilization. These results reveal a sophisticated posttranslational regulatory pathway necessary for the adaptation to iron depletion.IMPORTANCE Iron is a vital element for many metabolic pathways, including the synthesis of DNA and proteins, and the generation of energy via oxidative phosphorylation. Therefore, living organisms have developed tightly controlled mechanisms to properly distribute iron, since imbalances lead to nutritional deficiencies, multiple diseases, and vulnerability against pathogens. Saccharomyces cerevisiae Cth2 is a conserved mRNA-binding protein that coordinates a global reprogramming of iron metabolism in response to iron deficiency in order to optimize its utilization. Here we report that the phosphorylation of Cth2 at specific serine residues is essential to regulate the stability of the protein and adaptation to iron depletion. We identify the kinase and ubiquitination machinery implicated in this process to establish a posttranscriptional regulatory model. These results and recent findings for both mammals and plants reinforce the privileged position of E3 ubiquitin ligases and phosphorylation events in the regulation of eukaryotic iron homeostasis.

Vivencias de familiares en sala de espera de trabajo de parto / Experiences of Family Members in the Labor Room / Vivências de familiares na sala do parto

Objetivo: describir las vivencias de los familiares en sala de espera de trabajo de parto. Materiales y métodos: estudio cualitativo etnográfico. Se entrevistaron diez participantes y cuatro grupos focales; la saturación se logró cuando los investigadores no encontraron más explicación, interpretación o descripción de la experiencia. Para el análisis, se usó el método de Spradley, se construyeron categorías y dominios, y se realizó análisis taxonómico. Se desarrollaron notas de campo y observación participante. Se utilizó el software Atlas ti. Resultados: los familiares experimentan necesidades de información oportuna y eficiente. El lenguaje verbal y no verbal y el contenido de la información les produjo ansiedad e incertidumbre. Los familiares sienten la necesidad de acompañar a la gestante durante el trabajo de parto para brindarle apoyo. El ambiente en la sala de espera depende de los factores internos del familiar y los factores externos de la sala. La educación en la sala de espera representó una excelente oportunidad para aprovechar el tiempo. Emergieron los dominios: comunicación terapéutica, acompañamiento, ambiente y educación. Conclusión: el significado cultural de esperar es un acontecimiento de la vida altamente significativo, atravesado por cuatro circunstancias: la comunicación, el acompañamiento, el ambiente de la sala y la educación, situaciones que cambiaron la experiencia del nacimiento.

Objective: Describe the experiences of family members in the labor room. Materials and Methods: This is a qualitative ethnographic study in which ten participants and four focus groups were interviewed; Saturation was achieved when the researchers found no further explanation, interpretation or description of the experience. Spradley's method was used for the analysis. Categories and domains were constructed and a taxonomic analysis was done. Field notes and participant observation were developed. Atlas ti software was used. Results: Family members want and feel they need timely and efficient information. Verbal and non-verbal language and the content of the information provided can cause them anxiety and uncertainty. Family members want to accompany and support the expectant mother during labor prior to childbirth. The atmosphere in the labor room depends on the internal factors of the family member and the external factors of the room. Education in the waiting room proved to be an excellent opportunity to take advantage of the time. Several domains emerged; namely, therapeutic communication, accompaniment, environment and education. Conclusion: The cultural significance of waiting for birth to occur is a highly meaningful event in life and is marked by four factors: communication, accompaniment, the environment in the room and education. These are situations that changed the birth experience.

Objetivo: descrever as vivências dos familiares na sala de espera de trabalho de parto. Materiais e métodos: estudo qualitativo etnográfico. Foram entrevistados dez participantes e quatro grupos focais. A saturação foi atingida quando os pesquisadores não encontraram mais explicação, interpretação ou descrição da experiência. Para a análise, usou-se o método de Spradley e foram construídos categorias e domínios, além de realizada análise taxonómica. Desenvolveram-se anotações de campo e observação participante. Utilizouse o software Atlas ti. Resultados: os familiares experimentaram necessidades de informação oportuna e eficiente. A linguagem verbal e não verbal, e o conteúdo da informação lhes produziram ansiedade e incerteza. Os familiares sentem a necessidade de acompanhar a gestante durante o trabalho de parto para oferecer-lhe apoio. O ambiente na sala de espera depende dos fatores internos do familiar e dos fatores externos da sala. A educação na sala de espera representou uma excelente oportunidade para aproveitar o tempo. Emergiram os domínios: comunicação terapêutica, acompanhamento, ambiente e educação. Conclusão: o significado cultural de esperar é um acontecimento da vida altamente significativo, permeado por quatro circunstâncias: a comunicação, o acompanhamento, o ambiente da sala e a educação, situações que mudaram a experiência do nascimento.

Frecuencia de infecciones vaginales y lesiones intraepiteliales en las usuariasde los laboratorios clínicos de DinámicaIPS de la ciudad de Medellín (Colombia), 2005-2010: estudio descriptivo / Frequency of vaginal infections and intraepithelial lesions in a female population sample of Dinámica IPS, a clinical laboratory in Medellin, attended between 2005 and 2010

Determinar la frecuencia de infecciones vaginales y lesiones intraepiteliales en los resultados de laboratorio de las usuarias de los laboratorios clínicos de Dinámica IPS de la ciudad de Medellín, atendidas entre el 2005 y el 2010. Materiales y métodos:estudio descriptivo transversal con fuentes secundarias de los resultados de pruebas realizadas a usuarias de Dinámica IPS atendidas en el periodo de estudio, en el que se evaluaron variables como la edad y los resultados de citología vaginal (n= 261 789),Gram (n= 70 447) y directo de flujo vaginal (n= 89 527). Se excluyeron registros con información incompleta. Se realizó análisis estadístico con medianas y proporciones.Resultados: del total de muestras analizadas por citología vaginal (n=261 789), el 1,99% correspondían a lesiones escamosas, de éstas el 0,038% corresponde a muestras positivas de cáncer de cuello uterino confirmada por patólogo; el 8,01% corresponde a lesiones intraepiteliales de alto grado y el 36,13% a lesiones escamosas de bajo grado.En el examen de flujo vaginal por directo se encontraron 14 803 pruebas positivas(16,51%) para vaginitis por hongos, 19 079 (21,31%) para vaginosis bacteriana y 414(0,46%) para vaginitis por Trichomona; en el Gram se observó que el desequilibrio de la flora normal generado por Gardnerella ocupan la mayor frecuencia con 19 186 resultados positivos (27,23%). Conclusiones: los datos encontrados con relación a las frecuencias de lesiones escamosas intraepiteliales y de infecciones vaginales guardan relación con lo reportado en la literatura nacional; sin embargo, para los casos de atipia en células escamosas de significado no determinado se encuentra variación, probablemente por las características mismas de este tipo de atipias...

Negative feedback regulation of the yeast CTH1 and CTH2 mRNA binding proteins is required for adaptation to iron deficiency and iron supplementation.

Iron (Fe) is an essential element for all eukaryotic organisms because it functions as a cofactor in a wide range of biochemical processes. Cells have developed sophisticated mechanisms to tightly control Fe utilization in response to alterations in cellular demands and bioavailability. In response to Fe deficiency, the yeast Saccharomyces cerevisiae activates transcription of the CTH1 and CTH2 genes, which encode proteins that bind to AU-rich elements (AREs) within the 3' untranslated regions (3'UTRs) of many mRNAs, leading to metabolic reprogramming of Fe-dependent pathways and decreased Fe storage. The precise mechanisms underlying Cth1 and Cth2 function and regulation are incompletely understood. We report here that the Cth1 and Cth2 proteins specifically bind in vivo to AREs located at the 3'UTRs of their own transcripts in an auto- and cross-regulated mechanism that limits their expression. By mutagenesis of the AREs within the CTH2 transcript, we demonstrate that a Cth2 negative-feedback loop is required for the efficient decline in Cth2 protein levels observed upon a rapid rise in Fe availability. Importantly, Cth2 autoregulation is critical for the appropriate recovery of Fe-dependent processes and resumption of growth in response to a change from Fe deficiency to Fe supplementation.

Asistencia biopsicosocial a través del uso del tic (línea de atención) a cuidadores de pacientes oncológicos / Biopsychosocial assistance through the use of ict (helpline) to caregivers of oncology patients / Assistência biopsicossocial através do uso de tic (helpline) a keepers de oncologia pacientes

Objetivo: Brindar asistencia Biopsicosocial a través del uso del TIC (Línea de Atención) a cuidadores de pacientes oncológicos que asisten a la IPS Oncomedical en la ciudad de Cúcuta. Materiales y Métodos: estudio transversal de tipo cuantitativo. La muestra estuvo conformada por 46 cuidadores de pacientes oncológicos que actualmente reciben tratamiento médico en la IPS Oncomedical. Se aplicó la encuesta de caracterización de los cuidadores familiares de personas con enfermedad oncológica, para medir el soporte social, se empleó el instrumento Inventario de Soporte Social en Enfermedad Crónica (ISSEC) de Hilbert. La encuesta se aplicó antes de iniciar el apoyo a los cuidadores por medio de la línea telefónica y después del apoyo social brindado a cada uno de ellos. Resultados: se encontró que el 60% de los cuidadores se encuentra satisfecho en esta categoría sintiéndose importantes al tener quien se preocupe por ellos en medio de toda la situación que atraviesan, esto es producto de las llamadas semanales hechas a cada uno de ellos donde se ofreció apoyo emocional, consuelo en los momentos difíciles, y escucha activa entre otros. Conclusión: El uso del TIC (Línea de Atención), generó espacios de comunicación donde el cuidador expresa libremente sus sentimientos y preocupaciones facilitando así una adecuada intervención en aspectos como: apoyo emocional, educación sobre el mantenimiento de su propia salud y la de su objeto de cuidado, fortalecimiento de lazos familiares, por parte del personal que brinda el soporte, logrando así mejoría tanto en la salud física como mental de los cuidadores.

Goal: To provide assistance Bio psychosocial through the use of ICT (Hotline) caregivers of cancer patients attending the IPS Oncomedical in Cucuta city. Materials and Methods: Cross-sectional quantitative study. The sample consisted of 46 caregivers of cancer patients currently receiving medical treatment in Oncomedical IPS. Characterization survey of family caregivers of people with cancer disease was applied to measure social support, the Social Support Inventory Report (ISSEC) Hilbert Disease instrument was used. The survey was conducted before beginning the support to caregivers through the phone line and then the social support given to each of them. Results: It was found that 60% of caregivers were satisfied in this category , they themselves feel important people in having someone who cares about them amidst all the situation facing, this is the result of weekly calls made to each of them where offered emotional support, comfort in difficult times, and active listening among others. Conclusions: The use of ICT (Hotline) generated communication spaces where the caregiver freely express their feelings and concerns and providing appropriate intervention in aspects such as emotional support, education about maintaining their own health and that of their subject care, strengthening family ties, by staff providing support, achieving improvement in both physical and mental health of caregivers.

Objetivo: prestar assistência biopsicossocial através do uso de TIC (Hotline) cuidadores de pacientes com câncer que frequentam o IPS Oncomedical na cidade de Cucuta. Materiais e Métodos: estudo quantitativo transversal. A amostra foi composta de 46 cuidadores de pacientes com câncer atualmente recebem tratamento médico em Oncomedical IPS. Pesquisa Caracterização de cuidadores familiares de pessoas com doença de câncer foi aplicado para medir o apoio social, utilizou-se o Inventário de Relatório de Apoio Social (ISSEC) instrumento de Doenças Hilbert. A pesquisa foi realizada antes de iniciar os cuidadores de apoio através da linha de telefone e, em seguida, o apoio social dado a cada um deles. Resultados: Verificou-se que 60% dos cuidadores estavam satisfeitos nesta categoria sentiendose importante ter alguém que se preocupa com eles no meio de toda a situação que enfrentam, este é o resultado de chamadas semanais feitas a cada um deles, onde ofereceram apoio emocional, conforto em tempos difíceis, e escuta ativa, entre outros. Conclusão: A utilização das TIC (Hotline) gerado espaços de comunicação onde o cuidador expressar livremente seus sentimentos e preocupações e fornecendo intervenção adequada em aspectos como apoio emocional, a educação sobre a manutenção de sua própria saúde ea de seu assunto cuidar, fortalecendo os laços familiares, pelo pessoal que presta apoio, alcançar a melhoria na saúde física e mental dos cuidadores.

Early recruitment of AU-rich element-containing mRNAs determines their cytosolic fate during iron deficiency.

The yeast Cth2 protein is a CX(8)CX(5)CX(3)H tandem zinc finger protein that binds AU-rich element (ARE)-containing transcripts to enhance their decay in response to iron (Fe) deficiency. Mammalian members of this family of proteins are known to undergo nucleocytoplasmic shuttling, but little is known about the role of shuttling in the mechanism of ARE-dependent mRNA decay. Here we demonstrate that, like its mammalian homologues, Cth2 is a nucleocytoplasmic shuttling protein whose nuclear export depends on mRNA transport to the cytosol. The nuclear import information of Cth2 is contained within its tandem zinc finger domain, but it is independent of mRNA-binding function. Moreover, we also demonstrate that nucleocytoplasmic shuttling of Cth2 requires active transcription and that disruption of shuttling leads to defects in Cth2 function in mRNA decay under Fe deficiency. Taken together, our data suggest that under conditions of Fe deficiency Cth2 travels into the nucleus to recruit target mRNAs, perhaps cotranscriptionally, that are destined for cytosolic degradation as part of the mechanism of adaptation to growth under Fe limitation. These data also suggest an important role for nucleocytoplasmic shuttling in this conserved family of proteins in the mechanism of ARE-mediated mRNA decay.

Ironing out a midlife crisis.

There is a strong correlation between age, genomic instability, and the development of cancer. Working in yeast, Veatch et al. (2009) now propose that defects in the biogenesis of iron-sulfur clusters arising as a consequence of mitochondrial dysfunction contribute to the increase in genomic instability as cells age.

Post-transcriptional regulation of gene expression in response to iron deficiency: co-ordinated metabolic reprogramming by yeast mRNA-binding proteins.

Saccharomyces cerevisiae (baker's yeast) is an excellent model for understanding fundamental biological mechanisms that are conserved in Nature and that have an impact on human disease. The metal iron is a redox-active cofactor that plays critical biochemical roles in a broad range of functions, including oxygen transport, mitochondrial oxidative phosphorylation, chromatin remodelling, intermediary metabolism and signalling. Although iron deficiency is the most common nutritional disorder on the planet, little is known about the metabolic adjustments that cells undergo in response to iron deficit and the regulatory mechanisms that allow these adaptive responses. In the present article, we summarize recent work on genome-wide metabolic reprogramming in response to iron deficiency, mediated by specific mRNA degradation mechanisms that allow S. cerevisiae cells to adapt to iron deficiency.

The Cth2 ARE-binding protein recruits the Dhh1 helicase to promote the decay of succinate dehydrogenase SDH4 mRNA in response to iron deficiency.

Iron is an essential nutrient that participates as a redox co-factor in a broad range of cellular processes. In response to iron deficiency, the budding yeast Saccharomyces cerevisiae induces the expression of the Cth1 and Cth2 mRNA-binding proteins to promote a genome-wide remodeling of cellular metabolism that contributes to the optimal utilization of iron. Cth1 and Cth2 proteins bind to specific AU-rich elements within the 3'-untranslated region of many mRNAs encoding proteins involved in iron-dependent pathways, thereby promoting their degradation. Here, we show that the DEAD box Dhh1 helicase plays a crucial role in the mechanism of Cth2-mediated mRNA turnover. Yeast two-hybrid experiments indicate that Cth2 protein interacts in vivo with the carboxyl-terminal domain of Dhh1. We demonstrate that the degradation of succinate dehydrogenase SDH4 mRNA, a known target of Cth2 on iron-deficient conditions, depends on Dhh1. In addition, we localize the Cth2 protein to cytoplasmic processing bodies in strains defective in the 5' to 3' mRNA decay pathway. Finally, the degradation of trapped SDH4 mRNA intermediates by Cth2 supports the 5' to 3' directionality of mRNA turnover. Taken together, these results suggest that Cth2 protein recruits the Dhh1 helicase to ARE-containing mRNAs to promote mRNA decay.

Cooperation of two mRNA-binding proteins drives metabolic adaptation to iron deficiency.

Iron (Fe) is an essential cofactor for a wide range of cellular processes. We have previously demonstrated in yeast that Cth2 is expressed during Fe deficiency and promotes degradation of a battery of mRNAs leading to reprogramming of Fe-dependent metabolism and Fe storage. We report here that the Cth2-homologous protein Cth1 is transiently expressed during Fe deprivation and participates in the response to Fe deficiency through the degradation of mRNAs primarily involved in mitochondrially localized activities including respiration and amino acid biosynthesis. In parallel, wild-type cells, but not cth1Deltacth2Delta cells, accumulate mRNAs encoding proteins that function in glucose import and storage and store high levels of glycogen. In addition, Fe deficiency leads to phosphorylation of Snf1, an AMP-activated protein kinase family member required for the cellular response to glucose starvation. These studies demonstrate a metabolic reprogramming as a consequence of Fe starvation that is dependent on the coordinated activities of two mRNA-binding proteins.

Biochemical and functional characterization of the actin-binding activity of the B subunit of yeast vacuolar H+-ATPase.

Vacuolar H+-ATPase (V-ATPase) is a fundamentally important enzyme in eukaryotic cells that is responsible for acidification of endocytic compartments. The B subunits of V-ATPases from mammals and tobacco hornworm have been shown to bind actin filaments. Actin-binding activity by the B subunit is required for targeting V-ATPases to the plasma membrane of osteoclasts. Bacterially expressed B subunit from the yeast Saccharomyces cerevisiae bound actin filaments with a Kd of 195 nmol l(-1). The actin-binding domain of the B subunit was altered by mutations that reduced or eliminated the actin-binding activity. Mutants assembled properly with endogenous yeast subunits when expressed in B subunit-null yeast and bafilomycin-sensitive ATPase activity was not significantly different from yeast transformed with wild-type B subunit. Yeast containing the mutant subunits grew as well at pH 7.5 as wild-type. Screening null yeast or null yeast transformed with wild-type or mutant B subunits with sub-lethal doses of various drugs revealed that yeast containing the mutant B subunits were more sensitive to cycloheximide and wortmannin than those transformed with wild-type B subunits. These results suggest that actin-binding activity confers on the B subunit of yeast a function that is distinct from its role in the enzymatic activity of the proton pump.

Actin binding activity of subunit B of vacuolar H+-ATPase is involved in its targeting to ruffled membranes of osteoclasts.

UNLABELLED: Adeno-associated virus was used to transduce primary mouse osteoclasts with the B1 isoform of vacuolar H(+)-ATPase. B1, which is not normally expressed in osteoclasts, was correctly targeted to ruffled membranes of resorbing osteoclasts. Mutant subunit B1 that lacked a functional actin-binding site did not accumulate in ruffled membranes. INTRODUCTION: The B1 "kidney" and B2 "brain" isoforms of subunit B of vacuolar H(+)-ATPase (V-ATPase) have actin binding sites that mediate interactions between the intact enzyme and filamentous-actin. Accumulating data support the hypothesis that the actin binding activity in subunit B is required for targeting of V-ATPases to the ruffled plasma membrane of osteoclasts. This study was designed to directly test this hypothesis. MATERIALS AND METHODS: Osteoclasts express B2, but not B1. Adeno-associated virus vectors were used to transduce mouse osteoclasts with wildtype B1 or B1(mut), a full-length B subunit that contained minor alterations that disrupted actin-binding activity. Immunofluorescence was performed using polyclonal antibodies specific for subunit E, B2, and B1 of V-ATPase. Immunoprecipitations were performed using an anti-E subunit antibody. Microfilaments were detected with phalloidin and actin rings were stained with phalloidin or anti-vinculin antibodies. Images were collected using a confocal microscope. RESULTS: Immunoprecipitations of transduced osteoclasts suggested that both B1 and B1(mut) assembled with endogenous V-ATPase subunits to form intact enzyme in osteoclasts. Both B1 and B1(mut) were localized like endogenous V-ATPase subunits in unactivated osteoclasts. Wildtype B1 associated with the detergent-insoluble cytoskeleton and was transported to ruffled membranes of resorbing osteoclasts. In contrast, B1(mut) failed to associate with the actin cytoskeleton and was not transported efficiently to ruffled membranes. CONCLUSIONS: The B1 isoform of B subunit contains the necessary information for targeting to the ruffled membranes of osteoclasts even though it is not normally expressed in osteoclasts. The actin binding activity of B1 is involved in proper ruffled membrane targeting.

The amino-terminal domain of the E subunit of vacuolar H(+)-ATPase (V-ATPase) interacts with the H subunit and is required for V-ATPase function.

Vacuolar H(+)-ATPases (V-ATPases) are highly conserved proton pumps that couple hydrolysis of cytosolic ATP to proton transport out of the cytosol. Although it is generally believed that V-ATPases transport protons by a rotary catalytic mechanism analogous to that used by F(1)F(0)-ATPases, the structure and subunit composition of the central or peripheral stalk of the multisubunit complex are not well understood. We searched for proteins that bind to the E subunit of V-ATPase using the yeast two-hybrid assay and identified the H subunit as an interacting partner. Physical association between the E and H subunits of V-ATPase was confirmed in vitro by precipitation assays. Deletion mapping analysis revealed that a 78-amino acid fragment at the amino terminus of the E subunit was sufficient for binding to the H subunit. Expression of the amino-terminal fragments of the E subunits from human and yeast as dominant-negative mutants resulted in dramatic decreases in bafilomycin A(1)-sensitive ATP hydrolysis and proton transport activities of V-ATPase. Our data demonstrate the physiological significance of the interaction between the E and H subunits of V-ATPase and extend previous studies on the arrangement of subunits on the peripheral stalk of V-ATPase.