Chaperone-mediated autophagy and disease: Implications for cancer and neurodegeneration.

Chaperone-mediated autophagy (CMA) is a proteolytic process whereby selected intracellular proteins are degraded inside lysosomes. Owing to its selectivity, CMA participates in the modulation of specific regulatory proteins, thereby playing an important role in multiple cellular processes. Studies conducted over the last two decades have enabled the molecular characterization of this autophagic pathway and the design of specific experimental models, and have underscored the importance of CMA in a range of physiological processes beyond mere protein quality control. Those findings also indicate that decreases in CMA function with increasing age may contribute to the pathogenesis of age-associated diseases, including neurodegeneration and cancer. In the context of neurological diseases, CMA impairment is thought to contribute to the accumulation of misfolded/aggregated proteins, a process central to the pathogenesis of neurodegenerative diseases. CMA therefore constitutes a potential therapeutic target, as its induction accelerates the clearance of pathogenic proteins, promoting cell survival. More recent evidence has highlighted the important and complex role of CMA in cancer biology. While CMA induction may limit tumor development, experimental evidence also indicates that inhibition of this pathway can attenuate the growth of established tumors and improve the response to cancer therapeutics. Here, we describe and discuss the evidence supporting a role of impaired CMA function in neurodegeneration and cancer, as well as future research directions to evaluate the potential of this pathway as a target for the prevention and treatment of these diseases.

Autophagy and the hallmarks of aging.

Autophagy, an essential cellular process that mediates degradation of proteins and organelles in lysosomes, has been tightly linked to cellular quality control for its role as part of the proteostasis network. The current interest in identifying the cellular and molecular determinants of aging, has highlighted the important contribution of malfunctioning of autophagy with age to the loss of proteostasis that characterizes all old organisms. However, the diversity of cellular functions of the different types of autophagy and the often reciprocal interactions of autophagy with other determinants of aging, is placing autophagy at the center of the aging process. In this work, we summarize evidence for the contribution of autophagy to health- and lifespan and provide examples of the bidirectional interplay between autophagic pathways and several of the so-called hallmarks of aging. This central role of autophagy in aging, and the dependence on autophagy of many geroprotective interventions, has motivated a search for direct modulators of autophagy that could be used to slow aging and extend healthspan. Here, we review some of those ongoing therapeutic efforts and comment on the potential of targeting autophagy in aging.

PKCλ/ι inhibition activates an ULK2-mediated interferon response to repress tumorigenesis.

The interferon (IFN) pathway is critical for cytotoxic T cell activation, which is central to tumor immunosurveillance and successful immunotherapy. We demonstrate here that PKCλ/ι inactivation results in the hyper-stimulation of the IFN cascade and the enhanced recruitment of CD8+ T cells that impaired the growth of intestinal tumors. PKCλ/ι directly phosphorylates and represses the activity of ULK2, promoting its degradation through an endosomal microautophagy-driven ubiquitin-dependent mechanism. Loss of PKCλ/ι results in increased levels of enzymatically active ULK2, which, by direct phosphorylation, activates TBK1 to foster the activation of the STING-mediated IFN response. PKCλ/ι inactivation also triggers autophagy, which prevents STING degradation by chaperone-mediated autophagy. Thus, PKCλ/ι is a hub regulating the IFN pathway and three autophagic mechanisms that serve to maintain its homeostatic control. Importantly, single-cell multiplex imaging and bioinformatics analysis demonstrated that low PKCλ/ι levels correlate with enhanced IFN signaling and good prognosis in colorectal cancer patients.

PKCλ/ι Loss Induces Autophagy, Oxidative Phosphorylation, and NRF2 to Promote Liver Cancer Progression.

Oxidative stress plays a critical role in liver tissue damage and in hepatocellular carcinoma (HCC) initiation and progression. However, the mechanisms that regulate autophagy and metabolic reprogramming during reactive oxygen species (ROS) generation, and how ROS promote tumorigenesis, still need to be fully understood. We show that protein kinase C (PKC) λ/ι loss in hepatocytes promotes autophagy and oxidative phosphorylation. This results in ROS generation, which through NRF2 drives HCC through cell-autonomous and non-autonomous mechanisms. Although PKCλ/ι promotes tumorigenesis in oncogene-driven cancer models, emerging evidence demonstrate that it is a tumor suppressor in more complex carcinogenic processes. Consistently, PKCλ/ι levels negatively correlate with HCC histological tumor grade, establishing this kinase as a tumor suppressor in liver cancer.

Pros and Cons of Chaperone-Mediated Autophagy in Cancer Biology.

Autophagy contributes to cellular quality control and energetics through lysosomal breakdown and recycling of essential cellular components. Chaperone-mediated autophagy (CMA) adds to these autophagic functions the ability to timely and selectively degrade single tagged proteins to terminate their cellular function and, in this way, participate in the regulation of multiple cellular processes. Many cancer cells upregulate CMA for protumorigenic and prosurvival purposes. However, growing evidence supports a physiological role for CMA in limiting malignant transformation. Understanding the mechanisms behind this functional switch of CMA from antioncogenic to pro-oncogenic is fundamental for targeting CMA in cancer treatment. We summarize current understanding of CMA functions in cancer biology and discuss the basis for its context-dependent dual role in oncogenesis.

Sarcosine Is Uniquely Modulated by Aging and Dietary Restriction in Rodents and Humans.

A hallmark of aging is a decline in metabolic homeostasis, which is attenuated by dietary restriction (DR). However, the interaction of aging and DR with the metabolome is not well understood. We report that DR is a stronger modulator of the rat metabolome than age in plasma and tissues. A comparative metabolomic screen in rodents and humans identified circulating sarcosine as being similarly reduced with aging and increased by DR, while sarcosine is also elevated in long-lived Ames dwarf mice. Pathway analysis in aged sarcosine-replete rats identify this biogenic amine as an integral node in the metabolome network. Finally, we show that sarcosine can activate autophagy in cultured cells and enhances autophagic flux in vivo, suggesting a potential role in autophagy induction by DR. Thus, these data identify circulating sarcosine as a biomarker of aging and DR in mammalians and may contribute to age-related alterations in the metabolome and in proteostasis.

Transcription factor NFE2L2/NRF2 modulates chaperone-mediated autophagy through the regulation of LAMP2A.

Chaperone-mediated autophagy (CMA) is a selective degradative process for cytosolic proteins that contributes to the maintenance of proteostasis. The signaling mechanisms that control CMA are not fully understood but might involve response to stress conditions including oxidative stress. Considering the role of CMA in redoxtasis and proteostasis, we sought to determine if the transcription factor NFE2L2/NRF2 (nuclear factor, erythroid derived 2, like 2) has an impact on CMA modulation. In this work, we identified and validated 2 NFE2L2 binding sequences in the LAMP2 gene and demonstrated in several human and mouse cell types that NFE2L2 deficiency and overexpression was linked to reduced and increased LAMP2A levels, respectively. Accordingly, lysosomal LAMP2A levels were drastically reduced in nfe2l2-knockout hepatocytes, which also displayed a marked decrease in CMA activity. Oxidant challenge with paraquat or hydrogen peroxide, or pharmacological activation of NFE2L2 with sulforaphane or dimethyl fumarate also increased LAMP2A levels and CMA activity. Overall, our study identifies for the first time basal and inducible regulation of LAMP2A, and consequently CMA activity, by NFE2L2. ABBREVIATIONS: ACTB: actin, beta, ARE: antioxidant response element; ATG5: autophagy related 5; BACH1: BTB domain and CNC homolog 1; ChIP: chromatin immunoprecipitation; CMA: chaperone-mediated autophagy; DHE: dihydroethidium; DMF: dimethyl fumarate; ENCODE: Encyclopedia of DNA elements at the University of California, Santa Cruz; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GBA: glucosylceramidase beta; GFP: green fluorescent protein; HMOX1: heme oxygenase 1; H2O2: hydrogen peroxide; HSPA8/HSC70: heat shock protein family A (Hsp70) member 8; KEAP1: kelch like ECH associated protein 1; LAMP2A: lysosomal associated membrane protein 2A; LAMP2B: lysosomal associated membrane protein 2B; LAMP2C: lysosomal associated membrane protein 2C; LAMP1: lysosomal associated membrane protein 1; MAFF: MAF bZIP transcription factor F; MAFK: MAF bZIP transcription factor K; NFE2L2/NRF2: nuclear factor, erythroid derived 2, like 2; NQO1: NAD(P)H quinone dehydrogenase 1; PQ: paraquat; PI: protease inhibitors; qRT-PCR: quantitative real-time polymerase chain reaction; RNASE: ribonuclease A family member; SFN: sulforaphane; SQSTM1/p62: sequestosome 1; TBP: TATA-box binding protein.

Factors influencing family care by immigrant women in Spain: a qualitative study / Fatores que influem no cuidado familiar prestado por mulheres imigrantes na Espanha: um estudo qualitativo / Factores que influyen en el cuidado familiar prestado por mujeres inmigrantes en España: un estudio cualitativo

Abstract Objective. To identify and understand factors that influence the relationships in the environment of family care provided by live-in immigrant caregivers. Methods. Interpretive qualitative study from a phenomenological perspective, using in-depth interviews, discussion groups and participant observation. The observation unit was the Sevillian families (Spain) with elderly dependents and a live-in female immigrant caregiver. Analysis units considered were health, care, dependence, gender, ethnicity and social class. Categories were analysed using QSR-NUD*ISTVivo9. After saturation, we triangulated between researchers, disciplines, sources and techniques to validate the results. Results. Factors of cultural discovery or clash were: language, religion, food, concept of space and time, caregiver's name and the attitudes held by both the hiring family, related to its social class, and by caregivers. Conclusion. Interpersonal relationships are the most important factor: an egalitarian relationship based on good treatment is beneficial to all involved. Knowing these codes will improve the quality of professional care in the family.

Resumo Objetivo. Identificar e compreender os fatores que influem nas relações no contexto do cuidado familiar prestado por mulheres imigrantes internas contratadas. Métodos. Estudo qualitativo interpretativo desde uma perspectiva fenomenológica, se utilizaram entrevistas em profundidade, grupos de discussão e observação participante. A unidade de observação a constituem famílias sevilhanas (Espanha) com adultos maiores dependentes a seu cargo e cuidadora imigrante interna contratada. Como unidades de análise se contemplaram: saúde, cuidados, dependência, gênero, etnia, classe social. As categorias se analisaram com o programa informático QSR NUD*ISTVivo9. Após chegar à saturação, se triangularam investigadoras, disciplinas, fontes e técnicas, para validar os resultados. Resultados. Como elementos de encontro/choque cultural se encontraram: a linguagem, a religião, a alimentação, a noção espaço-tempo, o nome da cuidadora e as atitudes, tanto da família que contratadora, relacionada com sua classe social, como das cuidadoras. Conclusão. As relações interpessoais é o fator mais importante: uma relação baseada no bom trato beneficia a todas as pessoas implicadas. Conhecer estas chaves pode favorecer a qualidade do cuidado profissional enfermeiro prestado à família.

Resumen Objetivo. Identificar y comprender los factores que influyen en las relaciones en el contexto del cuidado familiar prestado por mujeres inmigrantes internas contratadas. Métodos . Estudio cualitativo interpretativo desde una perspectiva fenomenológica. Para el efecto, se utilizaron entrevistas en profundidad, grupos de discusión y observación participante. La unidad de observación la constituyen familias sevillanas (España) con adultos mayores dependientes a su cargo y con una cuidadora inmigrante interna contratada. Como unidades de análisis se contemplaron: salud, cuidados, dependencia, género, etnicidad, clase social. Las categorías se analizaron con el programa informático QSR NUD*ISTVivo9. Tras llegar a la saturación, se triangularon investigadoras, disciplinas, fuentes y técnicas para validar los resultados. Resultados . Como elementos de encuentro/choque cultural se han encontrado: el lenguaje, la religión, la alimentación, la noción espacio-tiempo, el nombre de la cuidadora y las actitudes, tanto de la familia que contrata -relacionada con su clase social-, así como de las cuidadoras. Conclusión. Las relaciones interpersonales son el factor más importante: una relación basada en el buen trato beneficia a todas las personas implicadas. Conocer estas claves puede favorecer la calidad del cuidado profesional enfermero prestado a la familia.

Influence of Gender and Care Strategy in Family Caregivers´ Strain: A Cross-Sectional Study.

PURPOSE: To analyze the factors that influence the strain on family caregivers of elderly dependent people, relating it to the strategy of care, with a gender perspective. DESIGN: Cross-sectional study. METHODS: We interviewed 328 Spanish family caregivers in 2012. Main variable: Caregiver Strain Index (CSI). INDEPENDENT VARIABLES: relationship, sex, age, marital status, education level, employment status, socioeconomic status, family and/or institutional supports, time they devote to care, and how long they have been giving care. Data were analyzed using bivariate procedures and multiple linear regression. FINDINGS: Caregiver profile: women around 60 years old, housewives, with primary education. CSI average: 6.63 ± 3.36. Female sex, kinship being a son or daughter, housewife employment status, service of home care, and the care recipient being female were significantly associated with the subjective strain. CONCLUSIONS: Caregivers´ strain has a strong gender component: women are more tired, primarily those that practice a partial care strategy. CLINICAL RELEVANCE: Knowing the factors that predict burden, nurses may help caregivers to provide better care. A risk profile for strain and burden: women who practice a partial care strategy; they are adult women and daughters who do not want to give up their professional role and combine it with their duty of caregiving.

Structural and Biological Interaction of hsc-70 Protein with Phosphatidylserine in Endosomal Microautophagy.

hsc-70 (HSPA8) is a cytosolic molecular chaperone, which plays a central role in cellular proteostasis, including quality control during protein refolding and regulation of protein degradation. hsc-70 is pivotal to the process of macroautophagy, chaperone-mediated autophagy, and endosomal microautophagy. The latter requires hsc-70 interaction with negatively charged phosphatidylserine (PS) at the endosomal limiting membrane. Herein, by combining plasmon resonance, NMR spectroscopy, and amino acid mutagenesis, we mapped the C terminus of the hsc-70 LID domain as the structural interface interacting with endosomal PS, and we estimated an hsc-70/PS equilibrium dissociation constant of 4.7 ± 0.1 µm. This interaction is specific and involves a total of 4-5 lysine residues. Plasmon resonance and NMR results were further experimentally validated by hsc-70 endosomal binding experiments and endosomal microautophagy assays. The discovery of this previously unknown contact surface for hsc-70 in this work elucidates the mechanism of hsc-70 PS/membrane interaction for cytosolic cargo internalization into endosomes.

Factors influencing family care by immigrant women in Spain: a qualitative study.

OBJECTIVES: To identify and understand factors that influence the relationships in the environment of family care provided by live-in immigrant caregivers. METHODS: Interpretive qualitative study from a phenomenological perspective, using in-depth interviews, discussion groups and participant observation. The observation unit was the Sevillian families (Spain) with elderly dependents and a live-in female immigrant caregiver. Analysis units considered were health, care, dependence, gender, ethnicity and social class. Categories were analysed using QSR-NUD*ISTVivo9. After saturation, we triangulated between researchers, disciplines, sources and techniques to validate the results. RESULTS: Factors of cultural discovery or clash were: language, religion, food, concept of space and time, caregiver's name and the attitudes held by both the hiring family, related to its social class, and by caregivers. CONCLUSIONS: Interpersonal relationships are the most important factor: an egalitarian relationship based on good treatment is beneficial to all involved. Knowing these codes will improve the quality of professional care in the family.

Lysosomal mTORC2/PHLPP1/Akt Regulate Chaperone-Mediated Autophagy.

Chaperone-mediated autophagy (CMA), a selective form of degradation of cytosolic proteins in lysosomes, contributes to maintenance of proteostasis and to the cellular adaptation to stress. CMA substrates are delivered by a cytosolic chaperone to the lysosomal surface, where, upon unfolding, they are internalized through a membrane translocation complex. The molecular components that participate in CMA substrate targeting and translocation are well characterized, but those involved in CMA regulation remain mostly unknown. In this study, we have identified that CMA is under the positive control of the phosphatase PHLPP1 that associates with the lysosomal membrane and counteracts the inhibitory effect of mTORC2 on CMA. Lysosomal Akt, a target of the mTORC2/PHLPP1 kinase-phosphatase pair, modulates CMA activity by controlling the dynamics of assembly and disassembly of the CMA translocation complex at the lysosomal membrane. The lysosomal mTORC2/PHLPP1/Akt axis could become a target to restore CMA dysfunction in aging and disease.

Estrategias de provisión de cuidados familiares a personas mayores dependientes / Strategies of providing care for dependent older family

Objetivo: Explorar, identificar y caracterizar las distintas estrategias de provisión de cuidados a mayores dependientes que desarrollan las personas cuidadoras familiares. Metodología: Cualitativa. Unidad de observación: familias sevillanas con mayores dependientes. Unidades de análisis: cuidado, salud, género. Obtención de información: revisión bibliográfica literaria/bases de datos, entrevistas en profundidad, grupo de discusión. Análisis: Semántico y pragmático. Resultados: No existen trabajos indexados. Cuidar sigue siendo femenino, tiene repercusiones negativas en la salud de las personas cuidadoras. Las medidas institucionales son mejores pero insuficientes, no siempre fomentan la autonomía de las cuidadoras. Las familias desarrollan otras formas de cuidar: los hombres se están incorporando, y se contratan. La organización de los cuidados depende del proyecto de vida de la persona cuidadora; nivel económico y mandato de género. Conclusiones: Hay distintas estrategias de provisión de cuidados familiares: Asunción total de cuidados/Gestión en convivencia/Gestión en domicilios separados. Unas protegen más que otras la salud (AU)

Objective: To explore, identify an characterize the different strategies of providing care for dependent older family by family caregivers. Methods: Qualitative. Observation unit: sevillian families with elderly dependents. Analysis units: care, health, gender. Information research: literature review from data bases, deep interviews, discussion grous. Analysis: Semantic and pragmatic. Results: No indexed studies were found. Caring is still female and has a negative impact on the carers' health. The institutional support is now better but not enough and it doesn't always promote caregivers' autonomy. Different forms of care are developed by families: men who cares and caring employment. The care organization depends on the caregiver's life project, economic possibilities and gender mandate. Conclusions: There are different family caregiving strategies: Whole care assumption / Coexistence management / Separate homes management. Some of these are more protective than others for health (AU)

Interplay of LRRK2 with chaperone-mediated autophagy.

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease. We found LRRK2 to be degraded in lysosomes by chaperone-mediated autophagy (CMA), whereas the most common pathogenic mutant form of LRRK2, G2019S, was poorly degraded by this pathway. In contrast to the behavior of typical CMA substrates, lysosomal binding of both wild-type and several pathogenic mutant LRRK2 proteins was enhanced in the presence of other CMA substrates, which interfered with the organization of the CMA translocation complex, resulting in defective CMA. Cells responded to such LRRK2-mediated CMA compromise by increasing levels of the CMA lysosomal receptor, as seen in neuronal cultures and brains of LRRK2 transgenic mice, induced pluripotent stem cell-derived dopaminergic neurons and brains of Parkinson's disease patients with LRRK2 mutations. This newly described LRRK2 self-perpetuating inhibitory effect on CMA could underlie toxicity in Parkinson's disease by compromising the degradation of α-synuclein, another Parkinson's disease-related protein degraded by this pathway.

El cuidado familiar prestado por mujeres inmigrantes y su repercusión en la calidad del cuidado y en la salud / Family care provided by immigrant women and its impact on the quality of care and health

ObjetivoComprender las repercusiones del cuidado familiar ejercido por inmigrantes contratadas en régimen interno, en la salud de ellas mismas, de las personas mayores dependientes y de sus familias, en Sevilla.MétodoSe diseñó un estudio cualitativo, utilizando entrevistas en profundidad a informantes-clave, cuidadoras inmigrantes, personas mayores dependientes y familias, y grupos de discusión de profesionales sanitarios. El estudio se realizó en Sevilla entre los años 2006 y 2008. Unidad de observación: familias con mayores dependientes a su cargo y cuidadora inmigrante interna contratada. Unidades de análisis: salud, cuidados, dependencia, género, etnia y clase social. El análisis de categorías, predeterminadas y emergentes, se realizó con QSR NUD*ISTVivo1.3. Tras llegar a la saturación, se triangularon disciplinas, investigadoras, fuentes y técnicas, para enriquecer y validar los resultados.ResultadosEn la salud de las cuidadoras inmigrantes influyen, fundamentalmente, la repercusión del trabajo de cuidar y el proceso migratorio. Las relaciones interpersonales son el factor que más influye en la salud de todas las personas implicadas.ConclusionesEl cuidado familiar encargado a mujeres inmigrantes, unido al duelo migratorio, tiene importantes repercusiones en su salud. Si las relaciones interpersonales son de buen trato e igualitarias, se constituyen como factor de protección para todas las personas en contacto (AU)

Objective: To understand the effects of care within the family provided by live-in female immigrants onelderly dependents and their families and the carers themselves in Seville (Spain).Methods: We designed a qualitative study using in-depth interviews of key informants, immigrant careworkers, elderly dependents and their families, and discussion groups composed of health professionals.The study was carried out in Seville between 2006 and 2008. The observation unit consisted of thefamilies of elderly dependents with a live-in female immigrant care worker. The analysis units werehealth, care, dependence, gender, ethnicity and social class. Category analysis was carried out using QSRNUD*ISTVivo1.3.After saturation,we triangulatedamongdisciplines, researchers, sources andtechniquesto validate the results.Results: The most important factors for carers’ health were the migration process and care tasks. Interpersonal relationships constituted the principal factor affecting the health of all involved.Conclusions: The care tasks provided by immigrant women, together with the migration process, havean important impact on their health. Good and egalitarian interpersonal relationships are a protectivefactor for health (AU)

Sobrecarga sentida en personas cuidadoras informales de pacientes pluripatológicos en una zona urbana / Overload in the informal caregivers of patients with multiple comorbidities in an urban area

Objetivos: Determinar el perfil de la persona cuidadora familiar de pacientes pluripatológicos, identificar factores asociados a la sobrecarga sentida y manifestaciones de cansancio. Construir modelos predictivos mediante los ítems del Índice de Esfuerzo del Cuidador (IEC). Método Estudio descriptivo transversal. Población de estudio: personas cuidadoras de pacientes pluripatológicos de centro de salud urbano. Recogida de datos desde la historia clínica y mediante cuestionarios (índice de Barthel, índice de Pfeiffer, IEC). Análisis estadístico mediante medidas de centralización, de dispersión y mediante la construcción de modelos multivariantes con regresión logística binaria (RLB) con los ítems del IEC como predictoras (programa R versión 2.14.0). Resultados Muestra total de 67 personas cuidadoras, con una edad media de 64,69 años (desviación estándar=12,71; mediana 62 años); un 74,6% mujeres, un 35,8% esposas e hijas un 32,8%. El nivel de dependencia de las personas cuidadas fue total/severa del 77,6% y moderada del 12% (Barthel); un 47,8% tenían algún nivel de deterioro cognitivo (Pfeiffer). IEC>7 en el 47,8% de cuidadoras, identificándose en >40% inconvenientes para la vida, restricción de vida social, esfuerzo físico, molestias ante cambios, comportamientos molestos, cambios emocionales personales y familiares, y trastornos del sueño. El ítem n.° 4 del IEC que analiza la restricción social fue el que mostró una mayor significación en el modelo predictivo del estrés del cuidador. El ítem n.° 12 (sobrecarga económica) fue el más significativo en los pacientes con deterioro cognitivo. Conclusiones Las mujeres suelen adoptar el rol de cuidadora a una edad más temprana que los hombres en el entorno urbano estudiado, y con relación al IEC, son los ítems n.° 4 (restricción social) y n.° 12 (sobrecarga económica) los que tienen más significación en los modelos predictivos construidos con RLB (AU)

Objectives: The aim of the study was, to determine the profile of the family caregiver of patients with multiple pathologies, identify factors associated with overload, and construct predictive models using items from the Caregiver Strain Index (CSI). Method: A cross-sectional study of caregivers of patients with multiple comorbidities who attended an urban health centre. Data were collected from health records and questionnaires (Barthel index, Pfeiffer index, and CSI). Statistical analysis was performed using measures of central tendency and dispersion, and by building multivariate models with binary logistic regression with the CSI items as predictors (program R version 2.14.0). Results: The sample included 67 caregivers, with a mean age of 64.69 years (standard deviation = 12.71, median 62 years), of whom 74.6% were women, 35.8% were wives, and 32.8% were daughters. The level of dependence of the patients cared for was total/severe in 77.6%, and moderate in 12% (Barthel), and 47.8% had some level of cognitive impairment (Pfeiffer). A CSI equal or greater than 7 was seen in 47.8% of caregivers, identifying life problems in more than 40% of them such as, restriction of social life, physical exertion, discomfort with change, bad behaviour, personal and family emotional changes, and sleep disturbances. Item 4 of the CSI, analysing the social restriction, was the one that showed a greater significance in the predictive multivariate model. Item 12 (economic burden) was the most signifi can't with age in patients with cognitive impairment. Conclusions: Women tend to take the role of caregiver at an earlier age than men in the urban environment studied, and items from CSI showed that items 4 (social restrictions) and 12 (economic burden) have more significance in the predictive models constructed with Binary Logistic Regression (AU)

[Overload in the informal caregivers of patients with multiple comorbidities in an urban area]. / Sobrecarga sentida en personas cuidadoras informales de pacientes pluripatológicos en una zona urbana.

OBJECTIVES: The aim of the study was, to determine the profile of the family caregiver of patients with multiple pathologies, identify factors associated with overload, and construct predictive models using items from the Caregiver Strain Index (CSI). METHOD: A cross-sectional study of caregivers of patients with multiple comorbidities who attended an urban health centre. Data were collected from health records and questionnaires (Barthel index, Pfeiffer index, and CSI). Statistical analysis was performed using measures of central tendency and dispersion, and by building multivariate models with binary logistic regression with the CSI items as predictors (program R version 2.14.0). RESULTS: The sample included 67 caregivers, with a mean age of 64.69 years (standard deviation=12.71, median 62 years), of whom 74.6% were women, 35.8% were wives, and 32.8% were daughters. The level of dependence of the patients cared for was total/severe in 77.6%, and moderate in 12% (Barthel), and 47.8% had some level of cognitive impairment (Pfeiffer). A CSI equal or greater than 7 was seen in 47.8% of caregivers, identifying life problems in more than 40% of them such as, restriction of social life, physical exertion, discomfort with change, bad behaviour, personal and family emotional changes, and sleep disturbances. Item 4 of the CSI, analysing the social restriction, was the one that showed a greater significance in the predictive multivariate model. Item 12 (economic burden) was the most significant with age in patients with cognitive impairment. CONCLUSIONS: Women tend to take the role of caregiver at an earlier age than men in the urban environment studied, and items from CSI showed that items 4 (social restrictions) and 12 (economic burden) have more significance in the predictive models constructed with Binary Logistic Regression.

[Family care provided by immigrant women and its impact on the quality of care and health]. / El cuidado familiar prestado por mujeres inmigrantes y su repercusión en la calidad del cuidado y en la salud.

OBJECTIVE: To understand the effects of care within the family provided by live-in female immigrants on elderly dependents and their families and the carers themselves in Seville (Spain). METHODS: We designed a qualitative study using in-depth interviews of key informants, immigrant care workers, elderly dependents and their families, and discussion groups composed of health professionals. The study was carried out in Seville between 2006 and 2008. The observation unit consisted of the families of elderly dependents with a live-in female immigrant care worker. The analysis units were health, care, dependence, gender, ethnicity and social class. Category analysis was carried out using QSR-NUD*ISTVivo1.3. After saturation, we triangulated among disciplines, researchers, sources and techniques to validate the results. RESULTS: The most important factors for carers' health were the migration process and care tasks. Interpersonal relationships constituted the principal factor affecting the health of all involved. CONCLUSIONS: The care tasks provided by immigrant women, together with the migration process, have an important impact on their health. Good and egalitarian interpersonal relationships are a protective factor for health.