Analysis of the Psychosocial Sphere of Older Adults in Extreme Poverty in the Peruvian Amazon.

The situation of social exclusion in which older adults live in extreme poverty is a problem that leads to psychological alterations such as depression or cognitive deterioration. Our objective was to analyze the living conditions and the psychosocial sphere of older adult people living in extreme poverty in Requena del Tapiche in Peru. This was an observational, descriptive, cross-sectional study. Sixty participants between 60 and 100 years of age of both sexes were included who gave their informed consent. Sociodemographic variables were analyzed, and the Gijón, family Apgar, Yesavage, and Pfeiffer scales were used. The sample was composed of 55% women and 45% men, with a mean age of 79.2 years (SD 6.67). More than half live alone or with their spouse. Fifty-seven percent sleep on the floor or on wood, and about 82% do not have safe water. Family dysfunction is found in 40%, and 98% are at social risk or with an established social problem and a precarious economic situation. More than 60% suffer from depressive symptoms, which are more frequent in women. We conclude that older adults perceive deficient family support, observing a deteriorated social situation. Most of them are at risk of social exclusion and loneliness, making them more vulnerable. They show sadness, with a high rate of depression. People with more cognitive impairment live alone, and those in social exclusion suffer a higher degree of depression. More cooperative projects and health promotion interventions developed in the peripheral neighborhoods of Requena del Tapiche are needed to improve the impact on the health of older adult people in extreme poverty.

Value of estimating pulse wave velocity compared to SCORE in cardiovascular risk stratification in community pharmacies / Valor de la estimación de la velocidad de onda de pulso en comparación con SCORE en la estratificación del riesgo cardiovascular en farmacias comunitarias

Objectives Arterial stiffness is considered to be an intermediate marker with independent prognostic value. The objective of this study is to assess whether the estimation of arterial stiffness can improve CV risk stratification compared to SCORE in patients at community pharmacies. Methods Observational prospective epidemiological study in which consecutive individuals entering a participating Community Pharmacy are offered a voluntary measurement of blood pressure and estimation of pulse wave velocity by oscillometry (AGEDIO, IEM®) to stratify their CV risk according to SCORE compared to the use of arterial stiffness. Results After nine months of recruitment, data from 923 patients (570 women, 353 men) were collected. 16/122 (13.1%) patients under 40 years and 72/364 (19.8%) over 65 years of age presented pathological stiffness and could be classified as high-risk, even though being out of the age-range of SCORE. Of the 437 (47.3%) patients who were susceptible to calculating SCORE, 42/437 patients (9.6%) presented pathological arterial stiffness. Cholesterol values were available in 281 patients (64.3%). Among them, according to SCORE, only 6 (2.1%) fell into the high-risk category. Conclusions More than half of the subjects who randomly enter a community pharmacy had ages that make it impossible to calculate the CV risk by SCORE. Among them, arterial damage was detected in 18.1%. Of the other half, 9.6% presented arterial damage and, therefore, high CV risk, when SCORE only detected it in 2.1%. Therefore, estimating arterial stiffness in community pharmacies markedly improves detection of high CV risk compared to SCORE (AU)

Objetivos La rigidez arterial es un marcador intermedio con valor pronóstico independiente. Nuestro objetivo es valorar si la estimación de la rigidez arterial puede mejorar la estratificación del riesgo cardiovascular (CV) en comparación con SCORE. Métodos Estudio epidemiológico observacional prospectivo en el que se ofrece a pacientes consecutivos que entran en una farmacia participante la medición voluntaria de la presión arterial y de la velocidad de onda de pulso estimada por oscilometría (AGEDIO, IEM®) para estratificar su riesgo CV según SCORE o según la presencia de rigidez arterial. Resultados Tras 9 meses de reclutamiento, presentamos datos de 923 pacientes (570 mujeres, 353 hombres). Dieciséis/122 (13,1%) pacientes <40años y 72/364 (19,8%) >65años presentaron rigidez arterial patológica y fueron clasificados de alto riesgo, aun hallándose fuera del rango de edad de SCORE. De los 437 (47,3%) pacientes evaluables por SCORE, 42/437 pacientes (9,6%) mostraron rigidez elevada. Los valores de colesterol estaban disponibles en 281 de estos pacientes (64,3%). Entre ellos, según SCORE, solo 6 (2,1%) eran de la categoría de alto riesgo. Conclusiones Más de la mitad de sujetos que entran aleatoriamente en una farmacia comunitaria tenían edades situadas fuera de los rangos de SCORE, imposibilitando el cálculo del riesgo CV con SCORE. En este grupo se constató daño arterial en el 18,1%. En la otra mitad, el 9,6% presentaron daño vascular y, consecuentemente, riesgo elevado, mientras que SCORE solo detectó riesgo elevado en el 2,1%. Por tanto, la estimación de la rigidez arterial en farmacias comunitarias mejora claramente la detección de riesgo CV elevado en comparación con SCORE (AU)

Assessing Nutritional Status and Frailty among Poor Elderly Individuals in Requena del Tapiche, Peru.

Frailty is a biological syndrome that leads to a loss of physiological reserve, increasing susceptibility to adverse health events. In the Peruvian Amazon, the elderly live with hardly any economic resources, presenting a caloric deficit that is related to functional and cognitive deterioration. Our objective was to identify the health needs of elderly people living in extreme poverty in Requena (Peru) by means of a geriatric assessment of the nutritional and functional spheres to design, in the future, a cooperation project appropriate to the needs detected. This is an observational, descriptive, and cross-sectional study. Sixty participants were included, and sociodemographic and functional status variables were analyzed using the MNA and Barthel scales and the Get Up and Go test. The mean age of the participants was 79 ± 6.67 (women 55% and men 45%), where 60% had frailty. A statistically significant relationship was found between the MNA scores and Barthel test. Eighty-five percent were malnourished or at risk and thirteen percent had total or moderate dependence. We conclude that the nutritional status of the elderly was deficient. The high degree of living alone in which they live forces them to maintain their independence and their walking stability is normal. The situation of frailty exceeds the national average, a situation that has repercussions for their quality of life. We found a statistically significant association between nutritional status, dependence, and frailty. The better-nourished elderly are less frail and less dependent.

Value of estimating pulse wave velocity compared to SCORE in cardiovascular risk stratification in community pharmacies.

OBJECTIVES: Arterial stiffness is considered to be an intermediate marker with independent prognostic value. The objective of this study is to assess whether the estimation of arterial stiffness can improve CV risk stratification compared to SCORE in patients at community pharmacies. METHODS: Observational prospective epidemiological study in which consecutive individuals entering a participating Community Pharmacy are offered a voluntary measurement of blood pressure and estimation of pulse wave velocity by oscillometry (AGEDIO, IEM®) to stratify their CV risk according to SCORE compared to the use of arterial stiffness. RESULTS: After nine months of recruitment, data from 923 patients (570 women, 353 men) were collected. 16/122 (13.1%) patients under 40 years and 72/364 (19.8%) over 65 years of age presented pathological stiffness and could be classified as high-risk, even though being out of the age-range of SCORE. Of the 437 (47.3%) patients who were susceptible to calculating SCORE, 42/437 patients (9.6%) presented pathological arterial stiffness. Cholesterol values were available in 281 patients (64.3%). Among them, according to SCORE, only 6 (2.1%) fell into the high-risk category. CONCLUSIONS: More than half of the subjects who randomly enter a community pharmacy had ages that make it impossible to calculate the CV risk by SCORE. Among them, arterial damage was detected in 18.1%. Of the other half, 9.6% presented arterial damage and, therefore, high CV risk, when SCORE only detected it in 2.1%. Therefore, estimating arterial stiffness in community pharmacies markedly improves detection of high CV risk compared to SCORE.

Adaptation to spindle assembly checkpoint inhibition through the selection of specific aneuploidies.

Both the presence of an abnormal complement of chromosomes (aneuploidy) and an increased frequency of chromosome missegregation (chromosomal instability) are hallmarks of cancer. Analyses of cancer genome data have identified certain aneuploidy patterns in tumors; however, the bases behind their selection are largely unexplored. By establishing time-resolved long-term adaptation protocols, we found that human cells adapt to persistent spindle assembly checkpoint (SAC) inhibition by acquiring specific chromosome arm gains and losses. Independently adapted populations converge on complex karyotypes, which over time are refined to contain ever smaller chromosomal changes. Of note, the frequencies of chromosome arm gains in adapted cells correlate with those detected in cancers, suggesting that our cellular adaptation approach recapitulates selective traits that dictate the selection of aneuploidies frequently observed across many cancer types. We further engineered specific aneuploidies to determine the genetic basis behind the observed karyotype patterns. These experiments demonstrated that the adapted and engineered aneuploid cell lines limit CIN by extending mitotic duration. Heterozygous deletions of key SAC and APC/C genes recapitulated the rescue phenotypes of the monosomic chromosomes. We conclude that aneuploidy-induced gene dosage imbalances of individual mitotic regulators are sufficient for altering mitotic timing to reduce CIN.

Adaptation to high rates of chromosomal instability and aneuploidy through multiple pathways in budding yeast.

Both an increased frequency of chromosome missegregation (chromosomal instability, CIN) and the presence of an abnormal complement of chromosomes (aneuploidy) are hallmarks of cancer. To better understand how cells are able to adapt to high levels of chromosomal instability, we previously examined yeast cells that were deleted of the gene BIR1, a member of the chromosomal passenger complex (CPC). We found bir1Δ cells quickly adapted by acquiring specific combinations of beneficial aneuploidies. In this study, we monitored these yeast strains for longer periods of time to determine how cells adapt to high levels of both CIN and aneuploidy in the long term. We identify suppressor mutations that mitigate the chromosome missegregation phenotype. The mutated proteins fall into four main categories: outer kinetochore subunits, the SCFCdc4 ubiquitin ligase complex, the mitotic kinase Mps1, and the CPC itself. The identified suppressor mutations functioned by reducing chromosomal instability rather than alleviating the negative effects of aneuploidy. Following the accumulation of suppressor point mutations, the number of beneficial aneuploidies decreased. These experiments demonstrate a time line of adaptation to high rates of CIN.

Recruitment dynamics of ESCRT-III and Vps4 to endosomes and implications for reverse membrane budding.

The ESCRT machinery mediates reverse membrane scission. By quantitative fluorescence lattice light-sheet microscopy, we have shown that ESCRT-III subunits polymerize rapidly on yeast endosomes, together with the recruitment of at least two Vps4 hexamers. During their 3-45 s lifetimes, the ESCRT-III assemblies accumulated 75-200 Snf7 and 15-50 Vps24 molecules. Productive budding events required at least two additional Vps4 hexamers. Membrane budding was associated with continuous, stochastic exchange of Vps4 and ESCRT-III components, rather than steady growth of fixed assemblies, and depended on Vps4 ATPase activity. An all-or-none step led to final release of ESCRT-III and Vps4. Tomographic electron microscopy demonstrated that acute disruption of Vps4 recruitment stalled membrane budding. We propose a model in which multiple Vps4 hexamers (four or more) draw together several ESCRT-III filaments. This process induces cargo crowding and inward membrane buckling, followed by constriction of the nascent bud neck and ultimately ILV generation by vesicle fission.

ESCRT-III drives the final stages of CUPS maturation for unconventional protein secretion.

The unconventional secretory pathway exports proteins that bypass the endoplasmic reticulum. In Saccharomyces cerevisiae, conditions that trigger Acb1 secretion via this pathway generate a Grh1 containing compartment composed of vesicles and tubules surrounded by a cup-shaped membrane and collectively called CUPS. Here we report a quantitative assay for Acb1 secretion that reveals requirements for ESCRT-I, -II, and -III but, surprisingly, without the involvement of the Vps4 AAA-ATPase. The major ESCRT-III subunit Snf7 localizes transiently to CUPS and this was accelerated in vps4Δ cells, correlating with increased Acb1 secretion. Microscopic analysis suggests that, instead of forming intraluminal vesicles with the help of Vps4, ESCRT-III/Snf7 promotes direct engulfment of preexisting Grh1 containing vesicles and tubules into a saccule to generate a mature Acb1 containing compartment. This novel multivesicular / multilamellar compartment, we suggest represents the stable secretory form of CUPS that is competent for the release of Acb1 to cells exterior.

ESCRT-III and Vps4: a dynamic multipurpose tool for membrane budding and scission.

Complex molecular machineries bud, scission and repair cellular membranes. Components of the multi-subunit endosomal sorting complex required for transport (ESCRT) machinery are enlisted when multivesicular bodies are generated, extracellular vesicles are formed, the plasma membrane needs to be repaired, enveloped viruses bud out of host cells, defective nuclear pores have to be cleared, the nuclear envelope must be resealed after mitosis and for final midbody abscission during cytokinesis. While some ESCRT components are only required for specific processes, the assembly of ESCRT-III polymers on target membranes and the action of the AAA-ATPase Vps4 are mandatory for every process. In this review, we summarize the current knowledge of structural and functional features of ESCRT-III/Vps4 assemblies in the growing pantheon of ESCRT-dependent pathways. We describe specific recruitment processes for ESCRT-III to different membranes, which could be useful to selectively inhibit ESCRT function during specific processes, while not affecting other ESCRT-dependent processes. Finally, we speculate how ESCRT-III and Vps4 might function together and highlight how the characterization of their precise spatiotemporal organization will improve our understanding of ESCRT-mediated membrane budding and scission in vivo.

Coordinated binding of Vps4 to ESCRT-III drives membrane neck constriction during MVB vesicle formation.

Five endosomal sorting complexes required for transport (ESCRTs) mediate the degradation of ubiquitinated membrane proteins via multivesicular bodies (MVBs) in lysosomes. ESCRT-0, -I, and -II interact with cargo on endosomes. ESCRT-II also initiates the assembly of a ringlike ESCRT-III filament consisting of Vps20, Snf7, Vps24, and Vps2. The AAA-adenosine triphosphatase Vps4 disassembles and recycles the ESCRT-III complex, thereby terminating the ESCRT pathway. A mechanistic role for Vps4 in intraluminal vesicle (ILV) formation has been unclear. By combining yeast genetics, biochemistry, and electron tomography, we find that ESCRT-III assembly on endosomes is required to induce or stabilize the necks of growing MVB ILVs. Yet, ESCRT-III alone is not sufficient to complete ILV biogenesis. Rather, binding of Vps4 to ESCRT-III, coordinated by interactions with Vps2 and Snf7, is coupled to membrane neck constriction during ILV formation. Thus, Vps4 not only recycles ESCRT-III subunits but also cooperates with ESCRT-III to drive distinct membrane-remodeling steps, which lead to efficient membrane scission at the end of ILV biogenesis in vivo.

Membrane abscission: first glimpse at dynamic ESCRTs.

Advanced live-cell imaging of the endosomal sorting complexes required for transport (ESCRT) and computational modeling have provided insights into the Vps4-dependent dynamic rearrangements of ESCRT-III filaments during membrane constriction and abscission.

Assembly and disassembly of the ESCRT-III membrane scission complex.

The ESCRT (endosomal sorting complex required for transport) pathway promotes the final membrane scission step at the end of cytokinesis, assists viral budding and generates multivesicular bodies (MVBs). These seemingly unrelated processes require a topologically similar membrane deformation and scission event that buds membranes/vesicles out of the cytoplasm. The topology of this budding reaction is 'opposite' to reactions that bud endocytic and secretory vesicles into the cytoplasm. Here we summarize recent findings that help to understand how the ESCRT machinery, in particular the ESCRT-III complex, assembles on its target membranes, executes membrane scission and is disassembled by the AAA-ATPase Vps4.

Cobertura vacunal en la infancia en familias inmigrantes / Childhood vaccine cover in immigrant families

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