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We sequenced and assembled using multiple long-read sequencing technologies the genomes of chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, owl monkey, and marmoset. We identified 1,338,997 lineage-specific fixed structural variants (SVs) disrupting 1,561 protein-coding genes and 136,932 regulatory elements, including the most complete set of human-specific fixed differences. We estimate that 819.47 Mbp or â¼27% of the genome has been affected by SVs across primate evolution. We identify 1,607 structurally divergent regions wherein recurrent structural variation contributes to creating SV hotspots where genes are recurrently lost (e.g., CARD, C4, and OLAH gene families) and additional lineage-specific genes are generated (e.g., CKAP2, VPS36, ACBD7, and NEK5 paralogs), becoming targets of rapid chromosomal diversification and positive selection (e.g., RGPD gene family). High-fidelity long-read sequencing has made these dynamic regions of the genome accessible for sequence-level analyses within and between primate species.
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Genoma , Primates , Animales , Humanos , Secuencia de Bases , Primates/clasificación , Primates/genética , Evolución Biológica , Análisis de Secuencia de ADN , Variación Estructural del GenomaRESUMEN
Diverse inbred mouse strains are important biomedical research models, yet genome characterization of many strains is fundamentally lacking in comparison with humans. In particular, catalogs of structural variants (SVs) (variants ≥ 50 bp) are incomplete, limiting the discovery of causative alleles for phenotypic variation. Here, we resolve genome-wide SVs in 20 genetically distinct inbred mice with long-read sequencing. We report 413,758 site-specific SVs affecting 13% (356 Mbp) of the mouse reference assembly, including 510 previously unannotated coding variants. We substantially improve the Mus musculus transposable element (TE) callset, and we find that TEs comprise 39% of SVs and account for 75% of altered bases. We further utilize this callset to investigate how TE heterogeneity affects mouse embryonic stem cells and find multiple TE classes that influence chromatin accessibility. Our work provides a comprehensive analysis of SVs found in diverse mouse genomes and illustrates the role of TEs in epigenetic differences.
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To better understand the pattern of primate genome structural variation, we sequenced and assembled using multiple long-read sequencing technologies the genomes of eight nonhuman primate species, including New World monkeys (owl monkey and marmoset), Old World monkey (macaque), Asian apes (orangutan and gibbon), and African ape lineages (gorilla, bonobo, and chimpanzee). Compared to the human genome, we identified 1,338,997 lineage-specific fixed structural variants (SVs) disrupting 1,561 protein-coding genes and 136,932 regulatory elements, including the most complete set of human-specific fixed differences. Across 50 million years of primate evolution, we estimate that 819.47 Mbp or ~27% of the genome has been affected by SVs based on analysis of these primate lineages. We identify 1,607 structurally divergent regions (SDRs) wherein recurrent structural variation contributes to creating SV hotspots where genes are recurrently lost (CARDs, ABCD7, OLAH) and new lineage-specific genes are generated (e.g., CKAP2, NEK5) and have become targets of rapid chromosomal diversification and positive selection (e.g., RGPDs). High-fidelity long-read sequencing has made these dynamic regions of the genome accessible for sequence-level analyses within and between primate species for the first time.
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Unlike copy number variants (CNVs), inversions remain an underexplored genetic variation class. By integrating multiple genomic technologies, we discover 729 inversions in 41 human genomes. Approximately 85% of inversions <2 kbp form by twin-priming during L1 retrotransposition; 80% of the larger inversions are balanced and affect twice as many nucleotides as CNVs. Balanced inversions show an excess of common variants, and 72% are flanked by segmental duplications (SDs) or retrotransposons. Since flanking repeats promote non-allelic homologous recombination, we developed complementary approaches to identify recurrent inversion formation. We describe 40 recurrent inversions encompassing 0.6% of the genome, showing inversion rates up to 2.7 × 10-4 per locus per generation. Recurrent inversions exhibit a sex-chromosomal bias and co-localize with genomic disorder critical regions. We propose that inversion recurrence results in an elevated number of heterozygous carriers and structural SD diversity, which increases mutability in the population and predisposes specific haplotypes to disease-causing CNVs.
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Inversión Cromosómica , Duplicaciones Segmentarias en el Genoma , Inversión Cromosómica/genética , Variaciones en el Número de Copia de ADN/genética , Genoma Humano , Genómica , HumanosRESUMEN
While the COVID-19 pandemic has presented an immediate risk to human life around the world, climate change poses an arguably greater-although less immediate-threat to our species' survival. Within the framework of life-history theory (LHT), this pre-registered study investigated whether extrinsic risk (i.e., external factors that pose a risk to an individual's life, e.g., COVID-19) and existential risk (i.e., risks with outcomes that threaten the existence of humans as a species, e.g., climate change) had similar or different relationships with reproductive decision-making. A UK representative sample of 325 participants between 18 and 35 years of age was asked to indicate their ideal number of children, ideal age to start having children, and whether their desire for a child had recently changed. Participants were asked about their experiences of COVID-19 and given a series of scales with which to assess their beliefs about climate change. In support of LHT, the study found evidence that knowing people who had been hospitalized with or died of COVID-19 was associated with a greater ideal number of children. Conversely, there was no clear evidence of a relationship between climate change beliefs and reproductive decision-making. The repercussions for understanding how we interpret and respond to different forms of mortality risk are discussed.
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The divergence of chimpanzee and bonobo provides one of the few examples of recent hominid speciation1,2. Here we describe a fully annotated, high-quality bonobo genome assembly, which was constructed without guidance from reference genomes by applying a multiplatform genomics approach. We generate a bonobo genome assembly in which more than 98% of genes are completely annotated and 99% of the gaps are closed, including the resolution of about half of the segmental duplications and almost all of the full-length mobile elements. We compare the bonobo genome to those of other great apes1,3-5 and identify more than 5,569 fixed structural variants that specifically distinguish the bonobo and chimpanzee lineages. We focus on genes that have been lost, changed in structure or expanded in the last few million years of bonobo evolution. We produce a high-resolution map of incomplete lineage sorting and estimate that around 5.1% of the human genome is genetically closer to chimpanzee or bonobo and that more than 36.5% of the genome shows incomplete lineage sorting if we consider a deeper phylogeny including gorilla and orangutan. We also show that 26% of the segments of incomplete lineage sorting between human and chimpanzee or human and bonobo are non-randomly distributed and that genes within these clustered segments show significant excess of amino acid replacement compared to the rest of the genome.
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Evolución Molecular , Genoma/genética , Genómica , Pan paniscus/genética , Filogenia , Animales , Factor 4A Eucariótico de Iniciación/genética , Femenino , Genes , Gorilla gorilla/genética , Anotación de Secuencia Molecular/normas , Pan troglodytes/genética , Pongo/genética , Duplicaciones Segmentarias en el Genoma , Análisis de Secuencia de ADNRESUMEN
OBJECTIVE: To study the efficacy of middle meningeal artery (MMA) embolization for the treatment of chronic subdural hematoma (SDH) and characterize its post-embolization volumetric resolution. METHODS: Ten patients diagnosed with 13 cSDH underwent MMA embolization. SDH volumes were measured from time of initial discovery on imaging to pre-operative, post-operative, short-term and long-term follow-up. Time between procedure to obliteration was also measured. Volumetric analysis was done using the coniglobus formula, and recurrence rate as well as resolution timeline was defined using best-fit models. RESULTS: Out of 10 patients, five were recurrent lesions, three were bilateral and seven unilateral cSDH. Average and median pre-operative volumes were 105.3 cc and 97.4 cc, respectively. Embolization on average was performed 21 days after discovery. Sixty percent of patients had concurrent antiplatelets or anticoagulation use. Forty percent underwent embolization treatment as the primary therapy. Recurrence was not seen in any patients treated with embolization. There were no peri- or post-operative complications. Five patients experienced complete or near-complete obliteration, while those with partial resolution showed a composite average of 75% volumetric reduction in 45 days. Post-embolization, the volumetric resolution followed an exponential decay curve over time and was independent of initial volume. CONCLUSION: MMA embolization contributed to a marked reduction in SDH volume post-operatively and can be used as a curative therapy for primary or recurrent chronic SDH.
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Cooperation can be difficult to sustain when there is a temptation to free-ride on the efforts of others. In experiments, peer punishment often stabilizes cooperation but fails to improve earnings because of the costs associated with punishment. In addition, antisocial use of punishment-punishing cooperators, counterpunishing, and feuding-often leads to lower cooperation and earnings. The current study investigated if powerful individuals-individuals who can punish without cost or who are immune from punishment-police the antisocial use of punishment, thus reducing the undesirable effects of punishment. In order to create ample opportunities for antisocial punishment and identify the motives for the use of punishment, our modified public goods game implemented fixed groups, fixed participant identifiers, 2 punishment stages, and full information about participant actions. The powerful participants with cost-free punishment or immunity punished low contributors more often, and immune participants also punished those who punished cooperators. Intriguingly, we found that whenever all participants could be punished-regardless of the cost of punishing or asymmetry in the cost-cooperation and net earnings reached very high levels. However, participants who were immune cooperated at a markedly low level, reducing earnings in the group. The results show that in an environment with repeated interactions, plenty of information, and everyone being accountable, even inefficient punishment can maintain high cooperation and earnings, but immunity of the powerful leads to corrupt behavior and reduced efficiency. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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Perfluorohexane sulfonate (PFHxS) is a six-carbon perfluoroalkyl sulfonic acid that was used as an industrial surfactant, but is now found as an environmental contaminant worldwide. In addition to its use as an industrial surfactant, it is a legacy contaminant from the use of aqueous film-forming foams. Despite its widespread occurrence in the environment and evidence of biological activity associated with PFHxS and similar perfluoroalkyl sulfonic acids in rodents, there is no oral toxicity value currently available from the IRIS Database. To derive an oral reference dose (RfD) for PFHxS, available toxicity studies were reviewed using a weight-of-evidence approach. A 42-day mouse reproductive study was chosen as the critical study for the derivation of the oral RfD. Benchmark dose modeling was utilized to derive a point of departure (POD) for a reduction in litter size. A 95% lower confidence limit on the benchmark dose (BMDL) of 13,900â¯ng/mL (serum PFHxS) was modeled for a reduction in litter size. An oral RfD for PFHxS of 4.0â¯ng/kg/d was calculated by conversion of the BMDL to a human equivalent oral dose using a human half-life adjusted dosimetric conversion factor and the application of a total uncertainty factor of 300. Additional research is needed to better characterize the toxicity associated with oral exposure to PFHxS and refine the development of toxicity values.
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Ácidos Sulfónicos/normas , Tensoactivos/normas , Administración Oral , Animales , Fluorocarburos , Humanos , Tamaño de la Camada/efectos de los fármacos , Concentración Máxima Admisible , Ratones , Reproducción/efectos de los fármacos , Medición de Riesgo , Ácidos Sulfónicos/farmacocinética , Ácidos Sulfónicos/toxicidad , Tensoactivos/farmacocinética , Tensoactivos/toxicidadRESUMEN
Evidence for a role of supplemental vitamin D and marine omega-3 fatty acids in preventing cancer and cardiovascular disease (CVD) remains inconclusive and insufficient to inform nutritional recommendations for primary prevention. The VITamin D and Omega-A 3 TriaL (VITAL) is an ongoing nationwide, randomized, double-blind, placebo-controlled clinical trial designed to fill this knowledge gap. The study population consists of 25,874 U.S. adults without cancer or CVD at baseline, who were selected only on age (men aged ≥50 and women aged ≥55), with an oversampling of African Americans (n=5,107). In a 2 × 2 factorial design, participants were randomized to one of four supplement groups: [1] active vitamin D3 (cholecalciferol; 2000 IU/d) and active marine omega-3 fatty acids (Omacor® fish oil, eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA], 1g/d); [2] active vitamin D and omega-3 placebo; [3] vitamin D placebo and active marine omega-3 fatty acids; or [4] vitamin D placebo and omega-3 placebo. The mean length of the randomized treatment period will be 5 years. The randomization was successful, as evidenced by similar distributions of baseline demographic, health, and behavioral characteristics across treatment groups. The similar distribution of known potential confounders across treatment groups strongly suggests that unmeasured or unknown potential confounders are also equally distributed. VITAL is expected to provide important information on the benefit-risk balance of vitamin D and omega-3 fatty acid supplementation when taken for the primary prevention of cancer and CVD.
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Enfermedades Cardiovasculares/prevención & control , Colecalciferol/uso terapéutico , Suplementos Dietéticos , Ácidos Docosahexaenoicos/uso terapéutico , Ácido Eicosapentaenoico/uso terapéutico , Neoplasias/prevención & control , Prevención Primaria/métodos , Vitaminas/uso terapéutico , Anciano , Anciano de 80 o más Años , Protocolos Clínicos , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente , Proyectos de InvestigaciónRESUMEN
Third party punishment can be evolutionarily stable if there is heterogeneity in the cost of punishment or if punishers receive a reputational benefit from their actions. A dominant position might allow some individuals to punish at a lower cost than others and by doing so access these reputational benefits. Three vignette-based studies measured participants' judgements of a third party punisher in comparison to those exhibiting other aggressive/dominant behaviours (Study 1), when there was variation in the success of punishment (Study 2), and variation in the status of the punisher and the type of punishment used (Study 3). Third party punishers were judged to be more likeable than (but equally dominant as) those who engaged in other types of dominant behaviour (Study 1), were judged to be equally likeable and dominant whether their intervention succeeded or failed (Study 2), and participants believed that only a dominant punisher could intervene successfully (regardless of whether punishment was violent or non-violent) and that subordinate punishers would face a higher risk of retaliation (Study 3). The results suggest that dominance can dramatically reduce the cost of punishment, and that while individuals can gain a great deal of reputational benefit from engaging in third party punishment, these benefits are only open to dominant individuals. Taking the status of punishers into account may therefore help explain the evolution of third party punishment.
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Conducta Cooperativa , Teoría del Juego , Castigo , Adulto , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
OBJECTIVE: This study investigates the safety and efficacy of a multimodality approach combining staged endovascular embolizations with subsequent SRS for the management of larger AVMs. METHODS: Ninety-five patients with larger AVMs were treated with staged endovascular embolization followed by SRS between 1996 and 2011. RESULTS: The median volume of AVM in this series was 28 cm(3) and 47 patients (48%) were Spetzler-Martin grade IV or V. Twenty-seven patients initially presented with hemorrhage. Sixty-one patients underwent multiple embolizations while a single SRS session was performed in 64 patients. The median follow-up after SRS session was 32 months (range 9-136 months). Overall procedural complications occurred in 14 patients. There were 13 minor neurologic complications and 1 major complication (due to embolization) while four patients had posttreatment hemorrhage. Thirty-eight patients (40%) were cured radiographically. The postradiosurgery actuarial rate of obliteration was 45% at 5 years, 56% at 7 years, and 63% at 10 years. In multivariate analysis, larger AVM size, deep venous drainage, and the increasing number of embolization/SRS sessions were negative predictors of obliteration. The number of embolizations correlated positively with the number of stereotactic radiosurgeries (P < 0.005). CONCLUSIONS: Multimodality endovascular and radiosurgical approach is an efficacious treatment strategy for large AVM.
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Malformaciones Arteriovenosas/cirugía , Embolización Terapéutica , Terapia Neoadyuvante , Radiocirugia , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Técnicas Estereotáxicas , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Subarachnoid hemorrhage (SAH) is found to have no vascular origin by initial catheter angiography in approximately 15% of cases. The most appropriate course for the type and frequency of additional diagnostic workup remains controversial. OBJECTIVE: To retrospectively assess the diagnostic yield of short-term and long-term repeat catheter angiography in the era of advanced imaging. METHODS: Between 2003 and 2011, 254 consecutive patients diagnosed with SAH had negative initial angiography. SAH was perimesencephalic (PM) in 46.5% and nonperimesencephalic (NPM) in 53.5%. Angiography was repeated at 1-week (short-term) and 6-week (long-term) intervals from the initial negative angiogram. RESULTS: Ten of 254 patients had a vascular source of hemorrhage on short-term follow-up angiography with a diagnostic yield of 3.9%. One hundred seventy-four patients with negative findings on the first 2 angiograms received a third angiogram, and 7 of these patients were found to have a vascular abnormality. The estimated yield of this third angiogram was 4.0%. The overall diagnostic yield of repeat angiography was 0% in the PM group and 12.5% in the NPM group. The diagnostic yield of short-term and long-term follow-up angiography in patients with NPM SAH was 7.3% and 7.8%, respectively. NPM patients were more likely to experience vasospasm and hydrocephalus requiring external ventricular drainage or cerebrospinal fluid diversion than PM patients. CONCLUSION: Our results support a protocol of short-term and long-term angiographic follow-up in patients with NPM SAH and negative initial angiography. Aggressive protocols of follow-up angiography may not be necessary in patients with PM SAH.
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Cateterismo/métodos , Angiografía Cerebral/métodos , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/terapia , Cateterismo/tendencias , Angiografía Cerebral/tendencias , Estudios de Seguimiento , Humanos , Estudios Prospectivos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: To assess the impact of tobacco smoking on the survival of men and women in different social positions. DESIGN: A cohort observational study. SETTING: Renfrew and Paisley, two towns in west central Scotland. PARTICIPANTS: 8353 women and 7049 men aged 45-64 years recruited in 1972-6 (almost 80% of the population in this age group). The cohort was divided into 24 groups by sex (male, female), smoking status (current, former, or never smokers), and social class (classes I + II, III non-manual, III manual, and IV + V) or deprivation category of place of residence. MAIN OUTCOME MEASURE: Relative mortality (adjusted for age and other risk factors) in the different groups; Kaplan-Meier survival curves and survival rates at 28 years. RESULTS: Of those with complete data, 4387/7988 women and 4891/6967 men died over the 28 years. Compared with women in social classes I + II who had never smoked (the group with lowest mortality), the adjusted relative mortality of smoking groups ranged from 1.7 (95% confidence interval 1.3 to 2.3) to 4.2 (3.3 to 5.5). Former smokers' mortalities were closer to those of never smokers than those of smokers. By social class (highest first), age adjusted survival rates after 28 years were 65%, 57%, 53%, and 56% for female never smokers; 41%, 42%, 33%, and 35% for female current smokers; 53%, 47%, 38%, and 36% for male never smokers; and 24%, 24%, 19%, and 18% for male current smokers. Analysis by deprivation category gave similar results. CONCLUSIONS: Among both women and men, never smokers had much better survival rates than smokers in all social positions. Smoking itself was a greater source of health inequality than social position and nullified women's survival advantage over men. This suggests the scope for reducing health inequalities related to social position in this and similar populations is limited unless many smokers in lower social positions stop smoking.
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Fumar/mortalidad , Clase Social , Distribución por Edad , Causas de Muerte , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escocia/epidemiología , Análisis de SupervivenciaRESUMEN
OBJECTIVES: Have places in Scotland with the worst/best levels of health and the worst/best experience of health determinants changed since the early 1980s? Twenty-year trends and local-level changes in a selection of health-related indicators were examined to answer this question. STUDY DESIGN AND METHODS: Routine data for seven health-related indicators, principally derived from Scottish government 'social justice milestones', were collated and analysed at postcode-sector level across four 5-year periods covering the 1980s and 1990s. Analysis was carried out by decile, deprivation quintile, individual postcode sector and for selected 'regeneration areas'. RESULTS: There was little change in the ranking of areas with the worst and best health in Scotland over the 20-year period. The worst and best initial deciles remained in those positions throughout, while analysis by deprivation showed that the most disadvantaged areas had become relatively worse over the period. The regeneration areas, with one exception, showed little long-term improvement across the indicators. However, a number of postcode sectors across Scotland did buck this overall trend. CONCLUSIONS: This study confirmed the enduring nature of health differences between areas in Scotland, and provided further evidence of widening health inequalities between affluent and deprived areas. The positive experiences of a small number of areas may warrant further investigation since they may hold important lessons for area-based health improvement. The research highlights the potential of this type of analysis to monitor and evaluate area-based initiatives.
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Disparidades en el Estado de Salud , Características de la Residencia/estadística & datos numéricos , Población Urbana/tendencias , Servicios de Salud Comunitaria/tendencias , Humanos , Estudios Retrospectivos , Escocia/epidemiología , Análisis de Área PequeñaRESUMEN
OBJECTIVE: The present study investigated variables associated with delay of disclosure of child sexual abuse and tested a model of time to disclosure. METHOD: Data were obtained for 218 alleged child sexual abuse victims whose cases had been referred to District Attorneys' Offices. Five variables were posited to influence the delay between an abusive event and children's disclosure of that event to a reporting adult: child's age, gender, type of abuse experienced (intrafamilial or extrafamilial), perceived responsibility for the abuse, and fear of negative consequences of disclosure. These variables were used to create a model of factors influencing children's disclosure of sexual abuse. RESULTS: Results indicated that age, type of abuse, fear of negative consequences, and perceived responsibility all contributed to predicting time to disclosure. There was significant support for the model, suggesting that children who were older, came from incestuous families, felt greater responsibility for the abuse, and feared negative consequences of disclosure took longer to disclose. CONCLUSIONS: Children's cognitive appraisal of others' tolerance of disclosure of child sexual abuse, and their own perceptions of responsibility for the abuse, are crucial to the decision to disclose. When evaluating children for possible sexual abuse, developmental, cognitive, and socio-emotional factors need to be taken into consideration.
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Abuso Sexual Infantil/psicología , Autorrevelación , Delitos Sexuales/psicología , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Familia , Miedo , Femenino , Humanos , Masculino , Modelos Psicológicos , Factores Sexuales , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
Little information is available on the specific roles of different cellular mechanisms involved in extracellular K(+) homeostasis during neuronal activity in situ. These studies have been hampered by the lack of an adequate experimental paradigm able to separate K(+)-buffering activity from the superimposed extrusion of K(+) from variably active neurons. We have devised a new protocol that allows for such an analysis. We used paired field- and K(+)-selective microelectrode recordings from CA3 stratum pyramidale during maximal Schaffer collateral stimulation in the presence of excitatory synapse blockade to evoke purely antidromic spikes in CA3. Under these conditions of controlled neuronal firing, we studied the [K(+)]o baseline during 0.05 Hz stimulation, and the accumulation and rate of recovery of extracellular K(+) at higher frequency stimulation (1-3 Hz). In the first set of experiments, we showed that neuronal hyperpolarization by extracellular application of ZD7288 (11 microM), a selective blocker of neuronal I(h) currents, does not affect the dynamics of extracellular K(+). This indicates that the K(+) dynamics evoked by controlled pyramidal cell firing do not depend on neuronal membrane potential, but only on the balance between K(+) extruded by firing neurons and K(+) buffered by neuronal and glial mechanisms. In the second set of experiments, we showed that di-hydro-ouabain (5 microM), a selective blocker of the Na(+)/K(+)-pump, yields an elevation of baseline [K(+)]o and abolishes the K(+) recovery during higher frequency stimulation and its undershoot during the ensuing period. In the third set of experiments, we showed that Ba(2+) (200 microM), a selective blocker of inwardly rectifying K(+) channels (KIR), does not affect the posttetanus rate of recovery of [K(+)]o, nor does it affect the rate of K(+) recovery during high-frequency stimulation. It does, however, cause an elevation of baseline [K(+)]o and an increase in the amplitude of the ensuing undershoot. We show for the first time that it is possible to differentiate the specific roles of Na(+)/K(+)-pump and KIR channels in buffering extracellular K(+). Neuronal and glial Na(+)/K(+)-pumps are involved in setting baseline [K(+)]o levels, determining the rate of its recovery during sustained high-frequency firing, and determining its postactivity undershoot. Conversely, glial KIR channels are involved in the regulation of baseline levels of K(+), and in decreasing the amplitude of the postactivity [K(+)]o undershoot, but do not affect the rate of K(+) clearance during neuronal firing. The results presented provide new insights into the specific physiological role of glial KIR channels in extracellular K(+) homeostasis.
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Espacio Extracelular/metabolismo , Hipocampo/metabolismo , Ouabaína/análogos & derivados , Canales de Potasio de Rectificación Interna , Canales de Potasio/metabolismo , Potasio/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Animales , Bario/farmacología , Estimulación Eléctrica , Potenciales Evocados/efectos de los fármacos , Potenciales Evocados/fisiología , Hipocampo/efectos de los fármacos , Técnicas In Vitro , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ouabaína/farmacología , Bloqueadores de los Canales de Potasio/farmacología , Ratas , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidoresRESUMEN
Research has revealed the importance of characteristics of the supporter, the care-recipient, and circumstances of caregiving in the success or failure of community-based care of older people. The Dundee Study of Carers and Dementia examined factors associated with the maintenance and care of older people in the community, and with the impact of dementia on family supporters. Two hundred and twenty-eight family supporters of community-resident older people (>/=65) (50% with dementia, 50% without, matched for age and sex) were interviewed. Supporters' responses to their relative's condition and circumstances, their ways of coping with stressful caregiving problems, and their willingness to continue their caregiving role, were assessed. Findings indicated that willingness to care and stress were associated in different ways with the supporter's response to his/her relative. Coping was found to be significantly associated with stress, response to relative, and willingness to care in only three out of a total of 45 tests. Willingness to care was positively associated with the coping behaviour internalization. The findings are discussed in the context of developing interventions for improving the well-being of supporters of an older relative in the community.