Pro-inflammatory flagellin proteins of prevalent motile commensal bacteria are variably abundant in the intestinal microbiome of elderly humans

Some Eubacterium and Roseburia species are among the most prevalent motile bacteria present in the intestinal microbiota of healthy adults. These flagellate species contribute "cell motility" category genes to the intestinal microbiome and flagellin proteins to the intestinal proteome. We reviewed and revised the annotation of motility genes in the genomes of six Eubacterium and Roseburia species that occur in the human intestinal microbiota and examined their respective locus organization by comparative genomics. Motility gene order was generally conserved across these loci. Five of these species harbored multiple genes for predicted flagellins. Flagellin proteins were isolated from R. inulinivorans strain A2-194 and from E. rectale strains A1-86 and M104/1. The amino-termini sequences of the R. inulinivorans and E. rectale A1-86 proteins were almost identical. These protein preparations stimulated secretion of interleukin-8 (IL-8) from human intestinal epithelial cell lines, suggesting that these flagellins were pro-inflammatory. Flagellins from the other four species were predicted to be pro-inflammatory on the basis of alignment to the consensus sequence of pro-inflammatory flagellins from the beta- and gamma-proteobacteria. Many fliC genes were deduced to be under the control of sigma(28). The relative abundance of the target Eubacterium and Roseburia species varied across shotgun metagenomes from 27 elderly individuals. Genes involved in the flagellum biogenesis pathways of these species were variably abundant in these metagenomes, suggesting that the current depth of coverage used for metagenomic sequencing (3.13-4.79 Gb total sequence in our study) insufficiently captures the functional diversity of genomes present at low (<= 1%) relative abundance. E. rectale and R. inulinivorans thus appear to synthesize complex flagella composed of flagellin proteins that stimulate IL-8 production. A greater depth of sequencing, improved evenness of sequencing and improved metagenome assembly from short reads will be required to facilitate in silico analyses of complete complex biochemical pathways for low-abundance target species from shotgun metagenomes.

Clinicopathologic correlates in the oldest-old: Commentary on "No disease in the brain of a 115-year-old woman".

den Dunnen et al. [den Dunnen, W.F.A., Brouwer, W.H., Bijlard, E., Kamphuis, J., van Linschoten, K., Eggens-Meijer, E., Holstege, G., 2008. No disease in the brain of a 115-year-old woman. Neurobiol. Aging] had the opportunity to follow up the cognitive functioning of one of the world's oldest woman during the last 3 years of her life. They performed two neuropsychological evaluations at age 112 and 115 that revealed a striking preservation of immediate recall abilities and orientation. In contrast, working memory, retrieval from semantic memory and mental arithmetic performances declined after age 112. Overall, only a one-point decrease of MMSE score occurred (from 27 to 26) reflecting the remarkable preservation of cognitive abilities. The neuropathological assessment showed few neurofibrillary tangles (NFT) in the hippocampal formation compatible with Braak staging II, absence of amyloid deposits and other types of neurodegenerative lesions as well as preservation of neuron numbers in locus coeruleus. This finding was related to a striking paucity of Alzheimer disease (AD)-related lesions in the hippocampal formation. The present report parallels the early descriptions of rare "supernormal" centenarians supporting the dissociation between brain aging and AD processes. In conjunction with recent stereological analyses in cases aged from 90 to 102 years, it also points to the marked resistance of the hippocampal formation to the degenerative process in this age group and possible dissociation between the occurrence of slight cognitive deficits and development of AD-related pathologic changes in neocortical areas. This work is discussed in the context of current efforts to identify the biological and genetic parameters of human longevity.

Statins are associated with decreased mortality risk after status epilepticus.

BACKGROUND AND PURPOSE: Statins display anti-inflammatory and anti-epileptogenic properties in animal models, and may reduce the epilepsy risk in elderly humans; however, a possible modulating role on outcome in patients with status epilepticus (SE) has not been assessed. METHODS: This cohort study was based on a prospective registry including all consecutive adults with incident SE treated in our center between April 2006 and September 2012. SE outcome was categorized at hospital discharge into 'return to baseline', 'new disability' and 'mortality'. The role of potential predictors, including statins treatment on admission, was evaluated using a multinomial logistic regression model. RESULTS: Amongst 427 patients identified, information on statins was available in 413 (97%). Mean age was 60.9 (±17.8) years; 201 (49%) were women; 211 (51%) had a potentially fatal SE etiology; and 191 (46%) experienced generalized-convulsive or non-convulsive SE in coma. Statins (simvastatin, atorvastatin or pravastatin) were prescribed prior to admission in 76 (18%) subjects, mostly elderly. Whilst 208 (50.4%) patients returned to baseline, 58 (14%) died. After adjustment for established SE outcome predictors (age, etiology, SE severity score), statins correlated significantly with lower mortality (relative risk ratio 0.38, P = 0.046). CONCLUSION: This study suggests for the first time that exposure to statins before an SE episode is related to its outcome, involving a possible anti-epileptogenic role. Other studies are needed to confirm this intriguing finding.

Asociación de la concentración de material particulado en Bogotá con infarto agudo de miocardio

Introducción: la contaminación atmosférica no solo tiene efectos sobre el sistema respiratorio sino también sobre el cardiovascular. El objetivo de este estudio es generar evidencia que permita establecer una asociación entre el infarto agudo del miocardio y la concentración de PM10 en el ambiente como un estudio preliminar para un grupo de pacientes en Bogotá. Metodología: la asociación entre la concentración del material particulado (en este caso PM10 medido en la estación más cercana del lugar reportado por el paciente) y el infarto agudo del miocardio se estableció utilizando el diseño case crossover. Se utilizó información de las historias clínicas de los pacientes con infarto agudo del miocardio que ingresaron al Servicio de Urgencias de la FSFB, y las concentraciones de PM10 medido en la estación más cercana al lugar de inicio de los síntomas de síndrome coronario agudo, reportado por el paciente. Resultados: se encontró que la asociación entre la concentración de PM10 y el diagnóstico de infarto agudo del miocardio es estadísticamente significativa teniendo en cuenta tres momentos de control: 2 horas antes del evento, 24 horas antes del evento y 48 horas antes del evento. Discusión: este estudio sugiere que las altas concentraciones de material particulado en el ambiente son un factor de riesgo para el desarrollo de infarto agudo del miocardio especialmente en personas con enfermedad coronaria subyacente. Con esta investigación se demuestra la importancia de generar acciones que disminuyan la contaminación de la ciudad y de esta forma proteger la salud de las personas.

Muscle coordination during rapid force production by young and older adults

Background. Older adults typically exhibit dramatic reductions in the rate of force development and deficits in the execution of rapid coordinated movements. The purpose of the current study was to investigate the association between the reduced rate of force development exhibited by older adults and the ability to coordinate groups of muscles. Methods. The performance of a visually guided aiming task that required the generation of isometric torque about the elbow joint was compared in 10 young adults (age range, 19 to 29 years) and 10 older adults (age range, 65 to 80 years). Participants were required to exert isometric torque in flexion, extension, pronation, or supination, or in combinations of these directions, to reach a target in minimum time. Surface electromyograms were obtained from the biceps brachii, triceps brachii, brachioradialis, and flexor carpi radialis. Results. Older participants exhibited slower target acquisition times compared with young participants (p < .05), with the extent of the differences between the groups varying markedly between target locations. Conclusions. The impairment in performance, although partially attributable to a general decline in the ability to produce force rapidly, was also affected by the requirements for muscular coordination. At the neuromuscular level, differences between the young and the elderly were expressed most prominently in the bifunctional muscle biceps brachii and in certain temporal aspects of muscular coordination.

Pentoxifylline and the behaviour of 29-month female mice

The dimethyl-xanthine derivative pentoxifylline (PTX) increases blood flow through capillaries. In elderly humans the drug leads to improvement in a number of imapired neuropsychological parameters. We now report that oral administration to 29-month female mice (C57, black and tan) over six days induced four different patterns of behavioural reponse: (1) consistent improvement in grooming behaviour throughout the six day trial; (2) significant improvement in light/dark zone curiosity and curiosity towards a strange object on day three, which declined but remained significantly above pre-treatment levels at day 6; (3) an improvement in general activity which only becomes detectable on day six; (4) a significant improvement in rod-walking, rearing an shuttle-box crosses on day three which returned to pre-treatment levels by day 6. Age-related deficits in general activity, grooming and curiosity were completely eliminated by the drug - the mean group performance levels attained those seen in 9-12 month individuals of this strain.

A neuroimaging investigation of the association between aerobic fitness, hippocampal volume and memory performance in preadolescent children

Because children are becoming increasingly overweight, unhealthy and unfit, understanding the neurocognitive benefits of an active lifestyle in childhood has important public health and educational implications. Animal research has indicated that aerobic exercise is related to increased cell proliferation and survival in the hippocampus as well as enhanced hippocampal-dependent learning and memory. Recent evidence extends this relationship to elderly humans by suggesting that high aerobic fitness levels in older adults are associated with increased hippocampal volume and superior memory performance. The present study aimed to further extend the link between fitness, hippocampal volume, and memory to a sample of preadolescent children. To this end, magnetic resonance imaging was employed to investigate whether high- and low-fit 9- and 10-year-old children showed differences in hippocampal volume and if the differences were related to performance on an item and relational memory task. Relational but not item memory is primarily supported by the hippocampus. Consistent with predictions, high-fit children showed greater bilateral hippocampal volumes. Furthermore, hippocampal volume was positively associated with performance on the relational but not the item memory task. The findings are the first to suggest that aerobic fitness can impact the structure and function of the developing human brain.

Measuring attachment to life in old age: the Portuguese version of the Positive Valuation of Life Scale (Positive VOL)

Purpose This study aims to present the psychometric properties of the Portuguese version of the Positive Valuation of Life Scale (Lawton et al. in J Aging Ment Healt 13:3–31, 2001). Method Sample included 207 community-dwelling elders (129 women; MAge = 77.2 years, SD = 7.5). The data collection included the translated and adapted Portuguese version of Positive Valuation of Life Scale, Life Satisfac- tion Index Z, Meaning in Life Questionnaire and Geriatric Depression Scale. Results From exploratory factor analysis, two factors emerged, existential beliefs and perceived control, ex- plaining 49 % of the total variance. Both factors were positively related with meaning in life and life satisfaction and negatively related with depression (p\0.05). The values obtained for internal consistency for the total scale and for each subscale were good (a [ 0.75). Conclusion The Portuguese version of Positive VOL Scale represents a reliable and valid measure to capture the subjective experience of attachment to one’s life. The two-factor structure is an update to Lawton’s previous work and in line with findings obtained in the USA (Dennis et al. in What is valuation of life for frail community-dwelling older adults: factor structure and criterion validity of the VOL, Thomas Jefferson University, Center for Applied Research on Aging and Health Research, 2005) and Japan (Nakagawa et al. in Shinrigaku Kenkyu 84:37–46, 2013). Future research is required to investigate VOL predictors and the potential changes toward the end of the life span.

Adherence, adaptation and acceptance of elderly chronic heart failure patients to receiving healthcare via telephone-monitoring

Background: Although the potential to reduce hospitalisation and mortality in chronic heart failure (CHF) is well reported, the feasibility of receiving healthcare by structured telephone support or telemonitoring is not. Aims: To determine; adherence, adaptation and acceptability to a national nurse-coordinated telephone-monitoring CHF management strategy. The Chronic Heart Failure Assistance by Telephone Study (CHAT). Methods: Triangulation of descriptive statistics, feedback surveys and qualitative analysis of clinical notes. Cohort comprised of standard care plus intervention (SC + I) participants who completed the first year of the study. Results: 30 GPs (70% rural) randomised to SC + I recruited 79 eligible participants, of whom 60 (76%) completed the full 12 month follow-up period. During this time 3619 calls were made into the CHAT system (mean 45.81 SD ± 79.26, range 0-369), Overall there was an adherence to the study protocol of 65.8% (95% CI 0.54-0.75; p = 0.001) however, of the 60 participants who completed the 12 month follow-up period the adherence was significantly higher at 92.3% (95% CI 0.82-0.97, p ≤ 0.001). Only 3% of this elderly group (mean age 74.7 ±9.3 years) were unable to learn or competently use the technology. Participants rated CHAT with a total acceptability rate of 76.45%. Conclusion: This study shows that elderly CHF patients can adapt quickly, find telephone-monitoring an acceptable part of their healthcare routine, and are able to maintain good adherence for a least 12 months. © 2007.

Characterization of inflammatory responses to eccentric exercise in humans

Eccentric exercise commonly results in muscle damage. The primary sequence of events leading to exercise-induced muscle damage is believed to involve initial mechanical disruption of sarcomeres, followed by impaired excitation-contraction coupling and calcium signaling, and finally, activation of calcium-sensitive degradation pathways. Muscle damage is characterized by ultrastructural changes to muscle architecture, increased muscle proteins and enzymes in the bloodstream, loss of muscular strength and range of motion and muscle soreness. The inflammatory response to exercise-induced muscle damage is characterized by leukocyte infiltration and production of pro-inflammatory cytokines within damaged muscle tissue, systemic release of leukocytes and cytokines, in addition to alterations in leukocyte receptor expression and functional activity. Current evidence suggests that inflammatory responses to muscle damage are dependent on the type of eccentric exercise, previous eccentric loading (repeated bouts), age and gender. Circulating neutrophil counts and systemic cytokine responses are greater after eccentric exercise using a large muscle mass (e.g. downhill running, eccentric cycling) than after other types of eccentric exercise involving a smaller muscle mass. After an initial bout of eccentric exercise, circulating leukocyte counts and cell surface receptor expression are attenuated. Leukocyte and cytokine responses to eccentric exercise are impaired in elderly individuals, while cellular infiltration into skeletal muscle is greater in human females than males after eccentric exercise. Whether alterations in intracellular calcium homeostasis influence inflammatory responses to muscle damage is uncertain. Furthermore, the effects of antioxidant supplements are variable, and the limited data available indicates that anti-inflammatory drugs largely have no influence on inflammatory responses to eccentric exercise. In this review, we compare local versus systemic inflammatory responses, and discuss some of the possible mechanisms regulating the inflammatory responses to exercise-induced muscle damage in humans.

A joined analysis of two European Organization for the Research and Treatment of Cancer (EORTC) studies to evaluate the role of pegylated liposomal doxorubicin (Caelyx) in the treatment of elderly patients with metastatic breast cancer.

We have performed a retrospective analysis to evaluate the impact of age, using a 70 year cutoff, on the safety and efficacy of pegylated liposomal doxorubicin (Caelyx) given at 60 mg/m(2) every 6 weeks (treatment A) or 50 mg/m(2) every 4 weeks (treatment B) to 136 metastatic breast cancer patients in two EORTC trials, of whom 65 were 70 years of age or older. No difference in terms of toxicity was observed between younger and older patients treated with the 4-week schedule, while a higher incidence of hematological toxicity, anorexia, asthenia, and stomatitis was observed in older patients when the 6-week schedule was used. Antitumor activity was not affected by age. In the older cohort of patients, no dependence was found between the incidence of grade 3-4 toxicity or antitumor activity and patients' baseline performance status, number and severity of comorbidities, or number of concomitant medications. The higher therapeutic index of Caelyx 50 mg/m(2) every 4 weeks makes it, of the two dose schedules investigated, the preferred regimen in the elderly.

Adjuvant therapy in elderly patients with breast cancer.

The elderly population has been neglected by the traditional approach to clinical breast cancer research. Elderly women have been underrepresented in breast cancer clinical trials, with the majority of studies being restricted to patients aged < 70 years. Elderly patients frequently have comorbidities and/or impaired organ function. These facts may often lead to death from causes other than cancer, thus nullifying any possible benefit of adjuvant treatment; furthermore, they render extrapolation of standard treatment recommendations to the elderly potentially hazardous, particularly with respect to chemotherapy. Therefore, specific clinical trials are needed to investigate adjuvant treatments tailored for the heterogeneous older population.

Adjuvant chemotherapy in elderly patients with breast cancer: a survey of the Breast International Group (BIG).

BACKGROUND: To collect oncologists' experience and opinion on adjuvant chemotherapy in elderly breast cancer patients. MATERIALS AND METHODS: A questionnaire was circulated among the members of the Breast International Group. RESULTS: A total of 277 oncologists from 28 countries participated in the survey. Seventy years is the age cut-off commonly used to define a patient as elderly. Biological age and the biological characteristics of the tumor are the most frequently used criteria to propose adjuvant chemotherapy to an elderly patient. Combination therapy with cyclophosphamide, methotrexate and fluorouracil on days 1 and 8 is the most frequently prescribed regimen. Great interest exists in oral chemotherapy. CONCLUSION: There is interest among those who responded to the survey to validate a comprehensive geriatric assessment for use as a predictive instrument of toxicity and/or activity of anticancer therapy and to evaluate the role of a treatment option that is potentially less toxic and possibly as effective as polychemotherapy.