Remote ischaemic preconditioning ameliorates anthracycline-induced cardiotoxicity and preserves mitochondrial integrity.

AIMS: Anthracycline-induced cardiotoxicity (AIC) is a serious adverse effect among cancer patients. A central mechanism of AIC is irreversible mitochondrial damage. Despite major efforts, there are currently no effective therapies able to prevent AIC. METHODS AND RESULTS: Forty Large-White pigs were included. In Study 1, 20 pigs were randomized 1:1 to remote ischaemic preconditioning (RIPC, 3 cycles of 5 min leg ischaemia followed by 5 min reperfusion) or no pretreatment. RIPC was performed immediately before each intracoronary doxorubicin injections (0.45 mg/kg) given at Weeks 0, 2, 4, 6, and 8. A group of 10 pigs with no exposure to doxorubicin served as healthy controls. Pigs underwent serial cardiac magnetic resonance (CMR) exams at baseline and at Weeks 6, 8, 12, and 16, being sacrifice after that. In Study 2, 10 new pigs received 3 doxorubicin injections (with/out preceding RIPC) and were sacrificed at week 6. In Study 1, left ventricular ejection fraction (LVEF) depression was blunted animals receiving RIPC before doxorubicin (RIPC-Doxo), which had a significantly higher LVEF at Week 16 than doxorubicin treated pigs that received no pretreatment (Untreated-Doxo) (41.5 ± 9.1% vs. 32.5 ± 8.7%, P = 0.04). It was mainly due to conserved regional contractile function. In Study 2, transmission electron microscopy (TEM) at Week 6 showed fragmented mitochondria with severe morphological abnormalities in Untreated-Doxo pigs, together with upregulation of fission and autophagy proteins. At the end of the 16-week Study 1 protocol, TEM revealed overt mitochondrial fragmentation with structural fragmentation in Untreated-Doxo pigs, whereas interstitial fibrosis was less severe in RIPC+Doxo pigs. CONCLUSION: In a translatable large-animal model of AIC, RIPC applied immediately before each doxorubicin injection resulted in preserved cardiac contractility with significantly higher long-term LVEF and less cardiac fibrosis. RIPC prevented mitochondrial fragmentation and dysregulated autophagy from AIC early stages. RIPC is a promising intervention for testing in clinical trials in AIC.

Metoprolol blunts the time-dependent progression of infarct size.

Early metoprolol administration protects against myocardial ischemia-reperfusion injury, but its effect on infarct size progression (ischemic injury) is unknown. Eight groups of pigs (total n = 122) underwent coronary artery occlusion of varying duration (20, 25, 30, 35, 40, 45, 50, or 60 min) followed by reperfusion. In each group, pigs were randomized to i.v. metoprolol (0.75 mg/kg) or vehicle (saline) 20 min after ischemia onset. The primary outcome measure was infarct size (IS) on day7 cardiac magnetic resonance (CMR) normalized to area at risk (AAR, measured by perfusion computed tomography [CT] during ischemia). Metoprolol treatment reduced overall mortality (10% vs 26%, p = 0.03) and the incidence and number of primary ventricular fibrillations during infarct induction. In controls, IS after 20-min ischemia was ≈ 5% of the area AAR. Thereafter, IS progressed exponentially, occupying almost all the AAR after 35 min of ischemia. Metoprolol injection significantly reduced the slope of IS progression (p = 0.004 for final IS). Head-to-head comparison (metoprolol treated vs vehicle treated) showed statistically significant reductions in IS at 30, 35, 40, and 50-min reperfusion. At 60-min reperfusion, IS was 100% of AAR in both groups. Despite more prolonged ischemia, metoprolol-treated pigs reperfused at 50 min had smaller infarcts than control pigs undergoing ischemia for 40 or 45 min and similar-sized infarcts to those undergoing 35-min ischemia. Day-45 LVEF was higher in metoprolol-treated vs vehicle-treated pigs (41.6% vs 36.5%, p = 0.008). In summary, metoprolol administration early during ischemia attenuates IS progression and reduces the incidence of primary ventricular fibrillation. These data identify metoprolol as an intervention ideally suited to the treatment of STEMI patients identified early in the course of infarction and requiring long transport times before primary angioplasty.

Emerging Technologies and Synergies for Airborne and Space-Based Measurements of Water Vapor Profiles.

A deeper understanding of how clouds will respond to a warming climate is one of the outstanding challenges in climate science. Uncertainties in the response of clouds, and particularly shallow clouds, have been identified as the dominant source of the discrepancy in model estimates of equilibrium climate sensitivity. As the community gains a deeper understanding of the many processes involved, there is a growing appreciation of the critical role played by fluctuations in water vapor and the coupling of water vapor and atmospheric circulations. Reduction of uncertainties in cloud-climate feedbacks and convection initiation as well as improved understanding of processes governing these effects will result from profiling of water vapor in the lower troposphere with improved accuracy and vertical resolution compared to existing airborne and space-based measurements. This paper highlights new technologies and improved measurement approaches for measuring lower tropospheric water vapor and their expected added value to current observations. Those include differential absorption lidar and radar, microwave occultation between low-Earth orbiters, and hyperspectral microwave remote sensing. Each methodology is briefly explained, and measurement capabilities as well as the current technological readiness for aircraft and satellite implementation are specified. Potential synergies between the technologies are discussed, actual examples hereof are given, and future perspectives are explored. Based on technical maturity and the foreseen near-mid-term development path of the various discussed measurement approaches, we find that improved measurements of water vapor throughout the troposphere would greatly benefit from the combination of differential absorption lidar focusing on the lower troposphere with passive remote sensors constraining the upper-tropospheric humidity.

El grupo como recurso terapéutico en un centro terapéutico educativo / The group as a therapeutical resource in an educational therapy centre

El principal objetivo del presente artículo es el de proporcionar información acerca de la unidad terapéutico educativo de Ortuella incidiendo tanto en los aspectos de su funcionamiento interno; como en los programas grupales clínicos que se desarrollan en él. Los niños que llegan a este centro presentan pesadas patologías que les sitúan lejos del lazo social y de la posibilidad de entrada en el aprendizaje y lo que deseamos como salida de su recorrido institucional es que sean autónomos en sus comportamientos y que hayan entrado, o estén preparados para entrar en un recorrido escolar. Hemos podido comprobar que existe bastante literatura científica acerca de la eficacia de los dispositivos terciarios en el tratamiento de estas patologías, pero muy poca que explique el funcionamiento o la estructura óptima de estos dispositivos (AU)

This article aims to provide information about the Ortuella therapy and eduction centre both in terms of its internal operation and its clinical group therapy programs. Children arriving at the centre present severe pathologies that place them beyond the social fabric and the possibility of entering an educational programme, and our goal is that their institutionalization will enable them to be behaviorally autonomous and enter, or be prepared to enter, an educational programme. We have been able to verify that sufficient scientific literature exists on the effectiveness of tertiary mechanisms for treating these pathologies, but very little that explains the operation of the optimum structure for such mechanisms (AU)

Effectiveness of three interventions to improve participation in colorectal cancer screening.

BACKGROUND AND OBJECTIVE: Participation in colorectal cancer (CRC) screening varies widely among different countries and different socio-demographic groups. Our objective was to assess the effectiveness of three primary-care interventions to increase CRC screening participation among persons over the age of 50 years and to identify the health and socio-demographic-related factors that determine greater participation. METHODS: We conducted a randomized experimental study with only one post-test control group. A total of 1,690 subjects were randomly distributed into four groups: written briefing; telephone briefing; an invitation to attend a group meeting; and no briefing. Subjects were evaluated 2 years post-intervention, with the outcome variable being participation in CRC screening. RESULTS: A total of 1,129 subjects were interviewed. Within the groups, homogeneity was tested in terms of socio-demographic characteristics and health-related variables. The proportion of subjects who participated in screening was: 15.4% in the written information group (95% confidence interval [CI]: 11.2-19.7); 28.8% in the telephone information group (95% CI: 23.6-33.9); 8.1% in the face-to-face information group (95% CI: 4.5-11.7); and 5.9% in the control group (95% CI: 2.9-9.0), with this difference proving statistically significant (p < 0.001). Logistic regression showed that only interventions based on written or telephone briefing were effective. Apart from type of intervention, number of reported health problems and place of residence remained in the regression model. CONCLUSIONS: Both written and telephone information can serve to improve participation in CRC screening. This preventive activity could be optimized by means of simple interventions coming within the scope of primary health-care professionals.

Intervenciones psicoterapéuticas con el entorno de niños con problemas psiquiátricos graves desde un centro de día / Psychotherapeutic interventions with the environment of children with serious mental problems from a day care centre

A través de esta exposición y valiéndome de un caso clínico, me gustaría acercar el trabajo realizado con el entorno familiar de niños con problemas psiquiátricos graves en un centro terapéutico-educativo (AU)

Through this exhibition and availing myself of a clinical case, I would bring the work done with the family environment of children with serious psychiatric problems in a therapeutic-educational center (AU)

Visual function versus visual acuity in older people.

PURPOSE: To determine visual function (VF) status in older people, to establish its degree of correlation with visual acuity (VA), and to assess its association with other physical and mental functional limitations. PARTICIPANTS: A sample of 1,160 persons aged 65 years or over were selected by simple randomization. METHODS: The participants' VF (The Visual Function Index - VF-14), VA, self-reported vision, mental and physical function (Katz Index, Pfeiffer's test, and Geriatric Depression Scale), and socio-demographic data were determined. Multiple linear regression was used to assess the association between VF and its conditioning factors. Statistical adjustment was made for the possible confounding variables. RESULTS: Of the studied subjects, 6.3% (95% confidence interval (CI) = 4.93-7.82) had VA of less than 6/18 in the better eye and 20.9% (95% CI = 18.6-23.3) had VA of less than 6/12. The best corrected VA of each participant demonstrated moderate correlation with his or her VF-14 score (r = 0.416; p < 0.001). Using multiple regression analysis, the variables associated with VF status were: visual impairment, self-reported poor vision, dependence in daily activities, cognitive impairment, depressive symptoms, female gender and older age. These independent variables explain 34.4% (r(2) = 0.344) of the variation in the data. CONCLUSIONS: VF impairment is common in older persons and when associated with other limitations, it may be considered a major health problem with important consequences. As a complement to the preventive care guidelines on VA in older persons, assessment of VF impairment in clinical practice, using appropriate visual screening tools, is advisable.

The Hearing-Dependent Daily Activities Scale to evaluate impact of hearing loss in older people.

PURPOSE: We wanted to design and validate the Hearing-Dependent Daily Activities (HDDA) Scale as a means of identifying the impact of hearing loss in older persons by measuring capacity to carry out hearing-dependent activities. METHODS: We undertook a cross-sectional, observational study to validate a scale administered during a personal interview with 1,160 participants aged 65 years and older. When using the instrument to identify patients with hearing impairment, sensitivity and specificity were determined using an audiogram with Ventry and Weinstein criteria as the criterion standard. Standardized audiometries were performed blindly, without knowledge of results of the HDDA Scale. RESULTS: According to the criterion standard, 506 participants had hearing impairment (43.6%; 95% confidence interval [CI], 40.8%-46.5%). The HDDA scale showed high internal consistency (Cronbach's alpha =0.91). Regarding hearing impairment criteria, the HDDA scale obtained a sensitivity of 80.0% (95% CI, 76.3%-83.3%) and a specificity of 70.2% (95% CI, 66.5%-73.5%). CONCLUSIONS: The HDDA scale constitutes a clinically useful instrument for identifying the impact of hearing loss on daily life in the elderly, a condition frequently overlooked during routine medical check-ups. This tool has acceptable psychometric properties and high internal consistency.

Functional status in the elderly with insomnia.

BACKGROUND: Insomnia causes psychological distress in the elderly. Besides primary insomnia (PI), illness, medications and psychosocial factors contribute to development of sleep disorders. Although elderly insomniacs usually complain of poorer daytime functioning, it is unknown whether the disorder affects capacity to carry out activities. OBJECTIVE: To assess the relationship in the elderly between PI, level of physical functioning, depression and anxiety symptoms, state of psychological well-being and consumption of psychopharmaceuticals. DESIGN: Cross-sectional, observational study. SETTING: Populational. SUBJECTS: About 424 non-institutionalized elderly patients. METHODS: Subjects were interviewed at public Health Centres or at home. They were considered to have PI if DSM-IV criteria were met. The remaining variables measured were: depression and anxiety symptoms (The Goldberg's Depression and Anxiety Scale), cognitive state (Short Portable Mental Status Questionnaire), physical functioning (The Katz Index and the Instrumental Activities of Daily Living Scale), life satisfaction (The Philadelphia Geriatric Center Morale Scale), health problems, consumption of pharmaceuticals and sociodemographic variables. RESULTS: About 34.2% of the elderly admitted to having problems with sleep, but only 20.3% (CI: 95%: 16.5-24.1) fulfilled the criteria for PI. The existence of an anxiety disorder, a score below the 50th percentile on The Philadelphia Geriatric Center Morale Scale (lower life satisfaction) and consumption of psychopharmaceuticals were variables associated with insomnia. Amongst the most common illnesses reported, only diabetes appeared with significantly higher frequency in the elderly with insomnia (24.4% vs. 14.7%) (p < 0.05). No statistically significant association was found between insomnia and level of dependence in carrying out basic or instrumental activities. CONCLUSIONS: Approximately one fifth of the non-institutionalized elderly meet the criteria for PI. Those affected present a poorer state of psychological and social well-being, although level of autonomy for conducting basic and instrumental activities does not appear to be modified by the disorder. The existence of an anxiety disorder, low life satisfaction and consumption of psychopharmaceuticals constitute variables associated with PI in the population we studied.