The Health-Related Effects of Alcohol Use in Older Persons: A Systematic Review

Increased alcohol consumption is associated with substantial morbidity and mortality in young and middle-aged adult populations, but its effects on the health of older adults have received less attention. The objective of the study was to review published studies that assessed the effects of alcohol on falls or fall injuries, functional impairment, cognitive impairment, and all-cause mortality among older adults. MEDLINE database and bibliographies of selected citations were searched for English language studies published between 1966 and 1998 that examined the relationship between alcohol and one or more of the above outcomes. Also a study was analyzed if it included participants 60 years of age or older, or a broader age range of participants and reported results for older subgroups, or predominantly older participants as evidenced by a mean age of 65 years of age or above. Information on studies' sample sizes, exposure and outcome measures, and risk estimates were extracted, and articles were evaluated for methodologic quality using predetermined criteria. Eighty-four studies were identified that examined 91 potential exposure–outcome associations including falls or fall injuries (n = 26); functional impairment (n = 13); cognitive impairment (n = 32); and all-cause mortality (n = 20). The percentage of studies demonstrating harm, no association, or benefit by outcome included falls (15% vs. 81% vs. 4%); functional disability (38% vs. 46% vs. 16%); cognitive impairment (31% vs. 66% vs. 3%); and all-cause mortality (15% vs. 65% vs. 20%). Studies (n = 84) inconsistently adhered to methodologic standards. Although 90% provided eligibility criteria; 61% cited participation rates; and 73% described the methods used to measure alcohol exposure; only 44% adjusted for potentially important confounding factors; and 26% distinguished former drinkers from nondrinkers. Of the cohort studies (n = 47), 30% assessed for change in participants' exposure status over time, and 17% determined whether losses to follow-up varied by exposure status. The magnitude of risk posed by alcohol use for falls or fall injuries, functional disability, cognitive impairment, and all-cause mortality among older adults remains uncertain. Prospective studies are needed to better define the health-related effects of alcohol use in older populations.     

Effects of diltiazem and isosorbide-5-mononitrate,alone and in combination,on patients with stable angina pectoris

Summary The anti-anginal effect of sustained release diltiazem, isosorbide-5-mononitrate (IS-5-MN) and their combination has been evaluated in 25 patients in 4 blinded treatment periods of 2 weeks each.The number of anginal attacks during each treatment period was reduced from a mean of 23 during placebo to 15 during diltiazem and 15 during combination therapy, but it was not significantly changed after IS-5-MN-20. A similar pattern was seen for nitroglycerin consumption and number of anginafree days. Maximal exercise capacity was also significantly improved following diltiazem and the drug combination, and it was not changed after IS-5-MN. ST segment depression was less pronounced after diltiazem and the combination compared to IS-5-MN. There was no difference in exercise capacity or ST segment change between diltiazem and the combination. The PR interval was slightly prolonged after diltiazem, but this was of no clinical importance. Adverse effects of diltiazem treatment were rare. Headache was common following IS-5-MN (13 patients) and the combination (11 patients).Thus, sustained-release diltiazem was of value in the treatment of chronic stable angina pectoris, whereas IS-5-MN was not effective, either as a single therapy or in combination with diltiazem. The reason for the inefficacy of IS-5-MN is not known, but the development of tolerance and an inadequate dose are possible explanations.     

Expression and function of CB1 receptor in the rat striatum: localization and effects on D1 and D2 dopamine receptor-mediated motor behaviors.

Cannabinoid CB1 receptors are densely expressed on striatal projection neurons expressing dopamine D1 or D2 receptors. However, the specific neuronal distribution of CB1 receptors within the striatum is not known. Previous research has established that the endocannabinoid system controls facilitation of behavior by dopamine D2 receptors, but it is not clear if endocannabinoids also modulate D1 receptor-mediated motor behavior. In the present study, we show that cannabinoid CB1 receptor mRNA is present in striatonigral neurons expressing substance P and dopamine D1 receptors, as well as in striatopallidal neurons expressing enkephalin and dopamine D2 receptors. We explored the functional relevance of the interaction between dopamine D1 and D2 receptors and cannabinoid CB1 receptors with behavioral pharmacology experiments. Potentiation of endogenous cannabinoid signaling by the uptake blocker AM404 blocked dopamine D1 receptor-mediated grooming and D2 receptor-mediated oral stereotypies. In addition, contralateral turning induced by unilateral intrastriatal infusion of D1 receptor agonists is counteracted by AM404 and potentiated by the cannabinoid antagonist SR141716A. These results indicate that the endocannabinoid system negatively modulates D1 receptor-mediated behaviors in addition to its previously described effect on dopamine D2 receptor-mediated behaviors. The effect of AM404 on grooming behavior was absent in dopamine D1 receptor knockout mice, demonstrating its dependence on D1 receptors. This study indicates that the endocannabinoid system is a relevant negative modulator of both dopamine D1 and D2 receptor-mediated behaviors, a finding that may contribute to our understanding of basal ganglia motor disorders.     

Morphological and Structural Transformations of Fe-Pd Powder Alloys Formed by Galvanic Replacement,Annealing and Acid Treatment

In this article, we report the preparation and structural features of Fe-Pd powder alloys formed by galvanic replacement, annealing and selective dissolution of iron via acid treatment. The alloys were studied by the X-ray diffraction phase analysis, Mössbauer spectroscopy, scanning electron microscopy, and energy-dispersive spectroscopy. The Fe@Pd core–shell particles were obtained by a galvanic replacement reaction occurring upon treatment of a body-centered cubic (bcc) iron powder by a solution containing PdCl₄²⁻ ions. It was found that the shells are a face-centered cubic (fcc) Pd(Fe) solid solution. HCl acid treatment of the Fe@Pd core–shell particles resulted in the formation of hollow Pd-based particles, as the bcc phase was selectively dissolved from the cores. Annealing of the Fe@Pd core–shell particles at 800 °C led to the formation of fcc Fe-Pd solid solution. Acid treatment of the Fe-Pd alloys formed by annealing of the core–shell particles allowed selectively dissolving iron from the bcc Fe-based phase (Fe(Pd) solid solution), while the fcc Fe-rich Fe-Pd solid solution remained stable (resistant to acid corrosion). It was demonstrated that the phase composition and the Fe/Pd ratio in the alloys (phases) can be tailored by applying annealing and/or acid treatment to the as-synthesized Fe@Pd core–shell particles.     

Etxadi–Gangoiti scale: a proposal to evaluate the family contexts of two-year-old children†

This paper makes a proposal for the comprehensive assessment of the family context of children aged two years. It offers an updated resource based on recent research into the assessment of family contexts and their influence on children's psychological development. The proposal explores the following areas: Presence of learning materials; Potential for play; Stimulation of cognitive development; Stimulation of language development; Emotional expressiveness; Setting of limits and optimal frustration; Enhancement of self-esteem and autonomy; Observation of mother–child interactions; Father's involvement; Quality of non-parental care; Relations with the extended family and social support network; Stability of the child's social relationships; Relations with the school; Diversity of experiences; Absence of exposure to conflict; Absence of parental stress; and Quality of the physical context. The areas explored are grouped into three blocks: Stimulation of cognitive and linguistic development; Stimulation of socio-emotional development; and Organisation of the social context and physical environment.     

Health Benefits of Methylxanthines in Cacao and Chocolate

One may wonder why methylxanthines are so abundant in beverages used by humans for centuries, or in cola-drinks that have been heavily consumed since their appearance. It is likely that humans have stuck to any brew containing compounds with psychoactive properties, resulting in a better daily life, i.e., more efficient thinking, exploring, hunting, etc., however, without the serious side effects of drugs of abuse. The physiological effects of methylxanthines have been known for a long time and they are mainly mediated by the so-called adenosine receptors. Caffeine and theobromine are the most abundant methylxanthines in cacao and their physiological effects are notable. Their health-promoting benefits are so remarkable that chocolate is explored as a functional food. The consequences of adenosine receptor blockade by natural compounds present in cacao/chocolate are here reviewed. Palatability and health benefits of methylxanthines, in general, and theobromine, in particular, have further contributed to sustain one of the most innocuous and pleasant habits: chocolate consumption.     

Escherichia coli: an unknown and infrequent cause of community acquired pneumonia

Our aim was to describe the incidence, clinical characteristics and outcome of community acquired pneumonia (CAP) caused by Escherichia coli through the analysis of a cohort of patients with this condition. This study includes all the patients who were admitted to our hospitals because of CAP caused by E. coli, diagnosed with highly reliable microbiological techniques, such as blood culture, bronchoscopic protected specimen brush (PSB) or transthoracic needle aspiration (TNA). 29 patients were enrolled, representing 0.4% of CAP cases admitted. Main symptoms were fever and dyspnoea. 18 patients were classified into class IV and class V of the Pneumonia Severity Index (PSI). Diagnosis was based on blood culture in 24 cases, PSB in 4 cases and by TNA in 1 case. Three of the patients died, the longer time evolution of the symptoms being the only factor related to higher mortality (p<0.05). Mean hospitalization time was 7.1+/-3.1 d, and correlated with severity at admission (r=0.43; p<0.003). This study demonstrates that CAP caused by E. coli is infrequent. It has an unspecific presentation and mortality rate is 10.3%, associated with longer time before admission to hospital.     

Stochastic transitions into silence cause noise correlations in cortical circuits

The spiking activity of cortical neurons is highly variable. This variability is generally correlated among nearby neurons, an effect commonly interpreted to reflect the coactivation of neurons due to anatomically shared inputs. Recent findings, however, indicate that correlations can be dynamically modulated, suggesting that the underlying mechanisms are not well understood. Here, we investigate the hypothesis that correlations are dominated by neuronal coinactivation: the occurrence of brief silent periods during which all neurons in the local network stop firing. We recorded spiking activity from large populations of neurons in the auditory cortex of anesthetized rats across different brain states. During spontaneous activity, the reduction of correlation accompanying brain state desynchronization was largely explained by a decrease in the density of the silent periods. The presentation of a stimulus caused an initial drop of correlations followed by a rebound, a time course that was mimicked by the instantaneous silence density. We built a rate network model with fluctuation-driven transitions between a silent and an active attractor and assumed that neurons fired Poisson spike trains with a rate following the model dynamics. Variations of the network external input altered the transition rate into the silent attractor and reproduced the relation between correlation and silence density found in the data, both in spontaneous and evoked conditions. This suggests that the observed changes in correlation, occurring gradually with brain state variations or abruptly with sensory stimulation, are due to changes in the likeliness of the microcircuit to transiently cease firing.Neuronal noise correlations are defined as common fluctuations in the spiking activity of neurons under conditions of constant sensory input or motor output. Traditionally, they have been thought to arise from the dense connectivity of the cortex, such that neighboring neurons sharing a fraction of their inputs should also share a fraction of their output variability (1). Several observations are consistent with this hypothesis: pairwise correlations in the cortex decrease with cell pair distance (2) or with the difference in stimulus selectivity (3), dependencies that could follow from a variation in shared input given the anatomy of cortical circuits. Recent findings, however, challenge this simple interpretation. Recordings in the primate visual cortex have shown that attention or task context can change correlation structure (4–6) and that the magnitude of averaged correlation can be very low (7). In anesthetized rodents correlations decrease with brain state desynchronization (8, 9) or when animals switch from quiet wakefulness to active whisking during waking (10). Moreover, the commonly observed drop of spiking variability following stimulus onset (11–13) seems to occur jointly with a transient decrease in correlation (2, 14, 15). These observations suggest that correlations reflect the dynamical state of the circuit more than its hardwired connectivity.Despite substantial progress in understanding the mechanisms giving rise to large individual variability in recurrent networks (9, 16–18), we still lack a canonical model that can generate correlations with the same magnitude and spatiotemporal structure as those observed in cortical circuits. Balanced networks, for instance, a common model that reproduces the large variability of cortical neurons (9, 18, 19), show near-zero averaged correlations (9). Numerous studies have investigated the generation of synchronous firing (20), but whether short bursts of population activity can quantitatively account for the spike count correlations found in the data is unclear. Recurrent networks can also generate fast oscillations in the population activity, but, in a regime of low rates, typical of cortical circuits, average spike count correlations are negligible (21). Network models producing nonzero average correlations are those exhibiting up and down dynamics (22–29). Most of these studies have focused on investigating the mechanisms underlying the slow oscillatory activity observed in cortical slices (30), under anesthesia (31, 32), or during slow-wave sleep (33). Only recently the impact of up and down switching on trial-to-trial response variability (25) and on the probability distribution of multiunit activity (29) across brain states has been investigated. Whether the alternation between up and down phases could quantitatively account for the pairwise correlations observed in different brain states and describe their stimulus-evoked dynamics remains an open question.To investigate the mechanisms producing correlated firing, we recorded the spiking activity of large populations of neurons from the auditory cortex of anesthetized rats. During spontaneous activity, changes in correlation were largely explained by variation of the occurrence rate of periods during which neurons in the circuit stopped firing. Furthermore, the time course of correlation in response to an acoustic stimulus reflected the transient variation of this silence density. A computational rate model with fluctuation-driven transitions between silent and active attractors could explain the experimentally observed time course of correlation and its relation to silence density. Our findings suggest that the dynamics of these transitions play a fundamental role in generating noise correlations among cortical neurons.