Determination of the 5-HT receptor subtype involved in 8-OH-DPAT-induced hyperlocomotion: potential difficulties arising from inadequate pharmacological tools

Selective 5-HT1A receptor agonists such as 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), flesinoxan, 5-methylurapidil and others, increased locomotor behaviour in rats following s.c. injection. Unfortunately, all available 5-HT1A receptor antagonists are non-selective, a fact which severely hampers their use. The inhibitory effects of (+)- and (-)-pindolol (1-10 mg/kg, -45 min s.c.) on locomotion induced by 8-OH-DPAT were investigated in rats pretreated with the beta-adrenoceptor antagonists, ICI 118,551 and betaxolol (both 1 mg/kg, -45 min s.c.). ICI 118,551 and betaxolol significantly enhanced the response to 8-OH-DPAT. Co-administration of (-)-pindolol (2-10 mg/kg) dose dependently antagonised the hyperlocomotion whereas (+)-pindolol was weakly effective at 10 mg/kg. The partial agonists ipsapirone (1-10 mg/kg, -45 min s.c.) and buspirone (0.1-1 mg/kg, -45 min) antagonised the effects of 8-OH-DPAT. This inhibition may, however, be due to alpha 1-adrenoceptor blockade and DA receptor antagonism, respectively. Finally, although spiroxatrine (0.1 and 1 mg/kg, -45 min s.c.) inhibited the response to 8-OH-DPAT, this inhibition may also be non-specific since spiroxatrine strongly reduced spontaneous locomotor activity. In conclusion, whilst much of our data is consistent with 8-OH-DPAT-induced locomotion being mediated by 5-HT1A receptors, only the data obtained with the pindolol enantiomers provide direct evidence for this. The results also suggest that, under normal circumstances, the 5-HT1A receptor antagonist effect of pindolol may be masked by the facilitating effect of beta-adrenoceptor blockade.     

Household Food Insecurity,Lung Function,and COPD in US Adults

Increasing epidemiological evidence suggests that optimal diet quality helps to improve preservation of lung function and to reduce chronic obstructive pulmonary disease (COPD) risk, but no study has investigated the association of food insecurity (FI) and lung health in the general population. Using data from a representative sample of US adults who participated in the National Health and Nutrition Examination Survey (NHANES) 2007–2012 cycles, we investigated the association between FI with lung function and spirometrically defined COPD in 12,469 individuals aged ≥ 18 years of age. FI (high vs. low) was defined using the US Department of Agriculture’s Food Security Scale). Population-weighted adjusted regression models were used to investigate associations between FI, and forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC), their ratio, and spirometrically defined restriction (FVC below the lower limit of normal) and airflow obstruction (COPD). The prevalence of household FI was 13.2%. High household FI was associated with lower FVC (adjusted β-coefficient −70.9 mL, 95% CI −116.6, −25.3), and with higher odds (OR) of spirometric restriction (1.02, 95% CI 1.00, 1.03). Stratified analyses showed similar effect sizes within specific ethnic groups. High FI was associated with worse lung health in a nationally representative sample of adults in the US.     

Basismaßnahmen zur Wiederbelebung Erwachsener (Basic Life Support)

Notfall + Rettungsmedizin - Der Europäische Rat für Wiederbelebung hat diese Leitlinie – Basismaßnahmen zur Wiederbelebung – auf Grundlage des...     

Hospitals: to the next millennium

Hospitals are changing. Throughout the OECD the hospital, that enduring and pervasive organization which has delivered the vast majority of acute care services for decades, is being reconceptualized. We briefly analyse trends which clearly indicate that the existing concept of the hospital is rapidly coming to an end. The emerging model consists of a core facility comprising only the most acute services, intensive care, operating theatres and an accident and emergency unit, with all other services and units linked by information technology to each other and to the core facility. We explore some of the management challenges confronting those who will be responsible for taking their organization through the transition to the boundaryless hospital arrangement, discuss a number of the existing problems with today's hospitals which the new model has the propensity to resolve, and deal with some of the emerging issues which it brings with it.     

Innovation as hospital culture: a trial and demonstration facility in an acute-care hospital ward

This short communication describes the establishment of a trial and demonstration facility for new products, technologies, methods and procedures in an acute-care hospital ward at Concord Hospital in Sydney, Australia. The importance of innovation for all businesses, including hospitals, is discussed; and, why a project like the Model Ward can promote innovation as part of the corporate culture. The Model Ward development, implementation and its benefits are reported on and discussed.     

Functional Differentiation of Mouse Visual Cortical Areas Depends upon Early Binocular Experience

The mammalian visual cortex contains multiple retinotopically defined areas that process distinct features of the visual scene. Little is known about what guides the functional differentiation of visual cortical areas during development. Recent studies in mice have revealed that visual input from the two eyes provides spatiotemporally distinct signals to primary visual cortex (V1), such that contralateral eye-dominated V1 neurons respond to higher spatial frequencies than ipsilateral eye-dominated neurons. To test whether binocular visual input drives the differentiation of visual cortical areas, we used two-photon calcium imaging to characterize the effects of juvenile monocular deprivation (MD) on the responses of neurons in V1 and two higher visual areas, LM (lateromedial) and PM (posteromedial). In adult mice of either sex, we find that MD prevents the emergence of distinct spatiotemporal tuning in V1, LM, and PM. We also find that, within each of these areas, MD reorganizes the distinct spatiotemporal tuning properties driven by the two eyes. Moreover, we find a relationship between speed tuning and ocular dominance in all three areas that MD preferentially disrupts in V1, but not in LM or PM. Together, these results reveal that balanced binocular vision during development is essential for driving the functional differentiation of visual cortical areas. The higher visual areas of mouse visual cortex may provide a useful platform for investigating the experience-dependent mechanisms that set up the specialized processing within neocortical areas during postnatal development.SIGNIFICANCE STATEMENT Little is known about the factors guiding the emergence of functionally distinct areas in the brain. Using in vivo Ca²⁺ imaging, we recorded visually evoked activity from cells in V1 and higher visual areas LM (lateromedial) and PM (posteromedial) of mice. Neurons in these areas normally display distinct spatiotemporal tuning properties. We found that depriving one eye of normal input during development prevents the functional differentiation of visual areas. Deprivation did not disrupt the degree of speed tuning, a property thought to emerge in higher visual areas. Thus, some properties of visual cortical neurons are shaped by binocular experience, while others are resistant. Our study uncovers the fundamental role of binocular experience in the formation of distinct areas in visual cortex.     

Progression of sleep disturbances in Parkinson’s disease: a 5-year longitudinal study

Journal of Neurology - Sleep disorders can occur in early Parkinson’s disease (PD). However, the relationship between different sleep disturbances and their longitudinal evolution has not...     

Is what goes in what comes out? Encoding and retrieval event-related potentials together determine memory outcome

Understanding memory function amounts to identifying how events (cognitive and neural) at study eventually influence events at test. Many of the proposed cognitive correlates of memory-related event-related potentials (ERPs) at study resemble proposed cognitive correlates of other memory-related ERPs, recorded at test. We wondered whether a given known ERP feature at study might in fact reflect an effective-encoding process that is, in turn, tapped by another specific ERP feature, recorded at test. To this end, we asked which pairs of known memory-related ERP features explain common variance across a large sample of participants, while they perform a word-recognition task. Two early ERP features, the Late Positive Component (study) and the FN400 (test), covaried significantly. These features also correlated with memory success (d′ and response time). Two later ERP features, the Slow Wave (study) and the Late Parietal Positivity (test), also covaried when lures were incorporated into the analysis. Interestingly, these later features were uncorrelated with memory outcome. This novel approach, exploiting naturally occurring subject variability (in strategy and ERP amplitudes), informs our understanding of the memory functions of ERP features in several ways. Specifically, they strengthen the argument that the earlier ERP features may drive old/new recognition (but perhaps not the later features). Our findings suggest the Late Positive Component at study, in some degree, may cause the FN400 to increase at test, together producing effective recognition memory. The Slow Wave at study appears to relate the Left Parietal Positivity at test, but these may play roles in more complex memory judgments and may be less critical for simple old/new recognition.