Stages of development and injury patterns in the early years: a population-based analysis

BACKGROUND: In Canada, there are many formal public health programs under development that aim to prevent injuries in the early years (e.g. 0–6). There are paradoxically no population-based studies that have examined patterns of injury by developmental stage among these young children. This represents a gap in the Canadian biomedical literature. The current population-based analysis explores external causes and consequences of injuries experienced by young children who present to the emergency department for assessment and treatment. This provides objective evidence about prevention priorities to be considered in anticipatory counseling and public health planning. METHODS: Four complete years of data (1999–2002; n = 5876 cases) were reviewed from the Kingston sites of the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP), an ongoing injury surveillance initiative. Epidemiological analyses were used to characterize injury patterns within and across age groups (0–6 years) that corresponded to normative developmental stages. RESULTS: The average annual rate of emergency department-attended childhood injury was 107 per 1000 (95% CI 91–123), with boys experiencing higher annual rates of injury than girls (122 vs. 91 per 1000; p < 0.05). External causes of injury changed substantially by developmental stage. This lead to the identification of four prevention priorities surrounding 1) the optimization of supervision; 2) limiting access to hazards; 3) protection from heights; and 4) anticipation of risks. CONCLUSION: This population-based injury surveillance analysis provides a strong evidence-base to inform and enhance anticipatory counseling and other public health efforts aimed at the prevention of childhood injury during the early years

Systematic Neighborhood Observations at High Spatial Resolution: Methodology and Assessment of Potential Benefits

There is a growing body of public health research documenting how characteristics of neighborhoods are associated with differences in the health status of residents. However, little is known about how the spatial resolution of neighborhood observational data or community audits affects the identification of neighborhood differences in health. We developed a systematic neighborhood observation instrument for collecting data at very high spatial resolution (we observe each parcel independently) and used it to collect data in a low-income minority neighborhood in Dallas, TX. In addition, we collected data on the health status of individuals residing in this neighborhood. We then assessed the inter-rater reliability of the instrument and compared the costs and benefits of using data at this high spatial resolution. Our instrument provides a reliable and cost-effect method for collecting neighborhood observational data at high spatial resolution, which then allows researchers to explore the impact of varying geographic aggregations. Furthermore, these data facilitate a demonstration of the predictive accuracy of self-reported health status. We find that ordered logit models of health status using observational data at different spatial resolution produce different results. This implies a need to analyze the variation in correlative relationships at different geographic resolutions when there is no solid theoretical rational for choosing a particular resolution. We argue that neighborhood data at high spatial resolution greatly facilitates the evaluation of alternative geographic specifications in studies of neighborhood and health

The Serotonin-6 Receptor as a Novel Therapeutic Target

Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter that is found in both the central and peripheral nervous systems. 5-HT mediates its diverse physiological responses through 7 different 5-HT receptor families: 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, and 5-HT7 receptors. Among them, the 5-HT6 receptor (5-HT6R) is the most recently cloned serotonin receptor and plays important roles in the central nervous system (CNS) and in the etiology of neurological diseases. Compared to other 5-HT receptors, the 5-HT6R has been considered as an attractive CNS therapeutic target because it is expressed exclusively in the CNS and has no known isoforms. This review evaluates in detail the role of the 5-HT6R in the physiology and pathophysiology of the CNS and the potential usefulness of 5-HT6R ligands in the development of therapeutic strategies for the treatment of CNS disorders. Preclinical studies provide support for the use of 5-HT6R ligands as promising medications to treat the cognitive dysfunction associated with Alzheimer's disease, obesity, depression, and anxiety

Neighbourhood ethnic density effects on behavioural and cognitive problems among young racial/ethnic minority children in the US and England: a cross-national comparison

Studies on adult racial/ethnic minority populations show that the increased concentration of racial/ethnic minorities in a neighbourhood—a so-called ethnic density effect—is associated with improved health of racial/ethnic minority residents when adjusting for area deprivation. However, this literature has focused mainly on adult populations, individual racial/ethnic groups, and single countries, with no studies focusing on children of different racial/ethnic groups or comparing across nations. This study aims to compare neighbourhood ethnic density effects on young children’s cognitive and behavioural outcomes in the US and in England. We used data from two nationally representative birth cohort studies, the US Early Childhood Longitudinal Study-Birth Cohort and the UK Millennium Cohort Study, to estimate the association between own ethnic density and behavioural and cognitive development at 5 years of age. Findings show substantial heterogeneity in ethnic density effects on child outcomes within and between the two countries, suggesting that ethnic density effects may reflect the wider social and economic context. We argue that researchers should take area deprivation into account when estimating ethnic density effects and when developing policy initiatives targeted at strengthening and improving the health and development of racial and ethnic minority children

Cooperativity and flexibility in enzyme evolution

Enzymes are flexible catalysts, and there has been substantial discussion about the extent to which this flexibility contributes to their catalytic efficiency. What has been significantly less discussed is the extent to which this flexibility contributes to their evolvability. Despite this, recent years have seen an increasing number of both experimental and computational studies that demonstrate that cooperativity and flexibility play significant roles in enzyme innovation. This review covers key developments in the field that emphasize the importance of enzyme dynamics not just to the evolution of new enzyme function(s), but also as a property that can be harnessed in the design of new artificial enzymes.The European Research Council has provided financial support under the European Community’s Seventh Framework Program (FP7/2007-2013)/ERC Grant Agreement No. 306474. This work was also funded by the Feder Funds, Grants from the Spanish Ministry of Economy and Competitiveness (BIO2015-66426-R and CSD2009-00088) and the Human Frontier Science Program (RGP0041/2017). A.P. is a Wenner-Gren Foundations Postdoctoral Fellow and S. C. L. K. is a Wallenberg Academy Fellow

The pathophysiology of restricted repetitive behavior

Restricted, repetitive behaviors (RRBs) are heterogeneous ranging from stereotypic body movements to rituals to restricted interests. RRBs are most strongly associated with autism but occur in a number of other clinical disorders as well as in typical development. There does not seem to be a category of RRB that is unique or specific to autism and RRB does not seem to be robustly correlated with specific cognitive, sensory or motor abnormalities in autism. Despite its clinical significance, little is known about the pathophysiology of RRB. Both clinical and animal models studies link repetitive behaviors to genetic mutations and a number of specific genetic syndromes have RRBs as part of the clinical phenotype. Genetic risk factors may interact with experiential factors resulting in the extremes in repetitive behavior phenotypic expression that characterize autism. Few studies of individuals with autism have correlated MRI findings and RRBs and no attempt has been made to associate RRB and post-mortem tissue findings. Available clinical and animal models data indicate functional and structural alterations in cortical-basal ganglia circuitry in the expression of RRB, however. Our own studies point to reduced activity of the indirect basal ganglia pathway being associated with high levels of repetitive behavior in an animal model. These findings, if generalizable, suggest specific therapeutic targets. These, and perhaps other, perturbations to cortical basal ganglia circuitry are mediated by specific molecular mechanisms (e.g., altered gene expression) that result in long-term, experience-dependent neuroadaptations that initiate and maintain repetitive behavior. A great deal more research is needed to uncover such mechanisms. Work in areas such as substance abuse, OCD, Tourette syndrome, Parkinson’s disease, and dementias promise to provide findings critical for identifying neurobiological mechanisms relevant to RRB in autism. Moreover, basic research in areas such as birdsong, habit formation, and procedural learning may provide additional, much needed clues. Understanding the pathophysioloy of repetitive behavior will be critical to identifying novel therapeutic targets and strategies for individuals with autism

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Cross-Reactive Sensor Arrays for the Detection of Peptides in Aqueous Solution by Fluorescence Spectroscopy

A simple but powerful method for the sensing of peptides in aqueous solution has been developed. The transition-metal complexes [PdCl2(en)], [{RhCl2Cp*}2], and [{RuCl2(p-cymene)} 2] were combined with six different fluorescent dyes to build a cross-reactive sensor array. The fluorescence response of the individual sensor units was based on competitive complexation reactions between the peptide analytes and the fluorescent dyes. The collective response of the sensor array in a time-resolved fashion was used as an input for multivariate analyses. A sensor array comprised of only six metal-dye combinations was able to differentiate ten different dipeptides in buffered aqueous solution at a concentration of 50 uM. Furthermore, the cross-reactive sensor could be used to obtain information about the identity and the quantity of the pharmacologically interesting dipeptides carnosine and homocarnosine in a complex biological matrix, such as deproteinized human blood serum. The sensor array was also able to sense longer peptides, which was demonstrated by differentiating mixtures of the nonapeptide bradykinin and the decapeptide kallidin

Local Anesthesia: Evidence, Strategies, and Safety

The number of office-based procedures performed utilizing local anesthesia continues to rise, particularly in dermatologic settings. As more emphasis is placed on cost effectiveness in medicine, it is important to understand the role that office-based procedures can play in providing excellent dermatologic care. In addition, it is essential to continually demonstrate that local anesthesia administered in office-based settings is safe and effective in order to maintain a high standard of care within the specialty. Achieving adequate local anesthesia is imperative to ensure patient comfort, reduce anxiety, and promote optimal outcomes. The clinician should have a comprehensive understanding of the pathophysiology, mechanism of action, practical applications and techniques, and potential adverse events of various topical and injectable anesthetics in order to enhance patient satisfaction and safety. Lidocaine, which is the most commonly used local anesthetic, has a rapid onset, moderate duration, and excellent safety profile, making it a staple in office-based procedures