The plausibility of a role for mercury in the etiology of autism: a cellular perspective

Autism is defined by a behavioral set of stereotypic and repetitious behavioral patterns in combination with social and communication deficits. There is emerging evidence supporting the hypothesis that autism may result from a combination of genetic susceptibility and exposure to environmental toxins at critical moments in development. Mercury (Hg) is recognized as a ubiquitous environmental neurotoxin and there is mounting evidence linking it to neurodevelopmental disorders, including autism. Of course, the evidence is not derived from experimental trials with humans but rather from methods focusing on biomarkers of Hg damage, measurements of Hg exposure, epidemiological data, and animal studies. For ethical reasons, controlled Hg exposure in humans will never be conducted. Therefore, to properly evaluate the Hg-autism etiological hypothesis, it is essential to first establish the biological plausibility of the hypothesis. This review examines the plausibility of Hg as the primary etiological agent driving the cellular mechanisms by which Hg-induced neurotoxicity may result in the physiological attributes of autism. Key areas of focus include: (1) route and cellular mechanisms of Hg exposure in autism; (2) current research and examples of possible genetic variables that are linked to both Hg sensitivity and autism; (3) the role Hg may play as an environmental toxin fueling the oxidative stress found in autism; (4) role of mitochondrial dysfunction; and (5) possible role of Hg in abnormal neuroexcitory and excitotoxity that may play a role in the immune dysregulation found in autism. Future research directions that would assist in addressing the gaps in our knowledge are proposed

Computerized clinical documentation system in the pediatric intensive care unit

BACKGROUND: To determine whether a computerized clinical documentation system (CDS): 1) decreased time spent charting and increased time spent in patient care; 2) decreased medication errors; 3) improved clinical decision making; 4) improved quality of documentation; and/or 5) improved shift to shift nursing continuity. METHODS: Before and after implementation of CDS, a time study involving nursing care, medication delivery, and normalization of serum calcium and potassium values was performed. In addition, an evaluation of completeness of documentation and a clinician survey of shift to shift reporting were also completed. This was a modified one group, pretest-posttest design. RESULTS: With the CDS there was: improved legibility and completeness of documentation, data with better accessibility and accuracy, no change in time spent in direct patient care or charting by nursing staff. Incidental observations from the study included improved management functions of our nurse manager; improved JCAHO documentation compliance; timely access to clinical data (labs, vitals, etc); a decrease in time and resource use for audits; improved reimbursement because of the ability to reconstruct lost charts; limited human data entry by automatic data logging; eliminated costs of printing forms. CDS cost was reasonable. CONCLUSIONS: When compared to a paper chart, the CDS provided a more legible, compete, and accessible patient record without affecting time spent in direct patient care. The availability of the CDS improved shift to shift reporting. Other observations showed that the CDS improved management capabilities; helped physicians deliver care; improved reimbursement; limited data entry errors; and reduced costs

Rituximab therapy for juvenile-onset systemic lupus erythematosus

Rituximab (RTX), an anti-CD20 monoclonal antibody, has been proposed for use in the therapy of systemic lupus erythematosus (SLE). We present the initial long-term experience of the safety and efficacy of rituximab for treatment of SLE in children. Eighteen patients (mean age 14 ± 3 years) with severe SLE were treated with rituximab after demonstrating resistance or toxicity to conventional regimens. There was a predominance of female (16/18) and ethnic African (13/18) patients. All had lupus nephritis [World Health Organization (WHO) classes 3–5] and systemic manifestations of vasculitis. Clinical disease activity of the SLE was scored with the SLE-disease activity index 2K (SLEDAI-2K). Patients were followed-up for an average of 3.0 ± 1.3 years (range 0.5 to 4.8 years). B-cell depletion occurred within 2 weeks in all patients and persisted for up to 1 year in some. Clinical activity scores, double-stranded DNA (dsDNA) antibodies, renal function and proteinuria [urine protein to creatinine ratio (Upr/cr)] improved in 93% of the patients. Five patients required multiple courses of RTX for relapse, with B-cell repopulation. One died of infectious endocarditis related to severe immunosuppression. In conclusion, our data support the efficacy of rituximab as adjunctive treatment for SLE in children. Although rituximab was well tolerated by the majority of patients, randomized controlled trials are required to establish its long-term safety and efficacy

The search for stable prognostic models in multiple imputed data sets

<p>Abstract</p> <p>Background</p> <p>In prognostic studies model instability and missing data can be troubling factors. Proposed methods for handling these situations are bootstrapping (B) and Multiple imputation (MI). The authors examined the influence of these methods on model composition.</p> <p>Methods</p> <p>Models were constructed using a cohort of 587 patients consulting between January 2001 and January 2003 with a shoulder problem in general practice in the Netherlands (the Dutch Shoulder Study). Outcome measures were persistent shoulder disability and persistent shoulder pain. Potential predictors included socio-demographic variables, characteristics of the pain problem, physical activity and psychosocial factors. Model composition and performance (calibration and discrimination) were assessed for models using a complete case analysis, MI, bootstrapping or both MI and bootstrapping.</p> <p>Results</p> <p>Results showed that model composition varied between models as a result of how missing data was handled and that bootstrapping provided additional information on the stability of the selected prognostic model.</p> <p>Conclusion</p> <p>In prognostic modeling missing data needs to be handled by MI and bootstrap model selection is advised in order to provide information on model stability.</p

'Is your city pretty anyway?' Perspectives on graffiti and the urban landscape

Drawing on survey and focus group research completed in New Zealand in 2009 this article examines young peoples’ perspectives on graffiti and tagging. The results further demonstrate that graffiti writing is an activity invested with considerable cultural meaning by many of those engaged in it and that their understanding of graffiti is considerably at odds with prevailing political, media and policy discourse that sees it purely in terms of criminal damage and antisocial behaviour. While graffiti can be conceptualised as an alternative way of ‘reading’ urban space, the results of this study show that writers recognised that graffiti had damaging consequences and was inappropriate in some contexts. Graffiti was not simply nihilistic destructive behaviour but one in which perceptions of criminality were leavened by aesthetic judgements and the allure and excitement of potential local celebrity

Detecting failure of climate predictions

The practical consequences of climate change challenge society to formulate responses that are more suited to achieving long-term objectives, even if those responses have to be made in the face of uncertainty. Such a decision-analytic focus uses the products of climate science as probabilistic predictions about the effects of management policies. Here we present methods to detect when climate predictions are failing to capture the system dynamics. For a single model, we measure goodness of fit based on the empirical distribution function, and define failure when the distribution of observed values significantly diverges from the modelled distribution. For a set of models, the same statistic can be used to provide relative weights for the individual models, and we define failure when there is no linear weighting of the ensemble models that produces a satisfactory match to the observations. Early detection of failure of a set of predictions is important for improving model predictions and the decisions based on them. We show that these methods would have detected a range shift in northern pintail 20 years before it was actually discovered, and are increasingly giving more weight to those climate models that forecast a September ice-free Arctic by 2055

The Shortest Isoform of Dystrophin (Dp40) Interacts with a Group of Presynaptic Proteins to Form a Presumptive Novel Complex in the Mouse Brain

Duchenne muscular dystrophy (DMD) causes cognitive impairment in one third of the patients, although the underlying mechanisms remain to be elucidated. Recent studies showed that mutations in the distal part of the dystrophin gene correlate well with the cognitive impairment in DMD patients, which is attributed to Dp71. The study on the expression of the shortest isoform, Dp40, has not been possible due to the lack of an isoform specific antibody. Dp40 has the same promoter as that found in Dp71 and lacks the normal C-terminal end of Dp427. In the present study, we have raised polyclonal antibody against the N-terminal sequence common to short isoforms of dystrophin, including Dp40, and investigated the expression pattern of Dp40 in the mouse brain. Affinity chromatography with this antibody and the consecutive LC-MS/MS analysis on the interacting proteins revealed that Dp40 was abundantly expressed in synaptic vesicles and interacted with a group of presynaptic proteins, including syntaxin1A and SNAP25, which are involved in exocytosis of synaptic vesicles in neurons. We thus suggest that Dp40 may form a novel protein complex and play a crucial role in presynaptic function. Further studies on these aspects of Dp40 function might provide more insight into the molecular mechanisms of cognitive impairment found in patients with DMD

Atherogenic Dyslipidemia: Cardiovascular Risk and Dietary Intervention

Atherogenic dyslipidemia comprises a triad of increased blood concentrations of small, dense low-density lipoprotein (LDL) particles, decreased high-density lipoprotein (HDL) particles, and increased triglycerides. A typical feature of obesity, the metabolic syndrome, insulin resistance, and type 2 diabetes mellitus, atherogenic dyslipidemia has emerged as an important risk factor for myocardial infarction and cardiovascular disease. A number of genes have now been linked to this pattern of lipoprotein changes. Low-carbohydrate diets appear to have beneficial lipoprotein effects in individuals with atherogenic dyslipidemia, compared to high-carbohydrate diets, whereas the content of total fat or saturated fat in the diet appears to have little effect. Achieving a better understanding of the genetic and dietary influences underlying atherogenic dyslipidemia may provide clues to improved interventions to reduce the risk of cardiovascular disease in high-risk individuals

Exploring the role of Emotional Intelligence on disorder eating psychopathology

Purpose: This study aims to explore the role of emotional intelligence (EI) and specific facets that may underpin the aetiology of disordered eating attitudes and behaviours, as a means to understand what aspects of these deficits to target within treatments. Methods: Participants were recruited from the UK and Ireland. Among the sample of 355 participants, 84% were women and 16% were men. Regarding age, 59% were between 18 and 29, 30% were between 30 and 49, and 11% were 50 or older. Using a cross-sectional design, participants completed the Schutte Self-Report Emotional Intelligence Test to measure levels of trait EI and The Eating Attitudes Test (EAT-26) as a measure of eating disorder risk and presence of disordered eating attitudes. Results: EAT-26 scores were negatively correlated with total EI scores and with the following EI subscales: appraisal of own emotions, regulation of emotions, utilization of emotions, and optimism. Also, compared to those without an eating disorder history, participants who reported having had an eating disorder had significantly lower total EI scores and lower scores on four EI subscales: appraisal of others emotions, appraisal of own emotions, regulation of emotions, and optimism. Conclusions: Considering these findings, EI (especially appraisal of own emotions, regulation of emotions, and optimism) may need to be addressed by interventions and treatments for eating disorders