Altered ß-Cell Calcium Dynamics via Electric Field Exposure.

Electric field stimulation has long been investigated with results supporting its therapeutic potential; however, its effects on insulin secreting cells has yet to be fully elucidated. Herein we explored the effects of physiological direct current (DC) electric field stimulation on the intracellular calcium dynamics of mouse derived ßTC-6 insulinoma cells. This electrical stimulation resulted in an elevation in intracellular calcium along with a rise in calcium spiking activity. Further investigation indicated that the rise in intracellular calcium was mediated by an influx of calcium via L-type voltage gated calcium channels. Additionally, the effects of the electric field stimulation were able to induce insulin secretion in the absence of glucose stimulation. Given these results, DC electric field stimulation could be used as a non-invasive tool to modulate intracellular calcium dynamics and insulin secretion of ß-cells for therapeutic application.

CORNET Card Study #1: Do You See What I See? Provider Confidence in Caring for Children With Special Health Care Needs.

OBJECTIVE: Understanding differences between trainee and faculty experience with and confidence caring for children with special health care needs (CSHCN) can inform pediatric resident education. METHODS: Residents and faculty across the continuity research network (CORNET) reported on a consecutive series of 5 primary care encounters. Respondents answered questions about visit characteristics, patient demographics, and applied the CSHCN Screener. Respondents also reported on how confident they felt addressing the patient's health care needs over time. We dichotomized confidence at "very confident" versus all other values. We used logistic regression to describe the correlates of provider confidence managing the patient's care. RESULTS: We collected data on 381 (74%) resident-patient and 137 (26%) attending-patient encounters. A higher proportion of attending encounters compared to resident encounters were with CSHCN (49% vs 39%, P < .05), including children with complex needs (17% vs 10%, P < .05). The odds of feeling "very confident" (AOR [95% CI]) was lower with increasing CSHCN score (0.61[0.51-0.72]) and was lower for resident versus attending encounters (0.39 [0.16-0.95]). Confidence was higher if the provider had previously seen that patient (2.07 [1.15-3.72]), and for well (2.50 [1.35-4.64]) or sick visits (3.18 [1.46-6.94]) (vs follow-up). Differences between residents and attending pediatricians regarding the relationship between confidence and visit characteristics for subsets of CSHCN are reported. CONCLUSION: All providers felt less confident caring for CSHCN; however, for certain needs, resident confidence did not increase with level of training. The data suggest potential educational/programmatic opportunities.

Perspectives on Indigenous cultural competency and safety in Canadian hospital emergency departments: A scoping review.

BACKGROUND: Emergency departments are primary health care entry points for Indigenous persons in Canada. They are also among the settings where Indigenous patients report access barriers and discriminatory treatment. Cultural competency and cultural safety have been proposed as approaches to improving emergency care. AIM: To identify and elaborate upon barriers and facilitators of cultural competency and safety in Canadian Emergency Departments. METHODS: We conducted a scoping review to search published and grey literature to identify and extract data on definitions, measures, facilitators and barriers of cultural competency and safety. RESULTS: Six articles met inclusion criteria. Studies presented perspectives from patients, care providers, health care organizations, and Indigenous knowledge holders. Key themes emerged across studies and stakeholders. These include: Interpersonal relationships between patients and care providers; cultural competency training; Emergency Department capacity; and racism and discrimination. CONCLUSION: We recommend that Emergency Department cultural competency and safety initiatives i) be built upon post-colonial understanding and partnerships with local Indigenous communities ii) provide practitioners with competencies in relationship-building and self-awareness iii) orient ED resources and services to meet the needs of patients with limited access to non-emergency healthcare and iv) aim to prevent discrimination.

Simultaneous Venoarterial Extracorporeal Membrane Oxygenation and Percutaneous Left Ventricular Decompression Therapy with Impella Is Associated with Improved Outcomes in Refractory Cardiogenic Shock.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been used for refractory cardiogenic shock; however, it is associated with increased left ventricular afterload. Outcomes associated with the combination of a percutaneous left ventricular assist device (Impella) and VA-ECMO remains largely unknown. We retrospectively reviewed patients treated for refractory cardiogenic shock with VA-ECMO (2014-2016). The primary outcome was all-cause mortality within 30 days of VA-ECMO implantation. Secondary outcomes included duration of support, stroke, major bleeding, hemolysis, inotropic score, and cardiac recovery. Outcomes were compared between the VA-ECMO cohort and VA-ECMO + Impella (ECPELLA cohort). Sixty-six patients were identified: 36 VA-ECMO and 30 ECPELLA. Fifty-eight percent of VA-ECMO patients (n = 21) had surgical venting, as compared to 100% of the ECPELLA cohort (n = 30) which had Impella (±surgical vent). Both cohorts demonstrated relatively similar baseline characteristics except for higher incidence of ST-elevation myocardial infarction (STEMI) and percutaneous coronary intervention (PCI) in the ECPELLA cohort. Thirty-day all-cause mortality was significantly lower in the ECPELLA cohort (57% vs. 78%; hazard ratio [HR] 0.51 [0.28-0.94], log rank p = 0.02), and this difference remained intact after correcting for STEMI and PCI. No difference between secondary outcomes was observed, except for the inotrope score which was greater in VA-ECMO group by day 2 (11 vs. 0; p = 0.001). In the largest US-based retrospective study, the addition of Impella to VA-ECMO for patients with refractory cardiogenic shock was associated with lower all-cause 30 day mortality, lower inotrope use, and comparable safety profiles as compared with VA-ECMO alone.

Self-Awareness Without Awareness? Implicit Self-Focused Attention and Behavioral Self-Regulation.

Objective self-awareness theory contends that focusing attention on the self initiates an automatic comparison of self to standards. To gain evidence for automatic self-standard comparison processes, two experiments manipulated attention to self with subliminal first-name priming. People completed a computer-based parity task after being instructed that the standard was to be fast or to be accurate. Subliminal first name priming increased behavioral adherence to the explicit standard. When told to be fast, self-focused people made more mistakes and had faster response times; when told to be accurate, self-focused people made fewer mistakes. A manipulation of conscious self-awareness (via a mirror) had the same self-regulatory effects. The findings suggest that comparing self to standards can occur automatically and that it is attention to self, not awareness of the self per se, that evokes self-evaluation.

Oxytocin increases retention of social cognition in autism.

BACKGROUND: Oxytocin dysfunction might contribute to the development of social deficits in autism, a core symptom domain and potential target for intervention. This study explored the effect of intravenous oxytocin administration on the retention of social information in autism. METHODS: Oxytocin and placebo challenges were administered to 15 adult subjects diagnosed with autism or Asperger's disorder, and comprehension of affective speech (happy, indifferent, angry, and sad) in neutral content sentences was tested. RESULTS: All subjects showed improvements in affective speech comprehension from pre- to post-infusion; however, whereas those who received placebo first tended to revert to baseline after a delay, those who received oxytocin first retained the ability to accurately assign emotional significance to speech intonation on the speech comprehension task. CONCLUSIONS: These results are consistent with studies linking oxytocin to social recognition in rodents as well as studies linking oxytocin to prosocial behavior in humans and suggest that oxytocin might facilitate social information processing in those with autism. These findings also provide preliminary support for the use of oxytocin in the treatment of autism.

Infants' understanding of object-directed action.

When and in what ways do infants recognize humans as intentional actors? An important aspect of this larger question concerns when infants recognize specific human actions (e.g. a reach) as object-directed (i.e. as acting toward goal-objects). In two studies using a visual habituation technique, 12-month-old infants were tested to assess their recognition that an adult's reach is directed toward its target object. Infants in the experimental condition were habituated to a display in which an actor reached over a wall-like barrier with an arcing arm movement, to pick up a ball. After habituation infants saw two test displays, for which the barrier was removed. In the direct test event the actor reached directly for the ball, the arm tracing a visually new path, but the action consistent with attempting to reach for the object as directly as possible. In the indirect test event the actor traced the old path, reaching over in an arc, even though the wall was no longer present. This arm movement was identical to that in habituation but no longer displayed a reach going directly to its object. In a control condition infants saw the same movements but in a situation with no goal-object. In the experimental conditions, with a goal object present, infants looked longer at the indirect test event in comparison to the direct test event. In the control conditions infants looked equally at both indirect and direct test events. We conclude that sensitivity to human object-directed action is established by 12-month-olds and compare these results to recent findings by [Gergely, G., Nadasdy, Z., Csibra, G., & Biro S. (1995). Taking the intentional stance at 12 months of age. Cognition, 56, 165-193] and [Woodward, A. (1998). Infants selectively encode the goal object of an actor's reach. Cognition, 69, 1-34].

Self-awareness and the emotional consequences of self-discrepancies.

Several self theories explore the effects of discrepant self-beliefs on motivation and emotion. This research intersected two self theories: self-discrepancy theory and objective self-awareness theory. Self-discrepancy theory predicts that ideal and ought discrepancies cause different negative emotions; objective self-awareness theory predicts that high self-awareness will strengthen the relationship between self-discrepancies and emotions. People (N =112) completed measures of self-discrepancies and emotions (dejection, agitation, positive affect, and negative affect). Self-focused attention was manipulated with a large mirror. When self-awareness was low, self-discrepancies had weak, nonsignificant relations to emotion. When self-awareness was high, however, self-discrepancies strongly predicted emotional experience. These effects were general-ideal and ought discrepancies affected emotions because of their substantial shared variance, not their unique variance. Implications for theories of self-discrepancies and emotions are considered.

A placebo controlled crossover trial of liquid fluoxetine on repetitive behaviors in childhood and adolescent autism.

Repetitive behaviors are a core symptom domain in autism that has been linked to alterations in the serotonin system. While the selective serotonin-receptive inhibitor fluvoxamine has been shown to be effective in adults with autism, as yet no published placebo controlled trials with these agents document safety and efficacy in children with autism. This study examines the selective serotonin reuptake inhibitor liquid fluoxetine in the treatment of repetitive behaviors in childhood and adolescent autism spectrum disorders (ASDs). In total, 45 child or adolescent patients with ASD were randomized into two acute 8-week phases in a double-blind placebo-controlled crossover study of liquid fluoxetine. Study design included two randomized 8-week fluoxetine and placebo phases separated by a 4-week washout phase. Outcome measures included measures of repetitive behaviors and global improvement. Low-dose liquid fluoxetine (mean final dose: 9.9+/-4.35 mg/day) was superior to placebo in the treatment of repetitive behaviors by CY-BOCS compulsion scale. The effect size was in the moderate to large range, and the doses used were low. Liquid fluoxetine was only slightly, and not significantly, superior to placebo on CGI autism score partially due to a phase order effect. However, fluoxetine was marginally superior to placebo on a composite measure of global effectiveness. Liquid fluoxetine did not significantly differ from placebo on treatment emergent side effects. Liquid fluoxetine in low doses is more effective than placebo in the treatment of repetitive behaviors in childhood autism. Limitations include small sample size and the crossover design of the study. Further replication and long-term maintenance trials are needed.

Infant social attention predicts preschool social cognition.

Recent research examining infants' understanding of intentional action claims to be studying the early origins or precursors of children's later theories of mind If these infant understandings are continuous with later preschool achievements, there should be empirical connections between the two. We provide initial evidence that infants' social attention predicts later social cognition. Specifically, 14-month-olds' habituation to human intentional action significantly predicts later preschool mentalistic construal of persons, as measured on a Theory of Mind Scale.

Self-awareness, self-evaluation, and creativity.

The present research examined when self-evaluation influences creativity. Based on objective self-awareness theory, the authors predicted that feeling able to improve would buffer against the detrimental effects of self-evaluation on creativity. Two experiments manipulated self-evaluation (varying self-awareness, Study 1; providing objective performance standards, Study 2) and perceived ability to improve potential failure on the creativity task. Self-evaluation reduced creativity (generating remote associates, finding unusual uses for a knife) in both experiments, but only when people did not expect to improve. When people felt able to improve, self-evaluation did not affect creativity. Connections between self-motives, creativity, and defensiveness are discussed.

Increased repetitive behaviours and prolactin responsivity to oral m-chlorophenylpiperazine in adults with autism spectrum disorders.

Autism is a neurodevelopmental disorder characterized by dysfunction in three primary behavioural domains: repetitive behaviours, social deficits, and language abnormalities. There is evidence that abnormalities exist in the serotonin (5-HT) system in autism spectrum patients. Furthermore, 5-HT is known to play a role in repetitive and social behaviours. This study examined the effect of m-chlorophenylpiperazine (m-CPP) on repetitive behaviours and prolactin response in 11 adults with autism or Aspergers disorder and 8 age- and gender-matched healthy controls via randomized double-blind, m-CPP and placebo challenges. The primary outcome measure was an instrument rating six repetitive behaviours: need to know, repeating, ordering, need to tell/ask, self-injury, and touching. Patients with autism spectrum disorders showed a significant increase in repetitive behaviours at end-point following oral m-CPP in comparison to placebo. Additionally subjects with autism spectrum disorders showed a significantly increased prolactin response to m-CPP compared to normal controls, with neither group responding to placebo. This study provides further evidence for altered 5-HT sensitivity in individuals with autism spectrum disorders, as well as a possible relationship between repetitive behaviours in autism spectrum disorders and abnormalities in the 5-HT system.

Impact of recent findings on study design of future autism clinical trials.

There are specific challenges to studying the design of pharmacologic trials in child/adolescent and adult autism, such as subject stratification and parallel versus crossover designs. This article describes how optimal study design is influenced by subject selection and outcome measures chosen. Lessons learned in study design from the Research Units on Pediatric Psychopharmacology Autism Network trial with risperidone, Seaver Center trials with fluoxetine and valproate, Dartmouth trials with amantadine, and National Institutes of Health secretin trials are highlighted. The Internet System for Assessing Autistic Children system for managing multicenter clinical trials in autism and statistical issues in autism research are also described.

Targeted treatments for symptom domains in child and adolescent autism.

CONTEXT: The number of people with autism spectrum disorders has dramatically increased over the past decade, and problem behaviours in autism are an increasing challenge to families, schools, physicians, and other health-care professionals. Pharmacological treatments can effectively target problem behaviours associated with autism. STARTING POINT: Recently, L Namerow and colleagues (J Dev Behav Pediatr 2003; 24: 104-08) presented preliminary data in children and adolescents with autism treated with citalopram, which suggested that selective serotonin-reuptake inhibitors are useful in the reduction of symptom domains such as repetitive behaviours and mood disorders. J McCracken and colleagues (N Engl J Med 2000; 347: 314-21) showed that the atypical antipsychotic risperidone reduced serious behavioural problems, such as tantrums, aggression, or self-injury in children with autism and in children with below-average intelligence quotients. These and other studies show how developments in study design, selection of patients, and outcome measures have allowed treatment trials in autism to progress beyond anecdotal reports and case observations, and show reduction in the severity of specific symptom domains within these disorders. WHERE NEXT? In therapeutic intervention the risk of treatment toxicity must be balanced against the benefits of improved symptom severity. The newer methods enable informed decisions about which patients will benefit from which treatments. Other symptom domains within autism and effects on development need to be evaluated in adequately designed clinical trials. Future strategies include extending treatment to children as young as the preschool years.

Children's reasoning about physics within and across ontological kinds.

Reasoning about seven physics principles within and across ontological kinds was examined among 188 5- and 7-year-olds and 59 adults. Individuals in all age groups tended to appropriately generalize what they learned across ontological kinds. However, children also showed sensitivity to ontological kind in their projections: when learning principles with reference to people they were more likely to assume that the principles apply to another person than to an inanimate object, and when learning with reference to an inanimate object they were more likely to assume that the principles apply to another inanimate object than to a person. Five-year-olds, but not 7-year-olds, projected concepts learned about people to a greater extent than principles learned about inanimate objects, closely paralleling the findings of Carey for the biological domain (Carey, S. (1985). Conceptual change in childhood. Cambridge, MA: MIT Press). Results from a separate sample of 22 5-year-olds suggest that the primary findings cannot be explained by response perseveration. The present findings indicate that children understand physics principles that apply to both animate and inanimate objects, but distinguish between these ontological kinds.

More questions: 10 years later from glycogen storage disease patient support groups in Europe.

UNLABELLED: In 1990 the first Fulda Workshop on Glycogen Storage Disease (GSD) type I was held in November. Eight adult representatives from Patient groups in the UK, USA, Germany and the Netherlands were invited to come and set up an information table of posters, leaflets etc. We were also asked to present a short list of questions that can occur to parents after the initial shock of diagnosis and treatment of GSD has been made. These "Questions of Parents" were presented on the final day. Ten years later, patient representatives from Europe were invited to present "More Questions: 10 Years Later". On both occasions the questions centred around six broad areas: (1). treatments, (2). specific problems, (3). family planning, (4). long-term effects of having GSD type Ia and Ib, (5). research and (6). general questions. CONCLUSION: As representatives of GSD support groups, we hope that firm decisions can be agreed for common dietary and pharmacological treatment and follow-up procedures within the boundaries of cultural differences and financial circumstances. We anticipate that if there is a third Fulda workshop in 2010, the answer to the question "Is there a common set of protocols and guidelines among doctors and hospitals as to the correct treatment for glycogen storage disease type I?" will be a firm "Yes".

Infants' ability to connect gaze and emotional expression to intentional action.

Four studies investigated whether and when infants connect information about an actor's affect and perception to their action. Arguably, this may be a crucial way in which infants come to recognize the intentional behaviors of others. In Study 1 an actor grasped one of two objects in a situation where cues from the actor's gaze and expression could serve to determine which object would be grasped, specifically the actor first looked at and emoted positively about one object but not the other. Twelve-month-olds, but not 8-month-olds, recognized that the actor was likely to grasp the object which she had visually regarded with positive affect. Studies 2, 3, and 4 replicated the main finding from Study 1 with 12- and 14-month-olds and included several contrasting conditions and controls. These studies provide evidence that the ability to use information about an adult's direction of gaze and emotional expression to predict action is both present, and developing at the end of the first year of life.

Rotational Atherectomy in Octogenarians: Results and Follow Up.

We examined our first 390 rotational atherectomy procedures to determine success and complications rates of patients aged 80 or greater (Group I, N equals 35) as compared to those younger (Group II, N equals 355). Procedural success was achieved in 32/35 (91%) of Group I and 42/355 (96%) of Group II patients (p equals NS). Coronary artery bypass graft surgery was required in 2/35 (5.7%) of Group I and 7/355 (2%) of Group II patients. No deaths, Q wave infarctions, or perforations occurred in the elderly patients and only one of each was observed in the younger group. During clinical follow up (26 months, 3-50), 4/25 patients (16%) in the octogenarian group died. Two of the deaths were cardiac (including the only crossover to surgery). One patient who sustained a late non Q myocardial infarction was asymptomatic. Of the remaining 20 patients the anginal class was 0-II in 19 and III in one. Rotational atherectomy can achieve excellent short and long term outcomes in selected octogenarians. (c)2000 by CVRR, Inc.