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Despite the fact that seizures are commonly associated with autism spectrum disorder (ASD), the effectiveness of treatments for seizures has not been well studied in individuals with ASD. This manuscript reviews both traditional and novel treatments for seizures associated with ASD. Studies were selected by systematically searching major electronic databases

Despite the fact that seizures are commonly associated with autism spectrum disorder (ASD), the effectiveness of treatments for seizures has not been well studied in individuals with ASD. This manuscript reviews both traditional and novel treatments for seizures associated with ASD. Studies were selected by systematically searching major electronic databases and by a panel of experts that treat ASD individuals. Only a few anti-epileptic drugs (AEDs) have undergone carefully controlled trials in ASD, but these trials examined outcomes other than seizures. Several lines of evidence point to valproate, lamotrigine, and levetiracetam as the most effective and tolerable AEDs for individuals with ASD. Limited evidence supports the use of traditional non-AED treatments, such as the ketogenic and modified Atkins diet, multiple subpial transections, immunomodulation, and neurofeedback treatments. Although specific treatments may be more appropriate for specific genetic and metabolic syndromes associated with ASD and seizures, there are few studies which have documented the effectiveness of treatments for seizures for specific syndromes. Limited evidence supports l-carnitine, multivitamins, and N-acetyl-l-cysteine in mitochondrial disease and dysfunction, folinic acid in cerebral folate abnormalities and early treatment with vigabatrin in tuberous sclerosis complex. Finally, there is limited evidence for a number of novel treatments, particularly magnesium with pyridoxine, omega-3 fatty acids, the gluten-free casein-free diet, and low-frequency repetitive transcranial magnetic simulation. Zinc and l-carnosine are potential novel treatments supported by basic research but not clinical studies. This review demonstrates the wide variety of treatments used to treat seizures in individuals with ASD as well as the striking lack of clinical trials performed to support the use of these treatments. Additional studies concerning these treatments for controlling seizures in individuals with ASD are warranted.

ContributorsFrye, Richard E. (Author) / Rossignol, Daniel (Author) / Casanova, Manuel F. (Author) / Brown, Gregory L. (Author) / Martin, Victoria (Author) / Edelson, Stephen (Author) / Coben, Robert (Author) / Lewine, Jeffrey (Author) / Slattery, John C. (Author) / Lau, Chrystal (Author) / Hardy, Paul (Author) / Fatemi, S. Hossein (Author) / Folsom, Timothy D. (Author) / MacFabe, Derrick (Author) / Adams, James (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2013-09-13
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This manuscript reviews biological abnormalities shared by autism spectrum disorder (ASD) and epilepsy. Two neuropathological findings are shared by ASD and epilepsy: abnormalities in minicolumn architecture and γ-aminobutyric acid (GABA) neurotransmission. The peripheral neuropil, which is the region that contains the inhibition circuits of the minicolumns, has been found to

This manuscript reviews biological abnormalities shared by autism spectrum disorder (ASD) and epilepsy. Two neuropathological findings are shared by ASD and epilepsy: abnormalities in minicolumn architecture and γ-aminobutyric acid (GABA) neurotransmission. The peripheral neuropil, which is the region that contains the inhibition circuits of the minicolumns, has been found to be decreased in the post-mortem ASD brain. ASD and epilepsy are associated with inhibitory GABA neurotransmission abnormalities including reduced GABAA and GABAB subunit expression. These abnormalities can elevate the excitation-to-inhibition balance, resulting in hyperexcitablity of the cortex and, in turn, increase the risk of seizures. Medical abnormalities associated with both epilepsy and ASD are discussed. These include specific genetic syndromes, specific metabolic disorders including disorders of energy metabolism and GABA and glutamate neurotransmission, mineral and vitamin deficiencies, heavy metal exposures and immune dysfunction. Many of these medical abnormalities can result in an elevation of the excitatory-to-inhibitory balance. Fragile X is linked to dysfunction of the mGluR5 receptor and Fragile X, Angelman and Rett syndromes are linked to a reduction in GABA[subscript A] receptor expression. Defects in energy metabolism can reduce GABA interneuron function. Both pyridoxine dependent seizures and succinic semialdehyde dehydrogenase deficiency cause GABA deficiencies while urea cycle defects and phenylketonuria cause abnormalities in glutamate neurotransmission. Mineral deficiencies can cause glutamate and GABA neurotransmission abnormalities and heavy metals can cause mitochondrial dysfunction which disrupts GABA metabolism. Thus, both ASD and epilepsy are associated with similar abnormalities that may alter the excitatory-to-inhibitory balance of the cortex. These parallels may explain the high prevalence of epilepsy in ASD and the elevated prevalence of ASD features in individuals with epilepsy.

ContributorsFrye, Richard E. (Author) / Casanova, Manuel F. (Author) / Fatemi, S. Hossein (Author) / Folsom, Timothy D. (Author) / Reutiman, Teri J. (Author) / Brown, Gregory L. (Author) / Edelson, Stephen M. (Author) / Slattery, John C. (Author) / Adams, James (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2016-05-10
Description

Human societies are unique in the level of cooperation among non-kin. Evolutionary models explaining this behavior typically assume pure strategies of cooperation and defection. Behavioral experiments, however, demonstrate that humans are typically conditional co-operators who have other-regarding preferences. Building on existing models on the evolution of cooperation and costly punishment,

Human societies are unique in the level of cooperation among non-kin. Evolutionary models explaining this behavior typically assume pure strategies of cooperation and defection. Behavioral experiments, however, demonstrate that humans are typically conditional co-operators who have other-regarding preferences. Building on existing models on the evolution of cooperation and costly punishment, we use a utilitarian formulation of agent decision making to explore conditions that support the emergence of cooperative behavior. Our results indicate that cooperation levels are significantly lower for larger groups in contrast to the original pure strategy model. Here, defection behavior not only diminishes the public good, but also affects the expectations of group members leading conditional co-operators to change their strategies. Hence defection has a more damaging effect when decisions are based on expectations and not only pure strategies.

Created2014-07-01
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A major conundrum in evolution is that, despite natural selection, polymorphism is still omnipresent in nature: Numerous species exhibit multiple morphs, namely several abundant values of an important trait. Polymorphism is particularly prevalent in asymmetric traits, which are beneficial to their carrier in disruptive competitive interference but at the same

A major conundrum in evolution is that, despite natural selection, polymorphism is still omnipresent in nature: Numerous species exhibit multiple morphs, namely several abundant values of an important trait. Polymorphism is particularly prevalent in asymmetric traits, which are beneficial to their carrier in disruptive competitive interference but at the same time bear disadvantages in other aspects, such as greater mortality or lower fecundity. Here we focus on asymmetric traits in which a better competitor disperses fewer offspring in the absence of competition. We report a general pattern in which polymorphic populations emerge when disruptive selection increases: The stronger the selection, the greater the number of morphs that evolve. This pattern is general and is insensitive to the form of the fitness function. The pattern is somewhat counterintuitive since directional selection is excepted to sharpen the trait distribution and thereby reduce its diversity (but note that similar patterns were suggested in studies that demonstrated increased biodiversity as local selection increases in ecological communities). We explain the underlying mechanism in which stronger selection drives the population towards more competitive values of the trait, which in turn reduces the population density, thereby enabling lesser competitors to stably persist with reduced need to directly compete. Thus, we believe that the pattern is more general and may apply to asymmetric traits more broadly. This robust pattern suggests a comparative, unified explanation to a variety of polymorphic traits in nature.

Created2016-02-04
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Background: African American women are one of the least active demographic groups in the US, with only 36% meeting the national physical activity recommendations in comparison to 46% of White women. Physical activity begins to decline in African American women in adolescence and continues to decline into young adulthood. Yet, few

Background: African American women are one of the least active demographic groups in the US, with only 36% meeting the national physical activity recommendations in comparison to 46% of White women. Physical activity begins to decline in African American women in adolescence and continues to decline into young adulthood. Yet, few interventions have been developed to promote physical activity in African American women during this critical period of life. The purpose of this article was to evaluate the acceptability and feasibility of a culturally-relevant Internet-enhanced physical activity pilot intervention for overweight/obese African American college females and to examine psychosocial and behavioral characteristics associated with intervention adherence and completion.

Methods: A 6-month single group pre-posttest design was used. Participants (n = 27) accessed a culturally-relevant Social Cognitive Theory-based physical activity promotion website while engaging in a minimum of four moderate-intensity physical activity sessions each week. Acceptability and feasibility of the intervention was assessed by participant retention and a consumer satisfaction survey completed by participants.

Results: Fifty-six percent of participants (n = 15) completed the intervention. Study completers were more physically active at baseline (P = 0.05) and had greater social support for exercise from family members (P = 0.04). Sixty percent of study completers (n = 9) reported the website as “enjoyable” or “very enjoyable” to use and 60% (n = 9) reported increased motivation from participation in the physical activity program. Moreover, 87% (n = 13) reported they would recommend the website to a friend.

Conclusions: Results provide some preliminary support for the acceptability and feasibility of an Internet-enhanced physical activity program for overweight/obese African American women, while highlighting important limitations of the approach. Successful promotion of physical activity in college aged African American women as they emerge into adulthood may result in the development of life-long healthy physical activity patterns which may ultimately reduce physical activity-related health disparities in this high risk underserved population. Future studies with larger samples are needed to further explore the use of Internet-based programs to promote physical activity in this population.

Created2015-06-02
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Background: Increasing our understanding of the factors affecting the severity of the 2009 A/H1N1 influenza pandemic in different regions of the world could lead to improved clinical practice and mitigation strategies for future influenza pandemics. Even though a number of studies have shed light into the risk factors associated with severe

Background: Increasing our understanding of the factors affecting the severity of the 2009 A/H1N1 influenza pandemic in different regions of the world could lead to improved clinical practice and mitigation strategies for future influenza pandemics. Even though a number of studies have shed light into the risk factors associated with severe outcomes of 2009 A/H1N1 influenza infections in different populations (e.g., [1-5]), analyses of the determinants of mortality risk spanning multiple pandemic waves and geographic regions are scarce. Between-country differences in the mortality burden of the 2009 pandemic could be linked to differences in influenza case management, underlying population health, or intrinsic differences in disease transmission [6]. Additional studies elucidating the determinants of disease severity globally are warranted to guide prevention efforts in future influenza pandemics.

In Mexico, the 2009 A/H1N1 influenza pandemic was characterized by a three-wave pattern occurring in the spring, summer, and fall of 2009 with substantial geographical heterogeneity [7]. A recent study suggests that Mexico experienced high excess mortality burden during the 2009 A/H1N1 influenza pandemic relative to other countries [6]. However, an assessment of potential factors that contributed to the relatively high pandemic death toll in Mexico are lacking. Here, we fill this gap by analyzing a large series of laboratory-confirmed A/H1N1 influenza cases, hospitalizations, and deaths monitored by the Mexican Social Security medical system during April 1 through December 31, 2009 in Mexico. In particular, we quantify the association between disease severity, hospital admission delays, and neuraminidase inhibitor use by demographic characteristics, pandemic wave, and geographic regions of Mexico.

Methods: We analyzed a large series of laboratory-confirmed pandemic A/H1N1 influenza cases from a prospective surveillance system maintained by the Mexican Social Security system, April-December 2009. We considered a spectrum of disease severity encompassing outpatient visits, hospitalizations, and deaths, and recorded demographic and geographic information on individual patients. We assessed the impact of neuraminidase inhibitor treatment and hospital admission delay (≤ > 2 days after disease onset) on the risk of death by multivariate logistic regression.

Results: Approximately 50% of all A/H1N1-positive patients received antiviral medication during the Spring and Summer 2009 pandemic waves in Mexico while only 9% of A/H1N1 cases received antiviral medications during the fall wave (P < 0.0001). After adjustment for age, gender, and geography, antiviral treatment significantly reduced the risk of death (OR = 0.52 (95% CI: 0.30, 0.90)) while longer hospital admission delays increased the risk of death by 2.8-fold (95% CI: 2.25, 3.41).

Conclusions: Our findings underscore the potential impact of decreasing admission delays and increasing antiviral use to mitigate the mortality burden of future influenza pandemics.

Created2012-04-20
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Description

Tree-like structures are ubiquitous in nature. In particular, neuronal axons and dendrites have tree-like geometries that mediate electrical signaling within and between cells. Electrical activity in neuronal trees is typically modeled using coupled cable equations on multi-compartment representations, where each compartment represents a small segment of the neuronal membrane. The

Tree-like structures are ubiquitous in nature. In particular, neuronal axons and dendrites have tree-like geometries that mediate electrical signaling within and between cells. Electrical activity in neuronal trees is typically modeled using coupled cable equations on multi-compartment representations, where each compartment represents a small segment of the neuronal membrane. The geometry of each compartment is usually defined as a cylinder or, at best, a surface of revolution based on a linear approximation of the radial change in the neurite. The resulting geometry of the model neuron is coarse, with non-smooth or even discontinuous jumps at the boundaries between compartments. We propose a hyperbolic approximation to model the geometry of neurite compartments, a branched, multi-compartment extension, and a simple graphical approach to calculate steady-state solutions of an associated system of coupled cable equations. A simple case of transient solutions is also briefly discussed.

Created2014-07-09
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We formulate an in silico model of pathogen avoidance mechanism and investigate its impact on defensive behavioural measures (e.g., spontaneous social exclusions and distancing, crowd avoidance and voluntary vaccination adaptation). In particular, we use SIR(B)S (e.g., susceptible-infected-recovered with additional behavioural component) model to investigate the impact of homo-psychologicus aspects of

We formulate an in silico model of pathogen avoidance mechanism and investigate its impact on defensive behavioural measures (e.g., spontaneous social exclusions and distancing, crowd avoidance and voluntary vaccination adaptation). In particular, we use SIR(B)S (e.g., susceptible-infected-recovered with additional behavioural component) model to investigate the impact of homo-psychologicus aspects of epidemics. We focus on reactionary behavioural changes, which apply to both social distancing and voluntary vaccination participations. Our analyses reveal complex relationships between spontaneous and uncoordinated behavioural changes, the emergence of its contagion properties, and mitigation of infectious diseases. We find that the presence of effective behavioural changes can impede the persistence of disease. Furthermore, it was found that under perfect effective behavioural change, there are three regions in the response factor (e.g., imitation and/or reactionary) and behavioural scale factor (e.g., global/local) factors ρ–α behavioural space. Mainly, (1) disease is always endemic even in the presence of behavioural change, (2) behavioural-prevalence plasticity is observed and disease can sometimes be eradication, and (3) elimination of endemic disease under permanence of permanent behavioural change is achieved. These results suggest that preventive behavioural changes (e.g., non-pharmaceutical prophylactic measures, social distancing and exclusion, crowd avoidance) are influenced by individual differences in perception of risks and are a salient feature of epidemics. Additionally, these findings indicates that care needs to be taken when considering the effect of adaptive behavioural change in predicting the course of epidemics, and as well as the interpretation and development of the public health measures that account for spontaneous behavioural changes.

Created2015-10-14
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Objective: This cross sectional study aims to determine the effects of gender and parental perception of safety at school on children’s physical activity (PA) levels.

Materials and Methods: Parents of school aged Mexican children residing in Guadalajara, Mexico City, and Puerto Vallarta, completed surveys about their children’s PA measures. The physical

Objective: This cross sectional study aims to determine the effects of gender and parental perception of safety at school on children’s physical activity (PA) levels.

Materials and Methods: Parents of school aged Mexican children residing in Guadalajara, Mexico City, and Puerto Vallarta, completed surveys about their children’s PA measures. The physical activity indicators were evaluated using linear and logistical regression models.

Results: Analysis did not indicate that gender moderated the relationship between parental perception of safety and PA measures, but significant gender issues exist with girls participating less than boys in the three measures of PA in this study (p<0.001).

Conclusion: Results suggest the need for additional interventions promoting physical activity in girls in Mexico.

Created2016-01
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Description

Changes in distribution policies have increased median MELD at transplant with recipients requiring increasing intensive care perioperatively. We aimed to evaluate association of preoperative variables with postoperative respiratory failure (PRF)/increased intensive care unit length of stay (ICU LOS)/short-term survival in a high MELD cohort undergoing liver transplant (LT). Retrospective analysis

Changes in distribution policies have increased median MELD at transplant with recipients requiring increasing intensive care perioperatively. We aimed to evaluate association of preoperative variables with postoperative respiratory failure (PRF)/increased intensive care unit length of stay (ICU LOS)/short-term survival in a high MELD cohort undergoing liver transplant (LT). Retrospective analysis identified cases of PRF and increased ICU LOS with recipient, donor, and surgical variables examined. Variables were entered into regression with end points of PRF and ICU LOS > 3 days. 164 recipients were examined: 41 (25.0%) experienced PRF and 74 (45.1%) prolonged ICU LOS. Significant predictors of PRF with univariate analysis: BMI > 30, pretransplant MELD, preoperative respiratory failure, LVEF < 50%, FVC < 80%, intraoperative transfusion > 6 units, warm ischemic time > 4 minutes, and cold ischemic time > 240 minutes. On multivariate analysis, only pretransplant MELD predicted PRF (OR 1.14, 𝑝 = 0.01). Significant predictors of prolonged ICU LOS with univariate analysis are as follows: pretransplant MELD, FVC < 80%, FEV1 < 80%, deceased donor, and cold ischemic time > 240 minutes. On multivariate analysis, only pretransplant MELD predicted prolonged ICU LOS (OR 1.28, 𝑝 < 0.001). One-year survival among cohorts with PRF and increased ICU LOS was similar to subjects without. Pretransplant MELD is a robust predictor of PRF and ICU LOS. Higher MELDs at LT are expected to increase need for ICU utilization and modify expectations for recovery in the immediate postoperative period.

Created2016-10-24