Lacosamide-Induced Valproic Acid Toxicity

Valproic acid is commonly used in the treatment of both focal and generalized epilepsies and is often well tolerated. There are many reported cases of hyperammonemic encephalopathy and other well-known side effects reported during use of valproic acid either alone or in combination with other antiepileptics. This case report demonstrates valproic acid toxicity in the presence of lacosamide, which has not previously been reported. Full recovery occurred after withdrawal of both valproic acid and lacosamide.     

Recombinant AAV Serotype and Capsid Mutant Comparison for Pulmonary Gene Transfer of ��-1-Antitrypsin Using Invasive and Noninvasive Delivery

Recombinant adeno-associated viral (rAAV) vectors have been widely used in pulmonary gene therapy research. In this study, we evaluated the transduction and expression efficiencies of several AAV serotypes and AAV2 capsid mutants with specific pulmonary targeting ligands in the mouse lung. The noninvasive intranasal delivery was compared with the traditional intratracheal lung delivery. The rAAV8 was the most efficient serotype at expressing α-1-antitrypsin (AAT) in the lung among all the tested serotypes and mutants. A dose of 1 × 10¹⁰ vg of rAAV8-CB-AAT transduced a high percentage of cells in the lung when delivered intratrachealy. The serum and the broncho-alveolar lavage fluid (BALF) levels of human AAT (hAAT) were about 6- and 2.5-fold higher, respectively, than those of rAAV5 group. Among the rAAV2 capsid mutants, the rAAV2 capsid mutants that display a peptide sequence from hAAT (“long serpin”) indicated a twofold increase in transgene expression. For most vectors, the serum hAAT levels achieved after intranasal delivery were 1/2 to 1/3 of those with the intratracheal method. Overall, rAAV8 was the most promising vector for the future application in gene therapy of pulmonary diseases such as AAT deficiency–related emphysema.     

Predicting subject-driven actions and sensory experience in a virtual world with relevance vector machine regression of fMRI data

In this work we illustrate the approach of the Maastricht Brain Imaging Center to the PBAIC 2007 competition, where participants had to predict, based on fMRI measurements of brain activity, subject driven actions and sensory experience in a virtual world. After standard pre-processing (slice scan time correction, motion correction), we generated rating predictions based on linear Relevance Vector Machine (RVM) learning from all brain voxels. Spatial and temporal filtering of the time series was optimized rating by rating. For some of the ratings (e.g. Instructions, Hits, Faces, Velocity), linear RVM regression was accurate and very consistent within and between subjects. For other ratings (e.g. Arousal, Valence) results were less satisfactory. Our approach ranked overall second. To investigate the role of different brain regions in ratings prediction we generated predictive maps, i.e. maps of the weighted contribution of each voxel to the predicted rating. These maps generally included (but were not limited to) "specialized" regions which are consistent with results from conventional neuroimaging studies and known functional neuroanatomy. In conclusion, Sparse Bayesian Learning models, such as RVM, appear to be a valuable approach to the multivariate regression of fMRI time series. The implementation of the Automatic Relevance Determination criterion is particularly suitable and provides a good generalization, despite the limited number of samples which is typically available in fMRI. Predictive maps allow disclosing multi-voxel patterns of brain activity that predict perceptual and behavioral subjective experience.     

Memory systems involved in professional skills: A case of dense amnesia due to herpes simplex viral encephalitis

JL, a 25-year-old physiotherapist, became densely amnesic following herpes simplex viral encephalitis (HSVE), causing bilateral damage to medial and ventral areas of her frontal and temporal lobes and their associated circuitry. Three years post-onset, her WAIS-R full scale IQ (Verbal 74, Performance 102) showed an estimated loss of ± 50 points. She displayed severe global amnesia and markedly impaired social cognition. However, her immediate memory, perceptual priming, and cognitive problem-solving abilities were relatively spared. Her retention of professional skills was assessed using simulated physiotherapy scenarios. JL was able to demonstrate some procedural skills spontaneously, but was unable to apply them precisely and flexibly to individual patient needs. She showed no memory of theoretical or propositional physiotherapy knowledge, and could neither plan treatment nor reason clinically. Her performance was well below that of four other physiotherapists who had also not practised for 4 years. Thus, despite the relative sparing of her implicit memory, JL's performance lacked the co-ordinated operation of declarative and implicit long-term memory and the links to working memory that are necessary for the flexible performance of complex professional procedures.     

Assessing awareness in early-stage Alzheimer's disease: Development and piloting of the Memory Awareness Rating Scale

There are indications that awareness may have an important impact on functioning and response to rehabilitative interventions in early-stage Alzheimer's disease (AD), yet studies have so far produced few clear findings, and a comprehensive explanatory model is needed together with a reliable assessment method. A theory-driven approach to assessing awareness in early-stage Alzheimer's disease was used to develop the Memory Awareness Rating Scale (MARS), a measure that addresses key methodological limitations of the assessment methods adopted in existing studies. The MARS was piloted with 12 couples where one partner had a diagnosis of AD. This demonstrated that the MARS has satisfactory psychometric properties, and suggested some refinements to the scale that may improve its usefulness. Results obtained with the MARS allow further consideration of theoretical and methodological issues that arise in attempting to understand and assess awareness. The development of this rigorous method of assessing awareness of memory difficulties in early-stage AD provides a basis for further investigation of the relationship between awareness of memory difficulties and outcome of neuropsychological rehabilitation in early-stage AD.     

Prognostic value of thyrotropin receptor antibodies (TRAb) in Graves' disease: a 120 months prospective study

In most trials, at least 30-60% of patients with Graves' disease treated with antithyroid drugs relapse within 2 years after therapy withdrawal. At present, there are no prognostic parameters available early in treatment to indicate patients likely to achieve long-term remission. Because thyrotropin receptor autoantibodies (TRAb) are specific for Graves' disease, we evaluated the ability of their levels and of their rate of change to predict long-term prognosis. In our study 216 consecutive patients with newly diagnosed Graves' disease started a therapy with methimazole. Patients were treated until they achieved euthyroidism and TRAb were measured at 6-month intervals throughout a follow up of 120 months. Our study demonstrated that at the onset of hyperthyroidism patients' age, sex, fT4 levels and goiter size had no prognostic value in predicting long-term prognosis (respectively p = 0.79; p = 0.98; p = 0.83; p = 0.89). On the contrary, at the time of diagnosis TRAb titer was a good predictor of the final outcome (p<0.001); a titer equal to (or) more than 46.5 UI/L could identify patients who had never achieved long-term remission with a sensitivity of 52% and a specificity of 78%. Also fall rate of TRAb at 6 months of follow up and after therapy withdrawal were useful to predict the final outcome (p<0.001). At 6 months of follow up the time of therapy withdrawal, a decrease of TRAb lower than 52.3% or even its increase could identify patients who had never achieved permanent remission with a sensitivity of 55% and a specificity of 79.1%. No single parameter among TRAb, satisfactory identified a sub-set of patients who achieved long remission. Accordingly to our data, the best result in predicting long term remission is probably given by the presence of at least one of the two features evaluated at 6 months (TRAb titer and/or percentage of TRAb fall rate), with a sensitivity of 63% and specificity of 88%. TRAb titers evaluated both at the onset of hyperthyroidism that at 6 months of therapy or their rate of fall at 6 months and at ATD withdrawal are predictors of outcome. However, the presence of at least one, between titers of TRAb or their rate of fall at six months, resulted to be the best predictor of remission with the higher sensitivity and specificity.     

A case of head and neck cutaneous squamous cell carcinoma highlighting aggressive perineural features

Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer in the United States following basal cell carcinoma. The majority are successfully cured by surgical excision or Mohs microsurgery. A subset of cSCCs are more aggressive and likely to recur locally, spread to regional lymph nodes or even distantly, and can even result in death. High-risk features of cSCC including perineural invasion of nerve >0.1 mm in diameter and invasion beyond the subcutaneous fat are not routinely reported by Mohs microsurgery. Facial cSCC commonly involves branches of the facial nerve (VII) or trigeminal nerve (V). Clinical symptoms associated with cranial nerve VII and V involvement include pain, paresthesia of the face and tongue, facial paralysis. Assessment of nerve involvement by magnetic resonance imaging (MRI) is the most optimal imaging modality. Here, we present a case where Mohs microsurgery was performed on a facial cSCC 1.5 years prior to the development of facial paresis. We aim to highlight the interesting perineural path resulting in facial paralysis and associated symptomatology, the importance of MRI, and to remind clinicians of important high-risk features of cSCC.     

Association between Conflict and Cholera in Nigeria and the Democratic Republic of the Congo

Cholera outbreaks contribute substantially to illness and death in low- and middle-income countries. Cholera outbreaks are associated with several social and environmental risk factors, and extreme conditions can act as catalysts. A social extreme known to be associated with infectious disease outbreaks is conflict, causing disruption to services, loss of income, and displacement. To determine the extent of this association, we used the self-controlled case-series method and found that conflict increased the risk for cholera in Nigeria by 3.6 times and in the Democratic Republic of the Congo by 2.6 times. We also found that 19.7% of cholera outbreaks in Nigeria and 12.3% of outbreaks in the Democratic Republic of the Congo were attributable to conflict. Our results highlight the value of providing rapid and sufficient assistance during conflict-associated cholera outbreaks and working toward conflict resolution and addressing preexisting vulnerabilities, such as poverty and access to healthcare.     

Processed Food as a Risk Factor for the Development and Perpetuation of Crohn’s Disease—The ENIGMA Study

(1) Background: Developing countries have experienced a rapid recent rise in Inflammatory Bowel Disease (IBD) incidence and emerging evidence suggests processed foods and food additives may predispose one to the development and perpetuation of Crohn’s disease (CD). The aim of this study was to evaluate processed food and food additive intake in CD patients and controls, in Australia (high CD incidence), Hong Kong (intermediate incidence) and mainland China (emerging incidence). (2) Methods: In 274 CD patients (CD), 82 first-degree relatives (FDR), 83 household members (HM) and 92 healthy unrelated controls (HC) from Australia (n = 180), Hong Kong (HK) (n = 160) and mainland China (n = 191) we estimated early life (0–18 years), recent (12 months), and current processed and food additive intake, using validated questionnaires and a 3-day-food diary. (3) Results: Early life processed food intake: Combining all regions, CD were more likely to have consumed soft drinks and fast foods than HM, more likely to have consumed processed fruit and snacks than their FDR, and more likely to have consumed a range of processed foods than HC. HK and China CD patients were more likely to have consumed a range of processed foods than HC. Recent food-additive intake (12-months): Combining all regions, CD patients had significantly higher intakes of aspartame and sucralose, and polysorbate-80, than HC, and more total emulsifiers, artificial sweeteners, and titanium dioxide than FDR and HC. HK and China CD patients had a higher intake of almost all food additives than all controls. Current additive intake (3-days): Australian and HK CD patients had higher total food-additive intake than FDR, and HK CD patients had a higher intake of total food-additives and emulsifiers than HM. (4) Conclusions: CD patients have been exposed to more processed food and food additives than control groups, which may predispose them to CD development and ongoing inflammation.     

What Do People Know about Food,Nutrition and Health?—General Nutrition Knowledge in the Austrian Population

Background: Only limited information is available on the nutrition knowledge of the general Austrian population and how this relates to the nutrition knowledge of health professionals (medical doctors, pharmacists, nutritionist, dieticians) and school teachers. Methods: Adolescents and adults at the age of 14–75 years (n = 1000), medical doctors (n = 307), pharmacists (n = 295), nutritionists (n = 124), dieticians (n = 160) and school teachers (n = 873) completed an online survey using a German version of the General Nutrition Knowledge Questionnaire-Revised (GNKQ-R) including self-reported data on sex, age, BMI, and health status. Adolescent and adult participants were recruited by a research agency to be representative for the Austrian population for age, sex, and education. A convenience sample was used for health professionals (medical doctors, pharmacists, nutritionist, dieticians) and school teachers. All participants completed a computer-assisted web-based interviewing (CAWI) survey. Results: Total scores for nutrition knowledge of the general population (61.4%) were significantly lower than scores from all other groups (medical doctors 81.3%, pharmacists 83.0%, dieticians 87.5%, nutritionists 85.6%, school teachers 74.5%). The main drivers for better nutritional knowledge were female sex, higher age, and higher level of education, while BMI classification and self-reported health status had no impact. In regard to single questions, the most striking result was the misclassification of sugar as the nutrient with the most calories by 41.4% of the general population while only 29.0% correctly identified fat to be the nutrient with the most calories. Conclusions: The nutritional knowledge of the general population should be significantly improved in order to lay a basis for better dietary behavior. In view of the relatively low scores of teachers, their nutrition education should be improved in order to enable transfer of sound education in schools.