Aminoglycoside antibiotics and autism: a speculative hypothesis

BACKGROUND: Recently, it has been suspected that there is a relationship between therapy with some antibiotics and the onset of autism; but even more curious, some children benefited transiently from a subsequent treatment with a different antibiotic. Here, we speculate how aminoglycoside antibiotics might be associated with autism. PRESENTATION: We hypothesize that aminoglycoside antibiotics could a) trigger the autism syndrome in susceptible infants by causing the stop codon readthrough, i.e., a misreading of the genetic code of a hypothetical critical gene, and/or b) improve autism symptoms by correcting the premature stop codon mutation in a hypothetical polymorphic gene linked to autism. TESTING: Investigate, retrospectively, whether a link exists between aminoglycoside use (which is not extensive in children) and the onset of autism symptoms (hypothesis "a"), or between amino glycoside use and improvement of these symptoms (hypothesis "b"). Whereas a prospective study to test hypothesis "a" is not ethically justifiable, a study could be designed to test hypothesis "b". IMPLICATIONS: It should be stressed that at this stage no direct evidence supports our speculative hypothesis and that its main purpose is to initiate development of new ideas that, eventually, would improve our understanding of the pathobiology of autism

Recognition of Face Identity and Emotion in Expressive Specific Language Impairment

Objective: To study face and emotion recognition in children with mostly expressive specific language impairment (SLI-E). Subjects and Methods: A test movie to study perception and recognition of faces and mimic-gestural expression was applied to 24 children diagnosed as suffering from SLI-E and an age-matched control group of normally developing children. Results: Compared to a normal control group, the SLI-E children scored significantly worse in both the face and expression recognition tasks with a preponderant effect on emotion recognition. The performance of the SLI-E group could not be explained by reduced attention during the test session. Conclusion: We conclude that SLI-E is associated with a deficiency in decoding non-verbal emotional facial and gestural information, which might lead to profound and persistent problems in social interaction and development. Copyright (C) 2012 S. Karger AG, Base

Chapter 10: Deciding Whether to Complement a Systematic Review of Medical Tests with Decision Modeling

Limited by what is reported in the literature, most systematic reviews of medical tests focus on “test accuracy” (or better, test performance), rather than on the impact of testing on patient outcomes. The link between testing, test results and patient outcomes is typically complex: even when testing has high accuracy, there is no guarantee that physicians will act according to test results, that patients will follow their orders, or that the intervention will yield a beneficial endpoint. Therefore, test performance is typically not sufficient for assessing the usefulness of medical tests. Modeling (in the form of decision or economic analysis) is a natural framework for linking test performance data to clinical outcomes. We propose that (some) modeling should be considered to facilitate the interpretation of summary test performance measures by connecting testing and patient outcomes. We discuss a simple algorithm for helping systematic reviewers think through this possibility, and illustrate it by means of an example

The Use of Antisense Oligonucleotides in Evaluating Survivin as a Therapeutic Target for Radiation Sensitization in Lung Cancer

Elucidating the mechanism of over and under expression of proteins is critical in developing a better understanding of cancer. Multiple techniques are used to examine differential expression of proteins in cells and assess changes in protein expression in response to therapies such as radiation. Reduced expression can be caused by protein inactivation, mRNA instability, or reduced transcription. The following protocol was used to determine the mechanism for the reduced expression of an antiapoptotic factor, survivin, in normal tissues in response to radiation and the defect in cancer cells that prevents this reduction. We also examined ways to overcome survivin over expression in cancer cells in order to sensitize them to radiation. We will focus on the use of antisense oligonucleotides, cell cycle analysis, and luciferase reporter genes

Development of a brief multidisciplinary education programme for patients with osteoarthritis

Background Osteoarthritis (OA) is a prevalent progressive musculoskeletal disorder, leading to pain and disability. Patient information and education are considered core elements in treatment guidelines for OA; however, there is to our knowledge no evidence-based recommendation on the best approach, content or length on educational programmes in OA. Objective: to develop a brief, patient oriented disease specific multidisciplinary education programme (MEP) to enhance self-management in patients with OA. Method Twelve persons (80% female mean age 59 years) diagnosed with hand, hip or knee OA participated in focus group interviews. In the first focus group, six participants were interviewed about their educational needs, attitudes and expectations for the MEP. The interviews were transcribed verbatim and thereafter condensed. Based on results from focus group interviews, current research evidence, clinical knowledge and patients' experience, a multidisciplinary OA team (dietist, nurse, occupational therapist, pharmacist, physical therapist and rheumatologist) and a patient representative developed a pilot-MEP after having attended a work-shop in health pedagogics. Finally, the pilot-MEP was evaluated by a second focus group consisting of four members from the first focus group and six other experienced patients, before final adjustments were made. Results The focus group interviews revealed four important themes: what is OA, treatment options, barriers and coping strategies in performing daily activities, and how to live with osteoarthritis. Identified gaps between patient expectations and experience with the pilot-programme were discussed and adapted into a final MEP. The final MEP was developed as a 3.5 hour educational programme provided in groups of 6-9 patients. All members from the multidisciplinary team are involved in the education programme, including a facilitator who during the provision of the programme ensures that the individual questions are addressed. As part of an ongoing process, a patient representative regularly attends the MEP and gives feedback concerning content and perceived value. Conclusion A MEP has been developed to enhance self-management in patients with OA attending a multidisciplinary OA outpatient clinic. The effectiveness of the MEP followed by individual consultations with members of the multidisciplinary team is currently evaluated in a randomised controlled trial with respect to patient satisfaction and functioning

Don't lose sight of the importance of the individual in effective falls prevention interventions

Falls remain a major public health problem, despite strong growth in the research evidence of effective single and multifactorial interventions, particularly in the community setting. A number of aspects of falls prevention require individual tailoring, despite limitations being reported regarding some of these, including questions being raised regarding the role of falls risk screening and falls risk assessment. Being able to personalise an individual's specific risk and risk factors, increase their understanding of what interventions are likely to be effective, and exploring options of choice and preference, can all impact upon whether or not an individual undertakes and sustains participation in one or more recommendations, which will ultimately influence outcomes. On all of these fronts, the individual patient receiving appropriate and targeted interventions that are meaningful, feasible and that they are motivated to implement, remains central to effective translation of falls prevention research evidence into practice

Predictors of adherence to a multifaceted podiatry intervention for the prevention of falls in older people

<p>Abstract</p> <p>Background</p> <p>Despite emerging evidence that foot problems and inappropriate footwear increase the risk of falls, there is little evidence as to whether foot-related intervention strategies can be successfully implemented. The aim of this study was to evaluate adherence rates, barriers to adherence, and the predictors of adherence to a multifaceted podiatry intervention for the prevention of falls in older people.</p> <p>Methods</p> <p>The intervention group (n = 153, mean age 74.2 years) of a randomised trial that investigated the effectiveness of a multifaceted podiatry intervention to prevent falls was assessed for adherence to the three components of the intervention: (i) foot orthoses, (ii) footwear advice and footwear cost subsidy, and (iii) a home-based foot and ankle exercise program. Adherence to each component and the barriers to adherence were documented, and separate discriminant function analyses were undertaken to identify factors that were significantly and independently associated with adherence to the three intervention components.</p> <p>Results</p> <p>Adherence to the three components of the intervention was as follows: foot orthoses (69%), footwear (54%) and home-based exercise (72%). Discriminant function analyses identified that being younger was the best predictor of orthoses use, higher physical health status and lower fear of falling were independent predictors of footwear adherence, and higher physical health status was the best predictor of exercise adherence. The predictive accuracy of these models was only modest, with 62 to 71% of participants correctly classified.</p> <p>Conclusions</p> <p>Adherence to a multifaceted podiatry intervention in this trial ranged from 54 to 72%. People with better physical health, less fear of falling and a younger age exhibited greater adherence, suggesting that strategies need to be developed to enhance adherence in frailer older people who are most at risk of falling.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry <a href="http://www.anzctr.org.au/ACTRN12608000065392.aspx">ACTRN12608000065392</a>.</p

Treatment of chronic back pain by sensory discrimination training. A Phase I RCT of a novel device (FairMed) vs. TENS

Background: The causes of chronic low back pain (CLBP) remain obscure and effective treatment of symptoms remains elusive. A mechanism of relieving chronic pain based on the consequences of conflicting unpleasant sensory inputs to the central nervous system has been hypothesised. As a result a device was generated to deliver sensory discrimination training (FairMed), and this randomised controlled trial compared therapeutic effects with a comparable treatment modality, TENS. Methods: 60 patients with CLBP were recruited from physiotherapy referrals to a single-blinded, randomised controlled, non-inferiority trial. They were randomised to receive either FairMed or TENS and asked to use the allocated device for 30 minutes, twice a day, for 3 weeks. The primary outcome variable measured at 0 and 3 weeks was pain intensity measured using a visual analogue scale averaged over 7 days. Secondary outcome measures were Oswestry Disability Index, 3 timed physical tests, 4 questionnaires assessing different aspects of emotional coping and a global measure of patient rating of change. Data were analysed for the difference in change of scores between groups using one-way ANOVA. Results: Baseline characteristics of the two groups were comparable. The primary outcome, change in pain intensity (VAS) at 3 weeks showed a mean difference between groups of -0.1, (non significant p = 0.82). The mean difference in change in ODI scores was 0.4; (non significant p = 0.85). Differences in change of physical functioning showed that no significant difference in change of scores for any of these test (p = 0.58 – 0.90). Changes in scores of aspects of emotional coping also demonstrated no significant difference in change scores between the groups (p = 0.14 – 0.94). Conclusion: FairMed was not inferior to TENS treatment. The findings have implications for further research on current chronic pain theories and treatments. Further work to explore these mechanisms is important to expand our understanding of chronic pain and the role of neuro-modulation

Mechanism of nitrogen metabolism-related parameters and enzyme activities in the pathophysiology of autism

<p>Abstract</p> <p>Background</p> <p>There is evidence that impaired metabolism play an important role in the etiology of many neuropsychiatric disorders. Although this has not been investigated to date, several recent studies proposed that nitrogen metabolism-related parameters may have a pathophysiological role in autism.</p> <p>Methods</p> <p>The study enrolled 20 Saudi boys with autism aged 4 to 12 years and 20 healthy controls matched for age and gender. Levels of creatine, urea, ammonia, gamma-aminobutyric acid (GABA), glutamate:glutamine (Glu:Gln) ratio, and enzymatic activities of glutamate dehydrogenase, 5'-nucleotidase, and adenosine deaminase (ADA) were determined in plasma samples from both groups.</p> <p>Results</p> <p>We found a significant elevation of creatine, 5'-nucleotidase, GABA, and glutamic acid and a significant decrease in the enzymatic activity of ADA and glutamine level in patients with autism compared with healthy controls. The most significant variation between the two groups was found in the Glu:Gln ratio.</p> <p>Conclusion</p> <p>A raised Glu:Gln ratio together with positive correlations in creatine, GABA, and 5'-nucleotidase levels could contribute to the pathophysiology of autism, and might be useful diagnostic markers. The mechanism through which these parameters might be related to autism is discussed in detail.</p

Inhibition, flexibility, working memory and planning in autism spectrum disorders with and without comorbid ADHD-symptoms

<p>Abstract</p> <p>Background</p> <p>Recent studies have not paid a great deal of attention to comorbid attention-deficit/hyperactivity disorder (ADHD) symptoms in autistic children even though it is well known that almost half of children with autism spectrum disorder (ASD) suffer from hyperactivity, inattention and impulsivity. The goal of this study was to evaluate and compare executive functioning (EF) profiles in children with ADHD and in children with ASD with and without comorbid ADHD.</p> <p>Methods</p> <p>Children aged 6 to 18 years old with ADHD (n = 20) or ASD (High-Functioning autism or Asperger syndrome) with (n = 20) and without (n = 20) comorbid ADHD and a typically developing group (n = 20) were compared on a battery of EF tasks comprising inhibition, flexibility, working memory and planning tasks. A MANOVA, effect sizes as well as correlations between ADHD-symptomatology and EF performance were calculated. Age- and IQ-corrected z scores were used.</p> <p>Results</p> <p>There was a significant effect for the factor group (F = 1.55; dF = 42; p = .02). Post-hoc analysis revealed significant differences between the ADHD and the TD group on the inhibition task for false alarms (p = .01) and between the ADHD group, the ASD+ group (p = .03), the ASD- group (p = .02) and the TD group (p = .01) for omissions. Effect sizes showed clear deficits of ADHD children in inhibition and working memory tasks. Participants with ASD were impaired in planning and flexibility abilities. The ASD+ group showed compared to the ASD- group more problems in inhibitory performance but not in the working memory task.</p> <p>Conclusion</p> <p>Our findings replicate previous results reporting impairment of ADHD children in inhibition and working memory tasks and of ASD children in planning and flexibility abilities. The ASD + group showed similarities to the ADHD group with regard to inhibitory but not to working memory deficits. Nevertheless the heterogeneity of these and previous results shows that EF assessment is not useful for differential diagnosis between ADHD and ASD. It might be useful for evaluating strengths and weaknesses in individual children.</p