Seasonal variations in vitamin D do not change the musculoskeletal health of physically active ambulatory men with cerebral palsy: a longitudinal cross-sectional comparison study

Increased levels of vitamin D in the summer months from natural seasonal variations in sun exposure have been linked to improvements in musculoskeletal health and function in UK populations; however, studies have shown that differences in lifestyles because of disability can inhibit the natural vitamin D increase in these populations. We hypothesized that men with cerebral palsy (CP) will experience smaller increases in 25-hydroxyvitamin D (25(OH)D) from winter to summer and men with CP will not experience any improvements in musculoskeletal health and function during the summer. A longitudinal observational study in 16 ambulant men with CP aged 21.0 ± 1.3 years and 16 healthy, physical activity matched, typically developed controls aged 25.4 ± 2.6 years, completed assessments of serum 25(OH)D and parathyroid hormone during winter and summer. Neuromuscular outcomes included vastus lateralis size, knee extensor strength, 10-m sprint, vertical jumps, and grip strength. Bone ultrasounds were performed to obtain radius and tibia T and Z scores. Men with CP and typically developed controls showed a 70.5% and 85.7% increase in serum 25(OH)D from winter to summer months, respectively. Neither group showed seasonal effect on neuromuscular outcomes muscle strength, size, vertical jump, or tibia and radius T and Z scores. A seasonal interaction effect was seen in the tibia T and Z scores (P < .05). In conclusion, there were similar seasonal increases in 25(OH)D observed in men with CP and typically developed controls, but serum 25(OH)D levels were still considered insufficient to improve bone or neuromuscular outcomes

Adverse Drug Reactions Related Hospital Admissions in Persons Aged 60 Years and over, The Netherlands, 1981–2007: Less Rapid Increase, Different Drugs

Background: Epidemiologic information on time trends of Adverse Drug Reactions (ADR) and ADR-related hospitalizations is scarce. Over time, pharmacotherapy has become increasingly complex. Because of raised awareness of ADR, a decrease in ADR might be expected. The aim of this study was to determine trends in ADR-related hospitalizations in the older Dutch population. Methodology and Principal Findings: Secular trend analysis of ADR-related hospital admissions in patients ≥60 years between 1981 and 2007, using the National Hospital Discharge Registry of the Netherlands. Numbers, age-specific and age-adjusted incidence rates (per 10,000 persons) of ADR-related hospital admissions were used as outcome measures in each year of the study. Between 1981 and 2007, ADR-related hospital admissions in persons ≥60 years increased by 143%. The overall standardized incidence rate increased from 23.3 to 38.3 per 10,000 older persons. The increase was larger in males than in females. Since 1997, the increase in incidence rates of ADR-related hospitalizations flattened (percentage annual change 0.65%), compared to the period 1981-1996 (percentage annual change 2.56%). Conclusion/Significance: ADR-related hospital admissions in older persons have shown a rapidly increasing trend in the Netherlands over the last three decades with a temporization since 1997. Although an encouraging flattening in the increasing trend of ADR-related admissions was found around 1997, the incidence is still rising, which warrants sustained attention to this problem

Melanoma cells break down LPA to establish local gradients that drive chemotactic dispersal.

The high mortality of melanoma is caused by rapid spread of cancer cells, which occurs unusually early in tumour evolution. Unlike most solid tumours, thickness rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive melanoma cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real tumours. In a chamber-based assay for melanoma dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive chemotaxis rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all tumour stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor LPAR1. LPA induces chemotaxis of remarkable accuracy, and is both necessary and sufficient for chemotaxis and invasion in 2-D and 3-D assays. Growth factors, often described as tumour attractants, cause negligible chemotaxis themselves, but potentiate chemotaxis to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of melanomas in vivo, confirming the physiological importance of our results. We conclude that LPA chemotaxis provides a strong drive for melanoma cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the tumour and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the tumour growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient

Association study of promoter polymorphisms at the dopamine transporter gene in Attention Deficit Hyperactivity Disorder

<p>Abstract</p> <p>Background</p> <p>Attention deficit hyperactivity disorder (ADHD) is a complex neurobehavioral disorder. The dopamine transporter gene (DAT1/<it>SLC6A3</it>) has been considered a good candidate for ADHD. Most association studies with ADHD have investigated the 40-base-pair variable number of tandem repeat (VNTR) polymorphism in the 3'-untranslated region of DAT1. Only few studies have reported association between promoter polymorphisms of the gene and ADHD.</p> <p>Methods</p> <p>To investigate the association between the polymorphisms -67A/T (rs2975226) and -839C/T (rs2652511) in promoter region of DAT1 in ADHD, two samples of ADHD patients from the UK (n = 197) and Taiwan (n = 212) were genotyped, and analysed using within-family transmission disequilibrium test (TDT).</p> <p>Results</p> <p>A significant association was found between the T allele of promoter polymorphism -67A/T and ADHD in the Taiwanese population (<it>P </it>= 0.001). There was also evidence of preferential transmission of the T allele of -67A/T polymorphism in combined samples from the UK and Taiwan (<it>P </it>= 0.003). No association was detected between the -839C/T polymorphism and ADHD in either of the two populations.</p> <p>Conclusion</p> <p>The finding suggests that genetic variation in the promoter region of DAT1 may be a risk factor in the development of ADHD.</p

The 5-HTTLPR polymorphism of the serotonin transporter gene and short term behavioral response to methylphenidate in children with ADHD

<p>Abstract</p> <p>Background</p> <p>Animal models of ADHD suggest that the paradoxical calming effect of methylphenidate on motor activity could be mediated through its action on serotonin transmission. In this study, we have investigated the relationship between the 5-HTTLPR polymorphism in the serotonin transporter gene (<it>SLC6A4</it>) and the response of ADHD relevant behaviors with methylphenidate treatment.</p> <p>Methods</p> <p>Patients between ages 6-12 (n = 157) were assessed with regard to their behavioral response to methylphenidate (0.5 mg/kg/day) using a 2-week prospective within-subject, placebo-controlled (crossover) trial. The children were then genotyped with regard to the triallelic 5-HTTLPR polymorphism in the <it>SLC6A4 </it>gene. Main outcome measure: Conners' Global Index for parents (CGI-Parents) and teachers (CGI-Teachers) at baseline and at the end of each week of treatment with placebo and methylphenidate. For both outcome measurements, we used a mixed model analysis of variance to determine gene, treatment and gene × treatment interaction effects.</p> <p>Results</p> <p>Mixed model analysis of variance revealed a gene × treatment interaction for CGI-Parents but not for CGI-Teachers. Children homozygous for the lower expressing alleles (<it>s+l_G= s'</it>) responded well to placebo and did not derive additional improvement with methylphenidate compared to children carrying a higher expressing allele (<it>l_A</it>). No genotype main effects on either CGI-Parents or CGI-teachers were observed.</p> <p>Conclusions</p> <p>A double blind placebo-controlled design was used to assess the behavioral effects of methylphenidate in relation to the triallelic 5-HTTLPR polymorphism of the <it>SLC6A4 </it>gene in children with ADHD. This polymorphism appears to modulate the behavioral response to methylphenidate in children with ADHD as assessed in the home environment by parents. Further investigation is needed to assess the clinical implications of this finding.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00483106</p

No evidence for the association of DRD4 with ADHD in a Taiwanese population within-family study

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent and highly heritable childhood disorder. The dopamine D4 receptor (DRD4) gene has shown a genetic association with ADHD in Caucasian populations with meta-analysis indicating a small but significant effect across datasets. It remains uncertain whether this association can be generalised to non-Caucasian ethnic groups. Here we investigate two markers within the DRD4 gene in a Taiwanese population, the exon 3 variable number tandem repeat (VNTR) and a 5' 120 base-pair duplication. METHODS: Within-family transmission disequilibrium tests of association of the 5' 120 base-pair duplication, and exon 3 VNTR in a Taiwanese population. RESULTS: No evidence of association of ADHD with either polymorphism in this population was observed. CONCLUSION: The DRD4 gene markers investigated were not found to be associated with ADHD in this Taiwanese sample. Further work in Taiwanese and other Asian populations will therefore be required to establish whether the reports of association of DRD4 genetic variants in Caucasian samples can be generalised to Asian populations

The association of breast mitogens with mammographic densities

Radiologically dense breast tissue (mammographic density) is strongly associated with risk of breast cancer, but the biological basis for this association is unknown. In this study we have examined the association of circulating levels of hormones and growth factors with mammographic density. A total of 382 subjects, 193 premenopausal and 189 postmenopausal, without previous breast cancer or current hormone use, were selected in each of five categories of breast density from mammography units. Risk factor information, anthropometric measures, and blood samples were obtained, and oestradiol, progesterone, sex hormone binding globulin, growth hormone, insulin-like growth factor-I and its principal binding protein, and prolactin measured. Mammograms were digitised and measured using a computer-assisted method. After adjustment for other risk factors, we found in premenopausal women that serum insulin-like growth factor-I levels, and in postmenopausal women, serum levels of prolactin, were both significantly and positively associated with per cent density. Total oestradiol and progesterone levels were unrelated to per cent density in both groups. In postmenopausal women, free oestradiol (negatively), and sex hormone binding globulin (positively), were significantly related to per cent density. These data show an association between blood levels of breast mitogens and mammographic density, and suggest a biological basis for the associated risk of breast cancer

Evidence-Based Assessment of Child Obsessive Compulsive Disorder: Recommendations for Clinical Practice and Treatment Research

Obsessive-compulsive disorder (OCD) presents heterogeneously and can be difficult to assess in youth. This review focuses on research-supported assessment approaches for OCD in childhood. Content areas include pre-visit screening, diagnostic establishment, differential diagnosis, assessment of comorbid psychiatric conditions, tracking symptom severity, determining psychosocial functioning, and evaluating clinical improvement. Throughout this review, similarities and differences between assessment approaches geared towards clinical and research settings are discussed

Chiropractic care for paediatric and adolescent Attention-Deficit/Hyperactivity Disorder: A systematic review

<p>Abstract</p> <p>Background</p> <p>Psychostimulants are first line of therapy for paediatric and adolescent AD/HD. The evidence suggests that up to 30% of those prescribed stimulant medications do not show clinically significant outcomes. In addition, many children and adolescents experience side-effects from these medications. As a result, parents are seeking alternate interventions for their children. Complementary and alternative medicine therapies for behavioural disorders such as AD/HD are increasing with as many as 68% of parents having sought help from alternative practitioners, including chiropractors.</p> <p>Objective</p> <p>The review seeks to answer the question of whether chiropractic care can reduce symptoms of inattention, impulsivity and hyperactivity for paediatric and adolescent AD/HD.</p> <p>Methods</p> <p>Electronic databases (Cochrane CENTRAL register of Controlled Trials, Cochrane Database of Systematic reviews, MEDLINE, PsycINFO, CINAHL, Scopus, ISI Web of Science, Index to Chiropractic Literature) were searched from inception until July 2009 for English language studies for chiropractic care and AD/HD. Inclusion and exclusion criteria were applied to select studies. All randomised controlled trials were evaluated using the Jadad score and a checklist developed from the CONSORT (Consolidated Standards of Reporting Trials) guidelines.</p> <p>Results</p> <p>The search yielded 58 citations of which 22 were intervention studies. Of these, only three studies were identified for paediatric and adolescent AD/HD cohorts. The methodological quality was poor and none of the studies qualified using inclusion criteria.</p> <p>Conclusions</p> <p>To date there is insufficient evidence to evaluate the efficacy of chiropractic care for paediatric and adolescent AD/HD. The claim that chiropractic care improves paediatric and adolescent AD/HD, is only supported by low levels of scientific evidence. In the interest of paediatric and adolescent health, if chiropractic care for AD/HD is to continue, more rigorous scientific research needs to be undertaken to examine the efficacy and effectiveness of chiropractic treatment. Adequately-sized RCTs using clinically relevant outcomes and standardised measures to examine the effectiveness of chiropractic care verses no-treatment/placebo control or standard care (pharmacological and psychosocial care) are needed to determine whether chiropractic care is an effective alternative intervention for paediatric and adolescent AD/HD.</p