Multifactor effects and evidence of potential interaction between complement factor H Y402H and LOC387715 A69S in age-related macular degeneration.

BACKGROUND: Variants in the complement cascade genes and the LOC387715/HTRA1, have been widely reported to associate with age-related macular degeneration (AMD), the most common cause of visual impairment in industrialized countries. METHODS/PRINCIPAL FINDINGS: We investigated the association between the LOC387715 A69S and complement component C3 R102G risk alleles in the Finnish case-control material and found a significant association with both variants (OR 2.98, p = 3.75 x 10(-9); non-AMD controls and OR 2.79, p = 2.78 x 10(-19), blood donor controls and OR 1.83, p = 0.008; non-AMD controls and OR 1.39, p = 0.039; blood donor controls), respectively. Previously, we have shown a strong association between complement factor H (CFH) Y402H and AMD in the Finnish population. A carrier of at least one risk allele in each of the three susceptibility loci (LOC387715, C3, CFH) had an 18-fold risk of AMD when compared to a non-carrier homozygote in all three loci. A tentative gene-gene interaction between the two major AMD-associated loci, LOC387715 and CFH, was found in this study using a multiplicative (logistic regression) model, a synergy index (departure-from-additivity model) and the mutual information method (MI), suggesting that a common causative pathway may exist for these genes. Smoking (ever vs. never) exerted an extra risk for AMD, but somewhat surprisingly, only in connection with other factors such as sex and the C3 genotype. Population attributable risks (PAR) for the CFH, LOC387715 and C3 variants were 58.2%, 51.4% and 5.8%, respectively, the summary PAR for the three variants being 65.4%. CONCLUSIONS/SIGNIFICANCE: Evidence for gene-gene interaction between two major AMD associated loci CFH and LOC387715 was obtained using three methods, logistic regression, a synergy index and the mutual information (MI) index.

A comparative study of different in vitro lung cell culture systems to assess the most beneficial tool for screening the potential adverse effects of carbon nanotubes

To determine the potential inhalatory risk posed by carbon nanotubes (CNTs), a tier-based approach beginning with an in vitro assessment must be adopted. The purpose of this study therefore was to compare 4 commonly used in vitro systems of the human lung (human blood monocyte-derived macrophages [MDM] and monocyte-derived dendritic cells [MDDC], 16HBE14o- epithelial cells, and a sophisticated triple cell co-culture model [TCC-C]) via assessment of the biological impact of different CNTs (single-walled CNTs [SWCNTs] and multiwalled CNTs [MWCNTs]) over 24h. No significant cytotoxicity was observed with any of the cell types tested, although a significant (p < .05), dose-dependent increase in tumor necrosis factor (TNF)-α following SWCNT and MWCNT exposure at concentrations up to 0.02mg/ml to MDM, MDDC, and the TCC-C was found. The concentration of TNF-α released by the MDM and MDDC was significantly higher (p < .05) than the TCC-C. Significant increases (p < .05) in interleukin (IL)-8 were also found for both 16HBE14o- epithelial cells and the TCC-C after SWCNTs and MWCNTs exposure up to 0.02mg/ml. The TCC-C, however, elicited a significantly (p < .05) higher IL-8 release than the epithelial cells. The oxidative potential of both SWCNTs and MWCNTs (0.005-0.02mg/ml) measured by reduced glutathione (GSH) content showed a significant difference (p < .05) between each monoculture and the TCC-C. It was concluded that because only the co-culture system could assess each endpoint adequately, that, in comparison with monoculture systems, multicellular systems that take into consideration important cell type-to-cell type interactions could be used as predictive in vitro screening tools for determining the potential deleterious effects associated with CNTs.

Adverse effects of fillers and their histopathology.

Injectable fillers nowadays represent a pillar in facial rejuvenation and make a significant contribution to the success of the treatment. Despite their obvious benefits, a wide range of possible complications such as immediate, late, delayed, temporary, or irreversible adverse effects have to be respected. Differentiating the various filler materials, these effects are assigned to histopathology findings and currently available treatment options.

Enduring effects of evidence-based psychotherapies in acute depression and anxiety disorders versus treatment as usual at follow-up — A longitudinal meta-analysis

This meta-analysis examined the enduring efficacy of evidence-based psychotherapies (EBP) in comparison to treatment as usual (TAU) by examining effects from termination to follow-up for acute anxiety and depression in an adult outpatient population. It was hypothesized that EBPs might extend their efficacy at follow-up assessment (Tolin, 2010). METHOD: Longitudinal multilevel meta-analyses were conducted that examined the magnitude of difference between EBP and TAU. Targeted (disorder-specific) outcomes were examined, along with dropout rates at follow-up assessments. RESULTS: A total of 15 comparisons (including 30 repeated effect sizes [ES]) were included in this meta-analysis (average of 8.9 month follow-up). Small to moderate ES differences were found to be in favor of EBPs at 0-4 month assessments (Hedges' g=0.40) and up to 12-18 month assessments (g=0.20), indicating no extended efficacy at follow-up. However, the TAU-conditions were heterogeneous, ranging from absence of minimal mental health treatment to legitimate psychotherapeutic interventions provided by trained professionals, the latter of which resulted in smaller ES differences. Furthermore, samples where substance use comorbidities were not actively excluded indicated smaller ES differences. TAU-conditions produced slightly higher dropout rates than EBP-conditions. CONCLUSION: Findings indicate small and no extended superiority of EBP for acute depression and anxiety disorders in comparison to TAU at follow-up assessment. There are a limited number of studies investigating the transportability and lasting efficacy of EBP compared to TAU, especially to TAU with equivalent conditions between treatment groups.

A comprehensive policy to ameliorate adverse effects of transportation facilities. Appendix.

Transportation Department, Office of the Assistant Secretary for Environment, Safety, and Consumer Affairs, Washington, D.C.

Airborne ultrasound : measurement and possible adverse effects /

Mode of access: Internet.

The bat and the ball; or, Negative evidence, a farce in one act,

Mode of access: Internet.

Anticholinergic burden in older adults with intellectual disability; relationships with multimorbidity and adverse effects

Background: Anticholinergic medications may be associated with adverse clinical outcomes, including acute impairments in cognition and anticholinergic side effects, the risk of adverse outcomes increasing with increasing anticholinergic exposure. Older people with intellectual disability may be at increased risk of exposure to anticholinergic medicines due to their higher prevalence of comorbidities. We sought to determine anticholinergic burden in ageing people with intellectual disability. Methods: Medication data (self-report/proxy-report) was drawn from Wave 1 of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA), a study on the ageing of 753nationally representative people with an IDC40 years randomly selected from the National Intellectual Disability Database. Each individual’s cumulative exposure to anticholinergic medications was calculated using the Anticholinergic Cognitive Burden Scale (ACB) amended by a multi-disciplinary group with independent advice to account for the range of medicines in use in this population. Results: Overall, 70.1 % (527) reported taking medications with possible or definite anticholinergic properties (ACBC1), with a mean (±SD) ACB score of 4.5 (±3.0) (maximum 16). Of those reporting anticholinergic exposure (n=527), 41.3 % (217) reported an ACB score o fC5. Antipsychotics accounted for 36.4 % of the total cumulative ACB score followed by anticholinergics (16 %) and antidepressants (10.8 %). The most frequently reported medicine with anticholinergic activity was carbamazepine 16.8 % (127). The most frequently reported medicine with high anticholinergic activity (ACB 3) was olanzapine13.4 % (101). There was a significant association between higher anti-cholinergic exposure and multimorbidity, particularly mental health morbidity, and some anticholinergic adverse effects such as constipation and day-time drowsiness but not self-rated health. Conclusion: Using simple cumulative measures proved an effective means to capture total burden and helped establish that anticholinergic exposure in the study population was high. The finding highlights the need for comprehensive reviews of medications.

Association of anticholinergic burden with adverse effects in older people with intellectual disabilities:an observational cross-sectional study

BACKGROUND: No studies to date have investigated cumulative anticholinergic exposure and its effects in adults with intellectual disabilities. AIMS: To determine the cumulative exposure to anticholinergics and the factors associated with high exposure. METHOD: A modified Anticholinergic Cognitive Burden (ACB) scale score was calculated for a representative cohort of 736 people over 40 years old with intellectual disabilities, and associations with demographic and clinical factors assessed. RESULTS: Age over 65 years was associated with higher exposure (ACB 1-4 odds ratio (OR) = 3.28, 95% CI 1.49-7.28, ACB 5+ OR = 3.08, 95% CI 1.20-7.63), as was a mental health condition (ACB 1-4 OR = 9.79, 95% CI 5.63-17.02, ACB 5+ OR = 23.74, 95% CI 12.29-45.83). Daytime drowsiness was associated with higher ACB (P<0.001) and chronic constipation reported more frequently (26.6% ACB 5+ v. 7.5% ACB 0, P<0.001). CONCLUSIONS: Older people with intellectual disabilities and with mental health conditions were exposed to high anticholinergic burden. This was associated with daytime dozing and constipation.