The impact of natural and anthropogenic Dissolved Organic Carbon (DOC), and pH on the toxicity of triclosan to the crustacean Gammarus pulex (L.).

Regulatory ecotoxicology testing rarely accounts for the influence of natural water chemistry on the bioavailability and toxicity of a chemical. Therefore, this study identifies whether key omissions in relation to Dissolved Organic Carbon (DOC) and pH have an impact on measured effect concentrations (EC). Laboratory ecotoxicology tests were undertaken for the widely used antimicrobial compound triclosan, using adult Gammarus pulex (L.), a wild-type amphipod using synthetic fresh water, humic acid solutions and wastewater treatment works effluent. The toxicity of triclosan was tested at two different pHs of 7.3 and 8.4, with and without the addition of DOC and 24 and 48hour EC values with calculated 95% confidence intervals calculated. Toxicity tests undertaken at a pH above triclosan's pKa and in the presents of humic acid and effluent, containing 11 and 16mgL(-1) mean DOC concentrations respectively, resulted in significantly decreased triclosan toxicity. This was most likely a result of varying triclosan speciation and complexation due to triclosan's pKa and high hydrophobicity controlling its bioavailability. The mean 48hour EC50 values varied between 0.75±0.45 and 1.93±0.12mgL(-1) depending on conditions. These results suggest that standard ecotoxicology tests can cause inaccurate estimations of triclosan's bioavailability and subsequent toxicity in natural aquatic environments. These results highlight the need for further consideration regarding the role that water chemistry has on the toxicity of organic contaminants and how ambient environmental conditions are incorporated into the standard setting and consenting processes in the future

Anticholinergic and sedative medicines: prescribing considerations for people with dementia

Backgroun

Reduced Cancer Incidence in Huntington's Disease: Analysis in the Registry Study

Background: People with Huntington's disease (HD) have been observed to have lower rates of cancers. Objective: To investigate the relationship between age of onset of HD, CAG repeat length, and cancer diagnosis. Methods: Data were obtained from the European Huntington's disease network REGISTRY study for 6540 subjects. Population cancer incidence was ascertained from the GLOBOCAN database to obtain standardised incidence ratios of cancers in the REGISTRY subjects. Results: 173/6528 HD REGISTRY subjects had had a cancer diagnosis. The age-standardised incidence rate of all cancers in the REGISTRY HD population was 0.26 (CI 0.22-0.30). Individual cancers showed a lower age-standardised incidence rate compared with the control population with prostate and colorectal cancers showing the lowest rates. There was no effect of CAG length on the likelihood of cancer, but a cancer diagnosis within the last year was associated with a greatly increased rate of HD onset (Hazard Ratio 18.94, p < 0.001). Conclusions: Cancer is less common than expected in the HD population, confirming previous reports. However, this does not appear to be related to CAG length in HTT. A recent diagnosis of cancer increases the risk of HD onset at any age, likely due to increased investigation following a cancer diagnosis

Clinical and genetic characteristics of late-onset Huntington's disease

Background: The frequency of late-onset Huntington's disease (&gt;59 years) is assumed to be low and the clinical course milder. However, previous literature on late-onset disease is scarce and inconclusive. Objective: Our aim is to study clinical characteristics of late-onset compared to common-onset HD patients in a large cohort of HD patients from the Registry database. Methods: Participants with late- and common-onset (30–50 years)were compared for first clinical symptoms, disease progression, CAG repeat size and family history. Participants with a missing CAG repeat size, a repeat size of ≤35 or a UHDRS motor score of ≤5 were excluded. Results: Of 6007 eligible participants, 687 had late-onset (11.4%) and 3216 (53.5%) common-onset HD. Late-onset (n = 577) had significantly more gait and balance problems as first symptom compared to common-onset (n = 2408) (P &lt;.001). Overall motor and cognitive performance (P &lt;.001) were worse, however only disease motor progression was slower (coefficient, −0.58; SE 0.16; P &lt;.001) compared to the common-onset group. Repeat size was significantly lower in the late-onset (n = 40.8; SD 1.6) compared to common-onset (n = 44.4; SD 2.8) (P &lt;.001). Fewer late-onset patients (n = 451) had a positive family history compared to common-onset (n = 2940) (P &lt;.001). Conclusions: Late-onset patients present more frequently with gait and balance problems as first symptom, and disease progression is not milder compared to common-onset HD patients apart from motor progression. The family history is likely to be negative, which might make diagnosing HD more difficult in this population. However, the balance and gait problems might be helpful in diagnosing HD in elderly patients