A potential vulnerability locus for schizophrenia on chromosome 6p24-22:evidence for genetic heterogeneity

In 265 Irish pedigrees, with linkage analysis we find evidence for a vulnerability locus for schizophrenia in region 6p24-22. The greatest lod score, assuming locus heterogeneity, is 3.51 (P = 0.0002) with D6S296. Another test, the C test, also supported linkage, the strongest results being obtained with D6S296 (P = 0.00001), D6S274 (P = 0.004) and D6S285 (P = 0.006). Non-parametric analysis yielded suggestive, but substantially weaker, findings. This locus appears to influence the vulnerability to schizophrenia in roughly 15 to 30% of our pedigrees. Evidence for linkage was maximal using an intermediate phenotypic definition and declined when this definition was narrowed or was broadened to include other psychiatric disorders.

Synthesis of the C(7)-C(22)-Sector of (+)-Acutiphycin Via O-Directed Double Free Radical Alkyne Hydrostannation with Ph3SnH/Et3B, Double I-Sn Exchange and Double Stille Coupling

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Herein a new double O-directed free radical hydrostannation reaction is reported on the structurally complex dialkyldiyne 11. Through our use of a conformation-restraining acetal to help prevent stereocenter-compromising 1,5-H-atom abstraction reactions by vinyl radical intermediates, the two vinylstannanes of 10 were concurrently constructed with high stereocontrol using Ph3SnH/Et3B/O2. Distannane 10 was thereafter elaborated into the bis-vinyl iodide 9 via O-silylation and double I–Sn exchange; double Stille coupling of 9, O-desilylation, and oxidation thereafter furnished 8.

Narrow-band ultraviolet B treatment boosts serum 25-hydroxyvitamin D in patients with psoriasis on oral vitamin D supplementation

A course of treatment with narrow-band ultraviolet B (NB-UVB) improves psoriasis and increases serum 25-hydroxyvitamin D (25(OH)D). In this study 12 patients with psoriasis who were supplemented with oral cholecalciferol, 20 µg daily, were given a course of NB-UVB and their response measured. At baseline, serum 25(OH)D was 74.14 ± 22.9 nmol/l. At the 9th exposure to NB-UVB 25(OH)D had increased by 13.2 nmol/l (95% confidence interval (95% CI) 7.2–18.4) and at the 18th exposure by 49.4 nmol/l (95% CI 35.9–64.6) above baseline. Psoriasis Area Severity Index score improved from 8.7 ± 3.5 to 4.5 ± 2.0 (p < 0.001). At baseline, psoriasis lesions showed low vitamin D metabolizing enzyme (CYP27A1, CYP27B1) and high human β-defensin-2 mRNA expression levels compared with those of the healthy subjects. In conclusion, NB-UVB treatment significantly increases serum 25(OH)D in patients with psoriasis who are taking oral vitamin D supplementation, and the concentrations remain far from the toxicity level. Healing psoriasis lesions show similar mRNA expression of vitamin D metabolizing enzymes, but higher antimicrobial peptide levels than NB-UVB-treated skin in healthy subjects.

Anti-TNF antibody-induced psoriasiform skin lesions in patients with inflammatory bowel disease are characterised by interferon-γ-expressing Th1 cells and IL-17A/IL-22-expressing Th17 cells and respond to anti-IL-12/IL-23 antibody treatment

Background We analysed incidence, predictors, histological features and specific treatment options of anti-tumour necrosis factor alpha (TNF-alpha) antibody-induced psoriasiform skin lesions in patients with inflammatory bowel diseases (IBD).

Design Patients with IBD were prospectively screened for anti-TNF-induced psoriasiform skin lesions. Patients were genotyped for IL23R and IL12B variants. Skin lesions were examined for infiltrating Th1 and Th17 cells. Patients with severe lesions were treated with the anti-interleukin (IL)-12/IL-23 p40 antibody ustekinumab.

Results Among 434 anti-TNF-treated patients with IBD, 21 (4.8%) developed psoriasiform skin lesions. Multiple logistic regression revealed smoking (p=0.007; OR 4.24, 95% CI 1.55 to 13.60) and an increased body mass index (p=0.029; OR 1.12, 95% CI 1.01 to 1.24) as main predictors for these lesions. Nine patients with Crohn's disease and with severe psoriasiform lesions and/or anti-TNF antibody-induced alopecia were successfully treated with the anti-p40-IL-12/IL-23 antibody ustekinumab (response rate 100%). Skin lesions were histologically characterised by infiltrates of IL-17A/IL-22-secreting T helper 17 (Th17) cells and interferon (IFN)-gamma-secreting Th1 cells and IFN-alpha-expressing cells. IL-17A expression was significantly stronger in patients requiring ustekinumab than in patients responding to topical therapy (p=0.001). IL23R genotyping suggests disease-modifying effects of rs11209026 (p.Arg381Gln) and rs7530511 (p.Leu310Pro) in patients requiring ustekinumab.

Conclusions New onset psoriasiform skin lesions develop in nearly 5% of anti-TNF-treated patients with IBD. We identified smoking as a main risk factor for developing these lesions. Anti-TNF-induced psoriasiform skin lesions are characterised by Th17 and Th1 cell infiltrates. The number of IL-17A-expressing T cells correlates with the severity of skin lesions. Anti-IL-12/IL23 antibody therapy is a highly effective therapy for these lesions.

Sediment accumulation rates in subarctic lakes: insights into age-depth modeling from 22 dated lake records from the Northwest Territories, Canada

Age-depth modeling using Bayesian statistics requires well-informed prior information about the behavior of sediment accumulation. Here we present average sediment accumulation rates (represented as deposition times, DT, in yr/cm) for lakes in an Arctic setting, and we examine the variability across space (intra- and inter-lake) and time (late Holocene). The dataset includes over 100 radiocarbon dates, primarily on bulk sediment, from 22 sediment cores obtained from 18 lakes spanning the boreal to tundra ecotone gradients in subarctic Canada. There are four to twenty-five radiocarbon dates per core, depending on the length and character of the sediment records. Deposition times were calculated at 100-year intervals from age-depth models constructed using the ‘classical’ age-depth modeling software Clam. Lakes in boreal settings have the most rapid accumulation (mean DT 20 ± 10 years), whereas lakes in tundra settings accumulate at moderate (mean DT 70 ± 10 years) to very slow rates, (>100 yr/cm). Many of the age-depth models demonstrate fluctuations in accumulation that coincide with lake evolution and post-glacial climate change. Ten of our sediment cores yielded sediments as old as c. 9,000 cal BP (BP = years before AD 1950). From between c. 9,000 cal BP and c. 6,000 cal BP, sediment accumulation was relatively rapid (DT of 20 to 60 yr/cm). Accumulation slowed between c. 5,500 and c. 4,000 cal BP as vegetation expanded northward in response to warming. A short period of rapid accumulation occurred near 1,200 cal BP at three lakes. Our research will help inform priors in Bayesian age modeling.

The welfare implications of large litter size in the domestic pig I:Biologica factors

Increasing litter size has long been a goal of pig breeders and producers, and may have implications for pig (Sus scrofa domesticus) welfare. This paper reviews the scientific evidence on biological factors affecting sow and piglet welfare in relation to large litter size. It is concluded that, in a number of ways, large litter size is a risk factor for decreased animal welfare in pig production. Increased litter size is associated with increased piglet mortality, which is likely to be associated with significant negative animal welfare impacts. In surviving piglets, many of the causes of mortality can also occur in non-lethal forms that cause suffering. Intense teat competition may increase the likelihood that some piglets do not gain adequate access to milk, causing starvation in the short term and possibly long-term detriments to health. Also, increased litter size leads to more piglets with low birth weight which is associated with a variety of negative long-term effects. Finally, increased production pressure placed on sows bearing large litters may produce health and welfare concerns for the sow. However, possible biological approaches to mitigating health and welfare issues associated with large litters are being implemented. An important mitigation strategy is genetic selection encompassing traits that promote piglet survival, vitality and growth. Sow nutrition and the minimisation of stress during gestation could also contribute to improving outcomes in terms of piglet welfare. Awareness of the possible negative welfare consequences of large litter size in pigs should lead to further active measures being taken to mitigate the mentioned effects. © 2013 Universities Federation for Animal Welfare.

The Impact of Multimedia Education on Uptake of Comprehensive Eye Examinations in Rural China: A Randomized, Controlled Trial

PURPOSE: To study the effect of multimedia education on acceptance of comprehensive eye examinations (CEEs), critical for detecting glaucoma and diabetic eye disease, among rural Chinese patients using a randomized, controlled design.
METHODS: Patients aged ≥40 years were recruited from 52 routine clinic sessions (26 intervention, 26 control) conducted at seven rural hospitals in Guangdong, China. Subjects answered demographic questionnaires, were tested on knowledge about CEEs and chronic eye disease, and were told the cost of examination (range US$0-8). At intervention sessions, subjects were cluster-randomized to view a 10-minute video on the value of CEEs and retested. Control subjects were not retested. Trial outcomes were acceptance of CEEs (primary outcome) and final knowledge scores (secondary outcome).
RESULTS: At baseline, >70% (p = 0.70) of both intervention (n = 241, 61.2 ± 12.3 years) and control (n = 218, 58.4 ± 11.7 years) subjects answered no knowledge questions correctly, but mean scores on the test (maximum 5 points) increased by 1.39 (standard deviation 0.12) points (p < 0.001) after viewing the video. Intervention (73.0%) and control (72.9%) subjects did not differ in acceptance of CEEs (p > 0.50). In mixed-effect logistic regression models, acceptance of CEEs was associated with availability of free CEEs (odds ratio 18.3, 95% confidence interval 1.32-253.0), but not group assignment or knowledge score. Acceptance was 97.5% (79/81) when free exams were offered.
CONCLUSIONS: Education increased knowledge about but not acceptance of CEEs, which was generally high. Making CEEs free could further increase acceptance.