Linkage disequilibrium (LD) pattern of <i>AHI1</i> gene.

<p>Figures represent pairwise r² values observed in control subjects from German (a) and Spanish (b) origin. Values are represented in a grayscale ranging from white (no LD) to black (high LD).</p

Single alleles and haplotypes of the <i>AHI1</i> region associated with schizophrenia in the present study.

<p>Significant values are marked in bold. The corrected P-values are indicated in brackets.</p>a<p>To avoid redundant information, other significant haplotypes, which are variations of other larger significant haplotypes from this table, have not been included.</p>b<p>SNP27 had significantly different genotypic distributions in the German and the Spanish sample (heterogeneity <i>P</i> value = 0.016 uncorrected).</p><p>Abbreviations: Cont, control; SCZ, schizophrenia; ns, not significant; perm, permutation; ref, reference haplotype.</p

List of SNPs included in the present study.

<p>Abbreviations: CEU, CEPH collection - DNA samples of Utah residents with ancestry from northern and western Europe; MAF, minor allele frequency.</p

Genomic region and SNPs analyzed in this study.

<p>The position of each SNP is indicated with an orange arrow.</p

Exploratory analysis of osteoarthritis progression among medication users: data from the Osteoarthritis Initiative

BACKGROUND: We conducted an exploratory analysis of osteoarthritis progression among medication users in the Osteoarthritis Initiative to identify interventions or pathways that may be associated with disease modification and therefore of interest for future clinical trials. METHODS: We used participants from the Osteoarthritis Initiative with annual medication inventory data between the baseline and 36-month follow-up visit (n = 2938). Consistent medication users were defined for each medication classification as a participant reporting at all four annual visits that they were regularly using an oral prescription medication at the time of the visit. The exploratory analysis focused on medication classes with 40 or more users. The primary outcome measures were medial tibiofemoral joint space width change and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) knee pain score change (12-36-month visits). Within each knee, we explored eight comparisons between users and matched or unmatched nonusers (defined two ways). An effect size of each comparison was calculated. Medication classes had potential signals if (a) both knees had less progression among users compared with nonusers, or (b) there was less progression based on structure and symptoms in one knee. RESULTS: We screened 28 medication classes. Six medication classes had signals for fewer structural changes and better knee pain changes: alpha-adrenergic blockers, antilipemic (excluding statins and fibric acid), anticoagulants, selective serotonin reuptake inhibitors, antihistamines, and antineoplastic agents. Four medication classes had signals for structural changes alone: anti-estrogen (median effect size = 0.28; range = -0.41-0.64), angiotensin-converting enzyme inhibitors (median effect size = 0.13; range = -0.08-0.28), beta-adrenergic blockers (median effect size = 0.09; range = 0.01-0.30), and thyroid agents (median effect size = 0.04; range = -0.05-0.14). Thiazide diuretics had evidence for symptom modification (median effect size = -0.12; range = -0.24-0.04). CONCLUSIONS: Users of neurovascular, antilipemic, or hormonal interventions may have less disease progression compared with nonusers

<i>AHI1</i> SNPs significantly associated with clinical traits in the Spanish sample.

<p>Significant <i>P</i> values (P<0.05) are indicated in bold.</p><p><b>^a</b>The corrected <i>P</i> value is indicated in brackets.</p><p>Abbreviations: SE, standard error; CI, confidence interval.</p

Experiment II: Training.

<p>(<b>A</b>) Latency to reach the arm, (<b>B</b>) latency to reach the hole, and (<b>C</b>) percentage of time spent at the hole in positive and negative trials across the four days of training for mice being later confronted with the near-negative (NN, n = 7), central (CE, n = 10), or near-positive (NP, n = 11) probe arm. Data are averaged per trial outcome and day and are presented as means ±SEM. Day 1: 5 positive trials, day 2+3: 3 positive and 3 negative trials, day 4: 2 positive and 2 negative trials. Statistics: day 1: ANOVA; day 2–4: Repeated Measures ANOVA for each day, main effect of trial outcome: ***p≤0.001, ^tp≤0.1, effect of group-by-trial outcome interaction: ^#p≤0.1.</p

Cognitive bias test apparatus.

<p>(<b>A</b>) Schematic diagram of the apparatus used in experiment I and II displaying the start box, the starting corridor, the central platform, the positive and negative reference arm, the three probe arms, and the sliding doors. In experiment I both reference arms had either a positive or a negative outcome and only the central probe arm was used for the probe trial. (<b>B</b>) Apparatus used in experiment III with the start cylinder positioned in the starting corridor, the central platform, the positive and negative reference arm, and the ambiguous probe arm. Unused arms were closed by reversing them so that their closed end functioned as barrier. Please note: The position of the positive and negative reference location in experiment II and III was counterbalanced between individuals.</p

Experiment I: Training.

<p>(<b>A</b>) Latency to reach the arm, (<b>B</b>) latency to reach the hole, and (<b>C</b>) percentage of time spent at the hole for mice being confronted with solely positive (optimistically-trained mice, n = 7) or solely negative (pessimistically-trained mice, n = 7) experience across the three days of training. Data are averaged per treatment group and day and are presented as means ±SEM. Day 1: 5 trials, day 2: 6 trials, day 3: 2 trials. See results section for details of statistical analysis.</p

Additional file 1: Table S1. of Low-dose lipopolysaccharide (LPS) inhibits aggressive and augments depressive behaviours in a chronic mild stress model in mice

Primer sequences for qPCR. Primers were custom designed and validated by PrimerDesign Ltd. (Southampton, UK). Figure S1. The effect of a low dose of LPS on locomotor activity at 24 and 48 h post-challenge in naïve mice. Naïve animals were subjected to a single dose of LPS (0.1 or 0.5 mg/kg) or vehicle injection and were tested at 24 or 48 h post-injection. (A) Neither the resting time was unaltered by the treatment in the TruScan open field nor (B) rearing in the novel cage test for the total number of rear. (C–E) Aggressive behaviour was also unaltered. Data are mean ± SEM, two-way ANOVA throughout. Figure S2. (A, B) Body weight in the chronic stress experiment. Experimental groups were balanced upon baseline mean values of body weight measured 7 days prior the start of the chronic stress experiment and LPS challenge. Mice exposed to chronic stress had a significant reduction in body weight as compared with baseline measurements (*p < 0.05, pairwise t test). Chronically stressed mice injected either with vehicle or LPS had similar mean body weight prior the LPS challenge. (C–E) Sucrose preference. Experimental groups were balanced upon baseline mean values of sucrose preference when evaluated 7 days prior the experiment chronic stress procedure and LPS challenge. Experimental groups had similar mean measures of sucrose and water intake. (p > 0.05, one-way ANOVA and post hoc Tukey test; see the text). (F) Naïve and stressed animals (10 days) were challenged with a single dose of LPS (0.1 mg/kg) or vehicle (saline) and tested 24 h thereafter in a novel cage test for total number of rears (see the text). Data are mean ± SEM. No differences between the groups were observed. Figure S3. (A–C) Baseline behaviour in a resident-intruder test. Experimental groups were balanced upon baseline mean scores of behaviours in a resident-intruder test that were studied 7 days prior the experimental chronic stress procedure and LPS challenge. Mice had similar mean measures of (A) latency to attack, (B) number of attack and (C )duration of crawl over behaviour. (p > 0.05, one-way ANOVA and post hoc Tukey test; see the text). (D) The latency to attack after the chronic stress was not significantly altered