Distribution of genetic diversity reveals colonization patterns and philopatry of the loggerhead sea turtles across geographic scales.

Understanding the processes that underlie the current distribution of genetic diversity in endangered species is a goal of modern conservation biology. Specifically, the role of colonization and dispersal events throughout a species' evolutionary history often remains elusive. The loggerhead sea turtle (Caretta caretta) faces multiple conservation challenges due to its migratory nature and philopatric behaviour. Here, using 4207 mtDNA sequences, we analysed the colonisation patterns and distribution of genetic diversity within a major ocean basin (the Atlantic), a regional rookery (Cabo Verde Archipelago) and a local island (Island of Boa Vista, Cabo Verde). Data analysis using hypothesis-driven population genetic models suggests the colonization of the Atlantic has occurred in two distinct waves, each corresponding to a major mtDNA lineage. We propose the oldest lineage entered the basin via the isthmus of Panama and sequentially established aggregations in Brazil, Cabo Verde and in the area of USA and Mexico. The second lineage entered the Atlantic via the Cape of Good Hope, establishing colonies in the Mediterranean Sea, and from then on, re-colonized the already existing rookeries of the Atlantic. At the Cabo Verde level, we reveal an asymmetric gene flow maintaining links across island-specific nesting groups, despite significant genetic structure. This structure stems from female philopatric behaviours, which could further be detected by weak but significant differentiation amongst beaches separated by only a few kilometres on the island of Boa Vista. Exploring biogeographic processes at diverse geographic scales improves our understanding of the complex evolutionary history of highly migratory philopatric species. Unveiling the past facilitates the design of conservation programmes targeting the right management scale to maintain a species' evolutionary potential

Long-term survey of sea turtles (Caretta caretta) reveals correlations between parasite infection, feeding ecology, reproductive success and population dynamics.

Long-term monitoring of host-parasite interactions is important for understanding the consequences of infection on host fitness and population dynamics. In an eight-year survey of the loggerhead sea turtle (Caretta caretta) population nesting in Cabo Verde, we determined the spatiotemporal variation of Ozobranchus margoi, a sanguivorous leech best known as a vector for sea turtle fibropapilloma virus. We quantified O. margoi association with turtles' δ15N and δ13C stable isotopes to identify where infection occurs. We then measured the influence of infection on reproduction and offspring fitness. We found that parasite prevalence has increased from 10% of the population in 2010, to 33% in 2017. Stable isotope analysis of host skin samples suggests transmission occurs within the host's feeding grounds. Interestingly, we found a significant interaction between individual size and infection on the reproductive success of turtles. Specifically, small, infected females produced fewer offspring of poorer condition, while in contrast, large, infected turtles produced greater clutch sizes and larger offspring. We interpret this interaction as evidence, upon infection, for a size-dependent shift in reproductive strategy from bet hedging to terminal investment, altering population dynamics. This link between infection and reproduction underscores the importance of using long-term monitoring to quantify the impact of disease dynamics over time

Correlation Between Anti-TNF Serum Levels and Endoscopic Inflammation in Inflammatory Bowel Disease Patients

Objectives: (a) To evaluate the diagnostic accuracy of anti-TNF trough levels to predict mucosal healing in inflammatory bowel disease (IBD); (b) to determine the best cut-off point to predict mucosal healing in IBD patients treated with anti-TNF. Methods: This is a multicenter, prospective study. IBD patients under anti-TNF treatment for at least 6 months that had to undergo an endoscopy were included. Mucosal healing was defined as: Simple endoscopic score for Crohn’s Disease < 3 for Crohn’s disease (CD), Rutgeerts score < i2 for CD in postoperative setting, or Mayo endoscopic score = 1 for ulcerative colitis (UC). Anti-TNF concentrations were measured using SMART ELISAs at trough. Results: A total of 182 patients were included. Anti-TNF trough levels were significantly higher among patients that had mucosal healing than among those who did not. The area under the curve of infliximab for mucosal healing was 0.63 (best cutoff value 3.4 µg/mL), and for adalimumab 0.60 (best cutoff value 7.2 µg/mL). In the multivariate analysis, having anti-TNF drug levels above the cutoff values [odds ratio (OR) 3.1]) and having UC instead of CD (OR 4) were associated with a higher probability of having mucosal healing. Additionally, the need for an escalated dosage (OR 0.2) and current smoking habit (OR 0.2) were also associated with a lower probability of mucosal healing. Conclusions: There was an association between anti-TNF trough levels and mucosal healing in IBD patients; however, the accuracy of the determination of infliximab and adalimumab concentrations able to predict mucosal healing was suboptimal

Differential association of two PTPN22 coding variants with Crohn’s disease and ulcerative colitis

2 páginas.-- Póster presentado al 5º European Workshop on Immune-Mediated Inflammatory Diseases celebrado en Sitges (Barcelona) dxel 1 al 3 de Diciembre de 2010.-- et al.The PTPN22 gene is an important risk factor for human autoimmunity. Two PTPN22 missense-SNPs, both with functional influence, the R620W (1858C>T, rs2476601) in exon 14 and the R263Q (788G>A, rs33996649) in exon 10 have been associated with autoimmune diseases [1-4].Peer reviewe

Assessing internet-based information used to aid patient decision-making about surgery for perianal Crohn's fistula.

BACKGROUND: Decision-making in perianal Crohn's fistula (pCD) is preference sensitive. Patients use the internet to access healthcare information. The aim of this study was to assess the online information and patient decision aids relating to surgery for pCD. METHODS: A search of Google™ and the Decision Aids Library Inventory (DALI) was performed using a predefined search strategy. Patient-focussed sources providing information about pCD surgery were included in the analysis. Written health information was assessed using the International Patient Decision Aids Standards (IPDAS) and DISCERN criteria. The readability of the source content was assessed using the Flesch-Kincaid score. RESULTS: Of the 201 sources found, 187 were excluded, leaving 14 sources for analysis. Three sources were dedicated to pCD, and six sources mentioned pCD-specific outcomes. The most common surgical intervention reported was seton insertion (n = 13). The least common surgical intervention reported was proctectomy (n = 1). The mean IPDAS and DISCERN scores were 4.43 ± 1.65 out of 12 (range = 2-8) and 2.93 ± 0.73 out of 5 (range = 1-5), respectively. The mean reading ease was US college standard. CONCLUSIONS: We found no patient decision aids relating to surgery for pCD. The online sources relating to surgery for pCD are few, and their quality is poor, as seen in the low IPDAS and DISCERN scores. Less than half of the sources mentioned pCD-specific outcomes, and three sources were solely dedicated to providing information on pCD. Healthcare professionals should look to create a patient tool to assist decision-making in pCD

CD209 in inflammatory bowel disease: a case-control study in the Spanish population

<p>Abstract</p> <p>Background</p> <p>The etiology of Ulcerative Colitis (UC) and Crohn's Disease (CD), considered together as Inflammatory Bowel Diseases (IBD), involves environmental and genetic factors. Although some genes are already known, the genetics underlying these diseases is complex and new candidates are continuously emerging. The <it>CD209 </it>gene is located in a region linked previously to IBD and a <it>CD209 </it>functional polymorphism (rs4804803) has been associated to other inflammatory conditions. Our aim was to study the potential involvement of this <it>CD209 </it>variant in IBD susceptibility.</p> <p>Methods</p> <p>We performed a case-control study with 515 CD patients, 497 UC patients and 731 healthy controls, all of them white Spaniards. Samples were typed for the <it>CD209 </it>single nucleotide polymorphism (SNP) rs4804803 by TaqMan technology. Frequency comparisons were performed using χ²tests.</p> <p>Results</p> <p>No association between <it>CD209 </it>and UC or CD was observed initially. However, stratification of UC patients by <it>HLA-DR3 </it>status, a strong protective allele, showed that carriage of the <it>CD209</it>_G allele could increase susceptibility in the subgroup of <it>HLA-DR3</it>-positive individuals (p = 0.03 OR = 1.77 95% CI 1.04–3.02, <it>vs. </it>controls).</p> <p>Conclusion</p> <p>A functional variant in the <it>CD209 </it>gene, rs4804803, does not seem to be influencing Crohn's disease susceptibility. However, it could be involved in the etiology or pathology of Ulcerative Colitis in <it>HLA-DR3</it>-positive individuals but further studies are necessary.</p

Antitumor Necrosis Factor Agents to Treat EndoscopicPostoperative Recurrence of Crohn’s Disease: A Nationwide Study With Propensity-Matched Score Analysis

INTRODUCTION:Patients with Crohn's disease experiencing endoscopic postoperative recurrence (POR) may benefit from antitumor necrosis factor (TNF) agents but scarce data on this are available. Our aim was to assess the efficacy of anti-TNF in improving mucosal lesions in patients with endoscopic POR.METHODS:Multicenter, retrospective, study of patients with Crohn's disease who underwent therapy with anti-TNF agents for endoscopic POR (Rutgeerts score > i1). Treatment outcomes were assessed by the findings in the last ileocolonoscopy performed after anti-TNF therapy was initiated. Endoscopic improvement and remission were defined as any reduction in the baseline Rutgeerts score and by a Rutgeerts score < i2, respectively.RESULTS:A total of 179 patients were included, 83 were treated with infliximab and 96 with adalimumab. Median time on anti-TNF therapy at the last endoscopic assessment was 31 months (interquartile range, 13-54). Endoscopic improvement was observed in 61%, including 42% who achieved endoscopic remission. Concomitant use of thiopurines and treatment with infliximab were associated with endoscopic improvement (odds ratio [OR] 2.15, 95% confidence interval [CI] 1.04-4.46; P = 0.03, and OR 2.34, 95% CI 1.18-4.62; P < 0.01, respectively) and endoscopic remission (OR 3.16, 95% CI 1.65-6.05; P < 0.01, and OR 2.01, 95% CI 1.05-3.88; P = 0.04, respectively) in the multivariable logistic regression analysis. These results were confirmed in a propensity-matched score analysis.DISCUSSION:In patients with endoscopic POR, anti-TNF agents improve mucosal lesions in almost two-thirds of the patients. In this setting, concomitant use of thiopurines and use of infliximab seem to be more effective in improving mucosal lesions.Fiorella Canete received a research grant from the Societat Catalana de Digestologia

Effectiveness and Safety of the Sequential Use of a Second and Third Anti-TNF Agent in Patients with Inflammatory Bowel Disease: Results from the Eneida Registry

Background: The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. Methods: We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. Results: A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn''s disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. Conclusions: Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response

Evolution after Anti-TNF Discontinuation in Patients with Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study

OBJECTIVES:The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed.METHODS:This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included.RESULTS:A total of 1, 055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn''s disease and ulcerative colitis patients, respectively. In both Crohn''s disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn''s disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe.CONCLUSIONS:The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe