Data Publication with the Structural Biology Data Grid Supports Live Analysis

Access to experimental X-ray diffraction image data is fundamental for validation and reproduction of macromolecular models and indispensable for development of structural biology processing methods. Here, we established a diffraction data publication and dissemination system, Structural Biology Data Grid (SBDG; data.sbgrid.org), to preserve primary experimental data sets that support scientific publications. Data sets are accessible to researchers through a community driven data grid, which facilitates global data access. Our analysis of a pilot collection of crystallographic data sets demonstrates that the information archived by SBDG is sufficient to reprocess data to statistics that meet or exceed the quality of the original published structures. SBDG has extended its services to the entire community and is used to develop support for other types of biomedical data sets. It is anticipated that access to the experimental data sets will enhance the paradigm shift in the community towards a much more dynamic body of continuously improving data analysis

Chirurgie bij patiënten met centraal gelegen niet-kleincellig longcarcinoom: longparenchymsparende ingreep versus pneumonectomie

To examine if lung-parenchymal sparing resection ('sleeve' resection) is a safe and oncologically responsible alternative to pneumonectomy in patients with central tumours. Further, to evaluate in how far this technique is being used in the Netherlands. Retrospective cohort study. Patients undergoing either lung-parenchymal sparing procedure or pneumonectomy for centrally situated non-small cell lung carcinoma (NSCLC) between January 1995 and January 2010 were included. Early mortality, perioperative complications, survival and disease-free survival in both groups were compared. Survival was calculated using the Kaplan-Meier method. A total 78 patients underwent sleeve resection and 89 pneumonectomy. Early mortality (during admission or within 30 days of operation) in the sleeve-resection group was 1.3% (1 patient), and 9.0% (8) (p = 0.038) in the pneumonectomy group. In the sleeve-resection group 6.4% (5) developed a bronchopleural fistula; in the pneumonectomy group this was 4.5% (4) (p=0.735). Median survival in the sleeve-resection group was 90 months, and 1- and 5-year-survival were 88 (SD: 4) and 61% (SD: 6), respectively. Median survival in the pneumonectomy group was 17 months, with a 1- and 5-year survival of 63 (SD: 5) and 24% (SD: 5), respectively. The difference in survival was significant (p <0.001; hazard ratio: 3.27; 95% CI: 2.11-5.08). The effect of TNM stage was not statistically significant in addition to operation (p = 0.079) and TNM stage was not a clear confounder: even after analysis the hazard ratio was 2.74. In the sleeve-resection group, after 5 years disease-free survival was 62% (SD: 7). In the pneumonectomy group, this was 34% (SD: 7) (p = 0.05). Patients with centrally-situated NSCLC who undergo a lung-parenchymal sparing procedure have lower mortality and better survival than patients who undergo pneumonectom

Long-term follow-up of thoracoscopic ablation in long-standing persistent atrial fibrillation

OBJECTIVES: Catheter ablation of long-standing persistent atrial fibrillation (LSPAF) remains challenging, with suboptimal success rates obtained following multiple procedures. Thoracoscopic ablation has shown effective at creating transmural lesions around the pulmonary veins and box; however, long-term rhythm follow-up data are lacking. This study aims, for the first time, to assess the long-term outcomes of thoracoscopic pulmonary vein and box ablation in LSPAF. METHODS: Rhythm follow-up consisted of continuous rhythm monitoring using implanted loop recorders or 24-h Holter recordings. Rhythm status and touch-up interventions were assessed up to 5 years. RESULTS: Seventy-seven patients with symptomatic LSPAF underwent thoracoscopic ablation in 2 centres. Freedom from atrial arrhythmias at 5 years was 50% following a single thoracoscopic procedure and 68% allowing endocardial touch-up procedures (performed in 21% of patients). The mean atrial fibrillation burden in patients with continuous monitoring was reduced from 100% preoperatively to 0.1% at the end of the blanking period and 8.0% during the second year. Antiarrhythmic drug use decreased from 49.4% preoperative to 12.1% and 14.3% at 2 and 5 years, respectively (P < 0.001). Continuous rhythm monitoring resulted in higher recurrence detection rates compared to 24-h Holter monitoring at 2-year follow-up (hazard ratio: 6.5, P = 0.003), with comparable recurrence rates at 5-year follow-up. CONCLUSIONS: Thoracoscopic pulmonary vein and box isolation are effective in long-term restoration of sinus rhythm in LSPAF, especially when complemented by endocardial touch-up procedures, as demonstrated by the 68% freedom rate at 5 years. Continuous rhythm monitoring revealed earlier, but not more numerous documentation of recurrences at 5-year follow-up

Tolerance develops in spinal cord, but not in brain with chronic [Dmt(1)]DALDA treatment

1. Previously, we reported that H-2′,6′-dimethyltyrosine [Dmt(1)]-D-Arg-Phe-Lys-NH(2) (DALDA), an analogue of the naturally occurring opioid peptide dermorphin, is a highly potent and selective mu receptor agonist with low cross-tolerance to morphine. In the present study, we investigated the effect of treating mice chronically with [Dmt(1)]DALDA. The AD(50) of [Dmt(1)]DALDA (s.c.) increased eight-fold in animals given this drug chronically; in contrast, the AD(50) increased two-fold in mice chronically treated with morphine. The AD(50) of morphine (s.c.) in these [Dmt(1)]DALDA-treated animals was increased more than 120 times, while that of the more selective μ agonist [D-Ala(2)-MePhe(4)-Gly-ol(5)]enkephalin (DAMGO) given intrathecally was increased more than 240 times. However, the AD(50) of DAMGO given intracerebroventricularly was essentially the same in animals treated chronically with [Dmt(1)]DALDA as in naïve animals. The dose of naloxone required to precipitate withdrawal in [Dmt(1)]DALDA-treated animals was 20 times lower than that in morphine-tolerant animals. 2. Using real-time quantitative PCR, we found that expression of the μ opioid receptor, δ opioid receptor, preproenkephalin and preprodynorphin genes was upregulated in the brain by [Dmt(1)]DALDA treatment. No significant changes in expression of opioid receptor or opioid peptide genes were detected in the spinal cord of [Dmt(1)]DALDA-treated mice, nor in the brain or spinal cord of morphine-treated mice. We conclude that a high degree of tolerance to [Dmt(1)]DALDA develops in the spinal cord but not brain, and cannot be accounted for by changes in expression of opioid receptors or opioid peptides in these tissues

Suppression of inflammatory immune responses in celiac disease by experimental hookworm infection

We present immunological data from two clinical trials where the effect of experimental human hookworm (Necator americanus) infection on the pathology of celiac disease was evaluated. We found that basal production of Interferon- (IFN-)γ and Interleukin- (IL-)17A from duodenal biopsy culture was suppressed in hookworm-infected participants compared to uninfected controls. Increased levels of CD4+CD25+Foxp3+ cells in the circulation and mucosa are associated with active celiac disease. We show that this accumulation also occurs during a short-term (1 week) oral gluten challenge, and that hookworm infection suppressed the increase of circulating CD4+CD25+Foxp3+ cells during this challenge period. When duodenal biopsies from hookworm-infected participants were restimulated with the immunodominant gliadin peptide QE65, robust production of IL-2, IFN-γ and IL-17A was detected, even prior to gluten challenge while participants were strictly adhering to a gluten-free diet. Intriguingly, IL-5 was produced only after hookworm infection in response to QE65. Thus we hypothesise that hookworm-induced TH2 and IL-10 cross-regulation of the TH1/TH17 inflammatory response may be responsible for the suppression of these responses during experimental hookworm infection

Data publication with the structural biology data grid supports live analysis.

Access to experimental X-ray diffraction image data is fundamental for validation and reproduction of macromolecular models and indispensable for development of structural biology processing methods. Here, we established a diffraction data publication and dissemination system, Structural Biology Data Grid (SBDG; data.sbgrid.org), to preserve primary experimental data sets that support scientific publications. Data sets are accessible to researchers through a community driven data grid, which facilitates global data access. Our analysis of a pilot collection of crystallographic data sets demonstrates that the information archived by SBDG is sufficient to reprocess data to statistics that meet or exceed the quality of the original published structures. SBDG has extended its services to the entire community and is used to develop support for other types of biomedical data sets. It is anticipated that access to the experimental data sets will enhance the paradigm shift in the community towards a much more dynamic body of continuously improving data analysis