The Biomedical Research Hub: a federated platform for patient research data

ObjectiveThe objective was to develop and operate a cloud-based federated system for managing, analyzing, and sharing patient data for research purposes, while allowing each resource sharing patient data to operate their component based upon their own governance rules. The federated system is called the Biomedical Research Hub (BRH).Materials and MethodsThe BRH is a cloud-based federated system built over a core set of software services called framework services. BRH framework services include authentication and authorization, services for generating and assessing findable, accessible, interoperable, and reusable (FAIR) data, and services for importing and exporting bulk clinical data. The BRH includes data resources providing data operated by different entities and workspaces that can access and analyze data from one or more of the data resources in the BRH.ResultsThe BRH contains multiple data commons that in aggregate provide access to over 6 PB of research data from over 400 000 research participants.Discussion and conclusionWith the growing acceptance of using public cloud computing platforms for biomedical research, and the growing use of opaque persistent digital identifiers for datasets, data objects, and other entities, there is now a foundation for systems that federate data from multiple independently operated data resources that expose FAIR application programming interfaces, each using a separate data model. Applications can be built that access data from one or more of the data resources.     

Investigation of the interleukin-1 gene cluster polymorphisms in Jordanian patients with chronic and aggressive periodontitis

Objective

Interleukin-1 (IL-1) is a proinflammatory cytokine that is highly elevated in response to bacterial biofilms and is a potential risk factor for periodontal diseases. IL-1 gene polymorphisms have been associated with the IL-1 level. The aim of this study was to investigate if IL-1 gene cluster polymorphisms are associated with chronic (CP) and aggressive (AgP) periodontitis in a Jordanian population.

Methods

A total of 100 CP, 80 AgP patients and 80 controls were genotyped using PCR for IL-1RN-86-bp VNTR and PCR-RFLP for IL-1A-889, IL-1B-511, -35, +3953, and IL-1RN +8006, +9589, +11100 SNPs. The distribution of alleles and genotypes between groups was compared using χ² analysis. Estimation of haplotype frequencies was carried out using the EH programme.

Results

The IL-1RN8006 SNP and the IL-1RN-VNTR were associated with CP but not with AgP. The C allele and TC genotype of IL-1RN8006 were increased in CP (P_corr = 0.002, 0.00026 respectively). The A1 allele and A1/A1 genotype of the IL1-RN-VNTR were significantly increased in CP (P_corr = 0.0007, <0.0001 respectively). The CA1 haplotype formed by both markers was present in 29 CP patients but not in any of the controls (P < 0.0001). No significant differences were found in the distribution of allele and genotype frequencies of the other markers between CP and AgP cases and controls.

Conclusions

IL-1RN 8006 and IL-1RN VNTR were associated with CP but not AgP in a Jordanian population, whilst other investigated markers in IL-1A, IL-1B and IL-1RN were not associated with either CP or AgP.     

Effects of inhaled nitric oxide on inflammation and apoptosis after cardiopulmonary bypass

BACKGROUND: Cardiopulmonary bypass (CPB), a procedure often used during cardiac surgery, is associated with an inflammatory process that leads to lung injury. We hypothesized that inhaled nitric oxide (INO), which has anti-inflammatory properties, possesses the ability to modulate lung cell apoptosis and prevent CPB-induced inflammation. METHODS: Twenty male pigs were randomly classified into four groups: sham, sham plus INO, CPB, and CPB plus INO. INO (20 ppm) was administered for 24 h after anesthesia. CPB was performed 90 min into INO treatment. BAL fluid and blood were collected at time 0 (before CPB), at 4 h after beginning CPB, and 24 h after beginning CPB (T24). RESULTS: At T(24), BAL interleukin (IL)-8 levels and neutrophil percentages were elevated significantly in the CPB group. At T(24), INO reduced IL-8 concentrations and attenuated the increase of neutrophil percentage in the CPB-plus-INO group. Nitrite-plus-nitrate (NOx) concentrations were decreased significantly in groups without INO. Moreover, animals treated with INO showed higher rates of pulmonary apoptosis compared to their respective control groups except for the sham-plus-INO group, in which they were diminished. CONCLUSION: These results demonstrate that NOx production is reduced after CPB, and that INO acts as an anti-inflammatory agent by decreasing neutrophil numbers and their major chemoattractant, IL-8. INO also increases cell apoptosis in the lungs during inflammatory conditions, which may explain, in part, how it resolves pulmonary inflammation.     

Ventricular diastolic function of ankylosing spondylitis patients by using conventional pulsed wave Doppler, myocardial performance index and tissue Doppler imaging

OBJECTIVE: The aim of this study was to evaluate ventricular functions by using standard Doppler echocardiography (SDE), myocardial performance index (MPI), and pulsed wave tissue Doppler imaging (PW-TDI) in patients with ankylosing spondylitis (AS) and healthy controls. METHODS: Forty-nine AS patients (38 +/- 11 years, 25 M/24 F) and 33 controls (36 +/- 9 years, 17 M/16 F) were studied. Two-dimensional, M-Mode, SDE, PW-TDI echocardiography examinations were performed. Spinal mobility was assessed by the Bath ankylosing spondylitis metrology index (BASMI) measurement. Patients were also evaluated using the Bath ankylosing spondylitis functional index (BASFI) and the Bath ankylosing spondylitis disease activity index (BASDAI). RESULTS: Four control subjects and six AS patients met the left ventricular (LV) diastolic dysfunction (DD) criteria by using conventional Doppler echocardiography (p > 0.05). However, using PW-TDI method 22 patients in the AS group and six subjects in the control group were diagnosed to have LV DD (Em/Am < 1). Pseudonormalized pattern was present in 16 AS patients and two control subjects. Correlation analysis revealed significant moderate negative correlations between Em/Am and BASMI, age and body mass index (p < 0.05; r =-0.3, -0.6, and -0.4, respectively). No correlation was observed between Em/Am and disease duration, BASFI, BASDAI, CRP, and ESR. We could not detect any right ventricular function involvement either by conventional or by recently introduced echocardiography methods. The risk of developing LV DD was found to be 3.7 times higher in AS patients. CONCLUSION: When sensitive echocardiographic Doppler techniques such as MPI, TDI-derived MPI, and PW-TDI are utilized, DD can be detected in a significant proportion of patients with AS without cardiovascular (CV) disease which may contribute CV mortality in these patients.     

Effects of radiofrequency catheter ablation on myocardial performance index and plasma NT-Pro-BNP levels in patients with Wolff-Parkinson-White syndrome

Background: The myocardial performance index (Tei index) is an echocardiographic index of combined systolic and diastolic functions. Brain natriuretic peptide (BNP) and its biologically inactive fragment N-terminal pro-BNP (NT-pro-BNP) are secreted by the heart in response to myocardial stretch. In this study, we investigated Tei index and NT-pro-BNP levels in patients with Wolff-Parkinson-White (WPW) syndrome before and after radiofrequency catheter ablation therapy (RFCA).
Methods: Thirty patients (19 males, 11 females, aged 35.5 ± 14.4 years) with WPW syndrome were enrolled in this study. Echocardiographic examination was performed before and 24 hours after RFCA. Tei index was calculated using Doppler echocardiography. Blood samples were taken before and 24 hours after RFCA to detect levels of NT-pro-BNP. Results: Although isovolumic contraction time (IVCT) and isovolumic relaxation time (IVRT) did not change, aortic ejection time (ET) was decreased after RFCA (276 ± 22 ms vs 254 ± 30 ms, P < 0.01). So Tei index was significantly higher in postablation period (0.36 ± 0.11 vs 0.42 ± 0.21, P < 0.05). NT-pro-BNP levels did not change significantly after RFCA. Conclusions: We demonstrated that restoration of normal atrioventricular conduction by RFCA, leads to increase in Tei index but does not effect plasma NT-pro-BNP levels .     

HCV associated glomerulopathy in Egyptian patients: clinicopathological analysis

BACKGROUND: Hepatitis C virus (HCV) infection in Egypt has reached an epidemic proportion and is associated with many extra hepatic manifestations; Glomerulonephritis (GN) is one of the most consequences of HCV infection often resulting in end stage renal disease in some cases. Detection of viral genome or particles within the kidney biopsies from HCV-infected patients has proven to be difficult. Histological characterization of renal lesions still represents a major challenge. The aim of our work was to describe the histological pattern of HCV-associated nephropathy. METHODS: Fifty Patients--out of 233--presented to Mansoura Urology and Nephrology clinic with manifestations of glomerular disease were screened for HCV antibodies by a 3rd generation ELISA test. Those tested positive for HCV antibodies were confirmed by PCR for HCV-RNA and subjected to more detailed clinical, biochemical and histological study. Kidney biopsies and in appropriate cases liver biopsies were examined by LM and electron microscopy (EM). RESULTS: Histological study of renal biopsies revealed membranoproliferative (MPGN) type 1 to be the most common lesion encountered (54%), followed by focal segmental glomerulosclerosis (FSGS) (24%), mesangioproliferative GN (18%), membranous nephropathy (MN) (4%) in that order. EM examinations of renal biopsies were successful in identifying HCV like particles in frozen renal tissue. CONCLUSION: HCV-associated glomerulopathy is a distinct category of glomerulonephritis. Results of LM showed some peculiar features. In addition, we were successful in location and detection of HCV particles in renal tissues by EM.     

Resident CD8+ T cells suppress CD4+ T cell-dependent late allergic airway responses

BACKGROUND: The role of CD8+ T cells in the immune response to airway challenge with an allergen is poorly understood. OBJECTIVE: The aim of this study was to test the hypothesis that resident naive CD8+ T cells modulate the magnitude of CD4+ T cell-dependent allergic airway responses. METHODS: Cervical lymph node CD4+ T cells (2 x 10(6)) were harvested from ovalbumin (OVA)- or sham-sensitized rats and injected intraperitoneally into naive Brown Norway recipients. The recipients were treated with a CD8alpha mAb (OX-8) to deplete the resident CD8+ T cells (n = 12) or mouse ascites (n = 12). Two days after adoptive transfer, the recipient animals were OVA challenged, lung resistance was measured for 8 hours, and bronchoalveolar lavage (BAL) was performed. RESULTS: After OVA challenge, primed CD4-transferred CD8-depleted rats had larger early airway responses and late airway responses compared with primed CD4-transferred CD8-nondepleted rats (early airway responses: 158.6% +/- 19.2% vs 115.7% +/- 5.9%, P < .05; late airway responses: 8.5% +/- 1.7% vs 4.4% +/- 0.9%, P < .05). BAL eosinophilia was also greater (4.67% +/- 0.45% vs 2.34 +/- 0.26%, P < .01). The cells in BAL fluid expressing IL-4 mRNA were not significantly changed by CD8 depletion, but IL-5 mRNA+ cells were higher in number, and IFN-gamma mRNA+ cells were fewer in the CD8-depleted group. CONCLUSIONS: Resident CD8+ T cells downregulate the late allergic response and airway inflammation evoked by CD4+ T-cell transfers in Brown Norway rats. This downregulation does not require antigen priming.