In silico prediction and ex vivo evaluation of potential T-cell epitopes in glycoproteins 4 and 5 and nucleocapsid protein of genotype-I (European) of porcine reproductive and respiratory syndrome virus

T-cell epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) glycoproteins 4 (GP4), 5 (GP5) and nucleocapsid (N) were predicted using bioinformatics and later tested by IFN-γ ELISPOT in pigs immunized with either a modified live vaccine (MLV) or DNA (open reading frames 4, 5 or 7). For MLV-vaccinated pigs, immunodominant epitopes were found in N but T-epitopes were also found in GP4 and GP5. For DNA-immunized pigs, some peptides were differently recognized. Using a large set of PRRSV sequences it was shown that N contains a conserved epitope and that for GP5, the genotype-I counterparts of previously reported epitopes of genotype-II strains were also immunogenic.     

Intake of high levels of vitamin A and polyunsaturated fatty acids during different developmental periods modifies the expression of morphogenesis genes in European sea bass (Dicentrarchus labrax)

The effect of the feeding period on larval development was investigated in European sea bass larvae by considering the expression level of some genes involved in morphogenesis. Larvae were fed a control diet except during three different periods (period A: from 8 to 13 d post-hatching (dph); period B: from 13 to 18 dph; period C: from 18 to 23 dph) with two compound diets containing high levels of vitamin A or PUFA. European sea bass morphogenesis was affected by these two dietary nutrients during the early stages of development. The genes involved in morphogenesis could be modulated between 8 and 13 dph, and our results indicated that retinoids and fatty acids influenced two different molecular pathways that in turn implicated two different gene cascades, resulting in two different kinds of malformation. Hypervitaminosis A delayed development, reducing the number of vertebral segments and disturbing bone formation in the cephalic region. These malformations were correlated to an upregulation of retinoic acid receptor gamma, retinoid X receptor (RXR) alpha and bone morphogenetic protein (BMP)4. An excess of PUFA accelerated the osteoblast differentiation process through the upregulation of RXRalpha and BMP4, leading to a supernumerary vertebra. These results suggest that the composition of diets devoted to marine fish larvae has a particularly determining effect before 13 dph on the subsequent development of larvae and juvenile fish.     

Elevated troponin I levels in patients with acute coronary syndrome without ST elevation are associated with increased complexity of the culprit lesion

INTRODUCTION: The prognosis in patients with acute coronary syndrome without persistent ST segment elevation (NSTEACS) differs depending on cardiac troponin levels. Clinical practice guidelines published by the Spanish Society of Cardiology and the ACC/AHA consider patients with NSTEACS and markedly elevated troponin levels as high risk patients. The aim of this study was to identify factors related to markedly elevated troponin I levels in NSTEACS. PATIENTS AND METHOD: We measured troponin I levels in 219 consecutive patients with NSTEACS and normal CK-MB values, and identified 2 groups: patients with markedly elevated troponin levels (more than 10-fold the normal upper limit), and patients with normal or slightly elevated troponin levels (less than a 10-fold increase above the normal limit). We also analyzed clinical and angiographic variables. Logistic regression was used to calculate age- and sex-adjusted associations for the main variables. RESULTS: Forty-one patients (19%) had markedly elevated troponin levels, and 178 (81%) showed normal or slightly elevated troponin I levels. Patients with markedly elevated levels had more frequently prolonged angina, class IIb angina, more severe ECG changes, a higher number of diseased vessels on coronary angiography, and greater severity of the culprit lesion. The culprit stenosis in these patients was more often characterized as ulcerated, showing visible thrombus, and excentric, bifurcated and irregular. Class IIIb angina (odds ratio [OR] = 3.1; CI 95%, 1.1-8.6), bifurcation (OR=6.04; CI 95%, 2.5-14.3), ulceration (OR=3.2; CI 95%, 1.07-9.7) and visible thrombus (OR=2.7; CI 95%, 1.1-6.3) in the culprit lesion were predictive factors associated with markedly elevated levels of troponin I independently of age or sex. CONCLUSIONS: Markedly elevated troponin I levels in patients with NSTEACS are associated with a more severe clinical presentation and increased complexity of the culprit lesion on coronary angiography.     

Secondary autoimmune diseases occurring after HSCT for an autoimmune disease: a retrospective study of the EBMT Autoimmune Disease Working Party

To specify the incidence and risk factors for secondary autoimmune diseases (ADs) after HSCT for a primary AD, we retrospectively analyzed AD patients treated by HSCT reported to EBMT from 1995 to 2009 with at least 1 secondary AD (cases) and those without (controls). After autologous HSCT, 29 of 347 patients developed at least 1 secondary AD within 21.9 (0.6-49) months and after allogeneic HSCT, 3 of 16 patients. The observed secondary ADs included: autoimmune hemolytic anemia (n = 3), acquired hemophilia (n = 3), autoimmune thrombocytopenia (n = 3), antiphospholipid syndrome (n = 2), thyroiditis (n = 12), blocking thyroid-stimulating hormone receptor antibody (n = 1), Graves disease (n = 2), myasthenia gravis (n = 1), rheumatoid arthritis (n = 2), sarcoidosis (n = 2), vasculitis (n = 1), psoriasis (n = 1), and psoriatic arthritis (n = 1). After autologous HSCT for primary AD, the cumulative incidence of secondary AD was 9.8% ± 2% at 5 years. Lupus erythematosus as primary AD, and antithymocyte globulin use plus CD34(+) graft selection were important risk factors for secondary AD by multivariate analysis. With a median follow-up of 6.2 (0.54-11) years after autologous HSCT, 26 of 29 patients with secondary AD were alive, 2 died during their secondary AD (antiphospholipid syndrome, hemophilia), and 1 death was HSCT-related. This European multicenter study underlines the need for careful management and follow-up for secondary AD after HSCT.     

Emerging importance of residual renal function in end-stage renal failure

Residual renal function (RRF) is well recognized as an important marker of outcomes in peritoneal dialysis (PD), and contributes vitally to solute clearance. Recently, its importance in hemodialysis (HD) has emerged with evidence that it is strongly associated with improved outcomes. The presence of RRF is associated with improved nutrition, reduced erythropoetin requirements, better potassium clearance, and improved quality of life. Retrospective and observational evidence is now available, which suggests that the presence of RRF is independently associated with survival and that this benefit goes beyond what is expected simply from augmentation of small solute clearance. Preservation of RRF is now considered by many to be an important aspect of dialysis strategy. Evidence in favor of one modality over another for preservation of RRF is conflicting, as are the potential benefits of biocompatible fluids in PD. In HD, the evidence in favor of biocompatible membranes is stronger. Emerging evidence is broadly in favor of angiotensin converting enzyme inhibitors for preservation of RRF. Diuretics appear to have a neutral effect. The complexities and practical difficulties in measurement of RRF have resulted in this important parameter being largely ignored in HD. Novel markers of renal function may provide alternative, simple methods of estimating RRF, which may remove the need for urine collections and simplify its measurement.