Comparation of the new rebound tonometer IOPen and the Goldmann tonometer, and their relationship to corneal properties

Purpose To compare the intraocular pressures (IOPs) obtained with the IOPen rebound tonometer, Goldmann applanation tonometer (GAT) and the ocular response analyzer (ORA) and investigate the effects of corneal biomechanical properties on IOPen measurements. Methods A total of 198 normal eyes were included in this cross-sectional and randomized study. Three measurements were taken using IOPen. Agreement between tonometers was calculated using the Bland and Altman limits of agreement (LoA) analysis. Results The median IOPen IOP was 3mmHg below the GAT (Po0.001), 3mmHg below the ORA IOP similar to Goldmann (IOPg), and 3mmHg below the ORA IOP corrected using corneal parameters (IOPcc)(Po0.01). The LoA width between the IOPen and GAT IOPs varied between 13.92 (mean IOPen IOP) and 15.99mmHg (third IOPen measurement). The central corneal thickness (CCT) was unrelated to IOPen measurements (P40.05). Corneal hysteresis (CH) and corneal rigidity factor (CRF) were correlated with IOPen and GAT. Conclusions IOPen underestimated the IOP compared with GAT and ORA. The effect of measurement quality or measurement order on IOPen was low. CCT did not affect the IOPen, but the CH and CRF did. The LoA width between the IOPen and GAT IOPs was higher than between the ORA IOPg or ORA IOPcc and GAT IOPs

Prediction of the response of chronic hepatitis C to interferon alfa: a statistical analysis of pretreatment variables

Pretreatment variables that could predict the response of chronic hepatitis C to interferon alfa treatment have not been fully assessed. Eighteen baseline variables were evaluated in a series of 100 consecutive patients treated with a 12 month course of interferon alfa. For the purposes of this study, response was defined as the return to normal of aminotransferase activities before the third month of treatment. Seventy per cent of the patients responded to treatment. Six variables were associated with an increased likelihood of response assessed by univariate analysis. With stepwise multiple regression analysis assessment, however, only three variables remained independently predictive of response: low gamma glutamyltransferase (gamma GT) activities (p 0.66 mu kat/l (n = 45) (p = 0.048). Response was attained in 75% of non-obese patients (n = 80), compared with only 50% of obese patients (n = 20) (p = 0.03). Finally, 80% of patients without cirrhosis (n = 76) responded, while among those with cirrhosis (n = 24) the response rate was only 37% (p 40 years old, and with gamma GT activities >0.66 mu kat/l responded to interferon alfa (p<0.001). Those findings may be useful when evaluating interferon alfa trials and it is suggested that this treatment should be applied early in the course of chronic hepatitis C

Detection of anti-hepatitis C virus antibodies by ELISA using synthetic peptides

A novel ELISA assay for the detection of anti-hepatitis C virus antibodies in the sera of infected individuals is described. This assay is based on a mixture of three 15-amino acid synthetic peptides encompassing regions of core and NS4 proteins of hepatitis C virus. Comparison with other available ELISA assays based on recombinant polypeptides shows that, short synthetic peptides have the advantage over some larger recombinant peptides by giving higher specificity without loss of sensitivity

Cellular immunity to hepatitis C virus core protein and the response to interferon in patients with chronic hepatitis C

To investigate the involvement of T-cell response against hepatitis C virus (HCV) antigens in viral clearance after interferon therapy, we measured interleukin-2 (IL-2) production by peripheral mononuclear cells in response to HCV core in patients with chronic hepatitis C. In a cohort of 43 patients, we investigated the frequency of circulating core-specific T-helper (Th) cell precursors by the limiting-dilution assay, and in a second cohort of 60 patients, we analyzed the response to specific core epitopes using 52 synthetic 15-mer overlapping peptides. We observed that the frequency of core-specific Th cell precursors was significantly higher in patients with sustained biochemical and virological response (SR) after interferon (IFN) therapy (median, 1/55,736) than in untreated patients (1/274,023) or that in patients who remained viremic after completion of the treatment-nonresponders (NR) plus transient responders (TR) (1/1,909,972). Patients who failed to respond to IFN (NR) and those who relapsed after IFN discontinuation (TR) had a similarly low number of precursors. The number of core peptides recognized by SR, TR, NR, UT, and healthy controls was 8.2 +/- 1.5, 6.5 +/- 1.2, 2.0 +/- 0.5, 2.7 +/- 0.9, and 0.3 +/- 0.2, respectively. In SR, the intensity of the proliferative response to core peptides as estimated by the summation of stimulation indexes (sigmaSI) was significantly higher than in NR and than in UT, but not different from that of TR. Our results indicate that both expansion of HCV-specific Th cell precursors and Th cell recognition of multiple core epitopes seem to be important in the elimination of HCV after IFN therapy

Interaction among sex, aging, and epigenetic processes concerning visceral fat, insulin resistance, and dyslipidaemia

The distribution of adipose tissue is influenced by gender and by age, shifting from subcutaneous to visceral depots with longevity, increasing the development of several aging-related diseases and manifestations such as obesity, metabolic syndrome, and insulin resistance. Epigenetics might have an important role in aging processes. The aim of this research was to investigate the interactions between aging and epigenetic processes and the role of visceral adipose tissue, insulin resistance, and dyslipidaemia. Two different study samples of 366 and 269 adult participants were analyzed. Anthropometric, biochemical (including the triglycerides-glucose (TyG) index), and blood pressure measurements were assessed following standardized methods. Body composition measurements by Dual-energy X-ray absorptiometry (DXA) were also performed for the second sample. Methylation data were assessed by Infinium Human Methylation BeadChip (Illumina) in peripheral white blood cells. Epigenetic age acceleration was calculated using the methods DNAmAge (AgeAcc) and GrimAge (AgeAccGrim). Age acceleration (AgeAccGrim) showed better correlations than AgeAcc with most of the measured variables (waist circumference, glucose, HOMA-IR, HDL-cholesterol, triglycerides, and TyG index) for the first sample. In the second sample, all the previous correlations were confirmed, except for HOMA-IR. In addition, many of the anthropometrical measurements assessed by DXA and C-reactive protein (CRP) were also statistically associated with AgeAccGrim. Associations separated by sex showed statistically significant correlations between AgeAccGrim and HDL-cholesterol or CRP in women, whereas, in men, the association was with visceral adipose tissue mass DXA, triglycerides and TyG index. Linear regression models (model 1 included visceral adipose tissue mass DXA and TyG index and model 2 included HDL-cholesterol and CRP) showed a significant association for men concerning visceral adipose tissue mass DXA and TyG index, while HDL-cholesterol and CRP were associated in women. Moreover, structural equation modeling showed that the TyG index was mediating the majority of the visceral adipose tissue mass action on age acceleration. Collectively, these findings showed that there are different mechanisms affecting epigenetic age acceleration depending on sex. The identified relationships between epigenetic age acceleration and disease markers will contribute to the understanding of the development of age-related diseases

Specific and general HLA-DR binding motifs: comparison of algorithms

Using panels of peptides well characterized for their ability to bind to HLA DR1, DRB1*1101, or DRB1*0401 molecules, algorithms were deduced to predict binding to these molecules. These algorithms consist of blocks of 8 amino acids containing an amino acid anchor (Tyr, Phe, Trp, Leu, Ile, or Val) at position i and different amino acid combinations at positions i+2 to i+7 depending on the class II molecule. The sensitivity (% of correctly predicted binder peptides) and specificity (% of correctly predicted non-binder peptides) of these algorithms, were tested against different independent panels of peptides and compared to other algorithms reported in the literature. Similarly, using a panel of 232 peptides able to bind to one or more HLA molecules as well as 43 non-binder peptides, we deduced a general motif for the prediction of binding to HLA-DR molecules. The sensitivity and specificity of this general motif was dependent on the threshold score used for the predictions. For a score of 0.1, the sensitivity and specificity were 84.7% and 69.8%, respectively. This motif was validated against several panels of binder and non-binder peptides reported in the literature, as well as against 35, 15-mer peptides from hepatitis C virus core protein, that were synthesized and tested in a binding assay against a panel of 19 HLA-DR molecules. The sensitivities and specificities against these panels of peptides were similar to those attained against the panels used to deduce the algorithm. These results show that comparison of binder and non-binder peptides, as well as correcting for the relative abundance of amino acids in proteins, is a useful approach to deduce performing algorithms to predict binding to HLA molecules

Prediction of sustained remission of chronic hepatitis C after a 12-month course of alfa interferon

alpha-Interferon therapy normalizes aminotransferase levels in approximately 50% of the patients with chronic hepatitis C, but post-therapy relapses are common and predictive factors of sustained response remain largely unknown. We retrospectively assessed several parameters as predictors of sustained remission after a 12-month course of lymphoblastoid alpha-interferon: the Knodell histological activity index, serum levels of procollagen type III peptide, serum HCV-RNA, anti-alpha-interferon antibodies, and anti-HCV antibodies (C-100-3), all at month 12. Thirty-seven patients were studied. Fourteen patients were non-responders (38%), 15 patients experienced a sustained response (40.5%) and eight patients responded similarly but relapsed after alpha-interferon withdrawal (21.5%). A decrease in the histological activity index above 5, normalization of procollagen type III peptide levels (< 12 ng/ml) and the absence of viremia after treatment were all significantly associated with a sustained response (p = 0.008, p = 0.007 and p = 0.037, respectively). Anti-interferon antibodies were detected in only one non-responder patient. Anti-C-100-3 antibodies became undetectable at month 12 in 5 of the 15 sustained responders. The best prediction of sustained response was obtained from the three variables independent of multivariate analysis according to the following equation: F = 0.872 + 0.067 x K (decrease of histological index) -0.052 x P (procollagen type III peptide levels at month 12) -0.28 x R (HCV-RNA at month 12; R = 2 when present and R = 1 when absent). A score higher than 0 predicted sustained remission with a 100% sensitivity and specificity in this series of patients

Phenotype and genotype predictors of BMI variability among European adults

Background/objective: Obesity is a complex and multifactorial disease resulting from the interactions among genetics, metabolic, behavioral, sociocultural and environmental factors. In this sense, the aim of the present study was to identify phenotype and genotype variables that could be relevant determinants of body mass index (BMI) variability. Subjects/methods: In the present study, a total of 1050 subjects (798 females; 76%) were included. Least angle regression (LARS) analysis was used as regression model selection technique, where the dependent variable was BMI and the independent variables were age, sex, energy intake, physical activity level, and 16 polymorphisms previously related to obesity and lipid metabolism. Results: The LARS analysis obtained the following formula for BMI explanation: (64.7 + 0.10 × age [years] + 0.42 × gender [0, men; 1, women] + -40.6 × physical activity [physical activity level] + 0.004 × energy intake [kcal] + 0.74 × rs9939609 [0 or 1-2 risk alleles] + -0.72 × rs1800206 [0 or 1-2 risk alleles] + -0.86 × rs1801282 [0 or 1-2 risk alleles] + 0.87 × rs429358 [0 or 1-2 risk alleles]. The multivariable regression model accounted for 21% of the phenotypic variance in BMI. The regression model was internally validated by the bootstrap method (r2 original data set = 0.208, mean r2 bootstrap data sets = 0.210). Conclusion: In conclusion, age, physical activity, energy intake and polymorphisms in FTO, APOE, PPARG and PPARA genes are significant predictors of the BMI trait

A weight-loss model based on baseline microbiota and genetic scores for selection of dietary treatments in overweight and obese population

Background & aims: The response to weight loss depends on the interindividual variability of determinants such as gut microbiota and genetics. The aim of this investigation was to develop an integrative model using microbiota and genetic information to prescribe the most suitable diet for a successful weight loss in individuals with excess of body weight. Methods: A total of 190 Spanish overweight and obese participants were randomly assigned to two hypocaloric diets for 4 months: 61 women and 29 men followed a moderately high protein (MHP) diet, and 72 women and 28 men followed a low fat (LF) diet. Baseline fecal DNA was sequenced and used for the construction of four microbiota subscores associated with the percentage of BMI loss for each diet (MHP and LF) and for each sex. Bootstrapping techniques and multiple linear regression models were used for the selection of families, genera and species included in the subscores. Finally, two total microbiota scores were generated for each sex. Two genetic subscores previously reported to weight loss were used to generate a total genetic score. In an attempt to personalize the weight loss prescription, several linear mixed models that included interaction with diet between microbiota scores and genetic scores for both, men and women, were studied. Results: The microbiota subscore for the women who followed the MHP-diet included Coprococcus, Dorea, Flavonifractor, Ruminococcus albus and Clostridium bolteaea. For LF-diet women, Cytophagaceae, Catabacteriaceae, Flammeovirgaceae, Rhodobacteriaceae, Clostridium-x1vb, Bacteriodes nordiiay, Alistipes senegalensis, Blautia wexlerae and Psedoflavonifractor phocaeensis. For MHP-diet men, Cytophagaceae, Acidaminococcaceae, Marinilabiliaceae, Bacteroidaceae, Fusicatenibacter, Odoribacter and Ruminococcus faecis; and for LF-men, Porphyromanadaceae, Intestinimonas, Bacteroides finegoldii and Clostridium bartlettii. The mixed models with microbiota scores facilitated the selection of diet in 72% of women and in 84% of men. The model including genetic information allows to select the type of diet in 84% and 73%, respectively