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Context: Osteoporosis (OP) is a progressive systemic bone disease. Dual-energy X-ray absorptiometry (DXA) is routinely employed and is considered the gold standard method for the diagnosis of OP., Objective: We aimed to investigate the potential use of combined information from multiple bone turnover markers (BTMs) as a clinical diagnostic tool for OP., Materials and Methods: A total of 9053 Chinese postmenopausal women (2464 primary OP patients and 6589 healthy controls) were recruited. Serum levels of six common BTMs, including BAP, BSP, CTX, OPG, OST and sRANKL were assayed. Models based on support vector machine (SVM) were constructed to explore the efficiency of different combinations of multiple BTMs for OP diagnosis., Results: Increasing the number of BTMs used in generating the models increased the predictive power of the SVM models for determining the disease status of study subjects. The highest kappa coefficient for the model with one BTM (BAP) compared to DXA was 0.7783. The full model incorporating all six BTMs resulted in a high kappa coefficient of 0.9786., Conclusion: Our findings showed that although single BTMs were not sufficient for OP diagnosis, appropriate combinations of multiple BTMs incorporated into the SVM models showed almost perfect agreement with the DXA.

Aims and Background: Chronic inflammation leading to malignancy in the esophagus may be due to errors in mismatch repair (MMR) genes such as hMLH1. Promoter hypermethylation has been suggested as the main cause of hMLH1 silencing. In this study we assessed hMLH1 promoter hypermethylation in a range of esophageal diseases. Further, we evaluated the role of factors affecting the methylation cycle: (1) methylenetetrahydrofolate reductase (MTHFR) C677T mutation and (2) serum homocysteine levels., Methods: We endoscopically and histologically categorized 124 paired tissue and blood samples from patients into cancer, precancer, reflux esophagitis, other inflammatory esophagitis and controls (endoscopically normal). Restriction enzyme-based methylation analysis was carried out to assess hMLH1 promoter hypermethylation., Results and Conclusions: hMLH1 promoter hypermethylation in tissue was seen in 63.5% of patients with cancer and 53.8% of those with precancer, which was significantly increased when compared with controls (P < 0.001). There appears to be an increasing degree of hMLH1 hypermethylation with disease progression. Patients with gastroesophageal reflux disease (GERD) showed a high degree of hMLH1 hypermethylation (88.8%), indicating that local environment due to reflux may be promoting hypermethylation. We suggest that GERD is a progressive condition with an increased risk for developing into cancer. Only 14.5% of cases exhibited hypermethylation both in tissue and blood. Hence, we conclude that hMLH1 promoter hypermethylation is a tissue-specific change in the esophagus and blood testing cannot be used as a noninvasive tool to assess it. DNA methylation is dependent on the methylation cycle; MTHFR is a major enzyme in this pathway. MTHFR mutations did not correlate with hypermethylation or clinical pathology (P > 0.5). Elevated homocysteine levels, independent of MTHFR mutation, correlated significantly with hMLH1 hypermethylation in tissue (P < 0.005). Our study shows that hMLH1 hypermethylation in tissue may be the primary event caused by endogenous/exogenous factors in esophageal diseases, aiding disease progression.

Hepatitis B virus infection is responsible of an important number of world morbimortality. This is associated to severe liver outcome such as cirrhosis and hepatocellular carcinoma. Diverse factors influence the severity of liver injury produced by Hepatitis B Virus (HBV): the emergence of HBV mutants unable to secrete "e" antigen (pre-core mutants), the virus and host genetic heterogenicity and immune system competence. Particularly, the presence of pre-core mutants in chronic carriers is associated a low response to interferon therapy. We present paper is to present evidence as to the presence of these mutants in chronically infected, HBeAg negative patients (HBsAg positive) in Argentina. Viral DNAs were extracted from sera of nine patients, amplified by PCR and characterized by restriction enzyme assay. All of them appear to be pre-core mutants according with serological markers and a very low level of viral DNA detected in serum. Further genetic characterization of one of them by nucleotide sequence analysis of the pre-core region let allowed us to show modifications at codon 15 and 28 both of them previously described for pre-core mutants.