Soluble Fas might serve as a diagnostic tool for gastric adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>Fas (Apo-1/CD95) and its specific ligand (FasL) are key elements in apoptosis. They have been studied in different malignancies but there are few published studies about the soluble forms of these markers (i.e. sFas/sFasL) in gastric cancer. We have compared the serum levels of sFas/sFasL in gastric adenocarcinoma patients and cases with pre-neoplastic lesions as potential markers for early diagnosis, and investigated their relation with clinicopathological characteristics.</p> <p>Methods</p> <p>Fifty-nine newly-diagnosed cases of gastric adenocarcinoma who had undergone gastrectomy, along with 62 endoscopically- and histologically-confirmed non-cancer individuals were enrolled in this study. sFas/sFasL serum levels were detected by Enzyme Linked Immunosurbent Assay.</p> <p>Results</p> <p>Mean serum sFas level was significantly higher in gastric cancer patients than in control group (305.97 ± 63.71 (pg/ml) vs. 92.98 ± 4.95 (pg/ml), P < 0.001); while the mean serum level of sFasL was lower in patients with gastric adenocarcinoma (0.138 ± 0.04 (pg/ml) vs. 0.150 ± 0.02 (pg/ml), P < 0.001). Mean serum levels of sFas/sFasL were significantly different in both intestinal/diffuse and cardiac/non-cardiac subtypes when compared to the control group (P < 0.001). There was an increase in the serum level of sFas from the first steps of pre-neoplastic lesions to gastric adenocarcinoma (P < 0.001). Patients who had no lymph node involvement (<it>N₀</it>) showed significantly higher serum levels of sFas compared to others (P = 0.044).</p> <p>Conclusions</p> <p>Production of sFas may play a critical role in the carcinogenesis of intestinal-type gastric cancer. sFas serum level may serve as a non-invasive tool for early diagnosis of gastric cancer.</p

p16INK4a hypermethylation and p53, p16 and MDM2 protein expression in Esophageal Squamous Cell Carcinoma

<p>Abstract</p> <p>Background</p> <p>Tumor suppressor genes <it>p53 </it>and <it>p16</it>^INK4aand the proto-oncogene <it>MDM2 </it>are considered to be essential G1 cell cycle regulatory genes whose loss of function is associated with ESCC carcinogenesis. We assessed the aberrant methylation of the <it>p16 </it>gene and its impact on <it>p16</it>^{<it>INK4a </it>}protein expression and correlations with <it>p53 </it>and <it>MDM2 </it>protein expressions in patients with ESCC in the Golestan province of northeastern Iran in which ESCC has the highest incidence of cancer, well above the world average.</p> <p>Methods</p> <p>Cancerous tissues and the adjacent normal tissue obtained from 50 ESCC patients were assessed with Methylation-Specific-PCR to examine the methylation status of <it>p16</it>. The expression of <it>p16</it>, <it>p53 </it>and <it>MDM2 </it>proteins was detected by immunohistochemical staining.</p> <p>Results</p> <p>Abnormal expression of <it>p16 </it>and <it>p53</it>, but not <it>MDM2</it>, was significantly higher in the tumoral tissue. <it>p53 </it>was concomitantly accumulated in ESCC tumor along with <it>MDM2 </it>overexpression and <it>p16 </it>negative expression. Aberrant methylation of the <it>p16</it>^{<it>INK4a </it>}gene was detected in 31/50 (62%) of esophageal tumor samples, while two of the adjacent normal mucosa were methylated (P < 0.001). <it>p16</it>^{<it>INK4a </it>}aberrant methylation was significantly associated with decreased <it>p16 </it>protein expression (P = 0.033), as well as the overexpression of <it>p53 </it>(P = 0.020).</p> <p>Conclusions</p> <p><it>p16 </it>hypermethylation is the principal mechanism of <it>p16 </it>protein underexpression and plays an important role in ESCC development. It is associated with p53 protein overexpression and may influence the accumulation of abnormally expressed proteins in <it>p53-MDM2 </it>and <it>p16-Rb </it>pathways, suggesting a possible cross-talk of the involved pathways in ESCC development.</p

Frequency and genotypic distribution of GB virus C (GBV-C) among Colombian population with Hepatitis B (HBV) or Hepatitis C (HCV) infection

<p>Abstract</p> <p>Background</p> <p>GB virus C (GBV-C) is an enveloped positive-sense ssRNA virus belonging to the <it>Flaviviridae </it>family. Studies on the genetic variability of the GBV-C reveals the existence of six genotypes: genotype 1 predominates in West Africa, genotype 2 in Europe and America, genotype 3 in Asia, genotype 4 in Southwest Asia, genotype 5 in South Africa and genotype 6 in Indonesia. The aim of this study was to determine the frequency and genotypic distribution of GBV-C in the Colombian population.</p> <p>Methods</p> <p>Two groups were analyzed: i) 408 Colombian blood donors infected with HCV (n = 250) and HBV (n = 158) from Bogotá and ii) 99 indigenous people with HBV infection from Leticia, Amazonas. A fragment of 344 bp from the 5' untranslated region (5' UTR) was amplified by nested RT PCR. Viral sequences were genotyped by phylogenetic analysis using reference sequences from each genotype obtained from GenBank (n = 160). Bayesian phylogenetic analyses were conducted using Markov chain Monte Carlo (MCMC) approach to obtain the MCC tree using BEAST v.1.5.3.</p> <p>Results</p> <p>Among blood donors, from 158 HBsAg positive samples, eight 5.06% (n = 8) were positive for GBV-C and from 250 anti-HCV positive samples, 3.2%(n = 8) were positive for GBV-C. Also, 7.7% (n = 7) GBV-C positive samples were found among indigenous people from Leticia. A phylogenetic analysis revealed the presence of the following GBV-C genotypes among blood donors: 2a (41.6%), 1 (33.3%), 3 (16.6%) and 2b (8.3%). All genotype 1 sequences were found in co-infection with HBV and 4/5 sequences genotype 2a were found in co-infection with HCV. All sequences from indigenous people from Leticia were classified as genotype 3. The presence of GBV-C infection was not correlated with the sex (p = 0.43), age (p = 0.38) or origin (p = 0.17).</p> <p>Conclusions</p> <p>It was found a high frequency of GBV-C genotype 1 and 2 in blood donors. The presence of genotype 3 in indigenous population was previously reported from Santa Marta region in Colombia and in native people from Venezuela and Bolivia. This fact may be correlated to the ancient movements of Asian people to South America a long time ago.</p

Use of Transnational Services to Prevent Treatment Interruption in Tuberculosis-Infected Persons Who Leave the United States

A major problem resulting from interrupted tuberculosis (TB) treatment is the development of drug-resistant TB, including multidrug-resistant TB (MDR TB), a more deadly and costly-to-treat form of the disease. Global health systems are not equipped to diagnose and treat the current burden of MDR TB. TB-infected foreign visitors and temporary US residents who leave the country during treatment can experience treatment interruption and, thus, are at greater risk for drug-resistant TB. Using epidemiologic and demographic data, we estimated TB incidence among this group, as well as the proportion of patients referred to transnational care–continuity and management services during relocation; each year, ≈2,827 visitors and temporary residents are at risk for TB treatment interruption, 222 (8%) of whom are referred for transnational services. Scale up of transnational services for persons at high risk for treatment interruption is possible and encouraged because of potential health gains and reductions in healthcare costs for the United States and receiving countries

Postoperative <i>Staphylococcus aureus</i> Infections in Medicare Beneficiaries

<div><p><i>Staphylococcus aureus (S. aureus)</i> infections are important because of their increasing frequency, resistance to antibiotics, and high associated rates of disabilities and deaths. We examined the incidence and correlates of <i>S. aureus</i> infections following 219,958 major surgical procedures in a 5% random sample of fee-for-service Medicare beneficiaries from 2004–2007. Of these surgical patients, 0.3% had <i>S. aureus</i> infections during the hospitalizations when index surgical procedures were performed; and 1.7% and 2.3%, respectively, were hospitalized with infections within 60 days or 180 days following admissions for index surgeries. <i>S. aureus</i> infections occurred within 180 days in 1.9% of patients following coronary artery bypass graft surgery, 2.3% following hip surgery, and 5.9% following gastric or esophageal surgery. Of patients first hospitalized with any major infection reported during the first 180 days after index surgery, 15% of infections were due to <i>S. aureus</i>, 18% to other documented organisms, and no specific organism was reported on claim forms in 67%. Patient-level predictors of <i>S. aureus</i> infections included transfer from skilled nursing facilities or chronic hospitals and comorbid conditions (e.g., diabetes, congestive heart failure, chronic obstructive pulmonary disease, and chronic renal disease). In a logarithmic regression, elective index admissions with <i>S. aureus</i> infection stayed 130% longer than comparable patients without that infection. Within 180 days of the index surgery, 23.9% of patients with <i>S. aureus</i> infection and 10.6% of patients without this infection had died. In a multivariate logistic regression of death within 180 days of admission for the index surgery with adjustment for demographics, co-morbidities, and other risks, <i>S. aureus</i> was associated with a 42% excess risk of death. Due to incomplete documentation of organisms in Medicare claims, these statistics may underestimate the magnitude of <i>S. aureus</i> infection. Nevertheless, this study generated a higher rate of <i>S. aureus</i> infections than previous studies.</p></div

Descriptive characteristics and outcomes of study population of Medicare beneficiaries with selected index surgeries.

<p>Note: SA denotes <i>Staphylococcus aureus</i>, SNF denotes skilled nursing facility, ERSD denotes end stage renal disease, COPD denotes chronic obstructive pulmonary disease, Pts. denotes patients.</p>+<p>Note that the co-morbodities are not mutually exclusive dummy variables. A patient can have multiple comorbities so the sums of the groups exceed the total population.</p><p>Descriptive characteristics and outcomes of study population of Medicare beneficiaries with selected index surgeries.</p

Adjusted predictors of <i>S. aureus</i> infection within 180-days following surgery by type of index surgery based on incidence rate ratio (IRR).

<p>Note: <i>S. aureus</i> denotes <i>Staphylococcus aureus</i>. <i>S. aureus</i> infection refers to first hospitalization coinciding or following surgery of interest with discharge diagnoses including any ICD-9 code specific for infection due to <i>S. aureus</i>. Rehab denotes rehabilitation; SNF denotes skilled nursing facility; ESRD denotes end-stage renal disease; NEast denotes northeast; MidAtlan denotes mid-Atlantic; COPD denotes chronic obstructive pulmonary disease; n.a. denotes not applicable, vs. denotes versus. IRR>1 denotes factor associated with higher risk; IRR<1 denotes lower risk. Each IRR regression was based on all cross-tabulated non-zero cells. Based on log likelihood ratio Chi-squared, the overall regression tests for all six procedures plus the pooled group were highly significant (p<0.0001). *denotes p<0.05.</p><p>Adjusted predictors of <i>S. aureus</i> infection within 180-days following surgery by type of index surgery based on incidence rate ratio (IRR).</p

Average Changes in Cardiac Risk Factor Levels from Baseline Values by Program and Time Point.

<p>Statistical significance: N denotes not significant, *p<0.05, †p<0.01, ‡p<0.001.</p><p>MBMI is the Benson-Henry Mind/Body Medical Institute. Ornish is The Dean Ornish Program for Reversing Heart Disease. BMI is body mass index; SBP is systolic blood pressure; DBP is diastolic blood pressure; mmHg is millimeters mercury; HDL is high density lipoprotein; LDL is low density lipoprotein; METs are metabolic equivalents; mos. denotes months of follow-up; ANY denotes all participants at the follow-up time; FULL denotes participants with final (24 month) data; n denotes the number of participants in that column. Data are not shown for 24 mos. ANY, but the patients and results are very similar to those for 24 mos. FULL.</p><p>Average Changes in Cardiac Risk Factor Levels from Baseline Values by Program and Time Point.</p

Risk Factor Changes in the Two Lifestyle Modification Programs Based on Multivariable Regressions with Quadratic Terms for Time.

<p>Notes: MBMI denotes the Cardiac Wellness Program of the Benson-Henry Mind Body Institute; Ornish is The Dean Ornish Program for Reversing Heart Disease. BMI denotes body mass index; LDL denotes low density lipoprotein; HDL denotes high density lipoprotein; SBP denotes systolic blood pressure; DBP denotes diastolic blood pressure.</p