Potential impact of Helicobacter pylori-related metabolic syndrome on upper and lower gastrointestinal tract oncogenesis

Both Helicobacter pylori infection and metabolic syndrome present significant global public health burdens. Metabolic syndrome is closely related to insulin resistance, the major underlying mechanism responsible for metabolic abnormalities, and Helicobacter pylori infection has been proposed to be a contributing factor. There is growing evidence for a potential association between Helicobacter pylori infection and insulin resistance, metabolic syndrome and related morbidity, including abdominal obesity, type 2 diabetes mellitus, dyslipidemia, hypertension, all of which increase mortality related to cardio-cerebrovascular disease, neurodegenerative disorders, nonalcoholic fatty liver disease and malignancies. More specifically, insulin resistance, metabolic syndrome and hyperinsulinemia have been associated with upper and lower gastrointestinal tract oncogenesis. Apart from cardio-cerebrovascular, degenerative diseases and nonalcoholic fatty liver disease, a number of studies claim that Helicobacter pylori infection is implicated in metabolic syndrome-related Barrett's esophagus and esophageal adenocarcinoma development, gastric and duodenal ulcers and gastric oncogenesis as well as lower gastrointestinal tract oncogenesis. This review summarizes evidence on the potential impact of Helicobacter pylori-related metabolic syndrome on gastroesophageal reflux disease-Barrett's esophagus-esophageal adenocarcinoma, gastric atrophy-intestinal metaplasia-dysplasia-gastric cancer and colorectal adenoma-dysplasia-colorectal cancer sequences. Helicobacter pylori eradication might inhibit these oncogenic processes, and thus further studies are warranted.     

Generalized partially linear single‐index model for zero‐inflated count data

Count data often arise in biomedical studies, while there could be a special feature with excessive zeros in the observed counts. The zero‐inflated Poisson model provides a natural approach to accounting for the excessive zero counts. In the semiparametric framework, we propose a generalized partially linear single‐index model for the mean of the Poisson component, the probability of zero, or both. We develop the estimation and inference procedure via a profile maximum likelihood method. Under some mild conditions, we establish the asymptotic properties of the profile likelihood estimators. The finite sample performance of the proposed method is demonstrated by simulation studies, and the new model is illustrated with a medical care dataset. Copyright © 2014 John Wiley & Sons, Ltd.     

Early neuroinflammation is associated with lower amyloid and tau levels in cognitively normal older adults

CNS inflammation is a key factor in Alzheimer’s Disease (AD), but its relation to pathological Aβ, tau, and APOE4 is poorly understood, particularly prior to the onset of cognitive symptoms. To better characterize early relationships between inflammation, APOE4, and AD pathology, we assessed correlations between cerebrospinal fluid (CSF) inflammatory markers and brain levels of Aβ and tau in cognitively normal older adults.Each participant received a lumbar puncture to collect and quantify CSF levels of TNFα, IL-6, IL-8, and IL-10, a T1-weighted MRI, and PET scanning with [¹⁸F]flortaucipir (FTP; n = 57), which binds to tau tangles and/or [¹⁸F]florbetapir (FBP; n = 58), which binds to Aβ. Parallel voxelwise regressions assessed relationships between each CSF inflammatory marker and FTP and FBP SUVR, as well as APOE4*CSF inflammation interactions.Unexpectedly, we detected significant negative associations between regional Aβ and tau PET uptake and CSF inflammatory markers. For Aβ PET, we detected negative associations with CSF IL-6 and IL-8 in regions known to show early accumulation of Aβ (i.e. lateral and medial frontal lobes). For tau PET, negative relationships were observed with CSF TNFα and IL-8, predominantly in regions known to exhibit early tau accumulation (i.e. medial temporal lobe). In subsequent analyses, significant interactions between APOE4 status and IL-8 on Aβ and tau PET levels were observed in spatially distinct regions from those showing CSF–Aβ/tau relationships.Results from the current cross-sectional study support previous findings that neuroinflammation may be protective against AD pathology at a given stage of the disease, and extend these findings to a cognitively normal aging population. This study provides new insight into a dynamic relationship between neuroinflammation and AD pathology and may have implications for whom and when neuroinflammatory therapies may be appropriate.     

Detection and genotyping of human papillomavirus by real-time PCR assay

BackgroundDiagnosis of human papillomavirus (HPV) disease remains a challenge due to several factors related to the cost, the workload of available commercial assays to detect and genotype HPV, and to the low prevalence of infected patients.ObjectiveOur study aimed to develop a real-time PCR, based on SPF10 primers, in order to combine HPV-DNA detection and genotype identification avoiding the negative samples.Study designValidation of SYBR-green based SPF10 real-time PCR on HPV-DNA plasmids followed by the investigation of the viral status in 92 samples from oropharyngeal (94%) cutaneous biopsies (3%) and anal smears (3%) which had previously been HPV-genotyped by LiPA hybridization. In-house HPV viral loads were performed to evaluate the SPF10 real-time PCR sensitivity.ResultsData showed that 100% of HPV plasmids, assessable by LiPA hybridization, were detected and genotyped appropriately after SPF10 real-time PCR assays. These results defined a range of melting temperature peaks for HPV positivity by real-time PCR. The efficient determination of the presence of HPV-DNA by SPF10 real-time PCR was validated for 98% of clinical samples compared to commercial method. Discordant results were due to a low HPV-DNA amount and to a supplementary HPV genotype identified. The SPF10 real-time PCR sensitivity was evaluated between 1 and 10 copies/10³ cells using in-house HPV (6, 11 and 16) viral load assays.ConclusionThe real-time PCR method was efficient in combining screening and genotyping of HPV-DNA. Cost and workload reduction by SPF10 real-time PCR approach may facilitate earlier diagnosis and clinical management of HPV infected patients.     

The outcome and long-term follow-up of 94 patients with recurrent and refractory Clostridium difficile infection using single to multiple fecal microbiota transplantation via retention enema

Clostridium difficile infection (CDI) is one of the most frequent causes of healthcare-associated infections, and its rates are also increasing in the community. The management of CDI has become a major challenge, given growing rates of recurrences and failures with standard antibiotic therapy. Mounting evidence suggests that fecal microbiota transplantation (FMT) may be effective; however, as there is a paucity of data with regard to repeat FMT for primary non-response to this treatment, this study examined the outcome of multiple FMTs for recurrent CDI. Case records were reviewed for 94 patients who underwent FMT via retention enema for recurrent or refractory CDI during the period 2008–2012. Demographic information, treatment data, and clinical resolution rates were examined for single FMT and cumulative resolution was assessed for multiple FMTs in the context of ongoing symptoms. The cumulative clinical resolution following four or more FMTs was 86 %. When antibiotic therapy was used between FMTs, the clinical resolution rate increased to 92 %. There were no reported adverse events and no patients who were cured with FMT had further episodes of CDI at 6–24 months follow-up. Multiple FMTs administered through enemas is an effective, safe, and simple therapy for the management of recurrent or refractory CDI.     

Hepatitis B Virus Core Promoter Mutations in Patients With Chronic Hepatitis B and Hepatocellular Carcinoma in Bucharest,Romania

Background:

Accurate and personalized molecular virological diagnosis of hepatitis B virus (HBV) infection is crucial for individualized selection of patients for antiviral therapy in Romania.

Objectives:

We aimed to investigate HBV mutations in Romanian patients with chronic HBV infection, also to match HBV genotypes with HBV mutations identified and clinical outcomes.

Patients and Methods:

This was a cross-sectional study. A total of 484 Romanian patients with chronic HBV infection and hepatocellular carcinoma (HCC) were investigated. This was performed in Fundeni Clinical Institute, Bucharest, Romania during January 2005 to August 2010. HBsAg positive patients with chronic HBV infection admitted to Fundeni Clinical Institute were randomly enrolled in the study. Analysis was performed in the Centre for Immunogenetics and Virology, Fundeni Clinical Institute, Bucharest, Romania. Indirect diagnosis was performed with enhanced chemiluminescence method using Architect i2000SR and HBV-DNA was quantified with COBAS TaqMan HBV PCR. Direct sequencing of the PCR-products was performed with the PCR-product sequencing kit. HBV genotyping was performed with INNO-LiPA DR Amplification and INNO-LiPA HBV precore-core.

Results:

We detected two HBV genotypes; A (8.1%) and D (60.5%), and a mixture of genotypes A and D (31.4%) (P < 0.001). Basal core promoter (BCP) A1762T/G1764A and precore (PC) G1896A mutations were detected in these Romanian patients with chronic HBV infection. HBV chronic carriers had mainly genotype D (54.4%) and HBV WT (64.0%). BCP A1762T, G1764A and PC G1896A were significantly associated with HCC-tissue HBV sequencing (75.3%) (P < 0.001). PC G1896A alone was detected in HCC-serum HBV sequencing group (66.7%).

Conclusions:

Genotype D was the main genotype detected in Romanian patients with chronic HBV infection. Genotype D presented both BCP and PC mutations more frequently.