Association between Selected Oral Pathogens and Gastric Precancerous Lesions

We examined whether colonization of selected oral pathogens is associated with gastric precancerous lesions in a cross-sectional study. A total of 119 participants were included, of which 37 were cases of chronic atrophic gastritis, intestinal metaplasia, or dysplasia. An oral examination was performed to measure periodontal indices. Plaque and saliva samples were tested with real-time quantitative PCR for DNA levels of pathogens related to periodontal disease (Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola, Actinobacillus actinomycetemcomitans) and dental caries (Streptococcus mutans and S. sobrinus). There were no consistent associations between DNA levels of selected bacterial species and gastric precancerous lesions, although an elevated but non-significant odds ratio (OR) for gastric precancerous lesions was observed in relation to increasing colonization of A. actinomycetemcomitans (OR = 1.36 for one standard deviation increase, 95% Confidence Interval = 0.87–2.12), P. gingivalis (OR = 1.12, 0.67–1.88) and T. denticola (OR = 1.34, 0.83–2.12) measured in plaque. To assess the influence of specific long-term infection, stratified analyses by levels of periodontal indices were conducted. A. actinomycetemcomitans was significantly associated with gastric precancerous lesions (OR = 2.51, 1.13–5.56) among those with ≥ median of percent tooth sites with PD≥3 mm, compared with no association among those below the median (OR = 0.86, 0.43–1.72). A significantly stronger relationship was observed between the cumulative bacterial burden score of periodontal disease-related pathogens and gastric precancerous lesions among those with higher versus lower levels of periodontal disease indices (p-values for interactions: 0.03–0.06). Among individuals with periodontal disease, high levels of colonization of periodontal pathogens are associated with an increased risk of gastric precancerous lesions

Predictive value of pathological and immunohistochemical parameters for axillary lymph node metastasis in breast carcinoma

<p>Abstract</p> <p>Background/Objective</p> <p>While several prognostic factors have been identified in breast carcinoma, the clinical outcome remains hard to predict for individual patients. Better predictive markers are needed to help guide difficult treatment decisions. Axillary lymph node metastasis (ALNM) is one of the most important prognostic determinants in breast carcinoma; however, the reasons why tumors vary in their capability to result in axillary metastasis remain unclear. Identifying breast carcinoma patients at risk for ALNM would improve treatment planning. This study aimed to identify the factors associated with ALNM in breast carcinoma, with particular emphasis on basal-like phenotype.</p> <p>Methods</p> <p>Breast carcinoma patients (n = 210) who underwent breast conserving surgery and axillary lymph node dissection (ALND) (level I and II) or modified radical mastectomy were included in this study. Pathological and immunohistochemical data including individual receptor/gene status was collected for analysis. The basal phenotype status was ascertained using the basal cytokeratin markers CK5, CK14, CK17 and EGFR.</p> <p>Results</p> <p>ALNM was found in 55% (n = 116) of the patients. On univariate analysis, multicentric disease, large tumor size (>2 cm), vascular and lymphatic invasion, epithelial hyperplasia, necrosis, in situ carcinoma and perineural invasion were associated with higher risk for ALNM, whereas CK5, CK14, EGFR positivity and basal-like tumor type were associated with lower risk. On multivariate analysis, CK5 positivity (OR 0.003, 95%CI 0.000-0.23, p = 0.009) and lymphatic/vascular invasion (OR 17.94, 95%CI 4.78-67.30, p < 0.001) were found to be independent predictors.</p> <p>Conclusions</p> <p>Although the value of complete ALND has been questioned in invasive breast cancer patients, treatment decisions for breast carcinoma have been influenced by many parameters, including lymph node status. Since histopathologic characteristics and expression of biological markers varies among the same histologic subtypes of breast carcinoma, specific clinical and histopathologic features of the primary tumor and ALN status like sentinel node might be used to tailor the loco-regional and systemic treatment in different clinical settings.</p

Retrieval of Context-Associated Memory is Dependent on the Cav3.2 T-Type Calcium Channel

Among all voltage-gated calcium channels, the T-type Ca2+ channels encoded by the Cav3.2 genes are highly expressed in the hippocampus, which is associated with contextual, temporal and spatial learning and memory. However, the specific involvement of the Cav3.2 T-type Ca2+ channel in these hippocampus-dependent types of learning and memory remains unclear. To investigate the functional role of this channel in learning and memory, we subjected Cav3.2 homozygous and heterozygous knockout mice and their wild-type littermates to hippocampus-dependent behavioral tasks, including trace fear conditioning, the Morris water-maze and passive avoidance. The Cav3.2 −/− mice performed normally in the Morris water-maze and auditory trace fear conditioning tasks but were impaired in the context-cued trace fear conditioning, step-down and step-through passive avoidance tasks. Furthermore, long-term potentiation (LTP) could be induced for 180 minutes in hippocampal slices of WTs and Cav3.2 +/− mice, whereas LTP persisted for only 120 minutes in Cav3.2 −/− mice. To determine whether the hippocampal formation is responsible for the impaired behavioral phenotypes, we next performed experiments to knock down local function of the Cav3.2 T-type Ca2+ channel in the hippocampus. Wild-type mice infused with mibefradil, a T-type channel blocker, exhibited similar behaviors as homozygous knockouts. Taken together, our results demonstrate that retrieval of context-associated memory is dependent on the Cav3.2 T-type Ca2+ channel

Molecular dynamics simulations and drug discovery

This review discusses the many roles atomistic computer simulations of macromolecular (for example, protein) receptors and their associated small-molecule ligands can play in drug discovery, including the identification of cryptic or allosteric binding sites, the enhancement of traditional virtual-screening methodologies, and the direct prediction of small-molecule binding energies. The limitations of current simulation methodologies, including the high computational costs and approximations of molecular forces required, are also discussed. With constant improvements in both computer power and algorithm design, the future of computer-aided drug design is promising; molecular dynamics simulations are likely to play an increasingly important role