A huge intraductal papillary mucinous carcinoma of the bile duct treated by right trisectionectomy with caudate lobectomy

<p>Abstract</p> <p>Background</p> <p>Because intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) is believed to show a better clinical course than non-papillary biliary neoplasms, it is important to make a precise diagnosis and to perform complete surgical resection.</p> <p>Case presentation</p> <p>We herein report a case of malignant IPMN-B treated by right trisectionectomy with caudate lobectomy and extrahepatic bile duct resection. Radiologic images showed marked dilatation of the left medial sectional bile duct (B4) resulting in a bulky cystic mass with multiple internal papillary projections. Duodenal endoscopic examination demonstrated very patulous ampullary orifice with mucin expulsion and endoscopic retrograde cholangiogram confirmed marked cystic dilatation of B4 with luminal filling defects. These findings suggested IPMN-B with malignancy potential. The functional volume of the left lateral section was estimated to be 45%. A planned extensive surgery was successfully performed. The remnant bile ducts were also dilated but had no macroscopic intraluminal tumorous lesion. The histopathological examination yielded the diagnosis of mucin-producing oncocytic intraductal papillary carcinoma of the bile duct with poorly differentiated carcinomas showing neuroendocrine differentiation. The tumor was 14.0 × 13.0 cm-sized and revealed no stromal invasiveness. Resection margins of the proximal bile duct and hepatic parenchyma were free of tumor cell. The patient showed no postoperative complication and was discharged on 10^thpostoperative date. He has been regularly followed at outpatient department with no evidence of recurrence.</p> <p>Conclusion</p> <p>Considering a favorable prognosis of IPMN-B compared to non-papillary biliary neoplasms, this tumor can be a good indication for aggressive surgical resection regardless of its tumor size.</p

Echinacea purpurea Significantly Induces Cytochrome P450 3A Activity but Does Not Alter Lopinavir‐Ritonavir Exposure in Healthy Subjects

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90291/1/phco.30.8.797.pd

Phase 1b study of pegylated arginine deiminase (ADI-PEG 20) plus Pembrolizumab in advanced solid cancers

[[abstract]]Background Pegylated arginine deiminase (ADI-PEG 20) is a metabolism-based strategy that depletes arginine, resulting in tumoral stress and cytotoxicity. Preclinically, ADI-PEG 20 modulates T-cell activity and enhances the therapeutic efficacy of programmed death-1 (PD-1) inhibition. Methods A phase 1b study, including a dose-escalation cohort and an expansion cohort, was undertaken to explore the effects of ADI-PEG 20 in combination with pembrolizumab, an anti-PD-1 antibody, for safety, pharmacodynamics, and response. CD3 levels and programmed death-ligand 1 (PD-L1) expression were assessed in paired biopsies collected prior to and after ADI-PEG 20 treatment but before pembrolizumab. Results Twenty-five patients, nine in the dose-escalation cohort and sixteen in the expansion cohort, were recruited. Treatment was feasible with adverse events consistent with those known for each agent, except for Grade 3/4 neutropenia which was higher than expected, occurring in 10/25 (40%) patients. Mean arginine levels were suppressed for 1-3 weeks, but increased gradually. CD3(+) T cells increased in 10/12 (83.3%) subjects following ADI-PEG 20 treatment, including in three partial responders (p = .02). PD-L1 expression was low and increased in 3/10 (30%) of subjects. Partial responses occurred in 6/25 (24%) heavily pretreated patients, in both argininosuccinate synthetase 1 proficient and deficient subjects. Conclusions The immunometabolic combination was safe with the caveat that the incidence of neutropenia might be increased compared with either agent alone. ADI-PEG 20 treatment increased T cell infiltration in the low PD-L1 tumor microenvironment. The recommended phase 2 doses are 36 mg/m(2) weekly for ADI-PEG 20 and 200 mg every 3 weeks for pembrolizumab

Quantum Criticality in Heavy Fermion Metals

Quantum criticality describes the collective fluctuations of matter undergoing a second-order phase transition at zero temperature. Heavy fermion metals have in recent years emerged as prototypical systems to study quantum critical points. There have been considerable efforts, both experimental and theoretical, which use these magnetic systems to address problems that are central to the broad understanding of strongly correlated quantum matter. Here, we summarize some of the basic issues, including i) the extent to which the quantum criticality in heavy fermion metals goes beyond the standard theory of order-parameter fluctuations, ii) the nature of the Kondo effect in the quantum critical regime, iii) the non-Fermi liquid phenomena that accompany quantum criticality, and iv) the interplay between quantum criticality and unconventional superconductivity.Comment: (v2) 39 pages, 8 figures; shortened per the editorial mandate; to appear in Nature Physics. (v1) 43 pages, 8 figures; Non-technical review article, intended for general readers; the discussion part contains more specialized topic

Constraints on Nucleon Decay via "Invisible" Modes from the Sudbury Neutrino Observatory

Data from the Sudbury Neutrino Observatory have been used to constrain the lifetime for nucleon decay to ``invisible'' modes, such as n -> 3 nu. The analysis was based on a search for gamma-rays from the de-excitation of the residual nucleus that would result from the disappearance of either a proton or neutron from O16. A limit of tau_inv > 2 x 10^{29} years is obtained at 90% confidence for either neutron or proton decay modes. This is about an order of magnitude more stringent than previous constraints on invisible proton decay modes and 400 times more stringent than similar neutron modes.Comment: Update includes missing efficiency factor (limits change by factor of 2) Submitted to Physical Review Letter

Identifying significant genetic regulatory networks in the prostate cancer from microarray data based on transcription factor analysis and conditional independency

<p>Abstract</p> <p>Background</p> <p>Prostate cancer is a world wide leading cancer and it is characterized by its aggressive metastasis. According to the clinical heterogeneity, prostate cancer displays different stages and grades related to the aggressive metastasis disease. Although numerous studies used microarray analysis and traditional clustering method to identify the individual genes during the disease processes, the important gene regulations remain unclear. We present a computational method for inferring genetic regulatory networks from micorarray data automatically with transcription factor analysis and conditional independence testing to explore the potential significant gene regulatory networks that are correlated with cancer, tumor grade and stage in the prostate cancer.</p> <p>Results</p> <p>To deal with missing values in microarray data, we used a K-nearest-neighbors (KNN) algorithm to determine the precise expression values. We applied web services technology to wrap the bioinformatics toolkits and databases to automatically extract the promoter regions of DNA sequences and predicted the transcription factors that regulate the gene expressions. We adopt the microarray datasets consists of 62 primary tumors, 41 normal prostate tissues from Stanford Microarray Database (SMD) as a target dataset to evaluate our method. The predicted results showed that the possible biomarker genes related to cancer and denoted the androgen functions and processes may be in the development of the prostate cancer and promote the cell death in cell cycle. Our predicted results showed that sub-networks of genes SREBF1, STAT6 and PBX1 are strongly related to a high extent while ETS transcription factors ELK1, JUN and EGR2 are related to a low extent. Gene SLC22A3 may explain clinically the differentiation associated with the high grade cancer compared with low grade cancer. Enhancer of Zeste Homolg 2 (EZH2) regulated by RUNX1 and STAT3 is correlated to the pathological stage.</p> <p>Conclusions</p> <p>We provide a computational framework to reconstruct the genetic regulatory network from the microarray data using biological knowledge and constraint-based inferences. Our method is helpful in verifying possible interaction relations in gene regulatory networks and filtering out incorrect relations inferred by imperfect methods. We predicted not only individual gene related to cancer but also discovered significant gene regulation networks. Our method is also validated in several enriched published papers and databases and the significant gene regulatory networks perform critical biological functions and processes including cell adhesion molecules, androgen and estrogen metabolism, smooth muscle contraction, and GO-annotated processes. Those significant gene regulations and the critical concept of tumor progression are useful to understand cancer biology and disease treatment.</p

Capsid and Infectivity in Virus Detection

The spectacular achievements and elegance of viral RNA analyses have somewhat obscured the importance of the capsid in transmission of viruses via food and water. The capsid’s essential roles are protection of the RNA when the virion is outside the host cell and initiation of infection when the virion contacts a receptor on an appropriate host cell. Capsids of environmentally transmitted viruses are phenomenally durable. Fortuitous properties of the capsid include antigenicity, isoelectric point(s), sometimes hemagglutination, and perhaps others. These can potentially be used to characterize capsid changes that cause or accompany loss of viral infectivity and may be valuable in distinguishing native from inactivated virus when molecular detection methods are used

Effects of ambient air pollution on functional status in patients with chronic congestive heart failure: a repeated-measures study

<p>Abstract</p> <p>Background</p> <p>Studies using administrative data report a positive association between ambient air pollution and the risk of hospitalization for congestive heart failure (HF). Circulating levels of B-type natriuretic peptide (BNP) are directly associated with cardiac hemodynamics and symptom severity in patients with HF and, therefore, serves as a marker of functional status. We tested the hypothesis that BNP levels would be positively associated with short-term changes in ambient pollution levels among 28 patients with chronic stable HF and impaired systolic function.</p> <p>Methods</p> <p>BNP was measured in whole blood at 0, 6, and 12 weeks. We used linear mixed models to evaluate the association between fine particulate matter (PM_2.5), carbon monoxide, sulfur dioxide, nitrogen dioxide, ozone, and black carbon and log(BNP). Lags of 0 to 3 days were considered in separate models. We calculated the intraclass correlation coefficient and within-subject coefficient of variation as measures of reproducibility.</p> <p>Results</p> <p>We found no association between any pollutant and measures of BNP at any lag. For example, a 10 μg/m³increase in PM_2.5was associated with a 0.8% (95% CI: -16.4, 21.5; p = 0.94) increase in BNP on the same day. The within-subject coefficient of variation was 45% on the natural scale and 9% on the log scale.</p> <p>Conclusion</p> <p>These results suggest that serial BNP measurements are unlikely to be useful in a longitudinal study of air pollution-related acute health effects. The magnitude of expected ambient air pollution health effects appears small in relation to the considerable within-person variability in BNP levels in this population.</p

Prevalence and predictors of complementary and alternative medicine use among people with coronary heart disease or at risk for this in the sixth Tromsø study: a comparative analysis using protection motivation theory

Background Engagement in healthy lifestyle behaviors, such as healthy diet and regular physical activity, are known to reduce the risk of developing coronary heart disease (CHD). Complementary and alternative medicine (CAM) is known to be associated with having a healthy lifestyle. The primary aim of this study was to examine the prevalence and predictors of CAM use in CHD patients, and in those without CHD but at risk for developing CHD, using Protection Motivation Theory (PMT) as a guiding conceptual framework. Method Questionnaire data were collected from 12,981 adult participants in the cross-sectional sixth Tromsø Study (2007–8). Eligible for analyses were 11,103 participants who reported whether they had used CAM or not. Of those, 830 participants reported to have or have had CHD (CHD group), 4830 reported to have parents, children or siblings with CHD (no CHD but family risk), while 5443 reported no CHD nor family risk of CHD. We first compared the patterns of CAM use in each group, and then examined the PMT predictors of CAM use. Health vulnerability from the threat appraisal process of PMT was assessed by self-rated health and expectations for future health. Response efficacy from the coping appraisal process of PMT was assessed as preventive health beliefs and health behavior frequency. Results Use of CAM was most commonly seen in people with no CHD themselves, but family risk of developing CHD (35.8%), compared to people already diagnosed with CHD (30.2%) and people with no CHD nor family risk (32.1%). All four of the PMT factors; self-rated health, expectations for future health, preventive health beliefs, and the health behavior index – were predictors for CAM use in the no CHD but family risk group. Conclusion These findings suggest that people use CAM in response to a perceived risk of developing CHD, and to prevent disease and to maintain health

Use of generic medicines in Latvia : Awareness, opinions and experiences of the population

Funding Information: Funding was provided by EEA Financial Mechanism and Latvian state (award number 2012.EEZ/DAP/MIC/183). The project is financially supported by Iceland, Liechtenstein and Norway. Publisher Copyright: © 2019 The Author(s).Background: To stimulate use of generic medicines a combination of supply and demand side mechanisms are employed in the Latvian reimbursement system. It is reported that patients have high out-of-pocket pharmaceutical spending and that they overpay by not choosing generic medicines. Patient preferences may be an important obstacle in implementing generic policy. Objective of this study was to assess awareness, opinions and experience of the Latvian population regarding use of generic medicines. Methods: Survey of representative sample of the population of Latvia (n = 1005) aged 18-74 was conducted in March 2015. The survey was distributed in Latvian and Russian languages using Computer Assisted Web Interviews. Associations between experience with generic medicines, preference for medicines, and sociodemographic variables were tested with Pearson Chi-square statistics. Associations between the previous experience and information given by different sources versus choice between medicines were tested with Spearman's correlation test. Results: 72.3% of the population were informed about generic medicines. Men (66.9%) and respondents with primary or secondary education (58.3%; 69.3%) were less informed compared to total (72.3%). From those who recalled using generic medicines (n = 441), 94.4% evaluated their experience as positive or neutral. Despite this, only 21% of the population would opt for generic medicines. The strongest preference for brand-name medicines was in the age group > 55 (40.5%). Opinion of a physician was the most important factor when choosing between generic and brand-name medicines (88.7%). The more positive the information provided by general practitioners, physician specialists, pharmacists, family members, friends and internet is perceived, the more likely respondents are to choose generic medicines (p < 0.001). Conclusion: This study demonstrates that people in Latvia are aware of generic medicines but only a minority of the population would choose them when presented with a choice. It is therefore important that health care professionals provide objective and unbiased information about generic medicines to their patients. Interventions should aim to reach groups that are less informed and to improve providers' understanding and communication with patients about generics.publishersversionPeer reviewe