Experience with adjuvant chemotherapy for pseudomyxoma peritonei secondary to mucinous adenocarcinoma of the appendix with oxaliplatin/fluorouracil/leucovorin (FOLFOX4)

<p>Abstract</p> <p>Background</p> <p>Pseudomyxoma peritonei (PMP) is a rare condition characterized by mucinous tumors, disseminated intra-peritoneal implants, and mucinous ascites. So far its diagnosis remains challenging to most clinicians.</p> <p>Case presentation</p> <p>A 55-year-old male patient had suffered from acute onset of abdominal pain and abdominal distension for one day prior to his admission. Physical examination revealed tenderness over the right lower quadrant of the abdomen without diffuse muscle guarding. A large amount of ascites was identified by abdominal computed tomography (CT) scan. Paracentesis showed the appearance of sticky mucinous ascites. He underwent laparotomy under the impression of pseudomyxoma peritonei. There was a lot of mucinous ascites, one appendiceal tumor and multiple peritoneal implants disseminated from the subphrenic space to the recto-vesicle pouch. Pseudomyxoma Peritonei caused by mucinous adenocarcinoma of appendiceal origin, was confirmed by histopathology. We performed an excision of the appendiceal tumor combined with copious irrigation and debridement. After the operation, he received 10 cycles of systemic chemotherapy with FOLFOX4 regimen, without specific morbidity. Follow-up of abdominal CT and colonoscopy at post-operative 17 months showed excellent response without evidence of local recurrence or distal metastasis. He made an uneventful recovery (up to the present) for 21 months after the operation.</p> <p>Conclusion</p> <p>This case report emphasizes the possible new role of systemic chemotherapy in the treatment of patients with this rare clinical syndrome.</p

Small noncoding RNA modulates japanese encephalitis virus replication and translation in trans

<p>Abstract</p> <p>Background</p> <p>Sequence and structural elements in the 3'-untranslated region (UTR) of Japanese encephalitis virus (JEV) are known to regulate translation and replication. We previously reported an abundant accumulation of small subgenomic flaviviral RNA (sfRNA) which is collinear with the highly conserved regions of the 3'-UTR in JEV-infected cells. However, function of the sfRNA in JEV life cycle remains unknown.</p> <p>Results</p> <p>Northern blot and real-time RT-PCR analyses indicated that the sfRNA becomes apparent at the time point at which minus-strand RNA (antigenome) reaches a plateau suggesting a role for sfRNA in the regulation of antigenome synthesis. Transfection of minus-sense sfRNA into JEV-infected cells, in order to counter the effects of plus-sense sfRNA, resulted in higher levels of antigenome suggesting that the presence of the sfRNA inhibits antigenome synthesis. <it>Trans</it>-acting effect of sfRNA on JEV translation was studied using a reporter mRNA containing the luciferase gene fused to partial coding regions of JEV and flanked by the respective JEV UTRs. <it>In vivo </it>and <it>in vitro </it>translation revealed that sfRNA inhibited JEV translation.</p> <p>Conclusions</p> <p>Our results indicate that sfRNA modulates viral translation and replication <it>in trans</it>.</p

Mutation analysis of the cross-reactive epitopes of Japanese encephalitis virus envelope glycoprotein

Group and serocomplex cross-reactive epitopes have been identified in the envelope (E) protein of several flaviviruses and have proven critical in vaccine and diagnostic antigen development. Here, we performed site-directed mutagenesis across the E gene of a recombinant expression plasmid that encodes the Japanese encephalitis virus (JEV) premembrane (prM) and E proteins and produces JEV virus-like particles (VLPs). Mutations were introduced at I135 and E138 in domain I; W101, G104, G106 and L107 in domain II; and T305, E306, K312, A315, S329, S331, G332 and D389 in domain III. None of the mutant JEV VLPs demonstrated reduced activity to the five JEV type-specific mAbs tested. Substitutions at W101, especially W101G, reduced reactivity dramatically with all of the flavivirus group cross-reactive mAbs. The group and JEV serocomplex cross-reactive mAbs examined recognized five and six different overlapping epitopes, respectively. Among five group cross-reactive epitopes, amino acids located in domains I, II and III were involved in one, five and three epitopes, respectively. Recognition by six JEV serocomplex cross-reactive mAbs was reduced by amino acid substitutions in domains II and III. These results suggest that amino acid residues located in the fusion loop of E domain II are the most critical for recognition by group cross-reactive mAbs, followed by residues of domains III and I. The amino acid residues of both domains II and III of the E protein were shown to be important in the binding of JEV serocomplex cross-reactive mAbs

Identification of the genetic determinants of Salmonella enterica serotype Typhimurium that may regulate the expression of the type 1 fimbriae in response to solid agar and static broth culture conditions

<p>Abstract</p> <p>Background</p> <p>Type 1 fimbriae are the most commonly found fimbrial appendages on the outer membrane of <it>Salmonella enterica </it>serotype Typhimurium. Previous investigations indicate that static broth culture favours <it>S</it>. Typhimurium to produce type 1 fimbriae, while non-fimbriate bacteria are obtained by growth on solid agar media. The phenotypic expression of type 1 fimbriae in <it>S</it>. Typhimurium is the result of the interaction and cooperation of several genes in the <it>fim </it>gene cluster. Other gene products that may also participate in the regulation of type 1 fimbrial expression remain uncharacterized.</p> <p>Results</p> <p>In the present study, transposon insertion mutagenesis was performed on <it>S</it>. Typhimurium to generate a library to screen for those mutants that would exhibit different type 1 fimbrial phenotypes than the parental strain. Eight-two mutants were obtained from 7,239 clones screened using the yeast agglutination test. Forty-four mutants produced type 1 fimbriae on both solid agar and static broth media, while none of the other 38 mutants formed type 1 fimbriae in either culture condition. The flanking sequences of the transposons from 54 mutants were cloned and sequenced. These mutants can be classified according to the functions or putative functions of the open reading frames disrupted by the transposon. Our current results indicate that the genetic determinants such as those involved in the fimbrial biogenesis and regulation, global regulators, transporter proteins, prophage-derived proteins, and enzymes of different functions, to name a few, may play a role in the regulation of type 1 fimbrial expression in response to solid agar and static broth culture conditions. A complementation test revealed that transforming a recombinant plasmid possessing the coding sequence of a NAD(P)H-flavin reductase gene <it>ubiB </it>restored an <it>ubiB </it>mutant to exhibit the type 1 fimbrial phenotype as its parental strain.</p> <p>Conclusion</p> <p>Genetic determinants other than the <it>fim </it>genes may involve in the regulation of type 1 fimbrial expression in <it>S</it>. Typhimurium. How each gene product may influence type 1 fimbrial expression is an interesting research topic which warrants further investigation.</p

Partially Neutralizing Potency against Emerging Genotype I Virus among Children Received Formalin- Inactivated Japanese Encephalitis Virus Vaccine

Background: Genotype I (GI) Japanese encephalitis virus (JEV) that replaced GIII virus has become the dominant circulating virus in Asia. Currently, all registered live and inactivated JEV vaccines are derived from genotype III viruses. In Taiwan, the compulsory JEV vaccination policy recommends that children receives four doses of formalin-inactivated Nakayama (GIII) JEV vaccine. Methodology/Principal Findings: To evaluate the influence of genotype replacement on the post-vaccination viral neutralizing ability by GIII and GI viruses, the small panel of vaccinated-children serum specimens was assembled, and the reciprocal 50% plaque-reduction neutralizing antibody titers (PRNT50) were measured against Nakayama vaccine strain, CJN GIII human brain isolate and TC2009-1 GI mosquito isolate. The seropositivity rate (PRNT50$1:10) and geometric mean titers (GMT) against the TC2009-1 virus were the lowest among the three viruses. The protective threshold against the CJN and TC2009-1 viruses could only be achieved when the GMT against Nakayama virus was$1:20 or $1:80, respectively. Using undiluted vaccinees’ sera, the enhancement of JEV infection in K562 cells was observed in some low or non-neutralizing serum specimens. Conclusions/Significance: Our preliminary study has shown that neutralizing antibodies, elicited by the mouse brainderived and formalin-inactivated JEV Nakayama vaccine among a limited number of vaccinees, have reduced neutralizing capacity against circulating GI virus, but more detailed studies are needed to address the potential impact on the future vaccine policy

Patients Infected with CRF07_BC Have Significantly Lower Viral Loads than Patients with HIV-1 Subtype B: Mechanism and Impact on Disease Progression

The circulating recombinant form (CRF) 07_BC is the most prevalent HIV-1 strain among injection drug users (IDUs) in Taiwan. It contains a 7 amino-acid deletion in its p6gag. We conducted a cohort study to compare viral loads and CD4 cell count changes between patients infected with subtype B and CRF07_BC and to elucidate its mechanism. Twenty-one patients infected with CRF07_BC and 59 patients with subtype B were selected from a cohort of 667 HIV-1/AIDS patients whom have been followed up for 3 years. Generalized estimated equation was used to analyze their clinical data and the results showed that patients infected with CRF07_BC had significantly lower viral loads (about 58,000 copies per ml less) than patients with subtype B infection (p = 0.002). The replicative capacity of nine CRF07_BC and four subtype B isolates were compared and the results showed that the former had significantly lower replicative capacity than the latter although all of them were CCR5- tropic and non-syncytium inducing viruses. An HIV-1-NL4-3 mutant virus which contains a 7 amino-acid deletion in p6gag (designated as 7d virus) was generated and its live cycle was investigated. The results showed that 7d virus had significantly lower replication capacity, poorer protease-mediated processing and viral proteins production. Electron microscopic examination of cells infected with wild-type or 7d virus demonstrated that the 7d virus had poorer and slower viral maturation processes: more viruses attached to the cell membrane and higher proportion of immature virions outside the cells. The interaction between p6gag and Alix protein was less efficient in cells infected with 7d virus. In conclusion, patients infected with CRF07_BC had significantly lower viral loads than patients infected with subtype B and it may due to the deletion of 7 amino acids which overlaps with Alix protein-binding domain of the p6gag

The effect of exercise on the risk of metabolic syndrome associated with sleep insufficiency: a cross-sectional study

IntroductionSleep disturbance and insufficient sleep have been linked to metabolic syndrome, increasing cardiovascular disease and mortality risk. However, few studies investigate the joint effect of sleep and exercise on metabolic syndrome. We hypothesized that regular exercise can mitigate the exacerbation of metabolic syndrome by sleep insufficiency.ObjectiveThe aim of this study was to investigate whether exercise can attenuate or eliminate the relationship between sleep insufficiency and metabolic syndrome.MethodA total of 6,289 adults (mean age = 33.96 years; women: 74.81%) were included in the study, a cross-sectional study conducted based on the results of employee health screening questionnaires and databases from a large healthcare system in central Taiwan. Participants reported sleep insufficiency or not. Self-reported exercise habits were classified into 3 levels: no exercise, exercise &lt;150 min/week, and exercise ≧150 min/week. Multiple logistic regression and sensitivity analyses were conducted to understand the joint associations of sleep patterns and exercise with metabolic syndrome with exposure variables combining sleep duration/disturbances and PA.ResultsCompared with the reference group (sufficient sleep), individuals with sleep insufficiency had a higher risk for metabolic syndrome [adjusted odds ratio (AOR) = 1.40, 95% confidence interval (95% CI): 1.01–1.94, p &lt; 0.05] in females aged 40–64 years, but not in other populations. Sleep insufficiency was not associated with the risk of metabolic syndrome among individuals achieving an exercise level of &lt;150 min/week, and in particular among those achieving ≧150 min/week in all populations in our study.ConclusionSleep insufficiency was related to a higher risk of metabolic syndrome in female healthcare staff aged 40–64 years. Being physically active with exercise habits in these individuals, the risk of metabolic syndrome was no longer significant

Functionalization of zirconia ceramic with fibronectin proteins enhanced bioactivity and osteogenic response of osteoblast-like cells

Introduction: To overcome the genuine bioinert properties of zirconia ceramic, functionalization of the surface with the bioactive protein fibronectin was conducted.Methods: Glow discharge plasma (GDP)-Argon was first used to clean the zirconia surface. Then allylamine was treated at three different powers of 50 W, 75 W, and 85 W and immersed into 2 different fibronectin concentrations (5 µg/ml and 10 µg/ml).Results and Discussion: After surface treatment, irregularly folded protein-like substances were attached on the fibronectin coated disks, and a granular pattern was observed for allylamine grafted samples. Infrared spectroscopy detected C-O, N-O, N-H, C-H, and O-H functional groups for fibronectin treated samples. Surface roughness rose and hydrophilicity improved after the surface modification, with MTT assay showing the highest level of cell viability for the A50F10 group. Cell differentiation markers also showed that fibronectin grafted disks with A50F10 and A85F10 were the most active, which in turn encouraged late-stage mineralization activity on 21d. Up-regulation of osteogenic related mRNA expression from 1d to 10d can be observed in RT-qPCR data for ALP, OC, DLX5, SP7, OPG and RANK biomarkers. These physical and biological properties clearly indicate that an allylamine and fibronectin composite grafted surface significantly stimulated the bioactivity of osteoblast-like cells, and can be utilized for future dental implant applications