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BACKGROUND AND PURPOSE: Perioperative chemotherapy (periCTX) based on the "MAGIC" scheme has become a standard treatment in Europe for locally advanced oesophagogastric cancer. We assessed implementation and long-term oncological outcomes of MAGIC periCTX for locally advanced gastric cancer. METHODS: Population-based cohort study of all patients with locally advanced gastric cancer undergoing surgical resection with curative intent in Catalonia and Navarra (the first two autonomous communities included in the EURECCA Upper GI Spanish Working Group) between January 2011 and December 2013. The main variable was the percentage of patients treated with MAGIC periCTX. Kaplan-Meier analysis and Cox proportional hazards model were used to assess the survival benefit of periCTX. RESULTS: Among 814 patients, 217 (26.6%) received periCTX (especially patients more likely to receive it: aged < 70 years, with proximal tumors, low anesthetic risk, and cT3-4/cN+ clinical stage). 35% did not complete perioperative chemotherapy, with no relationship with age. PeriCTX showed no effect on postoperative morbimortality. Histological tumor regression was more often absent or poor (38.2%) than total or almost total (27.8%), although clinico-pathological lymph-node downstaging was higher than expected by staging inaccuracy (38.7% vs. 24.2%). PeriCTX was associated with a better survival only in cT3-4 and cN+ patients, showing less prognostic relevance than optimal oncological surgery with D2 lymphadenectomy. CONCLUSIONS: Only 26.6% of locally advanced resectable gastric cancer patients received PeriCTX. Pathological response was poor, although some degree of nodal downstaging was observed. Survival benefit of periCTX was limited to cT3-4 and cN+ patients, being less relevant than D2 lymphadenectomy.

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The combination of synthetic anthelmintics and bioactive phytochemicals may be a pharmacological tool for improving nematode control in livestock. Carvone (R-CNE) has shown in vitro activity against gastrointestinal nematodes; however, the anthelmintic effect of bioactive phytochemicals either alone or combined with synthetic drugs has been little explored in vivo. Here, the pharmacological interaction of abamectin (ABM) and R-CNE was assessed in vitro and in vivo. The efficacy of this combination was evaluated in lambs naturally infected with resistant gastrointestinal nematodes. Additionally, the ligand and molecular docking of both molecules to P-glycoprotein (P-gp) was studied in silico. The presence of R-CNE produced a significant (p < 0.05) increase of Rho123 and ABM accumulation in the intestinal explants. After 60 min of incubation, Rho123 incubated with R-CNE had a 67 ± 21% higher concentration (p < 0.01) than when it was incubated alone. In the case of ABM, a significant increase in the intestinal concentrations was observed at 15 and 30 min after incubation with R-CNE. In the in vivo assay, no undesirable effects were observed after the oral administration of R-CNE. The coadministration of the natural compound prolonged ABM absorption in lambs. ABM T ½ absorption was 1.57-fold longer (p < 0.05) in the coadministered group. Concentrations of R-CNE between 420 and 2,593 ng/mL were detected in the bloodstream between 1 and 48 h posttreatment. The in vivo efficacy of ABM against gastrointestinal nematodes increased from 94.9 to 99.8% in the presence of R-CNE, with the lower confidence interval limit being >90%. In vitro/in vivo pharmacoparasitological studies are relevant for the knowledge of the interactions and the efficacy of bioactive natural products combined with synthetic anthelmintics. While ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions and the molecular docking study showed a good interaction between ABM and P-gp, R-CNE does not appear to modulate this efflux protein. Therefore, the pharmacokinetic-pharmacodynamic effect of R-CNE on ABM should be attributed to its effect on membrane permeability. The development of pharmacology-based information is critical for the design of successful strategies for the parasite control.

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PURPOSE: Our objectives were to report species distribution and survival of patients with candidemia in Argentina's central region and to establish the prevalence of C.parapsilosis sensu lato species, their virulence factors and their antifungal susceptibility profiles. METHODS: Yeasts isolated from bloodstream infections in Córdoba (Argentina) (n=35) were molecularly identified. The production of lipase and acid aspartic protease (Sap), the adhesion capacity, and the isolates' ability to form biofilm were evaluated. The in vitro activity of 7 antifungal drugs was evaluated (CLSIdocument M27-4thed). RESULTS: C. albicans was the most prevalent species (48.57%) followed by C. parapsilosis sensu lato (28.57%). The 30-day survival rate for C. albicans candidemia was slightly lower than non-albicans blood infections (50.00% vs. 57.90%). C. parapsilosis sensu stricto and C. orthopsilosis account for 60% and 40% of the cryptic species. Sap production and biofilm formation capacity were higher in C. parapsilosis sensu strico than in C.orthopsilosis. All the strains were susceptible to caspofungin (CAS), anidulafungin (AFG), amphotericin B (AMB), posaconazole (POS) and voriconazole (VRC). Azoles were the most potent agent against C. parapsilosis sensu lato followed by echinocandins and AMB. There were no differences between MICs for fluconazole, VRC, POS and AMB. Contrarily, C. parapsilosis sensu stricto strains showed lower MIC than C. orthopsilopsis isolates for itraconazole and higher MIC values for echinocandins (P<0.01). CONCLUSIONS: We report a high frequency of isolation of C.orthopsilosis in candidemia patients of central region. Data on the prevalence, virulence capability and antifungal susceptibility of C. parapsilosis complex provide new epidemiological information about these cryptic species in Argentina.

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AIMS: To examine the antioxidant activity of Bacterioruberin (Bctr)-rich extracts isolated from a hyperpigmented, genetically modified Haloferax volcanii strain (HVLON3) and to investigate the effect on cold-sensitive ram sperm cells. METHODS AND RESULTS: The strain HVLON3 produces higher Bctr amounts than most haloarchaea (220 ± 13 mg g-1 DW). HVLON3-Bctr extract has higher antioxidant activity than ß-carotene (threefold) as evaluated using 2,2 diphenyl-1-picrylhydrazyl combined with Electron Paramagnetic Resonance analysis (EC50 4·5 × 10-5  mol l-1 vs 13·9 × 10-5  mol l-1 respectively). Different concentrations of HVLON3-Bctr extracts were assayed on ram sperm after freezing/thawing and physiologically relevant parameters were examined. Extracts containing 7 and 20 µmol l-1 Bctr significantly improved cell viability (P < 0·0001), total and progressive motility (P < 0·0001) and sperm velocities (P = 0·0172 for curvilinear velocity VCL, P = 0·0268 for average path velocity VAP and P = 0·0181 for straight line velocity VSL) and did not affect other parameters evaluated. CONCLUSIONS: HVLON3 is an excellent source of natural microbial C50 carotenoids with applicability in Biotechnology, Biomedical and Veterinary fields. HVLON3 Bctr extract improves the quality of cryopreserved ram sperm cells and could be applied to increase insemination yields. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides an insight on the bioactive properties of a bioproduct derived from haloarchaea (carotenoids) which are so far underexploited.

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Hepatitis C virus (HCV) infection is a major worldwide problem. Chronic hepatitis C is recognized as one of the major causes of cirrhosis, hepatocellular carcinoma, and liver failure. Although new, directly acting antiviral therapies are suggested to overcome the low efficacy and adverse effects observed for the current standard of treatment, an effective vaccine would be the only way to certainly eradicate HCV infection. Recently, polyhydroxybutyrate beads produced by engineered Escherichia coli showed efficacy as a vaccine delivery system. Here, an endotoxin-free E. coli strain (ClearColi) was engineered to produce polyhydroxybutyrate beads displaying the core antigen on their surface (Beads-Core) and their immunogenicity was evaluated in BALB/c mice. Immunization with Beads-Core induced gamma interferon (IFN-γ) secretion and a functional T cell immune response against the HCV Core protein. With the aim to target broad T and B cell determinants described for HCV, Beads-Core mixed with HCV E1, E2, and NS3 recombinant proteins was also evaluated in BALB/c mice. Remarkably, only three immunization with Beads-Core+CoE1E2NS3/Alum (a mixture of 0.1 µg Co.120, 16.7 µg E1.340, 16.7 µg E2.680, and 10 µg NS3 adjuvanted in aluminum hydroxide [Alum]) induced a potent antibody response against E1 and E2 and a broad IFN-γ secretion and T cell response against Core and all coadministered antigens. This immunological response mediated protective immunity to viremia as assessed in a viral surrogate challenge model. Overall, it was shown that engineered biopolyester beads displaying foreign antigens are immunogenic and might present a particulate delivery system suitable for vaccination against HCV.

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BACKGROUND: Modern management of Oesophageal and oesophagogastric junction (OGJ) cancers requires a multidisciplinary approach, which was implemented at our health centre in 2005. This study aimed to assess the impact of this change on clinical outcomes. METHODS: A retrospective cohort study was conducted, covering all patients treated for oesophageal and OGJ cancer at the cancer centre established by the Bellvitge University Hospital and Catalonian Institute of Oncology, over two time periods, i.e. 2000-2004 and 2005-2008. Descriptive and multivariate analyses were performed using survival at 1 and 3 years as dependent variables. RESULTS: Between 1 January 2000 and 31 December 2008, 586 patients were included. Number of patients with unknown stage at diagnosis was significantly reduced. Preoperative strategies at the oesophageal location clearly increased in the recent period. A multidisciplinary approach resulted in a significant reduction in surgical mortality (11.8 vs. 2 %) in the period 2005-2008. Analysis restricted to patients undergoing surgery with curative intent indicated a significant increase in 1- and 3-year survival in the latter period (68.4 vs. 89.8 and 38.2 vs. 57.1 %, respectively). Multivariate analysis showed that variables associated with improved survival were: age; tumour stage; radical intent of treatment (surgery and radical combined chemoradiotherapy); and therapeutic strategy. CONCLUSION: Better selection of patients for therapy together with improved staging resulted in a significant improvement in 1- and 3-year survival in cases undergoing surgery with curative intent. These changes would support the adoption of a multidisciplinary approach to clinical decision-making in cases of oesophageal and OGJ cancer.

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The present review focuses on the numerous experimental models used to study the complexity of hepatic ischemia/reperfusion (I/R) injury. Although experimental models of hepatic I/R injury represent a compromise between the clinical reality and experimental simplification, the clinical transfer of experimental results is problematic because of anatomical and physiological differences and the inevitable simplification of experimental work. In this review, the strengths and limitations of the various models of hepatic I/R are discussed. Several strategies to protect the liver from I/R injury have been developed in animal models and, some of these, might find their way into clinical practice. We also attempt to highlight the fact that the mechanisms responsible for hepatic I/R injury depend on the experimental model used, and therefore the therapeutic strategies also differ according to the model used. Thus, the choice of model must therefore be adapted to the clinical question being answered.

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This research was performed with the purpose of learning about effect of oral rinsing, every two weeks, with mineralizing solution (Minersol) on recently erupted permanent dentition. Reduction obtained in the incidence of caries at one year term ranged between 49.2 and 82.1% for first molar teeth and 23.4 and 36.3% for second molar teeth; both differences were significant, but no reduction was obtained in the incidence of caries in the bicuspid teeth. Preventing effect obtained is attributed to ionic incorporation in enamel superficial levels, which decreases the diffusion of acids acting in demineralization. It is concluded that the use of mineralizing solution in those ages of eruption of permanent dentition reduces incidence of caries and, therefore, its use as preventing method is recommended.

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This research was carried out with the purpose of learning about relationship between degree of infection by Streptococcus mutans in saliva and prevalence of caries and further incidence in a one year term. A total of 931 children aged 2-3 years of Havana City and Sancti Spiritus Province, and 10 different series of school children aged 6-12 years of both provinces, with a total of 848 children, were studied. A direct significant relationship between degree of infection by S. mutans and prevalence of caries (percentage of affected children and co/COPD index) was found in the groups under study. Likewise, in the relationship between previous degree of infection and incidence of caries, differences were significative in children aged 2-3 years and in six of the 10 series of school children, with a correlation (r) of 0.216. It is analyzed that despite that degree of infection by Streptococcus mutans is the parameter with higher correlation with cariogenic activity, its predictive value is not enough by itself, therefore, a joint valuation with other parameters also related to cariogenic activity is required, in order to be able to reach necessary validity in the prognosis.

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Nursing care is reviewed in six patients hospitalized with diagnosis of insulin-dependent diabetes mellitus (type I), three of them with poor metabolic control of disease (hospitalized in miscellaneous ward) and three with diagnosis of diabetic ketoacidosis (hospitalized in intensive care ward). Importance of nurse's work in the hospital assistance staff is pointed out.

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Relationship existing between enamel resistance (by developed colorimetric technique) and previous experience of caries and with further incidence, at a term of a year, was studied in schoolchildren aged 6, 8, 10 and 12 years. The study comprised 336 children in 1985-1986 period and 385 children in 1985-1987 period. Non significant positive correlation was found between values of colorimetric test and previous experience of caries; but, certainly, positive correlation was found with further incidence on permanent dentition. It is concluded that colorimetric test is useful for the selection of children with a very susceptible enamel, as well as for the prognosis of cariogenic activity valued together with other parameters.

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Degree of mineralization of enamel is one of the parameters mediating in its resistance to acid dissolution and at the stage of teething, the enamel is immature and, therefore, present a higher susceptibility to dental caries. This investigation was carried out with 38 preschool children (means = 5.5 years) and 19 children coursing second grade (means = 7.6 years). They were treated with 10 oral rinsing with mineralizing solution in order to evaluate its effect on enamel resistance to acid dissolution; colorimetric technique was used for such purpose. A study in vitro was also performed in impacted third molars extracted by surgery and to two halves of the clinical crowns of such molars the treatment was applied; the other two halves were taken as control. Increase of enamel resistance found was 18.6% in the study of preschool children and 34.6% in the children attending to second grade school. In both groups, 89.5% of the children increased enamel resistance and in the study in vitro increaser enamel was 14.9%.. It is concluded that the use of risings with mineralizing solution at the outbreak of permanent teething increase, significatively, enamel resistance, and that at the age of seven the enamel is still immature, thus its resistance to acid dissolution can be also increased using mineralizing solution.

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This investigation was performed to evaluate, comparatively, the effect of topical application of Duraphat, Flulak, Fluor-Protector, Bifluorid 12, Profilac, Fluoro-gel-P and Fluocal-gel. Colorimetric technique was used for such purposes. It was found that 67.5% of 283 children treated with those different treatments increased their enamel resistance to acid dissolution, although notable differences were found in the use of these products. Average of increase ranged between 10.7 and 23.5%. Lacs and varnishes provide best results than gels with regard to acid dissolution rate of enamel. Behave of the two national products evaluated (Flulak and Profilac) was similar to the rest of lacs and varnishes, justifying their use at national level for the prevention of caries, avoiding in that way unnecessary importations.

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An investigation was carried out in hypercaries-producing children, who had have previously curative treatment. Twenty three children were treated with semestral applications of fluorine-chlorhexidine varnish and daily brushing for 15 days every three months, with dental creme with chlorhexidine, while 21 children were selected as control group. Four analysis of Str. mutants in saliva (Matsukubo technique) were performed to each child in both groups, during a year. It was found that children treated reduced, remarkably, the degree of infection by Str. mutans, while degree of infection did not suffer modification in those children of the control group. The final examination performed after one year showed that 15 children of the control group resulted affected by caries (71.4%) with an incidence of 27 caries (1.29 index), while in the group under treatment only a child resulted affected with a caries. Reduction found in the incidence of caries was 96.9%. Problematic of hypercaries-producing child is analyzed and it is concluded that it is necessary to control and record him, and that investment in a strict treatment, such as that successfully assayed by us, should be rentable, since it should reduce amount of extractions of teeth and to contribute in that way to a real promotion of oral health with the infantile population.

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