The use of alpha 1 thymosin as an immunomodulator of the response against SARS-Cov2.

BACKGROUND: Since the beginning of SARS-CoV2 pandemic, the mortality rate among elderly patients (60-90 years) has been around 50%, so age has been a determining factor of a worse COVID-19 prognosis. Associated with age, the thymic function involution and depletion plays an important role, that could be related to a dysregulated and ineffective innate and adaptive immune response against SARS-CoV2. Our study aims to further in vitro effect of human Thymosin-alpha-1 (α1Thy) treatment on the immune system in population groups with different thymic function levels in the scenario of SARS-CoV2 infection. RESULTS: Activation markers such as CD40, CD80 and TIM-3 were upregulated in α1Thy presence, especially in plasmacytoid dendritic cells (pDCs) and, with increased TNFα production was observed compared to untreated condition. Co-cultures of CD4 + and CD8 + T cells with DCs treated with α1Thy in response to SARS-CoV2 peptides showed a decrease in the cytokine production compared to the condition without α1Thy pre-treated. A decrease in CD40L activation co-receptor expression in CD8 + LTs was also observed, as well as an increase in PD1 in CD4 + TLs expression in both age groups. In fact, there are no age-related differences in the immunomodulatory effect of the hormone, and it seems that effector memory and terminally differentiated memory T lymphocyte subsets were the most actively influenced by the immunomodulatory α1Thy effect. Finally, the polyfunctionality measured in SARS-CoV2 Specific-T cells response was maintained in α1Thy presence in total and memory subpopulations CD4 + and CD8 + T-cells, despite decreased proinflammatory cytokines production. CONCLUSION: The hormone α1Thy could reduce, through the modulation of DCs, the amount of proinflammatory cytokines produced by T cells. Moreover, α1Thy improve lymphocyte functionality and could become a beneficial therapeutic alternative as an adjuvant in SARS-CoV2 treatment either in the acute phase after infection or reinfection. In addition, the effect on the T immune response means that α1Thy can be incorporated into the vaccination regimen, especially in the most immunologically vulnerable individuals such as the elderly. SUBJECTS: Thymosin alpha 1, Dendritic cells, SARS-CoV2-specific T cells response, Immunomodulation.

Outcomes of an enhanced recovery after radical cystectomy program in a prospective multicenter study: compliance and key components for success.

OBJECTIVE: To investigate the effect of an Enhanced Recovery After Surgery (ERAS) program on complications and length of stay (LOS) after radical cystectomy (RC) and to assess if the number and type of components of ERAS play a key role on the decrease of surgical morbidity. MATERIALS AND METHODS: We analyzed the data of 277 patients prospectively recruited in 11 hospitals undergoing RC initially managed according to local practice (Group I) and later within an ERAS program (Group II). Two main outcomes were defined: 90-day complications rate and LOS. As secondary variables we studied 90-day mortality, 30-day readmission and transfusion rate. RESULTS: Patients in Group II had a higher use of ERAS measures (98.6%) than those in Group I (78.2%) (p < 0.05). Patients in Groups I and II experienced similar complications (70.5% vs. 66%, p = 0.42). LOS was not different between Groups I and II (12.5 and 14 days, respectively, p = 0.59). The risk of having any complication decreases for patients having more than 15 ERAS measures adopted [RR = 0.815; 95% confidence interval (CI) 0.667-0.996; p = 0.045]. Avoidance of transfusion and nasogastric tube, prevention of ileus, early ambulation and a fast uptake of a regular diet are independently associated with the absence of complications. CONCLUSIONS: Complications and LOS after RC were not modified by the introduction of an ERAS program. We hypothesize that at least 15 measures should be applied to maximize the benefit of ERAS.

Toll-Like Receptor 7 (TLR-7) and TLR-9 Agonists Improve Hepatitis C Virus Replication and Infectivity Inhibition by Plasmacytoid Dendritic Cells.

Plasmacytoid dendritic cells (pDCs) are innate immune cells with high antiviral activity triggered by Toll-like receptor 7 (TLR-7) and TLR-9 stimulation. Moreover, they are important mediators between innate and adaptive immunity. Although nowadays there is available an effective therapeutic arsenal against hepatitis C virus (HCV), a protective vaccine is not available. We have analyzed the pDCs' response to HCV infection in a hepatitis C virus (HCV)-Huh7.5 virus-cell system, which allows completion of the virus infectious cycle. pDCs were cocultured following human immunodeficiency virus (HIV) aldrithiol-2 (AT-2 [TLR-7 agonist]) inactivation and CpG (TLR-9 agonist) stimulation. We employed three virus derivatives-wild-type Jc1, interferon (IFN)-resistant virus IR, and high-replicative-fitness virus P100-in order to explore additional IFN-α-related virus inhibition mechanisms. pDCs inhibited HCV infectivity and replication and produced IFN-α. After TLR-7 and TLR-9 stimulation, inhibition of infectivity and IFN-α production by pDCs were enhanced. TLR-7 stimulation drove higher TNF-related apoptosis-inducing ligand (TRAIL) expression in pDCs. Additionally, TLR-7- and TLR-9-stimulated pDCs exhibited a mature phenotype, improving the antigen presentation and lymph node homing-related markers. In conclusion, pDCs could serve as a drug target against HCV in order to improve antiviral activity and as an enhancer of viral immunization.IMPORTANCE We implemented a coculture system of pDCs with HCV-infected hepatoma cell line, Huh7.5. We used three HCV derivatives in order to gain insight into pDCs' behavior against HCV and associated antiviral mechanisms. The results with this cell coculture system support the capacity of pDCs to inhibit HCV replication and infectivity mainly via IFN-α, but also through additional mechanisms associated with pDC maturation. We provided evidence that TLR agonists can enhance antiviral pDCs' function and can induce phenotypic changes that may facilitate the interplay with other immune cells. These findings suggest the possibility of including TLR agonists in the strategies of HCV vaccine development.

HLA-B*57 and IFNL4-related polymorphisms are associated with protection against HIV-1 disease progression in controllers.

Background: HIV-1-controllers maintain HIV-1 viremia at low levels (normally <2000 HIV-RNA copies/mL) without antiretroviral treatment. However, some HIV-1-controllers have evidence of immunologic progression with marked CD4+T-cell decline. We investigated host genetic factors associated with protection against CD4+T-cell loss in HIV-1-controllers. Methods: We analysed the association of interferon lambda 4 (IFNL4)-related polymorphisms and HLA-B haplotypes within Long Term Non-Progressor HIV-1-controllers ((LTNP-C), defined by maintaining CD4+T-cells counts >500 cells/mm3 for more than 7 years after HIV-1 diagnosis) versus non-LTNP-C, who developed CD4+T-cells counts <500 cells/mm3 Both a Spanish study cohort (n=140) and an international validation cohort (n=914) were examined. Additionally, in a subgroup of individuals HIV-1-specific T-cell responses and soluble cytokines were analysed RESULTS: HLA-B*57 was independently associated with the LTNP-C phenotype (OR=3.056 (1.029-9.069) p=0.044 and OR=1.924 (1.252-2.957) p=0.003) while IFNL4 genotypes represented independent factors for becoming non-LTNP-C (TT/TT, ss469415590, OR=0.401 (0.171-0.942) p=0.036 or A/A, rs12980275, OR=0.637 (0.434-0.934) p=0.021) in the Spanish and validation cohort, respectively, after adjusting for sex, age at HIV-1 diagnosis, IFNL4-related polymorphisms and different HLA-B haplotypes. LTNP-C showed lower plasma IP-10 (p=0.019) and higher IFN-γ (p=0.02) levels than the HIV-1-controllers with diminished CD4+T-cell numbers. Moreover, LTNP-C exhibited higher quantities of IL2+CD57- and IFN-γ+CD57- HIV-1-specific CD8+T-cells (p=0.002 and 0.041, respectively) than non-LTNP-C. Conclusions: We have defined genetic markers able to segregate stable HIV-1-controllers from those who experience CD4+T-cell decline. These findings allow for identification of HIV-1-controllers at risk for immunologic progression, and provide avenues for personalized therapeutic interventions and precision medicine for optimizing clinical care of these individuals.

Increased CD127+ and decreased CD57+ T cell expression levels in HIV-infected patients on NRTI-sparing regimens.

BACKGROUND: NRTIs-sparing regimens exert favourable profiles on T-cell homeostasis associated parameters. Our aim was to analyze the effect of NRTIs sparing regimen (NRTI-sparing-cART) vs NRTIs-containing regimen (NRTI-cART), on T-cell homeostasis associated parameters in naive HIV-infected patients. METHODS: Biomarkers of cell survival (CD127) and replicative senescence (CD57), were measured by multiparametric flow cytometry for T-cell phenotyping on peripheral blood mononuclear cells (PBMCs) samples just before (baseline) and after 48 weeks of undetectable viral load in patients on NRTI-sparing-cART (N = 13) and NRTI-cART (N = 14). After 48 weeks a subgroup of patients (n = 5) on NRTI-cART switched to NRTI-sparing-cART for another additional 48 weeks. In vitro assays were performed on PBMCs from HIV-uninfected healthy donors exposed or not to HIV. To analyze the independent factors associated with type of cART bivariate and stepwise multivariate analysis were performed after adjusting for basal CD4+, CD8+ and nadir CD4+ T-cell counts. RESULTS: After 48 weeks of a NRTI-sparing-cART vs NRTI-cART patients have higher effector memory (EM) CD4+ CD127+ T-cell levels, lower EM CD4+ CD57+ T-cell levels, higher CD8+ CD127+ T-cell levels, lower CD8+ CD57+ T-cell levels and higher memory CD8+ T-cell levels. This effect was confirmed in the subgroup of patients who switched to NRTI-sparing-cART. In vitro assays confirmed that the deleterious effect of a NRTIs-containing regimen was due to NRTIs. CONCLUSIONS: The implementation of NRTI-sparing regimens, with a favourable profile in CD127 and CD57 T-cell expression, could benefit cART-patients. These results could have potential implications in a decrease in the number of Non-AIDS events.

People with epilepsy receive more statins than the general population but have no higher cardiovascular risk: results from a cross-sectional study.

BACKGROUND AND PURPOSE: Epilepsy has been associated with cardiovascular comorbidity. Risk prediction equations are the standard tools in primary prevention of cardiovascular disease. Our aim was to compare the prevalence of cardiovascular risk factors (CVRFs), cardiovascular risk and statin use in people with epilepsy (PWE) and the general population. METHODS: The CVRFs and cardiovascular risk score were compared between 815 PWE from an outpatient register and 5336 participants from a general population cohort. RESULTS: People with epilepsy had less hypertension (43.3% vs. 50.4%), less diabetes (15.8% vs. 19.2%), more dyslipidemia (40.2% vs. 34.6%) and lower cardiovascular risk than the general population (P < 0.01). No etiology was associated with a worse CVRF profile or higher cardiovascular risk. Patients taking enzyme-inducing antiepileptic drugs (EIAEDs) had more dyslipidemia than the general population (41.6% vs. 34.6%) but similar cardiovascular risk. Independently of risk or CVRFs, PWE had 60% more probability of receiving statins than the general population. CONCLUSIONS: People with epilepsy had more dyslipidemia, related to EIAEDs, and lower cardiovascular risk but still took more statins than the general population. Physicians should use clinical judgement to decide on further treatment of CVRFs in PWE who are below the recommended risk threshold for treatment and should consider lipid abnormalities a potential side-effect of EIAEDs. Other therapy options may need to be evaluated before starting lipid-lowering treatment.

Validation of the HIV Tropism Test TROCAI Using the Virological Response to a Short-Term Maraviroc Monotherapy Exposure.

TROCAI is a phenotypic tropism test developed using the virological response to a short-term exposure to maraviroc monotherapy (Maraviroc Clinical Test [MCT]). It was found that with TROCAI, a cutoff of <0.5% of dual/mixed viruses was needed to predict R5 HIV tropism. Here, we have validated TROCAI, using this cutoff, in a new cohort of 42 patients, finding a very high concordance between TROCAI and MCT (98%), and a good concordance (71 to 87%) with other genotypic/phenotypic methods.

Canine mammary tumors: a review and consensus of standard guidelines on epithelial and myoepithelial phenotype markers, HER2, and hormone receptor assessment using immunohistochemistry.

Although there have been several studies on the use of immunohistochemical biomarkers of canine mammary tumors (CMTs), the results are difficult to compare. This article provides guidelines on the most useful immunohistochemical markers to standardize their use and understand how outcomes are measured, thus ensuring reproducibility of results. We have reviewed the biomarkers of canine mammary epithelial and myoepithelial cells and identified those biomarkers that are most useful and those biomarkers for invasion and lymph node micrometastatic disease. A 10% threshold for positive reaction for most of these markers is recommended. Guidelines on immunolabeling for HER2, estrogen receptors (ERs), and progesterone receptors (PRs) are provided along with the specific recommendations for interpretation of the results for each of these biomarkers in CMTs. Only 3+ HER2-positive tumors should be considered positive, as found in human breast cancer. The lack of any known response to adjuvant endocrine therapy of ER- and PR-positive CMTs prevents the use of the biological positive/negative threshold used in human breast cancer. Immunohistochemistry results of ER and PR in CMTs should be reported as the sum of the percentage of positive cells and the intensity of immunolabeling (Allred score). Incorporation of these recommendations in future studies, either prospective or retrospective, will provide a mechanism for the direct comparison of studies and will help to determine whether these biomarkers have prognostic significance. Finally, these biomarkers may ascertain the most appropriate treatment(s) for canine malignant mammary neoplasms.

[To go in-depth in the knowledge of the device to control fecal elimination in the critical patient]. / Profundizando en el conocimiento sobre el manejo del dispositivo para control de la eliminación fecal en el paciente crítico.

OBJECTIVE: To describe the general characteristics of the patient and device use. To know retention balloon pressure (RBP) and related factors. To identify rate of leakage incidence, relocation and perineal damage due to the device (PSD) and related risk factors. MATERIAL AND METHODS: An analytical observational, cross-sectional study conducted in a polyvalent ICU from June-December 2010 was performed. The sample included Flexi-Seal(®) carriers. Variables evaluated were patient and device use characteristics, RBP, leakage and quantity, relocation and reason, PSD, sedoanalgesia infusion, neuromuscular block, patient position, Flexi-Seal type catheter, ventilatory mode (VM), intra-abdominal pressure (IAP), mean intrathoracic pressure (MITP), PEEP, Glasgow, color-aspect, fecal consistency and volume. Significance P<.05. RESULTS: Twenty-one patients were included, 52% male, aged 54±17 with 30 insertion episodes, Flexi-Seal-Signal(®) 33%, 10±8 days permanency, main indication 33% «diarrhea and injured skin¼," 30% device removal «intolerance and/or spontaneous expulsion¼. Median (Me) PGR =40; RI (61-19) cmH2O. Factors associated to higher PGR: SCI absence, prone-decubitus position, leakage, relocation, conventional Flexi-Seal(®), MV, lower PEEP and IMP, Color-aspect, higher MITP. Leakage, relocation and PSD incidence density 43, 30 and 2 cases/100 days of catheter, respectively. Leakage and relocation risk factors: higher PGR, Glasgow and fecal volume, lower MITP, MV, assisted-spontaneous mode OR 2.5 CI (1.6-3.8) and OR 1.7(1.1-2.7), absence SCI OR 3.3 (2.2-5.1) and OR 2.4(1.5-3.8), absence neuromuscular block OR 2.4 (1.4-3.9) and OR 1.8 (1.1-3.1), Flexi-Seal(®) conventional OR 2.7(1.7-4.1) and OR 2 (1.2-3.3), respectively. Leakage risk factors: color-aspect, supine position, lower IMP and PEEP. CONCLUSIONS: Monitoring RBP may alert us about leakage presence and relocation need. Knowing associated risk factors to RBP, leakage and relocation would help to develop strategies to reduce their high incidence rate such as decreasing RBP by reducing inflated volume.

Immune modulation via dendritic cells by the effect of Thymosin-alpha-1 on immune synapse in HCMV infection.

Tα1 (Thymosin-alpha-1) is a thymus-derived hormone that has been demonstrated to be effective on diverse immune cell subsets. The objective of this study was to determine the in vitro immunomodulatory effect of Tα1 in human cytomegalovirus (HCMV) infection. Dendritic cells (DCs) were isolated from peripheral blood mononuclear cells (PBMCs) by negative selection and cultured in the presence or absence of Tα1. The immunophenotyping of DCs was characterised by multiparametric flow cytometry assessing CD40, CD80, TIM-3 and PDL-1 markers, as well as intracellular TNFα production. Then, autologous CD4+ or CD8+ T-Lymphocytes (TLs) isolated by negative selection from PBMCs were co-cultured with DCs previously treated with Tα1 in the presence or absence of HCMV. Intracellular TNFα, IFNγ, IL-2 production, CD40-L and PD-1 expression were assessed through immunophenotyping, and polyfunctionality in total TLs and memory subsets were evaluated. The results showed that Tα1 increased CD40, CD80, TIM-3 and TNFα intracellular production while decreasing PDL-1 expression, particularly on plasmacytoid dendritic cells (pDCs). Therefore, Tα1 modulated the production of TNFα, IFNγ and IL-2 in both total and memory subsets of CD4+ and CD8+ TLs by upregulating CD40/CD40-L and downregulating PDL-1/PD-1 expression. Our study concludes that Tα1 enhances antigen-presenting capacity of DCs, improves TLs responses to HCMV infection, and enhances the polyfunctionality of CD8+ TLs. Consequently, Tα1 could be an alternative adjuvant for use in therapeutic cell therapy for immunocompromised patients.

[Decubitus prone position in patient with extracorporeal CO2 removal device Novalung(®)]. / Decúbito prono en paciente portador de dispositivo de extracción extracorpórea de CO(2) Novalung(®).

OBJECTIVE: To describe the course of a patient with the extracorporeal CO2 removal device and discover the effect of Novalung on ventilation, considering the patient's prone position and its influence on the device's blood flow. To develop a protocol of managing and specific care of a patient with Novalung. MATERIAL AND METHODS: A case report of a patient with Novalung in a tertiary hospital ICU unit is reported. Parameters considered are hemodynamic, respiratory, pharmacological, analytical, neuromonitoring, managing of the Novalung and length of decubitus prone cycles. Anova Test, Student's T test, Wilcoxon-Mann Whitney and Spearman correlation. Significance p <0.05. RESULTS: A 46-year old women with nosocomial pneumonia and acute respiratory failure with indication of Novalung to decrease hypercapnia and optimize ventilatory management of refractory hypoxemia. ICU Stay 26 days, MBP 82 ± 9 mmHg, HR 110 ± 6l pm during the admission, monitoring PICCO 5 days CI 3.2 ± 0.8 l/min/m2, ELWI 33 ± 4 ml, continuous hemofiltration 13.2 days with a median removal 50 cc/h. Norepinephrine dose 0.68 ± 0.79 µ/kg/min for 15 days. Respiratory parameters during the admission: PO2 59 ± 13 mmHg, PCO2 68 ± 35 mmHg, SatO2 85 ± 12%, PO2/FIO2 69 ± 35, tidal volume 389 ± 141 cc. Novalung® 13 days, heparin dose 181.42 ± 145 mIU/Kg/min, Cephalin time 57.56 ± 16.41 sec, O2 flow 7 ± 3 l/min, median blood flow 1030 cc/h, interquartile range 1447-612 cc/h. Prone cycles 4, duration 53 ± 27 hours. With Novalung® PCO2 decreased regardless of position 66 ± 21:56 ± 9, p=0.005. Tidal volume 512 ± 67:267 ± 72, p=0.0001. Blood flow on supine-prone position 1053 ± 82:113 ± 112, p=0.001. There was no link between blood flow and PCO2 (p=0.2) and between O2 and PO2 flow (p=0.05). Specific care: pedal and tibial pulse monitoring, keep circuit safe to prevent and detect signs of bleeding, femoral arterial and venous catheter care, coagulation monitoring. COMMENTS: During the use of Novalung protective, ventilation, low tidal volumes, decreased pressure plateau, PEEP and hypercapnia were achieved. Blood flow decreased in prone position, but the PCO2 did not increase. The device did not coagulate.

Direct chiral liquid chromatography determination of aryloxyphenoxypropionic herbicides in soil: deconvolution tools for peak processing.

In this paper, the enantiomeric separation of two aryloxyphenoxypropionic esters (fluazifop-butyl and quizalofop-ethyl) and a safener herbicide (mefenpyr-diethyl), which is widely used for protecting crop plants, has been studied by direct liquid chromatography (LC) with UV detection on an α(1)-acid glycoprotein as chiral stationary phase. Optimization of separation conditions was done by factorial experimental design. Experimental factors and ranges selected were propanol (5-10%), phosphate buffer pH (6.5-7.0), and column temperature (15-25 °C). Responses were expressed in terms of enantioresolution (R(s)) and adjusted retention time of the second eluted enantiomer (t(r2)'). The chemometric method used to explore data was response surface analysis. Multiple response analyses were carried out to determine the combination of experimental factors which simultaneously optimize experimental responses. Under optimum conditions for enantioseparation of each herbicide, partially overlapped or fully resolved enantiomers were obtained. Deconvolution tools were employed as an integration method to fit chromatographic data and to achieve a more precise enantiomeric ratio (ER) and enantiomeric fraction (EF) values. Applicability of both direct chiral LC and peak deconvolution methods was evaluated in spiked soil samples at different R/S enantiomeric ratios. Acceptable and reproducible recoveries between 71% and 96% with precision in the range 1-6% were achieved for herbicide-spiked levels from 0.50 to 9.0 µg g(-1). In addition, parameters such as R(s), ER, and EF were calculated and compared with values obtained using the common valley drop integration method.

Tailoring interfacial effect in multilayers with Dzyaloshinskii-Moriya interaction by helium ion irradiation.

We show a method to control magnetic interfacial effects in multilayers with Dzyaloshinskii-Moriya interaction (DMI) using helium (He[Formula: see text]) ion irradiation. We report results from SQUID magnetometry, ferromagnetic resonance as well as Brillouin light scattering results on multilayers with DMI as a function of irradiation fluence to study the effect of irradiation on the magnetic properties of the multilayers. Our results show clear evidence of the He[Formula: see text] irradiation effects on the magnetic properties which is consistent with interface modification due to the effects of the He[Formula: see text] irradiation. This external degree of freedom offers promising perspectives to further improve the control of magnetic skyrmions in multilayers, that could push them towards integration in future technologies.

New approach to optimize HPLC separations of acid-base compounds with elution order involved, by using combined three-band resolution maps.

Some of the optimization methods in reversed phase high-performance liquid chromatography (RP-HPLC) are based on resolution of the critical band pair. Mobile phase composition is changed systematically to establish those conditions giving an acceptable resolution for such a critical band pair, but sometimes the critical pair may change with the separation conditions, which obliges to identify it for each of those conditions. In the case of ionizable compounds, more than two bands may be involved in resolution, showing--in some cases--changes in the elution order when the mobile phase composition was modified. In this paper, an alternative way that does not identify the critical pair after changing experimental conditions is proposed. The relative separation of the three bands involved in two alternating critical band pairs is evaluated as a sort of conjugate or combined resolution, represented as contour maps vs. two variables (content of organic modifier and pH). These maps are obtained from data of chromatograms made under different separation conditions; these conditions were generated by experimental design and data was mathematically processed with a computer program. Analytes of three families that have acid-base properties, triazines, phenoxyacids, and phenols, were used for this purpose. The chromatographic behavior when elution order reversion of ionizable compounds exists is studied.

Free D-amino acids determination in ready-to-eat cooked ham irradiated with electron-beam by indirect chiral HPLC.

Potential racemization of L-amino acids (AA) in ready-to-eat (RTE) cooked ham after hygienization by electron-beam irradiation between 1 and 8kGy was studied. An indirect chiral method based on the derivatization reaction of AA with o-phthaldialdehyde and N-acetyl-L-cysteine followed by reversed-phase HPLC and fluorimetric detection was applied to detect ten enantiomeric pairs of free AA (Asp, Ser, Thr, Ala, Tyr, Val, Trp, Phe and Leu). Five of the D-AA were not found in any of the samples analyzed; the other five remaining D-AA (D-Asp, D-Ser, D-Ala, D-Val and D-Leu) were detected both in irradiated and non-irradiated cooked ham samples, their content being in the range 1.25-13.79µg/g. Although significant differences appeared for a few of the samples and doses, no positive correlation between the D-AA content and the irradiation doses was observed. Therefore, the electron-beam irradiation technique could be useful for sanitation of packed RTE cooked ham at doses allowed by WHO and EU, since it remains chemically safe to eat.

Consensus on the treatment of pancreatic cancer in Spain.

Pancreatic cancer (PC) represents one of the greatest oncological challenges of our century, due to its high mortality and incidence. A group of Spanish experts in PC treatment reviewed data available on different therapeutic combinations and established consensus on what would be the best strategy in PC management, depending on the stage of the disease. Surgery with complete resection may produce 5-year survival rates of 18-24%, but definitive control is still precarious. In the absence of consensus, the best evidence suggests that adjuvant chemotherapy with gemcitabine for 6 months using the CONKO-001 regime is the treatment of choice after resection of PC for patients with acceptable functional status. This group recommends chemoradiotherapy (CT-RT) in patients with factors for poor loco-regional prognosis. However, chemotherapy is an option for the treatment of locally advanced PC in patients with good general status and in the absence of metastatic disease the recommended treatment is CT-RT followed by gemcitabine-based chemotherapy. A period of chemotherapy followed by consolidation CT-RT may be appropriate, as it allows selection of patients with locally advanced disease who may benefit most from combined treatment. Erlotinib combined with gemcitabine shows significant survival improvement in PC and must be considered an option in the first-line treatment of advanced and metastatic PC. The gemcitabine-erlotinib combination is proposed as the standard treatment for metastatic PC in patients with PS=/>2. In patients with PS<2, gemcitabine-erlotinib is recommended as the first-line treatment option, supported by a maximum degree of evidence, without ruling out other options, such as gemcitabine-oxaliplatin, gemcitabine-capecitabine or gemcitabine alone.

[Evaluation of a follow-up program for diabetes after hospital discharge]. / Evaluación de un protocolo de seguimiento para diabetes tras el alta hospitalaria.

BACKGROUND: Given the higher rate of hospital admissions among diabetic patients, discharge should be used to optimize outpatient treatment. We evaluate a follow-up program for diabetic patients after hospital discharge to determine the evolution of glycemic control. METHOD: Retrospective collection of data on 375 diabetic patients enrolled in the follow-up program for optimization treatment: telephonic follow-up where treatment was adjusted if needed; and three months after discharge an in-person consultation was scheduled. Factors potentially associated with a 1% improvement in HbA1c were studied by multivariate logistic regression. RESULTS: Seventy-three percent of enrolled patients completed the follow-up program; each patient received an average of 4.6 phone calls. Globally, basal mean HbA1c was significantly lower three months later regarding the initial value (8.6 vs. 7.2%); the most relevant lowering was found in the group of hyper-glycemia by poor metabolic control (from 9.9 to 7.7%), combined hyperglycemia (from 9.3 to 7.3%) and debut (from 8.3 to 6.4%). Twenty percent of patients reported capillary hypoglycemia, with two severe events. A shorter duration of diabetes, absence of corticotherapy and absence of hypoglycemia during the follow-up period were independent predictors for a 1% reduction in three-months HbA1c. CONCLUSION: In patients whose treatment is changed on hospital discharge, a program allowing frequent treatment adjustment would improve HbA1c levels. These results could help to organize health resources more rationally.

Synthesis and complexation ability of a novel bis- (guanidinium)-tetrakis-(beta-cyclodextrin) dendrimeric tetrapod as a potential gene delivery (DNA and siRNA) system. Study of cellular siRNA transfection.

The facile synthesis of a novel bis-(guanidinium)-tetrakis-(beta-cyclodextrin) tetrapod, the first example of a new host family, was described, and the ability of the cyclodextrin CyD tetrapod to form molecular association with siRNA and DNA guest molecules was demonstrated. Affinity capillary electrophoresis was used to determine the binding constant with the evaluation of the shift in the electrophoretic mobility mu of injected siRNA when various CyD tetrapod concentrations were added to the run buffer. A significant association constant (K(a) =16,000 M(-1)) was obtained with borate buffer when double-stranded siRNA was primarily opened with the help of temperature. An efficient cellular transfection of siRNA into human embryonic lung fibroblasts was observed by fluorescence microscopy.

Determination of carbamate, phenylurea and phenoxy acid herbicide residues by gas chromatography after potassium tert-butoxide/dimethyl sulphoxide/ethyl iodide derivatization reaction.

The usefulness of the potassium tert-butoxide/dimethyl sulphoxide/ethyl iodide reaction with carbamate and phenylurea herbicides, and its application to phenoxy acids as a way to prevent hazards and toxicity of the sodium hydride/dimethyl sulphoxide/methyl iodide reaction was studied. Using factorial design optimization of this reaction was carried out. A solid-phase extraction method using dimethyl sulphoxide as eluent on-line with this reaction was developed to determine these herbicides in water samples by gas chromatography-mass spectrometry. Relative standard deviation values were lower than 10% for most of the herbicides in multicomponent trace determinations. Detection limits were in the 0.110-0.652 ng L(-1) concentration range. The validity of the method was confirmed by recovery studies from natural water samples.