Failure modes and effects analysis of total skin electron irradiation technique.

PURPOSE: Total skin electron irradiation (TSEI) is a radiotherapy technique which consists of an homogeneous body surface irradiation by electrons. This treatment requires very strict technical and dosimetric conditions, requiring the implementation of multiple controls. Recently, the Task Group 100 report of the AAPM has recommended adapting the quality assurance program of the facility to the risks of their processes. MATERIALS AND METHODS: A multidisciplinary team evaluated the potential failure modes (FMs) of every process step, regardless of the management tools applied in the installation. For every FM, occurrence (O), severity (S) and detectability (D) by consensus was evaluated, which resulted in the risk priority number (RPN), which permitted the ranking of the FMs. Subsequently, all the management tools used, related to the TSEI process, were examined and the FMs were reevaluated, to analyze the effectiveness of these tools and to propose new management tools to cover the greater risk FMs. RESULTS: 361 FMs were identified, 103 of which had RPN ≥80, initially, and 41 had S ≥ 8. Taking this into account the quality management tools FMs were reevaluated and only 30 FMs had RPN ≥80. The study of these 30 FMs emphasized that the FMs that involved greater risk were related to the diffuser screen placement and the patient's position during treatment. CONCLUSIONS: The quality assurance program of the facility has been adapted to the risk of this treatment process, following the guidelines proposed by the TG-100. However, clinical experience continually reveals new FMs, so the need for periodic risk analysis is required.

Practical diagnosis of red cell disorders in southern Spain.

BACKGROUND: Hereditary red cell disorders are associated with a protective effect against malaria, which results in an increased prevalence in malaria-endemic areas. Migratory flows from these areas are resulting in a marked increase in such abnormalities in Southern Spain. METHODS: All hemoglobin disorders diagnosed between 1997 and 2010 have been recorded. Since 2008, we have performed systematic screening for hemoglobinopathies on African patients. A high-pressure liquid chromatography system was used as screening method for structural hemoglobinopathies and for separation of hemoglobin (Hb) F and A(2). RESULTS: We detected 666 cases in patients of foreign origin and 308 in native Spanish patients. Thalassemias (thal) are the most frequent disorders amongst the local population: ß-thal minor, 57.1% (176/308); α-thal, 18.2% (56/308), and δß-thal, 7.8% (24/308). In ethnic minorities, there is a huge variety of hemoglobinopathies: heterozygous Hb S, 45% (300/666); heterozygous Hb C, 15% (100/666); ß-thal minor, 13.7% (91/666); α-thal, 10.2% (68/666); Hb SS in 14 patients, and Hb CC in 9 patients. Of the native patients, 14 were found to have Hb AS and 9 Hb AC. CONCLUSION: Given the modern migratory flows, greater knowledge of these disorders is needed by all medical staff, and new practical and cost/time-effective diagnostic approaches have to be devised.

Restriction of trophic factors and nutrients induces PARKIN expression.

Parkinson's disease (PD) is the most frequent neurodegenerative movement disorder and manifests at old age. While many details of its pathogenesis remain to be elucidated, in particular the protein and mitochondrial quality control during stress responses have been implicated in monogenic PD variants. Especially the mitochondrial kinase PINK1 and the ubiquitin ligase PARKIN are known to cooperate in autophagy after mitochondrial damage. As autophagy is also induced by loss of trophic signaling and PINK1 gene expression is modulated after deprivation of cytokines, we analyzed to what extent trophic signals and starvation stress regulate PINK1 and PARKIN expression. Time course experiments with serum deprivation and nutrient starvation of human SH-SY5Y neuroblastoma cells and primary mouse neurons demonstrated phasic induction of PINK1 transcript up to twofold and PARKIN transcript levels up to sixfold. The corresponding threefold starvation induction of PARKIN protein was limited by its translocation to lysosomes. Analysis of primary mouse cells from PINK1-knockout mice indicated that PARKIN induction and lysosomal translocation occurred independent of PINK1. Suppression of the PI3K-Akt-mTOR signaling by pharmacological agents modulated PARKIN expression accordingly. In conclusion, this expression survey demonstrates that PARKIN and PINK1 are coregulated during starvation and suggest a role of both PD genes in response to trophic signals and starvation stress.

Extraction, purification and characterization of the plant-produced HPV16 subunit vaccine candidate E7 GGG.

Several studies indicated that biopharmaceuticals based on the recombinant protein E7 of human papillomavirus (HPV) can serve as therapeutic vaccines preventing the development of cancer in women infected with high-risk types of HPV such as HPV16. Here, we report effective extraction and purification of a plant-produced E7GGG-lichenase fusion protein, an HPV16 subunit vaccine candidate, from Nicotiana benthamiana plants, to a high yield. The target contains the modified HPV16 E7 protein internally fused to the surface loop of a truncated, hexa-His- and KDEL-tagged variant of bacterial lichenase, and has been previously shown to possess anti-cancer activity in an animal model. We purified the protein using a combination of immobilized metal-ion affinity chromatography and gel filtration. The achieved purity of the final product was 99% as confirmed by Coomassie or SYPRO Ruby staining after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by analytical size exclusion chromatography coupled with multi-angle laser light scattering. The overall yield was 50% corresponding to 0.1g of protein per 1 kg plant biomass. Only slight changes in these parameters were observed during the process scale-up from 50 g to 1 kg of processed leaf biomass.

NFATc3 is required for chronic hypoxia-induced pulmonary hypertension in adult and neonatal mice.

Pulmonary hypertension occurs with prolonged exposure to chronic hypoxia in both adults and neonates. The Ca(2+)-dependent transcription factor, nuclear factor of activated T cells isoform c3 (NFATc3), has been implicated in chronic hypoxia-induced pulmonary arterial remodeling in adult mice. Therefore, we hypothesized that NFATc3 is required for chronic hypoxia-induced pulmonary hypertension in adult and neonatal mice. The aim of this study was to determine whether 1) NFATc3 mediates chronic hypoxia-induced increases in right ventricular systolic pressure in adult mice; 2) NFATc3 is activated in neonatal mice exposed to chronic hypoxia; and 3) NFATc3 is involved in chronic hypoxia-induced right ventricular hypertrophy and pulmonary vascular remodeling in neonatal mice. Adult mice were exposed to hypobaric hypoxia for 2, 7, and 21 days. Neonatal mouse pups were exposed for 7 days to hypobaric chronic hypoxia within 2 days after delivery. Hypoxia-induced increases in right ventricular systolic pressure were absent in NFATc3 knockout adult mice. In neonatal mice, chronic hypoxia caused NFAT activation in whole lung and nuclear accumulation of NFATc3 in both pulmonary vascular smooth muscle and endothelial cells. In addition, heterozygous NFATc3 neonates showed less right ventricular hypertrophy and pulmonary artery wall thickness in response to chronic hypoxia than did wild-type neonates. Our results suggest that NFATc3 mediates pulmonary hypertension and vascular remodeling in both adult and neonatal mice.

Hipercoagulabilidad debida a resistencia adquirida a la proteína C activada: ¿primer signo de neoplasia de colon? / Hypercoagulable state due to acquired protein C resistance. Harbinger of colonic neoplasm?

La resistencia a la proteína C activada (RPCa) hereditaria se ha identificado como un importante factor de riesgo para sucesos tromboembólicos, y consiste en una mutación del factor V que lo hace irreconocible para la inhibición por la proteína C activada (Factor V Leiden, FVL). Sin embargo, la RPCa también se describe en pacientes sin FVL (RPCa adquirida) asociada a la presencia de anticoagulante lúpico, embarazo y neoplasias. Describimos un caso de TVP en una mujer de 54 años, sin síntomas digestivos y con marcadores tumorales negativos, que presentaba RPCa y fue diagnosticada un año después de adenocarcinoma de colon. Una vez consiguió remisión completa, se normalizó la RPCa y se descartó que presentara FVL. En el estudio de trombofilia, el hallazgo de RPCa puede verse influida por reactantes de fase aguda o por un proceso neoplásico, por lo que requiere una valoración evolutiva y un rastreo genético del FVL

Hereditary activated protein C resistance (aPCR) has been indentified as an important risk factor for the occurrence of thromboembolic events. It is most frequently hereditary, and caused by a point mutation in factor V, named Factor V Leiden (FVL), which renders it resistant to the anticoagulant action of circulating protein C. However, aPCR can also be found in absence of FVL (acquired aPCR), associated to lupus anticoagulant, pregnancy or neoplasms. We report a case of deep venous thrombosis (DVT) in a 54 year-old woman, with no digestive symptoms and negative screening for biochemical tumor markers, who presented with DVT from FVL-negative aPCR, one year before being diagnosed of colonic adenocarcinoma. Once complete remission of the carcinoma was reached, aPCR returned to normal values. In thrombophilia screening studies, the finding of aPCR may be caused by acute-phase reactants or neoplastic processes, and therefore require evolutive evaluation and genetic search for FVL

“Plasmocitoma-like” gástrico en un paciente trasplantado cardíaco. Revisión de algunos conceptos etiopatogénicos y terapéuticos / Gastric plasmacytoma-like in a patient with heart transplant: review of some etiopathogenic and therapeutic concepts

El Plasmocitoma-like es una entidad poco frecuenteenglobada dentro de los trastornos linfoproliferativospostransplante (TLPT). La inmunosupesióny la infección con virus de Epstein-Barr (VEB)juegan un papel primordial en su desarrollo. Sudiagnóstico preoperatorio es difícil si no se aplicanestudios inmunohistoquímicos sobre las biopsias, yel tratamiento adecuado debe ser quirúrgico y/o radioterápico,asociado a la reducción de la dosis deinmunosupresores. El seguimiento de estos enfermosdebe ser estrecho ya que puede ocurrir la recurrenciadel tumor, así como la aparición de rechazodel trasplante por la disminución de los inmunosupresores.Presentamos un paciente trasplantado cardíacoque desarrolló un TLPT tipo "plasmocitoma-like"en el estómago siete años después del trasplante, comentamoslas teorías etiopatogénicas, los criteriosdiagnósticos y sus posibilidades de tratamiento

Plasmacytoma-like tumour is an infrequent entityobserved among the post-transplant lymphoproliferativedisorders (PTLD). Immunosuppression andEpstein.Barr virus (EBV) infection play animportant role in the development of the process.The preoperative diagnosis is difficult, but it can bemade by means of immunohistochemical studies ofthe biopsies. The adequate treatment consists ofsurgery, radiotherapy and reduction of theadministered immunosuppressor drugs. The patientsneed a close follow up because the resultingimmusuppression facilitates the recurrence of thetumour or the rejection of the transplanted organ.We present the case of a patient with a hearttransplant who developed a gastric plasmacytomalikePTLD seven years after transplantation. Wediscuss the etiopathogenic theories, the diagnosticcriteria and the treatment options

[Hypercoagulable state due to acquired protein C resistance, harbinger of colonic neoplasm?]. / Hipercoagulabilidad debida a resistencia adquirida a la proteína C activada: primer signo de neoplasia de colon?

Hereditary activated protein C resistance (aPCR) has been identified as an important risk factor for the occurrence of thromboembolic events. It is most frequently hereditary, and caused by a point mutation in factor V, named Factor V Leiden (FVL), which renders it resistant to the anticoagulant action of circulating protein C. However, aPCR can also be found in absence of FVL (acquired aPCR), associated to lupus anticoagulant, pregnancy or neoplasms. We report a case of deep venous thrombosis (DVT) in a 54 year-old woman, with no digestive symptoms and negative screening for biochemical tumor markers, who presented with DVT from FVL-negative aPCR, one year before being diagnosed of colonic adenocarcinoma. Once complete remission of the carcinoma was reached, aPCR returned to normal values. In thrombophilia screening studies, the finding of aPCR may be caused by acute-phase reactants or neoplastic processes, and therefore require evolutive evaluation and genetic search for FVL.

Fístula biliar tras hepatorrafia por traumatismo hepático. Posibilidad de tratamiento postural / Biliary fistula associated with hepatorrhaphy for liver injury. A possible postural management

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Carotenoid photooxidation in photosystem II.

Carotenoids are known to function as light-harvesting pigments and they play important roles in photoprotection in both plant and bacterial photosynthesis. These functions are also important for carotenoids in photosystem II. In addition, beta-carotene recently has been found to function as a redox intermediate in an alternate pathway of electron transfer within photosystem II. This redox role of a carotenoid in photosystem II is unique among photosynthetic reaction centers and stems from the very highly oxidizing intermediates that form in the process of water oxidation. In this minireview, an overview of the electron-transfer reactions in photosystem II is presented, with an emphasis on those involving carotenoids. The carotenoid composition of photosystem II and the physical methods used to study the structure of the redox-active carotenoid are reviewed. Possible roles of carotenoid cations in photoprotection of photosystem II are discussed.

Photochemical behavior of xanthophylls in the recombinant photosystem II antenna complex, CP26.

The steady state absorption and fluorescence spectroscopic properties of the xanthophylls, violaxanthin, zeaxanthin, and lutein, and the efficiencies of singlet energy transfer from the individual xanthophylls to chlorophyll have been investigated in recombinant CP26 protein overexpressed in Escherichia coli and then refolded in vitro with purified pigments. Also, the effect of the different xanthophylls on the extents of static and dynamic quenching of chlorophyll fluorescence has been investigated. Absorption, fluorescence, and fluorescence excitation demonstrate that the efficiency of light harvesting from the xanthophylls to chlorophyll a is relatively high and insensitive to the particular xanthophyll that is present. A small effect of the different xanthophylls is observed on the extent of quenching of Chl fluorescence. The data provide the precise wavelengths of the absorption and fluorescence features of the bound pigments in the highly congested spectral profiles from these light-harvesting complexes. This information is important in assessing the mechanisms by which higher plants dissipate excess energy in light-harvesting proteins.

Utilidad diagnóstica del cuestionario "Alcohol Use Disorders Identification Test" (AUDIT) para detectar trastornos relacionados con el alcohol en pacientes hospitalizados / Diagnostic usefulness of "alcohol use discorders identifications tets" (audit) for detecting alcohol-related problems in hospitalized patients

Fundamento: Evaluar la utilidad diagnóstica del cuestionario AUDIT (Alcohol Use Disorders Identification Test) para detectar trastornos relacionados con el alcohol (TRA) en pacientes hospitalizados valorar las posibles diferencias en función del sexo o la edad y compararla con la de otros métodos utilizados habitualmente (CAGE y marcadores biológicos). Resultados: La sensibilidad del AUDIT para detectar TRA fue del 98 porciento, la especificidad del 94 porciento y el área bajo la curva ROC de 0,99 (IC 95 porciento: 0,98-1). Su sensibilidad fue menor en las mujeres (94 porciento frente a 99 porciento) y en los pacientes menores de 60 años (97 porciento frente a 100 porciento). El CAGE mostró una sensibilidad del 78 porciento y una especificidad del 99 porciento. Entre los marcadores biológicos destacaron la GGT y el VCM con sensibilidades del 83 y 74 porciento y especificidades del 53 y 74 porciento respectivamente. Conclusiones: El AUDIT es un cuestionario muy Efectivo y claramente superior a otros métodos utilizados habitualmente para detectar TRA en pacientes hospitalizados. Su utilidad diagnóstica es menor en mujeres, similar en los dos grupos de edad considerados y claramente superior a la de otros métodos utilizados habitualmente (AU)

Mechanism of nonphotochemical quenching in green plants: energies of the lowest excited singlet states of violaxanthin and zeaxanthin.

The xanthophyll cycle is an enzymatic, reversible process through which the carotenoids violaxanthin, antheraxanthin, and zeaxanthin are interconverted in response to the need to balance light absorption with the capacity to use the energy to drive the reactions of photosynthesis. The cycle is thought to be one of the main avenues for safely dissipating excitation energy absorbed by plants in excess of that needed for photosynthesis. One of the key factors needed to elucidate the molecular mechanism by which the potentially damaging excess energy is dissipated is the energy of the lowest excited singlet (S(1)) state of the xanthophyll pigments. Absorption from the ground state (S(0)) to S(1) is forbidden by symmetry, making a determination of the S(1) state energies of these molecules by absorption spectroscopy very difficult. Fluorescence spectroscopy is potentially the most direct method for obtaining the S(1) state energies. However, because of problems with sample purity, low emission quantum yields, and detection sensitivity, fluorescence spectra from these molecules, until now, have never been reported. In this work these technical obstacles have been overcome, and S(1) --> S(0) fluorescence spectra of violaxanthin and zeaxanthin are presented. The energies of the S(1) states deduced from the fluorescence spectra are 14 880 +/- 90 cm(-)(1) for violaxanthin and 14 550 +/- 90 cm(-)(1) for zeaxanthin. The results provide important insights into the mechanism of nonphotochemical dissipation of excess energy in plants.

[Diagnostic usefulness of the questionnaire "Alcohol Use Disorders Identification Test" (AUDIT) to detect conditions associated with alcohol in hospitalized patients]. / Utilidad diagnóstica del cuestionario "Alcohol Use Disorders Identification Test" (AUDIT) para detectar trastornos relacionados con el alcohol en pacientes hospitalizados.

OBJECTIVE: To evaluate the diagnostic usefulness of AUDIT (Alcohol Use Disorders Identification Test) for detection of alcohol-related problems (ARP) among hospitalized patients, to assess the potential differences according to age or sex and to compare its diagnostic value with that of some other conventionally used measures (CAGE questionnaire and biological markers). MATERIAL AND METHODS: This is a cross-sectional study for evaluation of diagnostic tests including 179 hospitalized patients in a Medicine Unit. Data about weekly alcohol intake were collected through a semistructured interview. AUDIT and CAGE questionnaires were administered and blood levels of GGT, MCV, AST, ALT, alkaline phosphatase, platelet count, trylicerides and uric acid were determined. RESULTS: AUDIT sensitivity in detecting ARP was of 98%, specificity was of 94% and area under ROC was 0.99 (95% CI: 0.98-1). Its sensitivity was shown to be lower both in the female group (94% vs. 99%) and in age group under 60 years (97% vs. 100%). CAGE showed a sensitivity of 78% and a specificity of 99%. Among biological markers GGT and MCV should be highlighted with sensitivities of 83% and 74% and specificities of 53% and 74% respectively. CONCLUSIONS: AUDIT is an effective tool for detection of ARP among hospitalized patients. Its diagnostic usefulness being lower for females, similar for both age groups considered and clearly higher than that of other commonly used measures.