Encapsulation of Tenebrio molitor Hydrolysate with DPP-IV Inhibitory Activity by Electrospraying and Spray-Drying.

This study investigates the encapsulation of Tenebrio molitor hydrolysate exhibiting DPP-IV inhibitory activity by spray-drying and electrospraying techniques. First, we optimized the feed formulation and processing conditions required to obtain nano-microcapsules by electrospraying when using Arabic gum as an encapsulating agent and pullulan and Tween 20 as additives. The optimum formulation was also dried by spray-drying, where the removal of the additives was also assayed. Morphology analysis reveals that electrosprayed capsules have a smaller size (1.2 ± 0.5 µm vs. 12.4 ± 8.7 µm) and greater uniformity compared to those obtained by spray-drying. Regarding the surface nitrogen content and DPP-IV inhibitory activity, our results show no significant difference between the electrosprayed capsules and spray-dried capsules containing additives (IC50 of ~1.5 mg protein/mL). Therefore, it was concluded that adding additives during spray-drying allows for a similar encapsulation efficiency and reduced degradation during processing, as achieved by electrospraying technique but providing higher productivity. On the other hand, spray-dried capsules without additives displayed a higher surface nitrogen content percentage, which was mainly due to the absence of Tween 20 in the feed formulation. Consequently, these capsules presented a higher IC50 value (IC50 of 1.99 ± 0.03 mg protein/mL) due to the potential degradation of surface-exposed peptides.

[Addressing sexual violence in health services]. / La violencia sexual y su abordaje en el sistema de salud.

Sexual violence is a very underdetected public health problem, with important short and long-term consequences on physical, mental, social, sexual and reproductive health, which must be taken into account by health services. Health systems are part of the set of resources necessary for a comprehensive approach from the ecological model: prevention and promotion of healthy sexuality with equality, adequate and coordinated care in the event of sexual assault and subsequent support to prevent sequelae. All sexual violence has health consequences, even those that may seem less serious such as sexual harassment or sexual cyberviolence. We must know the needs of the victim and their possible emotional reactions. A risk assessment will be carried out, the victim will be referred to a hospital if necessary and comprehensive and integrated care will be provided. Care and follow-up must focus on the survivor and with professionals trained in trauma to understand the consequences of sexual violence, offer a safe and trusting environment and know how to reinforce their qualities and support.

[The necessary response of health services to gender violence. Comprehensive care and provision of integrated services]. / La respuesta necesaria de los servicios de salud ante la violencia de género. Atención integral y prestación de servicios integrados.

Gender violence has multiple and serious consequences for the health of victims and their families, hence the reason for the important role that the health system plays in addressing it. Health professionals have a key role in the response, which must include early detection, care, and follow-up; actions in which primary care, because of its privileged position in the system, can play a fundamental part. This article establishes the necessary characteristics for the intervention to be effective: comprehensive care, multidisciplinary approach, intersectoral coordination, and integrated service provision; all of it community-oriented, person-centered, and adapted to its context (social factors and vulnerabilities) with an intersectional approach. The woman, her sons and daughters, and other cohabitants, as well as the perpetrator, are considered the object of intervention in the response, and specific guidelines for action are provided for detection, care, and follow-up. Reorientation of interventions, with emphasis on a community approach, is also proposed.

[Validity of predictive power of the Adjusted Morbidity Groups (AMG) with respect to others population stratification tools.] / Validación del poder predictivo de los Grupos de Morbilidad Ajustada (GMA) respecto de otras herramientas de estratificación de la población.

OBJECTIVE: This work was performed in order to get objective elements of judgment that support the improvement of a national population morbidity grouper based in the Adjusted Morbidity Groups (AMG). The study compared the performance in terms of predictive power on certain health and resource outcomes, in between the AMG and several existing morbidity groupers (ACG®, Adjusted Clinical Groups and CRG®, Clinical Risk Group) used in some Autonomous Regions in Spain (Aragón, Canarias y Castilla y León). METHODS: Cross-sectional analytical study in entitled/insured population with respect to rights of healthcare. Predictive capacity of the complexity weight obtained with the different stratification tools in the first year of the study period was evaluated using a simple classification method that compares the areas under the curves ROC for the following outcomes that occurred in the second year of the study period: Probability of death; probability of having at least one urgent hospital admission; total number of visits to hospital emergencies; total number of visits to primary care; total number of visits to hospital care and spending in pharmacy. RESULTS: The results showed that AMG complexity weight were good predictors for almost all the analyzed outcomes (AUC ROC>0.7; p<0.05), for the different Autonomous Regions and compared to ACG® or CRG®. Only for the outcome of visits to hospital emergencies in Aragon and Canarias; and visits to specialized care in Aragon, the predictive power was weak for all the compared stratification tools. CONCLUSIONS: GMA® is a population stratification tool adequate and as useful as others existing morbidity groupers.

OBJETIVO: Este trabajo se realizó con el objetivo de conseguir elementos objetivos de juicio que apoyasen la evolución de un estratificador de la población nacional desarrollado en base a los Grupos de Morbilidad Ajustada (GMA). Para ello se validó el poder predictivo de esta herramienta de estratificación sobre determinadas variables de resultado, mediante comparación con otros estratificadores como ACG® (Adjusted Clinical Groups) y CRG® (Clinical Risk Group), utilizados en algunas comunidades autónomas (CCAA) como Aragón, Canarias y Castilla y León. METODOS: Se realizó un estudio analítico transversal en la población con derecho a la asistencia sanitaria. Se evaluó la capacidad predictiva del peso de complejidad obtenido con cada una de las herramientas de estratificación en el primer año, mediante un método de clasificación simple que comparó las áreas bajo las curvas ROC sobre las siguientes variables de resultado que sucedieron en el año siguiente: probabilidad de muerte; probabilidad de tener al menos un ingreso hospitalario urgente; número total de asistencias a urgencias hospitalarias; número total de visitas a Atención Primaria (AP); número total de consultas externas de Atención Hospitalaria (AH) y gasto farmacéutico. RESULTADOS: Los resultados obtenidos mostraron que los GMA® fueron buenos predictores de casi todas las variables analizadas (Resultados Curvas ROC AUC>0,7; p<0,05) para las distintas comunidades autónomas, al comparar con los ACG® o los CRG®. Únicamente para la variable de asistencia a urgencias hospitalarias en el caso de Aragón y Canarias, y las derivaciones a AH en el caso de Aragón, la capacidad predictiva no fue adecuada con ninguna de las herramientas de estratificación comparadas. CONCLUSIONES: La herramienta GMA® es un sistema de estratificación de la población adecuado y tan útil como otras alternativas existentes.

[Benefits of mindfulness in pregnant women]. / Beneficios del mindfulness en mujeres embarazadas.

This article is intended to review the effect of mindfulness-based interventions on perinatal mental health. A search of the literature published until September 2019 in the Web of Science (WOS) database was carried out. Taking into account the inclusion and exclusion criteria and after reading the title and abstracts of the articles found, 26 of them have been selected. Finally we only analyzed randomized controlled trials (RCTs) that show data on anxiety, depression, perceived stress and mindfulness before and after intervention and with follow-up data. The results found show that mindfulness-based interventions (IBMs) are more effective than the usual healthcare (TAU) that pregnant women receive for the reduction of depressive, anxious and perceived stress symptoms as well as increasing their postintervention mindfulness levels. For future research, a postpartum follow-up would be considered interesting taking into account variables such as the quality of the mother-baby attachment, adherence to breastfeeding and the evolutionary development of the newborn.

Este trabajo tiene el propósito de revisar el efecto de las intervenciones basadas en mindfulness sobre la salud mental perinatal. Se efectuó una búsqueda de la literatura publicada hasta septiembre 2019 en la base de datos Web of Science (WOS). Teniendo en cuenta los criterios de inclusión y exclusión y después de leer el título y abstracts de los artículos encontrados, se han seleccionado 26 de ellos, de los que se han escogido solo ocho por tratarse de ensayos controlados y aleatorizados (RCTs) que estudian datos de ansiedad, depresión, estrés percibido y mindfulness pre y post-intervención y con datos de seguimiento. Los resultados encontrados muestran que las intervenciones basadas en mindfulness (IBMs) son más eficaces que la asistencia sanitaria habitual (TAU) para la mujer embarazada a la hora de reducir la sintomatología depresiva, ansiosa y estrés percibido e incrementar sus niveles de mindfulness post-intervención. Para futuras investigaciones se consideraría interesante realizar el seguimiento de estas variables en el posparto e incluir otras como la calidad del vínculo madre-bebé, la adherencia a la lactancia materna y el desarrollo evolutivo del recién nacido.

Beneficios del mindfulness en mujeres embarazadas / Benefits of mindfulness in pregnant women

Este trabajo tiene el propósito de revisar el efecto de las intervenciones basadas en mindfulness sobre la salud mental perinatal. Se efectuó una búsqueda de la literatura publicada hasta septiembre 2019 en la base de datos Web of Science (WOS). Teniendo en cuenta los criterios de inclusión y exclusión y después de leer el título y abstracts de los artículos encontrados, se han seleccionado 26 de ellos, de los que se han escogido solo ocho por tratarse de ensayos controlados y aleatorizados (RCTs) que estudian datos de ansiedad, depresión, estrés percibido y mindfulness pre y post-intervención y con datos de seguimiento. Los resultados encontrados muestran que las intervenciones basadas en mindfulness (IBMs) son más eficaces que la asistencia sanitaria habitual (TAU) para la mujer embarazada a la hora de reducir la sintomatología depresiva, ansiosa y estrés percibido e incrementar sus niveles de mindfulness post-intervención. Para futuras investigaciones se consideraría interesante realizar el seguimiento de estas variables en el posparto e incluir otras como la calidad del vínculo madre-bebé, la adherencia a la lactancia materna y el desarrollo evolutivo del recién nacido.

This article is intended to review the effect of mindfulness-based interventions on perinatal mental health. A search of the literature published until September 2019 in the Web of Science (WOS) database was carried out. Taking into account the inclusion and exclusion criteria and after reading the title and abstracts of the articles found, 26 of them have been selected. Finally we only analyzed randomized controlled trials (RCTs) that show data on anxiety, depression, perceived stress and mindfulness before and after intervention and with follow-up data. The results found show that mindfulness-based interventions (IBMs) are more effective than the usual healthcare (TAU) that pregnant women receive for the reduction of depressive, anxious and perceived stress symptoms as well as increasing their post-intervention mindfulness levels. For future research, a postpartum follow-up would be considered interesting taking into account variables such as the quality of the mother-baby attachment, adherence to breastfeeding and the evolutionary development of the newborn.

Validación del poder predictivo de los Grupos de Morbilidad Ajustada (GMA) respecto de otras herramientas de estratificación de la población / Validity of predictive power of the Adjusted Morbidity Groups (AMG) with respect to others population stratification tools

OBJETIVO: Este trabajo se realizó con el objetivo de conseguir elementos objetivos de juicio que apoyasen la evolución de un estratificador de la población nacional desarrollado en base a los Grupos de Morbilidad Ajustada (GMA). Para ello se validó el poder predictivo de esta herramienta de estratificación sobre determinadas variables de resultado, mediante comparación con otros estratificadores como ACG® (Adjusted Clinical Groups) y CRG® (Clinical Risk Group), utilizados en algunas comunidades autónomas (CCAA) como Aragón, Canarias y Castilla y León. MÉTODOS: Se realizó un estudio analítico transversal en la población con derecho a la asistencia sanitaria. Se evaluó la capacidad predictiva del peso de complejidad obtenido con cada una de las herramientas de estratificación en el primer año, mediante un método de clasificación simple que comparó las áreas bajo las curvas ROC sobre las siguientes variables de resultado que sucedieron en el año siguiente: probabilidad de muerte; probabilidad de tener al menos un ingreso hospitalario urgente; número total de asistencias a urgencias hospitalarias; número total de visitas a Atención Primaria (AP); número total de consultas externas de Atención Hospitalaria (AH) y gasto farmacéutico. RESULTADOS: Los resultados obtenidos mostraron que los GMA® fueron buenos predictores de casi todas las variables analizadas (Resultados Curvas ROC AUC>0,7; p < 0,05) para las distintas comunidades autónomas, al comparar con los ACG® o los CRG®. Únicamente para la variable de asistencia a urgencias hospitalarias en el caso de Aragón y Canarias, y las derivaciones a AH en el caso de Aragón, la capacidad predictiva no fue adecuada con ninguna de las herramientas de estratificación comparadas. CONCLUSIONES: La herramienta GMA® es un sistema de estratificación de la población adecuado y tan útil como otras alternativas existentes

OBJECTIVE: This work was performed in order to get objective elements of judgment that support the improvement of a national population morbidity grouper based in the Adjusted Morbidity Groups (AMG). The study compared the performance in terms of predictive power on certain health and resource outcomes, in between the AMG and several existing morbidity groupers (ACG®, Adjusted Clinical Groups and CRG®, Clinical Risk Group) used in some Autonomous Regions in Spain (Aragón, Canarias y Castilla y León). METHODS: Cross-sectional analytical study in entitled/insured population with respect to rights of healthcare. Predictive capacity of the complexity weight obtained with the different stratification tools in the first year of the study period was evaluated using a simple classification method that compares the areas under the curves ROC for the following outcomes that occurred in the second year of the study period: Probability of death; probability of having at least one urgent hospital admission; total number of visits to hospital emergencies; total number of visits to primary care; total number of visits to hospital care and spending in pharmacy. RESULTS: The results showed that AMG complexity weight were good predictors for almost all the analyzed outcomes (AUC ROC>0.7; p < 0.05), for the different Autonomous Regions and compared to ACG® or CRG®. Only for the outcome of visits to hospital emergencies in Aragon and Canarias; and visits to specialized care in Aragon, the predictive power was weak for all the compared stratification tools. CONCLUSIONS: GMA® is a population stratification tool adequate and as useful as others existing morbidity groupers

Isoprene Acts as a Signaling Molecule in Gene Networks Important for Stress Responses and Plant Growth.

Isoprene synthase converts dimethylallyl diphosphate to isoprene and appears to be necessary and sufficient to allow plants to emit isoprene at significant rates. Isoprene can protect plants from abiotic stress but is not produced naturally by all plants; for example, Arabidopsis (Arabidopsis thaliana) and tobacco (Nicotiana tabacum) do not produce isoprene. It is typically present at very low concentrations, suggesting a role as a signaling molecule; however, its exact physiological role and mechanism of action are not fully understood. We transformed Arabidopsis with a Eucalyptus globulus isoprene synthase The regulatory mechanisms of photosynthesis and isoprene emission were similar to those of native emitters, indicating that regulation of isoprene emission is not specific to isoprene-emitting species. Leaf chlorophyll and carotenoid contents were enhanced by isoprene, which also had a marked positive effect on hypocotyl, cotyledon, leaf, and inflorescence growth in Arabidopsis. By contrast, leaf and stem growth was reduced in tobacco engineered to emit isoprene. Expression of genes belonging to signaling networks or associated with specific growth regulators (e.g. gibberellic acid that promotes growth and jasmonic acid that promotes defense) and genes that lead to stress tolerance was altered by isoprene emission. Isoprene likely executes its effects on growth and stress tolerance through direct regulation of gene expression. Enhancement of jasmonic acid-mediated defense signaling by isoprene may trigger a growth-defense tradeoff leading to variations in the growth response. Our data support a role for isoprene as a signaling molecule.

Potential drug-drug interactions and nephrotoxicity in hematopoietic stem cell transplant adult recipients during bone marrow transplantation unit stay.

PURPOSE: Studies have documented potential drug-drug interactions (pDDIs) occurring in cancer patients mainly with solid malignancies, either in the ambulatory or hospital settings. While hematopoietic stem cell transplant (HSCT) patients during their bone marrow transplantation unit (BMTU) stay have rather complex medical regimens combining chemotherapy, anti-infectious agents, immunosuppressive agents, and supportive-care drugs, studies on potential DDIs are lacking. Our objective was to evaluate the prevalence and the density of pharmacokinetic and pharmacodynamic potential DDIs, and the evolution of the renal function in hematopoietic stem cell transplant (HSCT) adult recipients during their BMTU stay. METHODS: Retrospective study in 31 adult patients consecutively admitted to the BMTU. RESULTS: Prevalence of pharmacokinetic interactions was ten times lower than the pharmacodynamic interactions. The contraindications were rare, and only of pharmacokinetic origin. The main drugs involved in pharmacokinetic DDIs were ciclosporine, methotrexate, esomeprazole, tramadol, and vincristine. The median number of potential nephrotoxicity-related DDIs per patient was 7 and the median number of days during which nephrotoxicity-related DDIs potentially occurred was 77 days per patient. The decrease in glomerular filtration rate (GFR) throughout the BMTU stay (mean decrease of 13 ml/min) was correlated with the number of days of potential nephrotoxic drug interactions. CONCLUSIONS: Potential DDIs in HCST patients in BMTU were quite common. The DDIs from pharmacokinetic origin were less frequent, but of higher grade, than those of pharmacodynamic origin. The decrease in GFR suggests that the density of potential nephrotoxic drug interactions may be an issue to be considered in these patients.

Stratifying diffuse large B-cell lymphoma patients treated with chemoimmunotherapy: GCB/non-GCB by immunohistochemistry is still a robust and feasible marker.

Diffuse large B cell lymphoma (DLBCL) is a heterogeneous group of aggressive lymphomas that can be classified into three molecular subtypes by gene expression profiling (GEP): GCB, ABC and unclassified. Immunohistochemistry-based cell of origin (COO) classification, as a surrogate for GEP, using three available immunohistochemical algorithms was evaluated in TMA-arranged tissue samples from 297 patients with de novo DLBCL treated by chemoimmunotherapy (R-CHOP and R-CHOP-like regimens). Additionally, the prognostic impacts of MYC, BCL2, IRF4 and BCL6 abnormalities detected by FISH, the relationship between the immunohistochemical COO classification and the immunohistochemical expression of MYC, BCL2 and pSTAT3 proteins and clinical data were evaluated. In our series, non-GCB DLBCL patients had significantly worse progression-free survival (PFS) and overall survival (OS), as calculated using the Choi, Visco-Young and Hans algorithms, indicating that any of these algorithms would be appropriate for identifying patients who require alternative therapies to R-CHOP. Whilst MYC abnormalities had no impact on clinical outcome in the non-GCB subtype, those patients with isolated MYC rearrangements and a GCB-DLBCL phenotype had worse PFS and therefore might benefit from novel treatment approaches.

Adherencia al tratamiento farmacológico y no farmacológico en pacientes con falla cardiaca / Adherence to phararmacological and non - pharmacological treatment in patients with heart failure

Las consecuencias de la no adherencia al tratamiento se expresan en diversas esferas de la vida de la persona, en diversos componentes del sistema de salud y en el cuadro de morbilidad y mortalidad de la población, lo cual genera grandes repercusiones desde el punto de vista médico, económico y en la calidad de vida de la persona. Objetivo: Determinar la prevalencia de adherencia al tratamiento farmacológico y no farmacológico en pacientes con falla cardiaca. Métodos: Se realizó un estudio de corte transversal en pacientes con falla cardiaca en el 2012 en la Clínica de Falla Cardiaca y Trasplante Cardiaco de la Fundación Cardiovascular de Colombia. Se incluyeron 161 pacientes adultos con diagnóstico médico de falla cardiaca. Se evaluó la adherencia al tratamiento farmacológico y no farmacológico y el cumplimiento en los pacientes con falla cardiaca. Resultados: El 80.12% (n=129; IC 9 5% 73.11-85.98%) de los pacientes se encuentra frecuentemente adheridos al tratamiento farmacológico y no farmacológico, el cumplimiento al tratamiento farmacológico con el test de Morisky-Green fue de 53.42% (n=86; IC 95% 45.39-61.3%). Conclusiones: Los resultados del presente estudio son un acercamiento a la problemática de la adherencia al tratamiento farmacológico y no farmacológico de los pacientes con falla cardiaca. Se recomienda para futuras investigaciones, la realización de estudios multicéntricos con muestreos (AU)

Consequences of non-adherence to treatment are expressed in various spheres of the individual's life, in various components of the health system and in the population's morbidity and mortality, which generates repercussions in the medical and economical aspects and in the individual’s life quality. Objective: To determine the prevalence of adherence to pharmacological and non-pharmacological treatment in patients with heart failure. Methods: A cross sectional study was conducted in patients with heart failure during 2012 in the Heart Failure and Heart Transplant Clinic of the Fundación Cardiovascular de Colombia. 161 adult patients were included with the diagnosis of heart failure. Adherence to pharmacological and non-pharmacological treatment was evaluated as well as compliance of the patients with heart failure. Results: 80.12% (n=129; 95% CI 73.11-85.98%) of the patients are often adhered to pharmacological and non-pharmacological treatment, complian ce to pharmacological treatment with the Morisky-Green test was of 53.42% (n=86; 95% CI 45.39-61.3%). Conclusions: The results of this study are an approach to the problem of adherence to pharmacological and non-pharmacological treatment of patients with heart failure. It is recommended for future researches, the realization of multicenter studies with probabilistic samplings (AU)

An A91V SNP in the perforin gene is frequently found in NK/T-cell lymphomas.

NK/T-cell lymphoma (NKTCL) is the most frequent EBV-related NK/T-cell disease. Its clinical manifestations overlap with those of familial haemophagocytic lymphohistiocytosis (FHLH). Since PERFORIN (PRF1) mutations are present in FHLH, we analysed its role in a series of 12 nasal and 12 extranasal-NKTCLs. 12.5% of the tumours and 25% of the nasal-origin cases had the well-known g.272C>T(p.Ala91Val) pathogenic SNP, which confers a poor prognosis. Two of these cases had a double-CD4/CD8-positive immunophenotype, although no correlation was found with perforin protein expression. p53 was overexpressed in 20% of the tumoral samples, 80% of which were of extranasal origin, while none showed PRF1 SNVs. These results suggest that nasal and extranasal NKTCLs have different biological backgrounds, although this requires validation.

BET inhibition silences expression of MYCN and BCL2 and induces cytotoxicity in neuroblastoma tumor models.

BET family proteins are epigenetic regulators known to control expression of genes involved in cell growth and oncogenesis. Selective inhibitors of BET proteins exhibit potent anti-proliferative activity in a number of hematologic cancer models, in part through suppression of the MYC oncogene and downstream Myc-driven pathways. However, little is currently known about the activity of BET inhibitors in solid tumor models, and whether down-regulation of MYC family genes contributes to sensitivity. Here we provide evidence for potent BET inhibitor activity in neuroblastoma, a pediatric solid tumor associated with a high frequency of MYCN amplifications. We treated a panel of neuroblastoma cell lines with a novel small molecule inhibitor of BET proteins, GSK1324726A (I-BET726), and observed potent growth inhibition and cytotoxicity in most cell lines irrespective of MYCN copy number or expression level. Gene expression analyses in neuroblastoma cell lines suggest a role of BET inhibition in apoptosis, signaling, and N-Myc-driven pathways, including the direct suppression of BCL2 and MYCN. Reversal of MYCN or BCL2 suppression reduces the potency of I-BET726-induced cytotoxicity in a cell line-specific manner; however, neither factor fully accounts for I-BET726 sensitivity. Oral administration of I-BET726 to mouse xenograft models of human neuroblastoma results in tumor growth inhibition and down-regulation MYCN and BCL2 expression, suggesting a potential role for these genes in tumor growth. Taken together, our data highlight the potential of BET inhibitors as novel therapeutics for neuroblastoma, and suggest that sensitivity is driven by pleiotropic effects on cell growth and apoptotic pathways in a context-specific manner.

TCR-γ expression in primary cutaneous T-cell lymphomas.

Primary cutaneous γδ T-cell lymphomas (PCGD-TCLs) are considered a subgroup of aggressive cytotoxic T-cell lymphomas (CTCLs). We have taken advantage of a new, commercially available antibody that recognizes the T-cell receptor-γ (TCR-γ) subunit of the TCR in paraffin-embedded tissue. We have analyzed a series of 146 primary cutaneous T-cell lymphomas received for consultation or a second opinion in the CNIO Pathology Department. Cases were classified according to the World Health Organization 2008 classification as mycosis fungoides (MF; n=96), PCGD-TCLs (n=5), pagetoid reticulosis (n=6), CD30(+) primary cutaneous anaplastic large cell lymphomas (n=5), primary cutaneous CD8 aggressive epidermotropic CTCLs (n=3), primary cutaneous CTCL, not otherwise specified (n=4), and extranodal nasal-type NK/T-cell lymphomas primarily affecting the skin or subcutaneous tissue (n=11). Sixteen cases of the newly named lymphomatoid papulosis type D (LyP-D; n=16) were also included. In those cases positive for TCR-γ, a further panel of 13 antibodies was used for analysis, including TIA-1, granzyme B, and perforin. Clinical and follow-up data were recorded in all cases. Twelve cases (8.2%) were positive for TCR-γ, including 5 PCGD-TCLs, 2 MFs, and 5 LyP-Ds. All 5 PCGD-TCL patients and 1 MF patient died of the disease, whereas the other MF patient and all those with LyP-D were alive. All cases expressed cytotoxic markers, were frequently CD3(+)/CD8(+), and tended to lose CD5 and CD7 expressions. Eight of 12 and 5 of 11 cases were CD30(+) and CD56(+), respectively. Interestingly, 5/12 TCR-γ-positive cases also expressed TCR-BF1. All cases analyzed were negative for Epstein-Barr virus-encoded RNA. In conclusion, TCR-γ expression seems to be rare and is confined to cytotoxic primary cutaneous TCLs. Nevertheless, its expression is not exclusive to PCGD-TCLs, as TCR-γ protein can be found in other CTCLs. Moreover, its expression does not seem to be associated with bad prognosis by itself, as it can be found in cases with good and bad outcomes.

Expression of COX-2 on Reed-Sternberg cells is an independent unfavorable prognostic factor in Hodgkin lymphoma treated with ABVD.

Cyclooxygenase 2 (COX-2) is an inflammatory enzyme involved in the pathogenesis and prognosis of several malignancies. In the present study, we investigated the prognostic value of COX-2 expression in a large (N = 242), uniformly treated Hodgkin lymphoma (HL) population from the Spanish Network of HL using tissue microarrays. Univariate and multivariate analysis was done, including comparing the most recognized clinical variables: the early- and advanced-stage subgroups. COX-2 was expressed on Reed-Sternberg cells in 37% of patients. There were no differences in the distribution of clinical variables according to COX-2 expression. With a median follow-up time of 58 months, PFS at 5 years was 60% and 79% for COX-2(+) and COX-2(-) patients, respectively (P = .003). The overall survival was 73% and 91%, respectively (P < .001). The major impact on prognosis was observed in the early AA stage (I-II) group. In fact, in these low-risk groups the expression of COX-2 defined a group with significantly worse progression-free and overall survival. In conclusion, COX-2 was expressed on Reed-Sternberg cells in one-third of HL patients and was a major independent, unfavorable prognostic factor in early-stage HL. We conclude that COX-2 may be a major prognostic variable in HL and a potential therapeutic target.

Epstein-Barr virus-positive systemic NK/T-cell lymphomas in children: report of six cases.

AIMS: The World Health Organization lymphoma classification recognizes two different Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disorders of childhood: systemic EBV-positive T-cell lymphoproliferative disease of childhood, and hydroa vacciniforme-like lymphoma, which is more prevalent in Asia and Latin America. The aim of this study was to characterize six cases of paediatric EBV-positive peripheral T-cell lymphoma with distinct features. METHODS AND RESULTS: All cases were male, with a median patient age of 9 years (range: 5-17 years). Most of them presented suddenly with fever, weight loss, hepatosplenomegaly, peripheral lymphadenopathy, and high lactate dehydrogenase (LDH) levels. Moreover, gut, lung or soft tissues of the abdominal wall were also affected in four cases. Partial to total replacement of the lymph node by pleomorphic infiltration of atypical neoplastic cells was found in all cases. Vasculitis and geographical areas of necrosis were seen in three and four cases, respectively. Neoplastic cells showed expression of EBV-encoded RNA, T-cell markers (CD2 and CD3), and cytotoxic markers (TIA1, granzyme-B, and perforin). CD56 and T-cell receptor -γ were expressed in one case each. TCR-BF1, CD4, CD8 and anaplastic lymphoma kinase were negative. In all cases, the disease progressed rapidly, causing death of the patient, with a median survival of 7.1 months (range: 1-13 months). CONCLUSIONS: These cases probably represent a solid form of systemic EBV-positive T-cell lymphoproliferative disease of childhood, which requires identification and the development of appropriate therapy.

Detection of the first gross CDC73 germline deletion in an HPT-JT syndrome family.

Hereditary primary hyperparathyroidism (HPT) may develop as a solitary endocrinopathy (FIHP) or as part of multiple endocrine neoplasia Type 1, multiple endocrine neoplasia Type 2A, or hereditary HPT-jaw tumor syndrome. Inactivating germline mutations of the tumor suppressor gene CDC73 account for 14 and 50% of all FIHP and HPT-JT patients, respectively, and have also been found in almost 20% of apparently sporadic parathyroid carcinoma patients. Although more than 60 independent germline mutations have been described, to date no rearrangement affecting the CDC73 locus has been identified. By means of multiplex-PCR we found a large germline deletion affecting the whole gene in a two-generation HPT-JT family. Subsequently array-CGH and specific PCR analysis determined that the mutation spanned ∼ 547 kb, and included four additional genes: TROVE2, GLRX2, B3GALT2, and UCHL5. Although no clear mutation-specific phenotype was found associated to the presence of the mutation, further studies are needed to assess whether the loss of the neighboring genes could modify the phenotype of carriers. There was complete absence of nuclear staining in the two HPT-JT-related tumors available. The finding of the first rearrangement affecting the CDC73 gene warrants screening for this tumor suppressor gene inactivation mechanism not only in high-risk CDC73 point mutation-negative HPT-JT families, but also in FIHP patients.

EBV-associated cutaneous NK/T-cell lymphoma: review of a series of 14 cases from peru in children and young adults.

We have reviewed clinically, morphologically, and immunophenotypically a series of 14 Epstein-Bar virus (EBV)+ cutaneous natural killer cell (NK)/T-cell lymphoma from Peru. Most (11 out of 14) of these cases fit well into the category of Hydroa vacciniforme-like lymphoma (HVLL), but 3 have a different clinical presentation, without facial involvement. In all 14 cases, skin lesions present in both the sun-exposed and nonexposed areas exhibited a slowly progressive relapsing course, changing from edema, to blistering, ulceration, and final scarring. The immunophenotype had a cytotoxic T or NK-cell lineage. The mean time of disease before admission to hospital was 69 months (range, 6 mo to 31 y). Only 2 patients had fever, hepatosplenomegaly, systemic lymphadenopathy, and a high lactate dehydrodenage (LDH) level at the time of diagnosis, whereas 10 had facial swelling. After treatment, only 4 patients remain alive, although with persistent disease. Ten patients died after a mean follow-up of 11.6 months after the initial diagnosis (range, 1 to 32 mo), because of concurrent infections (4 cases), disease progression (4 patients) or both (2 patients). Endemic Epstein-Bar virus (EBV)-positive cutaneous NK/T-cell lymphoproliferative disorders in childhood and early adulthood are characterized by a protracted clinical course, eventually leading to an aggressive phase characterized by concurrent infections and disease progression.

Overexpression of RAD51 occurs in aggressive prostatic cancer.

AIMS: To test the hypothesis that, in a matched series of prostatic cancers, either with or without BRCA1 or BRCA2 mutations, RAD51 protein expression is enhanced in association with BRCA mutation genotypes. METHODS AND RESULTS: RAD51 expression identified immunohistochemically was compared between prostatic cancers occurring in BRCA1 or BRCA2 mutation carriers and controls. RAD51 protein expression in the cytoplasm and nuclei of the benign tissues was significantly less than in the malignant tissues (P < 0.001). In all cancers, cytoplasmic expression of RAD51 was more prevalent and associated with higher Gleason score (P < 0.05) irrespective of BRCA mutational status, than its expression in benign tissues (P < 0.001). Although nuclear immunoreactivity was not observed in BRCA-associated cancers with Gleason score < or =7, it was significantly increased in all other groups of prostatic cancers when compared with benign tissues (P < 0.001). CONCLUSIONS: RAD51 protein is strongly expressed in high-grade prostatic cancers, whether sporadic or associated with BRCA germ-line mutations. Distinct localization of RAD51 between cytoplasm and nucleus, particularly in cancers of Gleason score < or =7, reflects distinct levels of RAD51 regulatory activity, from transcription to DNA repair. This biomarker may be of value in identifying patients requiring urgent treatment at diagnosis as well as in analysing biological mechanisms underlying aggressive phenotype of human prostatic cancer.

Violencia y maltrato de género (y III). Nociones prácticas para su detección precoz y abordaje integral en urgencias / Gender-based violence and mistreatment (and III). Practice guidelines for early detection and an integrated approach to emergency care

Los servicios de urgencias son uno de los lugares más accesibles que pueden encontrarlas mujeres víctimas de malos tratos para solicitar ayuda, por lo que se detectan cifras altas de violencia doméstica entre las usuarias de estos centros. Consultan por muy diversas causas, será importante estar sensibilizados con el problema para detectarlo precozmente. Los dos aspectos más importantes en la atención urgente a la violencia hacia las mujeres son la detección precoz con las técnicas de anamnesis adecuadas y la valoración del riesgo vital que tiene la paciente antes de ser dada de alta de urgencias. Se recomienda realizar una entrevista dirigida ante la sospecha de malos tratos, conocer y aplicar el protocolo de actuación ante estos casos e informaremos a la paciente de los recursos existentes y trámites a seguir existentes respetando la decisión que tome (AU)

Emergency rooms are among the most accessible places available to battered women seeking help, and large numbers of domestic violence cases are detected annually during treatment in these facilities. Victims of abuse come to emergency rooms for a variety of reasons and we must raise our awareness of the problem if cases are to be detected early. Key aspects of emergency care of victims of gender-based violence are early detection of cases in the course of taking a full medical history and the assessment of threat to the patient's life before discharge. A directed interview should be undertaken if there is any suspicion of physical abuse, and the caregiver should know the protocol for action in such cases. The patient should be informed of resources that are available and what procedures to follow in order to carry out whatever decision she takes (AU)