[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.

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.

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.

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.

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.

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.

[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.

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.

A high-throughput study in melanoma identifies epithelial-mesenchymal transition as a major determinant of metastasis.

Metastatic disease is the primary cause of death in cutaneous malignant melanoma (CMM) patients. To understand the mechanisms of CMM metastasis and identify potential predictive markers, we analyzed gene-expression profiles of 34 vertical growth phase melanoma cases using cDNA microarrays. All patients had a minimum follow-up of 36 months. Twenty-one cases developed nodal metastatic disease and 13 did not. Comparison of gene expression profiling of metastatic and nonmetastatic melanoma cases identified 243 genes with a >2-fold differential expression ratio and a false discovery rate of <0.2 (206 up-regulated and 37 down-regulated). This set of genes included molecules involved in cell cycle and apoptosis regulation, epithelial-mesenchymal transition (EMT), signal transduction, nucleic acid binding and transcription, protein synthesis and degradation, metabolism, and a specific group of melanoma- and neural-related proteins. Validation of these expression data in an independent series of melanomas using tissue microarrays confirmed that the expression of a set of proteins included in the EMT group (N-cadherin, osteopontin, and SPARC/osteonectin) were significantly associated with metastasis development. Our results suggest that EMT-related genes contribute to the promotion of the metastatic phenotype in primary CMM by supporting specific adhesive, invasive, and migratory properties. These data give a better understanding of the biology of this aggressive tumor and may provide new prognostic and patient stratification markers in addition to potential therapeutic targets.

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.

Immunohistochemical expression of DNA repair proteins in familial breast cancer differentiate BRCA2-associated tumors.

PURPOSE: Morphologic and immunohistochemical studies of familial breast cancers have identified specific characteristics associated with BRCA1 mutation-associated tumors when compared with BRCA2 and non-BRCA1/2 tumors, but have not identified differences between BRCA2 and non-BRCA1/2 tumors. Because BRCA1 and BRCA2 genes participate in the DNA repair pathway, we have performed an immunohistochemical study with markers related to this pathway to establish the profile of the three groups. MATERIALS AND METHODS: We have studied two tissue microarrays that include 103 familial and 104 sporadic breast tumors, with a panel of DNA repair markers including ATM, CHEK2, RAD51, RAD50, XRCC3, and proliferating cell nuclear antigen. RESULTS: We found more frequent expression of CHEK2 in BRCA1 and BRCA2 tumors than in non-BRCA1/2 and sporadic tumors. We found absence of nuclear expression and presence of cytoplasmic expression of RAD51 in BRCA2 tumors that differentiate them from other familial tumors. We validated these results with a new series of patient cases. The final study with 253 familial patient cases (74 BRCA1, 71 BRCA2, 108 non-BRCA1/2), and 288 sporadic patient cases, has allowed us to confirm our preliminary results. Because BRCA2 tumors present a specific immunohistochemical profile for RAD51 and CHEK2 markers that is different from non-BRCA1/2 tumors, we have built a multivariate model with these markers that distinguish both tumors with an estimated probability of at least 76%. CONCLUSION: Our results suggest that BRCA2 tumors demonstrate more cytoplasmic and less nuclear RAD51 staining, and increased CHEK2 staining. This pattern may distinguish BRCA2 from familial non-BRCA1/2 tumors.

The presence of STAT1-positive tumor-associated macrophages and their relation to outcome in patients with follicular lymphoma.

BACKGROUND AND OBJECTIVES: The presence of tumor-associated macrophages (TAM) is a prognostic factor for survival in follicular lymphoma (FL). Overexpression and/or activation of the signal transducer and activator of transcription 1 (STAT1) in these TAM have also been observed. The aim of this study was to determine the extent to which macrophages are present in FL and to investigate the expression of STAT1 in these cells. DESIGN AND METHODS: We retrospectively analyzed 211 patients with distinct stages and grades of FL. Expression of the CD68 proteins, chosen as a marker for macrophages, and STAT1 was quantified by immunohistochemistry and double immunofluorescence. RESULTS: Automated determinations revealed the presence of CD68-positive macrophages in all FL tissues studied (mean 57.6+/-45.1 cells/field), while STAT1 protein was expressed in 29.94% of cases. Double-fluorescence staining confirmed that STAT1 protein co-localized exclusively with CD68, indicating the presence of a subset of STAT1-expressing TAM localized principally in the vicinity of tumor cells. Multivariate analysis showed that, besides the Follicular Lymphoma International Prognostic Index (FLIPI) classification, expression of STAT1 was an important independent prognostic factor for shorter overall survival in FL. INTERPRETATION AND CONCLUSIONS: These results demonstrate the presence of STAT1-expressing TAM in FL and their association with an adverse outcome, thus emphasizing the relevance of non-tumor cells in the control of the growth and survival of lymphoma cells.

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.

About the origin and development of hereditary conventional renal cell carcinoma in a four-generation t(3;8)(p14.1;q24.23) family.

Conventional renal cell carcinoma (CRCC) may appear in families with germline translocations involving chromosome 3, although a recurrent responsible gene has not been found. We recently described a family with CRCC and a constitutional t(3;8)(p14.1;q24.23), and we demonstrated that no genes were disrupted by the translocation breakpoints. In order to investigate the genetic origin and features of the CRCC tumors that occurred in this family, we have extended the pedigree up to four generations, and analyzed peripheral blood samples from 36 members, CRCC tumors, normal renal tissues, and a gastric tumor. (1) By means of comparative genomic hybridization (CGH), we have detected loss of the derivative chromosome carrying 3p in all CRCC but not in the corresponding normal renal tissue. In addition, by means of the fluorescence in situ hybridization technique, we have observed that not all tumoral cells lose the der(3p), which suggests that, previous to this loss, another hit should occur to initiate the transformation of normal into tumoral cells. (2) All known mechanisms of inactivation of the candidate von Hippel-Lindau (VHL) gene have been studied in the tumors, detecting alterations in 65% of them. This confirms that inactivation of the VHL gene is not always required to develop CRCC, and that (an)other suppressor gene(s) on 3p could be involved. (3) We discard FHIT as an alternative pathway to VHL. We have not found new candidate regions along 3p by using a 1-Mb resolution array-based CGH. (4) The tumorigenesis mechanism of a second gastric tumor developed in the probandus is different from that of CRCC.

Immunohistochemical characteristics defined by tissue microarray of hereditary breast cancer not attributable to BRCA1 or BRCA2 mutations: differences from breast carcinomas arising in BRCA1 and BRCA2 mutation carriers.

PURPOSE: Most familial breast cancers are not associated with BRCA1 or BRCA2 germ-line mutations. Therefore, it is of major importance to define the morphological, immunohistochemical, and molecular features of this group of tumors to improve genetic testing and also gain further insight into the biological characteristics of tumors. EXPERIMENTAL DESIGN: We evaluated the morphological characteristics of 37 tumors arising in women without BRCA1 or BRCA2 mutations, 20 tumors from BRCA1 mutation carriers, and 18 from BRCA2 mutation carriers, all of which were from index patients from breast cancer families. In addition, a tissue microarray was constructed with all tumoral samples to evaluate the immunohistochemical expression of a wide panel of antibodies (11 antibodies) and the amplification of HER-2 and c-MYC genes by fluorescence in situ hybridization. An age-matched group with 50 sporadic breast cancers as controls for non-BRCA1/2 was also included. RESULTS: Non-BRCA1/2 infiltrating ductal carcinomas (IDCs) showed specific differences from BRCA1 tumors. They were of lower grade (1 and 2); more frequently estrogen receptor, progesterone receptor, BCL2 positive, and p53 negative; had a low proliferation rate (Ki-67 immunostaining < 5%); and did not express P-cadherin. With respect to BRCA2 IDCs and control group, non-BRCA1/2 tumors were of lower grade and had a lower proliferation rate. No cases of HER-2 amplification and/or overexpression were observed except in the control group ( approximately 20%). In contrast, c-MYC amplification was present in 18.2, 62.5, and 12.5% of BRCA1, BRCA2, and non-BRCA1/2 IDCs, respectively, and 31% in the control group. CONCLUSIONS: This study thus reveals distinct morphological and immunohistochemical features in non-BRCA1/2 and BRCA1 tumors, whereas BRCA2 tumors present characteristics intermediate between the two phenotypes. In addition, the study also demonstrates the usefulness of tissue microarray technology in the evaluation of the immunophenotypic features of hereditary breast cancer.

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.

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.

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.