Overview of the Genetic Causes of Hereditary Breast and Ovarian Cancer Syndrome in a Large French Patient Cohort.

The use of multigene panel testing for patients with a predisposition to Hereditary Breast and Ovarian Cancer syndrome (HBOC) is increasing as the identification of mutations is useful for diagnosis and disease management. Here, we conducted a retrospective analysis of BRCA1/2 and non-BRCA gene sequencing in 4630 French HBOC suspected patients. Patients were investigated using a germline cancer panel including the 13 genes defined by The French Genetic and Cancer Group (GGC)-Unicancer. In the patients analyzed, 528 pathogenic and likely pathogenic variants (P/LP) were identified, including BRCA1 (n = 203, 38%), BRCA2 (n = 198, 37%), PALB2 (n = 46, 9%), RAD51C (n = 36, 7%), TP53 (n = 16, 3%), and RAD51D (n = 13, 2%). In addition, 35 novel (P/LP) variants, according to our knowledge, were identified, and double mutations in two distinct genes were found in five patients. Interestingly, retesting a subset of BRCA1/2-negative individuals with an expanded panel produced clinically relevant results in 5% of cases. Additionally, combining in silico (splicing impact prediction tools) and in vitro analyses (RT-PCR and Sanger sequencing) highlighted the deleterious impact of four candidate variants on splicing and translation. Our results present an overview of pathogenic variations of HBOC genes in the southeast of France, emphasizing the clinical relevance of cDNA analysis and the importance of retesting BRCA-negative individuals with an expanded panel.

Association and performance of polygenic risk scores for breast cancer among French women presenting or not a familial predisposition to the disease.

BACKGROUND: Three partially overlapping breast cancer polygenic risk scores (PRS) comprising 77, 179 and 313 SNPs have been proposed for European-ancestry women by the Breast Cancer Association Consortium (BCAC) for improving risk prediction in the general population. However, the effect of these SNPs may vary from one country to another and within a country because of other factors. OBJECTIVE: To assess their associated risk and predictive performance in French women from (1) the CECILE population-based case-control study, (2) BRCA1 or BRCA2 (BRCA1/2) pathogenic variant (PV) carriers from the GEMO study, and (3) familial breast cancer cases with no BRCA1/2 PV and unrelated controls from the GENESIS study. RESULTS: All three PRS were associated with breast cancer in all studies, with odds ratios per standard deviation varying from 1.7 to 2.0 in CECILE and GENESIS, and hazard ratios varying from 1.1 to 1.4 in GEMO. The predictive performance of PRS313 in CECILE was similar to that reported in BCAC but lower than that in GENESIS (area under the receiver operating characteristic curve (AUC) = 0.67 and 0.75, respectively). PRS were less performant in BRCA2 and BRCA1 PV carriers (AUC = 0.58 and 0.54 respectively). CONCLUSION: Our results are in line with previous validation studies in the general population and in BRCA1/2 PV carriers. Additionally, we showed that PRS may be of clinical utility for women with a strong family history of breast cancer and no BRCA1/2 PV, and for those carrying a predicted PV in a moderate-risk gene like ATM, CHEK2 or PALB2.

AXIN2 germline testing in a French cohort validates pathogenic variants as a rare cause of predisposition to colorectal polyposis and cancer.

Only a few patients with germline AXIN2 variants and colorectal adenomatous polyposis or cancer have been described, raising questions about the actual contribution of this gene to colorectal cancer (CRC) susceptibility. To assess the clinical relevance for AXIN2 testing in patients suspected of genetic predisposition to CRC, we collected clinical and molecular data from the French Oncogenetics laboratories analyzing AXIN2 in this context. Between 2004 and June 2020, 10 different pathogenic/likely pathogenic AXIN2 variants were identified in 11 unrelated individuals. Eight variants were from a consecutive series of 3322 patients, which represents a frequency of 0.24%. However, loss-of-function AXIN2 variants were strongly associated with genetic predisposition to CRC as compared with controls (odds ratio: 11.89, 95% confidence interval: 5.103-28.93). Most of the variants were predicted to produce an AXIN2 protein devoid of the SMAD3-binding and DIX domains, but preserving the ß-catenin-binding domain. Ninety-one percent of the AXIN2 variant carriers who underwent colonoscopy had adenomatous polyposis. Forty percent of the variant carriers developed colorectal or/and other digestive cancer. Multiple tooth agenesis was present in at least 60% of them. Our report provides further evidence for a role of AXIN2 in CRC susceptibility, arguing for AXIN2 testing in patients with colorectal adenomatous polyposis or cancer.

Identification and Characterization of an Exonic Duplication in PALB2 in a Man with Synchronous Breast and Prostate Cancer.

PALB2 (partner and localizer of BRCA2), as indicated by its name, is a BRCA2-interacting protein that plays an important role in homologous recombination (HR) and DNA double-strand break (DSB) repair. While pathogenic variants of PALB2 have been well proven to confer an increased risk of breast cancer, data on its involvement in prostate cancer (PrC) have not been clearly demonstrated. We investigated, using targeted next generation sequencing (NGS), a 59-year-old Caucasian man who developed synchronous breast and prostate cancers. This genetic investigation allowed to identify an intragenic germline heterozygous duplication in PALB2, implicating intronic repetitive sequences spanning exon 11. This variant was confirmed by multiplex ligation probe amplification (MLPA), and genomic breakpoints have been identified and characterized at the nucleotide level (c.3114-811_3202-1756dup) using an approach based on walking PCR, long range PCR, and Sanger sequencing. RT-PCR using mRNA extracted from lymphocytes and followed by Sanger sequencing revealed a tandem duplication r.3114_3201dup; p.(Gly1068Glufs * 14). This duplication results in the synthesis of a truncated, and most-likely, non-functional protein. These findings expand the phenotypic spectrum of PALB2 variants and may improve the yield of genetic diagnoses in this field.

I Look at my whole body and i feel better: attentional bias, emotional and psychophysiological response by pure exposure treatment in women with obesity.

Obesity is one of the most important health problems nowadays. In addition to the direct physical consequences, it is also a risk factor in the development of psychological (Eating disorders, body dissatisfaction, depression, anxiety, etc.) and social problems. Among there, body dissatisfaction is key for development and maintenance of such problems. OBJECTIVE: to deepen the effectiveness of the body exposure treatment, both in its pure form and guided modality in subjective, psychological and attentional levels in people with body dissatisfaction and obesity. METHODS: Evaluations were carried out in a total of 16 women with obesity and body dissatisfaction at the beginning and end of 6 treatment sessions of pure exposure in front of the mirror. The changes experienced at the subjective level (questionnaires and subjective discomfort during the sessions) and psychophysiological (eye-tracking and heart rate) were analyzed. RESULTS: Pure exposure treatment reduces negative thoughts and emotions towards the body itself, as well as the experienced discomfort towards the most conflictive parts. Selective attention to those parts of the body classified as uglier by the participants (especially the rear view of the body) show a decrease in physiological reactivity. CONCLUSIONS: Pure exposure treatment seems to be effective in reducing subjective and psychological symptoms associated with body dissatisfaction in people with obesity, this technique could be considered a good choice for the treatment of body dissatisfaction. This step is essential to guarantee the long-term therapeutic success of any other treatment (nutritional or/and physical activity) in the future.

Diagnostic chest X-rays and breast cancer risk among women with a hereditary predisposition to breast cancer unexplained by a BRCA1 or BRCA2 mutation.

BACKGROUND: Diagnostic ionizing radiation is a risk factor for breast cancer (BC). BC risk increases with increased dose to the chest and decreases with increased age at exposure, with possible effect modification related to familial or genetic predisposition. While chest X-rays increase the BC risk of BRCA1/2 mutation carriers compared to non-carriers, little is known for women with a hereditary predisposition to BC but who tested negative for a BRCA1 or BRCA2 (BRCA1/2) mutation. METHODS: We evaluated the effect of chest X-rays from diagnostic medical procedures in a dataset composed of 1552 BC cases identified through French family cancer clinics and 1363 unrelated controls. Participants reported their history of X-ray exposures in a detailed questionnaire and were tested for 113 DNA repair genes. Logistic regression and multinomial logistic regression models were used to assess the association with BC. RESULTS: Chest X-ray exposure doubled BC risk. A 3% increased BC risk per additional exposure was observed. Being 20 years old or younger at first exposure or being exposed before first full-term pregnancy did not seem to modify this risk. Birth after 1960 or carrying a rare likely deleterious coding variant in a DNA repair gene other than BRCA1/2 modified the effect of chest X-ray exposure. CONCLUSION: Ever/never chest X-ray exposure increases BC risk 2-fold regardless of age at first exposure and, by up to 5-fold when carrying 3 or more rare variants in a DNA repair gene. Further studies are needed to evaluate other DNA repair genes or variants to identify those which could modify radiation sensitivity. Identification of subpopulations that are more or less susceptible to ionizing radiation is important and potentially clinically relevant.

Eutanasia: ¿es esta la ley que necesitamos? / Euthanasia: is this the law we need?

La Ley de Eutanasia española introduce un nuevo derecho que se incorpora a la cartera de servicios del sistema sanitario, como una prestación cuya aplicación se garantiza en el plazo de 40 días. Desde la experiencia clínica se argumenta que, sin el derecho efectivo a unos cuidados paliativos de calidad, y con el actual déficit en las ayudas a la dependencia, esta ley puede ser un mensaje coactivo para aquellas personas especialmente frágiles y dependientes, que se sientan como una pesada carga para su familia y para la sociedad.Se razona de qué modo fundamentar el derecho a morir en la dignidad de la persona, puede tener repercusiones sociales inesperadas.El texto normativo muestra debilidades propias de una ley apresurada y sin apoyo de órganos consultivos. Hay cuestiones pendientes de aclarar en su aplicación dentro del contexto de la medicina de familia. Se concluye que esta nueva norma planteará más problemas de los que pretende resolver.(AU)

The Spanish Euthanasia Law introduces a new right that is added to the portfolio of services provided by the Spanish health system and whose application is guaranteed within a period of 40 days. From the perspective of clinical experience, it is argued that without the effective right to quality palliative care and given the current shortcomings in dependant care, this law may send a threatening message to particularly fragile and dependant individuals that will lead to them feeling like a burden to their families and society.It is reasoned that basing the right to die on the dignity of the individual may have unexpected social repercussions.The text of the law presents the flaws of having been written hastily and without the support of advisory entities. There are issues that require clarification with regard to the application of euthanasia within the context of general practice. The conclusion is that this new law will pose more problems of the type it aims to resolve.(AU)

[Euthanasia: is this the law we need?] / Eutanasia: ¿es esta la ley que necesitamos?

The Spanish Euthanasia Law introduces a new right that is added to the portfolio of services provided by the Spanish health system and whose application is guaranteed within a period of 40 days. From the perspective of clinical experience, it is argued that without the effective right to quality palliative care and given the current shortcomings in dependant care, this law may send a threatening message to particularly fragile and dependant individuals that will lead to them feeling like a burden to their families and society. It is reasoned that basing the right to die on the dignity of the individual may have unexpected social repercussions. The text of the law presents the flaws of having been written hastily and without the support of advisory entities. There are issues that require clarification with regard to the application of euthanasia within the context of general practice. The conclusion is that this new law will pose more problems of the type it aims to resolve.

Genetic characterization of B-cell prolymphocytic leukemia: a prognostic model involving MYC and TP53.

B-cell prolymphocytic leukemia (B-PLL) is a rare hematological disorder whose underlying oncogenic mechanisms are poorly understood. Our cytogenetic and molecular assessments of 34 patients with B-PLL revealed several disease-specific features and potential therapeutic targets. The karyotype was complex (≥3 abnormalities) in 73% of the patients and highly complex (≥5 abnormalities) in 45%. The most frequent chromosomal aberrations were translocations involving MYC [t(MYC)] (62%), deletion (del)17p (38%), trisomy (tri)18 (30%), del13q (29%), tri3 (24%), tri12 (24%), and del8p (23%). Twenty-six (76%) of the 34 patients exhibited an MYC aberration, resulting from mutually exclusive translocations or gains. Whole-exome sequencing revealed frequent mutations in TP53, MYD88, BCOR, MYC, SF3B1, SETD2, CHD2, CXCR4, and BCLAF1. The majority of B-PLL used the IGHV3 or IGHV4 subgroups (89%) and displayed significantly mutated IGHV genes (79%). We identified 3 distinct cytogenetic risk groups: low risk (no MYC aberration), intermediate risk (MYC aberration but no del17p), and high risk (MYC aberration and del17p) (P = .0006). In vitro drug response profiling revealed that the combination of a B-cell receptor or BCL2 inhibitor with OTX015 (a bromodomain and extra-terminal motif inhibitor targeting MYC) was associated with significantly lower viability of B-PLL cells harboring a t(MYC). We concluded that cytogenetic analysis is a useful diagnostic and prognostic tool in B-PLL. Targeting MYC may be a useful treatment option in this disease.

Endoscopic Phenotype of Monoallelic Carriers of MUTYH Gene Mutations in the Family of Polyposis Patients: A Prospective Study.

BACKGROUND: Almost no prospective data on endoscopy in MUTYH monoallelic carriers are available. OBJECTIVE: This study aimed to define the prevalence of colorectal and duodenal adenomas in a population of people presenting with a single mutation of the MUTYH gene and being first-degree relatives of biallelic MUTYH mutation carriers. DESIGN: This study is a prospective cohort evaluation. PATIENTS: Patients were first-degree relatives of a patient who had polyposis with biallelic MUTYH mutation and carrying a single gene mutation of the gene from 12 French centers. SETTINGS: This is a multicenter study. INTERVENTION: Detailed data on life habits (tobacco, alcohol, and nonsteroidal anti-inflammatory drugs), extraintestinal manifestations, and germline analysis were recorded. Complete endoscopic evaluation (colonoscopy and upper endoscopy) with chromoendoscopy was performed. RESULTS: Sixty-two patients were prospectively included (34 women (55%), mean age of 54, range 30-70 years). Thirty-two patients (52%) presented with colorectal polyps at colonoscopy. Of these patients with polyps, 15 (25%) had only adenomas, 8 (13%) had only hyperplastic polyps, 1 (1%) had sessile serrated adenomas, and 8 (13%) had adenomas and/or sessile serrated adenomas. We detected, in total, 29 adenomas with low-grade dysplasia, 5 adenomas with high-grade dysplasia, and 6 sessile serrated adenomas. Fourteen patients (23%) presented with a single adenoma, and 10 (16%) had 1 to 5 adenomas. No patient had more than 5 adenomas. At upper endoscopy, 3 had a limited number of fundic gland polyps; none had duodenal adenomas. The 2 main missense mutations c.1145G>A, p.Gly382Asp and c.494A>G, p.Tyr165Cys were associated with the development of colorectal adenomas/serrated polyps in these monoallelic carriers. LIMITATIONS: This study was limited by the small number of patients. CONCLUSIONS: This prospective study provides unique prospective data suggesting that monoallelic mutation carriers related to patients with polyposis show no colorectal polyposis and have very limited upper GI manifestations justifying an endoscopic follow-up. See Video Abstract at http://links.lww.com/DCR/A862.

Familial breast cancer and DNA repair genes: Insights into known and novel susceptibility genes from the GENESIS study, and implications for multigene panel testing.

Pathogenic variants in BRCA1 and BRCA2 only explain the underlying genetic cause of about 10% of hereditary breast and ovarian cancer families. Because of cost-effectiveness, multigene panel testing is often performed even if the clinical utility of testing most of the genes remains questionable. The purpose of our study was to assess the contribution of rare, deleterious-predicted variants in DNA repair genes in familial breast cancer (BC) in a well-characterized and homogeneous population. We analyzed 113 DNA repair genes selected from either an exome sequencing or a candidate gene approach in the GENESIS study, which includes familial BC cases with no BRCA1 or BRCA2 mutation and having a sister with BC (N = 1,207), and general population controls (N = 1,199). Sequencing data were filtered for rare loss-of-function variants (LoF) and likely deleterious missense variants (MV). We confirmed associations between LoF and MV in PALB2, ATM and CHEK2 and BC occurrence. We also identified for the first time associations between FANCI, MAST1, POLH and RTEL1 and BC susceptibility. Unlike other associated genes, carriers of an ATM LoF had a significantly higher risk of developing BC than carriers of an ATM MV (ORLoF = 17.4 vs. ORMV = 1.6; p Het = 0.002). Hence, our approach allowed us to specify BC relative risks associated with deleterious-predicted variants in PALB2, ATM and CHEK2 and to add MAST1, POLH, RTEL1 and FANCI to the list of DNA repair genes possibly involved in BC susceptibility. We also highlight that different types of variants within the same gene can lead to different risk estimates.

"Double-hit" chronic lymphocytic leukemia: An aggressive subgroup with 17p deletion and 8q24 gain.

Chronic lymphocytic leukemia (CLL) with 17p deletion (17p-) is associated with a lack of response to standard treatment and thus the worst possible clinical outcome. Various chromosomal abnormalities (including unbalanced translocations, deletions, ring chromosomes and isochromosomes) result in the loss of 17p and one copy of the TP53 gene. The objective of the present study was to determine whether the type of chromosomal abnormality leading to 17p- and the additional aberrations influenced the prognosis in a series of 195 patients with 17p-CLL. Loss of 17p resulted primarily from an unbalanced translocation (70%) with several chromosome partners (the most frequent being chromosome 18q), followed by deletion 17p (23%), monosomy 17 (8%), isochromosome 17q [i(17q)] (5%) and a ring chromosome 17 (2%). In a univariate analysis, monosomy 17, a highly complex karyotype (≥5 abnormalities), and 8q24 gain were associated with poor treatment-free survival, and i(17q) (P = .04), unbalanced translocations (P = .03) and 8q24 gain (P = .001) were significantly associated with poor overall survival. In a multivariate analysis, 8q24 gain remained a significant predictor of poor overall survival. We conclude that 17p deletion and 8q24 gain have a synergistic impact on outcome, and so patients with this "double-hit" CLL have a particularly poor prognosis. Systematic, targeting screening for 8q24 gain should therefore be considered in cases of 17p- CLL.

Psychophysiological Changes during Pure vs Guided Mirror Exposure Therapies in Women with High Body Dissatisfaction: What Are They Learning about Their Bodies?

This study aimed to examine the psychophysiological changes resulting from two mirror exposure treatments that are effective at reducing body dissatisfaction. Thirty-five university women with body dissatisfaction and subclinical eating disorders were randomly assigned to one of two groups: pure (n = 17) or guided exposure (n = 18). The participants received six sessions of treatment. Their thoughts, feelings and avoidance behaviours were assessed after each session. Their subjective discomfort, heart rate and skin conductance were assessed within the sessions. Both groups showed improvement in cognitive-affective and avoidance behaviour symptoms. Nevertheless, the pure exposure group showed faster habituation of subjective discomfort and a greater physiological response than the guided exposure group. These findings suggest that both procedures are effective interventions for improving body image disturbances, although psychophysiological changes observed within session suggest that each technique would act through different processes. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Metilación de genes supresores de tumores en pacientes venezolanos con leucemia linfoide aguda / Methylation of tumor suppressor genes in Venezuelan patients with acute lymphoid leukemia

La leucemia linfoide aguda (LLA) es la neoplasia maligna hematológica más común en niños. Se ha podido demostrar un perfil específico de metilación de islas CpG en las regiones promotoras de genes supresores de tumor, que desempeña un papel crítico en el silenciamiento transcripcional y puede ofrecer nuevas opciones de tratamiento. Con el objetivo de determinar este perfil, se analizó el estado de metilación de las islas CpG de la región promotora de cuatros genes supresores de tumor asociados a diferentes etapas del proceso de carcinogénesis, dos p15 y p73 asociados a la regulación del ciclo celular y a la apoptosis y dos E-cadherin y RARβ2, involucrados en la migración y metástasis tumoral. Se analizaron 30 muestras de sangre periférica mediante modificación del ADN con bisulfito sódico y reacción en cadena de la polimerasa específica para metilación y se obtuvo en todos los pacientes, al menos la metilación de un gen (100%) y frecuencias específicas de metilación de 76,67% para el gen p73 (23 pacientes); 56,67% para el p15 (7 pacientes); 16,67% para el E-cadherin (5 pacientes) y 20,0% para el RARβ2 (6 pacientes). La frecuencia de metilación observada en los genes p15 y p73, sugiere el papel importante de esos genes en la patogenia de la LLA y su probable utilidad en el asesoramiento de riesgo y en la selección del tratamiento más adecuado.

Acute lymphocytic leukemia (ALL) is the most common hematologic malignancy in children. A specific methylation profile of CpG islands in the promoter regions of tumor suppressor genes has been demonstrated, which plays a critical role in transcriptional silencing and may offer new treatment options. In order to determine this profile, the methylation status of CpG islands was analyzed in the promoter region of four tumor suppressor genes associated with different stages of carcinogenesis: two associated with the regulation of cell cycle and apoptosis: p15 and p73; and two involved in migration and tumor metastasis: E-cadherin and RARβ2. Thirty peripheral blood samples were analyzed by modification of DNA with sodium bisulfite and chain reaction polymerase specific for methylation. In all patients, the methylation of at least one gene was observed (100%) and additionally, there were specific methylation frequencies of 76.67% for the p73 gene (23 patients); 56.67% for p15 (seven patients); 16.67% for E-cadherin (five patients) and 20.0% for the RARβ2 (six patients). The frequency of methylation observed in p15 and p73 genes suggests the important role of these genes in the pathogenesis of ALL and its usefulness in risk assessment and the selection of the most appropriate treatment.

Cambios histomorfométricos en dentina al utilizar biomodificadores radiculares. Revisión sistemática / Histomorphometric changes in root dentine after using biomodifiers. A systematic review

Antecedentes: El éxito del tratamiento endodóntico depende de una óptima preparación biomecánica, la cual incluye la remoción del barro dentinario que se forma durante la instrumentación del conducto. Esta capa se adhiere a la superficie de la dentina, ocluye los túbulos dentinarios e impide la adhesión del material obturador. Debe ser removido por soluciones irrigadoras que causan cambios en la superficie dentinaria. Se han utilizado ácido etilendiaminotetracético (EDTA), ácido cítrico y tetraciclina como irrigantes. Objetivo: Identificar los cambios producidos en la dentina al aplicar EDTA, ácido cítrico y tetraciclina como agentes irrigadores, descritos en la literatura disponible. Métodos: En esta revisión sistemática se estudiaron los diferentes cambios histomorfométricos encontrados al utilizar biomodificadores radiculares sobre la estructura dentinaria, teniendo en cuenta el tiempo de aplicación y la concentración de las soluciones. La muestra consistió en 20 artículos seleccionados de 889 revisados, publicados entre 2009 y 2016. La medida global del resultado fue la diferencia estándar de la profundidad de desmineralización dentinaria, obtenida por los acondicionadores empleados. Resultados: De acuerdo con la literatura, la profundidad de desmineralización es directamente proporcional al tiempo de exposición y concentración de la solución después de su aplicación. Para otras variables, como el pH, no se contó con evidencia suficiente para hacer inferencias. Así, se sugiere que no existen las pruebas científicas suficientes para respaldar este tipo de estudio. Conclusiones: Los cambios que se presentan en la dentina al utilizar biomodificadores radiculares dependen del tiempo de aplicación y de su concentración.

Background: The success of endodontic therapy depends on an optimal biomechanical preparation, which includes removal of smear layer formed during root canal preparation. Smear layer adheres to the dentin surface and occludes the tubules, preventing the adhesion of the sealant material. It must be removed through irrigants that cause changes on the dentinal surface. Ethylenediaminetetraacetic acid (EDTA), citric acid, and tetracycline have been used as irrigants. Purpose: To identify changes in dentine after applying EDTA, citric acid, and tetracycline as irrigants, as described in available literature. Methods: In this systematic review, histomorphometric changes in dentin surface observed after using root biomodifiers, regarding application time and concentration of solution. The sample consisted of 20 articles selected from a population of 889 articles found and published between 2009 and 2016. The overall measure of results was the standard difference of dentinal demineralization depth, obtained for each solution. Results: According to the literature, the depth of demineralization is directly proportional to exposition time and concentration after application of the irrigant. Regarding other variables, such as pH, evidence was limited to draw conclusions. Thus, it is suggested there is not enough scientific evidence to support this type of study. Conclusions: Dentinal changes that occur after using root biomodifiers depend on the length of the application time and its concentration.

Testing the efficacy of pure versus guided mirror exposure in women with bulimia nervosa: A combination of neuroendocrine and psychological indices.

BACKGROUND AND OBJECTIVES: Body exposure improves body image problems in women with eating disorders. However it has almost always been combined with other interventions. Thus, the efficacy of body exposure alone (i.e., pure exposure) remains largely unclear. We aimed to compare the efficacy of two body exposure techniques through psychological and neuroendocrine indices recorded within and between successive sessions. METHOD: Twenty-nine women with high body dissatisfaction and diagnosis of bulimia nervosa were randomly assigned to one of two treatment groups: Pure Exposure (n = 14) or Guided Exposure (n = 15). Participants received 6 exposure sessions. After each session, changes in thoughts (positive/negative) and body satisfaction were assessed. Also, we assessed the body discomfort experienced by participants within and between sessions. Finally, the changes in salivary cortisol levels within and between the initial and final treatment sessions were measured. RESULTS: Both groups showed a reduction in negative thoughts and a progressive increase in positive thoughts throughout the treatment. However, the increase in body satisfaction and the reduction in subjective discomfort within the sessions were greater in the pure exposure group. The cortisol levels during the initial and final treatment sessions decreased in both groups. LIMITATIONS: Methodological limitations are reported. CONCLUSIONS: These results suggest that pure and guided exposures are effective interventions for improving thoughts and neuroendocrine responses, although pure exposure increased more body satisfaction feelings in bulimic women. Subjective discomfort also showed different patterns of change within and along sessions for each treatment. Reasons for these results are discussed.

Feeling bad posing as a model: an objective manner of study upward own-body comparisons in body-dissatisfied women.

Emotional effects of upward body comparisons are suggested to occur automatically. A startle reflex paradigm was used to objectively examine the emotions elicited by viewing a picture of one's own body adopting a model pose or a neutral pose, in 30 women with high body dissatisfaction (HBD) and 33 women with low body dissatisfaction (LBD). In-task emotional responses in perceived valence, arousal and control were assessed. Additionally, post-task positive/negative and body-related beauty feelings were recorded. The results revealed that HBD women, compared with LBD women, showed (i) less pleasure, higher activation and less control whilst viewing their own bodies and (ii) less pleasure, more negative/ugliness feelings and an increased startle response when viewing themselves posing as models. The data showed that their own bodies provoked an immediate negative emotional state in HBD women. However, greater aversive psychophysiological mechanisms were automatically activated only when these women posed as models, suggesting that they made upward own-body comparisons.

14q deletions are associated with trisomy 12, NOTCH1 mutations and unmutated IGHV genes in chronic lymphocytic leukemia and small lymphocytic lymphoma.

Deletions of the long arm of chromosome 14 [del(14q)] are rare but recurrently observed in mature B-cell neoplasms, particularly in chronic lymphocytic leukemia (CLL). To further characterize this aberration, we studied 81 cases with del(14q): 54 of CLL and 27 of small lymphocytic lymphoma (SLL), the largest reported series to date. Using karyotype and fluorescence in situ hybridization (FISH), the most frequent additional abnormality was trisomy 12 (tri12), observed in 28/79 (35%) cases, followed by del13q14 (12/79, 15%), delTP53 (11/80, 14%) delATM (5/79, 6%), and del6q21 (3/76, 4%). IGHV genes were unmutated in 41/53 (77%) patients, with a high frequency of IGHV1-69 (21/52, 40%). NOTCH1 gene was mutated in 14/45 (31%) patients. There was no significant difference in cytogenetic and molecular abnormalities between CLL and SLL. Investigations using FISH and SNP-array demonstrated the heterogeneous size of the 14q deletions. However, a group with the same del(14)(q24.1q32.33) was identified in 48% of cases. In this group, tri12 (P = 0.004) and NOTCH1 mutations (P = 0.02) were significantly more frequent than in the other patients. In CLL patients with del(14q), median treatment-free survival (TFS) was 27 months. In conclusion, del(14q) is associated with tri12 and with pejorative prognostic factors: unmutated IGHV genes (with over-representation of the IGHV1-69 repertoire), NOTCH1 mutations, and a short TFS.

Chronic lymphocytic leukemia and prolymphocytic leukemia with MYC translocations: a subgroup with an aggressive disease course.

Translocations involving MYC are rare in chronic lymphocytic leukemia (CLL), and up to now, their prognostic significance remains unclear. We report the characteristics of 21 patients with CLL and nine patients with prolymphocytic leukemia (PLL), diagnosed in multiple centers (n = 13), which showed an MYC translocation demonstrated by fluorescence in situ hybridization. The prevalence was estimated to be <1%. Advanced age and male predominance were observed. Morphological analysis frequently revealed the presence of prolymphocytes. A typical "CLL-immunophenotype" was found in four of nine cases with PLL. Moreover, CD5 and CD23 were frequently expressed in PLL. The latter findings are atypical for PLL and may suggest transformation or progression of an underlying CLL. MYC translocations were frequently observed with concomitant adverse cytogenetic markers, such as del(11q) (n = 8/30) and/or del(17p)/monosomy 17 (n = 7/30). In addition, the presence of unbalanced translocations (n = 24 in 13/30 cases) and complex karyotype (n = 16/30) were frequent in cases with MYC translocations. Altogether, del(17p)/monosomy 17, del(11q), and/or complex karyotype were observed in 22 of 30 patients. Survival outcome was poor: the median time to treatment was only 5 months, and overall survival (OS) from clinical diagnosis and from genetic detection was 71 and 19 months, respectively. In conclusion, CLL/PLL with MYC translocations is a rare entity, which seems to be associated with adverse prognostic features and unfavorable outcome.