RB loss contributes to aggressive tumor phenotypes in MYC-driven triple negative breast cancer

Triple negative breast cancer (TNBC) is characterized by multiple genetic events occurring in concert to drive pathogenic features of the disease. Here we interrogated the coordinate impact of p53, RB, and MYC in a genetic model of TNBC, in parallel with the analysis of clinical specimens. Primary mouse mammary epithelial cells (mMEC) with defined genetic features were used to delineate the combined action of RB and/or p53 in the genesis of TNBC. In this context, the deletion of either RB or p53 alone and in combination increased the proliferation of mMEC; however, the cells did not have the capacity to invade in matrigel. Gene expression profiling revealed that loss of each tumor suppressor has effects related to proliferation, but RB loss in particular leads to alterations in gene expression associated with the epithelial-to-mesenchymal transition. The overexpression of MYC in combination with p53 loss or combined RB/p53 loss drove rapid cell growth. While the effects of MYC overexpression had a dominant impact on gene expression, loss of RB further enhanced the deregulation of a gene expression signature associated with invasion. Specific RB loss lead to enhanced invasion in boyden chambers assays and gave rise to tumors with minimal epithelial characteristics relative to RB-proficient models. Therapeutic screening revealed that RB-deficient cells were particularly resistant to agents targeting PI3K and MEK pathway. Consistent with the aggressive behavior of the preclinical models of MYC overexpression and RB loss, human TNBC tumors that express high levels of MYC and are devoid of RB have a particularly poor outcome. Together these results underscore the potency of tumor suppressor pathways in specifying the biology of breast cancer. Further, they demonstrate that MYC overexpression in concert with RB can promote a particularly aggressive form of TNB

Metabolic syndrome and insulin resistance in pre-pubertal children with psoriasis

Psoriasis in adults is associated with an increased risk of metabolic disease. Various cardiometabolic comorbidities have been reported in childhood psoriasis, but only a few studies have analyzed the prevalence of metabolic syndrome. We performed a single-center prospective study investigating the prevalence of metabolic syndrome and insulin resistance in children with psoriasis. The prevalence of metabolic syndrome was evaluated in 60 pre-pubertal children with psoriasis (age: 3\u201310 years), accordingly to recently established criteria for the diagnosis of metabolic syndrome in children. Insulin resistance was considered altered when the homeostatic model assessment (HOMA-IR) for insulin resistance was 65 90th sex- and age-specific percentile and HOMA 2-IR was > 1.8. Eighteen (30%) children with psoriasis were found to have metabolic syndrome. Sixteen (27%) children were found to have insulin resistance. Conclusion: Our data underline the importance of assessing metabolic syndrome not only in adults and adolescents but also in young children with psoriasis.What is Known:\u2022 Psoriasis in adults is strongly associated with metabolic disease and insulin resistance.\u2022 Very limited data are available on the prevalence of metabolic syndrome and insulin resistance in pre-pubertal children with psoriasis.What is New:\u2022 This study reports that in pre-pubertal children with psoriasis, there is a high prevalence of metabolic syndrome and insulin resistance.\u2022 In children with psoriasis metabolic syndrome risk factors should be assessed

Dynamique du peuplement herbacé de la station sahélienne expérimentale de Toukounous (Filingué – Niger)

La dynamique spatio-temporelle de la végétation herbacée de la Station Sahélienne Expérimentale de Toukounous a été établie suivant la méthode des points quadrats alignés. L’analyse de la composition floristique et des types de pâturage herbacé dans les différents faciès morpho-pédologiques de la station a permis de recenser 75 espèces herbacées essentiellement annuelles, réparties dans 50 genres et 20 familles. L’année 2006 a enregistré un nombre d’espèces significativement plus grand que les autres années d’étude (P<0,05). Les espèces vivaces sont absentes et les légumineuses sont rares. La forte dominance des graminées annuelles témoigne de la perte de la biodiversité. Le recouvrement herbacé est globalement élevé (80,9%) et varie peu entre les différents types d’unités morpho-pédologiques et selon les années. L’analyse canonique des correspondances appliquée aux matrices relevés-espèces et relevés-variables environnementales montre l’existence de groupements végétaux évoluant sur les différentes unités de végétation (dune, plaine et bas fond) en fonction de la quantité de pluies tombées au cours de l’année considérée. La perte de biodiversité suppose une intervention rapide dont les grands axes d’aménagement passent par l’ensemencement des aires de pâture couplé à la rotation afin d’assurer l’enrichissement du couvert végétal surtout en légumineuses tout en évitant la fréquentation des endroits les moins pourvus en légumineuses pendant la saison pluvieuse.Mots clés : végétation, composition floristique, répartition spatio-temporelle, parcours, Toukounous, Niger

Diversité, structure et régénération de la végétation ligneuse de la Station Sahélienne Expérimentale de Toukounous, Niger

A la Station Sahélienne Expérimentale de Toukounous, le bétail est nourri essentiellement sur pâturage naturel. En saison sèche, l’herbe devient rare et subsiste à l’état de paille. Les animaux ont recours aux ligneux pour combler le déficit alimentaire. L’état de la végétation ligneuse a été établi à travers la détermination de la diversité, la structure et la régénération des espèces ligneuses par la méthode des transects. L’inventaire floristique a permis de recenser 15 espèces réparties entre 11 genres et 10 familles. La famille des Capparaceae et celle des Leguminosae-Mimosoïdeae sont les plus  représentées. Le peuplement est une formation arbustive à Maerua crassifolia avec comme espèces compagnes Balanites aegyptiaca et Acacia raddiana. La densité moyenne est de 172 pieds à l’hectare. La distribution par classes de diamètre montre une prédominance d'individus de petit diamètre. La majorité des ligneux a une hauteur inférieure à 2 mètres (46,4%). Le degré de couverture de la strate ligneuse, estimé à 12,67% est globalement faible. Le taux de renouvellement varie selon l’espèce. Maerua crassifolia (47,9%), Balanites aegyptiaca (17,4%) et Acacia raddiana (14,1%) ont les plus forts peuplements juvéniles. L’effectif de Maerua crassifolia est en baisse. La structure du peuplement fait état d’un milieu perturbé. La protection des jeunes plants devrait permettre de diversifier les sources d’aliments pour le bétail en période de soudure.Mots clés : Peuplement ligneux, parcours, caractéristiques structurales, Sahel, Niger

Dermoscopic changes in melanocytic naevi in children during digital follow-up.

(28.4%) after 4 years, in 5 of 37 lesions (13.5%) after 5 years, in 12 of 31 lesions (38.8%) after 6 years, and in 7 of 21 lesions (33.3%) after 7 years. Dermoscopic changes were detected in 25.3% of the lesions in patients aged 3–6 years, in 21% of the lesions in patients aged 7–12 years, and in 15.5% of the lesions in patients over 13 years. Main pattern changes consisted of transition from globular to globular-reticular (35 naevi), from globular to reticular (14 naevi) and from globular-reticular to reticular (24 naevi). These results are consistent with the view that melanocytic naevi generally undergo a characteristic transition from a globular pattern to a reticular pattern. Most of the changes are observed in the 3–6 years age group when hormonal and/or environmental factors are not thought to play a role in pattern alterations. Key words: melanocytic; naevi; dermoscopy; pattern; changes

Implementing Drill Technique in Teaching Speaking

Tujuan penelitian ini adalah untuk menemukan (1) masalah yang muncul pada saat proses belajar mengajar berlangsung, (2) implementasi proses belajar mengajar yang efektif dengan menggunakan teknik Drill. Penelitian ini menggunakan desain penelitian tindakan dengan menerapkan siklus-siklus. Data penelitian diperoleh dengan cara observasi, wawancara dan rekaman. Hasil penelitian menunjukkan bahwa (1) masalah yang sering muncul berasal dari sulitnya siswa memahami apa yang dikatakan oleh peneliti dalam bahasa Inggris, (2) implementasi belajar semakin baik pada setiap siklusnya, siswa lebih berani dan percaya diri pada siklus selanjutnya daripada pada siklus sebelumnya.The research aimed at finding (1) the problems occured during the teaching learning process, (2) the effective implementation in the teaching learning process using Drill Technique. The subject of this action research was the second grade students in class VIII J of SMP N 4 Bandar Lampung, consisting 22 students. This research used action research through cycles. The data were collected through observation sheet, interview and recording. The result showed that (1) the problems faced often by the researcher came from their lack ability in understanding the researcher‟s speaking, (2) the implementation of the teaching learning process was getting better cycle to cycle, they were more brave and more confident talking English on the next cycle than on the previous

Contact allergy to methylchloroisothiazolinone/methylisothiazolinone in north-eastern Italy: a temporal trend from 1996 to 2016

BACKGROUND: Methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI) (Kathon\uae CG) is a common preservative used in industrial products, owing to its strong biocide effect. Contact allergy to MCI/MI has been reported in different occupations, including mechanics, hairdressers and healthcare workers. OBJECTIVE: To retrospectively analyse the temporal trend of MCI/MI sensitization in north-eastern Italy and to evaluate the associations with occupations in our geographical area. METHODS: From 1996 to 2016, 27 381 patients with suspected allergic contact dermatitis were patch tested in eight departments of Dermatology or Occupational Medicine in north-eastern Italy. Individual characteristics were collected through a standardized questionnaire. RESULTS: The overall prevalence of MCI/MI sensitization was 4.2%, with the highest prevalence found in women and in patients younger than 25 years. MCI/MI sensitization was significantly associated with atopic eczema (OR: 1.34, 95% CI: 1.10-1.70), hand/forearm dermatitis (OR: 1.20, 95% CI: 1.05-1.36) and face dermatitis (OR 1.30, 95% CI: 1.10-1.40). There was a significant association between MCI/MI sensitization and chemical processing workers (OR 1.74, 95% CI: 1.03-2.94), while mechanics and healthcare workers resulted more sensitized to this hapten only in the last 3 years. CONCLUSIONS Sensitization to MCI/MI is rising in the last years in Triveneto region, the 'epidemic' of sensitization to MCI/MI is mainly driven by extra-occupational dermatitis, and sensitization in some occupational groups is emerging only in the last years. A full labelling is compulsory for all products that contain isothiazolinones, to permit to identify the culprit agent

Rejection-mediated Regression of Melanocytic Naevi in an Immunosuppressed Organ Transplant Recipient

© 2014 The Authors. doi: 10.2340/00015555-1789 Journal Compilation © 2014 Acta Dermato-Venereologica. ISSN 0001-5555 Eruptive melanocytic naevi and/or excess of melanocytic naevi have been reported in several groups of immunosuppressed patients. The eruption of melanocytic naevi after immunosuppression is a peculiar phenomenon indicating that the immune system may play a major role in limitating proliferation of melanocytes (1). In this article we describe a patient with excess of post-transplant melanocytic naevi that spontaneously disappeared after graft rejection