Conservative surgical treatment with fertility preservation in a young adult with NTRK rearranged spindle cell neoplasm of the uterine cervix

In depth molecular studies are constantly expanding our understanding and refining the classification of gynecological neoplasms. NTRK rearranged spindle cell neoplasms of the lower genital tract are an emerging entity, of particular interest due to possible targeted treatment with selective kinase inhibitors. Nonetheless, surgery remains the initial treatment of choice. We present the case of a 24-year-old patient suffering from a NTRK rearranged spindle cell neoplasm of the uterine cervix which was treated with a fertility preserving conservative surgical approach

BCL3-rearrangements in B-cell lymphoid neoplasms occur in two breakpoint clusters associated with different diseases

The t(14;19)(q32;q13) often juxtaposes BCL3 with IGH resulting in overexpression of the gene. In contrast to other oncogenic translocations, BCL3-rearrangement (BCL3-R) has been associated with a broad spectrum of lymphoid neoplasms. Here we report an integrative whole-genome sequence, transcriptomic, and DNA methylation analysis of 13 lymphoid neoplasms with BCL3-R. The resolution of the breakpoints at single base-pair revealed that they occur in two clusters at 5' (n=9) and 3' (n=4) regions of BCL3 associated with two different biological and clinical entities. Both breakpoints were mediated by aberrant class switch recombination of the IGH locus. However, the 5' breakpoints (upstream) juxtaposed BCL3 next to an IGH enhancer leading to overexpression of the gene whereas the 3' breakpoints (downstream) positioned BCL3 outside the influence of the IGH and were not associated with its expression. Upstream BCL3-R tumors had unmutated IGHV, trisomy 12, and mutated genes frequently seen in CLL but had an atypical CLL morphology, immunophenotype, DNA methylome, and expression profile that differ from conventional CLL. In contrast, downstream BCL3-R neoplasms were atypical splenic or nodal marginal zone lymphomas (MZL) with mutated IGHV, complex karyotypes and mutated genes typical of MZL. Two of the latter 4 tumors transformed to a large B-cell lymphoma. We designed a novel FISH assay that recognizes the two different breakpoints and validated these findings in 17 independent tumors. Overall, upstream or downstream breakpoints of BCL3-R are mainly associated with two subtypes of lymphoid neoplasms with different (epi)genomic, expression, and clinicopathological features resembling atypical CLL and MZL, respectively

BCL3-rearrangements in B-cell lymphoid neoplasms occur in two breakpoint clusters associated with different diseases

The t(14;19)(q32;q13) often juxtaposes BCL3 with immunoglobulin heavy chain (IGH) resulting in overexpression of the gene. In contrast to other oncogenic translocations, BCL3 rearrangement (BCL3-R) has been associated with a broad spectrum of lymphoid neoplasms. Here we report an integrative whole-genome sequence, transcriptomic, and DNA methylation analysis of 13 lymphoid neoplasms with BCL3-R. The resolution of the breakpoints at single base-pair revealed that they occur in two clusters at 5' (n=9) and 3' (n=4) regions of BCL3 associated with two different biological and clinical entities. Both breakpoints were mediated by aberrant class switch recombination of the IGH locus. However, the 5' breakpoints (upstream) juxtaposed BCL3 next to an IGH enhancer leading to overexpression of the gene whereas the 3' breakpoints (downstream) positioned BCL3 outside the influence of the IGH and were not associated with its expression. Upstream BCL3-R tumors had unmutated IGHV, trisomy 12, and mutated genes frequently seen in chronic lymphocytic leukemia (CLL) but had an atypical CLL morphology, immunophenotype, DNA methylome, and expression profile that differ from conventional CLL. In contrast, downstream BCL3-R neoplasms were atypical splenic or nodal marginal zone lymphomas (MZL) with mutated IGHV, complex karyotypes and mutated genes typical of MZL. Two of the latter four tumors transformed to a large B-cell lymphoma. We designed a novel fluorescence in situ hybridization assay that recognizes the two different breakpoints and validated these findings in 17 independent tumors. Overall, upstream or downstream breakpoints of BCL3-R are mainly associated with two subtypes of lymphoid neoplasms with different (epi)genomic, expression, and clinicopathological features resembling atypical CLL and MZL, respectively

Happiness around the world: A combined etic-emic approach across 63 countries.

What does it mean to be happy? The vast majority of cross-cultural studies on happiness have employed a Western-origin, or "WEIRD" measure of happiness that conceptualizes it as a self-centered (or "independent"), high-arousal emotion. However, research from Eastern cultures, particularly Japan, conceptualizes happiness as including an interpersonal aspect emphasizing harmony and connectedness to others. Following a combined emic-etic approach (Cheung, van de Vijver & Leong, 2011), we assessed the cross-cultural applicability of a measure of independent happiness developed in the US (Subjective Happiness Scale; Lyubomirsky & Lepper, 1999) and a measure of interdependent happiness developed in Japan (Interdependent Happiness Scale; Hitokoto & Uchida, 2015), with data from 63 countries representing 7 sociocultural regions. Results indicate that the schema of independent happiness was more coherent in more WEIRD countries. In contrast, the coherence of interdependent happiness was unrelated to a country's "WEIRD-ness." Reliabilities of both happiness measures were lowest in African and Middle Eastern countries, suggesting these two conceptualizations of happiness may not be globally comprehensive. Overall, while the two measures had many similar correlates and properties, the self-focused concept of independent happiness is "WEIRD-er" than interdependent happiness, suggesting cross-cultural researchers should attend to both conceptualizations

Suppressors of cytokine signalling (SOCS) in human immunodeficiency virus (HIV) pathogenesis

Aim: To screen the genetic regions of SOCS1 and SOCS3 for variations (mutations and polymorphisms). To genotype 176 individuals for the found mutations/polymorphisms and to calculate the allele frequencies and haplotypes. To establish robust genotyping assays for polymorphisms with a minor allele frequency of at least 1% for a further larger study in the Swiss HIV cohort study (SHCS). Methods: Screening for mutations has been carried out with denaturing high pressure liquid chromatography (dHPLC) and Sanger sequencing. Genotyping assays are based on four different methods: high resolution melting (HRM) without probes, HRM with unlabelled probes, allele specific amplification (ASA) and fluorescent resonance energy transfer (FRET) probe analysis. Statistical analysis was done using Excel and HaploView. Results: 8 mutations/polymorphisms were found in the screening experiment for SOCS1, 7 mutations/polymorphisms were found in SOCS3. Genotyping showed 7 polymorphisms in SOCS1 and 6 polymorphisms in SOCS3 which had a minor allele frequency (MAF) of at least 1%. All polymorphisms are in the 5’ or the 3’ region of the genes. No polymorphisms or mutations were found in the coding sequence. Conclusion: In the examined Swiss population different polymorphisms were identified. Some of these single nucleotide polymorphisms (SNP) are known to be functional and modify gene expression. The established assays allow now to investigate associations of these SNPs in SOCS1 and 3 and of their haplotypes with different acute and chronic infectious and inflammatory diseases

Wenn eine neue Brille nichts nützt - ausgeprägte Sehstörung trotz normalem Visus

Wir stellen den Fall einer 65-jährigen Frau vor mit seit wenigen Jahren bestehenden Sehstörungen bei unauffälligem ophthalmologischem Befund. Die neuropsychologische Untersuchung ergab eine komplexe Agnosie mit deutlichen Einschränkungen in visuell-konstruktiven und visuell-perzeptiven Leistungen bei nur leichten Defiziten in der Mnestik. Die Befunde passen zu einer posterioren kortikalen Atrophie. Der Störung liegt eine Neurodegeneration zugrunde, meist als Folge einer Alzheimerkrankheit. Da die Patienten über ein ausgeprägtes Störungsbewusstsein verfügen, sind eine gute Aufklärung sowie das Entwickeln geeigneter Kompensationsstrategien sehr wichtig. We report the case of a 65 year old woman with visual impairment for a few years and normal ophthalmological examination. Neuropsychological investigations revealed a complex agnosia with predominant visuospatial and visuoperceptual deficits, while only discrete mnestic deficits were found. These results are consistent with posterior cortical atrophy. The underlying cause is neurodegeneration, mostly due to Alzheimer’s disease. As patients are very aware of the deficits, it is important to provide good information about the disease and the coping strategies

Conservative surgical treatment with fertility preservation in a young adult with NTRK rearranged spindle cell neoplasm of the uterine cervix

In depth molecular studies are constantly expanding our understanding and refining the classification of gynecological neoplasms. NTRK rearranged spindle cell neoplasms of the lower genital tract are an emerging entity, of particular interest due to possible targeted treatment with selective kinase inhibitors. Nonetheless, surgery remains the initial treatment of choice. We present the case of a 24-year-old patient suffering from a NTRK rearranged spindle cell neoplasm of the uterine cervix which was treated with a fertility preserving conservative surgical approach

The combined expression of the stromal markers fibronectin and SPARC improves the prediction of survival in diffuse large B-cell lymphoma

Background In diffuse large B-cell lymphomas, gene expression profiling studies attributed a major biologic role to non-neoplastic cells of the tumour microenvironment as its composition and characteristics were shown to predict survival. In particular, the expression of selected genes encoding components of the extracellular matrix was reported to be associated with clinical outcome. Nevertheless, the translation of these data into robust, routinely applicable immunohistochemical markers is still warranted. Therefore, in this study, we analysed the combination of the expression of the extracellular matrix components Fibronectin and SPARC on formalin-fixed paraffin embedded tissue derived from 173 patients with DLBCL in order to recapitulate gene expression profiling data. Results The expression of Fibronectin and SPARC was detected in 77/173 (44.5%) and 125/173 (72.3%) cases, respectively, and 55/173 (31.8%) cases were double positive. Patients with lymphomas expressing Fibronectin showed significantly longer overall survival when compared to negative ones (6.3 versus 3.6 years). Moreover, patients with double positive lymphomas also presented with significantly longer overall survival when compared with the remaining cases (11.6 versus 3.6 years) and this combined expression of both markers results in a better association with overall survival data than the expression of SPARC or Fibronectin taken separately (Hazard ratio 0.41, 95% confidence interval 0.17 to 0.95, p = 0.037). Finally, neither Fibronectin nor SPARC expression was associated with any of the collected clinico-pathological parameters. Conclusions The combined immunohistochemical assessment of Fibronectin and SPARC, two components of the extracellular matrix, represents an important tool for the prediction of survival in diffuse large B-cell lymphomas. Our study suggests that translation of gene expression profiling data on tumour microenvironment into routinely applicable immunohistochemical markers is a useful approach for a further characterization of this heterogeneous type of lymphoma