Chiasma

Newspaper reporting on events at the Boston University School of Medicine in the 1960s

Síndrome de Stevens-Johnson. Apresentação de Caso Clínico

Introdução: A Síndrome de Stevens-Johnson (SSJ) é uma doença mucocutânea rara e potencialmente fatal, mais frequente no sexo masculino, cuja incidência aumenta com a idade e em determinados grupos de risco. A SSJ e a Necrólise Tóxica Epidérmica (NET) são duas entidades da mesma doença, com severidade diferente. A etiologia não é clara, mas pensa-se que se deva maioritariamente a reacções adversas a fármacos. Caso clínico: Um jovem de 17 anos de idade, sem antecedentes pessoais relevantes, foi observado no Serviço de Urgência por surgimento de lesões maculopapulares, com 3 dias de evolução, dispersas pela face, cavidade oral, tronco e extremidades, com prostração e taquicardia. Foi internado com o diagnóstico de SSJ. Discussão e Conclusões: O SSJ e a NET têm grande morbilidade e considerável mortalidade. O rápido reconhecimento desta identidade, com a remoção do fármaco desencadeador é essencial. A perda da função de barreira da pele, com a consequente alteração da homeostasia, implica muitas vezes a manutenção da terapêutica de suporte em Unidades de Cuidados Intensivos ou de Queimados.info:eu-repo/semantics/publishedVersio

Translating the Dutch walking stairs, walking ability and rising and sitting questionnaires into German and assessing their concurrent validity with VAS measures of pain and activities in daily living

<p>Abstract</p> <p>Background</p> <p>The Dutch Walking Stairs, Walking Ability and Rising and Sitting Questionnaires are three validated instruments to measure physical activity and limitations in daily living in patients with lower extremity disorders living at home of which no German equivalents are available. Our scope was to translate the Walking Stairs, Walking Ability and Rising and Sitting Questionnaires into German and to verify its concurrent validity in the two domains pain and activities in daily living by comparing them with the corresponding measures on the Visual Analogue Scale.</p> <p>Methods</p> <p>We translated the Walking Stairs, Walking Ability and Rising and Sitting Questionnaires according to published guidelines. Demographic data and validity were assessed in 52 consecutive patients with Complex Regional Pain Syndrome 1 of the lower extremity. Information on age, duration of symptoms, type of Complex Regional Pain Syndrome 1 and type of initiating event were obtained. We assessed the concurrent validity in the two domains pain and activities in daily living by comparing them with the corresponding measures on the Visual Analogue Scale.</p> <p>Results</p> <p>We found that variability in the German Walking Stairs, Walking Ability and Rising and Sitting Questionnaires was largely explained by measures of pain and activities in daily living on the Visual Analogue Scale.</p> <p>Conclusion</p> <p>Our study shows that the domains pain and activities in daily living are properly represented in the German versions of the Walking Stairs, Walking Ability and Raising and Sitting Questionnaires. We would like to propagate their use in clinical practice and research alike.</p

Transverse-momentum-dependent Multiplicities of Charged Hadrons in Muon-Deuteron Deep Inelastic Scattering

A semi-inclusive measurement of charged hadron multiplicities in deep inelastic muon scattering off an isoscalar target was performed using data collected by the COMPASS Collaboration at CERN. The following kinematic domain is covered by the data: photon virtuality $Q^{2}>1$ (GeV/$c$)$^2$, invariant mass of the hadronic system $W > 5$ GeV/$c^2$, Bjorken scaling variable in the range $0.003 < x < 0.4$, fraction of the virtual photon energy carried by the hadron in the range $0.2 < z < 0.8$, square of the hadron transverse momentum with respect to the virtual photon direction in the range 0.02 (GeV/$c)^2 < P_{\rm{hT}}^{2} < 3$ (GeV/$c$)$^2$. The multiplicities are presented as a function of $P_{\rm{hT}}^{2}$ in three-dimensional bins of $x$, $Q^2$, $z$ and compared to previous semi-inclusive measurements. We explore the small-$P_{\rm{hT}}^{2}$ region, i.e. $P_{\rm{hT}}^{2} < 1$ (GeV/$c$)$^2$, where hadron transverse momenta are expected to arise from non-perturbative effects, and also the domain of larger $P_{\rm{hT}}^{2}$, where contributions from higher-order perturbative QCD are expected to dominate. The multiplicities are fitted using a single-exponential function at small $P_{\rm{hT}}^{2}$ to study the dependence of the average transverse momentum $\langle P_{\rm{hT}}^{2}\rangle$ on $x$, $Q^2$ and $z$. The power-law behaviour of the multiplicities at large $P_{\rm{hT}}^{2}$ is investigated using various functional forms. The fits describe the data reasonably well over the full measured range.Comment: 28 pages, 20 figure

Leading-order determination of the gluon polarisation from semi-inclusive deep inelastic scattering data

Using a novel analysis technique, the gluon polarisation in the nucleon is re-evaluated using the longitudinal double-spin asymmetry measured in the cross section of semi-inclusive single-hadron muoproduction with photon virtuality $Q^2>1~({\rm GeV}/c)^2$. The data were obtained by the COMPASS experiment at CERN using a 160 GeV/$c$ polarised muon beam impinging on a polarised $^6$LiD target. By analysing the full range in hadron transverse momentum $p_{\rm T}$, the different $p_{\rm T}$-dependences of the underlying processes are separated using a neural-network approach. In the absence of pQCD calculations at next-to-leading order in the selected kinematic domain, the gluon polarisation $\Delta g/g$ is evaluated at leading order in pQCD at a hard scale of $\mu^2= \langle Q^2 \rangle = 3 ({\rm GeV}/c)^2$. It is determined in three intervals of the nucleon momentum fraction carried by gluons, $x_{\rm g}$, covering the range $0.04 \!<\! x_{ \rm g}\! <\! 0.28$~ and does not exhibit a significant dependence on $x_{\rm g}$. The average over the three intervals, $\langle \Delta g/g \rangle = 0.113 \pm 0.038_{\rm (stat.)}\pm 0.036_{\rm (syst.)}$ at $\langle x_{\rm g} \rangle \approx 0.10$, suggests that the gluon polarisation is positive in the measured $x_{\rm g}$ range.Comment: 14 pages, 6 figure

Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk

BACKGROUND: Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations. METHODS: We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls). RESULTS: Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network. CONCLUSION: We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development. IMPACT: Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization

Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer

BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer. METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients. RESULTS: The most significant global associations for all genes in the pathway were seen in endometrioid (p = 0.082) and clear cell (p = 0.083), with the most significant gene level association seen with TGFBR2 (p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 (p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA (p = 0.035, endometrioid and mucinous), LGALS1 (p = 0.03, mucinous), STAT5B (p = 0.022, clear cell), TGFBR1 (p = 0.021 endometrioid) and TGFBR2 (p = 0.017 and p = 0.025, endometrioid and mucinous, respectively). CONCLUSIONS: Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients

Radioactive Phosphorylation of Alcohols to Monitor Biocatalytic Diels-Alder Reactions

Nature has efficiently adopted phosphorylation for numerous biological key processes, spanning from cell signaling to energy storage and transmission. For the bioorganic chemist the number of possible ways to attach a single phosphate for radioactive labeling is surprisingly small. Here we describe a very simple and fast one-pot synthesis to phosphorylate an alcohol with phosphoric acid using trichloroacetonitrile as activating agent. Using this procedure, we efficiently attached the radioactive phosphorus isotope 32P to an anthracene diene, which is a substrate for the Diels-Alderase ribozyme—an RNA sequence that catalyzes the eponymous reaction. We used the 32P-substrate for the measurement of RNA-catalyzed reaction kinetics of several dye-labeled ribozyme variants for which precise optical activity determination (UV/vis, fluorescence) failed due to interference of the attached dyes. The reaction kinetics were analyzed by thin-layer chromatographic separation of the 32P-labeled reaction components and densitometric analysis of the substrate and product radioactivities, thereby allowing iterative optimization of the dye positions for future single-molecule studies. The phosphorylation strategy with trichloroacetonitrile may be applicable for labeling numerous other compounds that contain alcoholic hydroxyl groups

Interplay of ribosomal DNA Loci in nucleolar dominance: dominant NORs are up-regulated by chromatin dynamics in the wheat-rye system

Background: Chromatin organizational and topological plasticity, and its functions in gene expression regulation, have been strongly revealed by the analysis of nucleolar dominance in hybrids and polyploids where one parental set of ribosomal RNA (rDNA) genes that are clustered in nucleolar organizing regions (NORs), is rendered silent by epigenetic pathways and heterochromatization. However, information on the behaviour of dominant NORs is very sparse and needed for an integrative knowledge of differential gene transcription levels and chromatin specific domain interactions. Methodology/Principal Findings: Using molecular and cytological approaches in a wheat-rye addition line (wheat genome plus the rye nucleolar chromosome pair 1R), we investigated transcriptional activity and chromatin topology of the wheat dominant NORs in a nucleolar dominance situation. Herein we report dominant NORs up-regulation in the addition line through quantitative real-time PCR and silver-staining technique. Accompanying this modification in wheat rDNA trascription level, we also disclose that perinucleolar knobs of ribosomal chromatin are almost transcriptionally silent due to the residual detection of BrUTP incorporation in these domains, contrary to the marked labelling of intranucleolar condensed rDNA. Further, by comparative confocal analysis of nuclei probed to wheat and rye NORs, we found that in the wheat-rye addition line there is a significant decrease in the number of wheat-origin perinucleolar rDNA knobs, corresponding to a diminution of the rDNA heterochromatic fraction of the dominant (wheat) NORs. Conclusions/Significance: We demonstrate that inter-specific interactions leading to wheat-origin NOR dominance results not only on the silencing of rye origin NOR loci, but dominant NORs are alsomodified in their transcriptional activity and interphase organization. The results show a cross-talk between wheat and rye NORs, mediated by ribosomal chromatin dynamics, revealing a conceptual shift from differential amphiplasty to ‘mutual amphiplasty’ in the nucleolar dominance process.This work was supported by the Fundação para a Ciência e Tecnologia (projects POCI/BIA-BDE/57575/2004 to M.S. and POCI/BIA-BCM/59389/2004 to N.N.