Lifestyle, harassment at work and self-assessed health of female flight attendants, nurses and teachers.

Health-related lifestyle, harassment at work, and self-assessed health of female flight attendants in comparison to that of female nurses and female primary school teachers were surveyed. A higher proportion of flight attendants than nurses or teachers were smokers, 26% vs. 15% and 17% respectively; and consumed alcohol at least once a week, 40% vs. 21% and 16%. Repeated sexual harassment at work was more common among the flight attendants, 31% vs. 8% and 4%; whereas bullying, physical violence and threats were less prevalent among the flight attendants (12%) than among nurses (19%). Flight attendants were on average somewhat taller, but weighed on average less, 63.8 kg vs. 72.4 kg and 72.7 kg respectively. Repeated exposure to sexual harassment, bullying, violence and threats was related to less physical and psychological well-being in all the groups. Teachers scored on average significantly lower than did the flight attendants on general health and physical well-being, while nurses did not

How Do Bone Marrow Lesions Cause Osteoarthritis Pain? a Structural and Functional Tissue-Based Study

Background/Purpose: Susceptibility to ankylosing spondylitis (AS) is primarily genetic; thus far 113 susceptibility variants for AS have been identified. However, most of the AS associated SNPs do not directly affect protein-coding genes. Studies of disease- and trait-associated SNPs suggest they may act by affecting gene regulatory regions in specific cell types or tissues. Therefore, identifying the AS relevant cell types is crucial for further mechanistic studies. Methods: We applied several bioinformatics methods to utilize epigenetic, gene and protein expression information to identify the primary relevant cell types through which genetic variants associated with AS operate. In total, there are 113 AS associated loci; 39 of them show genome-wide significance in AS-only analyses, whereas the remainder are genome-wide significant in analyses leveraging pleiotrophy with other related diseases (Crohn’s disease (CD), psoriasis, primary sclerosing cholangitis (PSC) and ulcerative colitis (UC))1. Results: AS-associated SNPs are disproportionately found in regions bearing epigenetic marks indicating transcriptional activity found in immune cell types including monocytes, CD4+ and CD8+ T cells, NK cells, regulatory T cells, and B cells. Gene expression studies showed enrichment of AS associated loci in genes specifically expressed in monocytes and NK cells while protein expression study shows protein products of AS associated loci were significantly enriched in CD8+ T cells. Epigenetic analyses also showed evidence that AS-associated signals operate in gut cell types including in mucosa from the small intestine, sigmoid colon and rectum. These findings particularly relate to pleiotropic loci also associated with IBD, psoriasis, and PSC. Conclusion: These findings highlight the role of key immune cell types in the mechanism by which genetic associations with AS drive the disease, as well as providing further evidence for the involvement of the gut in the pathogenesis of AS. 1Ellinghaus D. at al, Nature Genetics 201

High effectiveness of self-help programs after drug addiction therapy

BACKGROUND: The self-help groups Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) are very well established. AA and NA employ a 12-step program and are found in most large cities around the world. Although many have argued that these organizations are valuable, substantial scepticism remains as to whether they are actually effective. Few treatment facilities give clear recommendations to facilitate participation, and the use of these groups has been disputed. The purpose of this study was to examine whether the use of self-help groups after addiction treatment is associated with higher rates of abstinence. METHODS: One hundred and fourteen patients, 59 with alcohol dependency and 55 with multiple drug dependency, who started in self-help groups after addiction treatment, were examined two years later using a questionnaire. Return rate was 66%. Six (5%) of the patients were dead. RESULTS: Intention-to-treat-analysis showed that 38% still participated in self-help programs two years after treatment. Among the regular participants, 81% had been abstinent over the previous 6 months, compared with only 26% of the non-participants. Logistic regression analysis showed OR = 12.6, 95% CI (4.1–38.3), p < 0.001, for participation and abstinence. CONCLUSION: The study has several methodological problems; in particular, correlation does not necessarily indicate causality. These problems are discussed and we conclude that the probability of a positive effect is sufficient to recommend participation in self-help groups as a supplement to drug addiction treatment. PREVIOUS PUBLICATION: This article is based on a study originally published in Norwegian: Kristensen O, Vederhus JK: Self-help programs in drug addiction therapy. Tidsskr Nor Laegeforen 2005, 125:2798–2801

SciClone: Inferring clonal architecture and tracking the spatial and temporal patterns of tumor evolution

The sensitivity of massively-parallel sequencing has confirmed that most cancers are oligoclonal, with subpopulations of neoplastic cells harboring distinct mutations. A fine resolution view of this clonal architecture provides insight into tumor heterogeneity, evolution, and treatment response, all of which may have clinical implications. Single tumor analysis already contributes to understanding these phenomena. However, cryptic subclones are frequently revealed by additional patient samples (e.g., collected at relapse or following treatment), indicating that accurately characterizing a tumor requires analyzing multiple samples from the same patient. To address this need, we present SciClone, a computational method that identifies the number and genetic composition of subclones by analyzing the variant allele frequencies of somatic mutations. We use it to detect subclones in acute myeloid leukemia and breast cancer samples that, though present at disease onset, are not evident from a single primary tumor sample. By doing so, we can track tumor evolution and identify the spatial origins of cells resisting therapy

Science, Nature and Beauty: Harmony and Cosmological Perspectives in Islamic Science

This is a brochure to accompany the exhibit: “Science, Nature and Beauty: Harmony and Cosmological Perspectives in Islamic Science” (October 19th, 2022- March 3rd, 2023).This exhibit showcases over 90 manuscripts, instruments and objects from the Muslim World Manuscript collection which are housed in the Rare Book and Manuscript Library (RBML), at the Columbia University Libraries (CUL). This exhibit is a collective curatorial effort that has involved many students, faculty members, librarians and library staff working hand-in-hand to exchange ideas and to select, research, engage with, and mount the items. Keywords: Islamic Science--Exhibits; Manuscripts--Islamic science; Islamic arts and sciences; material culture, codicology, Islamic cultures and societies

Axis I and II disorders as long-term predictors of mental distress: a six-year prospective follow-up of substance-dependent patients

<p>Abstract</p> <p>Background</p> <p>A high prevalence of lifetime psychiatric disorders among help-seeking substance abusers has been clearly established. However, the long-term course of psychiatric disorders and mental distress among help-seeking substance abusers is still unclear. The aim of this research was to examine the course of mental distress using a six-year follow-up study of treatment-seeking substance-dependent patients, and to explore whether lifetime Axis I and II disorders measured at admission predict the level of mental distress at follow-up, when age, sex, and substance-use variables measured both at baseline and at follow-up are controlled for. </p> <p>Methods</p> <p>A consecutive sample of substance dependent in- and outpatients (n = 287) from two counties of Norway were assessed at baseline (T1) with the Composite International Diagnostic Interview (Axis I), Millon's Clinical Multiaxial Inventory (Axis II), and the Hopkins Symptom Checklist (HSCL-25 (mental distress)). At follow-up (T2), 48% (137/287 subjects, 29% women) were assessed with the HSCL-25, the Alcohol Use Disorders Identification Test, and the Drug Use Disorders Identification Test. </p> <p>Results</p> <p>The stability of mental distress is a main finding and the level of mental distress remained high after six years, but was significantly lower among abstainers at T2, especially among female abstainers. Both the number of and specific lifetime Axis I disorders (social anxiety disorder, generalized anxiety disorder, and somatization disorder), the number of and specific Axis II disorders (anxious and impulsive personality disorders), and the severity of substance-use disorder at the index admission were all independent predictors of a high level of mental distress at follow-up, even when we controlled for age, sex, and substance use at follow-up.</p> <p>Conclusion</p> <p>These results underscore the importance of diagnosing and treating both substance-use disorder and non-substance-use disorder Axis I and Axis II disorders in the same programme.</p

Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders that often progress to chemotherapy-resistant secondary acute myeloid leukemia (sAML). We used whole-genome sequencing to perform an unbiased comprehensive screen to discover the somatic mutations in a sample from an individual with sAML and genotyped the loci containing these mutations in the matched MDS sample. Here we show that a missense mutation affecting the serine at codon 34 (Ser34) in U2AF1 was recurrently present in 13 out of 150 (8.7%) subjects with de novo MDS, and we found suggestive evidence of an increased risk of progression to sAML associated with this mutation. U2AF1 is a U2 auxiliary factor protein that recognizes the AG splice acceptor dinucleotide at the 3' end of introns, and the alterations in U2AF1 are located in highly conserved zinc fingers of this protein. Mutant U2AF1 promotes enhanced splicing and exon skipping in reporter assays in vitro. This previously unidentified, recurrent mutation in U2AF1 implicates altered pre-mRNA splicing as a potential mechanism for MDS pathogenesis

Analysis of AML genes in dysregulated molecular networks

<p>Abstract</p> <p>Background</p> <p>Identifying disease causing genes and understanding their molecular mechanisms are essential to developing effective therapeutics. Thus, several computational methods have been proposed to prioritize candidate disease genes by integrating different data types, including sequence information, biomedical literature, and pathway information. Recently, molecular interaction networks have been incorporated to predict disease genes, but most of those methods do not utilize invaluable disease-specific information available in mRNA expression profiles of patient samples.</p> <p>Results</p> <p>Through the integration of protein-protein interaction networks and gene expression profiles of acute myeloid leukemia (AML) patients, we identified subnetworks of interacting proteins dysregulated in AML and characterized known mutation genes causally implicated to AML embedded in the subnetworks. The analysis shows that the set of extracted subnetworks is a reservoir rich in AML genes reflecting key leukemogenic processes such as myeloid differentiation.</p> <p>Conclusion</p> <p>We showed that the integrative approach both utilizing gene expression profiles and molecular networks could identify AML causing genes most of which were not detectable with gene expression analysis alone due to the minor changes in mRNA level.</p

Clonal architecture of secondary acute myeloid leukemia

BACKGROUND: The myelodysplastic syndromes are a group of hematologic disorders that often evolve into secondary acute myeloid leukemia (AML). The genetic changes that underlie progression from the myelodysplastic syndromes to secondary AML are not well understood. METHODS: We performed whole-genome sequencing of seven paired samples of skin and bone marrow in seven subjects with secondary AML to identify somatic mutations specific to secondary AML. We then genotyped a bone marrow sample obtained during the antecedent myelodysplastic-syndrome stage from each subject to determine the presence or absence of the specific somatic mutations. We identified recurrent mutations in coding genes and defined the clonal architecture of each pair of samples from the myelodysplastic-syndrome stage and the secondary-AML stage, using the allele burden of hundreds of mutations. RESULTS: Approximately 85% of bone marrow cells were clonal in the myelodysplastic-syndrome and secondary-AML samples, regardless of the myeloblast count. The secondary-AML samples contained mutations in 11 recurrently mutated genes, including 4 genes that have not been previously implicated in the myelodysplastic syndromes or AML. In every case, progression to acute leukemia was defined by the persistence of an antecedent founding clone containing 182 to 660 somatic mutations and the outgrowth or emergence of at least one subclone, harboring dozens to hundreds of new mutations. All founding clones and subclones contained at least one mutation in a coding gene. CONCLUSIONS: Nearly all the bone marrow cells in patients with myelodysplastic syndromes and secondary AML are clonally derived. Genetic evolution of secondary AML is a dynamic process shaped by multiple cycles of mutation acquisition and clonal selection. Recurrent gene mutations are found in both founding clones and daughter subclones. (Funded by the National Institutes of Health and others.

Very Late Antigen-4 (α<inf>4</inf>β<inf>1</inf> Integrin) Targeted PET Imaging of Multiple Myeloma

Biomedical imaging techniques such as skeletal survey and 18F-fluorodeoxyglucose (FDG)/Positron Emission Tomography (PET) are frequently used to diagnose and stage multiple myeloma (MM) patients. However, skeletal survey has limited sensitivity as it can detect osteolytic lesions only after 30-50% cortical bone destruction, and FDG is a marker of cell metabolism that has limited sensitivity for intramedullary lesions in MM. Targeted, and non-invasive novel probes are needed to sensitively and selectively image the unique molecular signatures and cellular processes associated with MM. Very late antigen-4 (VLA-4; also called α4β1 integrin) is over-expressed on MM cells, and is one of the key mediators of myeloma cell adhesion to the bone marrow (BM) that promotes MM cell trafficking and drug resistance. Here we describe a proof-of-principle, novel molecular imaging strategy for MM tumors using a VLA-4 targeted PET radiopharmaceutical, 64Cu-CB-TE1A1P-LLP2A. Cell uptake studies in a VLA-4-positive murine MM cell line, 5TGM1, demonstrated receptor specific uptake (P<0.0001, block vs. non-block). Tissue biodistribution at 2 h of 64Cu-CB-TE1A1P-LLP2A in 5TGM1 tumor bearing syngeneic KaLwRij mice demonstrated high radiotracer uptake in the tumor (12±4.5%ID/g), and in the VLA-4 rich organs, spleen (8.8±1.0%ID/g) and marrow (11.6±2.0%ID/g). Small animal PET/CT imaging with 64Cu-CB-TE1A1P-LLP2A demonstrated high uptake in the 5TGM1 tumors (SUV 6.6±1.1). There was a 3-fold reduction in the in vivo tumor uptake in the presence of blocking agent (2.3±0.4). Additionally, 64Cu-CB-TE1A1P-LLP2A demonstrated high binding to the human MM cell line RPMI-8226 that was significantly reduced in the presence of the cold targeting agent. These results provide pre-clinical evidence that VLA-4-targeted imaging using 64Cu-CB-TE1A1P-LLP2A is a novel approach to imaging MM tumors. © 2013 Soodgupta et al