Multiple Keratoacanthomas, Philadelphia Chromosome+ Acute Lymphoblastic Leukemia, and Dasatinib: A Case Report

Background: Treatment for adult Philadelphia chromosome+ acute lymphoblastic leukemia includes using dasatinib, a tyrosine kinase inhibitor. Cutaneous squamous cell carcinomas and keratoacanthomas are common findings in patients treated with BRAF inhibitors of tyrosine kinases. No documentation of dasatinib inducing multiple keratoacanthomas, squamous cell carcinomas type during treatment of Philadelphia chromosome+ acute lymphoblastic leukemia is currently available. Case: A 77-year-old Caucasian male presented to the dermatology clinic two months after starting treatment with dasatinib for Philadelphia chromosome positive+ acute lymphoblastic leukemia. Biopsies confirmed the lesions on the arms, chest, legs and back as keratoacanthoma (KA) type of squamous cell carcinomas (SCCs). The cutaneous lesions were surgically removed and no new or recurrent lesions were detected since their initial rapid onset despite continued dasatinib therapy. Conclusion: This report of the rapid onset of keratoacanthoma type squamous cell carcinomas in a patient with Philadelphia chromosome+ acute lymphoblastic leukemia treated with dasatinib is presumed to be the first due to the rarity of adult Philadelphia chromosome+ acute lymphoblastic leukemia. This report documents another tyrosine kinase inhibitor that is associated with the eruption of keratoacanthomas, and adds to the literature regarding the regularity of this relatively common side effect, which may have treatment other than surgery if only a few lesions are present

Crisp1 and alopecia areata in C3H/HeJ mice

Alopecia areata (AA), a cell mediated autoimmune disease, is the second most common form of hair loss in humans. While the autoimmune disease is responsible for the underlying pathogenesis, the alopecia phenotype is ultimately due to hair shaft fragility and breakage associated with structural deficits. Quantitative trait genetic analyses using the C3H/HeJ mouse AA model identified cysteine-rich secretory protein 1 (Crisp1), a hair shaft structural protein, as a candidate gene within the major AA locus. Crisp1 transcripts in the skin at various times during disease development were barely detectable. In situ hybridization identified Crisp1 expression within the medulla of hair shafts from clinically normal strains of mice but not C3H/HeJ mice with AA. Follow-up work with 5-day-old C3H/HeJ mice with normal hair also had essentially no expression of Crisp1. Other non-inflammatory based follicular dystrophy mouse models with similar hair shaft abnormalities also have little or no Crisp1 expression. Shotgun proteomics, used to determine strain difference in hair proteins, confirmed that there was very little CRISP1 within normal C3H/HeJ mouse hair in comparison to 11 other strains. However, mutant mice with hair medulla defects also had undetectable levels of CRISP1 in their hair. Crisp1 null mice had normal skin, hair follicles, and hair shafts indicating that the lack of the CRISP1 protein does not translate directly into defects in the hair shaft or hair follicle. These results suggest that CRISP1 may be an important structural component of mouse hair and that its strain-specific dysregulation may indicate a predisposition to hair shaft disease such as AA.Fil: Sundberg, John P.. Vanderbilt University; Estados Unidos. The Jackson Laboratory; Estados UnidosFil: Awgulewitsch, Alejandro. Medical University of South Carolina; Estados UnidosFil: Pruett, Nathan D.. Medical University Of South Carolina; Estados UnidosFil: Potter, Cristhoper S.. The Jackson Laboratory; Estados UnidosFil: Silva, Kathleen A.. The Jackson Laboratory; Estados UnidosFil: Stearns, Timothy M.. The Jackson Laboratory; Estados UnidosFil: Sundberg, Beth A.. The Jackson Laboratory; Estados UnidosFil: Weigel Muñoz, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Cuasnicu, Patricia Sara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: King, Lloyd E. Jr. Vanderbilt University; Estados UnidosFil: Rice, Robert H.. University of California. Department of Nutrition and Department of Environmental Toxicology; Estados Unido

DermO; an ontology for the description of dermatologic disease

Background: There have been repeated initiatives to produce standard nosologies and terminologies for cutaneous disease, some dedicated to the domain and some part of bigger terminologies such as ICD-10. Recently, formally structured terminologies, ontologies, have been widely developed in many areas of biomedical research. Primarily, these address the aim of providing comprehensive working erminologies for domains of knowledge, but because of the knowledge contained in the relationships between terms they can also be used computationally for many purposes. Results: We have developed an ontology of cutaneous disease, constructed manually by domain experts. With more than 3000 terms, DermO represents the most comprehensive formal dermatological disease terminology available. The disease entities are categorized in 20 upper level terms, which use a variety of features such as anatomical location, heritability, affected cell or tissue type, or etiology, as the features for classification, in line with professional practice and nosology in dermatology. Available in OBO flatfile and OWL 2 formats, it is integrated semantically with other ontologies and terminologies describing diseases and phenotypes. We demonstrate the application of DermO to text mining the biomedical literature and in the creation of a network describing the phenotypic relationships between cutaneous diseases. Conclusions: DermO is an ontology with broad coverage of the domain of dermatologic disease and we demonstrate here its utility for text mining and investigation of phenotypic relationships between dermatologic disorders. We envision that in the future it may be applied to the creation and mining of electronic health records, clinical training and basic research, as it supports automated inference and reasoning, and for the broader integration of skin disease information with that from other domain

Why alternative teenagers self-harm: exploring the link between non-suicidal self-injury, attempted suicide and adolescent identity

Background: The term ‘self-harm’ encompasses both attempted suicide and non-suicidal self-injury (NSSI). Specific adolescent subpopulations such as ethnic or sexual minorities, and more controversially, those who identify as ‘Alternative’ (Goth, Emo) have been proposed as being more likely to self-harm, while other groups such as ‘Jocks’ are linked with protective coping behaviours (for example exercise). NSSI has autonomic (it reduces negative emotions) and social (it communicates distress or facilitates group ‘bonding’) functions. This study explores the links between such aspects of self-harm, primarily NSSI, and youth subculture.<p></p> Methods: An anonymous survey was carried out of 452 15 year old German school students. Measures included: identification with different youth cultures, i.e. Alternative (Goth, Emo, Punk), Nerd (academic) or Jock (athletic); social background, e.g. socioeconomic status; and experience of victimisation. Self-harm (suicide and NSSI) was assessed using Self-harm Behavior Questionnaire and the Functional Assessment of Self-Mutilation (FASM).<p></p> Results: An “Alternative” identity was directly (r ≈ 0.3) and a “Jock” identity inversely (r ≈ -0.1) correlated with self-harm. “Alternative” teenagers self-injured more frequently (NSSI 45.5% vs. 18.8%), repeatedly self-injured, and were 4–8 times more likely to attempt suicide (even after adjusting for social background) than their non-Alternative peers. They were also more likely to self-injure for autonomic, communicative and social reasons than other adolescents.<p></p> Conclusions: About half of ‘Alternative’ adolescents’ self-injure, primarily to regulate emotions and communicate distress. However, a minority self-injure to reinforce their group identity, i.e. ‘To feel more a part of a group’

Predictors of health-related quality of life in type II diabetic patients in Greece

<p>Abstract</p> <p>Background</p> <p>Diabetes Mellitus (DM) is a major cause of morbidity and mortality affecting millions of people worldwide, while placing a noteworthy strain on public health funding. The aim of this study was to assess health-related quality of life (HRQOL) of Greek Type II DM patients and to identify significant predictors of the disease in this patient population.</p> <p>Methods</p> <p>The sample (N = 229, 52.8% female, 70.0 years mean age) lived in a rural community of Lesvos, an island in the northeast of the Aegean Archipelagos. The generic SF-36 instrument, administered by trainee physicians, was used to measure HRQOL. Scale scores were compared with non-parametric Mann-Whitney and Kruskal-Wallis tests and multivariate stepwise linear regression analyses were used to investigate the effect of sociodemographic and diabetes-related variables on HRQOL.</p> <p>Results</p> <p>The most important predictors of impaired HRQOL were female gender, diabetic complications, non-diabetic comorbidity and years with diabetes. Older age, lower education, being unmarried, obesity, hypertension and hyperlipidaemia were also associated with impaired HRQOL in at least one SF-36 subscale. Multivariate regression analyses produced models explaining significant portions of the variance in SF-36 subscales, especially physical functioning (R²= 42%), and also showed that diabetes-related indicators were more important disease predictors, compared to sociodemographic variables.</p> <p>Conclusion</p> <p>The findings could have implications for health promotion in rural medical practice in Greece. In order to preserve a good HRQOL, it is obviously important to prevent diabetes complications and properly manage concomitant chronic diseases. Furthermore, the gender difference is interesting and requires further elucidation. Modifying screening methods and medical interventions or formulating educational programs for the local population appear to be steps in the correct direction.</p

Establishing Alpha Oph as a Prototype Rotator: Improved Astrometric Orbit

The nearby star Alpha Oph (Ras Alhague) is a rapidly rotating A5IV star spinning at ~89% of its breakup velocity. This system has been imaged extensively by interferometric techniques, giving a precise geometric model of the star's oblateness and the resulting temperature variation on the stellar surface. Fortuitously, Alpha Oph has a previously known stellar companion, and characterization of the orbit provides an independent, dynamically-based check of both the host star and the companion mass. Such measurements are crucial to constrain models of such rapidly rotating stars. In this study, we combine eight years of Adaptive Optics imaging data from the Palomar, AEOS, and CFHT telescopes to derive an improved, astrometric characterization of the companion orbit. We also use photometry from these observations to derive a model-based estimate of the companion mass. A fit was performed on the photocenter motion of this system to extract a component mass ratio. We find masses of 2.40^{0.23}_{0.37} solar masses and 0.85^{0.06}_{0.04} solar masses for Alpha Oph A and Alpha Oph B, respectively. Previous orbital studies of this system found a mass too high for this system, inconsistent with stellar evolutionary calculations. Our measurements of the host star mass are more consistent with these evolutionary calculations, but with slightly higher uncertainties. In addition to the dynamically-derived masses, we use IJHK photometry to derive a model-based mass for Alpha Oph B, of 0.77 +/- 0.05 solar masses marginally consistent with the dynamical masses derived from our orbit. Our model fits predict a periastron passage on 2012 April 19, with the two components having a ~50 milliarcsec separation from March to May 2012. A modest amount of interferometric and radial velocity data during this period could provide a mass determination of this star at the few percent level.Comment: Accepted to ApJ, 6 pages, 4 figure

Transmission of MRSA between Companion Animals and Infected Human Patients Presenting to Outpatient Medical Care Facilities

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant pathogen in both human and veterinary medicine. The importance of companion animals as reservoirs of human infections is currently unknown. The companion animals of 49 MRSA-infected outpatients (cases) were screened for MRSA carriage, and their bacterial isolates were compared with those of the infected patients using Pulsed-Field Gel Electrophoresis (PFGE). Rates of MRSA among the companion animals of MRSA-infected patients were compared to rates of MRSA among companion animals of pet guardians attending a “veterinary wellness clinic” (controls). MRSA was isolated from at least one companion animal in 4/49 (8.2%) households of MRSA-infected outpatients vs. none of the pets of the 50 uninfected human controls. Using PFGE, patient-pets MRSA isolates were identical for three pairs and discordant for one pair (suggested MRSA inter-specie transmission p-value = 0.1175). These results suggest that companion animals of MRSA-infected patients can be culture-positive for MRSA, representing a potential source of infection or re-infection for humans. Further studies are required to better understand the epidemiology of MRSA human-animal inter-specie transmission

Analysis of the diverse antigenic landscape of the malaria protein RH5 identifies a potent vaccine-induced human public antibody clonotype

The highly conserved and essential Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) has emerged as the leading target for vaccines against the disease-causing blood stage of malaria. However, the features of the human vaccine-induced antibody response that confer highly potent inhibition of malaria parasite invasion into red blood cells are not well defined. Here, we characterize 236 human IgG monoclonal antibodies, derived from 15 donors, induced by the most advanced PfRH5 vaccine. We define the antigenic landscape of this molecule and establish that epitope specificity, antibody association rate, and intra-PfRH5 antibody interactions are key determinants of functional anti-parasitic potency. In addition, we identify a germline IgG gene combination that results in an exceptionally potent class of antibody and demonstrate its prophylactic potential to protect against P. falciparum parasite challenge in vivo. This comprehensive dataset provides a framework to guide rational design of next-generation vaccines and prophylactic antibodies to protect against blood-stage malaria

The dominant ethnic moment: towards the abolition of 'whiteness'?

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