Knowledge and Perceptions of Pharmacy Students in Qatar on Anti-Doping in Sports and on Sports Pharmacy in Undergraduate Curricula

Objective. To assess pharmacy students’ knowledge and perceptions of doping and anti-doping in sports and to explore the curricular needs for undergraduate pharmacy in the field of sports pharmacy. Methods. A cross-sectional, descriptive, web-based survey of pharmacy students was conducted at Qatar University College of Pharmacy from March to May 2014. Data were analyzed using descriptive and inferential statistics. Results. Eighty respondents completed the online survey (80% response rate). Sixty percent were unaware of the World Anti-Doping Agency, and 85% were unaware of the International Pharmaceutical Federation’s statement on the pharmacist’s role in anti-doping. Students’ knowledge score regarding the prohibited status of drugs that may be used by athletes was around 50%. Fourth-year pharmacy students had significantly higher knowledge scores than the other groups of students. Respondents acknowledged the important role of health care professionals, including pharmacists, as advisors on the safe and effective use of drugs in sports. Ninety percent of the students supported the inclusion of sports pharmacy in the curriculum. Conclusion. Pharmacy students indicated a strong desire to play a role in doping prevention and ensure safe and rational use of drugs among athletes. They suggested requiring an education and training strategy for sports pharmacy in undergraduate pharmacy curricula.Qatar University Undergraduate Student Research Grant

Kv1.3-induced hyperpolarization is required for efficient Kaposi's sarcoma-associated herpesvirus lytic replication

Funding: This work was supported by a Rosetrees trust PhD studentship, M662, White Rose BBSRC Doctoral training Partnership in Mechanistic Biology (95519935), BBSRC project grant (BB/T00021X/1), and a Royal Society University Research Fellowship [g:480764 (to J.M.)].Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic herpesvirus that is linked directly to the development of Kaposi's sarcoma. KSHV establishes a latent infection in B cells, which can be reactivated to initiate lytic replication, producing infectious virions. Using pharmacological and genetic silencing approaches, we showed that the voltage-gated K+ channel Kv1.3 in B cells enhanced KSHV lytic replication. The KSHV replication and transcription activator (RTA) protein increased the abundance of Kv1.3 and led to enhanced K+ channel activity and hyperpolarization of the B cell membrane. Enhanced Kv1.3 activity promoted intracellular Ca2+ influx, leading to the Ca2+-driven nuclear localization of KSHV RTA and host nuclear factor of activated T cells (NFAT) proteins and subsequently increased the expression of NFAT1 target genes. KSHV lytic replication and infectious virion production were inhibited by Kv1.3 blockers or silencing. These findings highlight Kv1.3 as a druggable host factor that is key to the successful completion of KSHV lytic replication.Peer reviewe

Genome-wide and protein kinase-focused RNAi screens reveal conserved and novel damage response pathways in Trypanosoma brucei

All cells are subject to structural damage that must be addressed for continued growth. A wide range of damage affects the genome, meaning multiple pathways have evolved to repair or bypass the resulting DNA lesions. Though many repair pathways are conserved, their presence or function can reflect the life style of individual organisms. To identify genome maintenance pathways in a divergent eukaryote and important parasite, Trypanosoma brucei, we performed RNAi screens to identify genes important for survival following exposure to the alkylating agent methyl methanesulphonate. Amongst a cohort of broadly conserved and, therefore, early evolved repair pathways, we reveal multiple activities not so far examined functionally in T. brucei, including DNA polymerases, DNA helicases and chromatin factors. In addition, the screens reveal Trypanosoma- or kinetoplastid-specific repair-associated activities. We also provide focused analyses of repair-associated protein kinases and show that loss of at least nine, and potentially as many as 30 protein kinases, including a nuclear aurora kinase, sensitises T. brucei to alkylation damage. Our results demonstrate the potential for synthetic lethal genome-wide screening of gene function in T. brucei and provide an evolutionary perspective on the repair pathways that underpin effective responses to damage, with particular relevance for related kinetoplastid pathogens. By revealing that a large number of diverse T. brucei protein kinases act in the response to damage, we expand the range of eukaryotic signalling factors implicated in genome maintenance activities

Decision regret in men living with and beyond nonmetastatic prostate cancer in the United Kingdom: A population‐based patient‐reported outcome study

Objective: Clinical options for managing nonmetastatic prostate cancer (PCa) vary. Each option has side effects associated with it, leading to difficulty in decision‐making. This study aimed to assess the relationship between patient involvement in treatment decision‐making and subsequent decision regret (DR), and quantify the impact of health‐related quality of life (HRQL) outcomes on DR. Methods: Men living in the United Kingdom, 18 to 42 months after diagnosis of PCa, were identified from cancer registration data and sent a questionnaire. Measures included the Decision Regret Scale (DRS), Expanded Prostate cancer Index Composite short form (EPIC‐26), EQ‐5D‐5L, and an item on involvement in treatment decision‐making. Multivariable ordinal regression was utilized, with DR categorized as none, mild, or moderate/severe regret. Results: A total of 17 193 men with stage I‐III PCa completed the DRS: 36.6% reported no regret, 43.3% mild regret, and 20.0% moderate/severe regret. The odds of reporting DR were greater if men indicated their views were not taken into account odds ratio ([OR] = 6.42, 95% CI: 5.39‐7.64) or were involved “to some extent” in decision‐making (OR = 4.63, 95% CI: 4.27‐5.02), compared with men who were “definitely” involved. After adjustment, including for involvement, men reporting moderate/big problems with urinary, bowel, or sexual function were more likely to experience regret compared with men with no/small problems. Better HRQL scores were associated with lower levels of DR. Conclusions: This large‐scale study demonstrates the benefit of patient involvement in treatment decision‐making for nonmetastatic PCa. However, men experiencing side effects and poorer HRQL report greater DR. Promoting engagement in clinical decision‐making represents good practice and may reduce the risk of subsequent regret

PTF11eon/SN2011dh: Discovery of a Type IIb Supernova From a Compact Progenitor in the Nearby Galaxy M51

On May 31, 2011 UT a supernova (SN) exploded in the nearby galaxy M51 (the Whirlpool Galaxy). We discovered this event using small telescopes equipped with CCD cameras, as well as by the Palomar Transient Factory (PTF) survey, and rapidly confirmed it to be a Type II supernova. Our early light curve and spectroscopy indicates that PTF11eon resulted from the explosion of a relatively compact progenitor star as evidenced by the rapid shock-breakout cooling seen in the light curve, the relatively low temperature in early-time spectra and the prompt appearance of low-ionization spectral features. The spectra of PTF11eon are dominated by H lines out to day 10 after explosion, but initial signs of He appear to be present. Assuming that He lines continue to develop in the near future, this SN is likely a member of the cIIb (compact IIb; Chevalier and Soderberg 2010) class, with progenitor radius larger than that of SN 2008ax and smaller than the eIIb (extended IIb) SN 1993J progenitor. Our data imply that the object identified in pre-explosion Hubble Space Telescope images at the SN location is possibly a companion to the progenitor or a blended source, and not the progenitor star itself, as its radius (~10^13 cm) would be highly inconsistent with constraints from our post-explosion photometric and spectroscopic data

Project overview and update on WEAVE: the next generation wide-field spectroscopy facility for the William Herschel Telescope

We present an overview of and status report on the WEAVE next-generation spectroscopy facility for the William Herschel Telescope (WHT). WEAVE principally targets optical ground-based follow up of upcoming ground-based (LOFAR) and space-based (Gaia) surveys. WEAVE is a multi-object and multi-IFU facility utilizing a new 2-degree prime focus field of view at the WHT, with a buffered pick-and-place positioner system hosting 1000 multi-object (MOS) fibres, 20 integral field units, or a single large IFU for each observation. The fibres are fed to a single spectrograph, with a pair of 8k(spectral) x 6k (spatial) pixel cameras, located within the WHT GHRIL enclosure on the telescope Nasmyth platform, supporting observations at R~5000 over the full 370-1000nm wavelength range in a single exposure, or a high resolution mode with limited coverage in each arm at R~20000. The project is now in the final design and early procurement phase, with commissioning at the telescope expected in 2017.Comment: 11 pages, 11 Figures, Summary of a presentation to Astronomical Telescopes and Instrumentation 201

Metabolomics to unveil and understand phenotypic diversity between pathogen populations

Visceral leishmaniasis is caused by a parasite called Leishmania donovani, which every year infects about half a million people and claims several thousand lives. Existing treatments are now becoming less effective due to the emergence of drug resistance. Improving our understanding of the mechanisms used by the parasite to adapt to drugs and achieve resistance is crucial for developing future treatment strategies. Unfortunately, the biological mechanism whereby Leishmania acquires drug resistance is poorly understood. Recent years have brought new technologies with the potential to increase greatly our understanding of drug resistance mechanisms. The latest mass spectrometry techniques allow the metabolome of parasites to be studied rapidly and in great detail. We have applied this approach to determine the metabolome of drug-sensitive and drug-resistant parasites isolated from patients with leishmaniasis. The data show that there are wholesale differences between the isolates and that the membrane composition has been drastically modified in drug-resistant parasites compared with drug-sensitive parasites. Our findings demonstrate that untargeted metabolomics has great potential to identify major metabolic differences between closely related parasite strains and thus should find many applications in distinguishing parasite phenotypes of clinical relevance

Intrapersonal, interpersonal, and physical space in anorexia nervosa: a virtual reality and repertory grid study.

This document is the Accepted Manuscript version of a published work that appeared in final form in Psychiatry Research after peer review and technical editing by the publisher. To access the final edited and published work see doi: https://doi.org.10.1016/j.psychres.2017.02.060.Anorexia nervosa (AN) is an eating disorder characterized by severe body image disturbances. Recent studies from spatial cognition showed a connection between the experience of body and of space. The objectives of this study were to explore the meanings that characterize AN experience and to deepen the examination of spatiality in relational terms, through the study of how the patient construes herself and her interpersonal world. More specifically this study aimed (1) to verify whether spatial variables and aspects of construing differentiate patients with AN and healthy controls (HCs) and are related to severity of anorexic symptomatology; (2) to explore correlations between impairments in spatial abilities and interpersonal construing. A sample of 12 AN patients and 12 HCs participated in the study. The Eating Disorder Inventory, a virtual reality-based procedure, traditional measures of spatial abilities, and repertory grids were administered. The AN group compared to HCs showed significant impairments in spatial abilities, more unidimensional construing, and more extreme construing of the present self and of the self as seen by others. All these dimensions correlated with the severity of symptomatology. Extreme ways of construing characterized individuals with AN and might represent the interpersonal aspect of impairment in spatial reference frames.Peer reviewedFinal Accepted Versio

Drug Discovery for Kinetoplastid Diseases : Future Directions

International audienceKinetoplastid parasites have caused human disease for millennia. Significant achievements have been made toward developing new treatments for leishmaniasis (particularly on the Indian subcontinent) and for human African trypanosomiasis (HAT). Moreover, the sustained decrease in the incidence of HAT has made the prospect of elimination a tantalizing reality. Despite the gains, no new chemical or biological entities to treat kinetoplastid diseases have been registered in more than three decades, and more work is needed to discover safe and effective therapies for patients with Chagas disease and leishmaniasis. Advances in tools for drug discovery and novel insights into the biology of the host-parasite interaction may provide opportunities for accelerated progress. Here, we summarize the output from a gathering of scientists and physicians who met to discuss the current status and future directions in drug discovery for kinetoplastid diseases