Characterization, crystallization and preliminary X-ray investigation of glyceraldehyde-3-phosphate dehydrogenase from the hyperthermophilic archaeon Sulfolobus solfataricus.

Comparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tRecombinant Sulfolobus solfataricus glyceraldehyde-3-phosphate dehydrogenase has been purified and found to be a tetramer of 148 kDa. The enzyme shows dual cofactor specificity and uses NADP+ in preference to NAD+. The sequence has been compared with other GAPDH proteins including those from other archaeal sources. The purified protein has been crystallized from ammonium sulfate to produce crystals that diffract to 2.4 A with a space group of P43212 or P41212. A native data set has been collected to 2.4 A using synchrotron radiation and cryocooling.European UnionBBSR

Prospective memory functioning among ecstasy/polydrug users: evidence from the Cambridge Prospective Memory Test (CAMPROMPT)

Rationale: Prospective memory (PM) deficits in recreational drug users have been documented in recent years. However, the assessment of PM has largely been restricted to self-reported measures that fail to capture the distinction between event-based and time-based PM. The aim of the present study is to address this limitation. Objectives: Extending our previous research, we augmented the range laboratory measures of PM by employing the CAMPROMPT test battery to investigate the impact of illicit drug use on prospective remembering in a sample of cannabis only, ecstasy/polydrug and non-users of illicit drugs, separating event and time-based PM performance. We also administered measures of executive function and retrospective memory in order to establish whether ecstasy/polydrug deficits in PM were mediated by group differences in these processes. Results: Ecstasy/polydrug users performed significantly worse on both event and time-based prospective memory tasks in comparison to both cannabis only and non-user groups. Furthermore, it was found that across the whole sample, better retrospective memory and executive functioning was associated with superior PM performance. Nevertheless, this association did not mediate the drug-related effects that were observed. Consistent with our previous study, recreational use of cocaine was linked to PM deficits. Conclusions: PM deficits have again been found among ecstasy/polydrug users, which appear to be unrelated to group differences in executive function and retrospective memory. However, the possibility that these are attributable to cocaine use cannot be excluded

Lime stabilisation for earthworks: a UK perspective

Lime stabilisation is a versatile technique applied during earthworks operations. Modern soil recycling units are much more efficient at pulverising fill material and intermixing the added binder/water than machinery available 20 years ago. While supplier innovation adds flexibility to the site working method, specifications have not been sufficiently updated to permit optimal application. This review paper details the physico-chemical changes instigated through the lime-clay soil reaction, updating previous reviews. It aims to assist scientific debate, current practitioners and future specification changes. For example, the application of the minimum 24 h mellowing periods (mandatory to UK specifications) with high reactivity, quicklime powders is concluded to cause increased air voids in the compacted fill. Increased air voids are associated with reduced long-term strength and potential volume change from water ingress, which is of particular concern for sulfate swelling. Shorter mellowing periods and/or use of hydrated lime may lesson this issue; however, a 'one size fits all' approach is discouraged in preference to site-specific methodologies refined to suit the fill material and project requirements. The discussion also summarises working methods which may lower the risk of sulfate swell and defines areas requiring further practical research

Health services research in the public healthcare system in Hong Kong: An analysis of over 1 million antihypertensive prescriptions between 2004-2007 as an example of the potential and pitfalls of using routinely collected electronic patient data

<b>Objectives</b> Increasing use is being made of routinely collected electronic patient data in health services research. The aim of the present study was to evaluate the potential usefulness of a comprehensive database used routinely in the public healthcare system in Hong Kong, using antihypertensive drug prescriptions in primary care as an example.<p></p> <b>Methods</b> Data on antihypertensive drug prescriptions were retrieved from the electronic Clinical Management System (e-CMS) of all primary care clinics run by the Health Authority (HA) in the New Territory East (NTE) cluster of Hong Kong between January 2004 and June 2007. Information was also retrieved on patients’ demographic and socioeconomic characteristics, visit type (new or follow-up), and relevant diseases (International Classification of Primary Care, ICPC codes). <p></p> <b>Results</b> 1,096,282 visit episodes were accessed, representing 93,450 patients. Patients’ demographic and socio-economic details were recorded in all cases. Prescription details for anti-hypertensive drugs were missing in only 18 patients (0.02%). However, ICPC-code was missing for 36,409 patients (39%). Significant independent predictors of whether disease codes were applied included patient age > 70 years (OR 2.18), female gender (OR 1.20), district of residence (range of ORs in more rural districts; 0.32-0.41), type of clinic (OR in Family Medicine Specialist Clinics; 1.45) and type of visit (OR follow-up visit; 2.39). <p></p> In the 57,041 patients with an ICPC-code, uncomplicated hypertension (ICPC K86) was recorded in 45,859 patients (82.1%). The characteristics of these patients were very similar to those of the non-coded group, suggesting that most non-coded patients on antihypertensive drugs are likely to have uncomplicated hypertension. <p></p> <b>Conclusion</b> The e-CMS database of the HA in Hong Kong varies in quality in terms of recorded information. Potential future health services research using demographic and prescription information is highly feasible but for disease-specific research dependant on ICPC codes some caution is warranted. In the case of uncomplicated hypertension, future research on pharmaco-epidemiology (such as prescription patterns) and clinical issues (such as side-effects of medications on metabolic parameters) seems feasible given the large size of the data set and the comparability of coded and non-coded patients

Is preference for mHealth intervention delivery platform associated with delivery platform familiarity?

Published online: 22 July 2016Background: The aim of this paper was to ascertain whether greater familiarity with a smartphone or tablet was associated with participants’ preferred mobile delivery modality for eHealth interventions. Methods: Data from 1865 people who participated in the Australian Health and Social Science panel study were included into two multinomial logistic regression analyses in which preference for smartphone and tablet delivery for general or personalised eHealth interventions were regressed onto device familiarity and the covariates of sex, age and education. Results: People were more likely to prefer both general and personalised eHealth interventions presented on tablets if they reported high or moderate tablet familiarity (compared to low familiarity) and people were more likely to prefer both general and personalised eHealth interventions presented on smartphones if they reported high or moderate smartphone familiarity, were younger, and had university education (compared to completing high school or less). Conclusion: People prefer receiving eHealth interventions on the mobile devices they are most familiar with. These findings have important implications that should be considered when developing eHealth interventions, and demonstrates that eHealth interventions should be delivered using multiple platforms simultaneously to optimally cater for as many people as possible.Daniel Granger, Corneel Vandelanotte, Mitch J. Duncan, Stephanie Alley, Stephanie Schoeppe, Camille Short and Amanda Reba

Productive resistance within the public sector: exploring organisational culture

The article examines how South Korean civil servants responded to the introduction of pay for performance. Drawing upon 31 in-depth interviews with career civil servants, it identifies what became known as 1/n, a form of ‘discreet resistance’ that emerged and evolved. The analytical framework allows productive resistance to be seen as ebbing and flowing during organisational change that sees institutionalisation, deinstitutionalisation and re-institutionalisation. In understanding the cultural context of organisational resistance the contribution is three-fold. First, a nuanced definition and understanding of productive resistance. Second, it argues that productive resistance must be seen as part of a process that does not simply reflect ‘offer and counter-offer’ within the change management process. Thirdly, it identifies differences within groups and sub-cultures concerning commitment towards resistance and how these fissures contribute towards change as new interpretive schemes and justifications are presented in light of policy reformulations

Lentivirus-meditated frataxin gene delivery reverses genome instability in Friedreich ataxia patient and mouse model fibroblasts

Friedreich ataxia (FRDA) is a progressive neurodegenerative disease caused by deficiency of frataxin protein, with the primary sites of pathology being the large sensory neurons of the dorsal root ganglia and the cerebellum. FRDA is also often accompanied by severe cardiomyopathy and diabetes mellitus. Frataxin is important in mitochondrial iron–sulfur cluster (ISC) biogenesis and low-frataxin expression is due to a GAA repeat expansion in intron 1 of the FXN gene. FRDA cells are genomically unstable, with increased levels of reactive oxygen species and sensitivity to oxidative stress. Here we report the identification of elevated levels of DNA double strand breaks (DSBs) in FRDA patient and YG8sR FRDA mouse model fibroblasts compared to normal fibroblasts. Using lentivirus FXN gene delivery to FRDA patient and YG8sR cells, we obtained long-term overexpression of FXN mRNA and frataxin protein levels with reduced DSB levels towards normal. Furthermore, γ-irradiation of FRDA patient and YG8sR cells revealed impaired DSB repair that was recovered on FXN gene transfer. This suggests that frataxin may be involved in DSB repair, either directly by an unknown mechanism, or indirectly via ISC biogenesis for DNA repair enzymes, which may be essential for the prevention of neurodegeneration.Ataxia UK, FARA Australasia and FARA US

Anti-cancer drug validation: the contribution of tissue engineered models

Abstract Drug toxicity frequently goes concealed until clinical trials stage, which is the most challenging, dangerous and expensive stage of drug development. Both the cultures of cancer cells in traditional 2D assays and animal studies have limitations that cannot ever be unraveled by improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. Considering the NCI60, a panel of 60 cancer cell lines representative of 9 different cancer types: leukemia, lung, colorectal, central nervous system (CNS), melanoma, ovarian, renal, prostate and breast, we propose to review current Bstate of art^ on the 9 cancer types specifically addressing the 3D tissue models that have been developed and used in drug discovery processes as an alternative to complement their studyThis article is a result of the project FROnTHERA (NORTE-01-0145-FEDER-000023), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This article was also supported by the EU Framework Programme for Research and Innovation HORIZON 2020 (H2020) under grant agreement n° 668983 — FoReCaST. FCT distinction attributed to Joaquim M. Oliveira (IF/00423/2012) and Vitor M. Correlo (IF/01214/2014) under the Investigator FCT program is also greatly acknowledged.info:eu-repo/semantics/publishedVersio

Non-Motor and Motor Features in LRRK2 Transgenic Mice

10.1371/journal.pone.0070249PLoS ONE87-POLN

Effectiveness of influenza vaccine against laboratory-confirmed influenza, in the late 2011-2012 season in Spain, among population targeted for vaccination

Background: In Spain, the influenza vaccine effectiveness (VE) was estimated in the last three seasons using the observational study cycEVA conducted in the frame of the existing Spanish Influenza Sentinel Surveillance System. The objective of the study was to estimate influenza vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza-like illness (ILI) among the target groups for vaccination in Spain in the 2011-2012 season. We also studied influenza VE in the early (weeks 52/2011-7/2012) and late (weeks 8-14/2012) phases of the epidemic and according to time since vaccination. Methods: Medically attended patients with ILI were systematically swabbed to collect information on exposure, laboratory outcome and confounding factors. Patients belonging to target groups for vaccination and who were swabbed 4 months, respectively, since vaccination. A decrease in VE with time since vaccination was only observed in individuals aged ≥ 65 years. Regarding the phase of the season, decreasing point estimates were only observed in the early phase, whereas very low or null estimates were obtained in the late phase for the shortest time interval. Conclusions: The 2011-2012 influenza vaccine showed a low-to-moderate protective effect against medically attended, laboratory-confirmed influenza in the target groups for vaccination, in a late season and with a limited match between the vaccine and circulating strains. The suggested decrease in influenza VE with time since vaccination was mostly observed in the elderly population. The decreasing protective effect of the vaccine in the late part of the season could be related to waning vaccine protection because no viral changes were identified throughout the season