Post impact evaluation of an E-learning cross-infection control CD-ROM provided to all general dental practitioners in England

Aim To carry out a post-impact evaluation of a cross-infection control CD-ROM, developed for NHS dental teams as a continuing professional development e-learning tool. The program was commissioned by the Department of Health and developed by a project team through the UK Committee of Postgraduate Dental Deans. The Dental Practice Boardhad originally sent one copy of the CD-ROM to each dental practice in England in 2004. Method A quantitative statistical analysis of the results of 326 online respondents to the learning package and a survey of 118 dental practitioners drawn from the Dental Practice Board database. Results Practitioners felt the CD-ROM in this instance was well designed and appropriate for their needs. It is inclusive and accessible to a wide range of dental professionals including nurses and hygienists. Conclusions This form of continuing professional development is popular with dental practitioners, although it should not be the only form of continuing professional development available. However, whilst the project was generally regarded as successful, there were problems with the distribution of the CD-ROM. This suggests that anonline resource should be made available in the future

Structural basis for ligase-specific conjugation of linear ubiquitin chains by HOIP

Linear ubiquitin chains are important regulators of cellular signaling pathways that control innate immunity and inflammation through NF-κB activation and protection against TNFα-induced apoptosis(1-5). They are synthesized by HOIP, which belongs to the RBR (RING-between-RING) family of E3 ligases and is the catalytic component of LUBAC (linear ubiquitin chain assembly complex), a multi-subunit E3 ligase(6). RBR family members act as RING/HECT hybrids, employing RING1 to recognize ubiquitin-loaded E2 while a conserved cysteine in RING2 subsequently forms a thioester intermediate with the transferred or “donor” ubiquitin(7). Here we report the crystal structure of the catalytic core of HOIP in its apo form and in complex with ubiquitin. The C-terminal portion of HOIP adopts a novel fold that, together with a zinc finger, forms an ubiquitin-binding platform which orients the acceptor ubiquitin and positions its α-amino group for nucleophilic attack on the E3~ubiquitin thioester. The carboxy-terminal tail of a second ubiquitin molecule is located in close proximity to the catalytic cysteine providing a unique snapshot of the ubiquitin transfer complex containing both donor and acceptor ubiquitin. These interactions are required for activation of the NF-kB pathway in vivo and explain the determinants of linear ubiquitin chain specificity by LUBAC

A phase I trial to assess the pharmacology of the new oestrogen receptor antagonist fulvestrant on the endometrium in healthy postmenopausal volunteers

While tamoxifen use is associated with clear benefits in the treatment of hormone-sensitive breast cancer, it also exhibits partial oestrogen agonist activity that is associated with adverse events, including endometrial cancer. Fulvestrant (‘Faslodex’) is a new oestrogen receptor antagonist that downregulates the oestrogen receptor and has no known agonist effect. This single-centre, double-blind, randomised, parallel-group trial was conducted to determine the direct effects of fulvestrant on the female endometrium when given alone and in combination with the oestrogen, ethinyloestradiol. Following a 14-day, pretrial screening period, 30 eligible postmenopausal volunteers were randomised to receive fulvestrant 250 mg, fulvestrant 125 mg or matched placebo administered as a single intramuscular injection. Two weeks postinjection, volunteers received 2-weeks concurrent exposure to ethinyloestradiol 20 μg day−1. Endometrial thickness was measured before and after the 14-day screening period with further measurements predose (to confirm a return to baseline) and on days 14, 28 and 42 post-treatment with fulvestrant. Pharmacokinetic and safety assessments were performed throughout the trial. Fulvestrant at a dose of 250 mg significantly (P=0.0001) inhibited the oestrogen-stimulated thickening of the endometrium compared with placebo. Neither the 125 mg nor 250 mg doses of fulvestrant demonstrated oestrogenic effects on the endometrium over the initial 14-day assessment period. Fulvestrant was well tolerated and reduced the incidence of ethinyloestradiol-related side effects. At the same dose level that is being evaluated in clinical trials of postmenopausal women with advanced breast cancer, fulvestrant (250 mg) is an antioestrogen with no evidence of agonist activity in the endometrium of healthy postmenopausal women

Identifying critically important vascular access outcomes for trials in haemodialysis : an international survey with patients, caregivers and health professionals

BACKGROUND: Vascular access outcomes reported across haemodialysis (HD) trials are numerous, heterogeneous and not always relevant to patients and clinicians. This study aimed to identify critically important vascular access outcomes. METHOD: Outcomes derived from a systematic review, multi-disciplinary expert panel and patient input were included in a multilanguage online survey. Participants rated the absolute importance of outcomes using a 9-point Likert scale (7-9 being critically important). The relative importance was determined by a best-worst scale using multinomial logistic regression. Open text responses were analysed thematically. RESULTS: The survey was completed by 873 participants [224 (26%) patients/caregivers and 649 (74%) health professionals] from 58 countries. Vascular access function was considered the most important outcome (mean score 7.8 for patients and caregivers/8.5 for health professionals, with 85%/95% rating it critically important, and top ranked on best-worst scale), followed by infection (mean 7.4/8.2, 79%/92% rating it critically important, second rank on best-worst scale). Health professionals rated all outcomes of equal or higher importance than patients/caregivers, except for aneurysms. We identified six themes: necessity for HD, applicability across vascular access types, frequency and severity of debilitation, minimizing the risk of hospitalization and death, optimizing technical competence and adherence to best practice and direct impact on appearance and lifestyle. CONCLUSIONS: Vascular access function was the most critically important outcome among patients/caregivers and health professionals. Consistent reporting of this outcome across trials in HD will strengthen their value in supporting vascular access practice and shared decision making in patients requiring HD

Pathotyping the Zoonotic Pathogen Streptococcus suis: Novel Genetic Markers To Differentiate Invasive Disease-Associated Isolates from Non-Disease-Associated Isolates from England and Wales.

Streptococcus suis is one of the most important zoonotic bacterial pathogens of pigs, causing significant economic losses to the global swine industry. S. suis is also a very successful colonizer of mucosal surfaces, and commensal strains can be found in almost all pig populations worldwide, making detection of the S. suis species in asymptomatic carrier herds of little practical value in predicting the likelihood of future clinical relevance. The value of future molecular tools for surveillance and preventative health management lies in the detection of strains that genetically have increased potential to cause disease in presently healthy animals. Here we describe the use of genome-wide association studies to identify genetic markers associated with the observed clinical phenotypes (i) invasive disease and (ii) asymptomatic carriage on the palatine tonsils of pigs on UK farms. Subsequently, we designed a multiplex PCR to target three genetic markers that differentiated 115 S. suis isolates into disease-associated and non-disease-associated groups, that performed with a sensitivity of 0.91, a specificity of 0.79, a negative predictive value of 0.91, and a positive predictive value of 0.79 in comparison to observed clinical phenotypes. We describe evaluation of our pathotyping tool, using an out-of-sample collection of 50 previously uncharacterized S. suis isolates, in comparison to existing methods used to characterize and subtype S. suis isolates. In doing so, we show our pathotyping approach to be a competitive method to characterize S. suis isolates recovered from pigs on UK farms and one that can easily be updated to incorporate global strain collections.This work was supported by a Biotechnology and Biological Sciences Research Council (BBSRC) Knowledge Transfer Network CASE studentship co-funded by Zoetis (previously Pfizer Animal Health UK) and with significant contribution from BQP Ltd (Award Reference: BB/L502479/1). Funding bodies provided scholarship support but had no part in study design, data collection, analysis and interpretation of data or in writing the manuscript. AWT is supported by a BBSRC Longer and Larger (LoLa) grant (Award Reference: BB/G019274/1). LAW is supported by a Dorothy Hodgkin Fellowship funded by the Royal Society (Grant Number: DH140195) and a Sir Henry Dale Fellowship co-funded by the Royal Society and Wellcome Trust (Grant Number: 109385/Z/15/Z)

Tamoxifen-associated vasculitis in a breast cancer patient

BACKGROUND: Estrogen plays a critical role in breast cancer. Thereafter, endocrine therapy is a standard of care in patients with breast carcinoma, expressing ER or PR. CASE PRESENTATION: Herein we report the case of a 53-year old patient, who developed cholestasis and vasculitis during the treatment with tamoxifen. This toxicity was reversable after the removal of the drug. Thereafter she continued adjuvant treatment for breast carcinoma with anastrazole. Since tamoxifen has been widely indicated for patients with breast carcinoma, we did a literature review, looking for other cases with this type of toxicity. CONCLUSION: This case is the third with vasculitis informed in the literature, but the first one that additionally developed cholestasis and arthritis. Although it is rare, we discuss the indication of this drug in the actual era, where aromatase inhibitors offer a better security profile

Confined dense circumstellar material surrounding a regular type II supernova

With the advent of new wide-field, high-cadence optical transient surveys, our understanding of the diversity of core-collapse supernovae has grown tremendously in the last decade. However, the pre-supernova evolution of massive stars, which sets the physical backdrop to these violent events, is theoretically not well understood and difficult to probe observationally. Here we report the discovery of the supernova iPTF 13dqy = SN 2013fs a mere ∼3 h after explosion. Our rapid follow-up observations, which include multiwavelength photometry and extremely early (beginning at ∼6 h post-explosion) spectra, map the distribution of material in the immediate environment (≲1015 cm) of the exploding star and establish that it was surrounded by circumstellar material (CSM) that was ejected during the final ∼1 yr prior to explosion at a high rate, around 10-3 solar masses per year. The complete disappearance of flash-ionized emission lines within the first several days requires that the dense CSM be confined to within ≲1015 cm, consistent with radio non-detections at 70–100 days. The observations indicate that iPTF 13dqy was a regular type II supernova; thus, the finding that the probable red supergiant progenitor of this common explosion ejected material at a highly elevated rate just prior to its demise suggests that pre-supernova instabilities may be common among exploding massive stars. © 2017 Nature Publishing Grou

SINE indel polymorphism of AGL gene and association with growth and carcass traits in Landrace × Jeju black pig F2 population

Genetic polymorphisms in the glycogen debrancher enzyme (AGL) gene were assessed with regard to their association with growth and carcass traits in the F2 population crossbred Landrace and Jeju (Korea) Black pig. Three genotypes representing the insertion and/or deletion (indel) polymorphisms of short interspersed nuclear element were detected at frequencies of 0.278 (L/L), 0.479 (L/S), and 0.243 (S/S), respectively. The AGL S allele-containing pigs evidenced significantly heavier body weights at birth, the 3rd week, 10th week, and 20th week during developmental stages and higher average daily gains during the late period than were noted in the L/L homozygous pigs (P < 0.05), respectively. However, average daily gains during the early period were not significantly associated with genotype distribution (P > 0.05). With regard to the carcass traits, the S allele pigs (S/-) evidenced significantly heavier carcass weights and thicker backfat than was measured in L/L homozygous pigs (P < 0.05). However, body lengths, meat color, and marbling scores were all found not to be statistically significant (P > 0.05). Consequently, the faster growth rate during the late period and backfat deposition rather than intramuscular fat deposition cause differences in pig productivity according to genotypes of the AGL gene. These findings indicate that the AGL genotypes may prove to be useful genetic markers for the improvement of Jeju Black pig-related crossbreeding systems

Floral advertisement scent in a changing plant-pollinators market

Plant-pollinator systems may be considered as biological markets in which pollinators choose between different flowers that advertise their nectar/pollen rewards. Although expected to play a major role in structuring plant-pollinator interactions, community-wide patterns of flower scent signals remain largely unexplored. Here we show for the first time that scent advertisement is higher in plant species that bloom early in the flowering period when pollinators are scarce relative to flowers than in species blooming later in the season when there is a surplus of pollinators relative to flowers. We also show that less abundant flowering species that may compete with dominant species for pollinator visitation early in the flowering period emit much higher proportions of the generalist attractant β-ocimene. Overall, we provide a first community-wide description of the key role of seasonal dynamics of plant-specific flower scent emissions, and reveal the coexistence of contrasting plant signaling strategies in a plant-pollinator market