Positive correlation between serum immunoreactivity to Demodex-associated Bacillus proteins and erythematotelangiectatic rosacea

Background Rosacea is a chronic inflammatory condition that affects the skin of the face and the eyes. Erythematotelangiectatic rosacea is characterized by flushing, oedema and telangiectasia. Patients with rosacea demonstrate elevated densities of Demodex mites in their skin compared with controls. A bacterium (Bacillus oleronius) isolated from Demodex mites from a patient with papulopustular rosacea has been demonstrated to produce antigenic proteins that may play a role in papulopustular and ocular rosacea. Objectives To establish whether there was a correlation between the reactivity of sera from patients with erythematotelangiectatic rosacea to Bacillus antigens, and to characterize the proteins to which these patients showed reactivity. Methods Serum samples from patients with erythematotelangiectatic rosacea and controls were examined for reactivity to Bacillus proteins by Western blot analysis. Proteins to which the sera reacted were excised from gels, trypsin digested, and putative identities were assigned following liquid chromatography-mass spectrometry (LC-MS) analysis. Results Eighty per cent (21 ⁄26) of patients with erythematotelangiectatic rosacea showed serum reactivity to the 62- and 83-kDa proteins of B. oleronius, compared with 40% (9 ⁄22) of controls (P = 0Æ004). The 62-kDa protein was characterized by LC-MS and showed homology to groEL chaperonin, which provokes a strong immune response in mammals. The 83-kDa protein showed homology to aconitate hydratase, of which expression is increased in bacteria under oxidative stress, and which is highly immunogenic. Conclusions The majority of patients with erythematotelangiectatic rosacea show serum reactivity to two proteins from B. oleronius, suggesting that this bacterium may play a role in the induction of this condition. The two proteins to which patient sera reacted were found to be similar to a heat shock protein and an enzyme involved in regulating the stress response of the bacterium

Examining current provision, practice and experience of initial teacher training providers in Ireland preparing pre service teachers for the inclusion of students with special education needs in physical education classes.

Research from an international perspective in relation to the preparation of pre service teachers in physical education and special educational needs indicates that initial teacher training providers are inconsistent in the amount of time spent addressing the issue and the nature of curricular content (Vickerman, 2007). In Ireland, research of Meegan and MacPhail (2005) and Crawford (2011) indicates that physical education teachers do not feel adequately prepared to accommodate students with Special Educational Needs (SEN) in physical education classes. This study examined initial teacher training provision in Ireland in the training of pre service physical education teachers in SEN. The methodology used was qualitative and included questionnaires and interviews (n=4). Findings indicated that time allocation (semester long modules), working with children with disabilities in mainstream settings (school or leisure centre based), lack of collaboration with other PETE providers (n=4) and a need for continued professional development were themes in need of address. Using a combined approach where the recently designed European Inclusive Physical Education Training (Kudlácěk, Jesina, & Flanagan, 2010) model is infused through the undergraduate degree programme is proposed. Further, the accommodation of hands on experience for undergraduates in mainstream settings and the establishment of inter institutional communities of practice, with a national disability research initiative, is essential to ensure quality adapted physical activity training can be accommodated throughout Ireland

Population sensitivity of acute flaccid paralysis and environmental surveillance for serotype 1 poliovirus in Pakistan: an observational study

Background To support poliomyelitis eradication in Pakistan, environmental surveillance (ES) of wastewater has been expanded alongside surveillance for acute flaccid paralysis (AFP). ES is a relatively new method of surveillance, and the population sensitivity of detecting poliovirus within endemic settings requires estimation. Methods Data for wild serotype 1 poliovirus from AFP and ES from January 2011 to September 2015 from 14 districts in Pakistan were analysed using a multi-state model framework. This framework was used to estimate the sensitivity of poliovirus detection from each surveillance source and parameters such as the duration of infection within a community. Results The location and timing of poliomyelitis cases showed spatial and temporal variability. The sensitivity of AFP surveillance to detect serotype 1 poliovirus infection in a district and its neighbours per month was on average 30.0% (95% CI 24.8–35.8) and increased with the incidence of poliomyelitis cases. The average population sensitivity of a single environmental sample was 59.4% (95% CI 55.4–63.0), with significant variation in site-specific estimates (median varied from 33.3–79.2%). The combined population sensitivity of environmental and AFP surveillance in a given month was on average 98.1% (95% CI 97.2–98.7), assuming four samples per month for each site. Conclusions ES can be a highly sensitive supplement to AFP surveillance in areas with converging sewage systems. As ES for poliovirus is expanded, it will be important to identify factors associated with variation in site sensitivity, leading to improved site selection and surveillance system performance

A Meiotic Checkpoint Alters Repair Partner Bias to Permit Inter-sister Repair of Persistent DSBs

Accurate meiotic chromosome segregation critically depends on the formation of inter-homolog crossovers initiated by double-strand breaks (DSBs). Inaccuracies in this process can drive aneuploidy and developmental defects, but how meiotic cells are protected from unscheduled DNA breaks remains unexplored. Here we define a checkpoint response to persistent meiotic DSBs in C. elegans that phosphorylates the synaptonemal complex (SC) to switch repair partner from the homolog to the sister chromatid. A key target of this response is the core SC component SYP-1, which is phosphorylated in response to ionizing radiation (IR) or unrepaired meiotic DSBs. Failure to phosphorylate (syp-16A) or dephosphorylate (syp-16D) SYP-1 in response to DNA damage results in chromosome non-dysjunction, hyper-sensitivity to IR-induced DSBs, and synthetic lethality with loss of brc-1BRCA1. Since BRC-1 is required for inter-sister repair, these observations reveal that checkpoint-dependent SYP-1 phosphorylation safeguards the germline against persistent meiotic DSBs by channelling repair to the sister chromatid.Cancer Research UK FC0010048UK Medical Research Council FC0010048Wellcome Trust FC0010048Ministerio de Economía y Competitividad BFU2016-75058-PEuropean Research Council ERC2014 AdG669898 TARLOO

A Framework For Memory Performance Prediction From Brain Volume In Preterm-Born Adolescents

With advances in medical care, higher numbers of extremely preterm-born babies are now surviving, however the rate of neurodevelopmental and neurological complications has not improved at the same rate and the relative rate of disabilities and health problems is increasing, with associated high costs for health care systems and education. Understanding brain development after early birth is of great importance to be able to make informed decisions. Many studies have associated different areas of the preterm brain with poor cognitive performance, however it is less clear whether these associations persist into adult life. In this study, we investigate how well cortical volumes describe memory performance in 133 19 year-old adolescents, 61% of whom were born extremely preterm. We employ LASSO to identify brain regions that better explain memory performance. The brain regions identified by LASSO explained 27% and 32% of the variance in the visual working memory scores and the visual short term memory respectively. Furthermore, the correlation between the predicted scores and validation scores is statistically significant and it is 58% for the visual working memory task and 56% for the visual short term memory task

Communication in cross-cultural consultations in primary care in Europe: the case for improvement. The rationale for the RESTORE FP 7 project

The purpose of this paper is to substantiate the importance of research about barriers and levers to the implementation of supports for cross-cultural communication in primary care settings in Europe. After an overview of migrant health issues, with the focus on communication in cross-cultural consultations in primary care and the importance of language barriers, we highlight the fact that there are serious problems in routine practice that persist over time and across different European settings. Language and cultural barriers hamper communication in consultations between doctors and migrants, with a range of negative effects including poorer compliance and a greater propensity to access emergency services. It is well established that there is a need for skilled interpreters and for professionals who are culturally competent to address this problem. A range of professional guidelines and training initiatives exist that support the communication in cross-cultural consultations in primary care. However, these are commonly not implemented in daily practice. It is as yet unknown why professionals do not accept or implement these guidelines and interventions, or under what circumstances they would do so. A new study involving six European countries, RESTORE (REsearch into implementation STrategies to support patients of different ORigins and language background in a variety of European primary care settings), aims to address these gaps in knowledge. It uses a unique combination of a contemporary social theory, normalisation process theory (NPT) and participatory learning and action (PLA) research. This should enhance understanding of the levers and barriers to implementation, as well as providing stakeholders, with the opportunity to generate creative solutions to problems experienced with the implementation of such interventions

Machine Learning and Machine Vision Accelerate 3D Printed Orodispersible Film Development

Orodispersible films (ODFs) are an attractive delivery system for a myriad of clinical applications and possess both large economical and clinical rewards. However, the manufacturing of ODFs does not adhere to contemporary paradigms of personalised, on-demand medicine, nor sustainable manufacturing. To address these shortcomings, both three-dimensional (3D) printing and machine learning (ML) were employed to provide on-demand manufacturing and quality control checks of ODFs. Direct ink writing (DIW) was able to fabricate complex ODF shapes, with thicknesses of less than 100 µm. ML algorithms were explored to classify the ODFs according to their active ingredient, by using their near-infrared (NIR) spectrums. A supervised model of linear discriminant analysis was found to provide 100% accuracy in classifying ODFs. A subsequent partial least square algorithm was applied to verify the dose, where a coefficient of determination of 0.96, 0.99 and 0.98 was obtained for ODFs of paracetamol, caffeine, and theophylline, respectively. Therefore, it was concluded that the combination of 3D printing, NIR and ML can result in a rapid production and verification of ODFs. Additionally, a machine vision tool was used to automate the in vitro testing. These collective digital technologies demonstrate the potential to automate the ODF workflow

A stereoselective hydride transfer reaction with contributions from attractive dispersion force control

The experimentally determined stereochemical outcome of an unprecedented hydride transfer from a lithium alkoxide to an aldehyde is reported, as deconvoluted by the combined use of a single enantiomer alkoxide in conjunction with a deuterium label. The stereoselective outcome is consistent with a computationally predicted transition state model stabilised by contributions from attractive dispersion forces