A review of coronavirus infection in the central nervous system of cats and mice.

Feline infectious peritonitis (FIP) is a common cause of death in cats. Management of this disease has been hampered by difficulties identifying the infection and determining the immunological status of affected cats and by high variability in the clinical, pathological, and immunological characteristics of affected cats. Neurological FIP, which is much more homogeneous than systemic effusive or noneffusive FIP, appears to be a good model for establishing the basic features of FIP immunopathogenesis. Very little information is available about the immunopathogenesis of neurologic FIP, and it is reasonable to use research from the well-characterized mouse hepatitis virus (MHV) immune-mediated encephalitis system, as a template for FIP investigation, and to contrast findings from the MHV model with those of FIP. It is expected that the immunopathogenic mechanisms will have important similarities. Such comparative research may lead to better understanding of FIP immunopathogenesis and rational prospects for management of this frustrating disease

The associations between medical, allied and complementary medicine practitioner visits and childhood vaccine uptake

© 2018 The Authors Background: Vaccination rates have remained steady for a number of years in Australia, however geographical areas of lower vaccine coverage remains a day-to-day challenge. The study explores parental attitudes, beliefs and intentions in relation to vaccination and examines the early effects of recent No Jab No Pay legislation. Methods: A national survey of was conducted, using an online questionnaire. Parents from all states in Australia with at least one child aged <6 years were invited to participate. Results: A total of 429 parents participated in the study. The substantial majority of participants reported having their youngest child's vaccination status up to date (n = 401, 93.5%). A child's vaccinations were more likely to be up to date if they had consulted a paediatrician in the previous 12-months (OR 5.01; 95%CI 1.05, 23.92; p =.043). Conversely they were less likely to be vaccinated if they were influenced by information from a complementary medicine (CM) practitioner (OR 0.03; 95%CI 0.01, 0.15; p <.001) or had visited a CM-practitioner (OR 0.09; 95%CI 0.02, 0.33; p <.001) in the previous 12-months. A total of 2.6% of parents had immunised their child as a result of the No Jab No Pay legislation, while 3.9% stated the legislation had no effect, and 1.2% said it had made them less likely to vaccinate. A further 1.2% of parents stated they are considering vaccination as a result of the legislative changes. Conclusion: Parents who have not vaccinated their children appear to trust non-mainstream sources of information such as CM-practitioners. Further research is required to determine how to manage the challenges and opportunities of CM-practitioners as a source of vaccine information

Use of complementary medicine products: a nationally representative cross-sectional survey of 2019 Australian adults

© Author(s) (or their employer(s)) 2019. Objectives To provide a contemporary description of complementary medicine (CM) product use in Australia. Design Cross-sectional survey. Setting Online. Participants A nationally representative sample (n=2019) of the Australian adult population. Primary and secondary outcome measures Primary outcomes measures included the use and type of CM products used, and source of recommendation. Secondary measures included disclosure of CM product use to health practitioners, concomitant use of pharmaceuticals and predictors of use. Results Prevalence of CM product use was 50.3%, with the most frequently used being vitamin and mineral supplements (VMSs; 47.8%) and homoeopathic medicines the least used (6.8%). A majority of respondents using CM products were also using pharmaceutical products, and small but significant associations were found between the use of CM products and pharmaceuticals (p<0.05). Small statistically significant associations were found between use of vitamin products and disclosure of use to general practitioners (GPs; Cramer's V=0.13, p=0.004) and hospital doctors (Cramer's V=0.11, p=0.04), and between use of herbal medicines and disclosure to both GPs (Cramer's V=0.11, p=0.02) and hospital doctors (Cramer's V=0.12, p=0.03). Women, those with higher education and those with no private health insurance were more likely to use CM products (p<0.05), while those without chronic conditions were less likely to use CM products (p<0.05) (χ 2 (29)=174.70, p<0.001). Conclusions The number of Australians using CM products has remained relatively stable and substantial for nearly two decades. The majority of CM use relates to VMSs. Given the number of Australians using both CM products and pharmaceutical medicines, it is important to evaluate the potential clinical implications of such practices to ensure safe, effective and coordinated health policy and patient care

Achieving optimal adherence to medical therapy by telehealth: Findings from the ORBITA medication adherence sub-study

INTRODUCTION: The ORBITA trial of percutaneous coronary intervention (PCI) versus a placebo procedure for patients with stable angina was conducted across six sites in the United Kingdom via home monitoring and telephone consultations. Patients underwent detailed assessment of medication adherence which allowed us to measure the efficacy of the implementation of the optimization protocol and interpretation of the main trial endpoints. METHODS: Prescribing data were collected throughout the trial. Self-reported adherence was assessed, and urine samples collected at pre-randomization and at follow-up for direct assessment of adherence using high-performance liquid chromatography with tandem mass spectrometry (HPLC MS/MS). RESULTS: Self-reported adherence was >96% for all drugs in both treatment groups at both stages. The percentage of samples in which drug was detected at pre-randomization and at follow-up in the PCI versus placebo groups respectively was: clopidogrel, 96% versus 90% and 98% versus 94%; atorvastatin, 95% versus 92% and 92% versus 91%; perindopril, 95% versus 97% and 85% versus 100%; bisoprolol, 98% versus 99% and 96% versus 97%; amlodipine, 99% versus 99% and 94% versus 96%; nicorandil, 98% versus 96% and 94% versus 92%; ivabradine, 100% versus 100% and 100% versus 100%; and ranolazine, 100% versus 100% and 100% versus 100%. CONCLUSIONS: Adherence levels were high throughout the study when quantified by self-reporting methods and similarly high proportions of drug were detected by urinary assay. The results indicate successful implementation of the optimization protocol delivered by telephone, an approach that could serve as a model for treatment of chronic conditions, particularly as consultations are increasingly conducted online

Improved Somatic Mutagenesis in Zebrafish Using Transcription Activator-Like Effector Nucleases (TALENs)

Zinc Finger Nucleases (ZFNs) made by Context-Dependent Assembly (CoDA) and Transcription Activator-Like Effector Nucleases (TALENs) provide robust and user-friendly technologies for efficiently inactivating genes in zebrafish. These designer nucleases bind to and cleave DNA at particular target sites, inducing error-prone repair that can result in insertion or deletion mutations. Here, we assess the relative efficiencies of these technologies for inducing somatic DNA mutations in mosaic zebrafish. We find that TALENs exhibited a higher success rate for obtaining active nucleases capable of inducing mutations than compared with CoDA ZFNs. For example, all six TALENs tested induced DNA mutations at genomic target sites while only a subset of CoDA ZFNs exhibited detectable rates of mutagenesis. TALENs also exhibited higher mutation rates than CoDA ZFNs that had not been pre-screened using a bacterial two-hybrid assay, with DNA mutation rates ranging from 20%–76.8% compared to 1.1%–3.3%. Furthermore, the broader targeting range of TALENs enabled us to induce mutations at the methionine translation start site, sequences that were not targetable using the CoDA ZFN platform. TALENs exhibited similar toxicity to CoDA ZFNs, with >50% of injected animals surviving to 3 days of life. Taken together, our results suggest that TALEN technology provides a robust alternative to CoDA ZFNs for inducing targeted gene-inactivation in zebrafish, making it a preferred technology for creating targeted knockout mutants in zebrafish

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

National Coordinating Centre for Research Methodology; Medical Research Council, UK Department of Health; Chief Scientist OfficeNot peer reviewedPublisher PD

Usability of myfood24 Healthcare and Mathematical Diet Optimisation in Clinical Populations: A Pilot Feasibility Randomised Controlled Trial

Monitoring nutritional intake is of clinical value, but few existing tools offer electronic dietary recording, instant nutritional analysis, and a platform connecting healthcare teams with patients that provides timely, personalised support. This feasibility randomised controlled trial tests the usability of ‘myfood24 Healthcare’, a dietary assessment app and healthcare professional website, in two clinical populations. Patients were recruited from a weight management programme (n21) and from a group of gastroenterology surgery outpatients (n = 27). They were randomised into three groups: standard care, myfood24, or myfood24 + diet optimisation (automated suggestions for dietary improvement). The participants were asked to record their diet at least four times over eight weeks. During the study, healthcare professionals viewed recorded dietary information to facilitate discussions about diet and nutritional targets. The participants provided feedback on usability and acceptability. A total of 48 patients were recruited, and 16 were randomised to each of the three groups. Compliance among app users (n = 32) was reasonable, with 25 (78%) using it at least once and 16 (50%) recording intake for four days or more. Among users, the mean (standard deviation) number of days used was 14.0 (17.5), and the median (interquartile range) was six (2.5–17.0) over 2 months. Feedback questionnaires were completed by only 23 of 46 participants (50%). The mean System Usability Score (n = 16) was 59 (95% confidence interval, 48–70). Patient and healthcare professional feedback indicates a need for more user training and the improvement of some key app features such as the food search function. This feasibility study shows that myfood24 Healthcare is acceptable for patients and healthcare professionals. These data will inform app refinements and its application in a larger clinical effectiveness trial

Lithic technological responses to Late Pleistocene glacial cycling at Pinnacle Point Site 5-6, South Africa

There are multiple hypotheses for human responses to glacial cycling in the Late Pleistocene, including changes in population size, interconnectedness, and mobility. Lithic technological analysis informs us of human responses to environmental change because lithic assemblage characteristics are a reflection of raw material transport, reduction, and discard behaviors that depend on hunter-gatherer social and economic decisions. Pinnacle Point Site 5-6 (PP5-6), Western Cape, South Africa is an ideal locality for examining the influence of glacial cycling on early modern human behaviors because it preserves a long sequence spanning marine isotope stages (MIS) 5, 4, and 3 and is associated with robust records of paleoenvironmental change. The analysis presented here addresses the question, what, if any, lithic assemblage traits at PP5-6 represent changing behavioral responses to the MIS 5-4-3 interglacial-glacial cycle? It statistically evaluates changes in 93 traits with no a priori assumptions about which traits may significantly associate with MIS. In contrast to other studies that claim that there is little relationship between broad-scale patterns of climate change and lithic technology, we identified the following characteristics that are associated with MIS 4: increased use of quartz, increased evidence for outcrop sources of quartzite and silcrete, increased evidence for earlier stages of reduction in silcrete, evidence for increased flaking efficiency in all raw material types, and changes in tool types and function for silcrete. Based on these results, we suggest that foragers responded to MIS 4 glacial environmental conditions at PP5-6 with increased population or group sizes, 'place provisioning', longer and/or more intense site occupations, and decreased residential mobility. Several other traits, including silcrete frequency, do not exhibit an association with MIS. Backed pieces, once they appear in the PP5-6 record during MIS 4, persist through MIS 3. Changing paleoenvironments explain some, but not all temporal technological variability at PP5-6.Social Science and Humanities Research Council of Canada; NORAM; American-Scandinavian Foundation; Fundacao para a Ciencia e Tecnologia [SFRH/BPD/73598/2010]; IGERT [DGE 0801634]; Hyde Family Foundations; Institute of Human Origins; National Science Foundation [BCS-9912465, BCS-0130713, BCS-0524087, BCS-1138073]; John Templeton Foundation to the Institute of Human Origins at Arizona State Universit