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

ZFNGenome: A comprehensive resource for locating zinc finger nuclease target sites in model organisms

<p>Abstract</p> <p>Background</p> <p>Zinc Finger Nucleases (ZFNs) have tremendous potential as tools to facilitate genomic modifications, such as precise gene knockouts or gene replacements by homologous recombination. ZFNs can be used to advance both basic research and clinical applications, including gene therapy. Recently, the ability to engineer ZFNs that target any desired genomic DNA sequence with high fidelity has improved significantly with the introduction of rapid, robust, and publicly available techniques for ZFN design such as the Oligomerized Pool ENgineering (OPEN) method. The motivation for this study is to make resources for genome modifications using OPEN-generated ZFNs more accessible to researchers by creating a user-friendly interface that identifies and provides quality scores for all potential ZFN target sites in the complete genomes of several model organisms.</p> <p>Description</p> <p>ZFNGenome is a GBrowse-based tool for identifying and visualizing potential target sites for OPEN-generated ZFNs. ZFNGenome currently includes a total of more than 11.6 million potential ZFN target sites, mapped within the fully sequenced genomes of seven model organisms; <it>S. cerevisiae, C. reinhardtii, A. thaliana</it>, <it>D. melanogaster, D. rerio, C. elegans</it>, and <it>H. sapiens </it>and can be visualized within the flexible GBrowse environment. Additional model organisms will be included in future updates. ZFNGenome provides information about each potential ZFN target site, including its chromosomal location and position relative to transcription initiation site(s). Users can query ZFNGenome using several different criteria (e.g., gene ID, transcript ID, target site sequence). Tracks in ZFNGenome also provide "uniqueness" and ZiFOpT (Zinc Finger OPEN Targeter) "confidence" scores that estimate the likelihood that a chosen ZFN target site will function <it>in vivo</it>. ZFNGenome is dynamically linked to ZiFDB, allowing users access to all available information about zinc finger reagents, such as the effectiveness of a given ZFN in creating double-stranded breaks.</p> <p>Conclusions</p> <p>ZFNGenome provides a user-friendly interface that allows researchers to access resources and information regarding genomic target sites for engineered ZFNs in seven model organisms. This genome-wide database of potential ZFN target sites should greatly facilitate the utilization of ZFNs in both basic and clinical research.</p> <p>ZFNGenome is freely available at: <url>http://bindr.gdcb.iastate.edu/ZFNGenome</url> or at the Zinc Finger Consortium website: <url>http://www.zincfingers.org/</url>.</p

Predicting nursing home admission in the U.S: a meta-analysis

Background: While existing reviews have identified significant predictors of nursing home admission, this meta-analysis attempted to provide more integrated empirical findings to identify predictors. The present study aimed to generate pooled empirical associations for sociodemographic, functional, cognitive, service use, and informal support indicators that predict nursing home admission among older adults in the U.S. Methods: Studies published in English were retrieved by searching the MEDLINE, PSYCINFO, CINAHL, and Digital Dissertations databases using the keywords: "nursing home placement," "nursing home entry," "nursing home admission," and "predictors/institutionalization." Any reports including these key words were retrieved. Bibliographies of retrieved articles were also searched. Selected studies included sampling frames that were nationally- or regionally-representative of the U.S. older population. Results: Of 736 relevant reports identified, 77 reports across 12 data sources were included that used longitudinal designs and community-based samples. Information on number of nursing home admissions, length of follow-up, sample characteristics, analysis type, statistical adjustment, and potential risk factors were extracted with standardized protocols. Random effects models were used to separately pool the logistic and Cox regression model results from the individual data sources. Among the strongest predictors of nursing home admission were 3 or more activities of daily living dependencies (summary odds ratio [OR] = 3.25; 95% confidence interval [CI], 2.56–4.09), cognitive impairment (OR = 2.54; CI, 1.44–4.51), and prior nursing home use (OR = 3.47; CI, 1.89–6.37). Conclusion: The pooled associations provided detailed empirical information as to which variables emerged as the strongest predictors of NH admission (e.g., 3 or more ADL dependencies, cognitive impairment, prior NH use). These results could be utilized as weights in the construction and validation of prognostic tools to estimate risk for NH entry over a multi-year period

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

Selection-Free Zinc-Finger Nuclease Engineering by Context-Dependent Assembly (CoDA)

Engineered zinc-finger nucleases (ZFNs) enable targeted genome modification. Here we describe Context-Dependent Assembly (CoDA), a platform for engineering ZFNs using only standard cloning techniques or custom DNA synthesis. Using CoDA ZFNs, we rapidly altered 20 genes in zebrafish, Arabidopsis, and soybean. The simplicity and efficacy of CoDA will enable broad adoption of ZFN technology and make possible large-scale projects focused on multi-gene pathways or genome-wide alterations