Inhibition of CD26/DPP-IV enhances donor muscle cell engraftment and stimulates sustained donor cell proliferation

<p>Abstract</p> <p>Background</p> <p>Transplantation of myogenic stem cells possesses great potential for long-term repair of dystrophic muscle. In murine-to-murine transplantation experiments, CXCR4 expression marks a population of adult murine satellite cells with robust engraftment potential in <it>mdx </it>mice, and CXCR4-positive murine muscle-derived SP cells home more effectively to dystrophic muscle after intra-arterial delivery in <it>mdx^5cv</it>mice. Together, these data suggest that CXCR4 plays an important role in donor cell engraftment. Therefore, we sought to translate these results to a clinically relevant canine-to-canine allogeneic transplant model for Duchenne muscular dystrophy (DMD) and determine if CXCR4 is important for donor cell engraftment.</p> <p>Methods</p> <p>In this study, we used a canine-to-murine xenotransplantation model to quantitatively compare canine muscle cell engraftment, and test the most effective cell population and modulating factor in a canine model of DMD using allogeneic transplantation experiments.</p> <p>Results</p> <p>We show that CXCR4 expressing cells are important for donor muscle cell engraftment, yet FACS sorted CXCR4-positive cells display decreased engraftment efficiency. However, diprotin A, a positive modulator of CXCR4-SDF-1 binding, significantly enhanced engraftment and stimulated sustained proliferation of donor cells <it>in vivo</it>. Furthermore, the canine-to-murine xenotransplantation model accurately predicted results in canine-to-canine muscle cell transplantation.</p> <p>Conclusions</p> <p>Therefore, these results establish the efficacy of diprotin A in stimulating muscle cell engraftment, and highlight the pre-clinical utility of a xenotransplantation model in assessing the relative efficacy of muscle stem cell populations.</p

Telling partners about chlamydia: how acceptable are the new technologies?

BACKGROUND Partner notification is accepted as a vital component in the control of chlamydia. However, in reality, many sexual partners of individuals diagnosed with chlamydia are never informed of their risk. The newer technologies of email and SMS have been used as a means of improving partner notification rates. This study explored the use and acceptability of different partner notification methods to help inform the development of strategies and resources to increase the number of partners notified. METHODS Semi-structured telephone interviews were conducted with 40 people who were recently diagnosed with chlamydia from three sexual health centres and two general practices across three Australian jurisdictions. RESULTS Most participants chose to contact their partners either in person (56%) or by phone (44%). Only 17% chose email or SMS. Participants viewed face-to-face as the "gold standard" in partner notification because it demonstrated caring, respect and courage. Telephone contact, while considered insensitive by some, was often valued because it was quick, convenient and less confronting. Email was often seen as less personal while SMS was generally considered the least acceptable method for telling partners. There was also concern that emails and SMS could be misunderstood, not taken seriously or shown to others. Despite these, email and SMS were seen to be appropriate and useful in some circumstances. Letters, both from the patients or from their doctor, were viewed more favourably but were seldom used. CONCLUSION These findings suggest that many people diagnosed with chlamydia are reluctant to use the new technologies for partner notification, except in specific circumstances, and our efforts in developing partner notification resources may best be focused on giving patients the skills and confidence for personal interaction.The study was funded by the Australian Federal Government Department of Health and Ageing Chlamydia Pilot Program of Targeted Grants

Better than nothing? Patient-delivered partner therapy and partner notification for chlamydia: the views of Australian general practitioners

BACKGROUND Genital chlamydia is the most commonly notified sexually transmissible infection (STI) in Australia and worldwide and can have serious reproductive health outcomes. Partner notification, testing and treatment are important facets of chlamydia control. Traditional methods of partner notification are not reaching enough partners to effectively control transmission of chlamydia. Patient-delivered partner therapy (PDPT) has been shown to improve the treatment of sexual partners. In Australia, General Practitioners (GPs) are responsible for the bulk of chlamydia testing, diagnosis, treatment and follow up. This study aimed to determine the views and practices of Australian general practitioners (GPs) in relation to partner notification and PDPT for chlamydia and explored GPs' perceptions of their patients' barriers to notifying partners of a chlamydia diagnosis. METHODS In-depth, semi-structured telephone interviews were conducted with 40 general practitioners (GPs) from rural, regional and urban Australia from November 2006 to March 2007. Topics covered: GPs' current practice and views about partner notification, perceived barriers and useful supports, previous use of and views regarding PDPT.Transcripts were imported into NVivo7 and subjected to thematic analysis. Data saturation was reached after 32 interviews had been completed. RESULTS Perceived barriers to patients telling partners (patient referral) included: stigma; age and cultural background; casual or long-term relationship, ongoing relationship or not. Barriers to GPs undertaking partner notification (provider referral) included: lack of time and staff; lack of contact details; uncertainty about the legality of contacting partners and whether this constitutes breach of patient confidentiality; and feeling both personally uncomfortable and inadequately trained to contact someone who is not their patient. GPs were divided on the use of PDPT--many felt concerned that it is not best clinical practice but many also felt that it is better than nothing.GPs identified the following factors which they considered would facilitate partner notification: clear clinical guidelines; a legal framework around partner notification; a formal chlamydia screening program; financial incentives; education and practical support for health professionals, and raising awareness of chlamydia in the community, in particular amongst young people. CONCLUSIONS GPs reported some partners do not seek medical treatment even after they are notified of being a sexual contact of a patient with chlamydia. More routine use of PDPT may help address this issue however GPs in this study had negative attitudes to the use of PDPT. Appropriate guidelines and legislation may make the use of PDPT more acceptable to Australian GPs.The Australian Federal Government Department of Health and Ageing Chlamydia Pilot Program of Targeted Grants funded the study

Pattern Recognition for Mass-Spectrometry-Based Proteomics

Multiomic analysis comprises genomics, proteomics, and metabolomics leads to meaningful insights but necessitates sifting through voluminous amounts of complex data. Proteomics in particular focuses on the end product of gene expression – i.e., proteins. The mass spectrometric approach has proven to be a workhorse for the qualitative and quantitative study of protein interactions as well as post-translational modifications (PTMs). A key component of mass spectrometry (MS) is spectral data analysis, which is complex and has many challenges as it involves identifying patterns across a multitude of spectra in combination with the meta-data related to the origin of the spectrum. Artificial Intelligence (AI) along with Machine Learning (ML), and Deep Learning (DL) algorithms have gained more attention lately for analyzing the complex spectral data to identify patterns and to create networks of value for biomarker discovery. In this chapter, we discuss the nature of MS proteomic data, the relevant AI methods, and demonstrate their applicability. We also show that AI can successfully identify biomarkers and aid in the diagnosis, prognosis, and treatment of specific diseases

The influence of photoperiod on the reproductive physiology of the greater red musk shrew (Crocidura flavescens)

Photoperiodism involves the use of both absolute measures of day length and the direction in which day length is changing as a cue for regulating seasonal changes in physiology and behaviour so that birth and lactation coincide with optimal resource availability, increasing offspring survival. Induced ovulation and opportunistic breeding is often found in species that are predominantly solitary and territorial. In this study, the photoperiodic reproductive responses of male greater red musk shrews (Crocidura flavescens (I. Geoffroy Saint-Hilaire, 1827)) were investigated in the laboratory. The presence of spermatozoa regardless of the light cycle, suggest that although the shrews are photoresponsive, they may be capable of breeding throughout the year. Significantly greater testicular volume and seminiferous tubule diameter following exposure to a short day-light cycle suggests that these animals may have breeding peaks that correspond to short days. The presence of epidermal spines on the penis indicates that the shrew is likely also an induced ovulator. Flexible breeding patterns combined with induced ovulation affords this solitary species the greatest chance of reproductive success.National Research Foundation (NRF; GUN 64756).http://www.nrcresearchpress.com/journal/cjzhb2016Zoology and Entomolog

Carbon dioxide and ocean acidification observations in UK waters. Synthesis report with a focus on 2010–2015

Key messages: 1.1 The process of ocean acidification is now relatively well-documented at the global scale as a long-term trend in the open ocean. However, short-term and spatial variability can be high. 1.2 New datasets made available since Charting Progress 2 make it possible to greatly improve the characterisation of CO2 and ocean acidification in UK waters. 3.1 Recent UK cruise data contribute to large gaps in national and global datasets. 3.2 The new UK measurements confirm that pH is highly variable, therefore it is important to measure consistently to determine any long term trends. 3.3 Over the past 30 years, North Sea pH has decreased at 0.0035±0.0014 pH units per year. 3.4 Upper ocean pH values are highest in spring, lowest in autumn. These changes reflect the seasonal cycles in photosynthesis, respiration (decomposition) and water mixing. 3.5 Carbonate saturation states are minimal in the winter, and lower in 7 more northerly, colder waters. This temperature-dependence could have implications for future warming of the seas. 3.6 Over the annual cycle, North-west European seas are net sinks of CO2. However, during late summer to autumn months, some coastal waters may be significant sources. 3.7 In seasonally-stratified waters, sea-floor organisms naturally experience lower pH and saturation states; they may therefore be more vulnerable to threshold changes. 3.8 Large pH changes (0.5 - 1.0 units) can occur in the top 1 cm of sediment; however, such effects are not well-documented. 3.9 A coupled forecast model estimates the decrease in pH trend within the North Sea to be -0.0036±0.00034 pH units per year, under a high greenhouse gas emissions scenario (RCP 8.5). 3.10 Seasonal estimates from the forecast model demonstrate areas of the North Sea that are particularly vulnerable to aragonite undersaturation

Recurrent delirium over 12 months predicts dementia: results of the Delirium and Cognitive Impact in Dementia (DECIDE) study.

BACKGROUND: Delirium is common, distressing and associated with poor outcomes. Previous studies investigating the impact of delirium on cognitive outcomes have been limited by incomplete ascertainment of baseline cognition or lack of prospective delirium assessments. This study quantified the association between delirium and cognitive function over time by prospectively ascertaining delirium in a cohort aged ≥ 65 years in whom baseline cognition had previously been established. METHODS: For 12 months, we assessed participants from the Cognitive Function and Ageing Study II-Newcastle for delirium daily during hospital admissions. At 1-year, we assessed cognitive decline and dementia in those with and without delirium. We evaluated the effect of delirium (including its duration and number of episodes) on cognitive function over time, independently of baseline cognition and illness severity. RESULTS: Eighty two of 205 participants recruited developed delirium in hospital (40%). One-year outcome data were available for 173 participants: 18 had a new dementia diagnosis, 38 had died. Delirium was associated with cognitive decline (-1.8 Mini-Mental State Examination points [95% CI -3.5 to -0.2]) and an increased risk of new dementia diagnosis at follow up (OR 8.8 [95% CI 1.9-41.4]). More than one episode and more days with delirium (>5 days) were associated with worse cognitive outcomes. CONCLUSIONS: Delirium increases risk of future cognitive decline and dementia, independent of illness severity and baseline cognition, with more episodes associated with worse cognitive outcomes. Given that delirium has been shown to be preventable in some cases, we propose that delirium is a potentially modifiable risk factor for dementia

An immunoaffinity tandem mass spectrometry (iMALDI) assay for detection of Francisella tularensis

Francisella tularensis (F. tularensis) has been designated by the CDC as one of the ten organisms most likely to be engineered for bioterrorism. Symptoms of tularemia in humans are non-specific, thus making the disease difficult to diagnose. If not quickly diagnosed and treated, the disease has a high mortality rate - thus methods for early and specific diagnosis are of critical importance

Hospitalisation without delirium is not associated with cognitive decline in a population-based sample of older people-results from a nested, longitudinal cohort study

Background: Acute hospitalisation and delirium have individually been shown to adversely affect trajectories of cognitive decline but have not previously been considered together. This work aimed to explore the impact on cognition of hospital admission with and without delirium, compared to a control group with no hospital admissions. Methods: The Delirium and Cognitive Impact in Dementia (DECIDE) study was nested within the Cognitive Function and Ageing Study II (CFAS II)-Newcastle cohort. CFAS II participants completed two baseline interviews, including the Mini-Mental State Examination (MMSE). During 2016, surviving participants from CFAS II-Newcastle were recruited to DECIDE on admission to hospital. Participants were reviewed daily to determine delirium status. During 2017, all DECIDE participants and age, sex and years of education matched controls without hospital admissions during 2016 were invited to repeat the CFAS II interview. Delirium was excluded in the control group using the Informant Assessment of Geriatric Delirium Scale (i-AGeD). Linear mixed effects modelling determined predictors of cognitive decline. Results: During 2016, 82 of 205 (40%) DECIDE participants had at least one episode of delirium. At 1 year, 135 of 205 hospitalised participants completed an interview along with 100 controls. No controls experienced delirium (i-AGeD>4). Delirium was associated with a faster rate of cognitive decline compared to those without delirium (β =-2.2, P < 0.001), but number of hospital admissions was not (P = 0.447). Conclusions: These results suggest that delirium during hospitalisation rather than hospitalisation per se is a risk factor for future cognitive decline, emphasising the need for dementia prevention studies that focus on delirium intervention

Anti-DFS70/LEDGF Antibodies Are More Prevalent in Healthy Individuals Compared to Patients with Systemic Autoimmune Rheumatic Diseases

Objective.Antinuclear antibodies (ANA) are a serological hallmark of systemic autoimmune rheumatic diseases (SARD) such as systemic lupus erythematosus (SLE). While a number of ANA patterns detected by indirect immunofluorescence (IIF) have diagnostic significance, autoantibodies producing the dense fine speckled (DFS) pattern have been reported to be more prevalent in healthy individuals than in SARD.Methods.Sequential samples submitted for ANA testing were screened for anti-DFS antibodies by IIF (n = 3263). Samples with the DFS pattern were tested for anti-DFS70/lens epithelium–derived growth factor (LEDGF) antibodies by ELISA and by a novel chemiluminescence assay (CIA, Quanta Flash DFS70). Sera from patients with various diseases and healthy individuals were tested for anti-DFS70/LEDGF antibodies by CIA. A cohort of 251 patients with SLE was used to analyze serological and clinical associations of anti-DFS70 antibodies.Results.The frequency of anti-DFS antibodies by IIF was 1.62%. The prevalence of anti-DFS70/LEDGF antibodies as detected by CIA in the different cohorts was 8.9% in healthy individuals, 2.8% in SLE, 2.6% in rheumatoid arthritis, 4.0% in asthma, 5.0% in interstitial cystitis, 1.7% in Graves' disease, and 6.0% in Hashimoto's thyroiditis. Of note, the prevalence of anti-DFS70/LEDGF antibodies was significantly higher in healthy individuals compared to patients with SARD (p = 0.00085). In SLE results, anti-DFS70/LEDGF antibodies were not significantly associated with clinical features or other autoantibodies typically found in SLE. Only 1/7 SLE sera showed anti-DFS70/LEDGF, but no other autoantibody reactivity.Conclusion."Monospecific" anti-DFS70/LEDGF antibodies may represent a biomarker for differentiating SARD from non-SARD individuals, but there is a need for a reliable assay to ensure reactivity to DFS70