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Access to commercial CD19 CAR-T cells remains limited even in wealthy countries like Canada due to clinical, logistical, and financial barriers related to centrally manufactured products. We created a non-commercial academic platform for end-to-end manufacturing of CAR-T cells within Canada’s publicly funded healthcare system. We report initial results from a single-arm, open-label study to determine the safety and efficacy of in-house manufactured CD19 CAR-T cells (entitled CLIC-1901) in participants with relapsed/refractory CD19 positive hematologic malignancies. Using a GMP compliant semi-automated, closed process on the Miltenyi Prodigy, T cells were transduced with lentiviral vector bearing a 4-1BB anti-CD19 CAR transgene and expanded. Participants underwent lymphodepletion with fludarabine and cyclophosphamide, followed by infusion of non-cryopreserved CAR-T cells. Thirty participants with non-Hodgkin’s lymphoma (n=25) or acute lymphoblastic leukemia (n=5) were infused with CLIC-1901: 21 males (70%), median age 66 (range 18-75). Time from enrollment to CLIC-1901 infusion was a median of 20 days (range 15-48). The median CLIC-1901 dose infused was 2.3 × 106 CAR-T cells/kg (range 0.13-3.6 × 106/kg). Toxicity included ≥ grade 3 cytokine release syndrome (n=2) and neurotoxicity (n=1). Median follow-up was 6.5 months. Overall response rate at day 28 was 76.7%. Median progression-free and overall survival was 6 months (95%CI 3-not estimable) and 11 months (95% 6.6-not estimable), respectively. This is the first trial of in-house manufactured CAR-T cells in Canada and demonstrates that administering fresh CLIC-1901 product is fast, safe, and efficacious. Our experience may provide helpful guidance for other jurisdictions seeking to create feasible and sustainable CAR-T cell programs in research-oriented yet resource-constrained settings.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03765177, identifier NCT03765177.

Introduction: The Westmead Centre for Adolescent and Young Adult Health is a purpose-built facility supporting integrated care for young patients with a variety of long-term health conditions transitioning from paediatric services at the Children's Hospital at Westmead to adult services at Westmead Hospital, Australia., Methods and Analysis: This protocol outlines a prospective, within-subjects, repeated-measures longitudinal cohort study to measure self-reported experiences and outcomes of patients (12-25 years) and carers accessing transition care at the Centre for Adolescent and Young Adult Health. Longitudinal self-report data will be collected using Research Electronic Data Capture surveys at the date of service entry (recruitment baseline), with follow-ups occurring at 6 months, 12 months, 18 months and after transfer to adult services. Surveys include validated demographic, general health and psychosocial questionnaires. Participant survey responses will be linked to routinely recorded data from hospital medical records. Hospital medical records data will be extracted for the 12 months prior to service entry up to 18 months post service entry. All young people accessing services at the Centre for Adolescent and Young Adult Health that meet inclusion criteria will be invited to join the study with research processes to be embedded into routine practices at the site. We expect a sample of approximately 225 patients with a minimum sample of 65 paired responses required to examine pre-post changes in patient distress. Data analysis will include standard descriptive statistics and paired-sample tests. Regression models and Kaplan-Meier method for time-to-event outcomes will be used to analyse data once sample size and test requirements are satisfied., Ethics and Dissemination: The study has ethics approval through the Sydney Children's Hospitals Network Human Research Ethics Committee (2021/ETH11125) and site-specific approvals from the Western Sydney Local Health District (2021/STE03184) and the Sydney Children's Hospitals Network (2039/STE00977). Patients under the age of 18 will require parental/carer consent to participate in the study. Patients over 18 years can provide informed consent for their participation in the research. Dissemination of research will occur through publication of peer-reviewed journal reports and conference presentations using aggregated data that precludes the identification of individuals. Through this work, we hope to develop a digital common that can be shared with other researchers and clinicians wanting to develop a standardised and shared approach to the measurement of patient outcomes and experiences in transition care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Government policies that support the health and wellbeing of young people (aged 10 to 25) can have important individual and societal impacts. The aim of this study was to explore policy actor perspectives on the development and implementation of Australian government policies focussed on the health and wellbeing of young people., Methods: We utilised a qualitative research design consisting of semi-structured interviews with policy actors with experience working with Australian youth health policies. Our interview guide and analyses were informed by the Consolidated Framework for Implementation Research (CFIR). We interviewed 19 participants from various national, state, and territory bodies., Results: Several specific barriers and facilitators to policy development and implementation were identified using the Consolidated Framework for Implementation Research. Key policy development barriers were limited available resources (e.g. staffing and funding) and low relative priority within health and political systems. Key policy implementation barriers were limited available resources, limited policy compatibility with health services, cosmopolitanism issues related to interagency collaboration, and a lack of policy evaluation. Meaningful engagement of young people could also be improved., Conclusions: Although Australian youth health policies are perceived as evidence-based and comprehensively developed, the ability to promote implementation remains stalled., Implications for Public Health: The development of policy implementation plans, monitoring and evaluation mechanisms, funding and resources, and a strong commitment to removing barriers to working across multiple departments and systems is required to improve outcomes for young people., Competing Interests: Conflicts of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The main causes of morbidity and mortality for adolescents and young adults are preventable and stem from psychosocial and behavioural concerns. Psychosocial assessments can help clinicians to identify and respond holistically to risks and strengths that may impact upon a young person's physical and mental health. Despite broad support at a policy level, the implementation of routine psychosocial screening for young people remains varied in Australian health settings. The current study focused on the pilot implementation of a digital patient-completed psychosocial assessment (the e-HEEADSSS) at the Sydney Children's Hospital Network. The aim of this research was to evaluate patient and staff barriers and facilitators to local implementation., Methods: The research used a qualitative descriptive research design. Semi-structured interviews were conducted online with 8 young patients and 8 staff members who had completed or actioned an e-HEEADSSS assessment within the prior 5 weeks. Qualitative coding of interview transcripts was carried out in NVivo 12. The Consolidated Framework for Implementation Research guided the interview framework and qualitative analyses., Results: Results demonstrated strong support for the e-HEEADSSS from patients and staff. Key reported facilitators included strong design and functionality, reduced time requirements, greater convenience, improved disclosure, adaptability across settings, greater perceived privacy, improved fidelity, and reduced stigma for young people. The key barriers were related to concerns over available resources, the sustainability and continuity of staff training, perceived availability of clinical pathways for follow-up and referrals, and risks related to off-site completions. Clinicians need to adequately explain the e-HEEADSSS assessment to patients, educate them about it, and make sure that they receive timely feedback on the results. Greater reassurance and education regarding the rigour of confidentiality and data handling procedures is required for patients and staff., Conclusions: Our findings indicate that continued work is required to support the integration and sustainability of digital psychosocial assessments for young people at the Sydney Children's Hospital Network. The e-HEEADSSS shows promise as an implementable intervention to achieve this goal. Further research is required to determine the scalability of this intervention across the broader health system., (© 2023. The Author(s).)

The domestic cat (Felis catus) is an obligate carnivore, and as such has a meat-based diet. Several studies on the taste perception of cats have been reported, indicating that their sense of taste has evolved based on their carnivorous diet. Here, we propose that umami (mediated by Tas1r1-Tas1r3) is the main appetitive taste modality for the domestic cat by characterizing the umami taste of a range of nucleotides, amino acids, and their mixtures for cats obtained using complementary methods. We show for the first time that cats express Tas1r1 in taste papillae. The cat umami receptor responds to a range of nucleotides as agonists, with the purine nucleotides having the highest activity. Their umami receptor does not respond to any amino acids alone; however, 11 l-amino acids with a range of chemical characteristics act as enhancers in combination with a nucleotide. l-Glutamic acid and l-Aspartic acid are not active as either agonists or enhancers of the cat umami receptor due to changes in key binding residues at positions 170 and 302. Overall, cats have an appetitive behavioral response for nucleotides, l-amino acids, and their mixtures. We postulate that the renowned palatability of tuna for cats may be due, at least in part, to its specific combination of high levels of inosine monophosphate and free l-Histidine that produces a strong synergistic umami taste enhancement. These results demonstrate the critical role that the umami receptor plays in enabling cats to detect key taste compounds present in meat., (© The Author(s) 2023. Published by Oxford University Press.)

As the most favoured animal companion of humans, dogs occupy a unique place in society. Understanding the senses of the dog can bring benefits to both the dogs themselves and their owners. In the case of bitter taste, research may provide useful information on sensitivity to, and acceptance of, diets containing bitter tasting materials. It may also help to protect dogs from the accidental ingestion of toxic substances, as in some instances bitter tasting additives are used as deterrents to ingestion. In this study we examined the receptive range of dog bitter taste receptors (Tas2rs). We found that orthologous dog and human receptors do not always share the same receptive ranges using in vitro assays. One bitter chemical often used as a deterrent, denatonium benzoate, is only moderately active against dTas2r4, and is almost completely inactive against other dog Tas2rs, including dTas2r10, a highly sensitive receptor in humans. We substituted amino acids to create chimeric dog-human versions of the Tas2r10 receptor and found the ECL2 region partly determined denatonium sensitivity. We further confirmed the reduced sensitivity of dogs to this compound in vivo. A concentration of 100μM (44.7ppm) denatonium benzoate was effective as a deterrent to dog ingestion in a two-bottle choice test indicating higher concentrations may increase efficacy for dogs. These data can inform the choice and concentration of bitter deterrents added to toxic substances to help reduce the occurrence of accidental dog poisonings., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: M.G., D.W., D.W.L. N.D., and S.J.M. were all employees of Mars Petcare UK when the research was conducted. I.R. and M.W. are employees of Axxam S.p.A., Italy and Axxam GmbH, Germany. The study was funded by Mars Petcare UK. M.G. and S.J.M. are named inventors on a patent application on screening methods using canine Tas2r receptors for pet food products and compositions. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2022 Gibbs et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cannabidiol (CBD) containing dog food and treats are widely commercially available, mirroring the growing popularity of CBD as a supplement for humans. Despite this, experimental evidence of the safety and efficacy of long-term oral exposure in dogs is lacking. The purpose of this study was to address the gap in knowledge around the longer-term suitability and tolerance of a broad-spectrum CBD (THC-free) distillate in clinically healthy dogs. The study was a randomized, placebo-controlled, and blinded study where one group of twenty dogs received daily CBD capsules at a dose of 4 mg/kg of body weight (BW) for a period of 6 months. The control group of twenty dogs received placebo capsules. A comprehensive suite of physiological health measures was performed throughout the study at baseline, and after 2, 4, 10, 18, and 26 weeks of exposure, followed by 4 weeks of washout. CBD concentrations were measured at the same cadence in plasma, feces and urine. Health measures included biochemistry, hematology, urinalysis, in addition to fortnightly veterinary examinations, twice daily well-being observations, and a daily quality-of-life survey. Biochemistry and hematology showed no clinically significant alterations apart from a transient elevation in alkaline phosphatase (ALP) in just over half of the dogs receiving CBD. This elevation was observed in the absence of concurrent elevations of other liver parameters, and without any adverse effects on health and wellbeing. Furthermore, bone alkaline phosphatase (BALP) was simultaneously elevated with a significant, strong ( r > 0.9) positive correlation between the two measures, suggesting that the elevation of total ALP was at least partly due to the bone-derived isoform. This study provides evidence that a once-daily oral dose of 4 mg CBD/kg BW is well tolerated in clinically healthy dogs for a duration of 6-months., Competing Interests: SB, SY, AB, LH, DW, AH, KP, PW, and DL are employees of Mars Petcare, a manufacturer of pet food and provider of veterinary services., (Copyright © 2022 Bradley, Young, Bakke, Holcombe, Waller, Hunt, Pinfold, Watson and Logan.)

Background: Multiple theories, models and frameworks have been developed to assist implementation of evidence-based practice. However, to date there has been no review of implementation literature specific to adolescent healthcare. This integrative review therefore aimed to determine what implementation science theories, models and frameworks have been applied, what elements of these frameworks have been identified as influential in promoting the implementation and sustainability of service intervention, and to what extent, in what capacity and at what time points has the contribution of adolescent consumer perspectives on evidence implementation been considered.  METHODS: An integrative design was used and reported based on a modified form of the PRISMA (2020) checklist. Seven databases were searched for English language primary research which included any implementation science theory, model or framework developed for/with adolescents or applied in relation to adolescent healthcare services within the past 10 years. Content and thematic analysis were applied with the Consolidated Framework for Implementation Research (CFIR) used to frame analysis of the barriers and facilitators to effective implementation of evidence-informed interventions within youth health settings., Results: From 8717 citations, 13 papers reporting 12 studies were retained. Nine different implementation science theories, frameworks or approaches were applied; six of 12 studies used the CFIR, solely or with other models. All CFIR domains were represented as facilitators and barriers for implementation in included studies. However, there was little or no inclusion of adolescents in the development or review of these initiatives. Only three mentioned youth input, occurring in the pre-implementation or implementation stages., Conclusions: The few studies found for this review highlight the internationally under-developed nature of this topic. Flagging the importance of the unique characteristics of this particular age group, and of the interventions and strategies to target it, the minimal input of adolescent consumers is cause for concern. Further research is clearly needed and must ensure that youth consumers are engaged from the start and consistently throughout; that their voice is prioritised and not tokenistic; that their contribution is taken seriously. Only then will age-appropriate evidence implementation enable innovations in youth health services to achieve the evidence-based outcomes they offer., Trial Registration: PROSPERO 2020 CRD42020201142 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=201142., (© 2022. The Author(s).)

Background: Effective integration of evidence and youth perspectives into policy is crucial for supporting the future health and well-being of young people. The aim of this project was to translate evidence from the Access 3 project to support development of a new state policy on youth health and well-being within New South Wales (NSW), Australia. Ensuring the active contribution of young people within policy development was a key objective of the knowledge translation (KT) process., Methods: The KT activity consisted of a 1-day facilitated forum with 64 purposively sampled stakeholders. Participants included eight young people, 14 policy-makers, 15 academics, 22 clinicians or managers from NSW health services, four general practitioners and one mental health service worker. Research to be translated came from the synthesized findings of the NSW Access 3 project. The design of the forum included stakeholder presentations and group workshops, guided by the 2003 Lavis et al. KT framework that was improved by the Grimshaw et al. KT framework in 2012. Members of the Access 3 research team took on the role of knowledge brokers throughout the KT process. Participant satisfaction with the workshop was evaluated using a brief self-report survey. Policy uptake was determined through examination of the subsequent NSW Youth Health Framework 2017-2024., Results: A total of 25 policy recommendations were established through the workshop, and these were grouped into six themes that broadly aligned with the synthesized findings from the Access 3 project. The six policy themes were (1) technology solutions, (2) integrated care and investment to build capacity, (3) adolescent health checks, (4) workforce, (5) youth participation and (6) youth health indicators. Forum members were asked to vote on the importance of individual recommendations. These policy recommendations were subsequently presented to the NSW Ministry of Health, with some evidence of policy uptake identified. The majority of participants rated the forum positively., Conclusions: The utilization of KT theories and active youth engagement led to the successful translation of research evidence and youth perspectives into NSW youth health policy. Future research should examine the implementation of policy arising from these KT efforts., (© 2022. The Author(s).)

Molecular programs that underlie precursor progression in multiple myeloma are incompletely understood. Here, we report a disease spectrum-spanning, single-cell analysis of the Vκ*MYC myeloma mouse model. Using samples obtained from mice with serologically undetectable disease, we identify malignant cells as early as 30 weeks of age and show that these tumours contain subclonal copy number variations that persist throughout progression. We detect intratumoural heterogeneity driven by transcriptional variability during active disease and show that subclonal expression programs are enriched at different times throughout early disease. We then show how one subclonal program related to GCN2 stress response is progressively activated during progression in myeloma patients. Finally, we use chemical and genetic perturbation of GCN2 in vitro to support this pathway as a therapeutic target in myeloma. These findings therefore present a model of precursor progression in Vκ*MYC mice, nominate an adaptive mechanism important for myeloma survival, and highlight the need for single-cell analyses to understand the biological underpinnings of disease progression., (© 2021. The Author(s).)

Background: The health and wellbeing of young people are critical for the future of society but the extent to which they are addressed by overarching Australian Federal, State and Territory health policy is difficult to determine. Analysing high-level youth health policy will help establish how Australian governments are articulating and prioritising issues and may guide local and international health agendas., Methods: This scoping review aimed to determine the extent, range and nature of Australian high-level government policy focused on the general health and wellbeing of the general population of young people. Policies published by Australian Federal, State, or Territory government departments between 2008 and 2019 were thematically analysed employing Braun and Clark's six-step recursive framework., Findings: Twelve policy documents met inclusion criteria. Three meta-themes emerged, comprising policy development, youth health challenges, and policy goals. Policy goals fell into three ubiquitous and overarching categories focused on supporting public health, promoting equity, and improving the health system for young people., Conclusions: A number of youth-specific health policies have been developed by Australian governments in recent years. Whilst goals and strategies are clearly articulated, more can be done to ensure a youth voice in policy development. The policy goals of supporting public health, promoting equity and improving the health system deserve consideration from other countries developing youth health policies., Competing Interests: Declaration of Competing Interest The authors of this publication declare no conflicts of interest., (Copyright © 2021. Published by Elsevier B.V.)

Accelerometry data has been widely used to measure activity and the circadian rhythm of individuals across the health sciences, in particular with people with advanced dementia. Modern accelerometers can record continuous observations on a single individual for several days at a sampling frequency of the order of one hertz. Such rich and lengthy data sets provide new opportunities for statistical insight, but also pose challenges in selecting from a wide range of possible summary statistics, and how the calculation of such statistics should be optimally tuned and implemented. In this paper, we build on existing approaches, as well as propose new summary statistics, and detail how these should be implemented with high frequency accelerometry data. We test and validate our methods on an observed data set from 26 recordings from individuals with advanced dementia and 14 recordings from individuals without dementia. We study four metrics: Interdaily stability (IS), intradaily variability (IV), the scaling exponent from detrended fluctuation analysis (DFA), and a novel nonparametric estimator which we call the proportion of variance (PoV), which calculates the strength of the circadian rhythm using spectral density estimation. We perform a detailed analysis indicating how the time series should be optimally subsampled to calculate IV, and recommend a subsampling rate of approximately 5 minutes for the dataset that has been studied. In addition, we propose the use of the DFA scaling exponent separately for daytime and nighttime, to further separate effects between individuals. We compare the relationships between all these methods and show that they effectively capture different features of the time series., Competing Interests: The authors have declared that no competing interests exist.

Background: Frequent blood donors are an important resource as they contribute many donations over their lifetime. The aim of this research was to develop a demographic profile of Australian frequent whole blood donors and to determine predictors of lapse within this group., Study Design and Methods: Routinely collected data were used to profile individuals who had donated whole blood frequently (three or more times) between December 2010 and November 2011. Two segments were identified: 1) existing donors who had donated before December 2010 and 2) new donors who had not donated before December 2010. Donation records were followed to the end of December 2013 to examine retention., Results: A total of 90,867 donated frequently between December 2010 and November 2011. The group was composed of slightly more men (51.4%), was typically of middle socioeconomic status, and many were employed in skilled trades such as a builder or a plumber (21.3%). Existing donors (n = 81,762) were significantly older, more likely to be male, and more likely to have a D- blood type compared to the smaller group of new donors (n = 9105). For both segments, being older and male and having a D- blood type increased the likelihood of return in the follow-up period. Deferrals and adverse events had negative impacts on retention for both groups., Conclusions: This study highlights specific factors that blood collection agencies may focus on to support continued donation among frequent donors., (© 2016 AABB.)

Background: Each year, a large number of individuals in Australia are deferred from donating blood. A deferral may have a negative impact on donor satisfaction and subsequent word-of-mouth communication. The Australian Red Cross Blood Service (the Blood Service) is, therefore, investigating options for managing service interactions with deferred donors to maintain positive relationships. While public research institutes in Australia have established independent research donor registries, other countries provide programmes allowing deferred donors to donate blood for research via blood collection agencies. This study examined attitudes towards donating blood for research use in a sample of permanently deferred Australian donors., Materials and Methods: Donors permanently deferred because of a risk of variant Creutzfeldt-Jakob disease (n=449) completed a postal survey that examined attitudes towards research donation., Results: The majority of participants were interested in donating blood for research (96%), and joining a registry of research donors (93%). Participants preferred to donate for transfusion or clinical research, and were willing to travel large distances. Results indicated that positive attitudes towards the Blood Service would be extended if the opportunity to donate blood was provided. These findings indicate a desire for continued engagement with the Blood Service despite deferral., Discussion: Donating blood for research is a potential way of maintaining positive relationships with permanently deferred donors which also benefits the health research community. Through maintaining positive relationships with deferred donors, positive word-of-mouth activity can be stimulated. Further work is needed to determine the feasibility of implementing research donation through the Blood Service in Australia.

Background: Research demonstrates that anxiety elevates the risk of blood donors experiencing adverse events, which in turn deters the performance of repeat blood donations. Identifying donors suffering from heightened state anxiety is important to assess the impact of evidence-based interventions. This study analyzed the appropriateness of a shortened version of the state subscale of the State-Trait Anxiety Inventory (STAI) in a blood donation context., Study Design and Methods: STAI-State questionnaire data were collected from two separate samples of Australian blood donors (n = 919 and n = 824 after cleaning). Responses to demographic, donation history, and adverse reaction questions were also obtained. Identification of items and analysis was performed systematically to assess and compare internal reliability and content, construct, convergent, and criterion validity of three potential short-form state anxiety scales., Results: Of the three short-form scales tested, STAI-State six-item scale demonstrated the best metric properties with the least number of items across both sample groups. Cronbach's alpha was acceptable (α = 0.844 and α = 0.820), correlated positively with the original measure (r = 0.927 and r = 0.931) and criterion-related variables, and maintained the two-dimension factorial structure of the original measure., Conclusion: The six-item short version of the STAI-State subscale presented the most reliable and valid scale for use with blood donors. A validated donor anxiety tool provides a standardized assessment and record of donor anxiety to gauge the effectiveness of ongoing efforts to enhance the donation experience., (© 2016 AABB.)

Background: Vasovagal symptoms have implications for donor safety and retention. This study explored knowledge, attitudes and practices in donors experiencing a vasovagal reaction., Materials and Methods: Semi-structured interviews were conducted with donors (n = 30) who experienced a donation-related vasovagal reaction., Results: Donors were unaware of applied muscle tension or fluid loading techniques despite availability of information. Some donors engaged in excessive pre-donation hydration. Procedural knowledge was limited for first-time plasma donors., Discussion: Future interventions should focus on adherence to pre-donation fluid loading and muscle tensing exercises during key donation time-points. Education for new plasma donors also appears important., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Many nondonors are positive about blood donation and this motivates booking an appointment to donate. However, as their appointment approaches barriers to donating-such as anxiety-may become salient and deter attendance. Building on research of France and colleagues demonstrating the positive effect of enhanced preparation materials on donor recruitment, this study sought to determine whether these materials could effectively boost first donation appointment attendance., Study Design and Methods: A field study comprising a 3 (brochure: none, e-mail, hard copy) × 2 (national call center [NCC] contact: none, call) between-subjects design was conducted with 3646 nondonors who had scheduled their first appointment. Participants in the brochure conditions received either a hard copy or an e-mailed link to electronic materials modeled on the donor preparation research of France and colleagues. Participants in the NCC call condition also received a call scripted in line with these preparation materials. The key outcome was new donor attendance rate., Results: Although first-appointment attendance rates were high in the control (no additional contact) condition at 85.07% of those not canceling in advance, dual exposure to the preparation materials through a NCC call and an electronic brochure boosted attendance. The relative risk of attending in the NCC call and electronic brochure condition was 1.0836 (95% confidence interval, 1.0352-1.1343; p = 0.0006), with attendance 8.36% higher than in the control. This gain in attendance came at a relative increase in recruitment costs of 2%., Conclusion: The use of tailored communication to address new donors' concerns and prepare them for donating bolsters attendance rates., (© 2016 AABB.)

Background: This research examined the effect of autologous serum eye drops (ASED) on ocular symptoms, visual-related functioning and quality of life for patients failing other therapies., Methods: Patients (N = 77) were asked to complete a survey prior to ASED use, and 2 and 12 months post-treatment., Results: Significant improvements in symptom frequency and severity were documented for dryness, ocular pain and grittiness at 2 and 12 months. Patients felt more in control and required less help from others at 12 months., Conclusions: ASED produce sustained benefits to dry eye symptoms, improve feelings of control and reduce requirements for assistance from others., (Copyright © 2015. Published by Elsevier Ltd.)

Background: Using a predonation screening questionnaire, potential blood donors are screened for medical or behavioral factors associated with an increased risk for transfusion-transmissible infection. After disclosure of these risks, potential donors are deferred from donating. Understanding the degree of failure to disclose full and truthful information (termed noncompliance) is important to determine and minimize residual risk. This study estimates the prevalence of, and likely reasons for, noncompliance among Australian donors with the deferrals for injecting drug use, sex with an injecting drug user, male-to-male sex, sex worker activity or contact, and sex with a partner from a high-HIV-prevalence country., Study Design and Methods: An anonymous, online survey of a nationally representative sample of Australian blood donors was conducted. Prevalence of noncompliance with deferrable risk categories was estimated. Factors associated with noncompliance were determined using unadjusted and adjusted odds ratios., Results: Of 98,044 invited donors, 30,790 donors completed the survey. The estimated prevalence of overall noncompliance (i.e., to at least one screening question) was 1.65% (95% confidence interval CI, 1.51%-1.8%). Noncompliance with individual deferrals ranged from 0.05% (sex work) to 0.54% (sex with an injecting drug user). The prevalences of the disclosed exclusionary risk behaviors were three to 14 times lower than their estimated prevalence in the general population., Conclusion: The prevalence of noncompliance is relatively low but our estimate is likely to be a lower bound. The selected high-risk behaviors were substantially less common in blood donors compared to the general population suggesting that self-deferral is effective. Nevertheless, a focus on further minimization should improve the blood safety., (© 2014 AABB.)

Objective: To determine whether personality traits (conscientiousness, agreeableness, emotional regulation, extraversion, and openness to experience) are associated with glycemic control and blood glucose monitoring behavior, and change or stability of these outcomes over time, in young people with type 1 diabetes., Research Design and Methods: A 3-year longitudinal study was conducted using data from 142 individuals with type 1 diabetes, 8-19 years of age. Personality was assessed at baseline using the Five-Factor Personality Inventory for Children. Data relating to glycemic control (HbA1c) and frequency of blood glucose monitoring (based on meter memory) were collected annually. Relationships between personality traits and HbA1c and monitoring frequency were examined using regression models and mixed-design ANOVA., Results: Three of the Five-Factor domains were independently associated with glycemic control. Individuals high in conscientiousness and agreeableness had a lower and more stable HbA1c across the 3-year study period. In contrast, the HbA1c of individuals scoring low on these traits was either consistently worse or deteriorated over time. Low or high emotional regulation scores were also associated with worse glycemic control. By the third year, these domains, together with initial HbA1c, accounted for 39% of HbA1c variance. Conscientiousness was the only personality factor associated with blood glucose monitoring behavior., Conclusions: Results of this study underline the importance of personality in contributing to diabetes outcomes. Attention to a young person's personality, and appropriate tailoring of diabetes management to ensure an individualized approach, may help to optimize diabetes outcomes.

Most cystic fibrosis is caused by mutations in CFTR that prevent its trafficking from the ER to the plasma membrane and is associated with exaggerated inflammation, altered metabolism, and diminished responses to oxidative stress. PARP-1 is activated by oxidative stress and causes energy depletion and cell dysfunction. Inhibition of this enzyme protects against excessive inflammation and recent studies have also implicated it in intracellular protein trafficking. We hypothesized that PARP-1 activity is altered in CF and affects trafficking and function of the most common CF mutant ΔF508 CFTR. Indeed, PARP-1 activity was 2.9-fold higher in CF (ΔF508/ΔF508) human bronchial epithelial primary cells than in non-CF cells, and similar results were obtained by comparing CF vs. non-CF bronchial epithelial cell lines (2.5-fold higher in CFBE41o(-) vs. 16HBE14o(-), P < 0.002). A PARP-1 inhibitor (ABT-888, Veliparib) partially restored CFTR channel activity in CFBE41o(-) cells overexpressing ΔF508 CFTR. Similarly, reducing PARP-1 activity by 85% in ileum from transgenic CF mice (Cftr(tm1)Eur) partially rescued ΔF508 CFTR activity to 7% of wild type mouse levels, and similar correction (7.8%) was observed in vivo by measuring salivary secretion. Inhibiting PARP-1 with ABT-888 or siRNA partially restored ΔF508 CFTR trafficking in cell lines, and most ΔF508 CFTR was complex glycosylated when heterologously expressed in PARP-1(-/-) mouse embryonic fibroblasts. Finally, levels of the mature glycoform of CFTR were reduced by peroxynitrite, a strong activator of PARP-1. These results demonstrate that PARP-1 activity is increased in CF, and identify a novel pathway that could be targeted by proteostatic correctors of CFTR trafficking.