Magnetic nanoparticles for gene and drug delivery

Investigations of magnetic micro- and nanoparticles for targeted drug delivery began over 30 years ago. Since that time, major progress has been made in particle design and synthesis techniques, however, very few clinical trials have taken place. Here we review advances in magnetic nanoparticle design, in vitro and animal experiments with magnetic nanoparticle-based drug and gene delivery, and clinical trials of drug targeting

Canine Support Program: Student perceptions and preferences at a regional university and implications for health, well-being, and student support enhancements

Issue Addressed: Canine Support Programs (CSPs) are a potential solution to growing university student support demands. While current studies focus on the impacts of CSPs, there is limited understanding of the views and expectations of tertiary students about CSPs. This study explored the perceptions and preferences of students in an Australian regional university about CSPs. Methods: A questionnaire with multiple choice and open-ended questions surveyed residential students' perspectives about CSP. Data were analysed using descriptive statistical tests and thematic analysis for open responses. Results: Majority (98%) of participants (sample n = 48) would support a CSP on campus. Frequent, small-group interactions of ≥15 min involving physical contact were preferred. Dog disposition, welfare-trained handlers, and veterinary certification were important aspects of program safety. Participants strongly agreed a CSP would improve mental health and well-being, relieve stress, reduce feelings of homesickness, provide support, comfort, and enable social interactions. Conclusion: There is strong support among the study population for CSP to be established on campus. This study supports earlier research that CSP has benefit potential for new, stressed, and/or students who love dogs. The preferences of students should inform program design to enhance utility and impact. This aligns with Health Promoting Universities and College's Okanagan Charter principle of ‘engaging student voices’. More institutional awareness and support for CSPs will be necessary for integration. So What?: This study reveals the need for tailored and creative student support beyond traditional offerings including those that focus on student well-being and social initiatives. CSPs can be utilised as an advocate, enabler, and medium for mental health promotion action and well-being support for tertiary students; thereby, contributing to the ‘Health Promoting University’ agenda in Australia. It also reinforces the need for a Health in All Policies approach to be incorporated into our tertiary education sector. Future actions should focus on improving institutional awareness, support, and sector implementation

The reliability of inspiratory resistive load magnitude and detection testing

Objectives: To assess the test-retest reliability of inspiratory load detection and load magnitude perception tests in healthy volunteers. Design: Cohort of convenience. Setting: Respiratory physiology laboratory. Participants: Twenty healthy adults. Interventions: On two separate occasions participants performed tests of inspiratory loading. Participants breathed through custom made resistive tubing and were asked to indicate when they detected a different resistance during inspiration. In a second test participants rated the magnitude of presented inspiratory loads using the modified Borg score. Main Outcome Measures: Intra-class Correlation Coefficient (ICC2,1) values for repeated tests of inspiratory load detection threshold and load magnitude rating. Results: ICC2,1 values ranged from 0.657–0.786 for load detection testing and 0.739 to 0.969 for rating of load magnitude. Conclusions: The tests are simple and reliable measures of inspiratory load detection and magnitude rating. They can be used in future research to determine the effectiveness of interventions to reduce the effort of breathing in health and disease

Treatment options for progression or recurrence of glioblastoma: a network meta-analysis

For treatment of first recurrence of GBM, among people previously treated with surgery and standard chemoradiotherapy, the combination treatments evaluated did not improve overall survival compared with LOM monotherapy and were often associated with a higher risk of severe adverse events. Limited evidence suggested that re‐operation with or without re‐irradiation and chemotherapy may be suitable for selected candidates. Evidence on second recurrence is sparse. Re‐irradiation with or without bevacizumab may be of value in selected individuals, but more evidence is needed

Family-centred approaches to the prevention of mother to child transmission of HIV

Background: Prevention of mother to child transmission (PMTCT) programmes have traditionally been narrow in scope, targeting biomedical interventions during the perinatal period, rather than considering HIV as a family disease. This limited focus restricts programmes' effectiveness, and the opportunity to broaden prevention measures has largely been overlooked. Although prevention of vertical transmission is crucial, consideration of the family environment can enhance PMTCT. Family-centred approaches to HIV prevention and care present an important direction for preventing paediatric infections while improving overall family health. This paper reviews available literature on PMTCT programmatic models that have taken a broader or family-centred approach. We describe findings and barriers to the delivery of family-centred PMTCT and identify a number of promising new directions that may achieve more holistic services for children and families. Methods: Literature on the effectiveness of family-centred PMTCT interventions available via PubMed, EMBASE and PsycINFO were searched from 1990 to the present. Four hundred and three abstracts were generated. These were narrowed to those describing or evaluating PMTCT models that target broader aspects of the family system before, during and/or after delivery of an infant at risk of acquiring HIV infection (N = 14). Results: The most common aspects of family-centred care incorporated by PMTCT studies and programme models included counselling, testing, and provision of antiretroviral treatment for infected pregnant women and their partners. Antiretroviral therapy was also commonly extended to other infected family members. Efforts to involve fathers in family-based PMTCT counselling, infant feeding counselling, and general decision making were less common, though promising. Also promising, but rare, were PMTCT programmes that use interventions to enrich family capacity and functioning; these include risk assessments for intimate partner violence, attention to mental health issues, and the integration of early childhood development services. Conclusions: Despite barriers, numerous opportunities exist to expand PMTCT services to address the health needs of the entire family. Our review of models utilizing these approaches indicates that family-centred prevention measures can be effectively integrated within programmes. However, additional research is needed in order to more thoroughly evaluate their impact on PMTCT, as well as on broader family health outcomes

Reduced live birth rates in frozen versus fresh single cleavage stage embryo transfer cycles: A cross-sectional study

Background: Studies have suggested that embryo-endometrial developmental asynchrony caused by slow-growing embryos can be corrected by freezing the embryo and transferring it back in a subsequent cycle. Therefore, we hypothesized that live birth rates (LBR) would be higher in frozen embryo transfer (FET) compared with fresh embryo transfers. Objective: To compare LBR between fresh and FET cycles. Materials and Methods: A cross-sectional analysis of 10,744 single autologous embryo transfer cycles that used a single cleavage-stage embryo was performed. Multivariate analysis was performed to compare LBR between FET and fresh cycles, after correcting for various confounding factors. Sub-analysis was also performed in cycles using slow embryos. Results: Both LBR (19.13% vs 14.13%) and clinical pregnancy (22.48% vs 16.25%) rates (CPR) were higher in the fresh cycle group (p < 0.00). Multivariate analysis for confounding factors also confirmed that women receiving a frozen-thawed embryo had a significantly lower LBR rate compared to those receiving a fresh embryo (OR 0.76, 95% CI 0.68-0.86, p < 0.00). In the sub-analysis of 1,154 cycles using slow embryos, there was no statistical difference in LBR (6.40% vs 6.26%, p = 0.92) or CPR (8.10% vs 7.22%, p = 0.58) between the two groups. Conclusion: This study shows a lower LBR in FET cycles when compared to fresh cycles. Our results suggest that any potential gains in LBR due to improved embryo-endometrial synchrony following FET are lost, presumably due to freeze-thaw process-related embryo damage. Key words: Fresh, Frozen embryo transfer, Live birth, Embryo, Transfer

Management of type 2 diabetes mellitus in people with severe mental illness: an online cross-sectional survey of healthcare professionals

Objectives To establish healthcare professionals’ (HCPs) views about clinical roles, and the barriers and enablers to delivery of diabetes care for people with severe mental illness (SMI). Design Cross-sectional, postal and online survey. Setting Trusts within the National Health Service (NHS), mental health and diabetes charities and professional bodies. Participants HCPs who care for people with type 2 diabetes mellitus (T2DM) and/or SMI in the UK. Primary and secondary outcome measures The barriers, enablers and experiences of delivering T2DM care for people with SMI, informed by the Theoretical Domains Framework (TDF). Results Responders were 273 HCPs, primarily mental health nurses (33.7%) and psychiatrists (32.2%). Only 25% of respondents had received training in managing T2DM in people with SMI. Mental health professionals felt responsible for significantly fewer recommended diabetes care standards than physical health professionals (p<0.001). For those seeing diabetes care as part of their role, the significant barriers to its delivery in the regression analyses were a lack of knowledge (p=0.003); a need for training in communication and negotiation skills (p=0.04); a lack of optimism about the health of their clients (p=0.04) and their ability to manage T2DM in people with SMI (p=0.003); the threat of being disciplined (p=0.02); fear of working with people with a mental health condition (p=0.01); a lack of service user engagement(p=0.006) and a need for incentives (p=0.04). The significant enablers were an understanding of the need to tailor treatments (p=0.04) and goals (p=0.02) for people with SMI. Conclusions This survey indicates that despite current guidelines, diabetes care in mental health settings remains peripheral. Even when diabetes care is perceived as part of a HCP’s role, various individual and organisational barriers to delivering recommended T2DM care standards to people with SMI are experienced

Opposing effects of final population density and stress on Escherichia coli mutation rate

Evolution depends on mutations. For an individual genotype, the rate at which mutations arise is known to increase with various stressors (stress-induced mutagenesis-SIM) and decrease at high final population density (density-associated mutation-rate plasticity-DAMP). We hypothesised that these two forms of mutation-rate plasticity would have opposing effects across a nutrient gradient. Here we test this hypothesis, culturing Escherichia coli in increasingly rich media. We distinguish an increase in mutation rate with added nutrients through SIM (dependent on error-prone polymerases Pol IV and Pol V) and an opposing effect of DAMP (dependent on MutT, which removes oxidised G nucleotides). The combination of DAMP and SIM results in a mutation rate minimum at intermediate nutrient levels (which can support 7 × 10  cells ml ). These findings demonstrate a strikingly close and nuanced relationship of ecological factors-stress and population density-with mutation, the fuel of all evolution

Treatment options for recurrent glioblastoma: a network meta-analysis

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:. To evaluate the effectiveness of further treatment/s for first and subsequent recurrence of glioblastoma multiforme (GBM) among people who have received the standard of care for primary treatment of the disease (chemoradiotherapy) or following development of GBM from a lower grade (radiotherapy with subsequent temozolomide at relapse); and to prepare a brief economic commentary on the available evidence

Spontaneous mutation rate is a plastic trait associated with population density across domains of life

Rates of random, spontaneous mutation can vary plastically, dependent upon the environment. Such plasticity affects evolutionary trajectories and may be adaptive. We recently identified an inverse plastic association between mutation rate and population density at 1 locus in 1 species of bacterium. It is unknown how widespread this association is, whether it varies among organisms, and what molecular mechanisms of mutagenesis or repair are required for this mutation-rate plasticity. Here, we address all 3 questions. We identify a strong negative association between mutation rate and population density across 70 years of published literature, comprising hundreds of mutation rates estimated using phenotypic markers of mutation (fluctuation tests) from all domains of life and viruses. We test this relationship experimentally, determining that there is indeed density-associated mutation-rate plasticity (DAMP) at multiple loci in both eukaryotes and bacteria, with up to 23-fold lower mutation rates at higher population densities. We find that the degree of plasticity varies, even among closely related organisms. Nonetheless, in each domain tested, DAMP requires proteins scavenging the mutagenic oxidised nucleotide 8-oxo-dGTP. This implies that phenotypic markers give a more precise view of mutation rate than previously believed: having accounted for other known factors affecting mutation rate, controlling for population density can reduce variation in mutation-rate estimates by 93%. Widespread DAMP, which we manipulate genetically in disparate organisms, also provides a novel trait to use in the fight against the evolution of antimicrobial resistance. Such a prevalent environmental association and conserved mechanism suggest that mutation has varied plastically with population density since the early origins of life