Antenatal care of women who use opioids: a qualitative study of practitioners' perceptions of strengths and challenges of current service provision in Scotland.

BACKGROUND: The increasing rise of women using opioids during pregnancy across the world has warranted concern over the access and quality of antenatal care received by this group. Scotland has particularly high levels of opioid use, and correspondingly, pregnancies involving women who use opioids. The purpose of this study was to investigate the different models of antenatal care for women using opioids during pregnancy in three Scottish Health Board Areas, and to explore multi-disciplinary practitioners' perceptions of the strengths and challenges of working with women who use opioids through these specialist services. METHODS: Thirteen semi-structured interviews were conducted with health and social care workers who had experience of providing antenatal and postnatal care to women who use drugs across three Scottish Health Board Areas: NHS Greater Glasgow and Clyde, NHS Lothian, and NHS Tayside. Framework Analysis was used to analyse interview data. The five stages of framework analysis were undertaken: familiarisation, identifying the thematic framework, indexing, charting, and mapping and interpretation. RESULTS: Each area had a specialist antenatal pathway for women who used substances. Pathways varied, with some consisting of specialist midwives, and others comprising a multidisciplinary team (e.g. midwife, mental health nurse, social workers, and an obstetrician). Referral criteria for the specialist service differed between health board areas. These specialised pathways presented several key strengths: continuity of care with one midwife and a strong patient-practitioner relationship; increased number of appointments, support and scans; and highly specialised healthcare professionals with experience of working with substance use. In spite of this, there were a number of limitations to these pathways: a lack of additional psychological support for the mother; some staff not having the skills to engage with the complexity of patients who use substances; and problems with patient engagement. CONCLUSIONS: Across the three areas, there appears to be high-quality multi-disciplinary antenatal services for women who use opioids during pregnancy. However, referral criteria vary and some services appear more comprehensive than others. Further research is needed into the perceptions of women who use opioids on facilitators and barriers to antenatal care, and provision in rural regions of Scotland.

The power of effective study design in animal experimentation: Exploring the statistical and ethical implications of asking multiple questions of a data set.

One of the chief advantages of using highly standardised biological models including model organisms is that multiple variables can be precisely controlled so that the variable of interest is more easily studied. However, such an approach often obscures effects in sub-populations resulting from natural population heterogeneity. Efforts to expand our fundamental understanding of multiple sub-populations are in progress. However, such stratified or personalised approaches require fundamental modifications of our usual study designs that should be implemented in Brain, Behavior and Immunity (BBI) research going forward. Here we explore the statistical feasibility of asking multiple questions (including incorporating sex) within the same experimental cohort using statistical simulations of real data. We illustrate and discuss the large explosion in sample numbers necessary to detect effects with appropriate power for every additional question posed using the same data set. This exploration highlights the strong likelihood of type II errors (false negatives) for standard data and type I errors when dealing with complex genomic data, where studies are too under-powered to appropriately test these interactions. We show this power may differ for males and females in high throughput data sets such as RNA sequencing. We offer a rationale for the use of alternative experimental and statistical strategies based on interdisciplinary insights and discuss the real-world implications of increasing the complexities of our experimental designs, and the implications of not attempting to alter our experimental designs going forward.

A realist evaluation of the feasibility of a randomised controlled trial of a digital music and movement intervention for older people living in care homes.

BACKGROUND: Low physical activity in care home residents brings about negative mental health consequences, such as higher levels of depression and loneliness. With advancements in communication technology, particularly during the COVID-19 pandemic, the feasibility and effectiveness of a randomised controlled trial (RCT) of a digital Physical Activity (PA) resource in care homes deserve more research attention. A realist evaluation was used to uncover influencing factors of a feasibility study implementation to inform how a digital music and movement programme would work and under what circumstances this would be most effective. METHODS: Participants were 49 older adults (aged 65 years +) recruited across ten care homes in Scotland. Surveys were administered at baseline and post-intervention comprising psychometric questionnaires on multidimensional health markers validated in older adults with possible cognitive impairment. The intervention comprised 12 weeks of four prescribed digitally delivered movement (n = 3) and music-only (n = 1) sessions per week. An activity coordinator delivered these online resources in the care home. Post-intervention focus groups with staff and interviews with a sub-sample of participants were conducted to gain qualitative data on the acceptability of the intervention. RESULTS: Thirty three care home residents started the intervention, but only 18 residents (84% female) completed both pre- and post-intervention assessments. Activity coordinators (AC) offered 57% of the prescribed sessions, with an average residents' adherence of 60%. Delivery of the intervention did not go as planned due to Covid restrictions in care homes and delivery challenges, including (1) motivation and engagement, (2) changes in cognitive impairment and disabilities of the participants, (3) death or hospitalisation of the participants and (4) limited staffing and technology resources to deliver the programme as intended. Despite this, group participation and encouragement of residents supported the delivery and acceptance of the intervention, with ACs and residents reporting improved mood, physical health, job satisfaction and social support. Improvements with large effect sizes were found for anxiety, depression, loneliness, perceived stress and sleep satisfaction, but no changes in fear of falling, domains of general health or appetite. CONCLUSION: This realist evaluation suggested that this digitally delivered movement and music intervention is feasible. From the findings, the initial programme theory was refined for future implementation of an RCT in other care homes but future research exploring how to tailor the intervention to those with cognitive impairment and/or lacking capacity to consent is needed. TRIAL REGISTRATION: Retrospectively registered at ClinicalTrials.gov NCT05559203.

Myeloperoxidase inhibitor AZD5904 enhances human sperm function in vitro.

STUDY QUESTION: Does AZD5904, a myeloperoxidase inhibitor (MPOi), have any effect on human sperm function in vitro? SUMMARY ANSWER: AZD5904 improves sperm function in an in vitro model of oxidative stress (OS) and potentially offers a novel treatment approach for male infertility. WHAT IS KNOWN ALREADY: Male infertility is an underlying or contributory cause in half of all couples experiencing difficulties conceiving, yet there is currently no effective treatment or cure. OS is a common pathology in a significant proportion of infertile men. It can negatively affect sperm motility and the ability to fertilize a mature oocyte, as well as DNA integrity, and therefore represents an attractive target for therapeutic intervention. STUDY DESIGN, SIZE, DURATION: This study included population-based samples from men (23-50 years) attending Ninewells Assisted Conception Unit, Dundee for diagnostic semen analysis, July 2017-September 2018. Semen samples (n = 47) from 45 patients were used. PARTICIPANTS/MATERIALS, SETTING, METHODS: Neutrophils activated using zymosan were incubated with prepared human spermatozoa for 2 h (T2) and 24 h (T24) to create an in vitro model of OS. Parallel samples were co-incubated with AZD5904, an MPOi, to examine its effects. Sperm motility was assessed by computer-assisted sperm analysis at T2 and T24. Functional motility was assessed by sperm penetration assay. Statistical analysis was performed using GraphPad Prism. MAIN RESULTS AND THE ROLE OF CHANCE: There was no significant difference in total or progressive sperm motility between any treatment and control groups at T2 or T24. Nonetheless, significant positive effects on sperm function were observed with AZD5904, with 16/45 (35.6%) samples (with both normal and abnormal baseline semen analysis characteristics) displaying a ≥20% increase in sperm penetrated through viscous media (P < 0.003). LIMITATIONS, REASONS FOR CAUTION: This was an in vitro study. WIDER IMPLICATIONS OF THE FINDINGS: Treatment with AZD5904 resulted in significant increased sperm penetration in one of three samples treated, which is likely to represent improvement in sperm function required for fertilization. We are now planning a clinical trial to validate these results and hope that this could represent a new treatment for male infertility. STUDY FUNDING/COMPETING INTEREST(S): AZD5904 was shared through the AstraZeneca Open Innovation program. The study was funded by AstraZeneca and sponsored by the University of Dundee. Additional funding was provided by Chief Scientist Office/NHS Research Scotland (S.J.M.d.S.). A.W. and H.J.S. are both full time employees of AstraZeneca. A.W. and H.J.S. are inventors on a patent filed by AstraZeneca titled MPOi for use in medicine which includes MPOi for use in the treatment of male infertility (WO 2019/016074 Al). S.J.M.d.S. is Associate Editor of Human Reproduction and Editorial Board member of Reproduction & Fertility. C.L.R.B. is Editor of RBMO and has received lecturing fees from Merck and Ferring and is on the Scientific Advisory Panel for Ohana BioSciences. C.L.R.B. was chair of the World Health Organization Expert Synthesis Group on Diagnosis of Male infertility (2012-2016). C.L.R.B. has a patent WO2013054111 A1 issued. The other authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Factors impacting HIV testing: a review--perspectives from Australia, Canada, and the UK.

With the current global focus on strengthening HIV prevention through greater testing and treatment uptake, it is increasingly salient to identify and address barriers to testing. A review of the published, peer-reviewed literature and national reports from Australia, Canada, and the UK (2003-2013) on barriers to HIV testing was conducted to provide new information relevant to Australia and to complement earlier reviews from Canada and the UK. A systematic database search using keywords and a set of inclusion criteria yielded 36 studies (Australia = 13; Canada = 6; and the UK = 17). In addition 17 unpublished reports were included in the review. Our study uses a novel, comprehensive framework to describe barriers to HIV testing, and thus contributes to moving beyond the traditional patient-provider-system categorization. Within that framework, barriers are categorized as either intrapersonal (reported in 15 studies), interpersonal (21), or extrapersonal (16) and conceptualized within wider sociocultural and structural contexts. People's abilities and motivations to test (intrapersonal factors) are influenced by a host of interconnected factors spanning relationship (interpersonal) and broader socioeconomic, political and cultural (extrapersonal) factors. We suggest that the relative effects of interventions targeting barriers to HIV testing at the intrapersonal and interpersonal levels are limited by the extent to which the social determinants of health are addressed. The framework may also lend itself to thinking about the enabling factors for HIV testing, and future research may investigate the application of that framework for strategizing the most effective response. Future studies should also capture the lived experiences of barriers to HIV testing experienced by patients, especially in populations which are hard to reach based on social and geographic distance. Context-specific studies to evaluate the feasibility and effectiveness of various interventions proposed in the literature to address barriers to HIV testing are needed.

Factors associated with antiretroviral treatment uptake and adherence: a review. Perspectives from Australia, Canada, and the United Kingdom.

International focus on reducing onward HIV transmission emphasizes the need for routine HIV testing and early uptake of antiretroviral treatment (ART). Strategic targets have been set for 2020 to achieve the goal of 90% of people infected with HIV diagnosed, 90% of identified cases on treatment, and 90% of persons on treatment virally suppressed (90-90-90). It is vital to understand the complexity of factors influencing a person's treatment decisions over time and the context which may enable better adherence. In this paper we present findings from the review of published and gray literature (2003-2013) on the documented factors associated with treatment initiation and adherence in the general adult population of Australia, Canada, and the UK. A framework developed by Begley, McLaws, Ross, and Gold [2008. Cognitive and behavioural correlates of non-adherence to HIV anti-retroviral therapy: Theoretical and practical insight for clinical psychology and health psychology. Clinical Psychologist, 12(1), 9-17] in Australia was adapted to summarize the findings. A systematic database search using keywords and a set of inclusion criteria yielded 17 studies (Australia = 6; Canada = 8; UK = 3). In addition 11 reports were included in the review. We found that a person's abilities and motivations (intrapersonal factors, reported in 7 studies) to start and continue ART are influenced by a host of interconnected factors spanning relationship (interpersonal, 3 studies) and broader structural (extrapersonal, 15 studies) factors that are situated within social determinants of health. People therefore evaluate various costs and benefits of starting and staying on treatment, in which biomedical concerns play an important yet often subsidiary role. In this review the economic barriers to care were found to be significant and under-reported, highlighting the persistent health inequities in terms of access to services. Our understanding of the context around people's use of ART remains poor. Qualitative social research within HIV-positive communities is urgently needed to capture people's lived experiences and may address some of this deficit in understanding.

Women's expectations and experiences of hormone treatment for sexual dysfunction.

OBJECTIVES: There is a paucity of information regarding women's expectations of medical treatment for female sexual dysfunction (FSD) and their self-appraisal of treatment outcomes. The aims of this study were to explore women's perception and expectations of treatment and their experiences of treatment for FSD using a qualitative approach. METHODS: First-time attendees to an endocrinologist with the complaint of sexual difficulties were identified and were invited to take part in an in-depth interview on the same day as, but prior to, their medical consultation. Follow-up phone interview took place 3-4 months later. RESULTS: Seventeen women, aged 26-70 years, participated in the face-to-face interview. Ten of these participated in the follow-up interview. Four major themes emerged from the women's narrative stories: (1) personal psychological distress associated with FSD, (2) concern about the adverse effect of FSD on the relationship with their sexual partner, (3) a belief in a relationship between FSD and 'hormone deficiency', and (4) an expectation of treatment, which included positive physical and sexual changes. CONCLUSIONS: Health professionals should be aware of the high degree of psychological distress that can result from FSD and consider available treatment options, which may include hormone therapy.

Perineuronal net structure as a non-cellular mechanism contributing to affective state: A scoping review.

Affective state encompasses emotional responses to our physiology and influences how we perceive and respond within our environment. In affective disorders such as depression, cognitive adaptability is challenged, and structural and functional brain changes have been identified. However, an incomplete understanding persists of the molecular and cellular mechanisms at play in affective state. An exciting area of newly appreciated importance is perineuronal nets (PNNs); a specialised component of extracellular matrix playing a critical role in neuroprotection and synaptic plasticity. A scoping review found 24 studies demonstrating that PNNs are still a developing field of research with a promising general trend for stress in adulthood to increase the intensity of PNNs, whereas stress in adolescence reduced (potentially developmentally delayed) PNN numbers and intensity, while antidepressants correlated with reduced PNN numbers. Despite promising trends, limited research underscores the need for further exploration, emphasizing behavioral outcomes for validating affective states. Understanding PNNs' role may offer therapeutic insights for depression and inform biomarker development, advancing precision medicine and enhancing well-being.

A new member of the IL-1 receptor family highly expressed in hippocampus and involved in X-linked mental retardation.

We demonstrate here the importance of interleukin signalling pathways in cognitive function and the normal physiology of the CNS. Thorough investigation of an MRX critical region in Xp22.1-21.3 enabled us to identify a new gene expressed in brain that is responsible for a non-specific form of X-linked mental retardation. This gene encodes a 696 amino acid protein that has homology to IL-1 receptor accessory proteins. Non-overlapping deletions and a nonsense mutation in this gene were identified in patients with cognitive impairment only. Its high level of expression in post-natal brain structures involved in the hippocampal memory system suggests a specialized role for this new gene in the physiological processes underlying memory and learning abilities.

Blunted cardiovascular reactivity to acute psychological stress predicts low behavioral but not self-reported perseverance: A replication study.

Emerging evidence suggests that individuals with poor behavioral perseverance show low or blunted physiological responses to acute psychological stress. For example, a recent preliminary laboratory study demonstrated that blunted responders give up sooner and take fewer attempts when endeavoring to complete an impossible puzzle, but do not self-report poor perseverance. This present research is a replication of the previous study with an increased sample size, longer recovery periods between tasks and addition of social evaluation to the cold pressor. Participants (147) completed a self-report perseverance questionnaire (Short Grit Scale) and behavioral perseverance tasks (impossible Euler puzzle and socially evaluated cold-pressor (SECPT)). The number of attempts and time spent trying to complete the unsolvable puzzle, and duration of hand submergent during the SECPT, were recorded as behavioral perseverance measures. Difference in blood pressure (BP) and pulse rate (PR) from baseline to a 10-min paced auditory serial addition task (PASAT) were computed as reactivity. As previously, reactivity did not relate to self-reported perseverance and blunted BP reactivity to the PASAT was associated with less time persevering at the unsolvable puzzle. Additionally, blunted BP and PR reactivity to the PASAT related to poorer perseverance during the SECPT. These findings, replicating the previous study, increase confidence that blunted reactivity is a physiological marker of poor behavioral perseverance. Moreover, given that self-reported perseverance does not relate to reactivity, this suggests that blunted responders are not conscious of this detriment in perseverance, but likely need additional support when persistence is critical (e.g., during behavior change).

Investigation of the microstructure of milk protein concentrate powders during rehydration: alterations during storage.

The aim of this work was to use scanning electron microscopy to investigate the microstructure of rehydrated milk protein concentrate powder (MPC) particles. A sample preparation method for scanning electron microscopy analysis of rehydrated MPC particles is described and used to characterize the time course of dissolution and the effects of prior storage on the dissolution process. The results show that a combination of different types of interactions (e.g., bridges, direct contact) between casein micelles results in a porous, gel-like structure that restrains the dispersion of individual micelles into the surrounding liquid phase without preventing water penetration and solubilization of nonmicellar components. During storage of the powder, increased interactions occur between and within micelles, leading to compaction of micelles and the formation of a monolayer skin of casein micelles packed close together, the combination of which are proposed to be responsible for the slow dissolution of stored MPC powders.

Carbon: a new view of its high-temperature behavior.

An increasing body of research indicates that carbon can exist in a number of polymorphic "carbyne" forms. It is proposed that these forms occur because of a shift to triple bonding in the carbon system as temperature increases above 2600 K. It is also proposed that graphite can dissociate into triple-bonded molecules by a simple mechanism.

Carbon: a suggested new hexagonal crystal form.

Evidence for a new polymorphic form of carbon, similar to but distinct from chaoite, has been discovered. It is trigonal, with a(0) = 5.33 angstroms and c(0) = 12.24 angstroms. It is produced along with chaoite on the surfaces of graphitic carbons under free-vaporization conditions at low pressures, with temperatures above approximately 2550 degrees K.

Carbon: observations on the new allotropic form.

The recently characterized " white " allotropic form of carbon has been produced at high temperature and low pressure during graphite sublimation. Under free-vaporization conditions above approximately 2550 degrees K, the white carbon forms as small transparent crystals on the edges of the basal planes of graphite. The interplanar spacings of this material are identical to those of a carbon form noted in graphitic gneiss from the Ries Crater.

Carbynes: carriers of primordial noble gases in meteorites.

Five carbynes (triply bonded allotropes of carbon) have been found by electron diffraction in the Allende and Murchison carbonaceous chondrites: carbon VI, VIII, X, XI, and (tentatively) XII. From the isotopic composition of the associated noble-gas components, it appears that the carbynes in Allende (C3V chondrite) are local condensates from the solar nebula, whereas at least two carbynes in Murchison (C2 chondrite) are of exotic, presolar origin. They may be dust grains that condensed in stellar envelopes and trapped isotopically anomalous matter from stellar nucleosynthesis.

Stabling causes a significant increase in the pH of the equine airway.

Regulation of pH homeostasis in the equine lung is poorly understood. Measurement of exhaled breath condensate (EBC) pH provided a simple, highly repeatable and noninvasive method for the longitudinal investigation of changes in airway pH in response to environmental changes. Stabling of horses was found to lead to a small (approximately 100-200 parts/billion) but significant (P < 0.001) increase in ambient ammonia concentration when compared to pasture. This increase in exposure to ambient ammonia concentration was associated with significant (P = 0.002) increases in EBC pH and exhaled ammonia (P = 0.013). Stable feed/bedding management type had no effect on EBC pH or exhaled ammonia concentration, while ambient ammonia concentration was influenced by stable management type.

Impact of 3D echocardiography on grading of mitral stenosis and prediction of clinical events

Background: The mitral valve orifice area (MVOA) is difficult to assess accurately by 2D echocardiography because of geometric assumptions; therefore, 3D planimetry may offer advantages. We studied the differences in MVOA measurements between the most frequently used methods, to determine if 3D planimetry would result in the re-grading of severity in any cases, and whether it was a more accurate predictor of clinical outcomes. Methods: This was a head-to-head comparison of the three most commonly used techniques to grade mitral stenosis (MS) by orifice area and to assess their impact on clinical outcomes. 2D measurements (pressure half-time (PHT), planimetry) and 3D planimetry were performed retrospectively on patients with at least mild MS. The clinical primary endpoint was defined as a composite of MV balloon valvotomy, mitral valve repair or replacement (MVR) and/or acute heart failure (HF) admissions. Results: Forty-one consecutive patients were included; the majority were female (35; 85.4%), average age 55 (17) years. Mean and peak MV gradients were 9.4 (4) mmHg and 19 (6) mmHg, respectively. 2D and 3D measures of MVOA differed significantly; mean 2D planimetry MVOA was 1.28 (0.40) cm2, mean 3D planimetry MVOA 1.15 (0.29) cm2 (P = 0.003). Mean PHT MVOA was 1.43 (0.44) cm2 (P = 0.046 and P < 0.001 in comparison to 2D and 3D planimetry methods, respectively). 3D planimetry reclassified 7 (17%) patients from mild-to-moderate MS, and 1 (2.4%) from moderate to severe. Overall, differences between the two methods were significant (X2, P < 0.001). Only cases graded as severe by 3D predicted the primary outcome measure compared with mild or moderate cases (odds ratio 5.7). Conclusion: 3D planimetry in MS returns significantly smaller measurements, which in some cases results in the reclassification of severity. Routine use of 3D may significantly influence the management of MS, with a degree of prediction of clinical outcomes.

Female rats display fewer optimistic responses in a judgment bias test in the absence of a physiological stress response.

Metabolic cages are a type of housing used in biomedical research. Metabolic cage housing has been demonstrated to elicit behavioural and physiological changes in rodents housed within them. The nature of this effect has been characterized as anxiogenic. However, few studies have evaluated positive affect in response to metabolic cage housing and the interaction between this, sex and traditional physiological measures of stress. Cognitive biasing, as measured through a judgment bias paradigm has proven a reliable measure of animal affective state, particularly through its ability to measure positive affect. The current study investigated differences in cognitive biasing between male and female rats when transferred from open-top, grouped housing to a metabolic cage. Rats (Rattus norvegicus) (n=60) were trained in a judgment bias paradigm previously validated for use in the rat model. Upon exposure to an intermediate, ambiguous probe rats responded with either an optimistic or pessimistic decision. The animals were also subjected to the sucrose preference test to identify the presence of anhedonia. Faecal corticosterone and changes in adrenal tyrosine hydroxylase were also measured to establish whether a stress-like state was experienced. There was a significant interaction between sex and metabolic cage housing on the number of optimistic decisions made F (1, 56)=7.461, p=0.008. Female rats that remained in control housing responded with a reduced number of days featuring an optimistic decision compared to males in control housing (p=0.036). However, both males and females responded with significantly fewer optimistic decisions in the metabolic cage compared to control (p<0.001). There was a significant negative correlation between treatment and sucrose consumption (rpb=-0.654, n=195, p<0.001). There was also a significant sex effect for faecal corticosterone concentrations F (1, 30)=6.305, p=0.018) with female rats (4.050±1.285), displaying greater corticosterone concentrations than males (2.291±0.495). No differences between treatment were observed for either corticosterone or tyrosine hydroxylase levels. This data demonstrates that movement into a metabolic cage resulted in rats displaying significantly greater pessimistic cognitive biases as determined through the judgment bias test. Interestingly, male rats that remained in control housing demonstrated cognitive biases that were not equivalent to female rats. Furthermore, despite a behavioural change being evident, a physiological change in corticosterone or tyrosine hydroxylase levels was not observed.

Bioreactivity of particulate matter in Beijing air: results from plasmid DNA assay.

An in vitro plasmid assay was employed to study the bioreactivity of PM (particulate matter) in Beijing air. It was found that the TD20 (toxic dose of PM causing 20% of plasmid DNA damage) of Beijing PM can be as low as 28 microg ml(-1) and as high as >1000 microg ml(-1). Comparison of the physical properties, such as morphology and size distribution, and oxidative potential indicates that the PM(2.5) (particulate matter with an aerodynamic diameter of 2.5 microm or less) has a stronger oxidative capacity than PM(10) (particulate matter with an aerodynamic diameter of 10 microm or less), and that the higher number percentages of soot aggregates and lower number percentages of mineral and fly ashes are associated with the higher oxidative capacity. Although the mass of PM(10) during dust storms is commonly 5 times higher than that during non-dust storm episodes, the oxidative capacity of PM(10)s of dust storms is much lower than that of the non-dust storm PM(10)s. The water-soluble fractions and intact whole particle solutions of Beijing airborne particles produce similar plasmid assay results, demonstrating that the bioreactivity of Beijing airborne particles is mainly sourced from the water-soluble fraction. In the samples with stronger bioreactivity, the total analyzed water soluble Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As and Pb (ppm) concentrations are higher. The water soluble zinc shows a good negative correlation with TD20s, suggesting that the water-soluble zinc is probably the major element responsible for the plasmid DNA damage.