A Group Randomized Controlled Trial of Relationships Under Construction Sexual Risk Avoidance Education.

BACKGROUND: We analyzed data from a study to evaluate the effectiveness of the Relationships Under Construction (RUC) sexual risk avoidance education program promoting positive youth development and healthy relationships. METHODS: Twelve schools in the Midwestern region of the United States randomized to the intervention implemented RUC in health or science classes, while control schools collected study measures and implemented the standard curriculum. RESULTS: Post-randomization analyses revealed significant differences in grade, race/ethnicity, and prior relationship education at baseline between intervention and control students. Subsequent analyses controlled for these differences. We distributed parental notification letters to 641 students, and no parents requested that their adolescent opt out of data collection. We obtained assent and baseline computer-assisted survey interviews or paper-and-pencil instrument forms from 100% of these students. Findings suggest that RUC significantly reduced sexual activity (odds ratio = 0.56, p = .046) at 3-month follow-up, compared to those in the control group. RUC also reduced pornography viewing and improved attitudes about delayed gratification, beliefs, decision making, and negative outcome expectations. CONCLUSIONS: Our findings suggest that RUC improves sexual attitudes, beliefs, and behaviors among this population of adolescents. Additional research is needed to assess RUC impacts among diverse populations.

Intimate partner violence exposure during infancy and social functioning in middle childhood: An Australian mother and child cohort study.

Social functioning of children with experiences of intimate partner violence (IPV) between caregivers in early childhood has received less attention than emotional-behavioral outcomes. Drawing on data from 1507 ten-year-old Australian-born children and their mothers participating in a community-based longitudinal study, this study examined the associations between IPV exposure during infancy and social development during middle childhood. IPV during the first 12 months of life was associated with lower social skills, higher peer problems, and peer victimization at age 10 years, while accounting for concurrent IPV. This study provides evidence for the long-term impacts of early-life IPV exposure on children's social functioning, and the importance of prevention and early intervention programs focused on social development following experiences of IPV.

Mothers' experiences of emotional abuse from an intimate partner and its associations with children's developmental outcomes at 5 years.

BACKGROUND: Intimate partner violence (IPV) is associated with an increased risk of poorer child development. Existing research has focused on physical abuse with less known about the associations with emotional IPV. OBJECTIVE: To describe the period prevalence of mother's experiences of emotional IPV during children's preschool years and associations with child mental, physical, social, and cognitive development. METHODS: Secondary analysis of control group data (n = 194) from an Australian randomised trial (right@home), which recruited pregnant women experiencing social adversity from antenatal clinics in 2013-14. Women reported emotional abuse (Composite Abuse Scale) at child ages 3-5 years. Measures of child development at 5 years included: Strengths and Difficulties Questionnaire, Social Skills Improvement System, Pediatric Quality of Life Inventory, Clinical Evaluation of Language Fundamentals, School Entry Alphabetic and Phonological Awareness Readiness Test, NIH executive function subtests, sleep and health. The prevalence of emotional IPV from 3 to 5 years was estimated. Regression models compared developmental outcomes according to emotional IPV exposure, adjusted for child age, child gender, and maternal education. Missing data were accounted for using multiple imputation. RESULTS: From 3-5 years, emotional IPV was experienced by 57% of women. Emotional IPV exposure was consistently associated with poorer child developmental outcomes. Differences were most apparent for SDQ internalising (mean difference 1.2, 95% CI 0.2 to 2.1) and externalising difficulties (1.2, 95% CI -0.1 to 2.4). CONCLUSIONS: Emotional IPV was highly prevalent amongst families experiencing social adversity. Developing acceptable and effective identification processes and interventions that prioritise families experiencing co-occurring social adversities should be a public health priority.

A randomised controlled trial of long NY-ESO-1 peptide-pulsed autologous dendritic cells with or without alpha-galactosylceramide in high-risk melanoma.

AIM: We have previously reported that polyfunctional T cell responses can be induced to the cancer testis antigen NY-ESO-1 in melanoma patients injected with mature autologous monocyte-derived dendritic cells (DCs) loaded with long NY-ESO-1-derived peptides together with α-galactosylceramide (α-GalCer), an agonist for type 1 Natural Killer T (NKT) cells. OBJECTIVE: To assess whether inclusion of α-GalCer in autologous NY-ESO-1 long peptide-pulsed DC vaccines (DCV + α-GalCer) improves T cell responses when compared to peptide-pulsed DC vaccines without α-GalCer (DCV). DESIGN, SETTING AND PARTICIPANTS: Single-centre blinded randomised controlled trial in patients ≥ 18 years old with histologically confirmed, fully resected stage II-IV malignant cutaneous melanoma, conducted between July 2015 and June 2018 at the Wellington Blood and Cancer Centre of the Capital and Coast District Health Board. INTERVENTIONS: Stage I. Patients were randomised to two cycles of DCV or DCV + α-GalCer (intravenous dose of 10 × 106 cells, interval of 28 days). Stage II. Patients assigned to DCV + α-GalCer were randomised to two further cycles of DCV + α-GalCer or observation, while patients initially assigned to DCV crossed over to two cycles of DCV + α-GalCer. OUTCOME MEASURES: Primary: Area under the curve (AUC) of mean NY-ESO-1-specific T cell count detected by ex vivo IFN-γ ELISpot in pre- and post-treatment blood samples, compared between treatment arms at Stage I. Secondary: Proportion of responders in each arm at Stage I; NKT cell count in each arm at Stage I; serum cytokine levels at Stage I; adverse events Stage I; T cell count for DCV + α-GalCer versus observation at Stage II, T cell count before versus after cross-over. RESULTS: Thirty-eight patients gave written informed consent; 5 were excluded before randomisation due to progressive disease or incomplete leukapheresis, 17 were assigned to DCV, and 16 to DCV + α-GalCer. The vaccines were well tolerated and associated with increases in mean total T cell count, predominantly CD4+ T cells, but the difference between the treatment arms was not statistically significant (difference - 6.85, 95% confidence interval, - 21.65 to 7.92; P = 0.36). No significant improvements in T cell response were associated with DCV + α-GalCer with increased dosing, or in the cross-over. However, the NKT cell response to α-GalCer-loaded vaccines was limited compared to previous studies, with mean circulating NKT cell levels not significantly increased in the DCV + α-GalCer arm and no significant differences in cytokine response between the treatment arms. CONCLUSIONS: A high population coverage of NY-ESO-1-specific T cell responses was achieved with a good safety profile, but we failed to demonstrate that loading with α-GalCer provided an additional advantage to the T cell response with this cellular vaccine design. CLINICAL TRIAL REGISTRATION: ACTRN12612001101875. Funded by the Health Research Council of New Zealand.

A longitudinal study of the relationships between sleep problems in autistic children and maternal mental health.

LAY ABSTRACT: Autistic children experience increased the rates of sleep problems. These sleep problems have been associated with mother's mental health symptoms. However, the direction of these relationships is not well understood. This study investigated the relationships between autistic children's sleep problems and mothers' mental health over a 12-year period using data collected as part of the Longitudinal Study of Australian Children. Data from 397 autistic children and their mothers were included in this study. Mothers completed a questionnaire about their own mental health and common childhood sleep problems at four time points from 4-5 years to 14-15 years. The results showed important relationships between mothers' mental health symptoms and child sleep problems at two time points. Specifically, (1) mothers' mental health symptoms when the child was aged 4 to 5 years predicted child sleep problems at age 6 to 7 years; and (2) child sleep problems at age 12-13 years predicted mothers' mental health symptoms when the child was aged 14 to 15 years. Interestingly, these significant relationships also coincide with key developmental transition time points, when the child is transitioning in and out of primary school. These findings highlight the need for increased support for both the child and mother at these times to optimise outcomes for both.

Cytokine Activation Reveals Tissue-Imprinted Gene Profiles of Mesenchymal Stromal Cells.

Development of standardized metrics to support manufacturing and regulatory approval of mesenchymal stromal cell (MSC) products is confounded by heterogeneity of MSC populations. Many reports describe fundamental differences between MSCs from various tissues and compare unstimulated and activated counterparts. However, molecular information comparing biological profiles of activated MSCs across different origins and donors is limited. To better understand common and source-specific mechanisms of action, we compared the responses of 3 donor populations each of human umbilical cord (UC) and bone marrow (BM) MSCs to TNF-α, IL-1ß or IFN-γ. Transcriptome profiles were analysed by microarray and select secretome profiles were assessed by multiplex immunoassay. Unstimulated (resting) UC and BM-MSCs differentially expressed (DE) 174 genes. Signatures of TNF-α-stimulated BM and UC-MSCs included 45 and 14 new DE genes, respectively, while all but 7 of the initial 174 DE genes were expressed at comparable levels after licensing. After IL-1ß activation, only 5 of the 174 DE genes remained significantly different, while 6 new DE genes were identified. IFN-γ elicited a robust transcriptome response from both cell types, yet nearly all differences (171/174) between resting populations were attenuated. Nine DE genes predominantly corresponding to immunogenic cell surface proteins emerged as a BM-MSC signature of IFN-γ activation. Changes in protein synthesis of select analytes correlated modestly with transcript levels. The dynamic responses of licensed MSCs documented herein, which attenuated heterogeneity between unstimulated populations, provide new insight into common and source-imprinted responses to cytokine activation and can inform strategic development of meaningful, standardized assays.

From Vial to Vein: Crucial Gaps in Mesenchymal Stromal Cell Clinical Trial Reporting.

Retrospective analysis of clinical trial outcomes is a vital exercise to facilitate efficient translation of cellular therapies. These analyses are particularly important for mesenchymal stem/stromal cell (MSC) products. The exquisite responsiveness of MSCs, which makes them attractive candidates for immunotherapies, is a double-edged sword; MSC clinical trials result in inconsistent outcomes that may correlate with underlying patient biology or procedural differences at trial sites. Here we review 45 North American MSC clinical trial results published between 2015 and 2021 to assess whether these reports provide sufficient information for retrospective analysis. Trial reports routinely specify the MSC tissue source, autologous or allogeneic origin and administration route. However, most methodological aspects related to cell preparation and handling immediately prior to administration are under-reported. Clinical trial reports inconsistently provide information about cryopreservation media composition, delivery vehicle, post-thaw time and storage until administration, duration of infusion, and pre-administration viability or potency assessments. In addition, there appears to be significant variability in how cell products are formulated, handled or assessed between trials. The apparent gaps in reporting, combined with high process variability, are not sufficient for retrospective analyses that could potentially identify optimal cell preparation and handling protocols that correlate with successful intra- and inter-trial outcomes. The substantial preclinical data demonstrating that cell handling affects MSC potency highlights the need for more comprehensive clinical trial reporting of MSC conditions from expansion through delivery to support development of globally standardized protocols to efficiently advance MSCs as commercial products.

Working out dads (WOD): a study protocol for a randomised controlled trial of a group-based peer support intervention for men experiencing mental health difficulties in early fatherhood.

BACKGROUND: Approximately one in ten men experience mental health difficulties during the early years of fatherhood, and these can have negative impacts on children and families. However, few evidence-based interventions targeting fathers' mental health are available. The aim of the trial is to evaluate the effectiveness and cost-effectiveness of Working Out Dads (WOD) - a facilitated peer support group intervention for fathers of young children, in reducing psychological distress and other mental health symptoms. METHODS: This trial will employ a parallel-arm randomised controlled trial (RCT) to evaluate the effectiveness and cost effectiveness of WOD peer support group intervention compared to usual care (a 30-min mental health and service focused phone consultation with a health professional). A total of 280 fathers of young children (aged 0-4 years) who are experiencing mental health difficulties and/or are at risk of poor mental health will be recruited. Randomisation and analyses will be at the level of the individual participant. The primary outcome is psychological distress symptoms, measured by the Kessler Psychological Distress Scale (K10) from baseline to 24 weeks post randomisation. A range of secondary outcomes will be assessed including suicidal ideation; mental health disorders, specific symptoms of depression, anxiety, and stress; social support, quality of life, health service use, and health care costs. Data will be collected at baseline, 10- and 24 weeks post-randomisation. DISCUSSION: This trial will examine the effectiveness of a novel group-based peer support intervention in reducing the psychological distress and other mental health symptoms of fathers compared to usual care. The economic and process evaluation will guide policy decision making along with informing the future implementation of WOD on a larger scale if effectiveness is demonstrated. TRIAL REGISTRATION: The current trial has been registered with ClinicalTrials.gov (Registration ID - NCT04813042 ). Date of Registration: March 22nd, 2021.

Trajectories of interparental conflict and children's emotional-behavioural functioning at 10-11 years: an Australian population-based study.

Interparental conflict (IPC) has the potential to adversely affect children's social, emotional, and behavioural functioning. The overall objective of this study was to investigate the relationship between both the severity and chronicity of IPC across early and middle childhood and children's emotional-behavioural functioning at 10-11 years. Specifically, we aimed to: (1) identify distinct trajectories of IPC spanning 10-11 years since birth of the study child as reported by mothers, and (2) examine the emotional-behavioural functioning of children exposed to the identified IPC trajectories. Drawing from a nationally representative longitudinal study of Australian families (N = 4875), four distinct trajectories of IPC were identified: (1) consistently low exposure to IPC over time, (2) persistently elevated exposure to IPC, (3) increasing IPC exposure over time, and (4) decreasing IPC exposure over time. Children exposed to trajectories with high IPC at any point during the study period were reported by their mothers to be experiencing more emotional-behavioural difficulties than children exposed to low IPC over time. Based on teacher report, there were no differences in emotional-behavioural functioning of children exposed to the different patterns of IPC. Our findings reinforce that high parental conflict at any point in a child's life is a form of adversity that can have adverse consequences for their mental health, and that early interventions for parents and caregivers experiencing high IPC are critical.

The cost of pharmacovigilance: a time and motion study of an adverse drug reaction program.

OBJECTIVES: Adverse medication events are associated with a significant number of hospital admissions, and the appropriate recording of these events plays a vital role in medication safety. We set out to analyse the time and extrapolated cost in reporting adverse drug reactions (ADRs). METHODS: A time and motion study of the tasks involved in reviewing, assessing, reporting and communicating ADRs was done over a period of 2 months. KEY FINDINGS: We found a median of 69 min was needed in background work per ADR report. CONCLUSION: The commitment involved in the support of this program is considerable and will encourage further refinement to streamline the process.

"We're in the background": Facilitators and barriers to fathers' engagement and participation in a health intervention during the early parenting period.

ISSUES ADDRESSED: Little is known about the barriers and facilitators associated with engaging fathers in interventions targeting their physical and mental health. The current research therefore aimed to explore fathers' perceived barriers and facilitators to engagement and participation in a health intervention delivered during the early parenting period. METHODS: Eleven fathers of young children (0-4 years) were interviewed about their perceptions and experiences of facilitators and barriers to engaging and participating in an intervention (Working Out Dads) to target their mental and physical health. Interviews were recorded and transcribed. Transcripts were analysed using thematic analysis. RESULTS: Fathers identified a number of program-related and father-related facilitators and barriers which impacted their engagement and participation. Program-related facilitators included: accessibility of the program; father advocacy of the program; group fitness/exercise component; and having a father-specific program. Facilitating factors related to fathers included: making social connections; learning how to be a better dad/partner; and partner support and encouragement to attend. Program-related barriers included: travel; lack of awareness; and gender roles. While father-related barriers included: being time poor; sacrifices to family; and apprehension. CONCLUSIONS: The current findings identified many areas that facilitate, encourage and motivate men to participate in interventions which support their mental and physical health during the early parenting period. RELEVANCE: Generating evidence on barriers and facilitators to health interventions is important to improving the current intervention along with informing the development of engaging and targeted health interventions for fathers in early parenthood.

Mothers' Experiences of Parenting Within the Context of Intimate Partner Violence: Unique Challenges and Resilience.

Maternal and child health are strongly linked, particularly in the presence of intimate partner violence (IPV). Women who experience IPV are at increased risk of negative physical and mental health difficulties. However, little is known about the experience of mothering within the context of IPV and what mothers perceive as contributing to resilience. This study had two aims. First, to explore women's experience and perceived challenges associated with being a mother within the context of being in a relationship where IPV is being used. Second, to explore what mothers found helpful in coping during this experience. A nested qualitative sub-study was conducted within a prospective study of mothers during pregnancy and following the birth of their first child. Nine women who reported experiencing IPV since becoming pregnant with their first child participated in semi-structured qualitative interviews, which were then transcribed and analyzed using interpretive phenomenological analysis (IPA). Three subthemes emerged within the theme of unique challenges experienced by mothers. These were partner control over parenting, other disrespectful and controlling behavior, and emotional exhaustion. Within the theme of mothers' sense of resilience and coping, career development, making sense of experiences, focusing on children, and help-seeking played important roles in helping mothers manage these difficulties. Our findings highlighted the impact that IPV can have on the experience of mothering and the importance of prioritizing women's health and well-being. Finally, these findings emphasize the importance of health-care professionals identifying and acknowledging the signs of IPV to support women to speak out about their experiences.

Vitamin B12 deficiency and altered one-carbon metabolites in early pregnancy is associated with maternal obesity and dyslipidaemia.

Vitamin B12 (B12) is a micronutrient essential for one-carbon (1C) metabolism. B12 deficiency disturbs the 1C cycle and alters DNA methylation which is vital for most metabolic processes. Studies show that B12 deficiency may be associated with obesity, insulin resistance and gestational diabetes; and with obesity in child-bearing women. We therefore hypothesised that the associations between B12 deficiency, BMI and the metabolic risk could be mediated through altered 1C metabolites in early pregnancy. We explored these associations in two different early pregnancy cohorts in the UK (cohort 1; n = 244 and cohort 2; n = 60) with anthropometric data at 10-12 weeks and plasma/serum sampling at 16-18 weeks. B12, folate, total homocysteine (tHcy), methionine, MMA, metabolites of 1C metabolism (SAM, SAH) and anthropometry were measured. B12 deficiency (< 150 pmol/l) in early pregnancy was 23% in cohort 1 and 18% in cohort 2. Regression analysis after adjusting for likely confounders showed that B12 was independently and negatively associated with BMI (Cohort 1: ß = - 0.260, 95% CI (- 0.440, - 0.079), p = 0.005, Cohort 2: (ß = - 0.220, 95% CI (- 0.424, - 0.016), p = 0.036) and positively with HDL cholesterol (HDL-C) (ß = 0.442, 95% CI (0.011,0.873), p = 0.045). We found that methionine (ß = - 0.656, 95% CI (- 0.900, - 0.412), p < 0.0001) and SAH (ß = 0.371, 95% CI (0.071, 0.672), p = 0.017) were independently associated with triglycerides. Low B12 status and alteration in metabolites in 1C metabolism are common in UK women in early pregnancy and are independently associated with maternal obesity and dyslipidaemia. Therefore, we suggest B12 monitoring in women during peri-conceptional period and future studies on the pathophysiological relationship between changes in 1C metabolites and its association with maternal and fetal outcomes on larger cohorts. This in turn may offer potential to reduce the metabolic risk in pregnant women and their offspring.

Promoting resilience and wellbeing in children exposed to intimate partner violence: A qualitative study with mothers.

BACKGROUND: Children exposed to intimate partner violence (IPV) are at increased risk of disruptions to their health and development. Few studies have explored mothers' perceptions of what helps their children cope throughout this experience. OBJECTIVE: The aim of the study was to explore mothers' perceptions of their children's resilience and coping following IPV exposure, and the strategies they have used to support their children and promote resilience. METHODS: In depth semi-structured interviews were conducted with nine women from the Maternal Health Study (MHS), a prospective study of women during pregnancy and following the birth of their first child. All women involved in the qualitative interviews reported experiencing IPV during their involvement in the MHS. Transcribed interviews were analysed using interpretative phenomenological analysis which has a focus on how individuals make meaning of their experience. RESULTS: Women discussed parenting strategies such as role modelling, stable and consistent parenting, and talking with their children about healthy relationships to promote their children's resilience. Mothers also spoke about the ways they tried to reduce their child's direct exposure to IPV, as well as reflecting on the difficulty of attending to their child emotionally when they were experiencing distress. CONCLUSIONS: This study highlights that there are many strategies used by mothers who experience IPV to promote resilience and wellbeing in their children. Understanding what mothers see as useful for their children is essential in providing appropriate services to families following experiences of family violence.

Human umbilical cord perivascular cells: A novel source of the organophosphate antidote butyrylcholinesterase.

Human butyrylcholinesterase (BChE) is a well-characterized bioscavenger with significant potential as a prophylactic or post-exposure treatment for organophosphate poisoning. Despite substantial efforts, BChE has proven technically challenging to produce in recombinant systems. Recombinant BChE tends to be insufficiently or incorrectly glycosylated, and consequently exhibits a truncated half-life, compromised activity, or is immunogenic. Thus, expired human plasma remains the only reliable source of the benchmark BChE tetramer, but production is costly and time intensive and presents possible blood-borne disease hazards. Here we report a human BChE production platform that produces functionally active, tetrameric BChE enzyme, without the addition of external factors such as polyproline peptides or chemical or gene modification required by other systems. Human umbilical cord perivascular cells (HUCPVCs) are a rich population of mesenchymal stromal cells (MSCs) derived from Wharton's jelly. We show that HUCPVCs naturally and stably secrete BChE during culture in xeno- and serum-free media, and can be gene-modified to increase BChE output. However, BChE secretion from HUCPVCs is limited by innate feedback mechanisms that can be interrupted by addition of miR 186 oligonucleotide mimics or by competitive inhibition of muscarinic cholinergic signalling receptors by addition of atropine. By contrast, adult bone marrow-derived mesenchymal stromal cells neither secrete measurable levels of BChE naturally, nor after gene modification. Further work is required to fully characterize and disable the intrinsic ceiling of HUCPVC-mediated BChE secretion to achieve commercially relevant enzyme output. However, HUCPVCs present a unique opportunity to produce both native and strategically engineered recombinant BChE enzyme in a human platform with the innate capacity to secrete the benchmark human plasma form.

Accumulating Transcriptome Drift Precedes Cell Aging in Human Umbilical Cord-Derived Mesenchymal Stromal Cells Serially Cultured to Replicative Senescence.

In preclinical studies, mesenchymal stromal cells (MSCs) exhibit robust potential for numerous applications. To capitalize on these benefits, cell manufacturing and delivery protocols have been scaled up to facilitate clinical trials without adequately addressing the impact of these processes on cell utility nor inevitable regulatory requirements for consistency. Growing evidence indicates that culture-aged MSCs, expanded to the limits of replicative exhaustion to generate human doses, are not equivalent to early passage cells, and their use may underpin reportedly underwhelming or inconsistent clinical outcomes. Here, we sought to define the maximum expansion boundaries for human umbilical cord-derived MSCs, cultured in chemically defined xeno- and serum-free media, that yield consistent cell batches comparable to early passage cells. Two male and two female donor populations, recovered from cryostorage at mean population doubling level (mPDL) 10, were serially cultivated until replicative exhaustion (senescence). At each passage, growth kinetics, cell morphology, and transcriptome profiles were analyzed. All MSC populations displayed comparable growth trajectories through passage 9 (P9; mPDL 45) and variably approached senescence after P10 (mPDL 49). Transcription profiles of 14,500 human genes, generated by microarray, revealed a nonlinear evolution of culture-adapted MSCs. Significant expression changes occurred only after P5 (mPDL 27) and accumulated rapidly after P9 (mPDL 45), preceding other cell aging metrics. We report that cryobanked umbilical cord-derived MSCs can be reliably expanded to clinical human doses by P4 (mPDL 23), before significant transcriptome drift, and thus represent a mesenchymal cell source suited for clinical translation of cellular therapies. Stem Cells Translational Medicine 2019;8:945&958.

A randomized controlled feasibility trial of paracetamol during febrile neutropenia in hemato-oncology patients.

The efficacy of paracetamol (acetaminophen) as an antipyretic during febrile neutropenia (FN) has not previously been established. We conducted a randomized double-blind placebo-controlled feasibility trial: hemato-oncology patients at high FN risk were randomly assigned to six hourly oral paracetamol (1 g) or placebo during the first 42 hours of FN. Fifty-three participants were screened, thirty-seven enrolled; 22 developed FN and commenced treatment (13 paracetamol; 9 placebo); recruitment rates were below, and retention rates met, pre-defined feasibility criteria. During the first 24 hours of FN, paracetamol recipients had significantly lower peak temperature than placebo: mean 38.2 (standard deviation 0.8) °C versus 38.9 (0.4) °C; difference -0.78 °C (95% CI -1.38 to -0.18); p = .013. Bacterial load measurement was not informative. Paracetamol lowers body temperature during FN, and definitive trials to determine its impact on FN outcomes are needed. Australian New Zealand Clinical Trials Registry reference ACTRN12613000601730; funded by Health Research Council of New Zealand.

Bio-ecological factors associated with the psychological distress of fathers of children with autism spectrum disorder: A population-based study of Australian families.

Using a bio-ecological framework, the aim of this study was to examine factors associated with psychological distress experienced by fathers of children with autism spectrum disorder from a nationally representative sample of Australian children and their families. Individual (e.g. age and self-efficacy), interpersonal (e.g. partner distress, couple relationship, child behaviour and social support) and social environmental factors (e.g. job quality and financial hardship) were explored as potential predictors of fathers' distress. Data were drawn from the Longitudinal Study of Australian Children, where 159 fathers of children with autism spectrum disorder were identified. As comparison, 6578 fathers of children without developmental disabilities were identified. Multiple regression analyses showed that experiencing depression within the past year, job quality (e.g. autonomy and access to parental leave) and social support were significant predictors for fathers of children with autism spectrum disorder. The importance of supporting the well-being of fathers of children with autism spectrum disorder is discussed.

Intramuscular administration potentiates extended dwell time of mesenchymal stromal cells compared to other routes.

BACKGROUND: Mesenchymal stromal cells (MSCs) offer great potential for diverse clinical applications. However, conventional systemic infusion of MSCs limits their therapeutic benefit, since intravenously (IV) infused cells become entrapped in the lungs where their dwell time is short. METHODS: To explore possible alternatives to IV infusion, we used in vivo optical imaging to track the bio-distribution and survival of 1 million bioluminescent MSCs administered IV, intraperitoneally (IP), subcutaneously (SC) and intramuscularly (IM) in healthy athymic mice. RESULTS: IV-infused MSCs were undetectable within days of administration, whereas MSCs implanted IP or SC were only detected for 3 to 4 weeks. In contrast, MSCs sourced from human umbilical cord matrix or bone marrow survived more than 5 months in situ when administered IM. Long-term survival was optimally achieved using low passage cells delivered IM. However, MSCs could undergo approximately 30 doublings before their dwell time was compromised. Cryo-preserved MSCs administered IM promptly after thaw were predominantly cleared after 3 days, whereas equivalent cells cultured overnight prior to implantation survived more than 3 months. DISCUSSION: The IM route supports prolonged cell survival of both neo-natal and adult-derived MSCs, although short-term MSC survival was comparable between all tested routes up to day 3. IM implantation presents a useful alternative to achieve clinical benefits from prolonged MSC dwell time at a homeostatic implant site and is a minimally invasive delivery route suitable for many applications. However, optimized thaw protocols that restore full biological potential of cryo-preserved MSC therapies prior to implantation must be developed.