Understanding how parents influence their child’s medical procedures can inform future work to reduce pediatric procedural distress and improve recovery outcomes. Following a pediatric injury or ...illness diagnosis, the associated medical procedures can be potentially traumatic events that are often painful and distressing and can lead to the child experiencing long-term physical and psychological problems. Children under 6 years old are particularly at risk of illness or injury, yet their pain-related distress during medical procedures is often difficult to manage because of their young developmental level. Parents can also experience ongoing psychological distress following a child’s injury or illness diagnosis. The parent and parenting behavior is one of many risk factors for increased pediatric procedural distress. The impact of parents on pediatric procedural distress is an important yet not well-understood phenomenon. There is some evidence to indicate parents influence their child through their own psychological distress and through parenting behavior. This paper has three purposes: (1) review current empirical research on parent-related risk factors for distressing pediatric medical procedures, and longer-term recovery outcomes; (2) consider and develop existing theories to present a new model for understanding the parent–child distress relationship during medical procedures; and (3) review and make recommendations regarding current assessment tools and developing parenting behavior interventions for reducing pediatric procedural distress.
p53 and HSF1 are two major transcription factors involved in cell proliferation and apoptosis, whose dysregulation contributes to cancer and neurodegeneration. Contrary to most cancers, p53 is ...increased in Huntington’s disease (HD) and other neurodegenerative diseases, while HSF1 is decreased. p53 and HSF1 reciprocal regulation has been shown in different contexts, but their connection in neurodegeneration remains understudied. Using cellular and animal models of HD, we show that mutant HTT stabilized p53 by abrogating the interaction between p53 and E3 ligase MDM2. Stabilized p53 promotes protein kinase CK2 alpha prime and E3 ligase FBXW7 transcription, both of which are responsible for HSF1 degradation. Consequently, p53 deletion in striatal neurons of zQ175 HD mice restores HSF1 abundance and decrease HTT aggregation and striatal pathology. Our work shows the mechanism connecting p53 stabilization with HSF1 degradation and pathophysiology in HD and sheds light on the broader molecular differences and commonalities between cancer and neurodegeneration.
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•PolyQ expansion in HTT exon 1 interferes with Mdm2 E3 ligase and stabilizes p53•Stabilization of p53 in HD leads to the degradation of HSF1 transcription factor•Degradation of HSF1 in HD increases HTT aggregation and striatal pathology•p53cKO in MSNs in zQ175 mice restores HSF1 levels and HD-related phenotypes
Huntington’s disease (HD) is characterized by a selective degeneration of neurons in the striatum. Mansky et al. propose a mechanism by which these neurons degenerate in HD and show that dysregulation of two major transcription factors involved in apoptosis and stress response cooperate to promote protein aggregation and synaptic dysregulation.
To investigate the relation between mental health and disability after a road traffic crash (RTC) up to 24 months for claimants with predominantly minor injuries in an Australian sample.
Longitudinal ...cohort study with survey and telephone interview data collected at approximately 6, 12, and 24 months post-RTC.
Not applicable.
Claimants (N=382) within a common-law, fault-based compulsory third-party motor accident insurance scheme in Queensland, Australia, consented to participate when invited and were approached at each wave. Retention was high (65%) at 2-year follow-up. Disability scores from at least 1 wave were known for 363 participants, with the mean age of participants being 48.4 years and 62% being women.
Not applicable.
Self-reported disability (via the World Health Organization Disability Assessment Schedule 2).
Participants reported higher disability (mean, 10.9±9.3) compared with the Australian norms (mean, 3.1±5.3). A multilevel regression analysis found that predictors of disability included present diagnosis of posttraumatic stress disorder (PTSD), anxiety, or depression, mental health history, perceived threat to life, and pain. PTSD moderated the relation between age and disability such that older age predicted higher disability in the PTSD group only, whereas anxiety moderated the relation between expectation to return to work and disability such that those with low expectations and anxiety reported significantly higher disability.
Claimants with predominantly minor physical injuries report high disability, particularly when comorbid psychiatric disorders are present, pain is high, and expectations regarding return to work are low. Developing tools for detecting those at risk of poor recovery after an RTC is necessary for informing policy and practice in injury management and postinjury rehabilitation.
The sponging of microRNAs by a long non-coding RNA (lncRNA) away from their coding gene targets is a conceptually-simple, yet biologically-complex method of lncRNA-mediated gene regulation. ...Currently, predictions of genes that participate in sponge-based regulation are largely based on sequence homology alone, which may not adequately reflect the cellular environment in which lncRNA:miRNA pairs interact. The vast number of potential interactions generated by these predictions impedes the identification of functional gene regulatory relationships, which necessitates an approach that considers biological context. XIST, the female-specific lncRNA canonically involved in silencing the X chromosome, has been suggested by many studies to act as a miRNA sponge. The sex-specificity of XIST provides the opportunity to study the biological feasibility of proposed XIST-miRNA interactions. Here we take a comprehensive approach by considering factors that affect possible regulation through XIST-miRNA sponging.
To identify the most feasible candidates in a particular tissue (lung adenocarcinomas), we considered protein-coding genes that (1) were positively correlated with XIST expression within sexes, (2) were targeted by miRNAs shared with XIST, and (3) expressed in lung adenocarcinoma. This revealed a robust set of 124 genes potentially positively regulated by XIST through the sequestration of 804 shared miRNAs. We then used the basic sex-specific nature of XIST to compare the changes in miRNA-target gene relationships in endogenously high-XIST and low-XIST systems to discover a high-confidence set of only 13 miRNA-gene pairs. As XIST is expressed exclusively in the nucleus, we validated the nuclear presence of several of these high-confidence miRNAs using RT-qPCR, confirming the co-localization required for XIST to interact with these species.
We use a biology-driven approach to identify genes defended from miRNA-based inhibition by the lncRNA XIST. Importantly, we identify that only a small subset of miRNAs predicted by sequence homology alone have the capacity to mediate the XIST-target gene axis, as they are enriched in the nucleus and able to co-localize with XIST for sponging. Our results reinforce the necessary consideration of biological features in future studies of lncRNA:miRNA interactions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Up to 40% of patients aged ≤55 years undergo concomitant bilateral salpingo-oophorectomy at the time of benign hysterectomy, with practice variation in bilateral salpingo-oophorectomy occurring along ...the lines of patient health and social factors. Disability is common in premenopausal women and is an important determinant of reproductive health more broadly; however, studies on bilateral salpingo-oophorectomy rates among women with disabilities are lacking.
This study aimed to examine whether the use of concomitant bilateral salpingo-oophorectomy at the time of benign hysterectomy differs by preexisting disability status in adult females aged ≤55 years.
This population-based cross-sectional study used data from the 2016–2019 US National Inpatient Sample. Females undergoing inpatient hysterectomy for a benign gynecologic indication (n=74,315) were classified as having physical (6.1%), sensory (0.1%), intellectual or developmental (0.2%), or multiple (0.2%) disabilities and compared with those without a disability. Logistic regression was used to estimate risk ratios for differences in bilateral salpingo-oophorectomy rates by disability status, adjusted for patient and clinical factors. Models were stratified by potentially avoidable or potentially appropriate bilateral salpingo-oophorectomy based on the presence of clinical indications for ovarian removal and by age group.
Bilateral salpingo-oophorectomy at the time of benign hysterectomy occurred in 26.0% of females without a disability, with rates clearly elevated in those with a physical (33.2%; adjusted risk ratio, 1.10; 95% confidence interval, 1.05–1.14) or intellectual or developmental (31.1%; adjusted risk ratio, 1.32; 95% confidence interval, 1.02–1.64) disability, possibly elevated in those with multiple disabilities (38.2%; adjusted risk ratio, 1.20; 95% confidence interval, 0.94–1.45), and similar in those with a sensory disability (31.2%; adjusted risk ratio, 0.98; 95% confidence interval, 0.83–1.13). The results were similar but with lower statistical precision for potentially avoidable and potentially appropriate bilateral salpingo-oophorectomy, which occurred in 9.1% and 17.0% of females without a disability, respectively. The largest differences in bilateral salpingo-oophorectomy rates among women with any disability were observed in the perimenopausal 45- to 49-year age group.
Females with disabilities experienced elevated concomitant bilateral salpingo-oophorectomy rates at the time of benign hysterectomy, particularly those with an intellectual or developmental disability and those of perimenopausal age, although some estimates were imprecise. Equity-focused physician training in surgical counseling and research into the epidemiology and experiences of gynecologic conditions among females with a disability may be beneficial.
Abstract
STUDY QUESTION
What is the association between past infertility and the type and timing of menopause in midlife women?
SUMMARY ANSWER
Women with a history of infertility were more likely to ...experience surgical menopause overall and had elevated risk of earlier surgical menopause until age 43 years but experienced no differences in the timing of natural menopause.
WHAT IS KNOWN ALREADY
Infertility is experienced by 12–25% of women and is thought to reveal a propensity for poor health outcomes, such as chronic illness, later in life. However, little is known about whether infertility is linked with characteristics of the menopausal transition as women age, despite possible shared underlying pathways involving ovarian function and gynecologic disease.
STUDY DESIGN, SIZE, DURATION
Secondary analysis of a prospective cohort study of 13 243 midlife females recruited in Phase 1 of the Alberta’s Tomorrow Project (Alberta, Canada) and followed approximately every 4 years (2000–2022).
PARTICIPANTS/MATERIALS, SETTING, METHODS
Data were collected through standardized self-report questionnaires. History of infertility, defined as ever trying to become pregnant for more than 1 year without conceiving, was measured at baseline. Menopause characteristics were measured at each study follow-up. Menopause type was defined as premenopause, natural menopause, surgical menopause (bilateral oophorectomy), or indeterminate menopause (premenopausal hysterectomy with ovarian conservation). Timing of natural menopause was defined as the age at 1 full year after the final menstrual period, and timing of surgical and indeterminate menopause was defined as the age at the time of surgery. We used flexible parametric survival analysis for the outcome of menopause timing with age as the underlying time scale and multinomial logistic regression for the outcome of menopause type. Multivariable models controlled for race/ethnicity, education, parity, previous pregnancy loss, and smoking. Sensitivity analyses additionally accounted for birth history, menopausal hormone therapy, body mass index, chronic medical conditions, and age at baseline.
MAIN RESULTS AND THE ROLE OF CHANCE
Overall, 18.2% of women reported a history of infertility. Past infertility was associated with earlier timing of surgical menopause exclusively before age 43 years (age 35: adjusted hazard ratio 3.13, 95% CI 1.95–5.02; age 40: adjusted hazard ratio 1.83, 95% CI 1.40–2.40; age 45: adjusted hazard ratio 1.13, 95% CI 0.87–1.46) as well as greater odds of experiencing surgical menopause compared to natural menopause (adjusted odds ratio 1.40, 95% CI 1.18–1.66). Infertility was not associated with the timing of natural or indeterminate menopause.
LIMITATIONS, REASONS FOR CAUTION
Information on the underlying cause of infertility and related interventions was not collected, which precluded us from disentangling whether associations differed by infertility cause and treatment. Residual confounding is possible given that some covariates were measured at baseline and may not have temporally preceded infertility.
WIDER IMPLICATIONS OF THE FINDINGS
Women with a history of infertility were more likely to experience early surgical menopause and may therefore benefit from preemptive screening and treatment for gynecologic diseases to reduce bilateral oophorectomy, where clinically appropriate, and its associated health risks in midlife. Moreover, the lack of association between infertility and timing of natural menopause adds to the emerging knowledge that diminishing ovarian reserve does not appear to be a primary biological mechanism of infertility nor its downstream implications for women’s health.
STUDY FUNDING/COMPETING INTEREST(S)
Alberta’s Tomorrow Project is only possible due to the commitment of its research participants, its staff and its funders: Alberta Health, Alberta Cancer Foundation, Canadian Partnership Against Cancer and Health Canada, and substantial in-kind funding from Alberta Health Services. The views expressed herein represent the views of the author(s) and not of Alberta’s Tomorrow Project or any of its funders. This secondary analysis is funded by Project Grant Priority Funding in Women’s Health Research from the Canadian Institutes of Health Research (Grant no. 491439). N.V.S. is supported by a Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research. H.K.B. is supported by the Canada Research Chairs Program. E.A.B. is supported by an Early Career Investigator Award in Maternal, Reproductive, Child and Youth Health from the Canadian Institutes of Health Research. A.K.S. has received honoraria from Pfizer, Lupin, Bio-Syent, and Eisai and has received grant funding from Pfizer. N.V.S., H.K.B., and E.A.B. have no conflicts of interest to report.
TRIAL REGISTRATION NUMBER
N/A.
In this cardiovascular safety trial, lorcaserin facilitated sustained weight loss without a higher risk of major adverse cardiovascular events than that with placebo in a high-risk population of ...overweight or obese patients.
Children undergoing anaesthetic induction experience peri-operative anxiety associated with negative outcomes including emergence delirium, short- and long-term maladaptive behaviour and increased ...postoperative analgesic requirements. This stems from children's limited ability to communicate, cope, and regulate intense emotions, leading to high dependency on parental emotional regulation. Previous interventions including video modelling, education and distraction techniques before and during anaesthetic induction have demonstrated significant reduction of anxiety levels. No existing interventions combines evidenced-based psychoeducation video with distraction techniques to support parents to moderate peri-operative anxiety. This study aims to test the efficacy of the Take5 video (now referred to as 'Take5'), a short and cost-efficient intervention for child peri-operative anxiety.
A randomised, controlled, superiority trial of Take5 compared to standard care. Take5 was developed by paediatric anaesthetists, child psychologists and a consumer panel of parents of children who had experienced surgery and anaesthesia. Children aged 3-10 years presenting for elective surgery at a quaternary paediatric facility will be randomly allocated to the intervention group or standard care. Intervention group parents will be shown Take5 prior to accompanying their child for anaesthesia induction. Primary outcomes include child and parent anxiety at induction, measured by the Modified Yale Preoperative Anxiety Scale Short Form (mYPAS-SF), the Peri-operative Adult-Child Behavior Interaction Scale (PACBIS) and the Induction Compliance Checklist (ICC). Secondary outcomes include post-operative pain, emergence delirium, parental satisfaction, cost-effectiveness, parent and child psychological well-being at 3 months post procedure and video intervention acceptability.
Perioperative anxiety is associated with negative outcome in children including higher pharmacological intervention, delayed procedures, and poor post-recovery outcomes resulting in financial burden on health systems. Current strategies minimising paediatric procedural distress are resource-intensive and have been inconsistent in reducing anxiety and negative postoperative outcomes. The Take5 video is an evidence-driven resource that is designed to prepare and empower parents. The success of Take5 will be evaluated by measuring differences in patient (acute and 3-month), family (satisfaction, acceptability), clinician (feasibility) and health service (cost) outcomes, with each anticipated to benefit children.
Australian and New Zealand Clinical Trial Registry (ACTRN12621001337864) and Children's Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC/21/QCHQ/73894).
Fidelity to a past breeding site is widespread among animals and may confer both costs and benefits. Colonial species occur at specific sites that can accommodate multiple breeders, and the choice of ...whether to return to last year's site or disperse elsewhere can affect colony site use, the colony size distribution and individual fitness. For the colonial cliff swallow, Petrochelidon pyrrhonota, which occupies colonies of widely different sizes, we used a 30-year field study in western Nebraska to investigate how the extent of infestation by ectoparasites and colony size affected breeders' colony site fidelity between years. We compared philopatry at colonies where parasitic swallow bugs, Oeciacus vicarius, had been removed by fumigation with that at nonfumigated sites exposed to natural levels of ectoparasites. About 25% of birds at nonfumigated colonies returned to their previous year's site, whereas about 69% of birds at fumigated colonies did so. Site fidelity was greatest at nonfumigated sites that changed the least in size between years. Birds were less likely to return to a nonfumigated site as the colony there became increasingly larger. Individuals philopatric to both nonfumigated and fumigated sites resided in colonies more similar in size between years than did dispersing birds. Most cliff swallows settled within 6km of their previous year's site, indicating that many nonphilopatric birds still may have had some familiarity with the local landscape surrounding the site to which they moved. Removal of ectoparasites at a site allows large colonies to persist there perennially, probably contributing to higher philopatry because such large colonies are rare and would have been difficult to find had the residents dispersed. Cliff swallows are likely to be sensitive to both colony size and general familiarity with a given site or landscape region, and probably integrate these with other cues to select breeding colonies.
•Colony site fidelity for cliff swallows in Nebraska was measured, 1983–2013.•Fidelity to the past site was higher when the colony size changed the least.•Fidelity to the past site was higher if parasites had been removed from a site.•Most birds return to within 6km of their previous site even when not philopatric.•Cliff swallows use colony size and familiarity with the landscape to choose sites.
Ecologists often use mark-recapture to estimate demographic variables such as abundance, growth rate, or survival for samples of wild animal populations. A common assumption underlying mark-recapture ...is that all animals have an equal probability of detection, and failure to meet or correct for this assumption-as when certain members of the population are either easier or more difficult to capture than other animals-can lead to biased and inaccurate demographic estimates. We built within-year and among-years Cormack-Jolly-Seber recaptures-only models to identify causes of capture heterogeneity for a population of colonially nesting cliff swallows (Petrochelidon pyrrhonota) caught using mist-netting as a part of a 20-year mark-recapture study in southwestern Nebraska, U.S.A. Daily detection of cliff swallows caught in stationary mist nets at their colony sites declined as the birds got older and as the frequency of netting at a site within a season increased. Experienced birds' avoidance of the net could be countered by sudden disturbances that startled them into a net, such as when we dropped a net over the side of a bridge or flushed nesting cliff swallows into a stationary net positioned at a colony entrance. Our results support the widely held, but seldom tested, belief that birds learn to avoid stationary mist nets over time, but also show that modifications of traditional field methods can reduce this source of recapture heterogeneity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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