1,624 research outputs found

    Greatwall and Polo-like Kinase 1 Coordinate to Promote Checkpoint Recovery

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    Checkpoint recovery upon completion of DNA repair allows the cell to return to normal cell cycle progression and is thus a crucial process that determines cell fate after DNA damage. We previously studied this process in Xenopus egg extracts and established Greatwall (Gwl) as an important regulator. Here we show that preactivated Gwl kinase can promote checkpoint recovery independently of cyclin-dependent kinase 1 (Cdk1) or Plx1 (Xenopus polo-like kinase 1), whereas depletion of Gwl from extracts exhibits no synergy with that of Plx1 in delaying checkpoint recovery, suggesting a distinct but related relationship between Gwl and Plx1. In further revealing their functional relationship, we found mutual dependence for activation of Gwl and Plx1 during checkpoint recovery, as well as their direct association. We characterized the protein association in detail and recapitulated it in vitro with purified proteins, which suggests direct interaction. Interestingly, Gwl interaction with Plx1 and its phosphorylation by Plx1 both increase at the stage of checkpoint recovery. More importantly, Plx1-mediated phosphorylation renders Gwl more efficient in promoting checkpoint recovery, suggesting a functional involvement of such regulation in the recovery process. Finally, we report an indirect regulatory mechanism involving Aurora A that may account for Gwl-dependent regulation of Plx1 during checkpoint recovery. Our results thus reveal novel mechanisms underlying the involvement of Gwl in checkpoint recovery, in particular, its functional relationship with Plx1, a well characterized regulator of checkpoint recovery. Coordinated interplays between Plx1 and Gwl are required for reactivation of these kinases from the G2/M DNA damage checkpoint and efficient checkpoint recovery

    Provider Insight on Surmounting Specialty Practice Challenges to Improve Tdap Immunization Rates among Pregnant Women

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    Background Pertussis, or “whooping cough,” is an acute, contagious pulmonary disease that, despite being vaccine-preventable, has become an increasingly widespread problem in the United States. As a result, the Advisory Committee on Immunization Practices and American College of Obstetricians and Gynecologists updated recommendations stating clinicians should give a Tdap dose during every pregnancy, preferably at 27–36 weeks. Despite this recommendation, reported Tdap vaccine receipt rates during pregnancy vary from 16–61%, and previous studies have shown that clinician recommendation and vaccine administration are strongly associated with vaccine uptake among pregnant women. Methods Our aim was to inform new strategies to increase uptake of the Tdap vaccine among pregnant women and, ultimately, reduce pertussis-related morbidityand mortality in infants. We conducted interviewswith a sample of 24 ob-gyns. We subsequently performed grounded theory analyses of transcripts using deductive and inductive coding strategies followed by intercoder reliability assessment. Results All physicians interviewed were familiar with the most recent recommendation of giving the Tdap vaccine during the third trimester of every pregnancy, and the majority of physicians stated that they felt that the vaccine was important and effective due to the transfer of pertussis antibodies from the mother to the fetus. Most physicians indicated that they recommended the vaccine to patients during pregnancy, but not all reported administering it on site because it was not stocked at their practice. Implementation challenges for physicians included insurance reimbursement and other challenges (i.e., patient refusal). Tdap vaccinationduring pregnancy was a lower clinical priority for some physicians. Physicians recognized the benefits associated with Tdap vaccination during pregnancy. Conclusions Findings indicate while most ob-gyns recognize the benefits of Tdap and recommend vaccination during pregnancy, barriers such as insurance reimbursement and financial concerns for the practice can outweigh the perceived benefits. This resulted in some ob-gyns reporting choosing not to stock and administer the vaccine in their practice. Recommendations to address these concerns include 1) structural support for Tdap vaccine administration in ob-gyns practices; 2) Continuing medical education-equivalent educational interventions that address management techniques, vaccine coding, and other relevant information; and 3) interventions to assist physicians in communicating the importance of Tdap vaccination during pregnancy

    Exploring Nursery Growers’ Perceptions, Attitudes and Opinions about Water Usage to Inform Water Conservation Education

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    Research has shown the nursery industry needs to seek alternative water sources and adopt water conservation strategies to reduce water use in order to stay viable. This study used a qualitative approach to explore nursery growers’ perceptions, attitudes, and opinions about water usage to inform the development of Extension programs that encourage adoption of water conservation strategies. Interviews were conducted with 24 nursery growers across the U.S. The findings indicated growers interact with water in various ways, including meeting plant water needs, facilitating chemical distribution, controlling product quality, and facilitating business operations. The participants felt protecting water was the right thing to do and could provide economic benefits to their business, but water management was perceived as a task enforced by regulations. They reported their future interaction with water would include combatting water issues, engaging in the development and implementation of government regulations, seeking water conservation technologies and information, and dealing with financial challenges. Extension educators should be aware of these needs to alleviate concerns about integrating new processes into business plans. Educational programs should assist in the promotion of water conserving products based on knowledge gaps and provide assistance for easier adoption of new technologies by growers

    Sleep and nighttime energy consumption in early childhood:A population-based cohort study

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    BACKGROUND: Shorter sleep is a risk factor for weight gain in young children. Experimental studies show that sleep deprivation is associated with higher nighttime energy intake, but no studies have examined the patterning of energy intake in relation to nighttime sleep duration in young children. OBJECTIVES: The objectives of the study were to test the hypothesis that shorter‐sleeping children would show higher nighttime energy intake and to examine whether the additional calories were from drinks, snacks or meals. METHODS: Participants were 1278 families from the Gemini twin cohort, using data from one child per family selected at random to avoid clustering effects. Nighttime sleep duration was measured at 16 months of age using the Brief Infant Sleep Questionnaire. Energy intake by time of day and eating episode (meal, snack, drink) were derived from 3‐day diet diaries completed when children were 21 months. RESULTS: Consistent with our hypothesis, shorter‐sleeping children consumed more calories at night only (linear trend P < 0.001), with those sleeping <10 h consuming on average 120 calories (15.2% of daily intake) more at night than those sleeping ≄13 h. The majority of nighttime intake was from milk drinks. Associations remained after adjusting for age, sex, birth weight, gestational age, maternal education, weight and daytime sleep. CONCLUSIONS: Shorter‐sleeping, young children consume more calories, predominantly at night, and from milk drinks. Parents should be aware that providing milk drinks at night may contribute to excess intake. This provides a clear target for intervention that may help address associations between sleep and weight observed in later childhood

    A theory-based approach to understanding condom errors and problems reported by men attending an STI clinic

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    The official published version can be accessed from the link below - Copyright @ 2008 Springer VerlagWe employed the information–motivation–behavioral skills (IMB) model to guide an investigation of correlates for correct condom use among 278 adult (18–35 years old) male clients attending a sexually transmitted infection (STI) clinic. An anonymous questionnaire aided by a CD-recording of the questions was administered. Linear Structural Relations Program was used to conduct path analyses of the hypothesized IMB model. Parameter estimates showed that while information did not directly affect behavioral skills, it did have a direct (negative) effect on condom use errors. Motivation had a significant direct (positive) effect on behavioral skills and a significant indirect (positive) effect on condom use errors through behavioral skills. Behavioral skills had a direct (negative) effect on condom use errors. Among men attending a public STI clinic, these findings suggest brief, clinic-based, safer sex programs for men who have sex with women should incorporate activities to convey correct condom use information, instill motivation to use condoms correctly, and directly enhance men’s behavioral skills for correct use of condoms

    Phosphatase 1 Nuclear Targeting Subunit Is an Essential Regulator of M-phase Entry, Maintenance, and Exit

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    Background: Mitotic progression is regulated by reversible protein phosphorylation involving kinases and phosphatases. Results: Pnuts functions as a master regulator of mitosis by modulating PP1; Pnuts expression peaks in mitosis and is degraded at mitotic exit. Conclusion: This study reveals the function and regulation of a new and essential mitotic regulator. Significance: This study improves our understanding of M-phase regulation

    Biopsychosocial Intervention for Stroke Carers (BISC): protocol for a feasibility randomized controlled trial

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    Introduction Reducing length of hospital stay for stroke survivors often creates a shift in the responsibility of care towards informal carers. Adjustment to the caregiving process is experienced by many carers as overwhelming, complex and demanding, and can have a detrimental impact on mental and physical health and wellbeing. National policy guidelines recommend that carers’ needs are considered and addressed; despite this, few interventions have been developed and empirically evaluated. We developed a biopsychosocial intervention in collaboration with carers of stroke survivors. Our aim is to determine whether the intervention can be delivered in a group setting and evaluated using a randomised controlled trial (RCT). Methods and Analysis Feasibility randomised controlled trial (RCT) and nested qualitative interview study. We aim to recruit up to 40 stroke carers within one year of the stroke onset. Carers are randomised to usual care or usual care plus biopsychosocial intervention. Each intervention group will consist of five stroke carers. The intervention will focus on: psychoeducation, psychological adjustment to stroke, strategies for reducing unwanted negative thoughts and emotions, and problem solving strategies. The main outcome is the feasibility of conducting an RCT. Carer outcomes at six months include: anxiety and depression, quality of life, and carer strain. Data is also collected from stroke survivors at baseline and six months including: level of disability, anxiety and depression, and quality of life. Ethics and Dissemination Favourable ethical opinion was provided by East Midlands – Nottingham2 Research Ethics Committee (14/EMI/1264). This study will determine whether delivery of the biopsychosocial intervention is feasible and acceptable to stroke carers within a group format. It will also determine whether it is feasible to evaluate the effects of the biopsychosocial intervention in an RCT. We will disseminate our findings through peer-reviewed publications and presentations at national and international conferences

    Toll-like receptor and cytokine expression throughout the bone marrow differs between patients with low- and high-risk myelodysplastic syndromes

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    Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders, the pathogenesis of which involves enhanced immune signaling that promotes or selects for mutant hematopoietic stem and progenitor cells (HSPCs). In particular, toll-like receptor (TLR) expression and signaling are enhanced in MDS, and their inhibition is an attractive therapeutic strategy. Although prior studies have reported increased expression of TLR2 and its binding partners TLR1 and TLR6 in the CD3

    A Preliminary Study Investigating Maternal Neurocognitive Mechanisms Underlying a Child-Supportive Parenting Intervention

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    Although interventions that promote child-supportive parenting for children have been shown to positively impact caregiving behaviors as well as child behavioral and neurobiological functioning, less is known about which aspects of maternal brain functioning are affected by such interventions. In the present study, we conducted a preliminary evaluation of the impact of the Filming Interactions to Nurture Development (FIND) video coaching program on mothers with at least one child age four or younger. We employed a waitlist control design with pre-post data. Compared to mothers in the control condition (n = 16), mothers who received FIND (n = 16) showed changes in neural measures of inhibitory control and behavioral measures of parenting self-evaluation during a series of functional neuroimaging tasks. Specifically, we found a group by time interaction in clusters in the left inferior frontal gyrus (IFG) and insula for the Correct Stop &gt; Correct Go contrast of the stop signal task (SST), where FIND increased brain activity associated with inhibitory control compared to mothers in the control condition; and FIND increased mothers’ endorsement of child-supportive parenting traits in the parenting self-evaluation task (PSET). Exploratory moderators, study limitations, and the implications of these findings for strength-based parenting programs are discussed

    Association between workplace absenteeism and alcohol use disorder from the National Survey on Drug Use and Health, 2015-2019

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    Importance: Alcohol use disorder (AUD) is common and associated with increased morbidity. The degree to which AUD currently factors into workplace absenteeism needs further characterization in the US. Objective: To examine the association between AUD and workplace absenteeism in a nationally representative sample. Design, Setting, and Participants: This cross-sectional study used data from a nationally representative sample of noninstitutionalized US residents from the 2015-2019 National Survey on Drug Use and Health to examine the association of AUD with workplace absenteeism. Eligible respondents were aged 18 years and older who reported full-time employment. Data were analyzed from March to September 2021. Main Outcomes and Measures: Primary outcomes were markers of workplace absenteeism as defined by the number of days missed from work because of illness or injury and days skipped from work in the last 30 days. Descriptive statistics, prevalence ratios, and logistic regression analyses were performed to assess the association between AUD and absenteeism. Results: A total of 110 701 adults aged 18 years and older reported current full-time employment (58 948 [53.2%] men, 51 753 [46.8%] women; 12 776 [11.5%] Black, 18 096 [16.3%] Hispanic, and 69 506 [62.8%] White respondents). Weighted prevalence of AUD in this sample of working adults was 9.3% (95% CI, 9.0%-9.5%); 6.2% (95% CI, 6.0%-6.4%) of respondents met criteria for mild AUD, 1.9% (95% CI, 1.7%-2.0%) for moderate AUD, and 1.2% (95% CI, 1.1%-1.3%) for severe AUD. Mean days missed from work annually increased in a stepwise fashion with increasing AUD severity (no AUD, 13.0 days; 95% CI, 12.7-13.2 days; mild AUD, 17.7 days; 95% CI, 16.4-19.1 days; moderate AUD, 23.6 days; 95% CI, 21.5-25.7 days; severe AUD, 32.3 days; 95% CI, 27.5-37.0 days). People with AUD represented 9.3% of the full-time workforce and contributed to 14.1% of total reported workplace absences. Conclusions and Relevance: In this cross-sectional study, AUD was disproportionately associated with an increased prevalence of workplace absenteeism, with individuals with AUD contributing over 232 million missed workdays annually. These results provide economic incentive for increased investment in AUD prevention and treatment, both for employers and policy makers
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