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1.
Mol Cell ; 72(2): 341-354.e6, 2018 10 18.
Article in English | MEDLINE | ID: mdl-30270106

ABSTRACT

Androgen receptor splice variant 7 (AR-V7) is crucial for prostate cancer progression and therapeutic resistance. We show that, independent of ligand, AR-V7 binds both androgen-responsive elements (AREs) and non-canonical sites distinct from full-length AR (AR-FL) targets. Consequently, AR-V7 not only recapitulates AR-FL's partial functions but also regulates an additional gene expression program uniquely via binding to gene promoters rather than ARE enhancers. AR-V7 binding and AR-V7-mediated activation at these unique targets do not require FOXA1 but rely on ZFX and BRD4. Knockdown of ZFX or select unique targets of AR-V7/ZFX, or BRD4 inhibition, suppresses growth of castration-resistant prostate cancer cells. We also define an AR-V7 direct target gene signature that correlates with AR-V7 expression in primary tumors, differentiates metastatic prostate cancer from normal, and predicts poor prognosis. Thus, AR-V7 has both ARE/FOXA1 canonical and ZFX-directed non-canonical regulatory functions in the evolution of anti-androgen therapeutic resistance, providing information to guide effective therapeutic strategies.


Subject(s)
Alternative Splicing/genetics , Carcinogenesis/genetics , Kruppel-Like Transcription Factors/genetics , Oncogenes/genetics , Prostatic Neoplasms, Castration-Resistant/genetics , Receptors, Androgen/genetics , Animals , Cell Differentiation/genetics , Cell Line , Cell Line, Tumor , Drug Resistance, Neoplasm/genetics , Gene Expression Regulation, Neoplastic/genetics , HEK293 Cells , Hepatocyte Nuclear Factor 3-alpha/genetics , Humans , Male , Mice , Mice, Inbred NOD , Mice, SCID , Nuclear Proteins/genetics , Promoter Regions, Genetic/genetics
2.
Nat Immunol ; 14(5): 489-99, 2013 May.
Article in English | MEDLINE | ID: mdl-23563690

ABSTRACT

Newly activated CD8(+) T cells reprogram their metabolism to meet the extraordinary biosynthetic demands of clonal expansion; however, the signals that mediate metabolic reprogramming remain poorly defined. Here we demonstrate an essential role for sterol regulatory element-binding proteins (SREBPs) in the acquisition of effector-cell metabolism. Without SREBP signaling, CD8(+) T cells were unable to blast, which resulted in attenuated clonal expansion during viral infection. Mechanistic studies indicated that SREBPs were essential for meeting the heightened lipid requirements of membrane synthesis during blastogenesis. SREBPs were dispensable for homeostatic proliferation, which indicated a context-specific requirement for SREBPs in effector responses. Our studies provide insights into the molecular signals that underlie the metabolic reprogramming of CD8(+) T cells during the transition from quiescence to activation.


Subject(s)
CD8-Positive T-Lymphocytes/metabolism , Sterol Regulatory Element Binding Protein 1/metabolism , Sterol Regulatory Element Binding Protein 2/metabolism , Adaptive Immunity/genetics , Animals , CD8-Positive T-Lymphocytes/immunology , Cell Differentiation/genetics , Cell Proliferation , Cells, Cultured , Lymphocyte Activation/genetics , Mice , Mice, Inbred C57BL , Mice, Mutant Strains , RNA, Small Interfering/genetics , Signal Transduction/genetics , Signal Transduction/immunology , Sterol Regulatory Element Binding Protein 1/genetics , Sterol Regulatory Element Binding Protein 2/genetics , Transgenes/genetics
3.
Proc Natl Acad Sci U S A ; 119(26): e2115190119, 2022 06 28.
Article in English | MEDLINE | ID: mdl-35737845

ABSTRACT

Hearing depends on intricate morphologies and mechanical properties of diverse inner ear cell types. The individual contributions of various inner ear cell types into mechanical properties of the organ of Corti and the mechanisms of their integration are yet largely unknown. Using sub-100-nm spatial resolution atomic force microscopy (AFM), we mapped the Young's modulus (stiffness) of the apical surface of the different cells of the freshly dissected P5-P6 cochlear epithelium from wild-type and mice lacking either Trio and F-actin binding protein (TRIOBP) isoforms 4 and 5 or isoform 5 only. Variants of TRIOBP are associated with deafness in human and in Triobp mutant mouse models. Remarkably, nanoscale AFM mapping revealed unrecognized bidirectional radial stiffness gradients of different magnitudes and opposite orientations between rows of wild-type supporting cells and sensory hair cells. Moreover, the observed bidirectional radial stiffness gradients are unbalanced, with sensory cells being stiffer overall compared to neighboring supporting cells. Deafness-associated TRIOBP deficiencies significantly disrupted the magnitude and orientation of these bidirectional radial stiffness gradients. In addition, serial sectioning with focused ion beam and backscatter scanning electron microscopy shows that a TRIOBP deficiency results in ultrastructural changes of supporting cell apical phalangeal microfilaments and bundled cortical F-actin of hair cell cuticular plates, correlating with messenger RNA and protein expression levels and AFM stiffness measurements that exposed a softening of the apical surface of the sensory epithelium in mutant mice. Altogether, this additional complexity in the mechanical properties of the sensory epithelium is hypothesized to be an essential contributor to frequency selectivity and sensitivity of mammalian hearing.


Subject(s)
Actin Cytoskeleton , Deafness , Actin Cytoskeleton/metabolism , Actins/metabolism , Animals , Cochlea/metabolism , Deafness/metabolism , Hair Cells, Auditory/metabolism , Mammals/metabolism , Mice , Microfilament Proteins/metabolism , Organ of Corti , Protein Isoforms/metabolism
4.
Liver Transpl ; 30(5): 544-554, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38240602

ABSTRACT

The 2023 Joint International Congress of the International Liver Transplantation Society (ILTS), the European Liver and Intestine Transplant Association (ELITA), and the Liver Intensive Care Group of Europe (LICAGE) held in Rotterdam, the Netherlands, marked a significant recovery milestone for the liver transplant community after COVID-19. With 1159 participants and a surge in abstract submissions, the event focused on "Liver Disorders and Transplantation: Innovations and Evolving Indications." This conference report provides a comprehensive overview of the key themes discussed during the event, encompassing Hepatology, Anesthesia and Critical Care, Acute Liver Failure, Infectious Disease, Immunosuppression, Pediatric Liver Transplantation, Living Donor Liver Transplantation, Transplant Oncology, Surgical Approaches, and Machine Perfusion. The congress provided a platform for extensive discussions on a wide range of topics, reflecting the continuous advancements and collaborative efforts within the liver transplant community.


Subject(s)
Liver Transplantation , Child , Humans , Immunosuppression Therapy , Living Donors
5.
Anesth Analg ; 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38442076

ABSTRACT

Orthotopic liver transplantation (OLT) is the most effective treatment for patients with end-stage liver disease (ESLD). Hepatic insufficiency within a week of OLT, termed early allograft dysfunction (EAD), occurs in 20% to 25% of deceased donor OLT recipients and is associated with morbidity and mortality. Primary nonfunction (PNF), the most severe form of EAD, leads to death or retransplantation within 7 days. The etiology of EAD is multifactorial, including donor, recipient, and surgery-related factors, and largely driven by ischemia-reperfusion injury (IRI). IRI is an immunologic phenomenon characterized by dysregulation of cellular oxygen homeostasis and innate immune defenses in the allograft after temporary cessation (ischemia) and later restoration (reperfusion) of oxygen-rich blood flow. The rising global demand for OLT may lead to the use of marginal allografts, which are more susceptible to IRI, and thus lead to an increased incidence of EAD. It is thus imperative the anesthesiologist is knowledgeable about EAD, namely its pathophysiology and intraoperative strategies to mitigate its impact. Intraoperative strategies can be classified by 3 phases, specifically donor allograft procurement, storage, and recipient reperfusion. During procurement, the anesthesiologist can use pharmacologic preconditioning with volatile anesthetics, consider preharvest hyperoxemia, and attenuate the use of norepinephrine as able. The anesthesiologist can advocate for normothermic regional perfusion (NRP) and machine perfusion during allograft storage at their institution. During recipient reperfusion, the anesthesiologist can optimize oxygen exposure, consider adjunct anesthetics with antioxidant-like properties, and administer supplemental magnesium. Unfortunately, there is either mixed, little, or no data to support the routine use of many free radical scavengers. Given the sparse, limited, or at times conflicting evidence supporting some of these strategies, there are ample opportunities for more research to find intraoperative anesthetic strategies to mitigate the impact of EAD and improve postoperative outcomes in OLT recipients.

6.
Mol Ther ; 31(10): 2887-2900, 2023 Oct 04.
Article in English | MEDLINE | ID: mdl-37641406

ABSTRACT

The recruitment of cells with effector functions into the tumor microenvironment holds potential for delaying cancer progression. We show that subsets of human CD28-effector CD8 T cells, CCR7- CD45RO+ effector memory, and CCR7- CD45RO- effector memory RA phenotypes, express the chemerin receptor CMKLR1 and bind chemerin via the receptor. CMKLR1-expressing human CD8 effector memory T cells present gene, protein, and cytotoxic features of NK cells. Active chemerin promotes chemotaxis of CMKLR1-expressing CD8 effector memory cells and triggers activation of the α4ß1 integrin. In an experimental prostate tumor mouse model, chemerin expression is downregulated in the tumor microenvironment, which is associated with few tumor-infiltrating CD8+ T cells, while forced overexpression of chemerin by mouse prostate cancer cells leads to an accumulation of intra-tumor CD8+ T cells. Furthermore, α4 integrin blockade abrogated the chemerin-dependent recruitment of CD8+ T effector memory cells into implanted prostate tumors in vivo. The results identify a role for chemerin:CMKLR1 in defining a specialized NK-like CD8 T cell, and suggest the use of chemerin-dependent modalities to target effector CMKLR1-expressing T cells to the tumor microenvironment for immunotherapeutic purposes.


Subject(s)
CD8-Positive T-Lymphocytes , Neoplasms , Humans , Animals , Mice , CD8-Positive T-Lymphocytes/metabolism , Receptors, CCR7/metabolism , T-Lymphocyte Subsets/metabolism , Killer Cells, Natural/metabolism , Neoplasms/metabolism , Chemokines/genetics , Chemokines/metabolism , Tumor Microenvironment , Intercellular Signaling Peptides and Proteins/metabolism
7.
J Behav Med ; 47(3): 515-530, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38281260

ABSTRACT

Disparities in health outcomes between Black and White Americans are well-documented, including sleep quality, and disparities in sleep may lead to disparities in health over the life course. A meta-model indicates that cognitive processes may underly the connection between race and poor sleep quality, and ultimately, health disparities. That is, there are race-specific stressors that disproportionately affect Black Americans, which are associated with poor health through biological, cognitive, and behavioral mechanisms (e.g., sleep). Among these race-specific stressors is discrimination, which has been linked to poor sleep quality, and there is a body of literature connecting perseverative cognition (e.g., rumination and worry or vigilance) to poor sleep. Microaggressions, a more subtle but pervasive form of discrimination, are another race-specific stressor. Although less research has considered the connection of microaggressions to perseverative cognition, there are some studies linking microaggressions to health outcomes and sleep. Therefore, using a cross-sectional survey, we tested the following hypotheses: racism-related vigilance and rumination would mediate the relationship between discrimination and poor sleep as well as between microaggressions and poor sleep among Black Americans (N = 223; mean age = 35.77 years, 53.8% men, 86% employed, 66.8% with college degree or higher education). Results of seven parallel mediation models showed that neither rumination nor racism-related vigilance mediated a relationship between discrimination and poor sleep quality. However, rumination partially mediated relationships between the six microaggression sub-scales and poor sleep quality: there were significant indirect effects for Foreigner/Not Belonging (ß = .13, SE = 0.03, 95% CI 0.08, 0.20), Criminality (ß = .11, SE = 0.03, 95% CI 0.05, 0.17), Sexualization (ß = .10, SE = 0.03, 95% CI 0.05, 0.17), Low-Achieving/Undesirable (ß = .10, SE = 0.03, 95% CI 0.05, 0.15), Invisibility (ß = .15, SE = 0.04, 95% CI 0.08, 0.23), and Environmental Invalidations (ß = .15, SE = 0.04, 95% CI 0.08, 0.23). Overall, these findings indicate support for the meta-model, demonstrating a specific pathway from racial microstressors to poor sleep quality. Furthermore, these results suggest the importance of developing clinical and community approaches to address the impact of microaggressions on Black Americans' sleep quality.


Subject(s)
Microaggression , Racism , Rumination, Cognitive , Sleep Initiation and Maintenance Disorders , Sleep Quality , Adult , Female , Humans , Male , Black or African American , Cross-Sectional Studies , Racism/psychology , Health Status Disparities
8.
BMC Health Serv Res ; 24(1): 380, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38539191

ABSTRACT

OBJECTIVE: To determine the views of health care professionals (HCPs) in South Western Sydney Local Health District (SWSLHD) about the effectiveness of implementation strategies used to increase routine height/length and weight screening, advice, and referral for children and adolescents. A secondary aim was to explore the prevalence of weight bias among HCPs. METHODS: A questionnaire was sent to all HCPs who had undertaken online or face-to-face training between December 2018 and June 2020 in SWSLHD (n=840). The questionnaire collected data on their experience of routine height and weight screening and the effectiveness of strategies used in the implementation. It also included a weight bias assessment. Data were provided by the New South Wales (NSW) Ministry of Health on the performance of routine height/length and weight measures entered into the electronic medical records (eMR) in SWSLHD. RESULTS: Of the 840 questionnaires sent, 87 were undeliverable; of the remaining 753, 285 were returned (38% response rate). More than half (53%, 151/285) of the participants were nurses. Most HCPs agreed that there was a need for routine screening and reported that education, training, and access to resources were the most helpful implementation strategies. Most HCPs were confident in performing routine screening but were less confident in raising the issue of weight with children and their families. Barriers to implementation were lack of time, equipment, appropriate clinical setting, and HCPs' perceptions and beliefs about obesity. CONCLUSION: Routine screening is the first step in identifying children and adolescents at risk of overweight and obesity, but many HCP found it challenging to incorporate into daily practice. Multifaceted strategies are effective in increasing routine screening across diverse healthcare settings so that children and adolescents receive timely and appropriate intervention.


Subject(s)
Obesity , Overweight , Adolescent , Humans , Child , Obesity/prevention & control , Health Personnel/education , Delivery of Health Care , Referral and Consultation
9.
Matern Child Nutr ; 20(1): e13586, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37932246

ABSTRACT

This study examined sociodemographic factors associated with mothers seeking child feeding advice from health professionals (HPs). Cross-sectional analysis of survey data from linked randomized controlled trials was conducted. Surveys asked which sources of feeding information mothers used when their child was 6 months and 5 years old. Logistic regression was used to examine associations between sociodemographic characteristics and use of information from HPs. Here, 947 and 405 mothers completed 6-month and 5-year surveys, respectively. At 6 months, multiparous mothers were less likely to seek advice from child and family health nurses (CFHNs) (adjusted odds ratio [AOR]: 0.558, 95% confidence interval [95% CI]: 0.416-0.749) and other HPs (AOR: 0.706, 95% CI: 0.542-0.919), unmarried mothers were less likely to seek advice from other HPs (AOR: 0.582, 95% CI: 0.342-0.990). At 5 years, mothers with household income ≥$80,000 p.a. were less likely to seek advice from CFHNs (AOR: 0.514, 95% CI: 0.302-0.875) and working mothers less likely to seek advice from general practitioners (GPs) (AOR: 0.581, 95% CI: 0.374-0.905). Mothers born in Australia were less likely to seek information from CFHNs (AOR: 0.462, 95% CI: 0.257-0.833) and GPs (AOR: 0.431, 95% CI: 0.274-0.677). There was a greater likelihood that multiparous mothers (AOR: 2.114, 95% CI: 1.272-3.516) and mothers of children whose fathers had not attended university (AOR: 2.081, 95% CI: 1.256-3.449) had never sought advice from CFHNs, and that mothers who had not attended university (AOR: 1.769, 95% CI: 1.025-3.051), multiparous (AOR: 1.831, 95% CI: 1.105-3.035) and employed (AOR: 2.058, 95% CI: 1.135-3.733) mothers had never sought advice from other HPs. Understanding sociodemographic factors associated with seeking child feeding advice from HPs may inform priorities for engaging families in health promotion.


Subject(s)
Mothers , Sociodemographic Factors , Female , Child , Humans , Infant , Cross-Sectional Studies , Health Promotion , Logistic Models , Breast Feeding
10.
Matern Child Nutr ; : e13662, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38804571

ABSTRACT

Mobile health (mHealth) interventions provide a low-cost, scalable approach to supporting parents with infant feeding advice with the potential to reduce health care visits and associated costs for infant feeding support. This Australian study examined the impact of the Growing healthy (GH) app on health service utilisation and out-of-pocket costs for families in the first 9 months of their infants life. A quasi-experimental study with a comparison group was conducted in 2015-2016 with an mHealth intervention group (GH app, n = 301) and a nonrandomized usual care group (n = 344). The GH app aimed to support parents of young infants with healthy infant feeding behaviours from birth to 9 months of age. App-generated notifications directed parents to age-and feeding-specific content within the app. Both groups completed surveys at baseline when infants were less than 3 months old (T1), at 6 months (T2) and 9 months (T3) of age. At T3, participants reported health services used and any out-of-pocket costs for advice on infant feeding, growth or activity. App users had lower odds (odds ratio: 0.38 95% confidence interval: 0.25, 0.59) of using one or more services and had lower number of visits to a general practitioner (1.0 vs. 1.5 visits, p = 0.003) and paediatrician (0.3 vs. 0.4 visits, p = 0.049) compared to the usual care group. There was no difference in out-of-pocket costs between groups. Provision of an evidenced-based infant feeding app may provide substantial savings to the health system and potentially to parents through fewer primary health care and paediatrician visits.

11.
BMC Public Health ; 23(1): 932, 2023 05 23.
Article in English | MEDLINE | ID: mdl-37221519

ABSTRACT

BACKGROUND: The success of the COVID-19 vaccination roll-out depended on clear policy communication and guidance to promote and facilitate vaccine uptake. The rapidly evolving pandemic circumstances led to many vaccine policy amendments. The impact of changing policy on effective vaccine communication and its influence in terms of societal response to vaccine promotion are underexplored; this qualitative research addresses that gap within the extant literature. METHODS: Policy communicators and community leaders from urban and rural Ontario participated in semi-structured interviews (N = 29) to explore their experiences of COVID-19 vaccine policy communication. Thematic analysis was used to produce representative themes. RESULTS: Analysis showed rapidly changing policy was a barrier to smooth communication and COVID-19 vaccine roll-out. Continual amendments had unintended consequences, stimulating confusion, disrupting community outreach efforts and interrupting vaccine implementation. Policy changes were most disruptive to logistical planning and community engagement work, including community outreach, communicating eligibility criteria, and providing translated vaccine information to diverse communities. CONCLUSIONS: Vaccine policy changes that allow for prioritized access can have the unintended consequence of limiting communities' access to information that supports decision making. Rapidly evolving circumstances require a balance between adjusting policy and maintaining simple, consistent public health messages that can readily be translated into action. Information access is a factor in health inequality that needs addressing alongside access to vaccines.


Subject(s)
COVID-19 , Health Communication , Humans , Ontario , COVID-19 Vaccines , Health Status Disparities , Health Policy , Qualitative Research
12.
Health Promot Int ; 38(4)2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37549195

ABSTRACT

Vaccine hesitancy has been identified as one of the top 10 threats to global health. The causes of low vaccine uptake are many and vary at micro and macro levels. However, rural and remote coastal areas in the UK experience unique vaccine inequalities due to high levels of deprivation and their unique and complex access-related problems. This study aimed to explore community efforts to promote vaccine uptake during the COVID-19 pandemic and understand how the COVID-19 vaccination campaign was experienced by the public. We conducted an exploratory descriptive qualitative study using semi-structured interviews with decision-makers, health professionals and community members in Lincolnshire, a predominantly rural county with a long coastline, a large population of white minority ethnicities, and those living in caravan and temporary housing. Data were analysed using conventional content analysis. Overcoming the various access barriers to vaccination uptake involved working with local media stations, local communities and local community groups, translation of information, bringing vaccines closer to the people through pop-up and mobile clinics and provision of transport and ensuring confidentiality. There is a need to employ inclusive targeted non-conventional care interventions whilst dealing with complex problems as occur in rural and remote coastal regions.


Subject(s)
COVID-19 , Vaccines , Humans , COVID-19/prevention & control , COVID-19 Vaccines , Pandemics , Vaccination , Qualitative Research
13.
Health Promot J Austr ; 34(1): 237-245, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35718992

ABSTRACT

ISSUES ADDRESSED: People with severe mental illness have adverse health outcomes compared to the general population. Lifestyle interventions are effective in improving health outcomes in this population. Current cultural processes in mental health services do not generally incorporate physical health care practices. Innovative education is required to improve knowledge and confidence of staff in the delivery of preventative health measures. METHODS: The Keeping our Staff in Mind (KoSiM) program delivered a brief lifestyle intervention to mental health staff. A qualitative analysis following the Standards for Reporting Qualitative Research was undertaken. Semi-structured interviews designed to elicit information about the acceptability of the program and the impact of the intervention on participants' personal and professional lives. The interviews were analysed using thematic analysis, with coding independently developed and reviewed by three authors. RESULTS: Of the 103 eligible participants, 75 were interviewed. Responses revealed four main themes: (i) positive changes in clinician's approach to physical health care, (ii) improvements in attitudes to self-care and family wellbeing, (iii) positive changes in workplace culture associated with physical health care delivery and (iv) high levels of acceptability of the program. CONCLUSION: The KoSiM model may be useful in other settings as a means of changing the culture of mental health services to better integrate physical health care as a core part of mental health service provision. SO WHAT?: A novel approach using staff focussed lifestyle interventions model may cut through the resistance that is encountered when implementing proven methods of clinical intervention where cultural barriers exist.


Subject(s)
Mental Disorders , Mental Health Services , Humans , Life Style , Mental Disorders/therapy , Mental Health , Program Evaluation
14.
Matern Child Nutr ; 19(2): e13482, 2023 04.
Article in English | MEDLINE | ID: mdl-36725007

ABSTRACT

Despite the well-known benefits of breastfeeding, breastfeeding rates remain suboptimal, particularly for women with lower socioeconomic position. Although popular, breastfeeding apps are often poor quality; their impact on breastfeeding knowledge, attitudes, confidence and intentions is unknown. A mixed method pre-post feasibility study was conducted to: 1) explore the feasibility of the My Baby Now app in providing perinatal breastfeeding support; 2) examine the impact on breastfeeding knowledge, attitudes, confidence and intentions; 3) to examine any differences in acceptability and impact of the app according to maternal education. The My Baby Now app was offered to pregnant women 20-30 weeks gestation. Breastfeeding knowledge and intentions were collected at baseline (T1) and 36-38 weeks gestation (T2); attitudes and confidence were collected at baseline, T2 and T3 (8-12 weeks post-partum). App engagement was measured via app analytics. Qualitative interviews were conducted with a purposeful sample following T3. Of 266 participants recruited, 169 (64%) completed T2 and 157 (59%) completed T3. Mothers without university education rated the app to be higher quality, more useful and impactful than mothers with university education. From T1-T2, breastfeeding knowledge (59.6% vs. 66.5%, p < 0.001) and exclusive breastfeeding intentions (76.6% vs. 80.9%, p < 0.001) increased. Breastfeeding attitudes and confidence scores also increased significantly across T1-T2 and T1-T3. App engagement during pregnancy predicted changes in breastfeeding attitudes from T1-T2 among participants without university education. App engagement did not predict changes in breastfeeding knowledge, confidence or intentions. Future randomised controlled studies should examine the effectiveness of mHealth interventions on breastfeeding outcomes.


Subject(s)
Mobile Applications , Telemedicine , Infant , Female , Pregnancy , Humans , Breast Feeding , Feasibility Studies , Mothers , Health Knowledge, Attitudes, Practice
15.
Immunity ; 38(1): 5-7, 2013 Jan 24.
Article in English | MEDLINE | ID: mdl-23352218

ABSTRACT

Inflammatory cytokines shape CD8(+) T cell responses. In this issue of Immunity, Richer et al. (2013) and Raue et al. (2013) demonstrate that inflammatory cytokines dynamically fine-tune antigen sensitivity of CD8(+) T cells to potently detect and better eliminate infected cells.

16.
Int J Behav Nutr Phys Act ; 19(1): 153, 2022 12 15.
Article in English | MEDLINE | ID: mdl-36517797

ABSTRACT

BACKGROUND: Little is known about the pathways linking parent feeding practices with appetitive traits and BMIz throughout infancy. This study examined bidirectional associations between parental feeding practices, infant appetitive traits, and infant BMIz. METHODS: Parents (n = 380) of infants aged less than 6 months at baseline reported their feeding practices (using the Feeding Practices and Structure Questionnaire (FPSQ) for infants and toddlers), infant appetitive traits (using the Baby Eating Behaviour Questionnaire) and infant BMIz (parent-reported) at three timepoints (< 6 months, ~ 9 months, ~ 12 months) up to 12 months of age. Cross-lagged models examined bidirectional associations between parent feeding practices, infant appetitive traits and infant BMIz. RESULTS: There was strong continuity across the three timepoints for maternal feeding practices, infant appetitive traits, and infant BMIz. Infant food avoidance was prospectively associated with higher parental persuasive feeding. Infant BMIz was prospectively associated with higher parent-led feeding. Parent use of food to calm was prospectively associated with lower infant BMIz, and infant BMIz was prospectively associated with higher infant food approach. Feeding on demand was prospectively associated with lower infant food approach. CONCLUSION: This study highlights the complex associations between parental feeding practices, infant appetitive traits and infant BMIz. The study demonstrated that both child and parent effects are important, suggesting a need for tailored programs beginning in infancy to promote and support infant appetitive traits and parent feeding practices that support healthy development.


Subject(s)
Feeding Behavior , Parents , Infant , Humans , Longitudinal Studies , Cohort Studies , Surveys and Questionnaires
17.
Pain Med ; 23(8): 1355-1365, 2022 08 01.
Article in English | MEDLINE | ID: mdl-34931687

ABSTRACT

BACKGROUND: Persistent postsurgical pain (PPSP) is a common complication that impacts quality of life, often necessitating long-term opioid treatment. Certain neurocognitive factors, including reduced performance on cognitive flexibility tasks, are associated with increased risk of PPSP. We examine the perceptions of surgical patients and clinicians with regard to perioperative pain management activities and needs; patient acceptance and use of a perioperative neurocognitive training intervention; and implementation feasibility. METHODS: We conducted both individual and focus group interviews with patients undergoing thoracic surgery and clinicians in an academic medical center. The Consolidated Framework for Intervention Research guided the development of interview questions related to the adoption and implementation of a neurocognitive intervention to mitigate PPSP. A thematic analysis was used to analyze the responses. RESULTS: Forty patients and 15 clinicians participated. Interviews revealed that there is minimal discussion between clinicians and patients about PPSP. Most participants were receptive to a neurocognitive intervention to prevent PPSP, if evidence demonstrating its effectiveness were available. Potential barriers to neurocognitive training program adoption included fatigue, cognitive overload, lack of familiarity with the technology used for delivering the intervention, and immediate postoperative pain and stress. Implementation facilitators would include patient education about the intervention, incentives for its use, and daily reminders. CONCLUSION: The study identified several guiding principles for addressing patients' and clinicians' barriers to effectively implementing a neurocognitive training intervention to mitigate PPSP after surgery. To ensure the sustainability of neurocognitive interventions for preventing PPSP, such interventions would need to be adapted to meet patients' and clinicians' needs within the perioperative context.


Subject(s)
Pain, Postoperative , Quality of Life , Analgesics, Opioid/therapeutic use , Humans , Pain Management/adverse effects , Pain Measurement , Pain, Postoperative/etiology
18.
BMC Public Health ; 22(1): 1259, 2022 06 27.
Article in English | MEDLINE | ID: mdl-35761317

ABSTRACT

BACKGROUND: Hypertensive disorders of pregnancy have longer-term implications, increasing women's lifetime cardiovascular disease risk. The Blood Pressure Postpartum study is a multi-centre randomised three-arm trial of interventions, ranging in intensity and including education and lifestyle coaching, to support women to maintain or adopt healthy eating and physical activity during the first postpartum year. This qualitative sub-study nested within the main trial aimed to investigate whether and how women adopted healthy behaviours after a pregnancy complicated by a hypertensive disorder. METHODS: Semi-structured telephone interviews were recorded, transcribed and analysed thematically, following Braun and Clarke principles. They explored behaviour change among new mothers following their hypertensive pregnancy, and the intervention's effect on their capacity and motivation to pursue healthy lifestyles. RESULTS: Thirty-four women from all three trial arms participated at 10-12 months postpartum. The three main themes were 1) Awareness of cardiovascular risk: some did not acknowledge the health risks, whereas others embraced this information. 2) Sources of motivation: while the majority were motivated to make a concerted effort to adapt their health behaviour, motivation often centred on their baby and family rather than their own needs. 3) Sustaining behaviour change with a new baby: women in the more intensive intervention arm demonstrated increased recognition of the importance of reducing cardiovascular health risks, with greater motivation and guidance to change their health behaviour. There was minimal evidence of crossover amongst groups, with women largely accepting their randomised level of intervention and not seeking additional help when randomised to minimal intervention. CONCLUSIONS: Among women participating in an early post-hypertensive disorders of pregnancy randomised controlled trial aimed at improving their cardiovascular disease risk profile, the majority recognised the future health risks and appeared motivated to improve their lifestyle, particularly women in the highest-intensity intervention group. This highlights the importance of structured support to assist women embrace healthy lifestyles especially during the challenges of new parenthood. TRIAL REGISTRATION: The Blood Pressure Postpartum study was prospectively registered as a clinical trial with the Australian New Zealand Clinical Trials Registry (anzctr.org.au) on 13 December 2018 (registration number: ACTRN12618002004246).


Subject(s)
Cardiovascular Diseases , Hypertension, Pregnancy-Induced , Australia , Female , Health Behavior , Humans , Hypertension, Pregnancy-Induced/epidemiology , Hypertension, Pregnancy-Induced/prevention & control , Mothers , Pregnancy
19.
J Adv Nurs ; 78(2): 541-556, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34846073

ABSTRACT

AIMS: This study explored the acceptability of a workplace health promotion intervention embedded into a transition to practice (TTP) programme to assist new graduate nurses in establishing healthy dietary and physical activity (PA) behaviours from career commencement. DESIGN: A sequential mixed methods design. METHODS: The Start Healthy and Stay Healthy (SH&SH) intervention, informed by the Behaviour Change Wheel, was conducted in an Australian Local Health District. It included face-to-face education sessions, the use of a fitness tracker and twice-weekly short answer messages. Participants completed three online surveys: at orientation, 6 weeks and 6 months. A sub-sample participated in semi-structured interviews to explore their experience of the intervention. Interview data were analysed thematically. RESULTS: The intervention was delivered from February to December 2019. A total of 99 nurses completed the baseline survey, 62 at 6 weeks and 69 at 6 months. After 6 months, health knowledge increased as participants correctly identified recommended amounts of fruits, vegetables and PA. Fruit consumption increased at 6 months with little change to vegetable intake. Takeaway consumption decreased, but consumption of some discretionary foods increased. Across the three time points, there was a low engagement in PA during leisure time. The interviews identified three themes: (1) Support of Colleagues and Peers, (2) The Work Environment and (3) Engagement with SH&SH. CONCLUSION: Providing a targeted intervention for new graduate nurses embedded into a TTP programme improved their health knowledge, some dietary behaviours, and participation in PA by some participants. IMPACT: Ensuring a healthy nursing workforce is critical to retaining staff. Implementing a workplace health promotion intervention that targets new graduate nurses can help them adopt and maintain healthy lifestyle behaviours to support them in their future careers.


Subject(s)
Education, Nursing, Graduate , Nursing Staff , Australia , Health Promotion , Humans , Workplace
20.
Matern Child Nutr ; 18(2): e13309, 2022 04.
Article in English | MEDLINE | ID: mdl-34913262

ABSTRACT

The use of infant formula is widespread internationally. In Australia, 55% of infants receive formula before 6 months of age, with higher rates among disadvantaged communities. Infant formula use can contribute to childhood overweight and obesity, through formula composition and feeding behaviours, such as adding cereal to bottles and parental feeding style. While information abounds to promote and support breastfeeding, formula-feeding parents report a paucity of advice and support; many rely on formula packaging for information. This study systematically searched and reviewed online resources for infant formula and bottle feeding from Australian governments, health services, hospitals, and not-for-profit parenting organisations. A comprehensive search strategy located 74 current resources, mostly for parents. Researchers evaluated the resources against best practice criteria derived from Australian government and UNICEF guidelines on six topics. They assessed how comprehensively the resources addressed each topic and whether the resources provided all the information necessary for parents to understand each topic. The mean 'comprehensiveness' rating for topics across all resources was 54.36%. However, some topics were addressed more fully than others. Information on 'discussing infant formula with health workers' and on 'preparing infant formula' was more frequently accurate and comprehensive. However, there was much less comprehensive information on 'using infant formula', including amounts of formula to feed, use of bottle teats, appropriate bottle-feeding practice and responsiveness to infant satiety cues. Over half the resources were written at an acceptable reading level.


Subject(s)
Bottle Feeding , Pediatric Obesity , Australia , Breast Feeding , Child , Delivery of Health Care , Female , Humans , Infant , Infant Formula
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