The AGC kinase SGK1 regulates TH1 and TH2 differentiation downstream of the mTORC2 complex.

SGK1 is an AGC kinase that regulates the expression of membrane sodium channels in renal tubular cells in a manner dependent on the metabolic checkpoint kinase complex mTORC2. We hypothesized that SGK1 might represent an additional mTORC2-dependent regulator of the differentiation and function of T cells. Here we found that after activation by mTORC2, SGK1 promoted T helper type 2 (TH2) differentiation by negatively regulating degradation of the transcription factor JunB mediated by the E3 ligase Nedd4-2. Simultaneously, SGK1 repressed the production of interferon-γ (IFN-γ) by controlling expression of the long isoform of the transcription factor TCF-1. Consistent with those findings, mice with selective deletion of SGK1 in T cells were resistant to experimentally induced asthma, generated substantial IFN-γ in response to viral infection and more readily rejected tumors.

A longitudinal study of lifestyle behaviours in emerging adulthood and risk for symptoms of depression, anxiety, and stress.

BACKGROUND: Little research has examined how lifestyle behaviours cluster together to contribute to mental health outcomes. The current study aimed to identify latent classes of emerging adult lifestyle behaviours (diet, physical activity, sedentary time, smoking, alcohol, cannabis, and other drug use) at age 20 years and their associations with depression, anxiety, and stress symptoms at age 22 and 27 years. METHODS: Participants were 616 emerging adults enrolled in the Raine Study. Lifestyle classes at baseline were identified using latent class analysis. Longitudinal associations between latent class membership and risk of depression, anxiety, and stress symptoms were examined using logistic regression models. RESULTS: Three lifestyle classes were identified: Class 1 (healthier pattern, n = 399 [64.8 %]), Class 2 (predominantly female, high substance-use, low physical activity pattern, n = 121 [19.6 %]), and Class 3 (predominantly male, high substance-use, poor diet pattern, n = 96 [15.6 %]). Following adjustment, Class 2 were at a higher risk of depression, anxiety, and stress symptoms at age 22 years, and a higher risk of anxiety and stress symptoms at age 27 years, compared to Class 1. LIMITATIONS: This study was limited by reliance on self-report data, lack of available indicators for parental socioeconomic status, and some measurement inconsistencies across variables. Adherence to lifestyle clusters over time was not assessed. CONCLUSIONS: Latent classes of lifestyle behaviours were identified among emerging adults, and differences in mental health outcomes were found among the classes at two prospective time points. Future research and prevention strategies for common mental disorders should target emerging adults and focus on lifestyle patterns.

Parenting orientations in young adulthood: Predicting timing of parenthood and quality of postpartum caregiving.

Most but not all adults become parents, yet it remains unclear which characteristics indicate an orientation toward parenting. The aims of this study were to (a) distinguish profiles of individual and interpersonal resources in young adults that may orient them toward parenthood and (b) investigate whether profiles predicted timing of entering parenthood, postpartum parenting behavior, and parent-infant bonding. Participants were 1,429 young people (53% female) enrolled in an Australian 39-year longitudinal study. Predictor data for latent profile analysis were collected at 23-24 and 27-28 years. Parenthood timing was designated as "early" ≤ 25 years, "on-time" > 25 years, and "not a parent" by age 37 years. Parenting outcomes were assessed at 12 months postpartum in 684 parents of 1,144 children. Four-profile classes were identified: "connected" (n = 463, 32.4%), "constricted empathy" (n = 461, 32.3%), "insecure" (n = 343, 24%), and "disconnected" (n = 162, 11.3%). Connected young adults were characterized by close ties to family of origin and peers and by identity clarity and empathy. Connected participants were more likely than those in insecure and disconnected classes to be parents by 37 years and more likely to enter parenthood "on-time" compared to "early" parenthood in the constricted empathy class. Among those who became parents, the connected class reported the strongest bonds and warmest parenting and was least anxious or hostile in parenting their infants. Findings provide insights into preconception patterns among variables that together predict reproductive timing, postpartum bonding, and quality of parenting. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Enhancing older adult financial decision making through the use of self-evaluation worksheets.

Financial products and options are frequently complex and difficult for consumers to understand, which, alongside positively oriented sales pitches and predatory practices, may lead to uninformed and hazardous financial decisions. While several legal reforms have been implemented to improve consumers' understanding of financial products, these modifications have only achieved mixed results. An ongoing challenge is the passive nature of such modifications, giving rise to confirmation bias-noticing the information which confirms one's belief about a product, while ignoring or not paying enough attention to the potential risks. The aim of this study was to test an implementable form of public policy to help older adults successfully navigate these financial decisions. We tested whether a self-evaluation worksheet (in conjunction with a written disclosure), involving an active manipulation of financial content, would significantly impact older adult participants' responses in an experimental reverse mortgage scenario. Forty community-dwelling, healthy older adults were randomized to one of two conditions: Control Condition (passive manipulation of financial content) and Manipulation Condition (active manipulation of financial content). In addition to completing a comprehensive neuropsychological examination, participants were administered the Reverse Mortgage Task (RM Task). Results indicated that a simple yet active manipulation-imparting accurate and understandable information regarding a complex financial product that must be further manipulated-led to the following among participants in the Manipulation Condition: (1) declines in mood; (2) superior understanding of the financial product; and (3) reduced intention of purchasing the financial product. In order for older adults to be well informed about reverse mortgages, policies must be put in place to ensure that adequate and accurate information has been not only provided but also actively processed by the individual.

Multidimensional CNN-Based Deep Segmentation Method for Tumor Identification.

Weighted MR images of 421 patients with nasopharyngeal cancer were obtained at the head and neck level, and the tumors in the images were assessed by two expert doctors. 346 patients' multimodal pictures and labels served as training sets, whereas the remaining 75 patients' multimodal images and labels served as independent test sets. Convolutional neural network (CNN) for modal multidimensional information fusion and multimodal multidimensional information fusion (MMMDF) was used. The three models' performance is compared, and the findings reveal that the multimodal multidimensional fusion model performs best, while the two-modal multidimensional information fusion model performs second. The single-modal multidimensional information fusion model has the poorest performance. In MR images of nasopharyngeal cancer, a convolutional network can precisely and efficiently segment tumors.

Key measurement concepts and appropriate clinical outcome assessments in pediatric achondroplasia clinical trials.

BACKGROUND: This study aimed to identify fit-for-purpose clinical outcome assessments (COAs) to evaluate physical function, as well as social and emotional well-being in clinical trials enrolling a pediatric population with achondroplasia. Qualitative interviews lasting up to 90 min were conducted in the US with children/adolescents with achondroplasia and/or their caregivers. Interviews utilized concept elicitation methodology to explore experiences and priorities for treatment outcomes. Cognitive debriefing methodology explored relevance and understanding of selected COAs. RESULTS: Interviews (N = 36) were conducted with caregivers of children age 0-2 years (n = 8) and 3-7 years (n = 7) and child/caregiver dyads with children age 8-11 years (n = 15) and 12-17 years (n = 6). Children/caregivers identified pain, short stature, impacts on physical functioning, and impacts on well-being (e.g. negative attention/comments) as key bothersome aspects of achondroplasia. Caregivers considered an increase in height (n = 9/14, 64%) and an improvement in limb proportion (n = 11/14, 71%) as successful treatment outcomes. The Childhood Health Assessment Questionnaire (CHAQ) and Quality of Life in Short Stature Youth (QoLISSY-Brief) were cognitively debriefed. CHAQ items evaluating activities, reaching, and hygiene were most relevant. QoLISSY-Brief items evaluating reaching, height bother, being treated differently, and height preventing doing things others could were most relevant. The CHAQ and QoLISSY-Brief instructions, item wording, response scales/options and recall period were well understood by caregivers and adolescents age 12-17. Some children aged 8-11 had difficulty reading, understanding, or required caregiver input. Feedback informed minor amendments to the CHAQ and the addition of a 7-day recall period to the QoLISSY-Brief. These amendments were subsequently reviewed and confirmed in N = 12 interviews with caregivers of children age 0-11 (n = 9) and adolescents age 12-17 (n = 3). CONCLUSIONS: Achondroplasia impacts physical functioning and emotional/social well-being. An increase in height and improvement in limb proportion are considered to be important treatment outcomes, but children/adolescents and their caregivers expect that a successful treatment should also improve important functional outcomes such as reach. The CHAQ (adapted for achondroplasia) and QoLISSY-Brief are relevant and appropriate measures of physical function and emotional/social well-being for pediatric achondroplasia trials; patient-report is recommended for age 12-17 years and caregiver-report is recommended for age 0-11 years.

Paternal coping and psychopathology during the perinatal period: A mixed studies systematic review and meta-analysis.

How fathers cope with stress may be critical to their mental health during the perinatal period. Using a sequential explanatory design for systematic review and meta-analysis, we aimed to identify associations and causal relations between higher- and lower-order avoidant and approach coping strategies and paternal psychopathology. We searched five electronic databases and grey literature, and used random-effects models to calculate pooled effects from 11 quantitative studies. Meta-analytic results were integrated with findings from 18 qualitative studies. Fathers' avoidant coping was positively associated with global psychopathology and depression. Approach-oriented coping, particularly problem-solving, was associated with positive affect but not psychopathology. Qualitative findings indicate distressed fathers employ avoidant coping strategies such as suppression, distraction, and social withdrawal. Approach-oriented coping strategies such as problem-solving and cognitive reappraisals appeared to be constructive components of men's coping repertoires supporting adaptation to fatherhood. Different coping strategies and approaches may reflect enactment of constrictive, moderate, or reinterpreted masculine norms. Study designs did not allow conclusions about causal relations between coping and psychopathology. Screening for, and targeting of, high avoidant coping among expectant and new fathers may help detect men at risk of or experiencing mental health difficulties and inform clinical response to psychopathology. Research examining whether different patterns of avoidant and approach coping are associated with psychopathology over time could inform interventions to support men's mental health and adaptation to fatherhood.

Universal depression prevention: An umbrella review of meta-analyses.

Depression is a disabling, highly prevalent, frequently chronic, and difficult-to-treat disorder with an immense cognitive, social, and economic burden. Given that many of the advances in other non-communicable disorders like cancer have been in prevention rather than treatment, the prevention of depression is currently an unmet public health priority. We sought to provide an overview of the meta-analytic literature through conducting a systematic umbrella review of universally delivered preventive interventions for depression. The search was conducted on March 18, 2021 utilising the following databases (all accessed through EBSCOHost); Allied and Complementary Medicine Database, CINAHL Complete, Global Health, Health Source: Nursing/Academic Edition, MEDLINE Complete and APA PsychArticles. The following search terms related to depression, prevention, and trial study design. Two authors independently screened articles and a third resolved discrepancies. Eligibility criteria sought to identify meta-analyses that investigated the prevention of depression (i.e., reduced incidence) through intervention studies that were universal, in that they were designed to be delivered to entire populations Six meta-analyses on psychological interventions, two school-based meta-analyses, and one eHealth meta-analysis were included in this umbrella review. Findings indicated that all identified studies were of good quality and one was of fair quality. One previous meta-review that examined physical activity to prevent depression was included in results, comprising eight meta-analyses. Preventive interventions have primarily and successfully utilized psychological therapeutic components, delivered at the school, community, and workplace settings. Both school- and eHealth-based interventions hold some utility for depression prevention. There is meta-analytic evidence that physical activity is efficacious for depression prevention. However, universal prevention is inconsistently defined. There is a pressing need for well-designed randomized controlled preventative interventions for depression before recommendations can be universally accepted with convincing level of evidence.

The Dietary Inflammatory Index and Human Health: An Umbrella Review of Meta-Analyses of Observational Studies.

Numerous observational studies have investigated the role of the Dietary Inflammatory Index (DII®) in chronic disease risk. The aims of this umbrella review and integrated meta-analyses were to systematically synthesize the observational evidence reporting on the associations between the DII and health outcomes based on meta-analyses, and to assess the quality and strength of the evidence for each associated outcome. This umbrella review with integrated meta-analyses investigated the association between the DII and a range of health outcomes based on meta-analyses of observational data. A credibility assessment was conducted for each outcome using the following criteria: statistical heterogeneity, 95% prediction intervals, evidence for small-study effect and/or excess significance bias, as well as effect sizes and P values using calculated random effects meta-analyses. In total, 15 meta-analyses reporting on 38 chronic disease-related outcomes were included, incorporating a total population of 4,360,111 subjects. Outcomes (n = 38) were examined through various study designs including case-control (n = 8), cross-sectional (n = 5), prospective (n = 5), and combination (n = 20) study designs. Adherence to a pro-inflammatory dietary pattern had a significant positive association with 27 (71%) of the included health outcomes (P value < 0.05). Using the credibility assessment, Class I (Convincing) evidence was identified for myocardial infarction only, Class II (Highly suggestive) evidence was identified for increased risk of all-cause mortality, overall risk of incident cancer, and risk of incident site-specific cancers (colorectal, pancreatic, respiratory, and oral cancers) with increasing (more pro-inflammatory) DII score. Most outcomes (n = 31) presented Class III (Suggestive) or lower evidence (Weak or No association). Pro-inflammatory dietary patterns were nominally associated with an increased risk of many chronic disease outcomes. However, the strength of evidence for most outcomes was limited. Further prospective studies are required to improve the precision of the effect size.

Association of Child and Adolescent Mental Health With Adolescent Health Behaviors in the UK Millennium Cohort.

Importance: There is potential for mental health status to act as a determinant of an individual's ability to engage in healthful lifestyle behaviors. Objective: To investigate the associations of parent-reported mental health problems during childhood and self-reported mental health problems in adolescence with health behaviors in adolescence. Design, Setting, and Participants: This cohort study used data from wave 4 (collected in 2008) and wave 6 (collected in 2015) of the Millennium Cohort Study, a UK population-representative longitudinal study of young people born during 2000 to 2001. Wave 4 included data on parent-reported mental health issues for children at age 7 years. Wave 6 included data on self-reported mental health problems as well as health behaviors for the same children at age 14 years. Data were analyzed July 5, 2020. Exposures: Mental health problems at age 7 years were parent-reported using Strengths and Difficulties Questionnaire. Mental health problems at age 14 years were self-reported using the Short Mood and Feelings Questionnaire. Main Outcomes and Measures: Health behaviors at age 14 years were the main outcome of interest. Sleep duration; fruit, vegetable, and soft drink consumption; and social media use were self-reported using recall on a typical day. Regression models were calculated for each lifestyle variable, with mental health change from ages 7 to 14 years as the exposure variable. Data were weighted to account for the potential clustering of region of sampling and adjusted for nonresponse. Results: A total of 9369 participants were included in waves 4 and 6 of the Millennium Cohort Study, including 4665 (48.1%) girls and 6014 participants (81.9%) who were born in England. Adolescents who self-reported mental health problems at age 14 years only were less likely to have at least 9 hours of sleep (odds ratio [OR], 0.39; 95% CI, 0.34-0.45) and to consume fruit (OR, 0.55; 95% CI, 0.46-0.65) and vegetables (OR, 0.66; 95% CI, 0.52-0.83) reported greater use of social media (b = 0.62; 95% CI, 0.49-0.75) compared with individuals who did not have mental health problems at both time points. Similarly, those with mental health problems at both time points were less likely to achieve 9 hours sleep (OR, 0.68; 95% CI, 0.51-0.90), consume fruit (OR, 0.39; 95% CI, 0.26-0.58) and vegetables (OR, 0.57; 95% CI, 0.35-0.91), and reported greater social media use (b = 0.63; 95% CI, 0.34-0.91). Conclusions and Relevance: These findings suggest that the presence of depressive symptoms at ages 7 and 14 years and at age 14 years only were associated with some health behaviors in adolescence. These findings are particularly important given that independent health behaviors can deteriorate and become habitual during adolescence, and adolescence is a known time for the first emergence of mental health problems that continue into adulthood.

Steam explosion of oilseed rape straw: establishing key determinants of saccharification efficiency.

Oilseed rape straw was steam exploded into hot water at a range of severities. The residues were fractionated into solid and liquid phases and chemically characterised. The effect of steam explosion on enzymatic hydrolysis of the water-insoluble fractions was investigated by studying initial cellulase binding and hydrolysis yields for different cellulase doses. Time-course data was modelled to establish rate-dependent differences in saccharification as a function of pretreatment severity and associated chemical composition. The study concluded: (1) the initial hydrolysis rate was limited by the amount of (pectic) uronic acid remaining in the substrate; (2) the proportion of rapidly hydrolysable carbohydrate was most closely and positively related to lignin abundance and (3) the final sugar yield most closely related to xylan removal from the substrate. Comparisons between milled and un-milled steam exploded straw highlighted the influence that physical structure has on hydrolysis rates and yields, particularly at low severities.

Regulation of CD4⁺ and CD8⁺ effector responses by Sprouty-1.

TCR-induced NF-AT activation leads to the expression of both activating and inhibitory proteins. Previously, we had identified Egr-2 and Egr-3 as NF-AT-induced transcription factors which promote the inhibition of T cell activation. In this report we identify Sprouty1 as a downstream target of Egr-3. CD4⁺ T cells lacking Spry1 demonstrate enhanced proliferation and cytokine production. Likewise, Spry1(Flox/Flox) Lck Cre CD8⁺ T cells display increased cytolytic activity. Mechanistically, Spry1 acts at the level of PLC-γ promoting the inhibition of both Ca⁺⁺ induced NF-AT activation and MAP-kinase induced AP-1 activation while sparing NF-κB signaling. In vivo, mice in which Spry1 is selectively deleted in T cells demonstrate enhanced responses to a tumor vaccine and subsequently reject tumors more robustly than Wt mice. These findings suggest that targeting Spry1 might prove to be a novel means of enhancing tumor immunotherapy.

Opposing regulation of T cell function by Egr-1/NAB2 and Egr-2/Egr-3.

TCR-induced NF-AT activation leads to the up-regulation of multiple genes involved in T cell anergy. Since NF-AT is also involved in T cell activation, we have endeavored to dissect TCR-induced activating and inhibitory genetic programs. This approach revealed roles for the early growth response (Egr) family of transcription factors and the Egr coactivator/corepressor NGFI-A-binding protein (NAB)2 in regulating T cell function. TCR-induced Egr-1 and NAB2 enhance T cell function, while Egr-2 and Egr-3 inhibit T cell function. In this report, we demonstrate that Egr-2 and Egr-3 are induced by NF-AT in the absence of AP-1, while Egr-1 and NAB2 both require AP-1-mediated transcription. Our data suggest that Egr-3 is upstream of Egr-2, and that mechanistically Egr-2 and Egr-3 suppress Egr-1 and NAB2 expression. Functionally, T cells from Egr-2 and Egr-3 null mice are hyperresponsive while T cells from Egr-3 transgenic, overexpressing mice are hyporesponsive. Furthermore, an in vivo model of autoimmune pneumonitis reveals that T cells from Egr-3 null mice hasten death while Egr-3-overexpressing T cells cause less disease. Overall, our data suggest that just as the Egr/NAB network of genes control cell fate in other systems, TCR-induced Egr-1, 2, 3 and NAB2 control the fate of antigen recognition in T cells.