A paradigm shift in cystic fibrosis nutritional care: clinicians' views on the management of patients with overweight and obesity

Background Overweight and obesity among people with cystic fibrosis (pwCF) has become more prevalent since the widespread adoption of CF transmembrane conductance regulator (CFTR) modulator therapies and presents a new challenge for nutritional care. We aimed to explore how clinicians working in CF care approach the management of adults with overweight and obesity. Methods We conducted semi-structured interviews with n = 20 clinicians (n = 6 physiotherapists, n = 6 doctors and n = 8 dietitians) working in 15 adult CF centres in the United Kingdom. The interviews explored their perspectives and current practices caring for people with CF and overweight/obesity. Data were analysed using reflexive thematic analysis. Results Four main themes were identified: 1) challenges of raising the topic of overweight and obesity in the CF clinic (e.g., clinician-patient rapport and concerns around weight stigma); 2) the changing landscape of assessment due to CF-specific causes of weight gain: (e.g., impact of CFTR modulators and CF legacy diet) 3) presence of clinical equipoise for weight management due to the lack of CF-specific evidence on the consequences of obesity and intentional weight loss (e.g., unclear consequences on respiratory outcomes and risk of weight related co-morbidities) and 4) opportunities for a safe, effective, and acceptable weight management treatment for people with CF (e.g., working collaboratively with current multidisciplinary CF care). Conclusions Approaching weight management in the CF setting is complex. Trials are needed to assess the equipoise of weight management interventions in this group and CF-specific issues should be considered when developing such interventions

The utility of twins in developmental cognitive neuroscience research: How twins strengthen the ABCD research design

The ABCD twin study will elucidate the genetic and environmental contributions to a wide range of mental and physical health outcomes in children, including substance use, brain and behavioral development, and their interrelationship. Comparisons within and between monozygotic and dizygotic twin pairs, further powered by multiple assessments, provide information about genetic and environmental contributions to developmental associations, and enable stronger tests of causal hypotheses, than do comparisons involving unrelated children. Thus a sub-study of 800 pairs of same-sex twins was embedded within the overall Adolescent Brain and Cognitive Development (ABCD) design. The ABCD Twin Hub comprises four leading centers for twin research in Minnesota, Colorado, Virginia, and Missouri. Each site is enrolling 200 twin pairs, as well as singletons. The twins are recruited from registries of all twin births in each State during 2006–2008. Singletons at each site are recruited following the same school-based procedures as the rest of the ABCD study. This paper describes the background and rationale for the ABCD twin study, the ascertainment of twin pairs and implementation strategy at each site, and the details of the proposed analytic strategies to quantify genetic and environmental influences and test hypotheses critical to the aims of the ABCD study. Keywords: Twins, Heritability, Environment, Substance use, Brain structure, Brain functio

Peripheral Deletion of Autoreactive CD8 T Cells by Cross Presentation of Self-Antigen Occurs by a Bcl-2–inhibitable Pathway Mediated by Bim

By transgenic expression of ovalbumin (OVA) as a model self antigen in the β cells of the pancreas, we have shown that self tolerance can be maintained by the cross-presentation of this antigen on dendritic cells in the draining lymph nodes. Such cross-presentation causes initial activation of OVA-specific CD8 T cells, which proliferate but are ultimately deleted; a process referred to as cross-tolerance. Here, we investigated the molecular basis of cross-tolerance. Deletion of CD8 T cells was prevented by overexpression of Bcl-2, indicating that cross-tolerance was mediated by a Bcl-2 inhibitable pathway. Recently, Bim, a pro-apoptotic Bcl-2 family member whose function can be inhibited by Bcl-2, was found to play a critical role in the deletion of autoreactive thymocytes, leading us to examine its role in cross-tolerance. Bim-deficient T cells were not deleted in response to cross-presented self-antigen, strongly implicating Bim as the pro-apoptotic mediator of cross-tolerance

Genetic and Environmental Influences on Perceived Social Support: Differences by Sex and Relationship

Previous research has shown that self-reports of the amount of social support are heritable. Using the Kessler perceived social support (KPSS) measure, we explored sex differences in the genetic and environmental contributions to individual differences. We did this separately for subscales that captured the perceived support from different members of the network (spouse, twin, children, parents, relatives, friends and confidant). Our sample comprised 7059 male, female and opposite-sex twin pairs aged 18−95 years from the Australian Twin Registry. We found tentative support for different genetic mechanisms in males and females for support from friends and the average KPSS score of all subscales, but otherwise, there are no sex differences. For each subscale alone, the additive genetic (A) and unique environment (E) effects were significant. By contrast, the covariation among the subscales was explained - in roughly equal parts - by A, E and the common environment, with effects of different support constellations plausibly accounting for the latter. A single genetic and common environment factor accounted for between half and three-quarters of the variance across the subscales in both males and females, suggesting little heterogeneity in the genetic and environmental etiology of the different support sources

Distinct APC subtypes drive spatially segregated CD4+ and CD8+ T-Cell effector activity during skin infection with HSV-1

Efficient infection control requires potent T-cell responses at sites of pathogen replication. However, the regulation of T-cell effector function in situ remains poorly understood. Here, we show key differences in the regulation of effector activity between CD4+ and CD8+ T-cells during skin infection with HSV-1. IFN-γ-producing CD4+ T cells disseminated widely throughout the skin and draining lymph nodes (LN), clearly exceeding the epithelial distribution of infectious virus. By contrast, IFN-γ-producing CD8+ T cells were only found within the infected epidermal layer of the skin and associated hair follicles. Mechanistically, while various subsets of lymphoid- and skin-derived dendritic cells (DC) elicited IFN-γ production by CD4+ T cells, CD8+ T cells responded exclusively to infected epidermal cells directly presenting viral antigen. Notably, uninfected cross-presenting DCs from both skin and LNs failed to trigger IFN-γ production by CD8+ T-cells. Thus, we describe a previously unappreciated complexity in the regulation of CD4+ and CD8+ T-cell effector activity that is subset-specific, microanatomically distinct and involves largely non-overlapping types of antigen-presenting cells (APC).The work was funded by grant (APP628423 and APP1059514) and fellowship support from the National Health and Medical Research Council Australia (NHMRC)and the Australian Research Council (ARC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

\u3ci\u3eProsopis glandulosa\u3c/i\u3e persistence is facilitated by differential protection of buds during low- and high-energy fires

Rangelands worldwide have experienced significant shifts from grass-dominated to woody-plant dominated states over the past century. In North America, these shifts are largely driven by overgrazing and landscape-scale fire suppression. Such shifts reduce productivity for livestock, can have broad-scale impacts to biodiversity, and are often difficult to reverse. Restoring grass dominance often involves restoring fire as an ecological process. However, many resprouting woody plants persist following disturbance, including fire, by resprouting from protected buds, rendering fire ineffective for reducing resprouting woody plant density. Recent research has shown that extreme fire (high-energy fires during periods of water stress) may reduce resprouting capacity. This previous research did not examine whether high-energy fires alone would be sufficient to cause mortality. We created an experimental framework for assessing the “buds-protection-resources” hypothesis of resprouting persistence under different fire energies. In July–August 2018 we exposed 48 individuals of a dominant resprouting woody plant in the region, honey mesquite (Prosopis glandulosa), to two levels of fire energy (high and low) and root crown exposure (exposed vs unexposed) and evaluated resprouting capacity. We censused basal and epicormic resprouts for two years following treatment. Water stress was moderate for several months leading up to fires but low in subsequent years. Epicormic and basal buds were somewhat protected from lowand high-energy fire. However, epicormic buds were protected in very few mesquites subjected to high-energy fires. High-energy fires decreased survival, caused loss of apical dominance, and left residual dead stems, which may increase chances of mortality from future fires. Basal resprout numbers were reduced by high-energy fires, which may have additional implications for long-term mesquite survival. While the buds, protection, and resources components of resprouter persistence all played a role in resprouting, high-energy fire decreased mesquite survival and reduced resprouting. This suggests that high-energy fires affect persistence mechanisms to different extents than low-energy fires. In addition, high-energy fires during normal rainfall can have negative impacts on resprouting capacity; water stress is not a necessary precursor to honey mesquite mortality from highenergy fire

Exotic herbivores and fire energy drive standing herbaceous biomass but do not alter compositional patterns in a semiarid savanna ecosystem

Questions: Fire regime alterations are pushing open ecosystems worldwide past tipping points where alternative steady states characterized by woody dominance prevail. This reduces the frequency and intensity of surface fires, further limiting their effectiveness for controlling cover of woody plants. In addition, grazing pressure (exotic or native grazers) can reinforce woody encroachment by potentially reducing fine-fuel loads. We investigated the effects of different fire energies on the herbaceous plant community, together with mammalian wildlife herbivory (exotic and native combined) exclusion, to inform best management practices. Location: Texas semi-arid savanna, southern Great Plains, USA. Methods: We conducted an experiment in which we manipulated fire intensity and herbivore access to herbaceous biomass in a split-plot design. We altered fire energy via fuel addition rather than applying fire under different environmental conditions to control for differences in standing biomass and composition attributable to differential plant physiological status and fire season. Results: High-energy fire did not reduce herbaceous biomass or alter plant community composition, although it did increase among-plot variability in composition and forb biomass relative to low-energy fire and non-burned controls. Grazing pressure from native and non-native mammalian herbivores reduced above-ground herbaceous biomass regardless of fire treatments, but did not alter community composition. Conclusions: Managers seeking to apply high-intensity prescribed fire to reduce woody encroachment will not negatively impact herbaceous plant productivity or alter community composition. However, they should be cognizant that repeated fires necessary for greatly reducing woody plants in heavily invaded areas might be difficult to accomplish due to fine-fuel reduction from wild herbivores. High fencing to restrict access by wildlife herbivores or culling might be necessary to build fuels sufficient to conduct high-intensity burns for woody-plant reductio

Genetic and environmental variation in continuous phenotypes in the ABCD Study®

Twin studies yield valuable insights into the sources of variation, covariation and causation in human traits. The ABCD Study® (abcdstudy.org) was designed to take advantage of four universities known for their twin research, neuroimaging, population-based sampling, and expertise in genetic epidemiology so that representative twin studies could be performed. In this paper we use the twin data to: (i) provide initial estimates of heritability for the wide range of phenotypes assessed in the ABCD Study using a consistent direct variance estimation approach, assuring that both data and methodology are sound; and (ii) provide an online resource for researchers that can serve as a reference point for future behavior genetic studies of this publicly available dataset. Data were analyzed from 772 pairs of twins aged 9-10 years at study inception, with zygosity determined using genotypic data, recruited and assessed at four twin hub sites. The online tool provides twin correlations and both standardized and unstandardized estimates of additive genetic, and environmental variation for 14,500 continuously distributed phenotypic features, including: structural and functional neuroimaging, neurocognition, personality, psychopathology, substance use propensity, physical, and environmental trait variables. The estimates were obtained using an unconstrained variance approach, so they can be incorporated directly into meta-analyses without upwardly biasing aggregate estimates. The results indicated broad consistency with prior literature where available and provided novel estimates for phenotypes without prior twin studies or those assessed at different ages. Effects of site, self-identified race/ethnicity, age and sex were statistically controlled. Results from genetic modeling of all 53,172 continuous variables, including 38,672 functional MRI variables, will be accessible via the user-friendly open-access web interface we have established, and will be updated as new data are released from the ABCD Study. This paper provides an overview of the initial results from the twin study embedded within the ABCD Study, an introduction to the primary research domains in the ABCD study and twin methodology, and an evaluation of the initial findings with a focus on data quality and suitability for future behavior genetic studies using the ABCD dataset. The broad introductory material is provided in recognition of the multidisciplinary appeal of the ABCD Study. While this paper focuses on univariate analyses, we emphasize the opportunities for multivariate, developmental and causal analyses, as well as those evaluating heterogeneity by key moderators such as sex, demographic factors and genetic background