Breast Cancer Survivorship Rehabilitation Initiative: Community Report

The Breast Cancer Survivorship Rehabilitation Initiative (BCSRI) conducted an assessment of breast cancer survivorship services in the Greater Birmingham area, including Blount, Jefferson, Shelby, St. Clair, and Walker counties, over the course of four (4) months. Project staff disseminated surveys and conducted one-on-one interviews with self-identifying respondents. Following the conclusion of both the surveys and interviews, discussion groups were held. An Ad Hoc Committee was then formed from a group of community leaders and experts in the field of cancer survivorship to review the data and provide feedback. The BCSRI also conducted interviews with the directors of 12 cancer survivorship programs throughout the country. The aggregated data was presented in monthly meetings to a leadership team consisting of executive level hospital administrators in the Greater Birmingham area.This report will summarize the data and serve as a resource to develop programs throughout the community to provide breast cancer survivorship care and patient advocacy. Next steps include developing the infrastructure needed to build a survivorship program that will meet the needs of breast cancer survivors in the Greater Birmingham area, and potentially become a model that can be replicated for other cancer types and diseases or for breast cancer survivors in other communities

Plant-forward diets and the social cultural milieu

Humanity’s window for climate action is closing rapidly (Tollefson, 2022). Given the ecological footprint associated with animal husbandry, scholars and non-governmental organisations have called for a transition to a more sustainable food system: an increased focused on plant-derived proteins (Clark et al., 2022; Willett et al., 2019). Such a transformation will require the collaboration of many actors both in- and outside of academia (e.g., social scientists, food technologists, businesspeople, and advocates). The field of Psychology has a unique role to play in studying human behaviour and cognition as it pertains to societal eating norms and the acceptance of plant-forward diets. Research of this kind has demonstrated that decisions to forgo animal-derived foods constitute a social eating norm violation and as such ought to be understood against the wider context in which they exist. Indeed, food-related decision-making occurs at various levels of society and food systems – including at the micro- (e.g., an individual’s own attitudes, motivations, and capabilities), meso- (e.g., family roles, relational dynamics) and distal-level (e.g., societal, and cultural norms around food; Boulet et al., 2021). Yet, to the authors knowledge, there is limited psychological literature that has considered these processes as they relate to plant-forward diets, specifically. Accordingly, the current thesis presents a rich exploration into the influence that one’s social-cultural milieu has on their food-related cognitions and decision making as they pertain to plant-forward eating. Study 1 employed smartphone-based experience sampling methodology and engaged in a micro-level analysis, investigating an individual’s commitment to reducing their meat consumption as influences by the experience of social support. In summary, we were unable to demonstrate the facilitative effects of social support in study 1. The results of this study highlighted the need to differentiate between types of social support (incl. structural, functional, and enacted means of support) and prompted a progression of our research focus: a move from studying food decision-making at the micro- to the meso-level. Study 2 and 3 employed a mix of survey and experience-sampling methodology with an elevated focus on the meso-level (i.e., the household), where we considered the influence of one’s primary social units (i.e., family members and romantic partners) on decisions pertaining to plant-forward diets. Here we demonstrated that micro-level food decision-making takes place within the broader context of intra-family negotiations and is subject to the established leadership style and emotional connection of the relationship. Finally, study 4 and 5 considered the intergroup and social-cultural context of plant-forward diets at the distal-level. Specifically, we employed a mix of survey methodology, text, and behaviour analytics to investigate the collective identity and ideological motivations of individuals actively engaged in overt antagonism or opposition towards vegan ideology. Together, this body of research advances current knowledge of the social and cultural milieu of plant-forward by demonstrating how decisions around plant-forward diets depend upon the relational climate of cohabiting units and highlighting the importance of identity and inter-group processes in the wider societal debate about sustainable diets

Author Correction: Mutant p53 sustains serine-glycine synthesis and essential amino acids intake promoting breast cancer growth

Reprogramming of amino acid metabolism, sustained by oncogenic signaling, is crucial for cancer cell survival under nutrient limitation. Here we discovered that missense mutant p53 oncoproteins stimulate de novo serine/glycine synthesis and essential amino acids intake, promoting breast cancer growth. Mechanistically, mutant p53, unlike the wild-type counterpart, induces the expression of serine-synthesis-pathway enzymes and L-type amino acid transporter 1 (LAT1)/CD98 heavy chain heterodimer. This effect is exacerbated by amino acid shortage, representing a mutant p53-dependent metabolic adaptive response. When cells suffer amino acids scarcity, mutant p53 protein is stabilized and induces metabolic alterations and an amino acid transcriptional program that sustain cancer cell proliferation. In patient-derived tumor organoids, pharmacological targeting of either serine-synthesis-pathway and LAT1-mediated transport synergizes with amino acid shortage in blunting mutant p53-dependent growth. These findings reveal vulnerabilities potentially exploitable for tackling breast tumors bearing missense TP53 mutation

Mutant p53 sustains serine-glycine synthesis and essential amino acids intake promoting breast cancer growth

Reprogramming of amino acid metabolism, sustained by oncogenic signaling, is crucial for cancer cell survival under nutrient limitation. Here we discovered that missense mutant p53 oncoproteins stimulate de novo serine/glycine synthesis and essential amino acids intake, promoting breast cancer growth. Mechanistically, mutant p53, unlike the wild-type counterpart, induces the expression of serine-synthesis-pathway enzymes and L-type amino acid transporter 1 (LAT1)/CD98 heavy chain heterodimer. This effect is exacerbated by amino acid shortage, representing a mutant p53-dependent metabolic adaptive response. When cells suffer amino acids scarcity, mutant p53 protein is stabilized and induces metabolic alterations and an amino acid transcriptional program that sustain cancer cell proliferation. In patient-derived tumor organoids, pharmacological targeting of either serine-synthesis-pathway and LAT1-mediated transport synergizes with amino acid shortage in blunting mutant p53-dependent growth. These findings reveal vulnerabilities potentially exploitable for tackling breast tumors bearing missense TP53 mutations.Mutant p53 induces serine/glycine synthesis and essential amino acids intake. Under amino acid restriction, mutant p53 is stabilized and activates a transcriptional program that sustains a metabolic adaptive response promoting breast cancer cells growt

Levels, sources and chemical fate of persistent organic pollutants in the atmosphere and snow along the western Antarctic Peninsula

The Antarctic continent is among the most pristine regions; yet various organic contaminants have been measured there routinely. Air and snow samples were collected during the austral spring (October November, 2010) along the western Antarctic Peninsula and analyzed for organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) to assess the relative importance of long-range transport versus local primary or secondary emissions. Highest concentrations of PCBs, PBDEs and DDTs were observed in the glacier\u27s snow sample, highlighting the importance of melting glaciers as a possible secondary source of legacy pollutants to the Antarctic. In the atmosphere, contaminants were mainly found in the vapor phase (\u3e65%). Hexachlorobenzene (33.6 pg/m(3)), PCBs (11.6 pg/m(3)), heptachlor (5.64 pg/m(3)), PBDEs (4.22 pg/m(3)) and cis-chlordane (2.43 pg/m(3)) were the most abundant contaminants. In contrast to other compounds, PBDEs seem to have originated from local sources, possibly the research station itself. Gas-particle partitioning for analytes were better predicted using the adsorption partitioning model than an octanol-based absorption approach. Diffusive flux calculations indicated that net deposition is the dominant pathway for PBDEs and chlordanes, whereas re-volatilization from snow (during melting or metamorphosis) was observed for PCBs and some OCPs. (C) 2016 Elsevier Ltd. All rights reserved

Study Protocol: Type III hybrid Effectiveness-Implementation Study Implementing Age-Friendly Evidence-Based Practices in the VA to Improve Outcomes in Older Adults

Background Unmet care needs among older adults accelerate cognitive and functional decline and increase medical harms, leading to poorer quality of life, more frequent hospitalizations, and premature nursing home admission. The Department of Veterans Affairs (VA) is invested in becoming an “Age-Friendly Health System” to better address four tenets associated with reduced harm and improved outcomes among the 4 million Veterans aged 65 and over receiving VA care. These four tenets focus on “4Ms” that are fundamental to the care of older adults, including (1) what Matters (ensuring that care is consistent with each person’s goals and preferences); (2) Medications (only using necessary medications and ensuring that they do not interfere with what matters, mobility, or mentation); (3) Mentation (preventing, identifying, treating, and managing dementia, depression, and delirium); and (4) Mobility (promoting safe movement to maintain function and independence). The Safer Aging through Geriatrics-Informed Evidence-Based Practices (SAGE) Quality Enhancement Research Initiative (QUERI) seeks to implement four evidence-based practices (EBPs) that have shown efficacy in addressing these core tenets of an “Age-Friendly Health System,” leading to reduced harm and improved outcomes in older adults. Methods We will implement four EBPs in 9 VA medical centers and associated outpatient clinics using a type III hybrid effectiveness-implementation stepped-wedge trial design. We selected four EBPs that align with Age-Friendly Health System principles: Surgical Pause, EMPOWER (Eliminating Medications Through Patient Ownership of End Results), TAP (Tailored Activities Program), and CAPABLE (Community Aging in Place – Advancing Better Living for Elders). Guided by the Pragmatic Robust Implementation and Sustainability Model (PRISM), we are comparing implementation as usual vs. active facilitation. Reach is our primary implementation outcome, while “facility-free days” is our primary effectiveness outcome across evidence-based practice interventions. Discussion To our knowledge, this is the first large-scale randomized effort to implement “Age-Friendly” aligned evidence-based practices. Understanding the barriers and facilitators to implementing these evidence-based practices is essential to successfully help shift current healthcare systems to become Age-Friendly. Effective implementation of this project will improve the care and outcomes of older Veterans and help them age safely within their communities. Trial registration Registered 05 May 2021, at ISRCTN #60,657,985

NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease.

Genetic defects that affect intestinal epithelial barrier function can present with very early-onset inflammatory bowel disease (VEOIBD). Using whole-genome sequencing, a novel hemizygous defect in NOX1 encoding NAPDH oxidase 1 was identified in a patient with ulcerative colitis-like VEOIBD. Exome screening of 1,878 pediatric patients identified further seven male inflammatory bowel disease (IBD) patients with rare NOX1 mutations. Loss-of-function was validated in p.N122H and p.T497A, and to a lesser degree in p.Y470H, p.R287Q, p.I67M, p.Q293R as well as the previously described p.P330S, and the common NOX1 SNP p.D360N (rs34688635) variant. The missense mutation p.N122H abrogated reactive oxygen species (ROS) production in cell lines, ex vivo colonic explants, and patient-derived colonic organoid cultures. Within colonic crypts, NOX1 constitutively generates a high level of ROS in the crypt lumen. Analysis of 9,513 controls and 11,140 IBD patients of non-Jewish European ancestry did not reveal an association between p.D360N and IBD. Our data suggest that loss-of-function variants in NOX1 do not cause a Mendelian disorder of high penetrance but are a context-specific modifier. Our results implicate that variants in NOX1 change brush border ROS within colonic crypts at the interface between the epithelium and luminal microbes

Semantic computational analysis of anticoagulation use in atrial fibrillation from real world data

Atrial fibrillation (AF) is the most common arrhythmia and significantly increases stroke risk. This risk is effectively managed by oral anticoagulation. Recent studies using national registry data indicate increased use of anticoagulation resulting from changes in guidelines and the availability of newer drugs. The aim of this study is to develop and validate an open source risk scoring pipeline for free-text electronic health record data using natural language processing. AF patients discharged from 1st January 2011 to 1st October 2017 were identified from discharge summaries (N = 10,030, 64.6% male, average age 75.3 ± 12.3 years). A natural language processing pipeline was developed to identify risk factors in clinical text and calculate risk for ischaemic stroke (CHA2DS2-VASc) and bleeding (HAS-BLED). Scores were validated vs two independent experts for 40 patients. Automatic risk scores were in strong agreement with the two independent experts for CHA2DS2-VASc (average kappa 0.78 vs experts, compared to 0.85 between experts). Agreement was lower for HAS-BLED (average kappa 0.54 vs experts, compared to 0.74 between experts). In high-risk patients (CHA2DS2-VASc ≥2) OAC use has increased significantly over the last 7 years, driven by the availability of DOACs and the transitioning of patients from AP medication alone to OAC. Factors independently associated with OAC use included components of the CHA2DS2-VASc and HAS-BLED scores as well as discharging specialty and frailty. OAC use was highest in patients discharged under cardiology (69%). Electronic health record text can be used for automatic calculation of clinical risk scores at scale. Open source tools are available today for this task but require further validation. Analysis of routinely collected EHR data can replicate findings from large-scale curated registries.info:eu-repo/semantics/publishedVersio

Flower Girl Photo

Graphite, watercolor, digital collage.https://digitalcommons.hollins.edu/fbc2020_art/1008/thumbnail.jp