Search

Calreticulin (CRT) is a protein found mainly in the endoplasmic reticulum (ER) that maintains calcium levels and controls protein folding, but has recently been found at the cell surface, cytoplasm, and in the extracellular matrix. CRT participates in multiple physiological processes such as gene expression, the immune response, and cancer. Calreticulin has been shown to autoacetylate with the binding of preferred ligand 7,8-diacetoxy-4-methylcoumarin (DAMC). This project aims to develop a chemical biology approach to investigate importance of CRT acylating abilities on its nonendoplasmic reticulum functions by targeting the downstream substrates of CRT acetylation. Our goal was to use CRT to transfer a pentynoyl tag (using a novel ligand, DPeMC) to its substrates, which can then be used as a handle for protein identification. Molecular modelling using available data in the literature was used to approximate the binding interface between CRT and the acylation ligands. Molecular Operating Environment (MOE) software was used to perform sequence alignment, simulated annealing, positional refinement, and blind docking of acylated coumarins with the CRT model. Docking studies pointed to the P domain as the most thermodynamically and sterically favourable region for acylated coumarin binding with tryptophan residue 200 within the active site on CRT. Absorption and fluorescence spectra of all coumarin compounds in ethanol:PBS (1:9 v/v) solution were investigated. Stern-Volmer quenching constant (K

Indigenous experiences of hospitalisation may contribute to maintenance of Indigenous health inequities. We undertook a qualitative systematic review of Māori experiences of hospital care within New Zealand. We performed electronic database searches and used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to assist study selection. We were guided by Kaupapa Māori (Māori centred) research methodology and used the CONSolIDated critERtia statement to evaluate completeness of reporting against recommended Indigenous ethical guidelines. The Betancourt framework for addressing ethnic disparities in health care was utilised to synthesise findings. Seven studies were included. Studies enlisting Indigenous research expertise and Kaupapa Māori research methodology demonstrated clearer links between participant voices and critique of hospital experiences. Multiple barriers were identified within clinical, organisational and structural loci of practice. Proposed interventions focused on building cultural safety against these barriers. Strategies promoting access to care for Māori and cultural safety training for the workforce are needed.

OBJECTIVE At the outset of the coronavirus disease 2019 (COVID-19) pandemic, health care systems rapidly implemented telehealth services to maintain continuity of type 1 diabetes care. Youth of color are more likely to have suboptimal glycemic control and may benefit most from efforts to ensure continuity of care. However, research examining the perspectives of families of youth of color regarding telehealth for pediatric type 1 diabetes care is limited. We gathered perspectives from youth of color, their caregivers, and health care providers (HCPs) on telehealth for type 1 diabetes care during COVID-19. METHODS Fifty participants (22 caregivers, 19 youth, and nine HCPs) completed semi-structured interviews conducted in English (n = 44) or Spanish (n = 6). Transcripts containing mentions of telehealth (n = 33) were included for qualitative analysis to extract themes pertaining to perceptions of type 1 diabetes care and telehealth use during COVID-19. RESULTS Themes related to perceptions, feasibility, and quality of telehealth diabetes care were obtained. Most families had positive perceptions of telehealth. Families and HCPs described logistical and technical challenges and noted the potential for disparities in telehealth access and use. Furthermore, caregivers and HCPs felt that the lack of in-person interaction and limited access to clinical data affected the quality of care. CONCLUSION Families of youth of color with type 1 diabetes mostly had positive perceptions of telehealth but also identified issues with feasibility and quality of care. Our findings highlight a need for interventions promoting equal access to telehealth and quality care for all youth with type 1 diabetes to minimize disruptions in care.

There is an urgent need for high-quality evidence regarding post-operative mortality among Indigenous peoples. Our group recently published a national audit of 4,000,000 procedures conducted between 2005-2017, which identified considerable disparities in post-operative mortality between Indigenous Māori and non-Indigenous New Zealanders. Understanding the primary drivers of these disparities-for Māori, but likely also other Indigenous populations worldwide-requires us to consider the multiple levels at which these drivers might arise. To that end, in this paper we breakdown these drivers in detail, conceptualising these drivers as operating in layers with each factor leading to the next. These layers include structural factors, care system factors, care process factors, care team factors and patient factors. Each of these factors are presented within a framework that can be used to begin to understand them - with a view to rousing action and inspiring intervention to address inequities in post-operative outcomes experienced by Indigenous peoples.

Introduction: Patients with TNBC breast cancer have inferior treatment outcomes compared to other breast cancer subtypes and targeted therapies are lacking. S-equol is a novel oral Estrogen Receptor (ER) Beta agonist with preclinical data showing suppression of TNBC cellular proliferation, and recently presented data showed a decrease in Ki-67 in patients treated with S-equol. This abstract will present the molecular markers that correlate with Ki-67 change in patients with TNBC treated with neoadjuvant S-equol. Methods: We conducted a neoadjuvant window trial that enrolled 39 patients with confirmed TNBC on diagnostic core needle biopsy. Cohort A (20 patients) received a daily dose of 50 mg PO twice daily and Cohort B (19 patients) received a higher dose of 150 mg twice daily. Paired biopsies were evaluable for 36 patients. Both cohorts were treated for a duration of 10-21 days. Primary outcome was change from pre- to post-treatment Ki-67 evaluated by paired t-test and that data was previously published. Secondary endpoints include: Tumor infiltrating lymphocytes in intratumoral and peritumoral (stromal) locations using CD3 (pan T cell) and CD8 (cytotoxic T cell) immunohistochemistry, density of lymphocytes per high power field (40x) for both locations in pre-treatment and post-treatment specimens, Cyclin-D1 protein expression in pre-treatment and post-treatment biopsies as percentage of total tumor cells in pre-treatment and post-treatment specimens, and total estrogen receptor-beta protein expression using immunohistochemistry qualitatively and quantitatively using All-red score in pre-treatment and post-treatment specimens.Results: The primary outcome of Ki-67 decrease of at least 20% from baseline was observed in 28% of the patients. This is a placeholder abstract and an updated abstract with the correlative molecular markers as outlined above will be provided. Conclusion: S-equol is a novel well tolerated oral ER-Beta agonist with inhibition of proliferation in patients with TNBC as measured by a decrease in Ki-67. RNA-seq data, also previously presented, supports potential immune activation during this short period of drug exposure. Future studies aim to evaluate S-equol as an immune activating agent for combination with immunotherapies such as checkpoint inhibitors in TNBC. The pending molecular predictors of response will inform future therapeutic clinical trials for this novel therapy. Citation Format: Kate Lathrop, Virginia Kaklamani, Andrew Brenner, Rong Li, Alia Nazarullah, Sarah Hackman, Courtney Thomas, Jonathan Gelfond, Marisa Rodriguez, Richard Elledge. Molecular markers of response to s-equol, a novel oral estrogen receptor (ER) beta agonist for triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-31.

Background Distal pancreatic carcinoma is one of the most lethal cancers largely due to its high incidence of distant metastasis. This study aims to assess the prognostic value of splenic-vasculature involvement in resected distal pancreatic carcinoma. Methods In this retrospective study, we collected the clinicopathologic information of 454 patients with pancreatic cancer and performed univariate and multivariate analyses to identify factors associated with progression-free survival (PFS) and overall survival (OS), with an emphasis on the prognostic value of splenic-artery and -vein involvement. Results Univariate analysis revealed that larger tumor size, non-intraductal papillary mucinous neoplasm (non-IPMN)-associated adenocarcinoma, poor differentiation, stage pT3, nodal metastasis, lymphovascular invasion, perineural invasion, and pathologic and radiographic evidence of splenic-vein invasion were significantly associated with shorter PFS and OS (all P Conclusion Guidelines should be developed for a uniform approach with regard to the examination and reporting of the status of the splenic vasculature when dealing with distal-pancreatic-cancer specimens.

Smooth muscle tumors represent the second most common mural mesenchymal neoplasm in the gastrointestinal tract, but established criteria for prognostic assessment of these tumors are lacking. A large cohort of surgically resected intramural gastrointestinal smooth muscle tumors from 31 institutions was analyzed to identify potential prognostic features. Pathologic features were assessed by expert gastrointestinal and/or soft tissue pathologists at each center. Immunohistochemical confirmation was required. A total of 407 cases from the esophagus (n = 97, 24%), stomach (n = 180, 44%), small bowel (n = 74, 18%), and colorectum (n = 56, 14%) were identified. Patients ranged in age from 19 to 92 years (mean 55 years), with a slight female predominance (57%). Mean tumor size was 5.4 cm, with the largest tumor measuring 29 cm. Disease progression following surgery, defined as local recurrence, metastasis, or disease-related death, occurred in 56 patients (14%). Colorectal tumors were most likely to progress, followed by small bowel and gastric tumors. None of the esophageal tumors in this series progressed. Receiver operator characteristic analysis identified optimal cutoffs of 9.8 cm and 3 mitoses/5 mm2 for discriminating between progressive and non-progressive tumors. Histologic features strongly associated with progression by univariate analysis included moderate-to-severe atypia, high cellularity, abnormal differentiation (defined as differentiation not closely resembling that of normal smooth muscle), tumor necrosis, mucosal ulceration, lamina propria involvement, and serosal involvement (P 10 cm and/or showing ≥3 mitoses/5 mm2 may behave aggressively, and therefore close clinical follow-up is recommended in these cases.

BACKGROUND In order to improve risk stratification and clinical management of the pancreatic ductal adenocarcinoma (PDAC), the American Joint Committee on Cancer (AJCC) has published its eighth edition staging manual. Some major changes have been introduced in the new staging system for both T and N categories. Given the rarity of resectable disease, distal pancreatic cancer is likely underrepresented in the published clinical studies, and how the impact of the staging system actually reflects on to clinical outcomes remain unclear. AIM To validate the AJCC 8th edition of TNM staging in distal PDAC. METHODS A retrospective cohort study was performed in seven academic medical centers in the United States. Clinicopathological prognostic factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated through univariate and multivariate analyses. RESULTS Overall, 454 patients were enrolled in the study, and were divided into 2 subgroups: Invasive intraductal papillary mucinous neoplasms (IPMN) (115 cases) and non-IPMN associated adenocarcinoma (339 cases). Compared to invasive IPMN, non-IPMN associated adenocarcinomas are more common in relatively younger patients, have larger tumor size, are more likely to have positive lymph nodes, and are associated with a higher tumor (T) stage and nodal (N) stage, lymphovascular invasion, perineural invasion, tumor recurrence, and a worse PFS and OS. The cohort was predominantly categorized as stage 3 per AJCC 7th edition staging manual, and it’s more evenly distributed based on 8th edition staging manual. T and N staging of both 7th and 8th edition sufficiently stratify PFS and OS in the entire cohort, although dividing into N1 and N2 according to the 8th edition does not show additional stratification. For PDAC arising in IPMN, T staging of the 7th edition and N1/N2 staging of the 8th edition appear to further stratify PFS and OS. For PDAC without an IPMN component, T staging from both versions fails to stratify PFS and OS. CONCLUSION The AJCC 8th edition TNM staging system provides even distribution for the T staging, however, it does not provide better risk stratification than previous staging system for distal pancreatic cancer.

Background Providing high-quality psychosocial care to parents and other primary caregivers of children with cancer (henceforth referred to as caregivers) is important, given the numerous challenges associated with a pediatric cancer diagnosis and the increased risk for negative psychosocial sequelae among caregivers. The Electronic Surviving Cancer Competently Intervention Program (eSCCIP) is a psychosocial eHealth intervention for caregivers, developed using an iterative, user-centered process. Method eSCCIP was tested in a single-arm pilot trial at Nemours Children’s Hospital, Delaware (NCT05333601). The primary outcomes were intervention acceptability and feasibility, assessed via enrollment and retention targets, and item-level acceptability ratings. Enrollment and retention targets of 45% were set based on previous work, and an item-level acceptability threshold of 80% was set. A secondary exploratory analysis was conducted examining acute distress, anxiety, symptoms of post-traumatic stress, and family functioning. Results 44 caregivers enrolled in the study and 31 completed. The intervention was rated favorably by completers, with over 80% of the sample selecting “mostly true” or “very true” for all items of the eSCCIP Evaluation Questionnaire, which was used to assess acceptability and feasibility. Enrollment and retention rates were 54% and 70%, respectively. Exploratory psychosocial outcomes showed statistically significant decreases from pre-intervention to post-intervention for overall symptoms of post-traumatic stress disorder (PTSD), cluster D symptoms of PTSD (negative mood and cognitions), and anxiety. Small-moderate effect sizes were observed for all psychosocial outcomes of interest. Conclusions eSCCIP is an acceptable and feasible intervention for caregivers. Results are promising regarding reductions in symptoms of post-traumatic stress and anxiety.

Objectives: To identify coping profiles and evaluate their implications for depressive symptoms among Latinx adults. Methods: Data come from a community-dwelling sample of Latinx adults ages 45+ in Florida ( N = 461). Latent class analysis was used to identify profiles of personal coping resources based on patterns across spirituality (spiritual coping, divine fate), ethnic identity (centrality, connectedness), and personal control (mastery, self-esteem). Multivariable linear regression assessed differences in depressive symptoms across coping resource classes. Results: Four coping resource profiles were identified: (1) low resources overall, yet high spiritual coping; (2) high spirituality and personal control; (3) high spirituality and ethnic identity; and (4) high resources overall. Members of Class 4 had significantly fewer depressive symptoms than members of Class 1 and Class 3, controlling for sociodemographic characteristics, p < .001. Discussion: Results elucidate nuances in personal coping resources among aging Latinx adults, identify under-resourced groups, and suggest that resource profiles characterized by few personal coping resources are linked with more depressive symptoms. Findings clarify the underpinnings of the latent coping construct and have implications for mental health promotion interventions among aging Latinx adults.

Patients with d-looped transposition of the great arteries (d-TGA), especially those without an adequate atrial septal defect, can experience severe hypoxemia and hemodynamic compromise in the neonatal period. This can be mitigated by urgent balloon atrial septostomy (BAS). However, some patients with d-TGA are born at centers without this capability. The aim of this retrospective study of d-TGA patients who had urgent or emergent BAS at our institution between 2010 and 2021 was to evaluate time from birth to BAS for infants born at a tertiary care center as compared to those requiring transport from other institutions and to examine correlation between time to BAS and patient outcomes. Our primary outcome was time from birth to BAS. Secondary outcomes included hospital and ICU length of stay, mortality, and evidence of pulmonary or neurologic abnormalities including pulmonary hypertension, abnormal neuroimaging, or seizures. Of 96 patients, 67 (70%) were born at our institution. The median time to BAS was 4 hours for patients born at our institution vs. 14.1 hours for those born elsewhere (p

Supplemental Material for Loneliness Exacerbates the Association Between Bodily Pain and Depressive Symptoms Among Middle-Aged and Older Latinx Adults by Ángela Gutiérrez, Rosana L. Bravo and Courtney Thomas Tobin in Journal of Aging and Health

Young children who stay with their families in homeless shelters face chronic challenges related to extreme poverty and acute risks from stressful events surrounding the loss of housing and move to shelter. These adversities increase the likelihood of a range of poor developmental outcomes. Consistent with the risk and resilience perspective, however, many children who experience family homelessness succeed, functioning as well or better than their non-homeless peers. As such, efforts to support resilience should consider how best to enhance protective factors, such as supportive environments within shelter settings.With data from 60 caregivers of children ages birth to 5 years recruited from family shelters, we assessed caregivers' perceptions of community support as well as child and family well-being in terms of recent adverse experiences, parenting stress, access to social support, and child social-emotional functioning.Many caregivers experiencing family homelessness perceived negative aspects of the shelters where they were staying with their children. Furthermore, children whose caregivers had more negative perceptions of the shelter environment displayed worse social-emotional functioning, even when accounting for differences in parenting stress, recent family adversity, and other sources of social support.Because young children rely on their caregivers as primary resources for nurturance and support, we encourage family homelessness service providers to work in partnership with caregivers to create more inclusive and empowering practices within the shelter context. Doing so is likely to improve children's developmental outcomes and the overall well-being of the families.

The pressing need for SARS-CoV-2 controls has led to a reassessment of strategies to identify and develop natural product inhibitors of zoonotic, highly virulent, and rapidly emerging viruses. This review article addresses how contemporary approaches involving computational chemistry, natural product (NP) and protein databases, and mass spectrometry (MS) derived target-ligand interaction analysis can be utilized to expedite the interrogation of NP structures while minimizing the time and expense of extraction, purification, and screening in BioSafety Laboratories (BSL)3 laboratories. The unparalleled structural diversity and complexity of NPs is an extraordinary resource for the discovery and development of broad-spectrum inhibitors of viral genera, including Betacoronavirus, which contains MERS, SARS, SARS-CoV-2, and the common cold. There are two key technological advances that have created unique opportunities for the identification of NP prototypes with greater efficiency: (1) the application of structural databases for NPs and target proteins and (2) the application of modern MS techniques to assess protein-ligand interactions directly from NP extracts. These approaches, developed over years, now allow for the identification and isolation of unique antiviral ligands without the immediate need for BSL3 facilities. Overall, the goal is to improve the success rate of NP-based screening by focusing resources on source materials with a higher likelihood of success, while simultaneously providing opportunities for the discovery of novel ligands to selectively target proteins involved in viral infection.

To describe disparities in post-operative mortality experienced by Indigenous Māori compared to non-Indigenous New Zealanders.We completed a national study of all those undergoing a surgical procedure between 2005 and 2017 in New Zealand. We examined 30-day and 90-day post-operative mortality for all surgical specialties and by common procedures. We compared age-standardised rates between ethnic groups (Māori, Pacific, Asian, European, MELAA/Other) and calculated hazard ratios (HRs) using Cox proportional hazards regression modelling adjusted for age, sex, deprivation, rurality, comorbidity, ASA score, anaesthetic type, procedure risk and procedure specialty.From nearly 3.9 million surgical procedures (876,976 acute, 2,990,726 elective/waiting list), we observed ethnic disparities in post-operative mortality across procedures, with the largest disparities occurring between Māori and Europeans. Māori had higher rates of 30- and 90-day post-operative mortality across most broad procedure categories, with the disparity between Māori and Europeans strongest for elective/waiting list procedures (eg, elective/waiting list musculoskeletal procedures, 30-day mortality: adj. HR 1.93, 95% CI 1.56-2.39).The disparities we observed are likely driven by a combination of healthcare system, process and clinical team factors, and we have presented the key mechanisms within these factors.

Background Rhythm disorders are the leading cause of morbidity and mortality in adults with congenital heart disease (ACHD). Infrequent or asymptomatic arrhythmias may not be detected by routine monitoring. Implantable loop recorders (ILRs), such as the Reveal LINQTM , have been useful in long-term monitoring for arrhythmias in adults with cryptogenic stroke. Objective We propose the Reveal LINQTM will detect arrhythmias, not documented by other monitoring modalities, resulting in change in management in ACHD patients. Methods This is a single center retrospective review of Reveal LINQTM use in ACHD patients from 2014-2017. Medical records were reviewed to determine cardiac diagnosis, indication for implant, ILR findings, and changes in management. Results Twenty-two patients, median age 25 years, underwent ILR implantation. ILR findings resulted in change in management in nine (41%) patients. One-third (3/9) of the patients with clinically relevant events were asymptomatic. Patients with Fontan palliation had the highest number of pertinent positive events (57%). ACHD physiologic class D patients were more likely to have a positive finding (P = .034) compared to other physiologic classes. Majority (75%) of patients with positive events had arrhythmias documented on ILR which were not demonstrated on prior Holter/event monitors. Pertinent negative event occurred in one patient with Fontan palliation (5%) who had syncope corresponding to sinus rhythm. Conclusion ILRs are a useful adjunct for arrhythmia monitoring in the ACHD population with clinically relevant events in 41% of patients. A special consideration for ILRs could be made for high-risk asymptomatic patients.

Background: Diabetes-specific risk taking (DSRT) refers to unhealthy, risky behaviors that put someone with diabetes at increased risk for suboptimal health outcomes (e.g., drinking alcohol with others who are unaware you have T1D). DSRT is associated with less engagement in T1D management and higher HbA1c. This study set out to determine if lower levels of parental involvement in T1D care and higher levels of diabetes distress, also associated with less optimal T1D outcomes, were associated with DSRT among adolescents with T1D. Methods: Participants were 104 adolescents with T1D (Mage = 13.50 years, SDage = 1.69 years, 53.8% female, MHbA1c = 8.74%, SDHbA1c = 1.24%) who enrolled with their caregivers in a randomized controlled trial integrating psychologists and dietitians into T1D care visits (35% enrollment). Adolescents completed baseline measures of parental involvement, diabetes distress, and DSRT; caregivers reported demographics; and HbA1c was collected from the electronic medical record. Hierarchical linear regression was used to examine whether parental involvement and diabetes distress predicted DSRT after controlling for participants’ sex, race, ethnicity and HbA1c. Results: The full model was statistically significant and accounted for 29.7% of the variance in diabetes-specific risk taking (F(2, 91)= 19.1, p < .001). Neither HbA1c, sex, race nor ethnicity were statistically significant predictors of DSRT. Higher levels of diabetes distress (β = .23, p = .01) and lower parental involvement (β = -.44, p < .001) predicted more frequent DSRT. Conclusions: Adolescents with more diabetes distress and less collaborative parental involvement in T1D management reported more diabetes-specific risk taking. While causality cannot be asserted, these results can inform targeted behavioral interventions to help youth who are more likely to take risks in their T1D care. Future research should consider other factors contributing to diabetes-specific risk taking. Disclosure C. Thomas: None. T. Wysocki: None. M. A. Alderfer: None. P. Enlow: None. R. M. Wasserman: None. A. Milkes: None. J. Pierce: None. S. Gurnurkar: None. M. Carakushansky: None. D. A. Doyle: None. J. S. Pendley: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (DP3DK113235)

The Society for Archaeal Biology is building www.archaea.bio to provide a place where researchers are able to share data, protocols, and other relevant information in an open and efficient fashion. Ultimately, we aim to become a long term informational resource for both senior and early career researchers, as well as a community forum encouraging the free exchange of information/protocols driving the archaea field forward. visit our website here, All authors contributed equally

Ocean acidification is a global issue with particular regional significance in the California Current System, where social, economic, and ecological impacts are already occurring. Although ocean acidification is a concern that unifies the entire West Coast region, managing for this phenomenon at a regional scale is complex and further complicated by the large scale and dynamic nature of the region. Currently, data collection relevant to ocean acidification on the West Coast is piecemeal, and cannot capture the primary sources of variability in ocean acidification through time and across the region, hindering collaboration among regional managers. We developed a tool to analyze gaps in the West Coast ocean acidification monitoring network. We describe this tool and discuss how it can enable scientists and marine managers in the California Current System to fill information gaps and better understand and thus respond to ocean acidification through the implementation of management solutions at the local level.

This study evaluated the life course processes through which early life racial discrimination (ELRD) and racial centrality (i.e., the importance of Black identity to one’s sense of self) interact to shape allostatic load (AL) among African American (AA) adults aged 50+ in the Nashville Stress and Health Study (N=260). Adolescent ELRD was associated with greater racial centrality in adulthood and conferred 35% greater risk of high adult AL; greater centrality was also linked to high adult AL. Centrality accounts for 24% of the association between ELRD and AL. ELRD and centrality interact to shape adult AL, such that racial centrality is protective against high AL for adults who experienced racial discrimination as children or adolescents. Findings highlight the multiple pathways through which race-related stressors and psychosocial resources interact to shape physiological dysregulation in later life and underscore the health significance of racial identity for older AAs.

Aims Nodular regenerative hyperplasia (NRH) and obliterative portal venopathy (OPV), entities that comprise idiopathic non-cirrhotic portal hypertension (INCPH), are under-recognised diseases of uncertain aetiology and the diagnosis can be easily missed on liver biopsy. The expression of CD34 and von Willebrand factor (vWF) in liver sinusoidal endothelial cells (LSEC) and alpha-smooth muscle actin (ASMA) in hepatic stellate cells (HSCs) is unknown in NRH and OPV. We sought to investigate the pathogenesis and potential immunomarkers that might aid in making the diagnosis of NRH and OPV. Methods and results Immunohistochemical (IHC) staining for CD34, vWF and ASMA was performed in clinically and histologically well-characterised NRH (n = 15) and OPV (n = 47) liver specimens. Among the 47 OPV cases, 37 (78.7%) had concurrent features of NRH. CD34 positive staining was mainly confined to small vessels in the portal tracts and LSECs in periportal areas, a finding similar to that in non-NRH/OPV livers. However, expression of vWF in LSECs was positive in the compressed sinusoids of NRH and in a patchy or geographic pattern, particularly prominent in the perivenular areas and dilated sinusoids of OPV cases. HSCs were negative for ASMA in all NRH and OPV cases. Conclusion Our findings indicate that NRH may be a subtle but common concurrent morphological feature in OPV. The aberrant expression of vWF in LSECs suggests that endothelial injury may play a role in the pathogenesis, which may thus aid in the recognition and diagnosis of NRH and OPV, particularly when confronted with otherwise apparent normal liver histology on needle biopsy.

The aims of this study were to investigate the point prevalence, and associated independent factors, for foot disease (ulcers, infections and ischaemia) in a representative hospitalised population. We included 733 (83%) of 883 eligible adult inpatients across five representative Australian hospitals on one day. We collected an extensive range of self-reported characteristics from participants. We examined all participants to clinically diagnose foot disease (ulcers, infections and ischaemia) and amputation procedures. Overall, 72 participants (9·8%) [95% confidence interval (CI):7·2–11·3%] had foot disease. Foot ulcers, in 49 participants (6·7%), were independently associated with peripheral neuropathy, peripheral arterial disease, previous foot ulcers, trauma and past surgeon treatment (P < 0·05). Foot infections, in 24 (3·3%), were independently associated with previous foot ulcers, trauma and past surgeon treatment (P < 0·01). Ischaemia, in 33 (4·5%), was independently associated with older age, smokers and past surgeon treatment (P < 0·01). Amputation procedures, in 14 (1·9%), were independently associated with foot infections (P < 0·01). We found that one in every ten inpatients had foot disease, and less than half of those had diabetes. After adjusting for diabetes, factors linked with foot disease were similar to those identified in diabetes-related literature. The overall inpatient foot disease burden is similar in size to well-known medical conditions and should receive similar attention.

OBJECTIVES: The literature regarding the role of advanced glycation end products (AGEs) on tumor biology has shown only moderate promise reflected by increases in cell growth, migration and invasion in vitro which is not supported by increased tumor growth in vivo(14-16)– A caveat to these studies is that they are centered upon a single AGE peptide and a subsequent assessment of their molecular effects on tumor epithelial cells. The objective is to show that by feeding mice a high AGE diet we can recapitulate a microenvironment comprising of a wide spectrum of AGEs which can influence neoplastic growth. METHODS: We recapitulated a dietary-AGE induced microenvironment in syngeneic xenograft and spontaneous breast and prostate mouse cancer models and the effects on tumor growth assessed. The mechanistic consequences of dietary-AGEs on the tumor microenvironment were further defined using mouse and human primary and immortalized two-compartment co-culture ex vivo culture models. RESULTS: Dietary-AGE consumption in breast and prostate tumor models significantly accelerated tumor growth by functioning as ligand to the transmembrane receptor for AGE (RAGE). Our studies demonstrate that AGEs promote neoplastic growth by functioning as ligand to RAGE expressed in the tumor stroma not the tumor epithelial cells. Dietary-AGE activation of RAGE in both breast and prostate tumors caused a regulatory program of ‘activated fibroblasts’ defined by increased expression of cancer associated fibroblast markers, NFkB and MYC upregulation, and pro-tumorigenic paracrine secretion. Complementary to this, our published studies show that high intake of dietary AGE after BCa diagnosis increases risk of mortality in postmenopausal women. CONCLUSIONS: These data demonstrate, for the first time, the oncogenic potential of dietary-AGEs in promoting neoplastic growth. This lays the foundation for strategic changes aimed at reducing cancer incidence and mortality as pharmacological, educational and/or interventional strategies aimed at reducing the dietary-AGE accumulation pool may one day be viewed as universal cancer preventative and/or therapeutic initiatives especially when combined with existing therapies. FUNDING SOURCES: David P. Turner was supported by grants from the NIH/NCI, R21 CA194469 and U54 CA21096..

560 Background: Patients with TNBC breast cancer have inferior treatment outcomes compared to other breast cancer subtypes and targeted therapies are lacking. S-equol is a novel oral Estrogen Receptor (ER) Beta agonist with preclinical data showing suppression of TNBC cellular proliferation. We therefore conducted an early phase window of opportunity trial to evaluate the impact of S-equol on Ki-67 change in patients with TNBC. Methods: This neoadjuvant window trial enrolled 39 patients with confirmed TNBC on diagnostic core needle biopsy. Cohort A (20 patients) received a daily dose of 50 mg daily and Cohort B (19 patients) received a higher dose of 150 mg daily. Paired biopsies were evaluable for 36 patients. Both cohorts were treated for a duration of 10-21 days. Primary outcome was change from pre- to post-treatment Ki-67 evaluated by paired t-test. All tests were 2-sided with a significance level of 0.05. Statistics were conducted within an accountable data analysis process in R (ADAPR). Secondary outcomes included toxicity and correlative biomarkers. Results: The mean (SD) pre-treatment was 68% (21.99) and post-treatment 59% (20.62). The average decrease in Ki-67 was 8% (P = 0.00206, 95% CI -13.46 to -3.26). A Ki-67 decrease of at least 20% from baseline was observed in 28% of the patients. S-equol was well tolerated with the most common toxicities being nausea, constipation, diarrhea, and headache. All toxicities were grade one. Treatment compliance was greater than 95%. Planned correlative studies included RNA-seq. A total of 161 genes are differentially expressed with fold change > = 2 and p value < 0.05. The top genes of the differential expression list include BMP5, S100A7, FABP7, SCGB2A2, CH507-338C24.1, and DUSP1. Gene Set Enrichment Analysis (GSEA) indicates that top enriched gene modules are related to interferon function and immune response, most of which are downregulated in the post-treatment group. Conclusions: S-equol is a novel well tolerated oral ER-Beta agonist with inhibition of proliferation in patients with TNBC as measured by a decrease in Ki-67. RNA-seq data supports potential immune activation during this short period of drug exposure. Future studies aim to evaluate S-equol as an immune activating agent for combination with immunotherapies such as checkpoint inhibitors in TNBC. Clinical trial information: NCT02352025 .

Breastfeeding rates among urban, low-income populations are lower than the national average, creating a health disparity that greatly impacts mothers and children. Social support can affect breastfeeding initiation and duration both positively and negatively. This study aimed to determine the impact of the presence of a support person, as well as the breastfeeding knowledge and attitudes of that support person, on both a mother’s feeding …

Duchenne muscular dystrophy (DMD) is a disorder caused by a mutation in the dystrophin gene. In this population, cardiomyopathy has become the major cause of death and currently there are no clear methods to identify DMD patients at risk for myocardial dysfunction. Known electrocardiogram (ECG)

Background: Breastfeeding rates among urban, low-income populations are lower than the national average, and social support can affect breastfeeding initiation and duration both positively and negatively. Research aim: This study aimed to determine the effect of the presence of a support person and breastfeeding knowledge and attitudes of that person on a mother’s feeding choice and perceived level of support for her choice. Methods: Questionnaires were administered to 192 mothers receiving care for their infants in the Pediatric Practice at University Hospitals Rainbow Babies and Children’s Hospital in Cleveland, Ohio, along with 74 adults accompanying these mothers. Data on demographics, feeding characteristics, and breastfeeding knowledge and attitudes were collected. Results: Analysis of the entire group of mothers found that breastfeeding-supportive knowledge and attitudes were an independent predictor of exclusive breastfeeding (odds ratio [ OR] = 1.89, 95% confidence interval [CI] [1.38, 2.60]) and any breastfeeding ( OR = 2.28, 95% CI [1.62, 3.21]). The presence of an accompanying adult was not related to feeding choice. Analysis of the subgroup of mothers with surveyed accompanying adults found independent predictors of any breastfeeding include maternal intention to breastfeed ( OR = 23.68, 95% CI [1.48, 377.6]) and breastfeeding-supportive knowledge and attitudes of the mother ( OR = 2.71, 95% CI [1.36, 5.40]) and the accompanying adult ( OR = 2.78, 95% CI [1.17, 6.60]). The only independent predictor of exclusive breastfeeding was maternal intention to breastfeed ( OR = 7.64, 95% CI [2.22, 26.3]). The majority of mothers (91%) felt supported, regardless of presence or absence of an accompanying adult. Conclusion: These findings emphasize the importance of breastfeeding education for mothers and their support persons.

Objective: The aims of this point-prevalence study were to investigate a representative inpatient population to determine the prevalence of people admitted to hospital for the reason of a foot-related condition, and identify associated independent factors. Methods: Participants were adult inpatients in five different representative hospitals, admitted for any reason on the day of data collection. Maternity, mental health and cognitively impaired inpatients were excluded. Participants were surveyed on a range of self-reported demographic, social determinant, medical history, foot disease history, self-care, footwear, past foot treatment prior to hospitalisation and reason for admission variables. Physical examinations were performed to clinically-diagnose a range of foot disease and foot risk factor variables. Independent factors associated with being admitted to hospital for the primary or secondary reason of a foot-related condition were analysed using multivariate logistic regression. Results: Overall, 733 participants were included; mean(SD) age 62(19) years, male 55.8%. Foot-related conditions were the primary reason for admission in 54 participants (7.4% (95% CI: 5.7-9.5)); 36 for foot disease (4.9%), 15 foot trauma (2.1%). Being admitted for the primary reason of a foot-related condition was independently associated with foot infection, critical peripheral arterial disease, foot trauma and past foot treatment by a general practitioner and surgeon (p < 0.01). Foot-related conditions were a secondary reason for admission in 28 participants (3.8% (2.6-5.6)), and were independently associated with diabetes and current foot ulcer (p < 0.01). Conclusions: This study, the first in a representative inpatient population, suggests the direct inpatient burden caused by foot-related conditions is significantly higher than previously appreciated. Findings indicate one in every thirteen inpatients was primarily admitted because of a foot-related condition with most due to foot disease or foot trauma. Future strategies are recommended to investigate and intervene in the considerable inpatient burden caused by foot-related conditions.

Background Foot complications have been found to affect large proportions of hospital in patients with diabetes. However, no studies have investigated the proportion of foot complications affecting all people in general inpatient populations. The aims of this cross-sectional study were to investigate the point-prevalence of different foot complications in general inpatient populations, analyse differences in diabetes and non-diabetes sub-groups, and examine characteristics of people primarily admitted for a foot complication. Methods Eligible participants were all adults admitted overnight, for any reason, into five diverse hospitals on one day; excluding maternity, mental health and cognitively impaired patients. All participants underwent a physical foot examination, by trained podiatrists using validated measures, to clinically diagnose different foot complications; including foot wounds, infections, deformity, peripheral arterial disease (PAD) and peripheral neuropathy (PN). Data were also collected on participants' primary reason for admission and a range of demographic, social determinant, medical history, foot complication history, self-care and footwear risk factors. Results Overall, 733 participants consented (83% of eligible participants); mean(±SD) age 62(±19) years, 480 (55.8%) male and 172 (23.5%) had diabetes. Foot complication prevalence included: wounds 9.0% (95% CI) (5.1-8.7), infections 3.3% (2.2-4.9), deformity 22.4% (19.5-26.7), PAD 21.0% (18.2-24.1) and PN 22.0% (19.1-25.1). Diabetes populations had significantly more foot complications than non-diabetes (p < 0.01); wounds (15.7% vs 7.0%), infections (7.1% vs 2.2%), deformity (30.5% vs 19.9%), PAD (35.1% vs 16.7%) and PN (43.3% vs 15.4%). Foot complications were the primary reason for admission in 7.4% (95% CI) (5.7-9.5) of all participants. In a backwards stepwise multivariate analysis having a foot complication as the primary reason for admission was independently associated (OR (95% CI) with foot wounds (18.9 (7.3-48.7)), foot infections (6.0 (1.6-22.4)), history of amputation (4.7 (1.3-17.0) and PAD (2.9 (1.3-6.6)). Conclusions Findings of this study indicate one in every ten hospital inpatients had an active foot wound or infection. In patients with diabetes had significantly higher proportions of foot complications than non-diabetes inpatients. Remarkably one in every thirteen inpatients in this study were primarily hospitalised for a foot complication. Further research and policy is required to tackle this seemingly large inpatient foot complication burden.

Background Foot complications have been found to be predictors of mobility impairment and falls in community dwelling elderly patients. However, fewer studies have investigated the link between foot complications and mobility impairment in hospital in patient populations. The aim of this paper was to investigate the associations between mobility impairment and various foot complications in general inpatient populations. Methods Eligible participants were all adults admitted overnight, for any reason, into five diverse hospitals on one day; excluding maternity, mental health and cognitively impaired patients. Participants underwent a foot examination to clinically diagnose different foot complications; including foot wounds, infections, deformity, peripheral arterial disease and peripheral neuropathy. They were also surveyed on social determinant, medical history, self-care, footwear, foot complication history risk factors, and, mobility impairment defined as requiring a mobility aid for mobilisation prior to hospitalisation. Results Overall, 733 participants consented; mean(±SD) age 62(±19) years, 408 (55.8%) male, 172 (23.5%) diabetes. Mobility impairment was present in 242 (33.2%) participants; diabetes populations reported more mobility impairment than non-diabetes populations (40.7% vs 30.9%, p < 0.05). In a backwards stepwise multivariate analysis, and controlling for other risk factors, those people with mobility impairment were independently associated with increasing years of age (OR = 1.04 (95% CI) (1.02-1.05)), male gender (OR = 1.7 (1.2-2.5)), being born in Australia (OR = 1.7 (1.1-2.8), vision impairment (2.0 (1.2-3.1)), peripheral neuropathy (OR = 3.1 (2.0-4.6) and foot deformity (OR = 2.0 (1.3-3.0). Conclusions These findings support the results of other large studies investigating community dwelling elderly patients that peripheral neuropathy and foot deformity are independently associated with mobility impairment and potentially falls. Furthermore the findings suggest routine clinical diagnosis of foot complications as defined by national diabetic foot guidelines were sufficient to determine these associated foot complication risk factors for mobility impairment. Further research is required to establish if these foot complication risk factors for mobility impairment are predictors of actual falls in the inpatient environment.