Lack of Effect of Murine Norovirus Infection on a Mouse Model of Bacteria-Induced Colon Cancer

Murine norovirus (MNV) is endemic in mouse research facilities in the United States and Europe, with a prevalence as high as 58% to 64%. Because of MNV's orofecal route of infection, clinically silent persistent infections in some mouse strains, and proclivity for macrophage and dendritic cells, its presence in mouse colonies has potential to alter phenotypes in experimental mouse models, particularly those involving inflammation and immunologic responses. Although MNV is subclinical, not causing overt disease in immunocompetent mice, we found that MNV infection can accelerate bacteria-induced inflammatory bowel disease (IBD) progression in Mdr1a^(-/-) mice. The studies presented here examined whether MNV infection also affects the phenotype of a bacterially driven mouse model of inflammation-associated colon cancer in genetically susceptible Smad3^(-/-) mice. In vitro culture of bone-marrow—derived macrophages (BMDM) was used to determine whether MNV4 influenced macrophage cytokine production. For in vivo studies, Smad3-/- mice were infected with MNV4 one week prior to infection with Helicobacter. Mice were monitored for 17 to 32 wk for development of IBD and colon cancer, and tissues were analyzed histopathologically. Although in vitro infection of BMDM with MNV4 led to increased inflammatory cytokine production, infection with MNV4 in vivo did not result in any statistically significant differences in survival, IBD scores, tumor incidence, or tumor phenotype in Smad3^(-/-) mice. In addition, MNV infection alone did not result in IBD or colon cancer. Therefore MNV infection alone or in conjunction with Helicobacter does not alter the development or progression of IBD or colon cancer in Smad3^(-/-) mice

Enhancing Discharge Preparation for Adults With Substance Use Disorder Within a Residential Treatment Facility

The community reintegration process is a vital aspect of the recovery journey, which requires sufficient planning and preparation prior to discharge from treatment (Read & Stoffel, 2019). Individuals enrolled in a residential treatment program for SUD indicated that higher levels of assistance and preparation during the transition to community living and involvement in comprehensive discharge planning would better prepare them for community reintegration (Manuel et al., 2017). Historically, the role of occupational therapy (OT) with this population has been to facilitate the resumption of meaningful roles, identify supportive habits and routines, and address executive functioning deficits related to SUD (Champagne & Gray, 2016; Rojo-Mota et al., 2017). The purpose of this capstone project was to conduct a research study in order to determine OT interventions utilized with adults with SUD and the perceived effectiveness of those interventions, to evaluate the discharge needs of adults with SUD receiving residential treatment, and to develop programming to enhance discharge preparation and utilize the preliminary findings of the research study to advocate for the role of OT at a SUD treatment facility. A qualitative research study was designed and conducted with occupational therapy practitioners (OTP) from across the country to examine the question: “which OT interventions are utilized with adults with SUD and what are practitioners’ perceptions of their effectiveness?” There were a total of 15 OTP who participated in the 24-question online survey and two who participated in an interview via Zoom. Data was analyzed using Braun and Clarke’s (2006) thematic analysis and three overarching themes emerged: variety of interventions utilized, awareness of recovery supports and barriers, and continuum of care transitions. A needs assessment was conducted with adults receiving residential treatment for SUD at Gateway Foundation in Aurora, Illinois to determine discharge needs for community reentry. Interviews were conducted with 29 clients, which yielded the following needs: the importance of routines to support recovery and structure time, the establishment of sleep hygiene routines to improve sleep quality, opportunities to engage in meaningful roles, integration of skill application and practice, and stress management and self-advocacy skills for the workplace. Observation conducted at Gateway Foundation indicated the need for a framework for clients to utilize in order to write measurable goals and structured free time to promote the exploration of meaningful and purposeful activities while still in the treatment environment. Programming recommendations were given to Gateway Foundation in the form of enhancements to the current program and the development of a new group in order to meet the identified needs of the clients. The recommendations include a goal writing and setting workshop, suggested implementation of structured free time, opportunities for skill application, and integration of the routines and time management group developed. The preliminary results of the research study were incorporated into programming recommendations, used to articulate the value of OT when working with the SUD population, and advocate for the inclusion of an occupational therapist on the team at Gateway Foundation.https://soar.usa.edu/otdcapstonessummer2021/1003/thumbnail.jp

Teachers’ Preparedness and Professional Learning about Using Educational Technologies During the COVID-19 Pandemic

The COVID-19 pandemic has impacted education at multiple levels over the last ten months. One common thread that has remained is the online learning and meeting platform for teachers, students, administrators, and families. This study reports on a survey of 560 K-12 educators across one southernmost part of a south-central state who shared their levels of preparedness during the transition to virtual learning in the Spring of 2020/amid the COVID-19 pandemic. Data analysis revealed that educators continued to focus on professional development during the summer of 2020 in preparation for the new academic year. Additional analysis showed that participants’ self-efficacy of using technology to teach online remained high. This demonstrated the resiliency and adapt- ability of K-12 classroom teachers in the face of immediate changes affecting their preconceived notions of how a classroom looks and how learning is obtained

The Therapeutic Camping Needs Of Children: The Hole-In-The-Hills At Wa-Shawtee

This executive summary of the preliminary report documents the major findings, to date, of the first two components of a needs assessment being conducted for the Hole in the Hills at Wa-Shawtee (HITH). The purpose of the study is to determine if a new, medically-equipped and professionally-staffed therapeutic camp in the Great Plains region of the Midwest has the capacity to be a success. There are almost 3.5 million children between the ages of five and seventeen in the 6-state HITH region, 1 an unknown number of whom are seriously-ill and/or have special medical conditions and health care needs, who could potentially benefit from a therapeutic camping facility. The first two completed sections of the needs assessment are: 1) an inventory of existing camps and camp programs for selected pediatric conditions in the 6-state catchment area and 2) an inventory of the population to be served, including the prevalence of priority illnesses/conditions and the levels of unmet need or potential camp demand in the HITH region. The remaining two components of the assessment, which will be included in the final report are: 3) the identification and ranking of the needs of seriously-ill children in the priority disease groups, and 4) the identification and ranking of the needs of these children’s parents and families

The window period of NEUROGENIN3 during human gestation

The basic helix-loop-helix transcription factor, NEUROG3, is critical in causing endocrine commitment from a progenitor cell population in the developing pancreas. In human, NEUROG3 has been detected from 8 weeks postconception (wpc). However, the profile of its production and when it ceases to be detected is unknown. In this study we have defined the profile of NEUROG3 detection in the developing pancreas to give insight into when NEUROG3- dependent endocrine commitment is possible in the human fetus. Immunohistochemistry allowed counting of cells with positively stained nuclei from 7 wpc through to term. mRNA was also isolated from sections of human fetal pancreas and NEUROG3 transcription analyzed by quantitative reverse transcription and polymerase chain reaction. NEUROG3 was detected as expected at 8 wpc. The number of NEUROG3-positive cells increased to peak levels between 10 wpc and 14 wpc. It declined at and after 18 wpc such that it was not detected in human fetal pancreas at 35-41 wpc. Analysis of NEUROG3 transcription corroborated this profile by demonstrating very low levels of transcript at 35-41 wpc, more than 10-fold lower than levels at 12-16 wpc. These data define the appearance, peak and subsequent disappearance of the critical transcription factor, NEUROG3, in human fetal pancreas for the first time. By inference, the window for pancreatic endocrine differentiation via NEUROG3 action opens at 8 wpc and closes between 21 and 35 wpc

Managing Borders During Public Health Emergencies of International Concern: A Proposed Typology of Cross-Border Health Measures

Background The near universal adoption of cross-border health measures during the COVID-19 pandemic worldwide has prompted significant debate about their effectiveness and compliance with international law. The number of measures used, and the range of measures applied, have far exceeded previous public health emergencies of international concern. However, efforts to advance research, policy and practice to support their effective use has been hindered by a lack of clear and consistent definition. Results Based on a review of existing datasets for cross-border health measures, such as the Oxford Coronavirus Government Response Tracker and World Health Organization Public Health and Social Measures, along with analysis of secondary and grey literature, we propose six categories to define measures more clearly and consistently – policy goal, type of movement (travel and trade), adopted by public or private sector, level of jurisdiction applied, stage of journey, and degree of restrictiveness. These categories are then brought together into a proposed typology that can support research with generalizable findings and comparative analyses across jurisdictions. Addressing the current gaps in evidence about travel measures, including how different jurisdictions apply such measures with varying effects, in turn, enhances the potential for evidence-informed decision-making based on fuller understanding of policy trade-offs and externalities. Finally, through the adoption of standardized terminology and creation of an agreed evidentiary base recognized across jurisdictions, the typology can support efforts to strengthen coordinated global responses to outbreaks and inform future efforts to revise the WHO International Health Regulations (2005). Conclusions The widespread use of cross-border health measures during the COVID-19 pandemic has prompted significant reflection on available evidence, previous practice and existing legal frameworks. The typology put forth in this paper aims to provide a starting point for strengthening research, policy and practice

Laser Capture and Deep Sequencing Reveals the Transcriptomic Programmes Regulating the Onset of Pancreas and Liver Differentiation in Human Embryos.

To interrogate the alternative fates of pancreas and liver in the earliest stages of human organogenesis, we developed laser capture, RNA amplification, and computational analysis of deep sequencing. Pancreas-enriched gene expression was less conserved between human and mouse than for liver. The dorsal pancreatic bud was enriched for components of Notch, Wnt, BMP, and FGF signaling, almost all genes known to cause pancreatic agenesis or hypoplasia, and over 30 unexplored transcription factors. SOX9 and RORA were imputed as key regulators in pancreas compared with EP300, HNF4A, and FOXA family members in liver. Analyses implied that current in vitro human stem cell differentiation follows a dorsal rather than a ventral pancreatic program and pointed to additional factors for hepatic differentiation. In summary, we provide the transcriptional codes regulating the start of human liver and pancreas development to facilitate stem cell research and clinical interpretation without inter-species extrapolation.This project received support from the UK Medical Research Council (MRC) (R.E.J. was a clinical research training fellow; additional funding from MR/L009986/1 to N.B. and N.A.H.; and MR/J003352/1 to K.P.H.), the Academy of Medical Sciences (supported by Wellcome Trust, MRC, British Heart Foundation, Arthritis Research UK, the Royal College of Physicians and Diabetes UK) (R.E.J.), the Society for Endocrinology (R.E.J.), the Wellcome Trust (N.A.H. was a senior fellow in clinical science, 088566; additional support from grant 105610/Z/14/Z), and the British Council and JDRF (14BX15NHBG to N.A.H.)

Funding models in palliative care: lessons from international experience

Background:Funding models influence provision and development of palliative care services. As palliative care integrates into mainstream health care provision, opportunities to develop funding mechanisms arise. However, little has been reported on what funding models exist or how we can learn from them.Aim:To assess national models and methods for financing and reimbursing palliative care.Design:Initial literature scoping yielded limited evidence on the subject as national policy documents are difficult to identify, access and interpret. We undertook expert consultations to appraise national models of palliative care financing in England, Germany, Hungary, Republic of Ireland, New Zealand, The Netherlands, Norway, Poland, Spain, Sweden, Switzerland, the United States and Wales. These represent different levels of service development and a variety of funding mechanisms.Results:Funding mechanisms reflect country-specific context and local variations in care provision. Patterns emerging include the following:Provider payment is rarely linked to population need and often perpetuates existing inequitable patterns in service provision.Funding is frequently characterised as a mixed system of charitable, public and private payers.The basis on which providers are paid for services rarely reflects individual care input or patient needs.Conclusion:Funding mechanisms need to be well understood and used with caution to ensure best practice and minimise perverse incentives. Before we can conduct cross-national comparisons of costs and impact of palliative care, we need to understand the funding and policy context for palliative care in each country of interest

Breast Cancer Index is a predictive biomarker of treatment benefit and outcome from extended tamoxifen therapy: final analysis of the Trans-aTTom study

PURPOSE: The Breast Cancer Index (BCI) HOXB13/IL17BR (H/I) ratio predicts benefit from extended endocrine therapy in hormone receptor–positive (HR(+)) early-stage breast cancer. Here, we report the final analysis of the Trans-aTTom study examining BCI (H/I)'s predictive performance. EXPERIMENTAL DESIGN: BCI results were available for 2,445 aTTom trial patients. The primary endpoint of recurrence-free interval (RFI) and secondary endpoints of disease-free interval (DFI) and disease-free survival (DFS) were examined using Cox proportional hazards regression and log-rank test. RESULTS: Final analysis of the overall study population (N = 2,445) did not show a significant improvement in RFI with extended tamoxifen [HR, 0.90; 95% confidence interval (CI), 0.69–1.16; P = 0.401]. Both the overall study population and N0 group were underpowered due to the low event rate in the N0 group. In a pre-planned analysis of the N(+) subset (N = 789), BCI (H/I)-High patients derived significant benefit from extended tamoxifen (9.7% absolute benefit: HR, 0.33; 95% CI, 0.14–0.75; P = 0.016), whereas BCI (H/I)-Low patients did not (−1.2% absolute benefit; HR, 1.11; 95% CI, 0.76–1.64; P = 0.581). A significant treatment-to-biomarker interaction was demonstrated on the basis of RFI, DFI, and DFS (P = 0.037, 0.040, and 0.025, respectively). BCI (H/I)-High patients remained predictive of benefit from extended tamoxifen in the N(+)/HER2(−) subgroup (9.4% absolute benefit: HR, 0.35; 95% CI, 0.15–0.81; P = 0.047). A three-way interaction evaluating BCI (H/I), treatment, and HER2 status was not statistically significant (P = 0.849). CONCLUSIONS: Novel findings demonstrate that BCI (H/I) significantly predicts benefit from extended tamoxifen in HR(+) N(+) patients with HER2(−) disease. Moreover, BCI (H/I) demonstrates significant treatment to biomarker interaction across survival outcomes