miR-34a-/- mice are susceptible to diet-induced obesity

Objective: MicroRNA (miR)−34a regulates inflammatory pathways, and increased transcripts have been observed in serum and subcutaneous adipose of subjects who have obesity and type 2 diabetes. Therefore, the role of miR-34a in adipose tissue inflammation and lipid metabolism in murine diet-induced obesity was investigated. Methods: Wild-type (WT) and miR-34a−/− mice were fed chow or high-fat diet (HFD) for 24 weeks. WT and miR-34a−/− bone marrow-derived macrophages were cultured in vitro with macrophage colony-stimulating factor (M-CSF). Brown and white preadipocytes were cultured from the stromal vascular fraction (SVF) of intrascapular brown and epididymal white adipose tissue (eWAT), with rosiglitazone. Results: HFD-fed miR-34a−/− mice were significantly heavier with a greater increase in eWAT weight than WT. miR-34a−/− eWAT had a smaller adipocyte area, which significantly increased with HFD. miR-34a−/− eWAT showed basal increases in Cd36, Hmgcr, Lxrα, Pgc1α, and Fasn. miR-34a−/− intrascapular brown adipose tissue had basal reductions in c/ebpα and c/ebpβ, with in vitro miR-34a−/− white adipocytes showing increased lipid content. An F4/80high macrophage population was present in HFD miR-34a−/− eWAT, with increased IL-10 transcripts and serum IL-5 protein. Finally, miR-34a−/− bone marrow-derived macrophages showed an ablated CXCL1 response to tumor necrosis factor-α. Conclusions: These findings suggest a multifactorial role of miR-34a in controlling susceptibility to obesity, by regulating inflammatory and metabolic pathways

Post-termination Effects of Cover Crop Monocultures and Mixtures on Soil Inorganic Nitrogen and Microbial Communities on Two Organic Farms in Illinois

Cover crops can continue to affect agricultural systems even after they have been terminated by influencing nitrogen dynamics and by altering soil microbial communities. These post-termination effects can influence soil fertility, weed pressure, and the dynamics of potential plant pathogens in the narrow window of time between cover crop termination and cash crop emergence. We evaluated the post-termination effects of 12 different spring-sown cover crop mixtures and monocultures on soil nitrogen and microbial communities on two different organic farms in Central Illinois (on Lawson silt loam soil) and Northern Illinois (on Virgil silt loam soil). In comparison to control plots with no cover crops, all cover crop treatments significantly reduced soil nitrate levels but increased the potentially mineralizable nitrogen pool following termination. Nitrate levels of cover crop plots approached those of controls after 2 and 4 weeks, respectively, but potentially mineralizable nitrogen levels in cover plots remained elevated for at least 4 weeks following termination. Monocultures of Brassica cover crops showed the greatest decrease in soil nitrate, while Brassicas and unplanted control plots containing high biomass of weeds showed the greatest increase in potentially mineralizable nitrogen in comparison to plant-free control plots. In contrast to their effect on soil nitrogen, cover crops had very limited impact on the composition of soil microbial communities. Overall microbial community composition varied across sites and years, and only soil fungi significantly responded to cover cropping treatments. Nevertheless, we found that some highly correlated groups of soil microbes showed significant responses to soil nitrate and to high plant biomass. Key members of these correlated groups included ammonia-oxidizing organisms and saprotrophic fungi. Our results suggest that cover crops may reduce the potential for springtime nitrogen leaching losses by retaining nitrogen in the soil organic pool, and they may also have impacts on the soil microbial community that are particularly relevant for nitrogen cycling and decomposition of plant residues

Associations between Fall Distance, Age, and Trauma Outcomes in Older Adult Patients

Introduction. Falls are the leading cause of injury death amongolder adults. This study sought to determine if there are differencesbetween fall distance (ground level vs greater than groundlevel) and age (old vs very old) in terms of in-hospital mortality,orthopedic consultations, and neurological consultations. Methods. A retrospective trauma registry review was conductedof older adult patients (aged > 65 years), admitted to aMidwestern Level I trauma facility (2005 - 2010) due to a fall.Results. Of the 1,064 patients analyzed, the majority fell fromground level compared to greater than ground level (64% and36%, respectively). Median age was 80 years. Fall distance wasnot associated significantly with in-hospital mortality (OR0.88; CI 0.50 - 1.54) or neurological consultations (OR 1.02; CI0.72 - 1.43), but was associated with orthopedic consultations(OR 1.49; CI 1.09 - 2.04). Age was not associated with in-hospitalmortality or neurological or orthopedic consultations. Conclusions. Fall distance was not associated with in-hospitalmortality or receiving a neurological consultation.However, older adults who fell from greater than groundlevel were more likely to receive orthopedic consultations.There were no differences in in-hospital mortality or receivinga neurological or orthopedic consultation based onage. These findings indicated that as the older adult populationincreases, burden of care will increase for trauma centersand neurological services. KS J Med 2016;9(3):54-57

“Collaboration Toward One Collective Goal”: A Mixed-Methods Study of Short-Term Learning Outcomes and Long-Term Impacts Among Students Participating in an Undergraduate Community-Based Participatory Research (CBPR) Course

Background: Research shows positive learning outcomes for students participating in service learning. However, the impacts of undergraduate student participation in Community-Based Participatory Research (CBPR) courses are minimally studied.Methods: We used a triangulation mixed-methods design approach to analyze short- and long-term (1–5 years post-course) data collected from 59 undergraduate students across 5 cohorts of a CBPR course (2014–19). Thematic analysis was used to analyze the qualitative data and descriptive statistics and frequencies were generated to analyze the quantitative data.Results: We developed five key themes based on short-term qualitative data: integration of CBPR and traditional research skills; importance of community engagement in research; identity; accountability; and collaboration. Themes from qualitative course evaluations aligned with these findings. Long-term qualitative data revealed that former students gained research knowledge, research skills, and professional skills and then applied these in other settings. This aligns with quantitative findings, where >79% of respondents reported that course participation “extensively” improved their research skills. Post-course, students still reflected on the importance of community engagement in research and reported a substantially enhanced likelihood of civic engagement.Discussion/Conclusions: Students gained critical knowledge and skills that positively impact their ability to engage in community-based work well after the end of course participation. Some students reported considering research-oriented careers and graduate programs for the first time after course participation. Collaborative learning experiences with community partners and members encouraged students to reflect on research designs that center community voices. We stress here that community partnerships require extensive cultivation, but they can create opportunities to translate findings directly back to communities and provide numerous benefits to undergraduate students. We hope that our findings provide the information needed to consider pilot testing practice-based CBPR courses in a variety of public health training contexts

Androgen receptor phosphorylation at serine 81 and serine 213 in castrate-resistant prostate cancer

Background: Despite increases in diagnostics and effective treatments, over 300,000 men die from prostate cancer highlighting the need for specific and differentiating biomarkers. AR phosphorylation associates with castrate-resistance, with pARser213 promoting transcriptional activity. We hypothesise that combined pARser81 and pARser213 reduces survival and would benefit from dual-targeting androgen-dependent and Akt-driven disease. Methods: Immunohistochemistry and immunofluorescence were performed on matched hormone-naive and castrate-resistant prostate cancer samples. TempO-Seq gene profiling was analysed using DESeq2 package. LNCaP-AI cells were stimulated with DHT or EGF. WST-1 assays were performed to determine effects of Enzalutamide and BKM120 on cell viability. Results: Following the development of castrate-resistance, pARser81 expression reduced and pARser213 expression increased. Castrate-resistance pARser81 expression was not associated with survival but high pARser213 expression was associated with reduced survival from relapse. Combined high pARser81 and pARser213 was associated with reduced survival from relapse. pARser81 expression was induced by 10 nM DHT or 10 nM EGF and pARser213 expression was induced by treatment with 10 nM EGF in LNCaP-AI cells. Cell viability was reduced following treatment with 10 nM Enzalutamide and 10 nM BKM120. Eight genes were differentially expressed between hormone-naive and castrate-resistant tumours and twenty-five genes were differentially expressed between castrate-resistant tumours with high and low pARser213 expression. Conclusion: Combined pARser81 and pARser213 provides a novel prognostic biomarker for castrate-resistant disease and a potential predictive and therapeutic target for prostate cancer. Further studies will be required to investigate the combined effects of targeting AR and PI3K/AKT signalling

Leadership As We Know It

Leadership as We Know it is a collection of insights into modern leadership compiled by graduate students in Winona State University’s Leadership Education program during the Spring 2019 semester in a course aptly titled, Change Leadership. Each chapter was penned by one of 20 unique class members who offer their vision of leadership based upon their eclectic personal backgrounds and professional experiences, whose fields include athletics, business, education, and more. These diverse narratives offer something for everyone; whether it be a veteran or blossoming leader eager to continue their growth and evolution. Leadership as We Know it provides accounts from seasoned professionals who oversee their own organizational departments as well as emerging leaders just beginning their careers. Throughout these unique stories, clear patterns will emerge for the reader in what it takes to inspire change and provide authentic leadership for followers.https://openriver.winona.edu/leadershipeducationbooks/1003/thumbnail.jp

Pre-operative chemotherapy in early stage resectable non-small-cell lung cancer: a randomized feasibility study justifying a multicentre phase III trial

Surgical resection offers the best chance for cure for early stage non-small-cell lung cancer (NSCLC, stage I, II, IIIA), but the 5-year survival rates are only moderate, with systemic relapse being the major cause of death. Pre-operative (neo-adjuvant) chemotherapy has shown promise in small trials restricted to stage IIIA patients. We believe similar trials are now appropriate in all stages of operable lung cancer. A feasibility study was performed in 22 patients with early stage (IB, II, IIIA) resectable NSCLC; randomized to either three cycles of chemotherapy [mitomycin-C 8 mg m−2, vinblastine 6 mg m−2 and cisplatin 50 mg m−2 (MVP)] followed by surgery (n = 11), or to surgery alone. Of 40 eligible patients, 22 agreed to participate (feasibility 55%) and all complied with the full treatment schedule. All symptomatic patients achieved either complete (50%) or partial (50%) relief of tumour-related symptoms with pre-operative chemotherapy. Fifty-five per cent achieved objective tumour response, and a further 27% minor tumour shrinkage; none had progressive disease. Partial pathological response was seen in 50%. No severe (WHO grade III–IV) toxicities occurred. No significant deterioration in quality of life was detected during chemotherapy. Pre-operative MVP chemotherapy is feasible in early stage NSCLC, and this study has now been initiated as a UK-wide Medical Research Council phase III trial. © 1999 Cancer Research Campaig

Mobilization of genomic islands of Staphylococcus aureus by temperate bacteriophage

The virulence of Staphylococcus aureus, in both human and animal hosts, is largely influenced by the acquisition of mobile genetic elements (MGEs). Most S. aureus strains carry a variety of MGEs, including three genomic islands (νSaα, νSaβ, νSaγ) that are diverse in virulence gene content but conserved within strain lineages. Although the mobilization of pathogenicity islands, phages and plasmids has been well studied, the mobilization of genomic islands is poorly understood. We previously demonstrated the mobilization of νSaβ by the adjacent temperate bacteriophage ϕSaBov from strain RF122. In this study, we demonstrate that ϕSaBov mediates the mobilization of νSaα and νSaγ, which are located remotely from ϕSaBov, mostly to recipient strains belonging to ST151. Phage DNA sequence analysis revealed that chromosomal DNA excision events from RF122 were highly specific to MGEs, suggesting sequence-specific DNA excision and packaging events rather than generalized transduction by a temperate phage. Disruption of the int gene in ϕSaBov did not affect phage DNA excision, packaging, and integration events. However, disruption of the terL gene completely abolished phage DNA packing events, suggesting that the primary function of temperate phage in the transfer of genomic islands is to allow for phage DNA packaging by TerL and that transducing phage particles are the actual vehicle for transfer. These results extend our understanding of the important role of bacteriophage in the horizontal transfer and evolution of genomic islands in S. aureus

In Vivo Imaging of Tau Pathology Using Magnetic Resonance Imaging Textural Analysis

BACKGROUND: Non-invasive characterization of the pathological features of Alzheimer's disease (AD) could enhance patient management and the development of therapeutic strategies. Magnetic resonance imaging texture analysis (MRTA) has been used previously to extract texture descriptors from structural clinical scans in AD to determine cerebral tissue heterogeneity. In this study, we examined the potential of MRTA to specifically identify tau pathology in an AD mouse model and compared the MRTA metrics to histological measures of tau burden. METHODS: MRTA was applied to T2 weighted high-resolution MR images of nine 8.5-month-old rTg4510 tau pathology (TG) mice and 16 litter matched wild-type (WT) mice. MRTA comprised of the filtration-histogram technique, where the filtration step extracted and enhanced features of different sizes (fine, medium, and coarse texture scales), followed by quantification of texture using histogram analysis (mean gray level intensity, mean intensity, entropy, uniformity, skewness, standard-deviation, and kurtosis). MRTA was applied to manually segmented regions of interest (ROI) drawn within the cortex, hippocampus, and thalamus regions and the level of tau burden was assessed in equivalent regions using histology. RESULTS: Texture parameters were markedly different between WT and TG in the cortex (E, p < 0.01, K, p < 0.01), the hippocampus (K, p < 0.05) and in the thalamus (K, p < 0.01). In addition, we observed significant correlations between histological measurements of tau burden and kurtosis in the cortex, hippocampus and thalamus. CONCLUSIONS: MRTA successfully differentiated WT and TG in brain regions with varying degrees of tau pathology (cortex, hippocampus, and thalamus) based on T2 weighted MR images. Furthermore, the kurtosis measurement correlated with histological measures of tau burden. This initial study indicates that MRTA may have a role in the early diagnosis of AD and the assessment of tau pathology using routinely acquired structural MR images

eRAPID electronic patient self-Reporting of Adverse-events: Patient Information and aDvice: a pilot study protocol in pelvic radiotherapy.

Background: An estimated 17,000 patients are treated annually in the UK with radical radiotherapy (RT) for pelvic cancer. New treatment approaches in RT have increased survivorship and changed the subjective toxicity profile for patients who experience acute and long-term pelvic-related adverse events (AE). Multi-disciplinary follow-up creates difficulty for monitoring and responding to these events during treatment and beyond. Originally developed for use in systemic oncology therapy eRAPID (electronic patient self-Reporting of Adverse-events: Patient Information and aDvice) is an online system for patients to report AEs from home. eRAPID enables patient data to be integrated into the electronic patient records for use in clinical practice, provides patient management advice for mild and moderate AE and advice to contact the hospital for severe AE. The system has now been developed for pelvic RT patients, and we aim to test the intervention in a pilot study with staff and patients to inform a future randomised controlled trial (RCT). Methods: Eligible patients are those attending St James's University hospital cancer centre and The Christie Hospital Manchester undergoing pelvic radiotherapy+/-chemotherapy/hormonotherapy for prostate, lower gastrointestinal and gynaecological cancers. A prospective 1:1 randomised (intervention or usual care) parallel group design with repeated measures and mixed methods will be employed. We aim to recruit 168 patients following recommendations for sample size estimates for pilot studies. Participants using eRAPID will report AE (at least weekly) from home weekly for 6 weeks and 6 weeks post-treatment (12-week total) then at 18 and 24 weeks. Hospital staff will review eRAPID reports and use information during consultations. Notifications will be sent to the relevant clinical team when severe symptoms are reported. We will measure patient-reported outcomes using validated questionnaires (Functional Assessment in Cancer Therapy Scale-General (FACT-G), European Organisation for Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC-QLQ-C30), process of care impact (hospital records of patient contacts and admissions) and economic variables (EQ5D-5L, patient use of resources)). Staff and patient experiences will be explored via semi-structured interviews. Discussion: The objectives are to establish feasibility, recruitment, integrity of the system and attrition rates, determine effect sizes and aid selection of the primary outcome measure for a future RCT. We will also refine the intervention by exploring staff and patient views. The overall goal of this complex intervention is to improve the safe delivery of cancer treatments, enhance patient care and standardise documentation of AE within the clinical datasets. Trial registration: ClinicalTrials.gov NCT02747264