Students as neighbors: utilizing dialogue and deliberation to manage town-gown tensions

The integration of the university and its students into the broader Harrisonburg community has promoted increased interaction amongst JMU students, JMU faculty and staff, and community members. Navigating this complex relationship can be challenging and, in recent years, this relationship has become increasingly strained. The following research seeks to cultivate processes that aid in its improvement. The research finds that utilizing dialogue and deliberation as an approach to designing public process is a promising approach to mending and maintaining the relationship between JMU students and the broader Harrisonburg community, as well as to addressing town-gown tension at large. The research also employs a unique, flexible, methodology to allow for ongoing learning in developing a multi-phased, responsive process that helps participants move from understanding to finding sustainable solutions. The research offers insights into how information and perceptions that emerge in dialogic conversation can be used to design processes that transition into collaborative solutions for town-gown tensions

Indolo[2,3- e ]benzazocines and indolo[2,3- f ]benzazonines and their copper( ii ) complexes as microtubule destabilizing agents †

A series of four indolo[2,3-e]benzazocines HL1–HL4 and two indolo[2,3-f]benzazonines HL5 and HL6, as well as their respective copper(ii) complexes 1–6, were synthesized and characterized by 1H and 13C NMR spectroscopy, ESI mass spectrometry, single crystal X-ray diffraction (SC-XRD) and combustion analysis (C, H, N). SC-XRD studies of precursors Vd, VIa·0.5MeOH, of ligands HL4 and HL6·DCM, and complexes 2·2DMF, 5·2DMF, 5′·iPrOH·MeOH provided insights into the energetically favored conformations of eight- and nine-membered heterocycles in the four-ring systems. In addition, proton dissociation constants (pKa) of HL1, HL2 and HL5, complexes 1, 2 and 5, overall stability constants (log β) of 1, 2 and 5 in 30% (v/v) DMSO/H2O at 298 K, as well as thermodynamic solubility of HL1–HL6 and 1–6 in aqueous solution at pH 7.4 were determined by UV–vis spectroscopy. All compounds were tested for antiproliferative activity against Colo320, Colo205 and MCF-7 cell lines and showed IC50 values in the low micromolar to sub-micromolar concentration range, while some of them (HL1, HL5 and HL6, 1, 2 and 6) showed remarkable selectivity towards malignant cell lines. Ethidium bromide displacement studies provided evidence that DNA is not the primary target for these drugs. Rather, inhibition of tubulin assembly is likely the underlying mechanism responsible for their antiproliferative activity. Tubulin disassembly experiments showed that HL1 and 1 are effective microtubule destabilizing agents binding to the colchicine site. This was also confirmed by molecular modelling investigations. To the best of our knowledge, complex 1 is the first reported transition metal complex to effectively bind to the tubulin-colchicine pocket

Panel 6 : Vaccines

Objective. To review the literature on progress regarding (1) effectiveness of vaccines for prevention of otitis media (OM) and (2) development of vaccine antigens for OM bacterial and viral pathogens. Data Sources. PubMed database of the National Library of Science. Review Methods. We performed literature searches in PubMed for OM pathogens and candidate vaccine antigens, and we restricted the searches to articles in English that were published between July 2011 and June 2015. Panel members reviewed literature in their area of expertise. Conclusions. Pneumococcal conjugate vaccines (PCVs) are somewhat effective for the prevention of pneumococcal OM, recurrent OM, OM visits, and tympanostomy tube insertions. Widespread use of PCVs has been associated with shifts in pneumococcal serotypes and bacterial pathogens associated with OM, diminishing PCV effectiveness against AOM. The 10-valent pneumococcal vaccine containing Haemophilus influenzae protein D (PHiD-CV) is effective for pneumococcal OM, but results from studies describing the potential impact on OM due to H influenzae have been inconsistent. Progress in vaccine development for H influenzae, Moraxella catarrhalis, and OM-associated respiratory viruses has been limited. Additional research is needed to extend vaccine protection to additional pneumococcal serotypes and other otopathogens. There are likely to be licensure challenges for protein-based vaccines, and data on correlates of protection for OM vaccine antigens are urgently needed. Implications for Practice. OM continues to be a significant health care burden globally. Prevention is preferable to treatment, and vaccine development remains an important goal. As a polymicrobial disease, OM poses significant but not insurmountable challenges for vaccine development.Peer reviewe

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Field Evaluation of Low-Cost Particulate Matter Sensors for Measuring Wildfire Smoke

Until recently, air quality impacts from wildfires were predominantly determined based on data from permanent stationary regulatory air pollution monitors. However, low-cost particulate matter (PM) sensors are now widely used by the public as a source of air quality information during wildfires, although their performance during smoke impacted conditions has not been thoroughly evaluated. We collocated three types of low-cost fine PM (PM2.5) sensors with reference instruments near multiple fires in the western and eastern United States (maximum hourly PM2.5 = 295 µg/m3). Sensors were moderately to strongly correlated with reference instruments (hourly averaged r2 = 0.52–0.95), but overpredicted PM2.5 concentrations (normalized root mean square errors, NRMSE = 80–167%). We developed a correction equation for wildfire smoke that reduced the NRMSE to less than 27%. Correction equations were specific to each sensor package, demonstrating the impact of the physical configuration and the algorithm used to translate the size and count information into PM2.5 concentrations. These results suggest the low-cost sensors can fill in the large spatial gaps in monitoring networks near wildfires with mean absolute errors of less than 10 µg/m3 in the hourly PM2.5 concentrations when using a sensor-specific smoke correction equation

Identifying cirrhosis, decompensated cirrhosis and hepatocellular carcinoma in health administrative data: A validation study.

BACKGROUND:To evaluate screening and treatment strategies, large-scale real-world data on liver disease-related outcomes are needed. We sought to validate health administrative data for identification of cirrhosis, decompensated cirrhosis and hepatocellular carcinoma among patients with known liver disease. METHODS:Primary patient data were abstracted from patients of the Toronto Center for Liver Disease with viral hepatitis (2006-2014), and all patients with liver disease from the Kingston Health Sciences Centre Hepatology Clinic (2013). We linked clinical information to health administrative data and tested a range of coding algorithms against the clinical reference standard. RESULTS:A total of 6,714 patients had primary chart data abstracted. A single physician visit code for cirrhosis was sensitive (98-99%), and a single hospital diagnostic code for cirrhosis was specific (91-96%). The most sensitive algorithm for decompensated cirrhosis was one cirrhosis code with any of: a hospital diagnostic code, death code, or procedure code for decompensation (range 88-99% across groups). The most specific was one cirrhosis code and one hospital diagnostic code (range 89-98% across groups). Two physician visit codes or a single hospital diagnostic code, death code, or procedure code combined with a code for cirrhosis were sensitive and specific for hepatocellular carcinoma (sensitivity 94-96%, specificity 93-98%). CONCLUSION:These sensitive and specific algorithms can be used to define patient cohorts or detect clinical outcomes using health administrative data. Our results will facilitate research into the adequacy of screening and treatment for patients with chronic viral hepatitis or other liver diseases

Vegetable Nitrate Intakes Are Associated with Reduced Self-Reported Cardiovascular-Related Complications within a Representative Sample of Middle-Aged Australian Women, Prospectively Followed up for 15 Years

Nitric oxide (NO) facilitates anti-atherosclerotic effects. Vegetables are a major source of dietary nitrate. Experimental data indicates that dietary nitrate can significantly reduce major risk factors for atherosclerosis and subsequent cardiovascular disease (CVD), as nitrate can be metabolized to produce NO via the nitrate-nitrite-NO pathway. The purpose of this study was to prospectively investigate the association between habitual dietary nitrate intakes and the incidence of self-reported CVD-related complications within a representative sample of middle-aged Australian women (1946–1951 cohort of the Australian Longitudinal Study on Women’s Health). Women free from disease at baseline who had completed the food frequency questionnaire data were included. Generalized estimating equations were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) across quartiles for nitrate intakes. Of the 5324 women included for analysis, there were 1951 new cases of CVD-related complications over 15-years of follow-up. Women reporting higher total dietary nitrate intakes (Q4 > 78.2 mg/day) and vegetable nitrate intakes (Q4 > 64.4 mg/day) were 25% and 27% reduced risk of developing CVD-related complications respectively, compared with women reporting low total (Q1 < 45.5 mg/day) and vegetable nitrate intakes (Q1 < 34.8 mg/day). Our findings were consistent with other observational data indicating that dietary nitrate may explain some of the cardiovascular benefits of vegetable consumption