Uric Acid as a Potential Peripheral Biomarker for Disease Features in Huntington's Patients.

Oxidative stress has long been implicated in the pathophysiology and progression of Huntington's disease (HD). Uric acid (UA) is a naturally occurring antioxidant that is present in the brain and periphery. Growing evidence has implicated UA as a molecular biomarker for several neurodegenerative diseases, most notably Parkinson's disease (PD). In this study, we investigated UA levels in clinical samples from HD patients and normal controls (NCs) and assessed potential relationships between UA levels and disease and clinical data. UA levels were measured in plasma (n = 107) and saliva (n = 178) samples from premanifest (pre-HD) and manifest HD patients and control subjects. Gender effects of UA levels were observed in both biofluids, with male patients showing higher UA levels compared to female patients. Comparisons of UA levels across diagnostic groups, separated by gender, revealed that both plasma and salivary UA levels were significantly lower in female pre-HD and manifest HD patients compared to NCs. Salivary levels of UA were also significantly lower in male manifest HD patients versus controls, but not in plasma. Correlations of peripheral UA levels to clinical data also showed differences according to gender. In male HD patients, both plasma and salivary UA levels were significantly negatively correlated with total functional capacity (TFC), while positive correlations were observed with total motor score (TMS). Female HD patients showed a significant positive correlation between plasma UA levels and TMS, while salivary UA levels from female patients were significantly correlated to disease burden. Finally, in a separate cohort, we show that UA levels are decreased in postmortem prefrontal cortical samples (n = 20) from HD subjects compared to matched controls. These findings suggest that decreased levels of UA in the brains of HD patients can be reflected in peripheral fluids, with salivary measures of UA particularly offering significant promise as a potentially relevant, non-invasive biomarker of disease symptoms and burden. Our findings further highlight the impact of sexual dimorphism in HD pathophysiology

Ursolic acid enhances macrophage autophagy and attenuates atherogenesis

Macrophage autophagy has been shown to be protective against atherosclerosis. We previously discovered that ursolic acid (UA) promoted cancer cell autophagy. In the present study, we aimed to examine whether UA enhances macrophage autophagy in the context of atherogenesis. Cell culture study showed that UA enhanced autophagy of macrophages by increasing the expression of Atg5 and Atg16l1, which led to altered macrophage function. UA reduced pro-interleukin (IL)-1β protein levels and mature IL-1β secretion in macrophages in response to lipopolysaccharide (LPS), without reducing IL-1β mRNA expression. Confocal microscopy showed that in LPS-treated macrophages, UA increased LC3 protein levels and LC3 appeared to colocalize with IL-1β. In cholesterol-loaded macrophages, UA increased cholesterol efflux to apoAI, although it did not alter mRNA or protein levels of ABCA1 and ABCG1. Electron microscopy showed that UA induced lipophagy in acetylated LDL-loaded macrophages, which may result in increased cholesterol ester hydrolysis in autophagolysosomes and presentation of free cholesterol to the cell membrane. In LDLR(−/−) mice fed a Western diet to induce atherogenesis, UA treatment significantly reduced atherosclerotic lesion size, accompanied by increased macrophage autophagy. In conclusion, the data suggest that UA promotes macrophage autophagy and, thereby, suppresses IL-1β secretion, promotes cholesterol efflux, and attenuates atherosclerosis in mice

Sexual Violence Committed against University of Alaska Students, by Gender

This fact sheet presents past year estimates of sexual misconduct and sexual assault victimization against University of Alaska (UA) students both on and off campus. Women- and men-specific estimates are provided for the UA system as a whole only. The results presented here are based on the survey responses of a randomly selected sample of 1,982 undergraduate and graduate students who were enrolled at any of the three UA major administrative units (MAUs) — UA Anchorage (UAA), UA Fairbanks (UAF), or UA Southeast (UAS) during spring semester 2016. This survey was modeled on the Campus Climate Survey Recommendations prepared by the White House Task Force to Protect Students from Sexual Assault.Bureau of Justice Statistics, U.S. Department of JusticeUA Student Population / Sexual Misconduct / Sexual Assault / Results / Violence against women / Violence against men / Summar

Serum uric acid as a marker of microvascular damage in systemic sclerosis patients

Background: Microvascular damage of skin and internal organs is a hallmark of systemic sclerosis (SSc). Serum uric acid (UA) represents a marker of inflammation and endothelial dysfunction. The aims of this study were to evaluate the correlation between serum UA and intrarenal arterial stiffness evaluated by Doppler ultrasound in SSc patients with normal renal function. We also evaluated the correlation between serum UA and other clinical variables of the disease. Methods: Forty-five SSc patients underwent clinical assessment, Doppler ultrasound of intrarenal arteries with evaluation of resistive index (RI), pulsatile index (PI), and systolic/diastolic ratio (S/D), echocardiography with systolic pulmonary artery pressure (PAPs), baseline pulmonary function tests, and nailfold videocapillaroscopy (NVC). In all patients serum UA was measured. Results: The serum UA showed a significant positive correlation with sCr (r = 0.33, p < 0.0001) and PAPs (r = 0.38, p < 0.01) > and negative correlation with CKD-EPI (r = -0.35, p < 0.01). The mean value of serum UA increased with severity of NVC damage. Using this cut-off value of 4.7 mg/dl, the mean value of Doppler indices of intrarenal stiffness is significantly different (p < 0.05) in SSc patients with low normal or high normal serum UA. Conclusions: Serum UA concentration is higher in patients with high microvascular damage than in patients with low microvascular damage. These preliminary data must be confirmed in large prospective studies

Growing in Glasgow: Innovative practices and emerging policy pathways for urban agriculture

Driven by shared concerns about climate change, social justice and health and wellbeing, Urban Agriculture (UA) is an emergent global movement. In this paper, we present an exploratory case study of UA practice on the Southside of Glasgow, UK that traced the emergence and development of four UA projects. Data from the four projects revealed a diversity of practices, including temporary gardening projects organised by local volunteers, a community and market garden operated by a charity, a food shop and vegetable distribution service run by a social enterprise, and a permanent growing space for charities and schools provided by local government. UA practitioners in Glasgow have sought to re-purpose vacant and derelict land, build social cohesion, contribute to environmental and food sustainability and provide participation space for marginalised groups. Reflecting on future avenues for research on UA in Glasgow, we have identified two broad policy pathways that are emerging both at the local level and through national legislation in Scotland to harness local urban food growing and support UA. We conclude by pointing to a need to preserve the self-organising spirit of UA in Scotland as new legislation comes into force

Urban agriculture: a global analysis of the space constraint to meet urban vegetable demand

Urban agriculture (UA) has been drawing a lot of attention recently for several reasons: the majority of the world population has shifted from living in rural to urban areas; the environmental impact of agriculture is a matter of rising concern; and food insecurity, especially the accessibility of food, remains a major challenge. UA has often been proposed as a solution to some of these issues, for example by producing food in places where population density is highest, reducing transportation costs, connecting people directly to food systems and using urban areas efficiently. However, to date no study has examined how much food could actually be produced in urban areas at the global scale. Here we use a simple approach, based on different global-scale datasets, to assess to what extent UA is constrained by the existing amount of urban space. Our results suggest that UA would require roughly one third of the total global urban area to meet the global vegetable consumption of urban dwellers. This estimate does not consider how much urban area may actually be suitable and available for UA, which likely varies substantially around the world and according to the type of UA performed. Further, this global average value masks variations of more than two orders of magnitude among individual countries. The variations in the space required across countries derive mostly from variations in urban population density, and much less from variations in yields or per capita consumption. Overall, the space required is regrettably the highest where UA is most needed, i.e., in more food insecure countries. We also show that smaller urban clusters (i.e., <100 km2 each) together represent about two thirds of the global urban extent; thus UA discourse and policies should not focus on large cities exclusively, but should also target smaller urban areas that offer the greatest potential in terms of physical space

Uric acid is more strongly associated with impaired glucose regulation in women than in men from the general population: the KORA F4-Study.

High serum uric acid (UA) levels are associated with the metabolic syndrome, type 2 diabetes and cardiovascular disease. It is largely unknown whether there are gender-specific differences regarding the association between UA and prediabetic states. We examined the possible association between UA levels and known as well as newly diagnosed diabetes (NDD), isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), and combined IFG/IGT in a population-based sample of 32-to-81-year-old men and women. An oral glucose tolerance test was carried out in all 2,740 participants without known diabetes of the Cooperative Health Research in the Region of Augsburg (KORA) F4 Study conducted between 2006 and 2008 in Southern Germany. Serum UA was analysed by the uricase method. In women after multivariable adjustment the associations between UA and i-IFG (OR 1.57, 95% CI 1.15-2.14), IFG/IGT (OR 1.52, 1.07-2.16), NDD (OR 1.67, 95% CI 1.28-2.17), and known diabetes (OR 1.47, 95% CI 1.18-1.82) remained significant, but the association with i-IGT (OR 1.14, 95% CI 0.95-1.36) lost significance. In contrast in men, after multivariable adjustment there was only a significant association between UA levels and i-IFG (OR 1.49, 95% CI 1.21-1.84), all other associations were non-significant (i-IGT: OR 1.09, IFG/IGT: OR 1.06, NDD: OR 0.91, known diabetes: OR 1.04; all p-values>0.05). Serum UA concentrations were associated with different categories of impaired glucose regulation in individuals from the general population, particularly in women. Further studies investigating the role of UA in the development of derangements in glucose metabolism are needed

MZnet : mail service for personal micro-computer systems

Traditional computer mail systems involve a co-resident User Agent (UA) and Mail Transfer System (MTS) on a time-shared host computer which may be connected to other hosts ina network, with new mail posted or delivered directly through co-resident mail-slot programs. To introduce personal micro-computers (PCs) into this environment requires modification of the traditional mail system architecture. To this end, the MZnet project uses a split-slot model, placing UA programs on the PCs while leaving MTA programs on a mail relay host which can provide authentication and buffering. The split-slot arrangement might be viewed as a new protocol level which operates somewhere between the currently defined MTS-MTS and UA-UA levels