Critical Reflections on Experiential Learning for Food Justice

This essay will reflect on Santa Clara University\u27s (SCU) forays into experiential learning around food justice through the Bronco Urban Gardens (BUG) program. BUG works with urban schools and a community center in San José, California, using a garden-based education approach. This program emerged out of our student garden, The Forge. University student farms and gardens provide opportunities for students to learn how to grow, manage, and market food. At Santa Clara University, our half-acre (0.2 hectare) garden plays that role. However, because of our institution\u27s commitment to social justice and a strong network of community partners, our campus garden has blossomed into a larger food justice outreach program. We will first discuss the motivation behind experiential learning for social justice and reflect on its connection to food justice. We then focus on several observations, challenges, and questions that have emerged out of our BUG experiences. Some of those observations involve the challenge of working with students and community partners where the interests of both groups must be served. We also explore what food justice means in this context, and what it means when a program expands beyond the committed few to an entire student body. By engaging in food justice with low-income communities of color through innovative campus programs such as BUG, our students are likely to see the food system from a very different vantage point than if they stayed on campus, resulting in deep learning experiences and also benefits for communities

Managing diabetes with nanomedicine: challenges and opportunities

Nanotechnology-based approaches hold substantial potential for improving the care of patients with diabetes. Nanoparticles are being developed as imaging contrast agents to assist in the early diagnosis of type 1 diabetes. Glucose nanosensors are being incorporated in implantable devices that enable more accurate and patient-friendly real-time tracking of blood glucose levels, and are also providing the basis for glucose-responsive nanoparticles that better mimic the body's physiological needs for insulin. Finally, nanotechnology is being used in non-invasive approaches to insulin delivery and to engineer more effective vaccine, cell and gene therapies for type 1 diabetes. Here, we analyse the current state of these approaches and discuss key issues for their translation to clinical practice.Leona M. and Harry B. Helmsley Charitable Trust (Grant 09PG-T1D027)Juvenile Diabetes Research Foundation International (17-2007-1063)Juvenile Diabetes Research Foundation International (3-2013-178)Juvenile Diabetes Research Foundation International (3-2011-310)United States. National Institutes of Health (EB000244)United States. National Institutes of Health (EB000351)United States. National Institutes of Health (DE013023)United States. National Institutes of Health (CA151884

Promoting tau secretion and propagation by hyperactive p300/CBP via autophagy-lysosomal pathway in tauopathy.

BackgroundThe trans-neuronal propagation of tau has been implicated in the progression of tau-mediated neurodegeneration. There is critical knowledge gap in understanding how tau is released and transmitted, and how that is dysregulated in diseases. Previously, we reported that lysine acetyltransferase p300/CBP acetylates tau and regulates its degradation and toxicity. However, whether p300/CBP is involved in regulation of tau secretion and propagation is unknown.MethodWe investigated the relationship between p300/CBP activity, the autophagy-lysosomal pathway (ALP) and tau secretion in mouse models of tauopathy and in cultured rodent and human neurons. Through a high-through-put compound screen, we identified a new p300 inhibitor that promotes autophagic flux and reduces tau secretion. Using fibril-induced tau spreading models in vitro and in vivo, we examined how p300/CBP regulates tau propagation.ResultsIncreased p300/CBP activity was associated with aberrant accumulation of ALP markers in a tau transgenic mouse model. p300/CBP hyperactivation blocked autophagic flux and increased tau secretion in neurons. Conversely, inhibiting p300/CBP promoted autophagic flux, reduced tau secretion, and reduced tau propagation in fibril-induced tau spreading models in vitro and in vivo.ConclusionsWe report that p300/CBP, a lysine acetyltransferase aberrantly activated in tauopathies, causes impairment in ALP, leading to excess tau secretion. This effect, together with increased intracellular tau accumulation, contributes to enhanced spreading of tau. Our findings suggest that inhibition of p300/CBP as a novel approach to correct ALP dysfunction and block disease progression in tauopathy

Trichostatin A accentuates doxorubicin-induced hypertrophy in cardiac myocytes

Histone deacetylase inhibitors represent a new class of anticancer therapeutics and the expectation is that they will be most effective when used in combination with conventional cancer therapies, such as the anthracycline, doxorubicin. The dose-limiting side effect of doxorubicin is severe cardiotoxicity and evaluation of the effects of combinations of the anthracycline with histone deacetylase inhibitors in relevant models is important. We used a well-established in vitro model of doxorubicin-induced hypertrophy to examine the effects of the prototypical histone deacetylase inhibitor, Trichostatin A. Our findings indicate that doxorubicin modulates the expression of the hypertrophy-associated genes, ventricular myosin light chain-2, the alpha isoform of myosin heavy chain and atrial natriuretic peptide, an effect which is augmented by Trichostatin A. Furthermore, we show that Trichostatin A amplifies doxorubicin-induced DNA double strand breaks, as assessed by γH2AX formation. More generally, our findings highlight the importance of investigating potential side effects that may be associated with emerging combination therapies for cancer

Declaring a tuberculosis outbreak over with genomic epidemiology

We report an updated method for inferring the time at which an infectious disease was transmitted between persons from a time-labelled pathogen genome phylogeny. We applied the method to 48 Mycobacterium tuberculosis genomes as part of a real-time public health outbreak investigation, demonstrating that although active tuberculosis (TB) cases were diagnosed through 2013, no transmission events took place beyond mid-2012. Subsequent cases were the result of progression from latent TB infection to active disease, and not recent transmission. This evolutionary genomic approach was used to declare the outbreak over in January 2015

Cost-effectiveness Analysis of Apixaban against Warfarin for Stroke Prevention in Patients with Nonvalvular Atrial Fibrillation in Japan

Abstract Purpose The aim of this study was to evaluate the cost-effectiveness of apixaban compared with to warfarin, current standard of care, for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) in Japan. Methods A previously published lifetime Markov model was adapted to evaluate the cost-effectiveness of apixaban compared with warfarin in patients with NVAF in Japan. In the same model, the costs associated with each clinical event and background mortality were replaced with Japanese data. Whenever available, some of the utility parameters were derived from Japanese published literature. Lifetime horizon was selected to evaluate the value of the treatment benefit (stroke prevention) against potential risks (such as major bleedings) among patients with NVAF. Direct medical cost, long-term care cost, and quality-adjusted life years (QALYs) were calculated from the payers' perspective. Findings Compared with warfarin, treatment with apixaban was estimated to increase life expectancy by 0.231 year or 0.240 QALYs while treatment cost increased by ¥511,692 (US $5117 at an exchange rate of US$1 = ¥100). The incremental cost-effectiveness ratio was ¥2,135,743 per QALY (US $21,357 per QALY). On the basis of the results of the probabilistic sensitivity analysis, when the willingness-to-pay threshold was set at approximately ≥¥2,250,000 (US$22,500) per QALY, the probability of apixaban being cost-effective was ≥50%. Assuming a willingness-to-pay threshold of ¥5,000,000 (US $50,000) and ¥6,700,000 (US$67,000) in Japan, the probability of apixaban being cost-effective was 85% and 91%, respectively. Conclusion Although most participants in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial used for the efficacy data of apixaban in the model were non-Japanese patients, the impact of the limitations on our results was considered small, and our results were deemed robust because of the additional effect in Japanese patients compared with that in the global population according to the subanalysis of Japanese patients in the trial. Therefore, based on an adaptation of a published Markov model, apixaban is a cost-effective alternative to warfarin in Japan for stroke prevention among patients with NVAF

Comparative study of healthy older and younger adults shows they have the same skin concentration of vitamin D3 precursor, 7-dehydrocholesterol, and similar response to UVR

Vitamin D3 synthesis in human skin is initiated by solar ultraviolet radiation (UVR) exposure of precursor 7-dehydrocholesterol (7DHC), but influence of age on the early stage of vitamin D3 metabolism is uncertain. We performed a prospective standardised study in healthy ambulant adults aged ≥65 and ≤40 years examining (1) if baseline skin 7DHC concentration differs between younger and older adults and (2) the impact of older age on serum vitamin D3 response to solar simulated UVR. Eleven younger (18–40 years) and 10 older (65–89 years) adults, phototype I–III, received low-dose UVR (95% UVA, 5% UVB, 1.3 SED) to ~35% of the body surface area. Biopsies were taken for 7DHC assay from unexposed skin, skin immediately and 24 h post-UVR, and blood sampled at baseline, 24 h and 7 d post-UVR for vitamin D3 assay. Samples were analysed by HPLC-MS/MS. Baseline skin 7DHC (mean ± SD) was 0.22 ± 0.07 and 0.25 ± 0.08 µg/mg in younger versus older adults (no significant difference). Baseline serum vitamin D3 concentration was 1.5 ± 1.5 and 1.5 ± 1.7 nmol/L in younger versus older adults, respectively, and showed a significant increase in both groups post-UVR (no significant differences between age groups). Thus, skin 7DHC concentration was not a limiting factor for vitamin D3 production in older relative to younger adults. This information assists public health guidance on sun exposure/vitamin D nutrition, with particular relevance to the growing populations of healthy ambulant adults ≥65 years

Chronic typhoid infection and the risk of biliary tract cancer and stones in Shanghai, China

Previous studies have shown a positive association between chronic typhoid carriage and biliary cancers. We compared serum Salmonella enterica serovar Typhi antibody titers between biliary tract cancer cases, biliary stone cases without evidence of cancer, and healthy subjects in a large population-based case-control study in Shanghai, China

Declaring a tuberculosis outbreak over with genomic epidemiology

We report an updated method for inferring the time at which an infectious disease was transmitted between persons from a time-labelled pathogen genome phylogeny. We applied the method to 48 Mycobacterium tuberculosis genomes as part of a real-time public health outbreak investigation, demonstrating that although active tuberculosis (TB) cases were diagnosed through 2013, no transmission events took place beyond mid-2012. Subsequent cases were the result of progression from latent TB infection to active disease, and not recent transmission. This evolutionary genomic approach was used to declare the outbreak over in January 2015

Durability of concrete structures in marine atmosphere zones – The use of chloride deposition rate on the wet candle as an environmental indicator

Durability of concrete structures under marine environments has been studied for a long time. This work was focused on marine atmosphere zone and studied the deposition of chlorides on wet candle devices and its relation with chlorides accumulated into concrete. Concrete specimens with three different mixtures were exposed at places located at four different distances from the sea. Periodically, chloride profiles were obtained and analysed taking into account environmental data. Results of numerical extrapolations show that chloride deposition rate on the wet candle can be used as an environmental indicator, helping to preview the expectancy of service life of concrete structures or suggesting minimum concrete cover thicknesses for a required service life. Regarding the studied region, service life decreases between 30% and 60% were observed when changing chloride deposition from 120 mg/m2 day to 500 mg/m2 day, which shows that chloride deposition plays an important role as an environmental indicator on service-life analysis of concrete structures in marine atmosphere zone