Micronutrients in Long-Term Care (LTC): Issues and opportunities for improvement

BACKGROUND: Malnutrition is common among long-term care (LTC) residents, yet there is limited research on micronutrient (vitamin and mineral) malnutrition in the LTC setting. Micronutrient deficiencies may exacerbate symptoms of dementia, depression, infections, osteoporosis, and other prevalent conditions in LTC. PURPOSE: This research accomplishes phase 1 of a multi-phase study, with the overall research objective of investigating the potential and extent of micronutrient malnutrition in LTC and identifying and developing food-first strategies to improve micronutrient intake in LTC residents. This was done through four sub-studies (detailed below): METHODS & FINDINGS: Each method and respective findings/conclusions are described below. Sub-Studies 1 and 2: Scoping Review Observational (SRO) and Intervention (SRI)--Methods: A rigorous scoping review was conducted using selected key terms in four health-related electronic databases. The initial search identified 2248 eligible titles and abstracts for screening with inclusion/exclusion criteria. Results: SRO (n=50 citations): Intake for vitamin D, folate, calcium, vitamin E and B6 were consistently <50% of the Recommended Dietary Allowance (RDA) regardless of divergent food intake assessment methods. More than one study found biomarkers to be low for vitamin D, C, folate, and iron in LTC residents. SRI (n=25 citations): Vitamin D and calcium were the most common micronutrients to be included in both pill supplementation and food fortification interventions. Different formulations (e.g. single vs. multi-nutrient) were trialed, making comparisons difficult. Supplementation and fortification demonstrated efficacy but no studies comparing these strategies were identified. Conclusion: Findings suggest that micronutrient intake and biochemical status are suboptimal for key nutrients in LTC. Single nutrient interventions predominated and more work on efficacy of multi-nutrient physiological doses, whether in supplemental or fortification formulations is needed. Limited fortification studies have been completed and there is a need to determine efficacy for prevention as compared to supplementation. More research on fortification doses and formulations that are acceptable and efficacious is also required. Menu Analysis (MA) and Super-Menus (SM)-- Methods: Regular, non-therapeutic menus (week 1, all meals) from diverse LTC homes (n=5) across Canada were analyzed for micronutrient content using Food Processor with the Canadian Nutrient File. EaTracker was used to determine Canada’s Food Guide servings. Site dietitians provided home recipes/portion sizes, and validated menu analyses. SM were designed to meet micronutrient needs without increasing volume and calories, considering the preferences and portion sizes used in LTC. Results: Despite planning to and generally meeting CFG recommendations, menus’ nutrient content varied significantly across homes. Micronutrients of greatest concern across all menus were vitamins D (8.90 ± 5.29 µg/d) and E (5.13 ± 1.74 mg/d). Folate, magnesium, and potassium were also below recommended values. SM were significantly higher in several nutrients as compared to home menus, but still were unable to meet vitamin D (11.2 ± 2.54 µg, mean 56% RDA), E (12.6 ± 4.08, 84% RDA) and potassium (4018 ± 489 mg, 85%) recommendations. Conclusion: Evidently, current guidelines for menu planning may be inadequate to address micronutrient needs, and more nutrient-dense strategies need to be explored in LTC. Careful menu planning results in most micronutrients recommendations being met. Acceptability Testing (AT)-- Prior to implementation, potential interventions should be assessed for their need, feasibility, and acceptability with knowledge users. Methods: Online LTC Staff webinar focus groups, expert Key Informant interviews and in-person focus groups (residents and family) were conducted to develop and determine the acceptability of a micronutrient fortification strategy. Polling and rating questions provided quantitative data to confirm qualitative data. Results: Focus groups and key informant interviews provided insight into potential food vehicles for fortification (e.g. soups, desserts, condiments), production and regulatory issues, and helped to develop the strategy to minimize anticipated barriers and promote uptake. Development of outsourced/pre-made fortified products was the preferred intervention, with mandatory training and clear protocols for preparers to ensure appropriate use. Conclusion: Knowledge users can envision food fortification as a potential intervention if products are easy to access and incorporate into current production systems. All stakeholders desire efficacy research to support use of this strategy in LTC. OVERALL CONCLUSION: Triangulation of methods (SRI, SRO, MA/SM, and AT) and findings offers a multidimensional understanding of potential micronutrient deficiencies in LTC and food-first strategies that can be used to prevent this form of malnutrition. In general, food-first interventions in LTC to prevent or ameliorate micronutrient deficiency are lacking and quality menu planning using the DRI as a guide and food fortification are plausible strategies. Further work is needed to determine the relationship between micronutrient intake and biomarkers of function; does sufficient micronutrient nutrition support the overall health and quality of life of residents. Greater knowledge and awareness of micronutrient qualities of foods and of best practices in food-preparation methods through better training and education of LTC health providers is needed. As a food fortification strategy is further developed, involvement of multi-level stakeholders is needed to ensure uptake. This work provides foundation for a micronutrient food fortification strategy to address malnutrition in LTC.4 month

Collecting Chinese Art in Hong Kong from 1949 to 1997: Collectors, Museums and the Art Market

This thesis is a study of Chinese art collecting in Hong Kong during the second half of the 20th century. Through reconstructing the biographies of four representative collectors, who also held other roles as art dealer, adviser, scholar or museum donor, it demonstrates the diversity of collecting practices which thrived in this British colony and characterises how individuals and their networks shaped private and public collections, Chinese art scholarship and developments in the art market. Four representative collectors are examined to show how the multicultural environment of Hong Kong enabled collecting activities to thrive, and how collectors in turn contributed to enriching the collecting environment in Hong Kong. Firstly, Edward T. Chow’s collecting is viewed in relation to the impact of Shanghai dealers and collectors in bringing their expertise and collections to Hong Kong; secondly, Dr Ip Yee’s collecting activities epitomise how a new group of Western-educated middle-class professionals built institutional as well as private collections while furthering scholarship on specific categories of Chinese art such as bamboo carving; thirdly, the Singaporean collector Low Chuck-Tiew demonstrates the sense of nationalism, shared by many Cantonese diasporic communities, which motivated him to collect Chinese art and ultimately donate his collection to Hong Kong; lastly, T. T. Tsui’s method of sharing art with a global audience through opening a private museum and sponsoring international institutions reveals how collecting in Hong Kong became intertwined with business and diplomacy around the time of the handover of Hong Kong to China. By comparing these four collectors’ approaches to collecting and reflecting upon the roles they played in private collecting, museums and the art market from 1949 to 1997 in Hong Kong and beyond, the current research identifies distinctive characteristics of Hong Kong collecting which were unique to this eventful time and place

High salt induces P-glycoprotein mediated treatment resistance in breast cancer cells through store operated calcium influx

Recent evidence from our laboratory has demonstrated that high salt (Δ0.05 M NaCl) induced inflammatory response and cancer cell proliferation through salt inducible kinase-3 (SIK3) upregulation. As calcium influx is known to effect inflammatory response and drug resistance, we examined the impact of high salt on calcium influx in breast cancer cells. Treatment of MCF-7 and MDA-MB-231 cells with high salt induced an enhanced intracellular calcium intensity, which was significantly decreased by store operated calcium entry (SOCE) inhibitor co-treatment. Further, high salt induced P-glycoprotein (P-gp) mediated paclitaxel drug resistance in breast cancer cells. Murine tumor studies demonstrated that injection of MCF-7 cells cultured in high salt, exerted higher tumorigenicity compared to the basal cultured counterpart. Knock down of SIK3 by specific shRNA inhibited tumorigenicty, expression of SOCE regulators and P-gp activity, suggesting SIK3 is an upstream mediator of SOCE induced calcium influx. Furthermore, small molecule inhibitor, prostratin, exerted anti-tumor effect in murine models through SIK3 inhibition. Taken together, we conclude that SIK3 is an upstream regulator of store operated calcium entry proteins, Orai1 and STIM1, and mediates high salt induced inflammatory cytokine responses and P-gp mediated drug resistance. Therefore, small molecule inhibitors, such as prostratin, could offer novel anti-cancer approaches

Transcriptomic-metabolomic reprogramming in EGFR-mutant NSCLC early adaptive drug escape linking TGFβ2-bioenergetics-mitochondrial priming.

The impact of EGFR-mutant NSCLC precision therapy is limited by acquired resistance despite initial excellent response. Classic studies of EGFR-mutant clinical resistance to precision therapy were based on tumor rebiopsies late during clinical tumor progression on therapy. Here, we characterized a novel non-mutational early adaptive drug-escape in EGFR-mutant lung tumor cells only days after therapy initiation, that is MET-independent. The drug-escape cell states were analyzed by integrated transcriptomic and metabolomics profiling uncovering a central role for autocrine TGFβ2 in mediating cellular plasticity through profound cellular adaptive Omics reprogramming, with common mechanistic link to prosurvival mitochondrial priming. Cells undergoing early adaptive drug escape are in proliferative-metabolic quiescent, with enhanced EMT-ness and stem cell signaling, exhibiting global bioenergetics suppression including reverse Warburg, and are susceptible to glutamine deprivation and TGFβ2 inhibition. Our study further supports a preemptive therapeutic targeting of bioenergetics and mitochondrial priming to impact early drug-escape emergence using EGFR precision inhibitor combined with broad BH3-mimetic to interrupt BCL-2/BCL-xL together, but not BCL-2 alone

An analysis of the need for columbaria facilities in Hong Kong : a policy tools approach to public action

published_or_final_versionPolitics and Public AdministrationMasterMaster of Public Administratio

Stimulation of Apolipoprotein A-IV expression in Caco-2/TC7 enterocytes and reduction of triglyceride formation in 3T3-L1 adipocytes by potential anti-obesity Chinese herbal medicines

<p>Abstract</p> <p>Background</p> <p>Chinese medicine has been proposed as a novel strategy for the prevention of metabolic disorders such as obesity. The present study tested 17 Chinese medicinal herbs were tested for their potential anti-obesity effects.</p> <p>Methods</p> <p>The herbs were evaluated in terms of their abilities to stimulate the transcription of Apolipoprotein A-IV (ApoA-IV) in cultured Caco-2/TC7 enterocytes. The herbs that showed stimulating effects on ApoA-IV transcription were further evaluated in terms of their abilities to reduce the formation of triglyceride in differentiated 3T3-L1 adipocytes.</p> <p>Results</p> <p>ApoA-IV transcription was stimulated by <it>Rhizoma Alismatis </it>and <it>Radix Angelica Sinensis </it>in a dose- and time-dependent manner in cultured Caco-2/TC7 cells. Moreover, these two herbs reduced the amount of triglyceride in differentiated 3T3-L1 adipocytes.</p> <p>Conclusion</p> <p>The results suggest that <it>Rhizoma Alistmatis </it>and <it>Radix Angelica Sinensis </it>may have potential anti-obesity effects as they stimulate ApoA-IV transcription and reduce triglyceride formation.</p

Arabidopsis MORC proteins function in the efficient establishment of RNA directed DNA methylation.

The Microrchidia (MORC) family of ATPases are required for transposable element (TE) silencing and heterochromatin condensation in plants and animals, and C. elegans MORC-1 has been shown to topologically entrap and condense DNA. In Arabidopsis thaliana, mutation of MORCs has been shown to reactivate silent methylated genes and transposons and to decondense heterochromatic chromocenters, despite only minor changes in the maintenance of DNA methylation. Here we provide the first evidence localizing Arabidopsis MORC proteins to specific regions of chromatin and find that MORC4 and MORC7 are closely co-localized with sites of RNA-directed DNA methylation (RdDM). We further show that MORC7, when tethered to DNA by an artificial zinc finger, can facilitate the establishment of RdDM. Finally, we show that MORCs are required for the efficient RdDM mediated establishment of DNA methylation and silencing of a newly integrated FWA transgene, even though morc mutations have no effect on the maintenance of preexisting methylation at the endogenous FWA gene. We propose that MORCs function as a molecular tether in RdDM complexes to reinforce RdDM activity for methylation establishment. These findings have implications for MORC protein function in a variety of other eukaryotic organisms

Utilizing small nutrient compounds as enhancers of exercise-induced mitochondrial biogenesis.

Endurance exercise, when performed regularly as part of a training program, leads to increases in whole-body and skeletal muscle-specific oxidative capacity. At the cellular level, this adaptive response is manifested by an increased number of oxidative fibers (Type I and IIA myosin heavy chain), an increase in capillarity and an increase in mitochondrial biogenesis. The increase in mitochondrial biogenesis (increased volume and functional capacity) is fundamentally important as it leads to greater rates of oxidative phosphorylation and an improved capacity to utilize fatty acids during sub-maximal exercise. Given the importance of mitochondrial biogenesis for skeletal muscle performance, considerable attention has been given to understanding the molecular cues stimulated by endurance exercise that culminate in this adaptive response. In turn, this research has led to the identification of pharmaceutical compounds and small nutritional bioactive ingredients that appear able to amplify exercise-responsive signaling pathways in skeletal muscle. The aim of this review is to discuss these purported exercise mimetics and bioactive ingredients in the context of mitochondrial biogenesis in skeletal muscle. We will examine proposed modes of action, discuss evidence of application in skeletal muscle in vivo and finally comment on the feasibility of such approaches to support endurance-training applications in humans

The blood vasculature instructs lymphatic patterning in a SOX7-dependent manner

Despite a growing catalog of secreted factors critical for lymphatic network assembly, little is known about the mechanisms that modulate the expression level of these molecular cues in blood vascular endothelial cells (BECs). Here, we show that a BEC-specific transcription factor, SOX7, plays a crucial role in a non-cell-autonomous manner by modulating the transcription of angiocrine signals to pattern lymphatic vessels. While SOX7 is not expressed in lymphatic endothelial cells (LECs), the conditional loss of SOX7 function in mouse embryos causes a dysmorphic dermal lymphatic phenotype. We identify novel distant regulatory regions in mice and humans that contribute to directly repressing the transcription of a major lymphangiogenic growth factor (Vegfc) in a SOX7-dependent manner. Further, we show that SOX7 directly binds HEY1, a canonical repressor of the Notch pathway, suggesting that transcriptional repression may also be modulated by the recruitment of this protein partner at Vegfc genomic regulatory regions. Our work unveils a role for SOX7 in modulating downstream signaling events crucial for lymphatic patterning, at least in part via the transcriptional repression of VEGFC levels in the blood vascular endothelium.Peer reviewe