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Concept: PReVENT

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BACKGROUND: In ancient times, plants were recognized for their medicinal properties. Later, the arrival of synthetic drugs pushed it to the backstage. However, from being merely used for food, plants are now been widely explored for their therapeutic value. The current study explores the potential of skin and flesh extracts from a hard-necked Rocambole variety of purple garlic in preventing cardiomyocyte hypertrophy and cell death. METHODS: Norepinephrine (NE) was used to induce hypertrophy in adult rat cardiomyocytes pretreated with garlic skin and flesh extracts. Cell death was measured as ratio of rod to round shaped cardiomyocytes. Fluorescent probes were used to measure apoptosis and oxidative stress in cardiomyocytes treated with and without extracts and NE. Pharmacological blockade of nitric oxide (NO) and hydrogen sulfide (H2S) were used to elucidate the mechanism of action of garlic extracts. Garlic extract samples were also tested for alliin and allicin concentrations. RESULTS: Exposure of cardiomyocytes to NE induced an increase in cell size and cell death; this increase was significantly prevented upon treatment with garlic skin and flesh extracts. Norepinephrine increased apoptosis and oxidative stress in cardiomyocytes which was prevented upon pretreatment with skin and flesh extracts; NO, and H2S blockers significantly inhibited this beneficial effect. Allicin and alliin concentration were significantly higher in garlic flesh extract when compared to the skin extract. CONCLUSION: These results suggest that both skin and flesh garlic extracts are effective in preventing NE induced cardiomyocyte hypertrophy and cell death. Reduction in oxidative stress may also play an important role in the anti-hypertrophic and anti-apoptotic properties of garlic extracts. These beneficial effects may in part be mediated by NO and H2S.

Concepts: Nitrogen, Radical, Zinc, Sulfur, Garlic, Hydrogen sulfide, PReVENT, Allicin

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Physical restraint is frequently used in the intensive care setting but little is known regarding its clinical scenario and effectiveness in preventing adverse events (AEs), defined as device removal.

Concepts: Clinical trial, Prevention, PReVENT, Medical restraint

8

The role of microglia in amyloid-β (Aβ) deposition is controversial. In the present study, an organotypic hippocampal slice culture (OHSC) system with an in vivo-like microglial-neuronal environment was used to investigate the potential contribution of microglia to Aβ plaque formation. We found that microglia ingested Aβ, thereby preventing plaque formation in OHSCs. Conversely, Aβ deposits formed rapidly in microglia-free wild-type slices. The capacity to prevent Aβ plaque formation was absent in forebrain microglia from young adult but not juvenile 5xFamilial Alzheimer’s disease (FAD) mice. Since no loss of Aβ clearance capacity was observed in both wild-type and cerebellar microglia from 5xFAD animals, the high Aβ1-42 burden in the forebrain of 5xFAD animals likely underlies the exhaustion of microglial Aβ clearance capacity. These data may therefore explain why Aβ plaque formation has never been described in wild-type mice, and point to a beneficial role of microglia in AD pathology. We also describe a new method to study Aβ plaque formation in a cell culture setting.

Concepts: Alzheimer's disease, Present, Gene, Brain, Culture, Prevention, Semantic memory, PReVENT

4

Background: A low intake of fruits and vegetables (F&Vs) is a major risk factor for cardiovascular disease (CVD) in the United States. Both mass media campaigns (MMCs) and economic incentives may increase F&V consumption. Few data exist on their comparative effectiveness.Objective: We estimated CVD mortality reductions potentially achievable by price reductions and MMC interventions targeting F&V intake in the US population.Design: We developed a US IMPACT Food Policy Model to compare 3 policies targeting F&V intake across US adults from 2015 to 2030: national MMCs and national F&V price reductions of 10% and 30%. We accounted for differences in baseline diets, CVD rates, MMC coverage, MMC duration, and declining effects over time. Outcomes included cumulative CVD (coronary heart disease and stroke) deaths prevented or postponed and life-years gained (LYGs) over the study period, stratified by age, sex, and race.Results: A 1-y MMC in 2015 would increase the average national F&V consumption by 7% for 1 y and prevent ∼18,600 CVD deaths (95% CI: 17,600, 19,500), gaining ∼280,100 LYGs by 2030. With a 15-y MMC, increased F&V consumption would be sustained, yielding a 3-fold larger reduction (56,100; 95% CI: 52,400, 57,700) in CVD deaths. In comparison, a 10% decrease in F&V prices would increase F&V consumption by ∼14%. This would prevent ∼153,300 deaths (95% CI: 146,400, 159,200), gaining ∼2.51 million LYGs. For a 30% price decrease, resulting in a 42% increase in F&V consumption, corresponding values would be 451,900 CVD deaths prevented or postponed (95% CI: 433,100, 467,500) and 7.3 million LYGs gained. Effects were similar by sex, with a smaller proportional effect and larger absolute effects at older ages. A 1-y MMC would be 35% less effective in preventing CVD deaths in non-Hispanic blacks than in whites. In comparison, price-reduction policies would have equitable proportional effects.Conclusion: Both national MMCs and price-reduction policies could reduce US CVD mortality, with price reduction being more powerful and sustainable.

Concepts: Comparison, Epidemiology, Disease, Effect, Heart, Effectiveness, Policy, PReVENT

4

This study explored whether chlorogenic acid (CGA) and coffee have protective effects against retinal degeneration. Under hypoxic conditions, viability of transformed retinal ganglion (RGC-5) cells was significantly reduced by treatment with the nitric oxide (NO) donor S-nitroso-N-acetyl-penicillamine (SNAP). However, pretreatment with CGA attenuated cell death in a concentration-dependent manner. In addition, coffee extract prevented the upregulation of apoptotic proteins such as Bad and cleaved caspase-3. Similar beneficial effects of both CGA and coffee extracts were observed in mice that had undergone an optic nerve crush (ONC) procedure. CGA and coffee extract reduced cell death by preventing the downregulation of Thy-1. Our in vitro and in vivo studies demonstrated that coffee and its major component, CGA, significantly reduces apoptosis of retinal cells induced by hypoxia and NO, and that coffee consumption may help in preventing retinal degeneration.

Concepts: Protein, Oxygen, Apoptosis, In vivo, Coffee, In vitro, Hypoxia, PReVENT

4

The flavolignan silibinin was studied for its ability to restore drug sensitivity to EGFR-mutant NSCLC xenografts with epithelial-to-mesenchymal transition (EMT)-driven resistance to erlotinib. As a single agent, silibinin significantly decreased the tumor volumes of erlotinib-refractory NSCLC xenografts by approximately 50%. Furthermore, the complete abrogation of tumor growth was observed with the co-treatment of erlotinib and silibinin. Silibinin fully reversed the EMT-related high miR-21/low miR-200c microRNA signature and repressed the mesenchymal markers SNAIL, ZEB, and N-cadherin observed in erlotinib-refractory tumors. Silibinin was sufficient to fully activate a reciprocal mesenchymal-to-epithelial transition (MET) in erlotinib-refractory cells and prevent the highly migratogenic phenotype of erlotinib-resistant NSCLC cells. Given that the various mechanisms of resistance to erlotinib result from EMT, regardless of the EGFR mutation status, a water-soluble, silibinin-rich milk thistle extract might be a suitable candidate therapy for upcoming clinical trials aimed at preventing or reversing NSCLC progression following erlotinib treatment.

Concepts: Gene, Clinical trial, Cancer, In vivo, Tumor, Prevention, PReVENT, Milk thistle

2

Our proof-of-concept study shows that omalizumab given during the winter respiratory viral season can prevent severe exacerbations but only while the drug is being taken.

Concepts: Asthma, PReVENT

2

Emergency physicians witness the effects of injury and violence every day. Traumatic brain injury, assault-related trauma, motor vehicle crashes, and opioid overdoses make up only some of these injuries-many of which can be prevented and better understood. The Centers for Disease Control and Prevention’s National Center for Injury Prevention and Control (Injury Center) is uniquely poised to measure the toll of injury and violence on the lives of Americans, to communicate this public health burden, and to reduce the factors that increase their risk. Injury is the leading cause of death for persons aged 1 to 44 years in the United States. The Injury Center seeks to prevent violence and injuries and to reduce their consequences. For more than 20 years, Injury Center researchers have investigated factors that put Americans at risk through surveillance and research and translated these findings into evidence-based strategies and interventions. Many of these efforts are directly relevant to emergency medicine through preventing injuries and violence to save lives.

Concepts: Public health, United States, Traumatic brain injury, Prevention, Urgent care, Physical trauma, Preventive medicine, PReVENT

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It is undisputed for more than 200 years that the use of a parachute prevents major trauma when falling from a great height. Nevertheless up to date no prospective randomised controlled trial has proven the superiority in preventing trauma when falling from a great height instead of a free fall. The aim of this prospective randomised controlled trial was to prove the effectiveness of a parachute when falling from great height.

Concepts: Epidemiology, Randomized controlled trial, English-language films, Pharmaceutical industry, Efficacy, Prevention, PReVENT

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A disruption of cholesterol homeostasis characterized by the physical-chemical imbalance of cholesterol solubility in bile often results in formation of cholesterol gallstones. Our earlier studies revealed that curcumin (1000 mg/kg) could prevent formation of gallstones. It has been proved that curcumin is poorly absorbed while piperine is a bioavailability-enhancer. Nevertheless, whether curcumin combined with piperine could enhance the effect of curcumin in preventing gallstones is still awaited.

Concepts: Cholesterol, Bile, Prevention, Bile duct, Gallstone, PReVENT