Currently there are 850,000 people with Alzheimer’s disease in the UK, with an estimated rise to 1.1 million by 2025. Alzheimer’s disease is characterised by the accumulation of amyloid-beta plaques ...and hyperphosphorylated tau in the brain causing a progressive decline in cognitive impairment. Small non-coding microRNA (miRNA) sequences have been found to be deregulated in the peripheral blood of Alzheimer patients. A systematic review was conducted to extract all miRNA found to be significantly deregulated in the peripheral blood. These deregulated miRNAs were cross-referenced against the miRNAs deregulated in the brain at Braak Stage III. This resulted in a panel of 10 miRNAs (hsa-mir-107, hsa-mir-26b, hsa-mir-30e, hsa-mir-34a, hsa-mir-485, hsa-mir200c, hsa-mir-210, hsa-mir-146a, hsa-mir-34c, and hsa-mir-125b) hypothesised to be deregulated early in Alzheimer’s disease, nearly 20 years before the onset of clinical symptoms. After network analysis of the 10 miRNAs, they were found to be associated with the immune system, cell cycle, gene expression, cellular response to stress, neuron growth factor signalling, wnt signalling, cellular senescence, and Rho GTPases.
Association between circulating lipopolysaccharide (LPS) and metabolic diseases (such as type 2 diabetes and atherosclerosis) has shifted the focus from high-fat high-cholesterol containing ...Western-type diet (WD)-induced changes in gut microbiota per se to release of gut bacteria-derived products (e.g., LPS) into circulation due to intestinal barrier dysfunction as the possible mechanism for the chronic inflammatory state underlying the development of these diseases. We demonstrated earlier that oral supplementation with curcumin attenuates WD-induced development of type 2 diabetes and atherosclerosis. Poor bioavailability of curcumin has precluded the establishment of a causal relationship between oral supplementation and it is in vivo effects. We hypothesized that curcumin attenuates WD-induced chronic inflammation and associated metabolic diseases by modulating the function of intestinal epithelial cells (IECs) and the intestinal barrier function. The objective of the present study was to delineate the underlying mechanisms. The human IEC lines Caco-2 and HT-29 were used for these studies and modulation of direct as well as indirect effects of LPS on intracellular signaling as well as tight junctions were examined. Pretreatment with curcumin significantly attenuated LPS-induced secretion of master cytokine IL-1β from IECs and macrophages. Furthermore, curcumin also reduced IL-1β-induced activation of p38 MAPK in IECs and subsequent increase in expression of myosin light chain kinase involved in the phosphorylation of tight junction proteins and ensuing disruption of their normal arrangement. The major site of action of curcumin is, therefore, likely the IECs and the intestinal barrier, and by reducing intestinal barrier dysfunction, curcumin modulates chronic inflammatory diseases despite poor bioavailability.
This study was carried out to determine the effect of roadside vegetation on the reduction of road traffic noise under varying planting intensities. Roadside vegetation ranging from minimal planting ...through to moderate and dense plantings were used. The results showed that the traffic noise was reduced by 50% when vegetation was enhanced from a minimal to moderate planting intensity, and no enhancement in noise reduction was observed as vegetation was further increased to a dense intensity. A 5m depth of vegetation barrier was found to be an ideal depth for traffic noise reduction. Without the vegetative barrier, the observed mean noise levels were 78dB. On average, vegetative barriers (moderate to dense) were able to reduce traffic noise by 9–11dB. Trunk size was found to be linearly related to traffic noise abatement and synthetic barriers were found to be inferior to tree belts both psychologically and in absolute values of noise. This report also investigated the effectiveness associated with setbacks where it was found that the greater the setback distance, the higher the level of noise amelioration and a 10m depth was identified as the threshold for an effective tree belt.
Neuroimaging has greatly enhanced the cognitive neuroscience understanding of the human brain and its variation across individuals (neurodiversity) in both health and disease. Such progress has not ...yet, however, propelled changes in educational or medical practices that improve people's lives. We review neuroimaging findings in which initial brain measures (neuromarkers) are correlated with or predict future education, learning, and performance in children and adults; criminality; health-related behaviors; and responses to pharmacological or behavioral treatments. Neuromarkers often provide better predictions (neuroprognosis), alone or in combination with other measures, than traditional behavioral measures. With further advances in study designs and analyses, neuromarkers may offer opportunities to personalize educational and clinical practices that lead to better outcomes for people.
Low temperature solid oxide fuel cell (LT-SOFC) can be a source of power for vehicles, online grid, and at the same time reduce system cost, offer high reliability, and fast start-up. A huge amount ...of research work, as evident from the literature has been conducted for the enhancement of the ionic conductivity of LT electrolytes in the last few years. The basic conduction mechanisms, advantages and disadvantages of different LT oxide ion conducting electrolytes {BIMEVOX systems, bilayer systems including doped cerium oxide/stabilised bismuth oxide and YSZ/DCO}, mixed ion conducting electrolytes {doped cerium oxides/alkali metal carbonate composites}, and proton conducting electrolytes {doped and undoped BaCeO3, BaZrO3, etc.} are discussed here based on the recent research articles. Effect of various material aspects (composition, doping, layer thickness, etc.), fabrication methods (to achieve different microstructures and particle size), design related strategies (interlayer, sintering aid etc.), characterization temperature & environment on the conductivity of the electrolytes and performance of the fuel cells made from these electrolytes are shown in tabular form and discussed. The conductivity of the electrolytes and performance of the corresponding fuel cells are compared. Other applications of the electrolytes are mentioned. A few considerations regarding the future prospects are pointed.
•Basic theories, advantages and disadvantages of different classes LT-SOEs covered.•Effects of composition, fabrication methods, and other strategies discussed.•Conductivity of different classes LT-SOEs is presented and compared.•Performance of the fuel cells fabricated from the electrolytes have been discussed.•Applications of the LT-SOEs in different fields are covered.
Abstract
The intestinal barrier is complex and consists of multiple layers, and it provides a physical and functional barrier to the transport of luminal contents to systemic circulation. While the ...epithelial cell layer and the outer/inner mucin layer constitute the physical barrier and are often referred to as the intestinal barrier, intestinal alkaline phosphatase (IAP) produced by epithelial cells and antibacterial proteins secreted by Panneth cells represent the functional barrier. While antibacterial proteins play an important role in the host defense against gut microbes, IAP detoxifies bacterial endotoxin lipopolysaccharide (LPS) by catalyzing the dephosphorylation of the active/toxic Lipid A moiety, preventing local inflammation as well as the translocation of active LPS into systemic circulation. The causal relationship between circulating LPS levels and the development of multiple diseases underscores the importance of detailed examination of changes in the “layers” of the intestinal barrier associated with disease development and how this dysfunction can be attenuated by targeted interventions. To develop targeted therapies for improving intestinal barrier function, it is imperative to have a deeper understanding of the intestinal barrier itself, the mechanisms underlying the development of diseases due to barrier dysfunction (eg, high circulating LPS levels), the assessment of intestinal barrier function under diseased conditions, and of how individual layers of the intestinal barrier can be beneficially modulated to potentially attenuate the development of associated diseases. This review summarizes the current knowledge of the composition of the intestinal barrier and its assessment and modulation for the development of potential therapies for barrier dysfunction-associated diseases.
Association between circulating lipopolysaccharide (LPS) and metabolic diseases (such as Type 2 Diabetes and atherosclerosis) has shifted the focus from Western diet-induced changes in gut microbiota ...per se to release of gut bacteria-derived products into circulation as the possible mechanism for the chronic inflammatory state underlying the development of these diseases. Under physiological conditions, an intact intestinal barrier prevents this release of LPS underscoring the importance of examining and modulating the direct effects of Western diet on intestinal barrier function. In the present study we evaluated two strategies, namely selective gut decontamination and supplementation with oral curcumin, to modulate Western-diet (WD) induced changes in intestinal barrier function and subsequent development of glucose intolerance and atherosclerosis. LDLR-/- mice were fed WD for 16 weeks and either received non-absorbable antibiotics (Neomycin and polymyxin) in drinking water for selective gut decontamination or gavaged daily with curcumin. WD significantly increased intestinal permeability as assessed by in vivo translocation of FITC-dextran and plasma LPS levels. Selective gut decontamination and supplementation with curcumin significantly attenuated the WD-induced increase in plasma LPS levels (3.32 vs 1.90 or 1.51 EU/ml, respectively) and improved intestinal barrier function at multiple levels (restoring intestinal alkaline phosphatase activity and expression of tight junction proteins, ZO-1 and Claudin-1). Consequently, both these interventions significantly reduced WD-induced glucose intolerance and atherosclerosis in LDLR-/- mice. Activation of macrophages by low levels of LPS (50 ng/ml) and its exacerbation by fatty acids is likely the mechanism by which release of trace amounts of LPS into circulation due to disruption of intestinal barrier function induces the development of these diseases. These studies not only establish the important role of intestinal barrier function, but also identify oral supplementation with curcumin as a potential therapeutic strategy to improve intestinal barrier function and prevent the development of metabolic diseases.
Mineral based metal working fluids used in machining, results in environmental pollution and occupational health hazards for the operators. Consequently it is necessary to evolve out machining ...techniques which are environment friendly. In the present work, techniques such as cryogenic cooling and cryogenic treatment have been compared with Al2O3 nanoparticles based MQL cooling method (nMQL) in turning of the nickel based Nimonic 90 alloy. The machining of nickel based alloy has been carried out using the AlTiN coated tungsten carbide inserts of different nose radii. The effects of these cutting environments have been studied by comparing the tool wear, cutting forces, work surface defects, surface finish, and chip underside surfaces. The application of liquid nitrogen as a cooling medium significantly reduced the tool flank wear of the 0.2 mm nose radius insert by 38% as compared to nMQL technique. The SEM investigation of rake face revealed that the cryogenic cooling technique has also prevented the groove formation and peeling of the coating. The effective cushioning effect of liquid nitrogen as coolant improved the surface finish as compared to other techniques. The cryogenic cooling reduced the defects such as material side flow, material redeposition and micro cavities over the machined surface. Overall the cryogenic cooling environment has been found to be the best mode for the machining of the Nimonic 90 alloy.
•Liquid Nitrogen as a coolant has been employed at the cutting zone for the cutting.•Cryogenic treatment of the cutting inserts has been carried out to improve the mechanical properties.•The use of cryogenic coolant significantly reduced the tool flank wear.•The application of cryogenic fluid has also reduced the work surface defects.
Objective
This narrative review focuses on the rationale and role of conventional and newer therapies in the management of oral lichen planus (OLP) with emphasis on randomized controlled trials ...(RCTs) reported over two decades.
Materials and Methods
Literature search was conducted to identify RCTs for the management of OLP from 1 January 1995 to 31 December 2015; Medline and Cochrane databases complemented with manual search were used. Primary outcome as resolution of pain was evaluated with the analysis of clinical resolution of erythema and ulceration as secondary outcome.
Results
The search provided 260 s, of which 70 full‐text articles were included. Majority of trials used topical steroids with very few trials on newer therapies. It was found that topical steroids are effective for symptomatic management of OLP with equal efficacy shown by topical calcineurin inhibitors and retinoids. However, the side effect of transient burning sensation with relapse was more with calcineurin inhibitors.
Conclusion
Although the newer therapies offer advantage over steroids for the management of OLP in recalcitrant cases, extensive lesions, and cases unresponsive to steroids, but sufficient clinical data on their use are still lacking. Hence, more RCTs with large sample size, adequate treatment duration, and long‐term follow‐up are required for clinical utility.
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