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This paper analyses challenges and opportunities for improving energy efficiency in small and medium enterprises (SMEs) by reviewing research design and results out of seven European projects: SPEEDIER, SMEmPower Efficiency, E2Driver, Innoveas, Triple-A, DEESME and ICCEE. These projects aim to improve SMEs’ awareness of energy efficiency and support an effective decision-making-oriented approach to it. Drivers and barriers to energy efficiency improvements in European SMEs of various industrial sectors have been investigated by means of surveys, focused group discussions and interviews. A meta-analysis of the results of the seven EU projects was carried out to discover trends related to energy efficiency in European SMEs; this was supported by the use of a unifying analytic framework that enabled merging and cross-validation of the findings of the seven projects. The analysis indicated, by means of new data collected by the seven projects, that staff training, facilitation of energy audits, development of corporate policy measures and collaboration between SMEs involved in the same supply chain are key mechanisms to improve the uptake of energy efficiency measures in SMEs which has significant potential to achieve higher energy savings and energy cost reductions.

The ε4 allele of apolipoprotein E (APOE) is the dominant genetic risk factor for late-onset Alzheimer’s disease (AD). However, the reason for the association between APOE4 and AD remains unclear. While much of the research has focused on the ability of the apoE4 protein to increase the aggregation and decrease the clearance of Aβ, there is also an abundance of data showing that APOE4 negatively impacts many additional processes in the brain, including bioenergetics. In order to gain a more comprehensive understanding of APOE4′s role in AD pathogenesis, we performed a transcriptomics analysis of APOE4 vs. APOE3 expression in the entorhinal cortex (EC) and primary visual cortex (PVC) of aged APOE mice. This study revealed EC-specific upregulation of genes related to oxidative phosphorylation (OxPhos). Follow-up analysis utilizing the Seahorse platform showed decreased mitochondrial respiration with age in the hippocampus and cortex of APOE4 vs. APOE3 mice, but not in the EC of these mice. Additional studies, as well as the original transcriptomics data, suggest that multiple bioenergetic pathways are differentially regulated by APOE4 expression in the EC of aged APOE mice in order to increase the mitochondrial coupling efficiency in this region. Given the importance of the EC as one of the first regions to be affected by AD pathology in humans, the observation that the EC is susceptible to differential bioenergetic regulation in response to a metabolic stressor such as APOE4 may point to a causative factor in the pathogenesis of AD.

The discovery of contact sites was a breakthrough in cell biology. We have learned that an organelle cannot function in isolation, and that many cellular functions depend on communication between two or more organelles. One such contact site results from the close apposition of the endoplasmic reticulum (ER) and mitochondria, known as mitochondria-associated ER membranes (MAMs). These intracellular lipid rafts serve as hubs for the regulation of cellular lipid and calcium homeostasis, and a growing body of evidence indicates that MAM domains modulate cellular function in both health and disease. Indeed, MAM dysfunction has been described as a key event in Alzheimer disease (AD) pathogenesis. Our most recent work shows that, by means of its affinity for cholesterol, APP-C99 accumulates in MAM domains of the ER and induces the uptake of extracellular cholesterol as well as its trafficking from the plasma membrane to the ER. As a result, MAM functionality becomes chronically upregulated while undergoing continual turnover. The goal of this review is to discuss the consequences of C99 elevation in AD, specifically the upregulation of cholesterol trafficking and MAM activity, which abrogate cellular lipid homeostasis and disrupt the lipid composition of cellular membranes. Overall, we present a novel framework for AD pathogenesis that can be linked to the many complex alterations that occur during disease progression, and that may open a door to new therapeutic strategies.

LGBTQ patients experience discrimination and poor access to quality health care, but there is little inquiry on the experiences of LGBTQ patients in student health clinic. The purpose of this study was to examine the quality of patient-provider communication (PPC) among sexual and gender minority patients, especially those who have intersecting minority identities, in a student healthcare setting. An online survey measured PPC using the Communication Assessment Tool (CAT) and contextual questions regarding identity and perceptions of judgment. Analysis tested intersectional variance in both. A convenience and snowball sample of 102 respondents, 18+, that utilized health services at a public university in the southeastern United States were surveyed in the summer of 2019. Patients of Color (M = 8.16, SD = 5.69) perceived stronger PPC than Whites (M = 5.41, SD = 5.27), which deviates from much of the current literature available. Heterosexuals (M = 7.82, SD = 5.65) perceived stronger PPC than LGBQ (M = 4.56, SD = 4.98) patients, which aligns with most current literature. Additional research is recommended for generalizability among student health populations in other university campuses and preliminary findings indicate a need to improve PPC between clinicians and sexual minority patients in student health settings. Experience Framework This article is associated with the Policy & Measurement lens of The Beryl Institute Experience Framework. (http://bit.ly/ExperienceFramework) Access other PXJ articles related to this lens. Access other resources related to this lens.

The link between cholesterol homeostasis and cleavage of the amyloid precursor protein (APP), and how this relationship relates to Alzheimer's disease (AD) pathogenesis, is still unknown. Cellular cholesterol levels are regulated through crosstalk between the plasma membrane (PM), where most cellular cholesterol resides, and the endoplasmic reticulum (ER), where the protein machinery that regulates cholesterol levels resides. The intracellular transport of cholesterol from the PM to the ER is believed to be activated by a lipid‐sensing peptide(s) in the ER that can cluster PM‐derived cholesterol into transient detergent‐resistant membrane domains (DRMs) within the ER, also called the ER regulatory pool of cholesterol. When formed, these cholesterol‐rich domains in the ER maintain cellular homeostasis by inducing cholesterol esterification as a mechanism of detoxification while attenuating its de novo synthesis. In this manuscript, we propose that the 99‐aa C‐terminal fragment of APP (C99), when delivered to the ER for cleavage by γ‐secretase, acts as a lipid‐sensing peptide that forms regulatory DRMs in the ER, called mitochondria‐associated ER membranes (MAM). Our data in cellular AD models indicates that increased levels of uncleaved C99 in the ER, an early phenotype of the disease, upregulates the formation of these transient DRMs by inducing the internalization of extracellular cholesterol and its trafficking from the PM to the ER. These results suggest a novel role for C99 as a mediator of cholesterol disturbances in AD, potentially explaining early hallmarks of the disease., When delivered to the ER, the C‐terminal BACE1 cleavage product of amyloid precursor protein APP acts as lipid‐sensing peptide, facilitating formation of detergent‐resistant mitochondria‐associated ER membranes (MAM) via internalization and retrograde transport of cholesterol.

The link between cholesterol homeostasis and the cleavage of the amyloid precursor protein (APP), and their relationship to the pathogenesis of Alzheimer’s disease (AD) is still unknown. Cellular cholesterol levels are regulated by a crosstalk between the plasma membrane (PM), where most of the cholesterol resides, and the endoplasmic reticulum (ER), where the protein machinery that regulates cholesterol resides. This crosstalk between PM and ER is believed to be regulated by lipid-sensing peptide(s) that can modulate the internalization of extracellular cholesterol and/or itsde novosynthesis in the ER. Our data here indicates that the 99-aa C-terminal fragment of APP (C99), a cholesterol-binding peptide, regulates cholesterol trafficking between the PM and the ER. In AD models, increases in C99 provoke the upregulation of cholesterol internalization and its delivery to the ER, which in turn result into the loss of lipid homeostasis and the appearance of AD signatures, such as higher production of longer forms of amyloid β. Our data suggest a novel role of C99 as mediator of cholesterol disturbances in AD, and as a potential early hallmark of the disease.

Sodium gluconate presented as a category of biomolecule found to be a proficient and recyclable organocatalyst for the synthesis of dihydropyrano[2,3-c]pyrazole derivatives via one-pot multicomponent reaction of aryl aldehyde, malononitrile, ethyl acetoacetate and hydrazine hydrate in water as a solvent. The catalyst is non-toxic in nature, commercially available, biodegradable and easily separated from the reaction mixture. Present protocol avoids the use of the heavy metal catalyst, harsh reaction condition and the reusability of catalyst, broad substrate scope, simple work-up procedure and excellent yield of products make this protocol greener. KEY WORDS: Pyrano[2,3-c]pyrazole, Sodium gluconate, Multicomponent reaction (MCR), Knovenagel condensation, Bio-based organocatalyst Bull. Chem. Soc. Ethiop. 2019, 33(2), 331-340.DOI: https://dx.doi.org/10.4314/bcse.v33i2.13

OBJECTIVES: To examine the outcomes of e-learning or blended learning interventions in undergraduate dental radiology curricula and analyze the nature of the knowledge levels addressed in learning interventions. METHODS: A systematic literature review was performed using a search strategy based on MeSH key words specific to the focus question and indexed in the MEDLINE database. The search again was supplemented by hand-searching of selected journals. Data were extracted relating to outcomes of knowledge and student perceptions. Analysis of the e-learning intervention was performed using a new framework to examine the level of knowledge undertaken: (1) remember/understand (2) analysis or evaluation or diagnosis and (3) performance (“knows how” or “shows how”). RESULTS: From the selected 17 papers, 11 were positive about student reported outcomes of the interventions, and 8 reported evidence that e-learning interventions enhanced learning. Out of the included studies, 8 used e-learning at the level of remember/understand, 4 at the level of analysis/evaluate/diagnosis, and 5 at the level of performance (“knows how,” “shows how”). CONCLUSIONS: The learning objectives, e-learning intervention, outcome measures and reporting methods were diverse and not well reported. This makes comparison between studies and an understanding of how interventions contributed to learning impractical. Future studies need to define “knowledge” levels and performance tasks undertaken in the planning and execution of e-learning interventions and their assessment methods. Such a framework and approach will focus our understanding in what ways e-learning is effective and how it contributes to better evidence-based e-learning experiences.

Objective— Tissue macrophages induce and perpetuate proinflammatory responses, thereby promoting metabolic and cardiovascular disease. Lipoprotein lipase (LpL), the rate-limiting enzyme in blood triglyceride catabolism, is expressed by macrophages in atherosclerotic plaques. We questioned whether LpL, which is also expressed in the bone marrow (BM), affects circulating white blood cells and BM proliferation and modulates macrophage retention within the artery. Approach and Results— We characterized blood and tissue leukocytes and inflammatory molecules in transgenic LpL knockout mice rescued from lethal hypertriglyceridemia within 18 hours of life by muscle-specific LpL expression (MCKL0 mice). LpL-deficient mice had ≈40% reduction in blood white blood cell, neutrophils, and total and inflammatory monocytes (Ly6C/G hi ). LpL deficiency also significantly decreased expression of BM macrophage-associated markers (F4/80 and TNF-α [tumor necrosis factor α]), master transcription factors (PU.1 and C/EBPα), and colony-stimulating factors (CSFs) and their receptors, which are required for monocyte and monocyte precursor proliferation and differentiation. As a result, differentiation of macrophages from BM-derived monocyte progenitors and monocytes was decreased in MCKL0 mice. Furthermore, although LpL deficiency was associated with reduced BM uptake and accumulation of triglyceride-rich particles and macrophage CSF–macrophage CSF receptor binding, triglyceride lipolysis products (eg, linoleic acid) stimulated expression of macrophage CSF and macrophage CSF receptor in BM-derived macrophage precursor cells. Arterial macrophage numbers decreased after heparin-mediated LpL cell dissociation and by genetic knockout of arterial LpL. Reconstitution of LpL-expressing BM replenished aortic macrophage density. Conclusions— LpL regulates peripheral leukocyte levels and affects BM monocyte progenitor differentiation and aortic macrophage accumulation.

In the amyloidogenic pathway associated with Alzheimer disease (AD), the amyloid precursor protein (APP) is cleaved by beta-secretase to generate a 99-aa C-terminal fragment (C99) that is then cleaved by c-secretase to generate the beta-amyloid (Ab) found in senile plaques. In previous reports, we and others have shown that c-secretase activity is enriched in mitochondria-associated endoplasmic reticulum (ER) membranes (MAM) and that ER-mitochondrial connectivity and MAM function are upregulated in AD. We now show that C99, in addition to its localization in endosomes, can also be found in MAM, where it is normally processed rapidly by c-secretase. In cell models of AD, however, the concentration of unprocessed C99 increases in MAM regions, resulting in elevated sphingolipid turnover and an altered lipid composition of both MAM and mitochondrial membranes. In turn, this change in mitochondrial membrane composition interferes with the proper assembly and activity of mitochondrial respiratory supercomplexes, thereby likely contributing to the bioenergetic defects characteristic of AD. We thank Drs. Orian Shirihai and Marc Liesa (UCLA) for assistance with the Seahorse measurements, Dr. Huaxi Xu (Sanford Burnham Institute) for the APP-DKO MEFs and Dr. Mark Mattson (NIH) for the PS1 knock-in mice, Drs. Arancio and Teich for the APP-KO mice tissues used in these studies, Dr. Hua Yang (Columbia University) for mouse husbandry, and Drs. Marc Tambini, Ira Tabas, and Serge Przedborski for helpful comments. This work was supported by the Fundacion Alfonso Martin Escudero (to M.P.); the Alzheimer's Drug Discovery Foundation, the Ellison Medical Foundation, the Muscular Dystrophy Association, the U.S. Department of Defense W911NF-12-1-9159 and W911F-15-1-0169), and the J. Willard and Alice S. Marriott Foundation (to E.A.S.); the U.S. National Institutes of Health (P01-HD080642 and P01-HD032062 to E.A.S.; NS071571 and HD071593 to M.F.M.; R01-NS056049 and P50-AG008702 to G.D.P.; 1S10OD016214-01A1 to G.S.P. and F.P.M, and K01-AG045335 to E.A.-G.), the Lucien Cote Early Investigator Award in Clinical Genetics from the Parkinson's Disease Foundation (PDF-CEI-1364 and PDF-CEI-1240) to C.G.-L., and National Defense Science and Engineering Graduate Fellowship (FA9550-11-C-0028) to R.R.A. Sí

ON THE ORDER OF THE COEFFICIENTS AND CONVERGENCE OF A FOURIER-BESSEL SERIES OF A DIFFERENTIABLE FUNCTION

Curcumin has diverse biological activities including antioxidant and anti-inflammatory activity. However, its clinical use for topical application is limited due to its poor aqueous solubility and thus, minimal cutaneous bioavailability. Elastic vesicles (EVs) of curcumin were prepared to improve its cutaneous bioavailability and to use it for topical anti-inflammatory effect. Ex vivo skin permeation and retention studies were performed to check if incorporation of curcumin into EVs could improve its permeation into and retention in the skin. Evaluation of acute and chronic anti-inflammatory effect was done using xylene-induced acute ear edema in mice and cotton pellet-induced chronic inflammation in rats, respectively. A significant improvement in flux (nine times) across murine skin was observed when aqueous dispersion of curcumin (flux − 0.46 ± 0.02 μg/h/cm2) was compared with curcumin-loaded EVs (flux − 4.14 ± 0.04 μg/h/cm2 ). Incorporation of these curcumin-loaded EVs into a hydrophilic ointment base resulted in higher skin retention (51.66%) in contrast to free curcumin ointment (1.64%) and a marketed formulation (VICCO® turmeric skin cream). The developed ointment showed an effect similar (p

We describe an interesting case of intramural duodenal hematoma in an otherwise healthy male who presented to emergency room with gradually progressive abdominal pain, nausea, and vomiting. This condition was missed on initial evaluation and patient was discharged from emergency room with diagnosis of acute gastritis. After 3 days, patient came back to emergency room and abdominal imaging studies were conducted which showed that patient had intramural duodenal hematoma associated with gastric outlet obstruction and pancreatitis. Hematoma was the cause of acute pancreatitis as pancreatic enzymes levels were normal at the time of first presentation, but later as the hematoma grew in size, it caused compression of pancreas and subsequent elevation of pancreatic enzymes. We experienced a case of pancreatitis which was caused by intramural duodenal hematoma. This case was missed on initial evaluation. We suggest that physicians should be more vigilant about this condition.

Department of Chemistry, D. D. U. Gorakhpur University, Gorakhpur-273 009, India E-mail: ishwar_das@rediffmail.com Fax: 91-551-342880 Manuscript received 20 September 2002 Some aspects of pattern formation during electrochemical deposition of metals.

Eleven patients suffering from hyperhidrosis were psychiatrically studied. Seven of them were given behaviour therapy. Majority of the patients had -an unhappy childhood and long - standing and continuing psychological stress. None of them had obvious, coexisting psychiatric condition.. Thus, hyperhidrosis was the sole, expression of their psychological conflicts. Of the 7 patients treated 71% showed improvement with relaxation and systemic desentiziation which,was maintained for a_ period of at least 6 months.

Research and Control Laboratory, Bharat Aluminium Co. Ltd., Korba-495 684 Chemistry Department, Government Tilak College, Katni-483 501 Manuscript received 12 August 1984, revised 8 March1985, accepted 3 June1985 The X-ray diffraction data or fifteen N-hydroxy-N-aryl-arylamides are described here, out of which 14 are reported for the first time. An attempt has been made to establishtheir diffraction patterns.

The reaction of 18 N-arylhydroxamic acids ·with V{V) in different acidities and under varying experimental conditions have been investigated. In concentrated HCl an intensely violet chelate of V(V), which is readily extracted into chloroform, is formed. The substitution in the hydroxamic acid functional grouping affects the hue and spectral characteristics of the V(V)-chelates. It is inferred that N-p-Cl-phenyl-p-methoxybenzohydroxamic acid retains all the useful features of N-phenylbenzohydroxamic acid as a reagent for V(V) but surpasses it in sensitivity and selectivity of the reaction. With this quick method vanadium has been determined in analysed steels without the recourse of masking agents or prior separations. The excellent results obtained on these samples are taken as a proof of the reliability, precision and accuracy of the method.

The Gattermann reaction on 2,3-, 2,4-, 2,5-, 2,6-, 3,4-, and 3,5-xylenols has been investigated and the identity of different aldehydes obtained has been established.

The infrared spectra of several metal complexes of N-phenylbenzohydroxamic acid and its analogues N-phenyl-2-furohydroxamic acid andN-p-tolylbenzohydroxamic acid are presented. The hydroxamic acids form chelates, by the replacement of hydrogen of the hydroxylamino group by metal ion and ring closure through coordination from oxygen of the carbonyl group. The bands due to O-H group in free ligand disappear, while bands due to N-O and C = O groups shift on complex forma­tion.

MDR infections in the ICU are not nosocomial all the time, as perceived commonly. We performed a 2-year retrospective study to analyze the source of culture positivity in a medical ICU and to identify which types of infections are more prevalent.