A New Selective PPARγ Modulator Inhibits Triglycerides Accumulation during Murine Adipocytes’ and Human Adipose-Derived Mesenchymal Stem Cells Differentiation

Understanding the molecular basis of adipogenesis is vital to identify new therapeutic targets to improve anti-obesity drugs. The adipogenic process could be a new target in the management of this disease. Our aim was to evaluate the effect of GMG-43AC, a selective peroxisome proliferator-activated receptor \u3b3 (PPAR\u3b3) modulator, during adipose differentiation of murine pre-adipocytes and human Adipose Derived Stem Cells (hADSCs). We differentiated 3T3-L1 cells and primary hADSCs in the presence of various doses of GMG-43AC and evaluated the differentiation efficiency measuring lipid accumulation, the expression of specific differentiation markers and the quantification of accumulated triglycerides. The treatment with GMG-43AC is not toxic as shown by cell viability assessments after the treatments. Our findings demonstrate the inhibition of lipid accumulation and the significant decrease in the expression of adipocyte-specific genes, such as PPAR\u3b3, FABP-4, and leptin. This effect was long lasting, as the removal of GMG-43AC from culture medium did not allow the restoration of adipogenic process. The above actions were confirmed in hADSCs exposed to adipogenic stimuli. Together, these results indicate that GMG-43AC efficiently inhibits adipocytes differentiation in murine and human cells, suggesting its possible function in the reversal of adipogenesis and modulation of lipolysis

Expanded carrier screening: A current perspective

Prenatal carrier screening has expanded to include a large number of genes offered to all couples considering pregnancy or with an ongoing pregnancy. Expanded carrier screening refers to identification of carriers of single-gene disorders outside of traditional screening guidelines. Expanded carrier screening panels include numerous autosomal recessive and X-linked genetic conditions, including those with a very low carrier frequency, as well as those with mild or incompletely penetrant phenotype. Therefore, the clinical utility of these panels is still subject of debate. Priority should be given to carrier screening panels that include a comprehensive set of severe childhood-onset disorders. Psychosocial support and genetic couseling should be available prior to screening and for the return of positive results. Systems are needed to reduce the risk of misinterpreting results. Finally, attention should be paid on the impact of expanded carrier screening on health care organizations and burden of cost

REBALANCING DISRUPTIVE BUSINESS OF MULTINATIONAL CORPORATIONS AND GLOBAL VALUE CHAINS WITHIN DEMOCRATIC AND INCLUSIVE CITIZENSHIP PROCESSES- REVIEW WORKING PAPER

The purpose of this working paper is to conduct a comprehensive review of existing literature that explores the relationship between business organizations and democracy. This review draws from various fields, including management, business ethics, sociology, international law, and other relevant disciplines for this Project and has several objectives. Firstly, it aims to provide insight into prior research on how democratic institutions regulate economic actors and how these actors, particularly large multinational corporations (MNCs), resist such regulation. Additionally, it examines how these economic actors develop behaviors and economic models that pose challenges to democratic governance, such as business-related human rights violations. In the initial part of the review, we delve into the historical and contemporary aspects of the relationship between business and democracy. Furthermore, the report explores how companies can contribute to shaping a more democratic future by addressing gaps in governance, especially in cases where populist governments fail to protect the rights of their citizens. It also considers the development of alternative business models, such as social enterprises and cross-sector partnerships. Moreover, it looks into how businesses can actively engage in democratic governance and promote principles of participation. The final section of the working paper involves a bibliometric analysis, including co authorship, co-citation, and keyword co-occurrence maps. This analysis is based on key references used by team members in their literature reviews and is designed to examine the connections that exist among various strands of research that support the research questions of the Rebalance Project

Serum amyloid A primes microglia for ATP-dependent interleukin-1\u3b2 release

Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves production of acute-phase proteins, including serum amyloid A (SAA). Interleukin-1\u3b2 (IL-1\u3b2), a master regulator of neuroinflammation produced by activated inflammatory cells of the myeloid lineage, in particular microglia, plays a key role in the pathogenesis of acute and chronic diseases of the peripheral nervous system and CNS. IL-1\u3b2 release is promoted by ATP acting at the purinergic P2X7 receptor (P2X7R) in cells primed with toll-like receptor (TLR) ligands

Graphene plasmonics

Two rich and vibrant fields of investigation, graphene physics and plasmonics, strongly overlap. Not only does graphene possess intrinsic plasmons that are tunable and adjustable, but a combination of graphene with noble-metal nanostructures promises a variety of exciting applications for conventional plasmonics. The versatility of graphene means that graphene-based plasmonics may enable the manufacture of novel optical devices working in different frequency ranges, from terahertz to the visible, with extremely high speed, low driving voltage, low power consumption and compact sizes. Here we review the field emerging at the intersection of graphene physics and plasmonics.Comment: Review article; 12 pages, 6 figures, 99 references (final version available only at publisher's web site

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

Basal cell carcinoma of the vulva: a case report and systematic review of the literature

The vulva is an unusual site for basal cell carcinoma (BCC). Vulvar BCC accounts for <1% of all BCCs and <5% of all vulvar malignancies. We report the case of an 83 year‐old woman who presented with a 2‐month history of a tender labial growth, with histopathology confirming nodular BCC. We conducted a systematic literature review of the characteristics of reported cases of vulvar BCCs. A comprehensive systematic review of articles indexed for MEDLINE and Embase yielded 96 reports describing 437 patients with 446 BCCs of the vulva. The mean age at presentation was 70 (range 20–100). Most women had no underlying vulvar disease. Approximately 60% of cases were of the nodular subtype. Treatment approach varied widely with over half of cases treated with wide local or local excision. Mohs micrographic surgery (MMS) for vulvar BCC was first reported in 1988 with seven total MMS cases reported. Twenty‐three cases of recurrence have been reported; 21 of these cases after local excision but none following MMS. Vulvar BCC is a rarely reported cancer that affects older women predominantly. MMS represents a promising treatment for BCC in this anatomic location.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150570/1/ijd14307.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150570/2/ijd14307_am.pd

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Suppressing molecular motions for enhanced room-temperature phosphorescence of metal-free organic materials

Metal-free organic phosphorescent materials are attractive alternatives to the predominantly used organometallic phosphors but are generally dimmer and are relatively rare, as, without heavy-metal atoms, spin-orbit coupling is less efficient and phosphorescence usually cannot compete with radiationless relaxation processes. Here we present a general design rule and a method to effectively reduce radiationless transitions and hence greatly enhance phosphorescence efficiency of metal-free organic materials in a variety of amorphous polymer matrices, based on the restriction of molecular motions in the proximity of embedded phosphors. Covalent cross-linking between phosphors and polymer matrices via Diels-Alder click chemistry is devised as a method. A sharp increase in phosphorescence quantum efficiency is observed in a variety of polymer matrices with this method, which is ca. two to five times higher than that of phosphor-doped polymer systems having no such covalent linkage.ope