Discrimination of lipid composition and cellular localization in human liver tissues by stimulated Raman scattering microscopy.

Significance: The molecular mechanisms driving the progression from nonalcoholic fatty liver (NAFL) to fibrosing steatohepatitis (NASH) are insufficiently understood. Techniques enabling the characterization of different lipid species with both chemical and spatial information can provide valuable insights into their contributions to the disease progression.

Aim: We extend the utility of stimulated Raman scattering (SRS) microscopy to characterize and quantify lipid species in liver tissue sections from patients with NAFL and NASH.

sTREM2 is a plasma biomarker for human NASH and promotes hepatocyte lipid accumulation.

Background: Pathogenetic mechanisms of the progression of NAFL to advanced NASH coupled with potential noninvasive biomarkers and novel therapeutic targets are active areas of investigation. The recent finding that increased plasma levels of a protein shed by myeloid cells -soluble Triggering Receptor Expressed on Myeloid cells 2 (sTREM2) -may be a biomarker for NASH has received much interest. We aimed to test sTREM2 as a biomarker for human NASH and investigate the role of sTREM2 in the pathogenesis of NASH.

Genetic deletion or pharmacologic inhibition of the Nlrp3 inflammasome did not ameliorate experimental NASH.

It has been postulated that inflammasomes, in particular the NLRP3 (NLR family pyrin domain containing 3) inflammasome, mediate the necroinflammation and fibrosis that characterize nonalcoholic steatohepatitis (NASH) by engaging innate immune responses. We aimed to investigate the impact of genetic deletion or pharmacologic inhibition of the NLRP3 inflammasome on experimental steatohepatitis. Global Nlrp3 KO (expected to inhibit the NLRP3 inflammasome) or Casp1 KO (expected to inhibit all inflammasomes) mice were compared to wild type controls after 6 months on a high-fat, high-cholesterol (HFHC, 1% cholesterol) diet known to induce fibrosing steatohepatitis.

Pcsk9 Deletion Promotes Murine Nonalcoholic Steatohepatitis and Hepatic Carcinogenesis: Role of Cholesterol.

Proprotein convertase subtilisin/kexin type 9 (Pcsk9) binds to hepatic low-density lipoprotein receptor (LDLR) and induces its internalization and degradation. Pcsk9 inhibition increases LDLR expression by hepatocytes, which causes increased uptake of circulating LDL, thereby reducing plasma LDL-cholesterol. However, by increasing the uptake of LDL by the liver, Pcsk9 inhibition increases the exposure of the liver to cholesterol, which may result in higher risk of steatohepatitis and ever carcinogenesis.

Effect of Polyoxymethylene (POM-H Delrin) offgassing within Pandora head sensor on direct sun and multi-axis formaldehyde column measurements in 2016 - 2019.

Analysis of formaldehyde measurements by the Pandora spectrometer systems between 2016 and 2019 suggested that there was a temperature dependent process inside Pandora head sensor that emitted formaldehyde. Some parts in the head sensor were manufactured from thermal plastic polyoxymethylene homopolimer (E.I.

Is the future magnetic? Magseed localisation for non palpable breast cancer. A multi-centre non randomised control study.

Introduction: Magseed is an alternative method of localising non-palpable breast lesions that has addressed many of the limitations of wire guided localisation (WGL). It consists of a paramagnetic seed that can be visualised on mammography and ultrasound. Intraoperative localisation of the seed is achieved with the use of the Sentimag probe.

Cholesterol Crystals in Hepatocyte Lipid Droplets Are Strongly Associated With Human Nonalcoholic Steatohepatitis.

It is unclear what drives the development of fibrosing nonalcoholic steatohepatitis (NASH). We aimed to determine whether cholesterol crystallization within hepatocyte lipid droplets (LDs) distinguishes patients with fibrosing NASH from patients with isolated hepatic steatosis and to study pathways leading to cholesterol accumulation in hepatocyte LDs Patients with fibrosing NASH (n = 16) were compared to patients with isolated steatosis (n = 14). Almost all patients with fibrosing NASH had free cholesterol staining by filipin (16/16) and cholesterol crystals (15/16) in hepatocyte LDs, mostly in association with the LD membrane, compared to only 3/14 with cholesterol crystals and 3/14 with faint filipin staining in patients with isolated steatosis ( < 0.

Cholesterol crystallization within hepatocyte lipid droplets and its role in murine NASH.

We recently reported that cholesterol crystals form in hepatocyte lipid droplets (LDs) in human and experimental nonalcoholic steatohepatitis. Herein, we assigned WT C57BL/6J mice to a high-fat (15%) diet for 6 months, supplemented with 0%, 0.25%, 0.

Gallstones: new insights into an old story.

Gallstones, particularly cholesterol gallstones, are common in Western populations and may cause symptoms such as biliary colic or complications such as acute cholecystitis or gallstone pancreatitis. Recent studies have allowed for a better understanding of the risk of symptoms or complications in patients with gallstones. In addition, newer data suggest an association of gallstones with overall mortality, cardiovascular disease, gastrointestinal cancers, and non-alcoholic fatty liver disease.

The changing faces of cholangitis.

A variety of diseases are included under the umbrella term 'cholangitis', including hepatobiliary diseases with an autoimmune pathogenesis (such as primary sclerosing cholangitis, primary biliary cholangitis, and IgG4-associated sclerosing cholangitis) and disease processes associated with intraductal stones and infectious etiologies (such as ascending bacterial cholangitis, recurrent pyogenic cholangitis, and liver fluke-associated cholangitis). Recent advances in the pathophysiologic bases of these disorders, particularly with respect to the autoimmune variety, are allowing improved diagnosis and prognostication as well as providing the opportunity to refine and re-imagine treatment modalities. The aim of this review is to highlight selected advances in cholangitis research that point to novel insights into the pathophysiology, diagnosis, and treatment of this diverse array of disorders.

Retrospective analysis of "new" flame retardants in the global atmosphere under the GAPS Network.

A retrospective analysis was conducted on air samples that were collected in 2005 under the Global Atmospheric Passive Sampling (GAPS) Network around the time period when the Stockholm Convention on Persistent Organic Pollutants came into force. Results are presented for several new flame retardants, including hexabromocyclododecane (HBCD), which was recently listed under the Convention (2013). These results represent the first global-scale distributions in air for these compounds.

Assessing polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans in air across Latin American countries using polyurethane foam disk passive air samplers.

A passive air sampling network has been established to investigate polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) at Global Atmospheric Passive Sampling (GAPS) sites and six additional sites in the Group of Latin American and Caribbean Countries (GRULAC) region. The air sampling network covers background, agricultural, rural, and urban sites. Samples have been collected over four consecutive periods of 6 months, which started in January 2011 [period 1 (January to June 2011), period 2 (July to December 2011), period 3 (January to June 2012), and period 4 (July 2012 to January 2013)].

Perfluoroalkyl acids in the Canadian environment: multi-media assessment of current status and trends.

In Canada, perfluoroalkyl acids (PFAAs) have been the focus of several monitoring programs and research and surveillance studies. Here, we integrate recent data and perform a multi-media assessment to examine the current status and ongoing trends of PFAAs in Canada. Concentrations of perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and other long-chain perfluorocarboxylates (PFCAs) in air, water, sediment, fish, and birds across Canada are generally related to urbanization, with elevated concentrations observed around cities, especially in southern Ontario.

Physical activity, maternal metabolic measures, and the incidence of gallbladder sludge or stones during pregnancy: a randomized trial.

Objective: To evaluate the effect of a physical activity intervention upon the incidence of gallbladder sludge or stones during pregnancy.

Study Design: Pregnant women without gallstones were randomized to an intervention to increase moderate to vigorous physical activity or control. Intervention group women received motivational materials and small-group instruction to increase physical activity.

East meets West: current issues relevant to integrating Chinese medicine.

This article describes the challenges that integration of Chinese medicine (CM) and biomedicine are likely to bring for improving safety, research, education, and cross-disciplinary communication. Potential strategies to meet these challenges are suggested, including the use of accessible language for the Western biomedical community, and further development of whole-system randomized controlled trials that support individualized treatment approaches.

Application of sorbent impregnated polyurethane foam (SIP) disk passive air samplers for investigating organochlorine pesticides and polybrominated diphenyl ethers at the global scale.

As part of continued efforts under the Global Atmospheric Passive Sampling (GAPS) Network to develop passive air samplers applicable to a wide-range of compounds, sorbent-impregnated polyurethane foam (SIP) disk samplers were codeployed and tested against conventional polyurethane foam (PUF) disk samplers. The SIP disk sampler has a higher sorptive capacity compared to the PUF disk sampler, due to its impregnation with ground XAD resin. The two sampler types were codeployed at 20 sites during the 2009, 3-month long spring sampling period of the GAPS Network.

Assessment of sorbent impregnated PUF disks (SIPs) for long-term sampling of legacy POPs.

Two field studies were conducted for one year using sorbent-impregnated polyurethane foam (SIP) disks for PCB and PBDE air sampling. SIP disks were introduced by Shoeib et al. (2008) as an alternative passive air sampling medium to the polyurethane foam (PUF) disk and have the advantage of a higher holding capacity for organic chemicals.

Liver fluke-induced hepatic oxysterols stimulate DNA damage and apoptosis in cultured human cholangiocytes.

Oxysterols are cholesterol oxidation products that are generated by enzymatic reactions through cytochrome P450 family enzymes or by non-enzymatic reactions involving reactive oxygen and nitrogen species. Oxysterols have been identified in bile in the setting of chronic inflammation, suggesting that biliary epithelial cells are chronically exposed to these compounds in certain clinical settings. We hypothesized that biliary oxysterols resulting from liver fluke infection participate in cholangiocarcinogenesis.

Hepatic free cholesterol accumulates in obese, diabetic mice and causes nonalcoholic steatohepatitis.

Background & Aims: Type 2 diabetes and nonalcoholic steatohepatitis (NASH) are associated with insulin resistance and disordered cholesterol homeostasis. We investigated the basis for hepatic cholesterol accumulation with insulin resistance and its relevance to the pathogenesis of NASH.

Methods: Alms1 mutant (foz/foz) and wild-type NOD.

Wastewater treatment plant and landfills as sources of polyfluoroalkyl compounds to the atmosphere.

Polyfluoroalkyl compounds (PFCs) were determined in air around a wastewater treatment plant (WWTP) and two landfill sites using sorbent-impregnated polyurethane foam (SIP) disk passive air samplers in summer 2009. The samples were analyzed for five PFC classes (i.e.

Global distribution of linear and cyclic volatile methyl siloxanes in air.

The global distribution of linear and cyclic volatile methyl silxoanes (VMS) was investigated at 20 sites worldwide, including 5 locations in the Arctic, using sorbent-impregnated polyurethane foam (SIP) disk passive air samplers. Cyclic VMS are currently being considered for regulation because they are high production volume chemicals that are potentially persistent, bioaccumulative, and toxic. Linear and cyclic VMS (including L3, L4, L5, D3, D4, D5, and D6) were analyzed for in air at all urban, background, and Arctic sites.

Indoor sources of poly- and perfluorinated compounds (PFCS) in Vancouver, Canada: implications for human exposure.

Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are widely detected in human blood and serum and are of concern due to their potential toxicity. This study investigated the indoor sources of these compounds and their neutral precursors through a survey of 152 homes in Vancouver, Canada. Samples were collected of indoor air, outdoor air, indoor dust, and clothes dryer lint and analyzed for neutral [i.

Assessing seasonal and spatial trends of persistent organic pollutants (POPs) in Indian agricultural regions using PUF disk passive air samplers.

The first survey of persistent organic pollutant (POP) concentrations in air across several Indian agricultural regions was conducted in 2006-2007. Passive samplers comprising polyurethane foam (PUF) disks were deployed on a quarterly basis at seven stations in agricultural regions, one urban site and one background site. The project was conducted as a sub-project of the Global Atmospheric Passive Sampling (GAPS) Network.

Global pilot study of legacy and emerging persistent organic pollutants using sorbent-impregnated polyurethane foam disk passive air samplers.

Sorbent-impregnated polyurethane foam (SIP) disk passive air samplers were deployed alongside polyurethane foam (PUF) disk samplers at 20 sites during the 2009 spring sampling period of the Global Atmospheric Passive Sampling (GAPS) Network. The SIP disk samplers consisted of PUF disks impregnated with finely ground XAD-4 resin. The addition of XAD-4 greatly improves the sorptive capacity of the PUF disk samplers for more volatile and polar chemicals, and allows for linear-phase sampling over several weeks for these compounds.

Effects of lipopolysaccharide on platelet-derived growth factor isoform and receptor expression in cultured rat common bile duct fibroblasts and cholangiocytes.

Background And Aim: Little is known about the role of platelet-derived growth factor (PDGF) in biliary fibrosis in the setting of bacterial colonization of the biliary tree. We therefore sought to investigate whether exposure to bacterial lipopolysaccharide (LPS) alters PDGF isoform and receptor expression in cultured rat common bile duct fibroblasts (CBDF) and normal rat cholangiocytes (NRC).

Methods: Collagen content in cells and media was assessed by colorimetric assay and gel electrophoresis.