Extracellular vesicles alter trophoblast function in pregnancies complicated by COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and resulting coronavirus disease (COVID-19) causes placental dysfunction, which increases the risk of adverse pregnancy outcomes. While abnormal placental pathology resulting from COVID-19 is common, direct infection of the placenta is rare. This suggests that pathophysiology associated with maternal COVID-19, rather than direct placental infection, is responsible for placental dysfunction and alteration of the placental transcriptome. We hypothesized that maternal circulating extracellular vesicles (EVs), altered by COVID-19 during pregnancy, contribute to placental dysfunction. To examine this hypothesis, we characterized maternal circulating EVs from pregnancies complicated by COVID-19 and tested their effects on trophoblast cell physiology in vitro . We found that the gestational timing of COVID-19 is a major determinant of circulating EV function and cargo. In vitro trophoblast exposure to EVs isolated from patients with an active infection at the time of delivery, but not EVs isolated from Controls, altered key trophoblast functions including hormone production and invasion. Thus, circulating EVs from participants with an active infection, both symptomatic and asymptomatic cases, can disrupt vital trophoblast functions. EV cargo differed between participants with COVID-19 and Controls, which may contribute to the disruption of the placental transcriptome and morphology. Our findings show that COVID-19 can have effects throughout pregnancy on circulating EVs and circulating EVs are likely to participate in placental dysfunction induced by COVID-19.

Ester-related volatile compounds reveal the diversity and commonalities of different types of late-ripening peaches.

To recognize the key ester-related volatile compounds, 5 types of peaches including 54 late-ripening peach materials were examined by headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry and E-nose. Here, a large number of esters were identified to be released by ripe peach fruits and were mainly characterized by fruity, green, and fatty notes. The variety and content of esters had greatly changed within or between cultivars, indicating that the fruit volatiles were highly differentiated depending on the specific genotypes and cultivation conditions. The ester types showed that fatty acid-derived C6 alcohols and methyl-/ethyl- short-chain alcohol were the main ester precursors, which were more likely to be utilized and well selected by alcohol acyltransferases, whereas the preference of acyl donors was not observed. The common peach type, which exhibited a unique volatile profile, displayed broader diversity and more abundant characteristics in ester-related volatiles than the other four types. A total of 19 key esters were identified as the main components and the content of most esters showed no significant difference among different peach types. Some key esters had even been enriched in nectarines. Moreover, the multiple discriminant analysis revealed a possible relationship between peach types and the domestication of the peach evolution. This study investigated ester-related volatiles released by different types of peach fruits and can be further used to evaluate the peach qualities, providing an important reference for peach breeding and processing.

Fibre-rich Foods to Treat Obesity and Prevent Colon Cancer trial study protocol: a randomised clinical trial of fibre-rich legumes targeting the gut microbiome, metabolome and gut transit time of overweight and obese patients with a history of noncancerous adenomatous polyps.

INTRODUCTION: Recently published studies support the beneficial effects of consuming fibre-rich legumes, such as cooked dry beans, to improve metabolic health and reduce cancer risk. In participants with overweight/obesity and a history of colorectal polyps, the Fibre-rich Foods to Treat Obesity and Prevent Colon Cancer randomised clinical trial will test whether a high-fibre diet featuring legumes will simultaneously facilitate weight reduction and suppress colonic mucosal biomarkers of colorectal cancer (CRC). METHODS/DESIGN: This study is designed to characterise changes in (1) body weight; (2) biomarkers of insulin resistance and systemic inflammation; (3) compositional and functional profiles of the faecal microbiome and metabolome; (4) mucosal biomarkers of CRC risk and (5) gut transit. Approximately 60 overweight or obese adults with a history of noncancerous adenomatous polyps within the previous 3 years will be recruited and randomised to one of two weight-loss diets. Following a 1-week run-in, participants in the intervention arm will receive preportioned high-fibre legume-rich entrées for two meals/day in months 1-3 and one meal/day in months 4-6. In the control arm, entrées will replace legumes with lean protein sources (eg, chicken). Both groups will receive in-person and written guidance to include nutritionally balanced sides with energy intake to lose 1-2 pounds per week. ETHICS AND DISSEMINATION: The National Institutes of Health fund this ongoing 5-year study through a National Cancer Institute grant (5R01CA245063) awarded to Emory University with a subaward to the University of Pittsburgh. The study protocol was approved by the Emory Institutional Review Board (IRB approval number: 00000563). TRIAL REGISTRATION NUMBER: NCT04780477.

Relationship of circulating levels of long-chain fatty acids to persistent organ failure in acute pancreatitis.

During acute pancreatitis (AP), free fatty acids (FFAs) are liberated from circulating triglycerides (TG) and injured adipocytes by pancreatic lipase. Circulating FFAs have been suspected as a source of systemic lipotoxicity in AP. However, assessment of FFAs is difficult and time-consuming, and little is known about relative levels of FFAs between patients with different severities of AP and controls. This study's aims were to assess early circulating levels of FFAs, (both saturated and unsaturated) in patients with AP vs. controls, and associations between FFA levels and AP severity. Serum samples from patients with AP were collected at enrollment (day 1 of hospital stay); serum samples were also collected from controls. FFAs including palmitic, palmitoleic, stearic, oleic, and linoleic acid were extracted and quantitated using gas chromatography separation. Severity of AP was determined by Revised Atlanta Classification. Differences in FFA levels and percentages of total FFAs were assessed between patients with AP and controls and patients with AP of different severity grades. A total of 93 patients with AP (48 female, 52%) and 29 controls (20 female, 69%) were enrolled. Of the patients with AP, 74 had mild/moderate and 19 had severe AP. Serum levels of all FFAs except stearic acid were significantly higher in patients with AP compared with controls. A strong and independent association between elevated palmitoleic acid levels and severe AP was found. Serum unsaturated FFA levels, specifically palmitoleic acid, appear to correlate with severe AP. These findings have potential clinical implications for targeted AP therapies.NEW & NOTEWORTHY Drivers of the inflammatory response in acute pancreatitis remain incompletely understood. Unsaturated fatty acids, specifically palmitoleic, appear to have an association with more severe acute pancreatitis. This finding presents a new clinical understanding of fatty acid toxicity and highlights a potential future target for treatment in severe acute pancreatitis.

The Hypolipidemic Characteristics of a Methanol Extract of Fermented Green Tea and Spore of Eurotium cristatum SXHBTBU1934 in Golden Hamsters.

Fuzhuan brick tea (FBT), a distinctive Chinese dark tea with the predominant fungus of Eurotium cristatum, offered significant health benefits to Chinese people. In the current study, the in vivo bioactivities of E. cristatum (SXHBTBU1934) fermented green tea and spores of E. cristatum fermented on wheat were investigated, respectively. The methanol extract of fermented green tea and spore of E. cristatum both showed potent lipid-lowering activity in the blood of a high-fat diet induced hyperlipidemia model in golden hamsters and significantly reduced the accumulation of fat granules in the liver. These results indicated that the key active components were produced by E. cristatum. Chemical investigations suggested similar components in the two extracts and led to the identification of a new alkaloid, namely variecolorin P (1), along with four known structurally related compounds, (-)-neoechinulin A (2), neoechinulin D (3), variecolorin G (4), and echinulin (5). The structure of the new alkaloid was elucidated by HRESIMS, 1H, 13C, and 2D NMR analysis. The lipid-lowering activity of these compounds was evaluated using an oleic acid-induced HepG2 cell line model. Compound 1 significantly reduced the lipid accumulation in the HepG2 cell line with an IC50 value of 0.127 µM.

Histone deacetylase inhibitors (HDACi) increase expression of KCa2.3 (SK3) in primary microvascular endothelial cells.

The small conductance calcium-activated potassium channel (KCa2.3) has long been recognized for its role in mediating vasorelaxation through the endothelium-derived hyperpolarization (EDH) response. Histone deacetylases (HDACs) have been implicated as potential modulators of blood pressure and histone deacetylase inhibitors (HDACi) are being explored as therapeutics for hypertension. Herein, we show that HDACi increase KCa2.3 expression when heterologously expressed in HEK cells and endogenously expressed in primary cultures of human umbilical vein endothelial cells (HUVECs) and human intestinal microvascular endothelial cells (HIMECs). When primary endothelial cells were exposed to HDACi, KCa2.3 transcripts, subunits, and functional current are increased. Quantitative RT-PCR (qPCR) demonstrated increased KCa2.3 mRNA following HDACi, confirming transcriptional regulation of KCa2.3 by HDACs. By using pharmacological agents selective for different classes of HDACs, we discriminated between cytoplasmic and epigenetic modulation of KCa2.3. Biochemical analysis revealed an association between the cytoplasmic HDAC6 and KCa2.3 in immunoprecipitation studies. Specifically inhibiting HDAC6 increases expression of KCa2.3. In addition to increasing the expression of KCa2.3, we show that nonspecific inhibition of HDACs causes an increase in the expression of the molecular chaperone Hsp70 in endothelial cells. When Hsp70 is inhibited in the presence of HDACi, the magnitude of the increase in KCa2.3 expression is diminished. Finally, we show a slower rate of endocytosis of KCa2.3 as a result of exposure of primary endothelial cells to HDACi. These data provide the first demonstrated approach to increase KCa2.3 channel number in endothelial cells and may partially account for the mechanism by which HDACi induce vasorelaxation.

High Sugar-Sweetened Beverage Consumption Is Associated with Increased Health Care Utilization in Patients with Inflammatory Bowel Disease: A Multiyear, Prospective Analysis.

BACKGROUND: Dietary factors like sugar-sweetened beverage (SSB) consumption are known to influence disease course in a variety of illnesses; however, long-term outcomes are not well documented for inflammatory bowel disease. OBJECTIVE: Does high consumption of SSBs lead to high healthcare utilization (ie, hospitalizations and emergency department visits), inflammation, and disease severity in patients with inflammatory bowel disease? DESIGN: A prospective cohort study was conducted from 2015 to 2019. Patients enrolled in the discovery study cohort were followed for 3 years, whereas patients in the validation cohort were followed for 2 years. They underwent nutrition assessment and received routine care. Dietary intakes of SSBs and fiber were quantified by a validated, self-reported questionnaire. PARTICIPANTS/SETTING: For the discovery study cohort, 1133 adult patients were recruited from the University of Pittsburgh Medical Center Digestive Disease Clinic in Pittsburgh, PA. Eligible patients had a preexisting diagnosis of Crohn's disease or ulcerative colitis and had at least annual follow-up at this tertiary referral center. High SSB consumption was defined as 7 or more SSBs per week. Moderate was defined as > 2 but < 7 SSBs per week. Low SSB consumption was defined as 2 or fewer SSBs per week. MAIN OUTCOME MEASURES: Primary outcome was time to hospitalization and emergency department visits. Secondary outcomes assessed laboratory markers of disease severity and inflammation. Tertiary outcomes assessed time to hospitalization and emergency department visits in a subsequent independent cohort of patients. STATISTICAL ANALYSIS PERFORMED: Multivariable logistic regression, Kaplan-Meier, and Cox proportional hazards modeling RESULTS: The discovery cohort included of 1,133 adult patients with inflammatory bowel disease (58% women, 70% with Chron's disease, 30% with ulcerative colitis, median age 46 years). Low SSB consumption, moderate SSB consumption, and high SSB consumption occurred in 57%, 17%, and 26% in the discovery cohort, respectively. Among patients without active disease at enrollment, high SSB consumption was associated with decreased time to hospitalization and emergency department visits when compared with low SSB consumption (hazard ratio 1.55, 95% CI 1.06 to 2.27; and hazard ratio 1.53, 95% CI 1.10 to 2.13). In terms of disease severity and inflammatory biomarkers, high SSB consumption was associated with increase odds of elevated erythrocyte sedimentation rate (odds ratio 2.04, 95% CI 1.31 to 3.18), elevated C-reactive protein level (odds ratio 1.60, 95% CI, 1.07-2.37), eosinophilia (odds ratio 1.88, 95% CI 1.06 to 3.335), and monocytosis (odds ratio 1.81, 95% CI 1.18 to 2.79) when compared with low SSB consumption after adjusting for baseline differences. Lastly, the validation cohort produced similar results to our primary outcome (ie, high SSB consumption was associated with decreased time to hospitalization and emergency department visits when compared with low SSB consumption). CONCLUSIONS: High SSB consumption was associated with decreased time to hospitalization and emergency department visits. Furthermore, high SSB consumption is associated with disease severity biomarkers and inflammation. Prospective studies assessing the therapeutic influence of nutrition counseling and decreased SSB consumption on long-term inflammatory bowel disease clinical course are warranted.

Dietary fibre to reduce colon cancer risk in Alaska Native people: the Alaska FIRST randomised clinical trial protocol.

INTRODUCTION: Diet, shown to impact colorectal cancer (CRC) risk, is a modifiable environmental factor. Fibre foods fermented by gut microbiota produce metabolites that not only provide food for the colonic epithelium but also exert regulatory effects on colonic mucosal inflammation and proliferation. We describe methods used in a double-blinded, randomised, controlled trial with Alaska Native (AN) people to determine if dietary fibre supplementation can substantially reduce CRC risk among people with the highest reported CRC incidence worldwide. METHODS AND ANALYSES: Eligible patients undergoing routine screening colonoscopy consent to baseline assessments and specimen/data collection (blood, urine, stool, saliva, breath and colon mucosal biopsies) at the time of colonoscopy. Following an 8-week stabilisation period to re-establish normal gut microbiota post colonoscopy, study personnel randomise participants to either a high fibre supplement (resistant starch, n=30) or placebo (digestible starch, n=30) condition, repeating stool sample collection. During the 28-day supplement trial, each participant consumes their usual diet plus their supplement under direct observation. On day 29, participants undergo a flexible sigmoidoscopy to obtain mucosal biopsy samples to measure the effect of the supplement on inflammatory and proliferative biomarkers of cancer risk, with follow-up assessments and data/specimen collection similar to baseline. Secondary outcome measures include the impact of a high fibre supplement on the oral and colonic microbiome and biofluid metabolome. ETHICS AND DISSEMINATION: Approvals were obtained from the Alaska Area and University of Pittsburgh Institutional Review Boards and Alaska Native Tribal Health Consortium and Southcentral Foundation research review bodies. A data safety monitoring board, material transfer agreements and weekly study team meetings provide regular oversight throughout the study. Study findings will first be shared with AN tribal leaders, health administrators, providers and community members. Peer-reviewed journal articles and conference presentations will be forthcoming once approved by tribal review bodies. TRIAL REGISTRATION NUMBER: NCT03028831.

FishChoice 2.0: Information on health benefits / risks and sustainability for seafood consumers.

Since seafood is a significant source of nutrients with known health benefits, its consumption is promoted as a healthy food choice. However, seafood can also contain potentially hazardous environmental pollutants. In the context of the ECsafeSEAFOOD FP7 project, FishChoice (www.fishchoice.eu) was developed as a communication tool to help to the consumers to take the most appropriate decisions on their seafood consumption habits. FishChoice relies on scientific information that allows calculating, on an individual basis, intakes of nutrients and pollutants derived from seafood consumption. In the framework of the EU-H2020 funded SEAFOODTOMORROW project, an optimized version of the online tool has been released. FishChoice is available in 25 EU languages with a customized list of seafood species per EU country, considering specific (national) consumption habits. The list of nutrients has been extended according to the latest EFSA recommendations, while pollutants data incorporate results from recent studies. The sustainability of seafood consumption has been also implemented, providing recommendations to help preserve the marine environment. Finally, FishChoice is suitable not only for consumers, but also health professionals, schools and academia, as well as the industrial sector and public health providers.

A simplified method for the quantitation of short-chain fatty acids in human stool.

A one-vial extraction method for the quantitation of short-chain fatty acids (SCFAs) in human stool was developed. Samples were extracted with an acidified aqueous internal standard solution, sodium sulfate, and diethyl ether, followed by analysis with GC-FID. Accuracy, in terms of relative recovery, was typically between 90 and 110% for most analytes; without internal standard, the accuracy was about 5-34%; the linear dynamic range (LDR) was 0.05-50 µmol per gram; the limit of detection (LOD) was less than or equal to 0.05 µmol per gram; and the (lower) limit of quantitation (LOQ) was 1 µmol per gram. The method is suitable for quantitating acetic acid, propanoic acid, isobutyric acid, butyric acid, isovaleric acid, valeric acid, isohexanoic acid, hexanoic acid, and heptanoic acid. It is not suitable for the quantitation of formic acid. Application to human biological research was tested by the measurement of SCFA in heathy humans. This confirmed that the method performed adequately, and even better than expected, with values up to 150 µmol per gram.

Diet and the Human Gut Microbiome: An International Review.

This review summarizes the key results of recently published studies on the effects of dietary change and nutritional intervention on the human microbiome from around the world, focusing on the USA, Canada, Europe, Asia, and Africa. It first explores mechanisms that might explain the ability of fiber-rich foods to suppress the incidence and mortality from westernized diseases, notably cancers of the colon, breast, liver, cardiovascular, infectious, and respiratory diseases, diabetes, and obesity (O'Keefe in Lancet Gastroenterol Hepatol 4(12):984-996, 2019; Am J Clin Nutr 110:265-266, 2019). It summarizes studies from Africa which suggest that disturbance of the colonic microbiome may exacerbate chronic malnutrition and growth failure in impoverished communities and highlights the importance of breast feeding. The American section discusses the role of the microbiome in the swelling population of patients with obesity and type 2 diabetes and examines the effects of race, ethnicity, geography, and climate on microbial diversity and metabolism. The studies from Europe and Asia extoll the benefits of whole foods and plant-based diets. The Asian studies examine the worrying changes from low-fat, high-carbohydrate diets to high-fat, low-carbohydrate ones and the increasing appearance of westernized diseases as in Africa and documents the ability of high-fiber traditional Chinese diets to reverse type 2 diabetes and control weight loss. In conclusion, most of the studies reviewed demonstrate clear changes in microbe abundances and in the production of fermentation products, such as short-chain fatty acids and phytochemicals following dietary change, but the significance of the microbiota changes to human health, with the possible exception of the stimulation of butyrogenic taxa by fiber-rich foods, is generally implied and not measured. Further studies are needed to determine how these changes in microbiota composition and metabolism can improve our health and be used to prevent and treat disease.

Peripheral Blood Eosinophilia and Long-term Severity in Pediatric-Onset Inflammatory Bowel Disease.

BACKGROUND: Peripheral blood eosinophilia (PBE) is a biomarker of an aggressive multiyear natural history in adults with inflammatory bowel diseases (IBDs). Additionally, PBE at diagnosis is associated with higher disease activity in pediatric-onset IBD. We sought to determine if PBE can function as a biomarker of long-term disease severity in pediatric-onset IBD patients who are followed into adulthood. METHODS: We analyzed a consented, prospective, natural history IBD registry at an adult tertiary center from 2009 to 2018. Prevalence of PBE was evaluated in both pediatric- and adult-onset IBD patients. Demographics, clinical characteristics, and health care utilization data were compared in patients with and without PBE. RESULTS: Among 2800 adult IBD patients, 23.4% had pediatric-onset disease. PBE was found in 34% of the pediatric-onset patients compared with 26.8% of the adult-onset IBD patients (P < 0.001). In the pediatric-onset IBD cohort, PBE was associated with higher rates of allergies (P < 0.0001), but not of asthma, allergic rhinitis, or primary sclerosing cholangitis. In the adult IBD patients with pediatric-onset disease, PBE was associated with higher rates of C-reactive protein elevation (P < 0.0001), erythrocyte sedimentation rate elevation (P < 0.0001), higher health care utilization, and higher average health care charges per year (P < 0.00001). CONCLUSIONS: Peripheral blood eosinophilia was more prevalent in adult IBD patients with pediatric-onset compared with adult-onset disease. Among all IBD patients with long-term follow-up, PBE defined a subgroup with more severe illness. These data suggest that PBE may be a biomarker for a high-risk subgroup with high cost trajectory and long-term severity in pediatric-onset IBD that persists into adulthood.

A prospective cohort analysis of gut microbial co-metabolism in Alaska Native and rural African people at high and low risk of colorectal cancer.

BACKGROUND: Alaska Native (AN) people have the world's highest recorded incidence of sporadic colorectal cancer (CRC) (∼91:100,000), whereas rural African (RA) people have the lowest risk (<5:100,000). Previous data supported the hypothesis that diet affected CRC risk through its effects on the colonic microbiota that produce tumor-suppressive or -promoting metabolites. OBJECTIVES: We investigated whether differences in these metabolites may contribute to the high risk of CRC in AN people. METHODS: A cross-sectional observational study assessed dietary intake from 32 AN and 21 RA healthy middle-aged volunteers before screening colonoscopy. Analysis of fecal microbiota composition by 16S ribosomal RNA gene sequencing and fecal/urinary metabolites by 1H-NMR spectroscopy was complemented with targeted quantification of fecal SCFAs, bile acids, and functional microbial genes. RESULTS: Adenomatous polyps were detected in 16 of 32 AN participants, but not found in RA participants. The AN diet contained higher proportions of fat and animal protein and less fiber. AN fecal microbiota showed a compositional predominance of Blautia and Lachnoclostridium, higher microbial capacity for bile acid conversion, and low abundance of some species involved in saccharolytic fermentation (e.g., Prevotellaceae, Ruminococcaceae), but no significant lack of butyrogenic bacteria. Significantly lower concentrations of tumor-suppressive butyrate (22.5 ± 3.1 compared with 47.2 ± 7.3 SEM µmol/g) coincided with significantly higher concentrations of tumor-promoting deoxycholic acid (26.7 ± 4.2 compared with 11 ± 1.9 µmol/g) in AN fecal samples. AN participants had lower quantities of fecal/urinary metabolites than RA participants and metabolite profiles correlated with the abundance of distinct microbial genera in feces. The main microbial and metabolic CRC-associated markers were not significantly altered in AN participants with adenomatous polyps. CONCLUSIONS: The low-fiber, high-fat diet of AN people and exposure to carcinogens derived from diet or environment are associated with a tumor-promoting colonic milieu as reflected by the high rates of adenomatous polyps in AN participants.

Fiber, Fat, and Colorectal Cancer: New Insight into Modifiable Dietary Risk Factors.

PURPOSE OF REVIEW: To review recent data on the role and interactions of fiber and fat as dietary risk factors associated with colorectal cancer (CRC) risk in humans. RECENT FINDINGS: Fiber intake shows convincing and linear dose-response negative correlation with CRC risk. Dietary fiber stimulates butyrogenic activity of the gut microbiota, providing high amounts of butyrate that shows extensive anti-neoplastic effects. A high-fat diet promotes CRC risk through stimulated bile acid metabolism, facilitating bile acid conversion by the gut microbiota to tumor-promoting deoxycholic acid. Comprehensive interactions of these microbial metabolites are likely to underlie mechanisms driving diet-dependent CRC risk in different populations, but require further experimental investigation. Dietary fiber and fat shape the composition and metabolic function of the gut microbiota, resulting in altered amounts of butyrate and deoxycholic acid in the colon. Fiber supplementation and restriction of fat intake represent promising strategies to reduce CRC risk in healthy individuals.

Activin in acute pancreatitis: Potential risk-stratifying marker and novel therapeutic target.

Acute Pancreatitis is a substantial health care challenge with increasing incidence. Patients who develop severe disease have considerable mortality. Currently, no reliable predictive marker to identify patients at risk for severe disease exists. Treatment is limited to rehydration and supporting care suggesting an urgent need to develop novel approaches to improve standard care. Activin is a critical modulator of inflammatory responses, but has not been assessed in pancreatitis. Here, we demonstrate that serum activin is elevated and strongly correlates with disease severity in two established murine models of acute pancreatitis induced by either cerulein or IL-12 + IL-18. Furthermore, in mice, inhibition of activin conveys survival benefits in pancreatitis. In addition, serum activin levels were measured from a retrospective clinical cohort of pancreatitis patients and high activin levels in patients at admission are predictive of worse outcomes, indicated by longer overall hospital and intensive care unit stays. Taken together, activin is a novel candidate as a clinical marker to identify those acute pancreatitis patients with severe disease who would benefit from aggressive treatment and activin may be a therapeutic target in severe acute pancreatitis.

Anthropogenic influence on sediment transport in the Whittard Canyon, NE Atlantic.

Unusual peaks in turbidity were detected in two branches of the Whittard Canyon in June 2013. Enhanced nepheloid layers (ENLs) were defined as layers with concentrations of suspended particulate matter exceeding those of nepheloid layers typically observed in a given region. Here, ENLs had peaks in turbidity and elevated suspended particulate matter concentrations exceeding ~1 mg L(-1) with the largest ENLs measuring between ~2-8 mg L(-1). The ENLs measured ~100-260 m in vertical height and were detected in water depths of between 640 and 2880 m. Vessel Monitoring System data showed that high spatial and temporal activity of potential bottom trawling vessels coincided with the occurrence of the ENLs. Molar C/N ratios of the suspended organic material from the ENLs showed a high degree of degradation. Regular occurrences of such events are likely to have implications for increased sediment fluxes, burial of organic carbon and alteration of benthic and canyon ecosystems.

Physical Inactivity Is Associated with Moderate-Severe Obstructive Sleep Apnea.

STUDY OBJECTIVE: To investigate whether low levels of physical activity were associated with an increased occurrence of obstructive sleep apnea (OSA), OSA-related symptoms, and cardiometabolic risk. METHODS: A case-control study design was used. OSA cases were patients referred to a sleep clinic for suspected OSA (n = 2,340). Controls comprised participants from the Busselton community (n = 1,931). Exercise and occupational activity were derived from questionnaire data. Associations were modelled using logistic and linear regression and adjusted for confounders. RESULTS: In comparison with moderate exercise, the high, low, and nil exercise groups had an odds ratio (OR) for moderate-severe OSA of 0.6 (95% CI 0.5-0.8), 1.6 (95% CI 1.2-2.0), and 2.7 (95% CI 1.9-3.7), respectively. Relative to men in heavy activity occupations, men in medium, light and sedentary occupations had an OR for moderate-severe OSA of 1.7 (95% CI 1.1-2.5), 2.1 (95% CI 1.4-3.2), and 1.8 (95% CI 1.2-2.8), respectively. Relative to women in medium activity occupations, women in light and sedentary occupations had an OR for moderate-severe OSA of 4.2 (95% CI 2.6-7.2) and 3.5 (2.0-6.0). OSA patients who adequately exercised had lower: levels of doctor-diagnosed depression (p = 0.047); symptoms of fatigue (p < 0.0001); systolic (p = 0.015) and diastolic blood pressure (p = 0.015); and C-reactive protein (CRP) (p = 0.003). CONCLUSIONS: Low levels of physical activity were associated with moderate-severe OSA. Exercise in individuals with OSA is associated with lower levels of depression, fatigue, blood pressure and CRP.

A vertical wall dominated by Acesta excavata and Neopycnodonte zibrowii, part of an undersampled group of deep-sea habitats.

We describe a novel biotope at 633 to 762 m depth on a vertical wall in the Whittard Canyon, an extensive canyon system reaching from the shelf to the deep sea on Ireland's continental margin. We explored this wall with an ROV and compiled a photomosaic of the habitat. The assemblage contributing to the biotope was dominated by large limid bivalves, Acesta excavata (mean shell height 10.4 cm), and deep-sea oysters, Neopycnodonte zibrowii, at high densities, particularly at overhangs. Mean density of N. zibrowii increased with depth, with densities of the most closely packed areas of A. excavata also increasing with depth. Other taxa associated with the assemblage included the solitary coral Desmophyllum dianthus, cerianthid anemones, comatulid crinoids, the trochid gastropod Margarites sp., the portunid crab Bathynectes longispina and small fish of the family Bythitidae. The scleractinian coral Madrepora oculata, the pencil urchin Cidaris cidaris and a species of Epizoanthus were also common. Prominent but less abundant species included the flytrap anemone Actinoscyphia saginata, the carrier crab Paramola cuvieri, and the fishes Lepidion eques and Conger conger. Observations of the hydrography of the canyon system identified that the upper 500 m was dominated by Eastern North Atlantic Water, with Mediterranean Outflow Water beneath it. The permanent thermocline is found between 600 and 1000 m depth, i.e., in the depth range of the vertical wall and the dense assemblage of filter feeders. Beam attenuation indicated nepheloid layers present in the canyon system with the greatest amounts of suspended material at the ROV dive site between 500 and 750 m. A cross-canyon CTD transect indicated the presence of internal waves between these depths. We hypothesise that internal waves concentrate suspended sediment at high concentrations at the foot of the vertical wall, possibly explaining the large size and high density of filter-feeding molluscs.

Inhibition of endothelin-1-mediated contraction of hepatic stellate cells by FXR ligand.

Activation of hepatic stellate cells (HSCs) plays an important role in the development of cirrhosis through the increased production of collagen and the enhanced contractile response to vasoactive mediators such as endothelin-1 (ET-1). The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that is highly expressed in liver, kidneys, adrenals, and intestine. FXR is also expressed in HSCs and activation of FXR in HSCs is associated with significant decreases in collagen production. However, little is known about the roles of FXR in the regulation of contraction of HSCs. We report in this study that treatment of quiescent HSCs with GW4064, a synthetic FXR agonist, significantly inhibited the HSC transdifferentiation, which was associated with an inhibition of the upregulation of ET-1 expression. These GW4064-treated cells also showed reduced contractile response to ET-1 in comparison to HSCs without GW4064 treatment. We have further shown that GW4064 treatment inhibited the ET-1-mediated contraction in fully activated HSCs. To elucidate the potential mechanism we showed that GW4064 inhibited ET-1-mediated activation of Rho/ROCK pathway in activated HSCs. Our studies unveiled a new mechanism that might contribute to the anti-cirrhotic effects of FXR ligands.