Dietary non-esterified oleic Acid decreases the jejunal levels of anorectic N-acylethanolamines

BACKGROUND AND AIMS: Oleoylethanolamide and several other N-acylethanolamines (NAEs), e.g. linoleoylethanolamide and palmitoylethanolamide, have anorectic properties in rats, and prolonged intake of a high-fat diet decreases the levels of the anorectic NAEs in jejunum. Jejunal anorectic NAEs are thought to add to the control of food intake via activation of PPARalpha and the vagus nerve. The fat-induced decrease may explain part of the hyperphagic effect of high-fat diets. In the present study, we investigated 1) whether the reduced levels of anorectic NAEs were reversible in rats, 2) whether mice respond to dietary fat (olive oil) by reducing levels of anorectic NAEs, and 3) whether dietary non-esterified oleic acid also can decrease levels of anorectic NAEs in mice. We are searching for the fat sensor in the intestine, which mediates the decreased levels of anorectic NAEs. METHODS: Male rats and mice were fed diets high (45 energy% fat) in either triacylglycerol or free fatty acids for 7-14 days, and jejunal NAE and N-acylphosphatidylethanolamine (NAPE) levels were determined by liquid-chromatography mass spectrometry. RESULTS: In rats, reduced levels of anorectic NAEs could be reversed after 3 days from changing the diet from high-fat to chow. Corresponding NAPE levels tended to show the same changes. In mice, jejunal levels of anorectic NAEs were also reduced when fed a high-fat diet. In addition, we found that non-esterified oleic acid were also able to reduce levels of anorectic NAEs in mice. CONCLUSIONS: These results suggest that the down-regulation of the jejunal level of anorectic NAEs by dietary fat is not restricted to rats, and that the fatty acid component oleic acid, in dietary olive oil may be sufficient to mediate this regulation. Thus, a fatty acid sensor may mediate this effect of dietary fat

Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain

SummaryStem cell factor (SCF) is overexpressed by neurons following brain injury as well as by glioma cells; however, its role in gliomagenesis remains unclear. Here, we demonstrate that SCF directly activates brain microvascular endothelial cells (ECs) in vitro and induces a potent angiogenic response in vivo. Primary human gliomas express SCF in a grade-dependent manner and induce normal neurons to express SCF in brain regions infiltrated by glioma cells, areas that colocalize with prominent angiogenesis. Downregulation of SCF inhibits tumor-mediated angiogenesis and glioma growth in vivo, whereas overexpression of SCF is associated with shorter survival in patients with malignant gliomas. Thus, the SCF/c-Kit pathway plays an important role in tumor- and normal host cell-induced angiogenesis within the brain

Tower 1978

1978 yearbook of Westbrook College in Portland, Maine.https://dune.une.edu/wchc_yearbooks/1007/thumbnail.jp

Higher risk for influenza-associated pulmonary aspergillosis (IAPA) in asthmatic patients: A Swiss multicenter cohort study on IAPA in critically ill influenza patients

Background: Influenza-associated pulmonary aspergillosis (IAPA) is an important complication of severe influenza with high morbidity and mortality. Methods: We conducted a retrospective multicenter study in tertiary hospitals in Switzerland during 2017/2018 and 2019/2020 influenza seasons. All adults with PCR-confirmed influenza infection and treatment on intensive-care unit (ICU) for >24 h were included. IAPA was diagnosed according to previously published clinical, radiological, and microbiological criteria. We assessed risk factors for IAPA and predictors for poor outcome, which was a composite of in-hospital mortality, ICU length of stay ≥7 days, mechanical ventilation ≥7 days, or extracorporeal membrane oxygenation. Results: One hundred fifty-eight patients (median age 64 years, 45% females) with influenza were included, of which 17 (10.8%) had IAPA. Asthma was more common in IAPA patients (17% vs. 4% in non-IAPA, P = 0.05). Asthma (OR 12.0 [95% CI 2.1-67.2]) and days of mechanical ventilation (OR 1.1 [1.1-1.2]) were associated with IAPA. IAPA patients frequently required organ supportive therapies including mechanical ventilation (88% in IAPA vs. 53% in non-IAPA, P = 0.001) and vasoactive support (75% vs. 45%, P = 0.03) and had more complications including ARDS (53% vs. 26%, P = 0.04), respiratory bacterial infections (65% vs. 37%, P = 0.04), and higher ICU-mortality (35% vs. 16.4%, P = 0.05). IAPA (OR 28.8 [3.3-253.4]), influenza A (OR 3.3 [1.4-7.8]), and higher SAPS II score (OR 1.07 [1.05-1.10]) were independent predictors of poor outcome. Interpretation: High clinical suspicion, early diagnostics, and therapy are indicated in IAPA because of high morbidity and mortality. Asthma is likely an underappreciated risk factor for IAPA. Keywords: asthma; influenza; influenza-associated aspergillosis; intensive care medicine; invasive aspergillosis

Higher risk for influenza-associated pulmonary aspergillosis (IAPA) in asthmatic patients: A Swiss multicenter cohort study on IAPA in critically ill influenza patients.

BACKGROUND Influenza-associated pulmonary aspergillosis (IAPA) is an important complication of severe influenza with high morbidity and mortality. METHODS We conducted a retrospective multicenter study in tertiary hospitals in Switzerland during 2017/2018 and 2019/2020 influenza seasons. All adults with PCR-confirmed influenza infection and treatment on intensive-care unit (ICU) for >24 h were included. IAPA was diagnosed according to previously published clinical, radiological, and microbiological criteria. We assessed risk factors for IAPA and predictors for poor outcome, which was a composite of in-hospital mortality, ICU length of stay ≥7 days, mechanical ventilation ≥7 days, or extracorporeal membrane oxygenation. RESULTS One hundred fifty-eight patients (median age 64 years, 45% females) with influenza were included, of which 17 (10.8%) had IAPA. Asthma was more common in IAPA patients (17% vs. 4% in non-IAPA, P = 0.05). Asthma (OR 12.0 [95% CI 2.1-67.2]) and days of mechanical ventilation (OR 1.1 [1.1-1.2]) were associated with IAPA. IAPA patients frequently required organ supportive therapies including mechanical ventilation (88% in IAPA vs. 53% in non-IAPA, P = 0.001) and vasoactive support (75% vs. 45%, P = 0.03) and had more complications including ARDS (53% vs. 26%, P = 0.04), respiratory bacterial infections (65% vs. 37%, P = 0.04), and higher ICU-mortality (35% vs. 16.4%, P = 0.05). IAPA (OR 28.8 [3.3-253.4]), influenza A (OR 3.3 [1.4-7.8]), and higher SAPS II score (OR 1.07 [1.05-1.10]) were independent predictors of poor outcome. INTERPRETATION High clinical suspicion, early diagnostics, and therapy are indicated in IAPA because of high morbidity and mortality. Asthma is likely an underappreciated risk factor for IAPA

Pressure transduction and fluid evacuation during conventional negative pressure wound therapy of the open abdomen and NPWT using a protective disc over the intestines

<p>Abstract</p> <p>Background</p> <p>Negative pressure wound therapy (NPWT) has gained acceptance among surgeons, for the treatment of open abdomen, since very high closure rates have been reported with this method, compared to other kinds of wound management for the open abdomen. However, the method has occasionally been associated with increased development of fistulae. We have previously shown that NPWT induces ischemia in the underlying small intestines close to the vacuum source, and that a protective disc placed between the intestines and the vacuum source prevents the induction of ischemia. In this study we compare pressure transduction and fluid evacuation of the open abdomen with conventional NPWT and NPWT with a protective disc.</p> <p>Methods</p> <p>Six pigs underwent midline incision and the application of conventional NPWT and NPWT with a protective disc between the intestines and the vacuum source. The pressure transduction was measured centrally beneath the dressing, and at the anterior abdominal wall, before and after the application of topical negative pressures of -50, -70 and -120 mmHg. The drainage of fluid from the abdomen was measured, with and without the protective disc.</p> <p>Results</p> <p>Abdominal drainage was significantly better (p < 0. 001) using NPWT with the protective disc at -120 mmHg (439 ± 25 ml vs. 239 ± 31 ml), at -70 mmHg (341 ± 27 ml vs. 166 ± 9 ml) and at -50 mmHg (350 ± 50 ml vs. 151 ± 21 ml) than with conventional NPWT. The pressure transduction was more even at all pressure levels using NPWT with the protective disc than with conventional NPWT.</p> <p>Conclusions</p> <p>The drainage of the open abdomen was significantly more effective when using NWPT with the protective disc than with conventional NWPT. This is believed to be due to the more even and effective pressure transduction in the open abdomen using a protective disc in combination with NPWT.</p

Comparison of the sensitivity of the UKCAT and A levels to sociodemographic characteristics: a national study

Background: The UK Clinical Aptitude Test (UKCAT) was introduced to facilitate widening participation in medical and dental education in the UK by providing universities with a continuous variable to aid selection; one that might be less sensitive to the sociodemographic background of candidates compared to traditional measures of educational attainment. Initial research suggested that males, candidates from more advantaged socioeconomic backgrounds and those who attended independent or grammar schools performed better on the test. The introduction of the A* grade at A level permits more detailed analysis of the relationship between UKCAT scores, secondary educational attainment and sociodemographic variables. Thus, our aim was to further assess whether the UKCAT is likely to add incremental value over A level (predicted or actual) attainment in the selection process. Methods: Data relating to UKCAT and A level performance from 8,180 candidates applying to medicine in 2009 who had complete information relating to six key sociodemographic variables were analysed. A series of regression analyses were conducted in order to evaluate the ability of sociodemographic status to predict performance on two outcome measures: A level ‘best of three’ tariff score; and the UKCAT scores. Results: In this sample A level attainment was independently and positively predicted by four sociodemographic variables (independent/grammar schooling, White ethnicity, age and professional social class background). These variables also independently and positively predicted UKCAT scores. There was a suggestion that UKCAT scores were less sensitive to educational background compared to A level attainment. In contrast to A level attainment, UKCAT score was independently and positively predicted by having English as a first language and male sex. Conclusions: Our findings are consistent with a previous report; most of the sociodemographic factors that predict A level attainment also predict UKCAT performance. However, compared to A levels, males and those speaking English as a first language perform better on UKCAT. Our findings suggest that UKCAT scores may be more influenced by sex and less sensitive to school type compared to A levels. These factors must be considered by institutions utilising the UKCAT as a component of the medical and dental school selection process

The Drosophila melanogaster PeptideAtlas facilitates the use of peptide data for improved fly proteomics and genome annotation

<p>Abstract</p> <p>Background</p> <p>Crucial foundations of any quantitative systems biology experiment are correct genome and proteome annotations. Protein databases compiled from high quality empirical protein identifications that are in turn based on correct gene models increase the correctness, sensitivity, and quantitative accuracy of systems biology genome-scale experiments.</p> <p>Results</p> <p>In this manuscript, we present the <it>Drosophila melanogaster </it>PeptideAtlas, a fly proteomics and genomics resource of unsurpassed depth. Based on peptide mass spectrometry data collected in our laboratory the portal <url>http://www.drosophila-peptideatlas.org</url> allows querying fly protein data observed with respect to gene model confirmation and splice site verification as well as for the identification of proteotypic peptides suited for targeted proteomics studies. Additionally, the database provides consensus mass spectra for observed peptides along with qualitative and quantitative information about the number of observations of a particular peptide and the sample(s) in which it was observed.</p> <p>Conclusion</p> <p>PeptideAtlas is an open access database for the <it>Drosophila </it>community that has several features and applications that support (1) reduction of the complexity inherently associated with performing targeted proteomic studies, (2) designing and accelerating shotgun proteomics experiments, (3) confirming or questioning gene models, and (4) adjusting gene models such that they are in line with observed <it>Drosophila </it>peptides. While the database consists of proteomic data it is not required that the user is a proteomics expert.</p

Sirtuin-2, NAD-Dependent Deacetylase, is a new potential therapeutic target for HIV-1 infection and HIV-related neurological dysfunction

The implementation and access to combined antiretroviral treatment (cART) have dramatically improved the quality of life of people living with HIV (PLWH). However, some comorbidities, such as neurological disorders associated with HIV infection still represent a serious clinical challenge. Soluble factors in plasma that are associated with control of HIV replication and neurological dysfunction could serve as early biomarkers and as new therapeutic targets for this comorbidity. We used a customized antibody array for determination of blood plasma factors in 40 untreated PLWH with different levels of viremia and found sirtuin-2 (SIRT2), an NAD-dependent deacetylase, to be strongly associated with elevated viral loads and HIV provirus levels, as well as with markers of neurological damage (a-synuclein [SNCA], brain-derived neurotrophic factor [BDNF], microtubule-associated protein tau [MAPT], and neurofilament light protein [NFL]). Also, longitudinal analysis in HIV-infected individuals with immediate (n = 9) or delayed initiation (n = 10) of cART revealed that after 1 year on cART, SIRT2 plasma levels differed between both groups and correlated inversely with brain orbitofrontal cortex involution. Furthermore, targeting SIRT2 with specific small-molecule inhibitors in in vitro systems using J-LAT A2 and primary glial cells led to diminished HIV replication and virus reactivation from latency. Our data thus identify SIRT2 as a novel biomarker of uncontrolled HIV infection, with potential impact on neurological dysfunction and offers a new therapeutic target for HIV treatment and cure. IMPORTANCE Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control. High plasma levels of sirtuin-2 (SIRT2), an NAD+ deacetylase, were detected in uncontrolled HIV infection and were strongly associated with plasma viral load and proviral levels. In parallel, SIRT2 levels in the peripheral blood and CNS were associated with markers of neurological damage and brain involution and were more pronounced in individuals who initiated cART later in infection. In vitro infection experiments using specific SIRT2 inhibitors suggest that specific targeting of SIRT2 could offer new therapeutic treatment options for HIV infections and their associated neurological dysfunction