Exploiting macrophage autophagy-lysosomal biogenesis as a therapy for atherosclerosis

Macrophages specialize in removing lipids and debris present in the atherosclerotic plaque. However, plaque progression renders macrophages unable to degrade exogenous atherogenic material and endogenous cargo including dysfunctional proteins and organelles. Here we show that a decline in the autophagy-lysosome system contributes to this as evidenced by a derangement in key autophagy markers in both mouse and human atherosclerotic plaques. By augmenting macrophage TFEB, the master transcriptional regulator of autophagy-lysosomal biogenesis, we can reverse the autophagy dysfunction of plaques, enhance aggrephagy of p62-enriched protein aggregates and blunt macrophage apoptosis and pro-inflammatory IL-1β levels, leading to reduced atherosclerosis. In order to harness this degradative response therapeutically, we also describe a natural sugar called trehalose as an inducer of macrophage autophagy-lysosomal biogenesis and show trehalose's ability to recapitulate the atheroprotective properties of macrophage TFEB overexpression. Our data support this practical method of enhancing the degradative capacity of macrophages as a therapy for atherosclerotic vascular disease

SARS-CoV-2 Infection Is at Herd Immunity in the Majority Segment of the Population of Qatar.

BACKGROUND: Qatar experienced a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic that disproportionately affected the craft and manual worker (CMW) population, who comprise 60% of the total population. This study aimed to assess ever and/or current infection prevalence in this population. METHODS: A cross-sectional population-based survey was conducted during July 26 to September 09, 2020, to assess both anti-SARS-CoV-2 positivity through serological testing and current infection positivity through polymerase chain reaction (PCR) testing. Associations with antibody and PCR positivity were identified through regression analyses. RESULTS: The study included 2641 participants, 69.3% of whom were <40 years of age. Anti-SARS-CoV-2 positivity was 55.3% (95% CI, 53.3%-57.3%) and was significantly associated with nationality, geographic location, educational attainment, occupation, and previous infection diagnosis. PCR positivity was 11.3% (95% CI, 9.9%-12.8%) and was significantly associated with nationality, geographic location, occupation, contact with an infected person, and reporting 2 or more symptoms. Infection positivity (antibody and/or PCR positive) was 60.6% (95% CI, 58.6%-62.5%). The proportion of antibody-positive CMWs who had a prior SARS-CoV-2 diagnosis was 9.3% (95% CI, 7.9%-11.0%). Only seven infections were ever severe, and only 1 was ever critical-an infection severity rate of 0.5% (95% CI, 0.2%-1.0%). CONCLUSIONS: Six in every 10 CMWs in Qatar have been infected, suggestive of reaching the herd immunity threshold. Infection severity was low, with only 1 in every 200 infections progressing to be severe or critical. Only 1 in every 10 infections had been previously diagnosed, which is suggestive of mostly asymptomatic or mild infections

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

Experimental investigation of hydrogen sulfide adsorption from drilling fluid wastes by functionalized carbon nanotubes

Aim: Hydrogen sulfide is one of the most harmful substances known in the drilling industry. Hydrogen sulfide can cause health, environmental, safety, and damage to property problems. Therefore, we conducted this study on a laboratory scale to make carboxylated carbon nanotubes and investigate their performance in removing hydrogen sulfide from drilling mud. Materials and Methods: In the first step, we prepared multi-walled carbon nanotubes with 90%–95% purity. In the next step, we provide the drilling fluid. The fluid used in these experiments was a simple water-based mud consisting of water and bentonite. In the last step, we used the Qualitek-4 software to design experiments, and the Taguchi model was used to investigate the obtained results. Results: Results show that pH is the most effective parameter in the adsorption process. Interaction of adsorbent concentration with retention time shows the highest SI = 85.85%. Optimal conditions of H2S adsorption are adsorbent concentration = 100 ppm, pH = 6, and retention time = 30 min. According to the Langmuir model, the adsorption capacity of carbon nanotube (CNT)-COOH was 2480 (mg/mg). By increasing CNT-COOH concentration from 50 ppm to 100 ppm, the adsorption percent of H2S increased from 51.6% to 66.1%. By increasing the retention time from 2 min to 30 min, an increase in adsorption will be seen from 57.5% to 65.3%. Conclusion: Using functionalized nanocarbon tube with at least 90% efficiency is a reliable method to remove hydrogen sulfide from drilling mud

Identification and classification of factors affecting the non-use of safety harness at height among construction workers in Tehran.

IntroductionThe accident of falling from a height is high among construction workers. Construction workers do not use harnesses. Thus, the present study was conducted to identify the factors affecting the non-use of harnesses among construction workers in Tehran, Iran.Materials and methodsIn this study was conducted by interviewing professors and construction workers in order to identify factors affecting the non-use of harness. Factors influencing the non-use of safety harnesses were identified from the workers' point of view. The obtained data were classified and coded using MAXQDA 10 software. After that, the most essential, effective and powerful factors were identified using the degree and intersectionality of social network analysis.ResultsAccording to the interview results, 27 factors were determined as factors affecting the non-use of harnesses by construction workers and divided into four main groups. The four groups were harness design, management factors, harness comfort, and attitudinal factors. Based on the results of the degree centrality, the non-ergonomic design and attitude of the harness inefficiency were identified as the most influential and powerful factors. The betweenness indicator also showed that the non-ergonomic design could mediate other factors in the non-use of the harness.ConclusionThe findings showed that by considering various factors such as considering more comfort in the design of the ergonomic harness, it produced a better product. Also, the use of safety harnesses by workers increases

Use of Sentinel-1 C-Band SAR Images for Convective System Surface Wind Pattern Detection

International audienceConvective systems (CS) through their downdrafts hitting the sea surface may produce wind patterns (or cold pools) with wind intensity exceeding 10–25 m s−1. The latter for a long time have been significant for weather forecast and meteorological studies, especially in the tropical regions like the Gulf of Guinea since it is hard to detect the CS-associated wind patterns. Based on Sentinel-1 images [C-band Synthetic Aperture Radar (SAR)] with high spatial resolution and large swath, the current study proposed the detection of surface wind patterns through wind speed estimation by C-band model 5.N (CMOD5.N; for vertically polarized images) and two models proposed by Sapp and Komarov (for horizontally polarized images). Relative to the X-band SAR, the effects of precipitation on C-band radar backscattering are negligible, and thereby it has little impact on wind speed estimation from Sentinel-1 images. The detected surface wind patterns include a squall line and a bow echo at the mesoscale (>100 km) and many submesoscale (<100 km) convection cells. They are accompanied by various degrees of precipitation (from light to heavy rain). This study also used Meteosat infrared images for monitoring and detection of deep convective clouds (with low brightness temperature) corresponding to surface wind patterns. The agreement in location and sometimes in shape between them strengthened the assumption that the CS downdrafts may induce the sea surface patterns with high wind intensity (10–25 m s−1). In particular, because of the Sentinel-1 high spatial resolution, the pattern spots with high winds (20–25 m s−1) are detected on the illustrated images, which was not reported in the literature. They are located close to the coldest convective clouds (about 200-K brightness temperature)

Effects of box size, frequency of lifting, and height of lift on maximum acceptable weight of lift and heart rate for male university students in Iran

Introduction: In spite of the widespread use of automation in industry, manual material handling (MMH) is still performed in many occupational settings. The emphasis on ergonomics in MMH tasks is due to the potential risks of workplace accidents and injuries. This study aimed to assess the effect of box size, frequency of lift, and height of lift on maximum acceptable weight of lift (MAWL) on the heart rates of male university students in Iran. Methods: This experimental study was conducted in 2015 with 15 male students recruited from Tehran University of Medical Sciences. Each participant performed 18 different lifting tasks that involved three lifting frequencies (1lift/min, 4.3 lifts/min and 6.67 lifts/min), three lifting heights (floor to knuckle, knuckle to shoulder, and shoulder to arm reach), and two box sizes. Each set of experiments was conducted during the 20 min work period using the free-style lifting technique. The working heart rates (WHR) were recorded for the entire duration. In this study, we used SPSS version 18 software and descriptive statistical methods, analysis of variance (ANOVA), and the t-test for data analysis. Results: The results of the ANOVA showed that there was a significant difference between the mean of MAWL in terms of frequencies of lifts (p = 0.02). Tukey's post hoc test indicated that there was a significant difference between the frequencies of 1 lift/minute and 6.67 lifts/minute (p = 0. 01). There was a significant difference between the mean heart rates in terms of frequencies of lifts (p = 0.006), and Tukey's post hoc test indicated a significant difference between the frequencies of 1 lift/minute and 6.67 lifts/minute (p = 0.004). But, there was no significant difference between the mean of MAWL and the mean heart rate in terms of lifting heights (p > 0.05). The results of the t-test showed that there was a significant difference between the mean of MAWL and the mean heart rate in terms of the sizes of the two boxes (p = 0.000). Conclusion: Based on the results of this study, it was concluded that MAWL and heart rate are influenced by the variables of lifting frequency and the size of the boxes

Effect of purslane seed supplementation on inflammatory cytokines, oxidative stress and muscle damage in response to high?intensity intermittent exercise in national athlete runners.

Background Purslane supplementation has anti-oxidative, anti-inflammatory, skeletal muscle-relaxant activities. However, it is unknown if the ingestion of purslane will affect the oxidative stress and cytokines in exercise-induced muscle damage. The aim of the present study was to examine the effect of purslane supplementation after high-intensity interval exercise (HIIE) on oxidative stress, cytokines, and muscle damage level in young athlete male runners. Methods Seven healthy young male runners performed 2.5 km HIIE treadmill protocol. Athletes repeated this protocol following 10 days of purslane seed supplementation (1000 mg/day). Blood samples were collected at baseline and following HIIE protocol and analyzed for oxidative stress (9-HODE and 13-HODE), cytokines (IL-17, and TNF-?), and muscle damage (LDH) biomarkers. Results At baseline and following HIIE protocol, 9-HODE, 13-HODE, IL-17, TNF-?, LDH levels were significantly (p < 0.001) lower after purslane supplementation in compared to before purslane supplementation. HIIE protocol induced a significant increase in 9-HODE, 13-HODE, IL-17, TNF-?, and LDH before and after purslane supplementation. Conclusion Purslane seed supplementation was able to reduce oxidative stress (9-HODE, 13-HODE), proinflammatory cytokines (IL-17 and TNF-?), and muscle damage (LDH) in male runners after HIIE performance compared to baseline levels. After 10 days of supplementation, the levels were reduced compared to levels pre-supplementation but not after HIIE supplementation in supplemented athletes

Plasma protein profiling reveals candidate biomarkers for multiple sclerosis treatment.

Multiple sclerosis (MS) treatment options have improved significantly over the past decades, but the consequences of MS can still be devastating and the needs for monitoring treatment surveillance are considerable. In the current study we used affinity proteomics technology to identify potential biomarkers which could ultimately be used to as facilitate treatment decisions. We profiled the intra-individual changes in the levels of 59 target proteins using an antibody suspension bead array in serial plasma samples from 44 MS patients during treatment with natalizumab followed by fingolimod. Nine proteins showed decreasing plasma levels during natalizumab treatment, with PEBP1 and RTN3 displaying the most significant changes. Protein levels remained stable during fingolimod treatment for both proteins. The decreasing PEBP1 levels during natalizumab treatment could be validated using ELISA and replicated in an independent cohort. These results support the use of this technology as a high throughput method of identifying potentially useful biomarkers of MS treatment