Pharmacological Inhibition of Nicotinamide Phosphoribosyltransferase/Visfatin Enzymatic Activity Identifies a New Inflammatory Pathway Linked to NAD

Nicotinamide phosphoribosyltransferase (NAMPT), also known as visfatin, is the rate-limiting enzyme in the salvage pathway of NAD biosynthesis from nicotinamide. Since its expression is upregulated during inflammation, NAMPT represents a novel clinical biomarker in acute lung injury, rheumatoid arthritis, and Crohn's disease. However, its role in disease progression remains unknown. We report here that NAMPT is a key player in inflammatory arthritis. Increased expression of NAMPT was confirmed in mice with collagen-induced arthritis, both in serum and in the arthritic paw. Importantly, a specific competitive inhibitor of NAMPT effectively reduced arthritis severity with comparable activity to etanercept, and decreased pro-inflammatory cytokine secretion in affected joints. Moreover, NAMPT inhibition reduced intracellular NAD concentration in inflammatory cells and circulating TNFα levels during endotoxemia in mice. In vitro pharmacological inhibition of NAMPT reduced the intracellular concentration of NAD and pro-inflammatory cytokine secretion by inflammatory cells. Thus, NAMPT links NAD metabolism to inflammatory cytokine secretion by leukocytes, and its inhibition might therefore have therapeutic efficacy in immune-mediated inflammatory disorders

Perceived risk of infection and death from COVID-19 among community members of low- and middle-income countries: A cross-sectional study [version 1; peer review: awaiting peer review]

Background: Risk perceptions of coronavirus disease 2019 (COVID-19) are considered important as they impact community health behaviors. The aim of this study was to determine the perceived risk of infection and death due to COVID-19 and to assess the factors associated with such risk perceptions among community members in low- and middle-income countries (LMICs) in Africa, Asia, and South America. Methods: An online cross-sectional study was conducted in 10 LMICs in Africa, Asia, and South America from February to May 2021. A questionnaire was utilized to assess the perceived risk of infection and death from COVID-19 and its plausible determinants. A logistic regression model was used to identify the factors associated with such risk perceptions. Results: A total of 1,646 responses were included in the analysis of the perceived risk of becoming infected and dying from COVID-19. Our data suggested that 36.4% of participants had a high perceived risk of COVID-19 infection, while only 22.4% had a perceived risk of dying from COVID-19. Being a woman, working in healthcare-related sectors, contracting pulmonary disease, knowing people in the immediate social environment who are or have been infected with COVID-19, as well as seeing or reading about individuals infected with COVID-19 on social media or TV were all associated with a higher perceived risk of becoming infected with COVID-19. In addition, being a woman, elderly, having heart disease and pulmonary disease, knowing people in the immediate social environment who are or have been infected with COVID-19, and seeing or reading about individuals infected with COVID-19 on social media or TV had a higher perceived risk of dying from COVID-19. Conclusions: The perceived risk of infection and death due to COVID-19 are relatively low among respondents; this suggests the need to conduct health campaigns to disseminate knowledge and information on the ongoing pandemic

Diversity and ethics in trauma and acute care surgery teams: results from an international survey

Background Investigating the context of trauma and acute care surgery, the article aims at understanding the factors that can enhance some ethical aspects, namely the importance of patient consent, the perceptiveness of the ethical role of the trauma leader, and the perceived importance of ethics as an educational subject. Methods The article employs an international questionnaire promoted by the World Society of Emergency Surgery. Results Through the analysis of 402 fully filled questionnaires by surgeons from 72 different countries, the three main ethical topics are investigated through the lens of gender, membership of an academic or non-academic institution, an official trauma team, and a diverse group. In general terms, results highlight greater attention paid by surgeons belonging to academic institutions, official trauma teams, and diverse groups. Conclusions Our results underline that some organizational factors (e.g., the fact that the team belongs to a university context or is more diverse) might lead to the development of a higher sensibility on ethical matters. Embracing cultural diversity forces trauma teams to deal with different mindsets. Organizations should, therefore, consider those elements in defining their organizational procedures. Level of evidence Trauma and acute care teams work under tremendous pressure and complex circumstances, with their members needing to make ethical decisions quickly. The international survey allowed to shed light on how team assembly decisions might represent an opportunity to coordinate team member actions and increase performance

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p &lt; 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Optimal sensor location for improved multifixture assembly system fault diagnosis: A methodology.

This thesis presents a multi-sensor placement methodology developed and implemented for dimensional fault diagnosis, and the process control of assembly lines such as those in sheet metal assembly. An assembly line is defined as consisting of a sequence of fixtures. Sensors are used to measure dimensional characteristics of the subassemblies as they move from fixture to fixture in the sequence. Fault diagnosis involves identifying the specific fixture and the functional part of the fixture at fault, if the assembly does not meet dimensional acceptance criteria. Fixture fault diagnosis is a critical component of techniques aimed at assembly variation reduction. The effectiveness of the diagnosis is contingent on the effectiveness of the sensor measurements of assembled parts. A novel means of enhancing diagnosability is proposed for multi-fixture sheet-metal assembly, using in-line measurement sensors, through a methodology which develops an optimized configuration of sensor locales for measurement. The methodology incorporates specifications (representations) of fixtures, assemblies, and sensor locations. Sensor placement optimization techniques are provided for three levels of system complexity in the development of the multi-sensor methodology: (i) for a single fixture assembly system, (ii) an enhancement for a multi-fixture assembly system with sensing at a measurement station in a single end-of-line location, and (iii) an enhancement to deal with multi-fixture assembly systems with sensing distributed at multiple locations in the assembly sequence. For a single fixture assembly system, the methodology involves optimization carried out on sensor location and number to achieve optimal diagnosability for that fixture. For a multi-fixture assembly system, a hierarchical group description of the assembly is used to build a state-transition representation which, with CAD fixture information, is used in multi-level hierarchical optimization to arrive at the optimal for the overall assembly. In the end-of-line sensing system, this can then optimally diagnose faults caused by failures anywhere in the multi-fixture assembly line upstream of the measurement station. The distributed sensing enhancement allows for enhanced fault diagnosis in an assembly line by finding an optimal locale of sensor positions at multiple, distributed, measurement stations. In each case, a configured optimal locale provides an optimally distinctive signature for each fault in the assembly, and optimally discriminates among all possible faults. The developed approach has significant utility in automotive body assembly, where system complexity makes the choice of sensor location vital to fault isolation. Examples using simulated and industrial automotive body assembly sequences are provided to help illustrate and validate the proposed methodology.Ph.D.Applied SciencesAutomotive engineeringIndustrial engineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/131687/2/9929861.pd

Sensitization of Nanocrystalline Titanium dioxide Solar Cells using Natural Dyes: Influence of Acids Medium on Coating Formulation

Dye Sensitzed solar cells (DSSC) has drawn attention as an alternative to the silicon based solar cells due to their low fabrication cost and reasonably high efficiency. This paper presents an approach on the development of DSSC and the photoelectrochemical effect and conversion efficiency available natural dye sensitized Titanium dioxide (TiO2) photoelectrode with respect to acid treatment of coating formulation. Acid treatment on TiO2 paste was observed using an organic acid (citric acid) and an inorganic acid (nitric acid) considering a base natural dye (red spinach). Optimal concentration of these acids (organic and inorganic) was determined by cell performance. Five different natural dyes were used as sensitizers of DSSC and their performance was observed considering photoelectrochemical output and UV-visible absorption using optimized acid concentrations. Citric Acid treated cells with red spinach dye as sensitizer produced the best performance with 1mAcm-2 current density with 505mV potential. It was found that DSSC showed better photovoltaic performance and higher conversion efficiency when the TiO2 paste was treated by organic acid than inorganic acid and red spinach dye proved to be the best sensitizer

Investigation of thermal energy storage systems in concentrated solar power

Azad, M ORCiD: 0000-0001-8258-6057This study presents computational fluid dynamics (CFD) modelling results obtained for the first cycle on a sensible thermal energy storage system based on rocks and pebbles freely poured into a mild steel tank. This study is primarily focused on proposing a plan to find an optimized particle size for the packed bed storage using various heat transfer fluids namely water, therminol-vp1, and air. The computational domain consists of an axisymmetric tank of cylindrical shape filled with a porous bed coupled with the wall. The governing equations have been solved for incompressible turbulent flow and fully developed forced convection, based on the two-phase transient model equation (SSTKW) to calculate the temperature of the fluid and solid phases. The porosity has been considered as 0.28 for the packed bed while the thermodynamic properties of both phases are temperature-dependent. The influence of the thermal dispersion within the porous bed, as well as the effective conductivity between the beads, were considered. The heat transfer coefficient was calculated according to the correlation for forced convection within porous media. Experimental temperature profile at the inlet of the bed is applied as a boundary condition in the simulation. Simulation results showed a good agreement with experimental data. © 2019 The Authors. Published by Elsevier Ltd

PGC-1[alpha] overexpression in primary hepatocytes increases fatty acid oxidation and mitochondrial content [abstract]

The role of peroxisome proliferator-activated receptor-[gamma] coactivator-1[alpha] (PGC-1[alpha]) in increasing mitochondrial content and fatty acid oxidation (FAO) in skeletal muscle has been well described. Often, this increase in mitochondrial content and FAO is observed to associate with increased skeletal muscle and systemic insulin sensitivity. However, to date no studies have documented the effect of elevated PGC-1[alpha] protein expression on hepatocyte mitochondrial function and FAO. Therefore, we examined whether adenoviral PGC-1alpha] protein overexpression would result in increased markers of mitochondrial content and FAO in primary hepatocytes. Additionally, would the increased mitochondrial content and FAO be associated with protection of hepatocyte insulin signaling following chronic exposure to lipids