The potential of additive manufacturing in the smart factory industrial 4.0: A review

Additive manufacturing (AM) or three-dimensional (3D) printing has introduced a novel production method in design, manufacturing, and distribution to end-users. This technology has provided great freedom in design for creating complex components, highly customizable products, and efficient waste minimization. The last industrial revolution, namely industry 4.0, employs the integration of smart manufacturing systems and developed information technologies. Accordingly, AM plays a principal role in industry 4.0 thanks to numerous benefits, such as time and material saving, rapid prototyping, high efficiency, and decentralized production methods. This review paper is to organize a comprehensive study on AM technology and present the latest achievements and industrial applications. Besides that, this paper investigates the sustainability dimensions of the AM process and the added values in economic, social, and environment sections. Finally, the paper concludes by pointing out the future trend of AM in technology, applications, and materials aspects that have the potential to come up with new ideas for the future of AM explorations

In preeclampsia, maternal third trimester subcutaneous adipocyte lipolysis is more resistant to suppression by insulin than in healthy pregnancy

Obesity increases preeclampsia risk, and maternal dyslipidemia may result from exaggerated adipocyte lipolysis. We compared adipocyte function in preeclampsia with healthy pregnancy to establish whether there is increased lipolysis. Subcutaneous and visceral adipose tissue biopsies were collected at caesarean section from healthy (n=31) and preeclampsia (n=13) mothers. Lipolysis in response to isoproterenol (200 nmol/L) and insulin (10 nmol/L) was assessed. In healthy pregnancy, subcutaneous adipocytes had higher diameter than visceral adipocytes (<i>P</i><0.001). Subcutaneous and visceral adipocyte mean diameter in preeclampsia was similar to that in healthy pregnant controls, but cell distribution was shifted toward smaller cell diameter in preeclampsia. Total lipolysis rates under all conditions were lower in healthy visceral than subcutaneous adipocytes but did not differ after normalization for cell diameter. Visceral adipocyte insulin sensitivity was lower than subcutaneous in healthy pregnancy and inversely correlated with plasma triglyceride (<i>r</i>=−0.50; <i>P</i>=0.004). Visceral adipose tissue had lower <i>ADRB3, LPL,</i> and leptin and higher insulin receptor messenger RNA expression than subcutaneous adipose tissue. There was no difference in subcutaneous adipocyte lipolysis rates between preeclampsia and healthy controls, but subcutaneous adipocytes had lower sensitivity to insulin in preeclampsia, independent of cell diameter (<i>P</i><0.05). In preeclampsia, visceral adipose tissue had higher <i>LPL</i> messenger RNA expression than subcutaneous. In conclusion, in healthy pregnancy, the larger total mass of subcutaneous adipose tissue may release more fatty acids into the circulation than visceral adipose tissue. Reduced insulin suppression of subcutaneous adipocyte lipolysis may increase the burden of plasma fatty acids that the mother has to process in preeclampsia

Relationship between blood pressure values, depressive symptoms and cardiovascular outcomes in patients with cardiometabolic disease

We studied joint effect of blood pressure-BP and depression on risk of major adverse cardiovascular outcome in patients with existing cardiometabolic disease. A cohort of 35537 patients with coronary heart disease, diabetes or stroke underwent depression screening and BP was recorded concurrently. We used Cox’s proportional hazards to calculate risk of major adverse cardiovascular event-MACE (myocardial infarction/heart failure/stroke or cardiovascular death) over 4 years associated with baseline BP and depression. 11% (3939) had experienced MACE within 4 years. Patients with very high systolic BP-SBP (160-240) hazard ratio-HR 1.28 and with depression (HR 1.22) at baseline had significantly higher adjusted risk. Depression had significant interaction with SBP in risk prediction (p=0.03). Patients with combination of SBP and depression at baseline had 83% higher adjusted risk of MACE, as compared to patients with reference SBP and without depression. Patients with cardiometabolic disease and comorbid depression may benefit from closer monitoring of SBP

Visceral adipose tissue activated macrophage content and inflammatory adipokine secretion is higher in pre-eclampsia than in healthy pregnancy

Obesity increases preeclampsia risk. Adipose tissue inflammation may contribute to the clinical syndrome of pre-eclampsia. We compared adipose tissue macrophage infiltration and release of pro-inflammatory adipokines in pre-eclampsia and healthy pregnancy. Subcutaneous and visceral adipose tissue biopsies were collected from healthy (n=13) and preeclampsia (n=13) mothers. Basal and lipopolysaccharide stimulated adipocyte TNFα, IL-6, CCL-2 and CRP release was measured. Adipose tissue cell densities of activated (cfms(+)) and total (CD68(+)) macrophages were determined. In pre-eclampsia only, visceral adipose tissue TNFα release was increased after lipopolysaccharide stimulation (57 [76] vs 81 [97] pg/mL/ug DNA, p=0.030). Basal TNFα release was negatively correlated insulin sensitivity of visceral adipocytes (r=-0.61, p=0.030) in pre-eclampsia. Visceral adipocyte IL-6 release was increased after lipopolysaccharide stimulation in pre-eclampsia only (566 [696] vs 852 [914] pg/mL/ugDNA, p=0.019). Visceral adipocyte CCL-2 basal (67 [61] vs 187 [219] pg/mL/ugDNA, p=0.049) and stimulated (46 [46] vs 224 [271] pg/mL/ugDNA, p=0.003) release was greater than in subcutaneous adipocytes in pre-eclampsia only. In pre-eclampsia, median TNF mRNA expression in visceral adipose tissue was higher than controls (1.94 [1.13-4.14] vs 0.8 [0.00-1.27] TNF / PPIA ratio, p=0.006). In visceral adipose tissue, CSF1R (a marker of activated macrophages) mRNA expression (24.8[11.0] vs 51.0[29.9] CSF1R/PPIA ratio, p=0.011) and activated (cfms+) macrophage count (6.7[2.6] vs 15.2[8.8] % cfms+/adipocyte, p=0.031) were higher in pre-eclampsia than in controls. In conclusion, our study demonstrates dysregulation of inflammatory pathways predominantly in visceral adipose tissue in pre-eclampsia. Inflammation of visceral adipose tissue may mediate many of the adverse metabolic effects associated with pre-eclampsia

Uloga adrenalnih žlijezda u nastanku promjena u metabolizmu ugljikohidrata izazvanih diazinonom u štakora

Treatment of rats with diazinon (40 mg/kg, i.p.) resulted in hyper-glycaemia and depletion of glycogen from the brain and peripheral tissues two hours after administration. The activities of glycogen phosphorylase and phosphoglucomutase were significantly higher in the brain and liver; that of glucose-6-phosphatase was not altered. The activities of the glycolytic enzymes hexokinase and lactate dehydrogenase were increased only in the brain. The cholinesterase activity in the brain was reduced by treatment with diazinon. The activities of the hepatic gluconeogenic enzymes fructose I.6-diphosphatase and phosphoenolpyruvate carboxykinase were significantly increased. The lactate level was increased in the brain and blood, whereas that of pyruvate was not changed. The activity of glucose-6-phosphate dehydrogenase was not changed to any major extent. Cholesterol and ascorbic acid contents of adrenals were depleted in diazinon-treated animals. The changes were pronounced after intraperitoneal administration of 40 mg/kg diazinon, they were slight but significant after 20 mg/kg, and absent after l0 mg/kg. Hyperglycaemia and changes in carbohydrate metabolism were abolished by adrenalectomy suggesting possible involvement of adrenals.U štakora koji su dobivali diazinon (40 mg/kg) intraperitonealno dva sata nakon pnm1ene utvrđena je hiperglikemija i smanjenje nivoa glikogena u tkivima mozga i živaca. Aktivnosti glikogen fosforilaze i fosfoglukomutaze u mozgu i jetri bile su značajno više, dok se aktivnost glukoza-6-fosfataze nije promijenila. Glikolitski enzimi heksokinaza i laktat dehidrogenaza imali su povišenu aktivnost samo u mozgu. Tretman diazinonom doveo je do smanjene aktivnosti kolinesteraze u mozgu. Aktivnosti glukoneogenih enzima jetre fruktoza 1,6-difosfataze i fosfoenolpiruvatne karboksikinaze značajno su porasle. Nivo laktata bio je povišen u mozgu i krvi, dok je koncentracija piruvata ostala nepromijenjena. Aktivnost glukoza-6-fosfatne dehidrogenaze nije se bitno promijenila. Sadržaj kolesterola i askorbinske kiseline u nadbubrežnim žlijezdama bioje niži u životinja koje su primale diazinon, Promjene su bile najizraženije nakon doze od 40 mg kg diazinona, male ali značajne nakon doze od 20 mg/kg, a nije ih bilo nakon doze od 10 mg/kg. Hiperglikemija i promjene u metabolizmu ugljikohidrata bile su spriječene adrenalektomijom što ukazuje na moguću ulogu nadbubrežnih žlijezda u biokemijskim promjenama izazvanima diazinonom

Acute-on-chronic Liver Failure: MELD Score 30-day Mortality Predictability and Etiology in a Pakistani Population

Background: Cirrhosis is a pathological condition that ultimately leads to liver failure. Acute on chronic liver failure (ACLF) has a high short term mortality rate. Viral hepatitis is the most common cause of liver failure in our local population. We carried out this study to identity the 30-day mortality and etiology of patients presenting with ACLF using Model for End-Stage Liver Disease (MELD) score predictability. Methodology: This was a descriptive case series, conducted at Sheikh Zayed Hospital, Lahore, Pakistan from January 31, 2018 to July 30, 2018. One hundred and eighty five patients who met the inclusion criteria were enrolled using 95% confidence level and 4% margin of error. Data was entered and analyzed with SPSS version 23.0. Numerical variables including age was presented by Mean ± S.D. Categorical variables i.e. gender, etiology of acute-on-chronic liver failure and 30-day mortality were presented by frequency and percentage. Data was stratified for age, gender, duration of chronic liver disease and MELD grade to address the effect modifiers. Post-stratification chi-square test was calculated using 95% significance (p≤0.05). Results: Majority of the enrolled patients were male (74.6%) while only 25.4% of the patients were female. One hundred and thirty patients (70.3%) had underlying viral hepatitis while twelve patients (6.5%) and forty three patients (23.2%) presented with alcoholic liver disease and drug-induced ACLF, respectively. Eighty patients (43.2%) died within 30 days of admission.The 30-day mortality with respect to MELD grade was statistically significant (p<0.001) with the highest mortality noted in grade-IV and thirty five patients (43.8%) dying within 30 days of admission (p<0.001). Grade-II and III MELD scores also contributed to the 30-day mortality with twenty three patients (28.8%) and nineteen patients (23.8%) dying within 30 days of admission (p<0.001). Conclusion: MELD scores are able to accurately predict the short-term mortality in patients with ACLF and viral hepatitis was the most common etiology in our population. Early detection and use of appropriate prognostic models may alleviate mortality and morbidity in paitents with ACLF

N-terminal pro-B-type natriuretic peptide and the prediction of primary cardiovascular events: results from 15-year follow-up of WOSCOPS

<b>Aims:</b>To test whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) was independently associated with, and improved the prediction of, cardiovascular disease (CVD) in a primary prevention cohort. <b>Methods and results:</b> In the West of Scotland Coronary Prevention Study (WOSCOPS), a cohort of middle-aged men with hypercholesterolaemia at a moderate risk of CVD, we related the baseline NT-proBNP (geometric mean 28 pg/mL) in 4801 men to the risk of CVD over 15 years during which 1690 experienced CVD events. Taking into account the competing risk of non-CVD death, NT-proBNP was associated with an increased risk of all CVD [HR: 1.17 (95% CI: 1.11–1.23) per standard deviation increase in log NT-proBNP] after adjustment for classical and clinical cardiovascular risk factors plus C-reactive protein. N-terminal pro-B-type natriuretic peptide was more strongly related to the risk of fatal [HR: 1.34 (95% CI: 1.19–1.52)] than non-fatal CVD [HR: 1.17 (95% CI: 1.10–1.24)] (P= 0.022). The addition of NT-proBNP to traditional risk factors improved the C-index (+0.013; P < 0.001). The continuous net reclassification index improved with the addition of NT-proBNP by 19.8% (95% CI: 13.6–25.9%) compared with 9.8% (95% CI: 4.2–15.6%) with the addition of C-reactive protein. N-terminal pro-B-type natriuretic peptide correctly reclassified 14.7% of events, whereas C-reactive protein correctly reclassified 3.4% of events. Results were similar in the 4128 men without evidence of angina, nitrate prescription, minor ECG abnormalities, or prior cerebrovascular disease. <b>Conclusion:</b> N-terminal pro-B-type natriuretic peptide predicts CVD events in men without clinical evidence of CHD, angina, or history of stroke, and appears related more strongly to the risk for fatal events. N-terminal pro-B-type natriuretic peptide also provides moderate risk discrimination, in excess of that provided by the measurement of C-reactive protein

An evaluation of risk factors for major adverse cardiovascular events during tocilizumab therapy

Objective: To evaluate associations between lipid levels, inflammation, and rheumatoid arthritis (RA) disease activity, at baseline and during treatment, with the risk of major adverse cardiovascular events (MACE) in tocilizumab‐treated patients with RA. Methods: In retrospective post hoc analyses, data were pooled for 3,986 adult patients with moderate to severe RA who received ≥1 dose of tocilizumab (4 mg/kg or 8 mg/kg) intravenously every 4 weeks in randomized controlled trials and extension studies. Cox proportional hazards modeling was used to evaluate associations between baseline characteristics and posttreatment changes in laboratory and disease characteristics (week 24) and change in disease activity and laboratory values from baseline to week 24 with the risk of future MACE during extended followup. Results: We identified 50 independently adjudicated cases of MACE during 14,683 patient‐years of followup (0.34 MACE cases/100 patient‐years). At baseline, age, a history of cardiac disorders, the Disease Activity Score in 28 joints (DAS28), and the total cholesterol:high‐density lipoprotein cholesterol ratio were independently associated with MACE in multivariable models (P < 0.05 for all). During treatment, a higher DAS28 and higher swollen and tender joint counts at week 24 were associated with future MACE. In separate models, greater reductions in the DAS28 and joint counts from baseline to week 24 were inversely associated with future MACE; changes in lipid parameters were not statistically significantly associated with the risk of MACE. Conclusion: In this population of patients treated with tocilizumab, an association was observed between the baseline total cholesterol:high‐density lipoprotein cholesterol ratio and an increased risk of MACE. The risk of MACE while receiving treatment, however, was associated with control of disease activity but not lipid changes. Larger studies are needed to confirm these findings