The role of interleukins 4, 17 and interferon gamma as biomarkers in patients with Systemic Lupus Erythematosus and their correlation with disease activity

AbstractAim of the workThis work was designed to study the production of proinflammatory cytokines in SLE patients and their correlation with disease activity and study if they can be used as biomarkers for renal activity in lupus nephritis patients.Patients and methodsThis study was carried out on 70 subjects divided into two groups: Group I (SLE group) which included 40 SLE patients and Group II (Control group) which included 30 apparently healthy controls. The patients were subjected to full history taking and complete clinical examination. Assessment of disease activity in SLE patients by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Sera of patients and controls were screened for the level of cytokine expression of T helper cells including interleukin 17 (IL-17), interleukin 4 (IL-4) and interferon gamma (IFN-γ).ResultsSerum levels of IL-4 were significantly lower while both IL-17 and IFN-γ were significantly higher in SLE patients than in the control group. The most powerful predictor and correlated cytokine with the SLEDAI in SLE patients was IL-17. Higher serum level of IFN-γ was associated with more pyuria and hematuria, while higher IL-17 was associated with more pyuria and proteinuria in SLE patients.ConclusionThe serum level of IL-17 and IFN-γ was proven to be significantly higher in SLE patients and can be used as biomarkers of renal activity

Comparative studies on the efficacy of lincomycin and bacitracin for the control of necrotic enteritis in broiler chickens

Background: The present study was conducted to evaluate the efficacy of lincomycin and/or bacitracin for control of experimentally-induced Clostridium perfringens (CP) infection in broiler chickens.Methods: A total of 100 one-day-old Cobb-mixed chicks were divided into five groups (A, B, C, D and E, each of 20 bird). At the 15th day of age, all birds (except group A) were inoculated orally with CP broth culture (109 CFU/mL). Two days later, drugs were orally administered once daily for five consecutive days as follow; Group A and B were left untreated. Group C, D, and E were treated with lincomycin (0.5 g/l), bacitracin (100 mg/l), lincomycin and bacitracin, respectively. The efficacy of used drugs was estimated based on clinical symptoms, body weight, weight gain, feed conversion rate. Hematobiochemical changes were also determined.Results: Necrotic enteritis in broiler chickens induced a significant decrease in body weight, weight gain, erythrocytic count, hemoglobin content, PCV %, serum proteins, catalase, and superoxide dismutase. Additionally, a marked decrease in serum lipids was obtained. Furthermore, a significant increase in feed conversion rate, leukocytic count, phagocytic activity, phagocytic index, serum total globulin, γ globulin and malondialdehyde coupled with a marked increase in β and α globulins were determined. Medication of infected broilers with lincomycin and/or bacitracin improved clinical signs and reduced mortality rate to 8, 6 and 2%, respectively, as well as restored the performance and hematobiochemical alterations.Conclusions: a combination of lincomycin and bacitracin was of considerable value for the control of necrotic enteritis in broiler chickens

Acetylsalicylic Acid Suppresses Alcoholism-Induced Cognitive Impairment Associated with Atorvastatin Intake by Targeting Cerebral miRNA155 and NLRP3: In Vivo, and In Silico Study

Alcoholism is one of the most common diseases that can lead to the development of several chronic diseases including steatosis, and cognitive dysfunction. Statins are lipid-lowering drugs that are commonly prescribed for patients with fatty liver diseases; however, the exact effect of statins on cognitive function is still not fully understood. In the present study, we have investigated the molecular and microscopic basis of cognitive impairment induced by alcohol and/or Atorvastatin (ATOR) administration to male Wistar albino rats and explored the possible protective effect of acetylsalicylic acid (ASA). The biochemical analysis indicated that either alcohol or ATOR or together in combination produced a significant increase in the nucleotide-binding domain–like receptor 3 (NLRP3), interleukin-1β (IL-1β) miRNA155 expression levels in the frontal cortex of the brain tissue. The histological and morphometric analysis showed signs of degeneration in the neurons and the glial cells with aggregations of inflammatory cells and a decrease in the mean thickness of the frontal cortex. Immunohistochemical analysis showed a significant increase in the caspase-8 immunoreaction in the neurons and glial cells of the frontal cortex. Interestingly, administration of ASA reversed the deleterious effect of the alcohol and ATOR intake and improved the cognitive function as indicated by biochemical and histological analysis. ASA significantly decreased the expression levels of miRNA155, NLRP3, and IL1B, and produced a significant decrease in caspase-8 immunoreaction in the neurons and glial cells of the frontal cortex with a reduction in the process of neuroinflammation and neuronal damage. To further investigate these findings, we have performed an extensive molecular docking study to investigate the binding affinity of ASA to the binding pockets of the NLRP3 protein. Our results indicated that ASA has high binding scores toward the active sites of the NLRP3 NACHT domain with the ability to bind to the NLRP3 pockets by a set of hydrophilic and hydrophobic interactions. Taken together, the present study highlights the protective pharmacological effect of ASA to attenuate the deleterious effect of alcohol intake and long term ATOR therapy on the cognitive function via targeting miRNA155 and NLRP3 proteins.Peer Reviewe

Acetylsalicylic Acid Suppresses Alcoholism-Induced Cognitive Impairment Associated with Atorvastatin Intake by Targeting Cerebral miRNA155 and NLRP3: In Vivo, and In Silico Study

Alcoholism is one of the most common diseases that can lead to the development of several chronic diseases including steatosis, and cognitive dysfunction. Statins are lipid-lowering drugs that are commonly prescribed for patients with fatty liver diseases; however, the exact effect of statins on cognitive function is still not fully understood. In the present study, we have investigated the molecular and microscopic basis of cognitive impairment induced by alcohol and/or Atorvastatin (ATOR) administration to male Wistar albino rats and explored the possible protective effect of acetylsalicylic acid (ASA). The biochemical analysis indicated that either alcohol or ATOR or together in combination produced a significant increase in the nucleotide-binding domain–like receptor 3 (NLRP3), interleukin-1β (IL-1β) miRNA155 expression levels in the frontal cortex of the brain tissue. The histological and morphometric analysis showed signs of degeneration in the neurons and the glial cells with aggregations of inflammatory cells and a decrease in the mean thickness of the frontal cortex. Immunohistochemical analysis showed a significant increase in the caspase-8 immunoreaction in the neurons and glial cells of the frontal cortex. Interestingly, administration of ASA reversed the deleterious effect of the alcohol and ATOR intake and improved the cognitive function as indicated by biochemical and histological analysis. ASA significantly decreased the expression levels of miRNA155, NLRP3, and IL1B, and produced a significant decrease in caspase-8 immunoreaction in the neurons and glial cells of the frontal cortex with a reduction in the process of neuroinflammation and neuronal damage. To further investigate these findings, we have performed an extensive molecular docking study to investigate the binding affinity of ASA to the binding pockets of the NLRP3 protein. Our results indicated that ASA has high binding scores toward the active sites of the NLRP3 NACHT domain with the ability to bind to the NLRP3 pockets by a set of hydrophilic and hydrophobic interactions. Taken together, the present study highlights the protective pharmacological effect of ASA to attenuate the deleterious effect of alcohol intake and long term ATOR therapy on the cognitive function via targeting miRNA155 and NLRP3 proteins

Canvass: a crowd-sourced, natural-product screening library for exploring biological space

NCATS thanks Dingyin Tao for assistance with compound characterization. This research was supported by the Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH). R.B.A. acknowledges support from NSF (CHE-1665145) and NIH (GM126221). M.K.B. acknowledges support from NIH (5R01GM110131). N.Z.B. thanks support from NIGMS, NIH (R01GM114061). J.K.C. acknowledges support from NSF (CHE-1665331). J.C. acknowledges support from the Fogarty International Center, NIH (TW009872). P.A.C. acknowledges support from the National Cancer Institute (NCI), NIH (R01 CA158275), and the NIH/National Institute of Aging (P01 AG012411). N.K.G. acknowledges support from NSF (CHE-1464898). B.C.G. thanks the support of NSF (RUI: 213569), the Camille and Henry Dreyfus Foundation, and the Arnold and Mabel Beckman Foundation. C.C.H. thanks the start-up funds from the Scripps Institution of Oceanography for support. J.N.J. acknowledges support from NIH (GM 063557, GM 084333). A.D.K. thanks the support from NCI, NIH (P01CA125066). D.G.I.K. acknowledges support from the National Center for Complementary and Integrative Health (1 R01 AT008088) and the Fogarty International Center, NIH (U01 TW00313), and gratefully acknowledges courtesies extended by the Government of Madagascar (Ministere des Eaux et Forets). O.K. thanks NIH (R01GM071779) for financial support. T.J.M. acknowledges support from NIH (GM116952). S.M. acknowledges support from NIH (DA045884-01, DA046487-01, AA026949-01), the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program (W81XWH-17-1-0256), and NCI, NIH, through a Cancer Center Support Grant (P30 CA008748). K.N.M. thanks the California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board for support. B.T.M. thanks Michael Mullowney for his contribution in the isolation, elucidation, and submission of the compounds in this work. P.N. acknowledges support from NIH (R01 GM111476). L.E.O. acknowledges support from NIH (R01-HL25854, R01-GM30859, R0-1-NS-12389). L.E.B., J.K.S., and J.A.P. thank the NIH (R35 GM-118173, R24 GM-111625) for research support. F.R. thanks the American Lebanese Syrian Associated Charities (ALSAC) for financial support. I.S. thanks the University of Oklahoma Startup funds for support. J.T.S. acknowledges support from ACS PRF (53767-ND1) and NSF (CHE-1414298), and thanks Drs. Kellan N. Lamb and Michael J. Di Maso for their synthetic contribution. B.S. acknowledges support from NIH (CA78747, CA106150, GM114353, GM115575). W.S. acknowledges support from NIGMS, NIH (R15GM116032, P30 GM103450), and thanks the University of Arkansas for startup funds and the Arkansas Biosciences Institute (ABI) for seed money. C.R.J.S. acknowledges support from NIH (R01GM121656). D.S.T. thanks the support of NIH (T32 CA062948-Gudas) and PhRMA Foundation to A.L.V., NIH (P41 GM076267) to D.S.T., and CCSG NIH (P30 CA008748) to C.B. Thompson. R.E.T. acknowledges support from NIGMS, NIH (GM129465). R.J.T. thanks the American Cancer Society (RSG-12-253-01-CDD) and NSF (CHE1361173) for support. D.A.V. thanks the Camille and Henry Dreyfus Foundation, the National Science Foundation (CHE-0353662, CHE-1005253, and CHE-1725142), the Beckman Foundation, the Sherman Fairchild Foundation, the John Stauffer Charitable Trust, and the Christian Scholars Foundation for support. J.W. acknowledges support from the American Cancer Society through the Research Scholar Grant (RSG-13-011-01-CDD). W.M.W.acknowledges support from NIGMS, NIH (GM119426), and NSF (CHE1755698). A.Z. acknowledges support from NSF (CHE-1463819). (Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH); CHE-1665145 - NSF; CHE-1665331 - NSF; CHE-1464898 - NSF; RUI: 213569 - NSF; CHE-1414298 - NSF; CHE1361173 - NSF; CHE1755698 - NSF; CHE-1463819 - NSF; GM126221 - NIH; 5R01GM110131 - NIH; GM 063557 - NIH; GM 084333 - NIH; R01GM071779 - NIH; GM116952 - NIH; DA045884-01 - NIH; DA046487-01 - NIH; AA026949-01 - NIH; R01 GM111476 - NIH; R01-HL25854 - NIH; R01-GM30859 - NIH; R0-1-NS-12389 - NIH; R35 GM-118173 - NIH; R24 GM-111625 - NIH; CA78747 - NIH; CA106150 - NIH; GM114353 - NIH; GM115575 - NIH; R01GM121656 - NIH; T32 CA062948-Gudas - NIH; P41 GM076267 - NIH; R01GM114061 - NIGMS, NIH; R15GM116032 - NIGMS, NIH; P30 GM103450 - NIGMS, NIH; GM129465 - NIGMS, NIH; GM119426 - NIGMS, NIH; TW009872 - Fogarty International Center, NIH; U01 TW00313 - Fogarty International Center, NIH; R01 CA158275 - National Cancer Institute (NCI), NIH; P01 AG012411 - NIH/National Institute of Aging; Camille and Henry Dreyfus Foundation; Arnold and Mabel Beckman Foundation; Scripps Institution of Oceanography; P01CA125066 - NCI, NIH; 1 R01 AT008088 - National Center for Complementary and Integrative Health; W81XWH-17-1-0256 - Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program; P30 CA008748 - NCI, NIH, through a Cancer Center Support Grant; California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board; American Lebanese Syrian Associated Charities (ALSAC); University of Oklahoma Startup funds; 53767-ND1 - ACS PRF; PhRMA Foundation; P30 CA008748 - CCSG NIH; RSG-12-253-01-CDD - American Cancer Society; RSG-13-011-01-CDD - American Cancer Society; CHE-0353662 - National Science Foundation; CHE-1005253 - National Science Foundation; CHE-1725142 - National Science Foundation; Beckman Foundation; Sherman Fairchild Foundation; John Stauffer Charitable Trust; Christian Scholars Foundation)Published versionSupporting documentatio

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

The role of Dickkopf-1 as a biomarker in systemic lupus erythematosus and active lupus nephritis

Abstract Background Systemic lupus erythematosus (SLE) is a chronic disease which is mainly attributed to autoantibodies, cytokines, and immune complex deposition. Studies have demonstrated that cytokines and autoantibodies were strongly associated with renal diseases and can be used for the prediction of patients with lupus nephritis (LN). However, antibodies to dsDNA and the reduction of complements were also detected in non-LN patients as well as clinically non-active SLE patients. The current study was performed to detect the role of serum DKK-1 as a biomarker for the identification of SLE patients and patients with LN and its relation to disease activity and severity. The study was conducted on fifty clinically diagnosed SLE patients who were diagnosed according to Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE, in addition to thirty healthy control volunteers matched for age and sex. Assessment of SLE disease activity was done using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Assessment of SLE disease severity was done using the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage index. Serum levels of DKK-1 were measured for all participants by ELISA using commercially available kits. Results DKK-1 serum levels were significantly higher among active lupus nephritis cases as compared with SLE cases with no LN and with healthy controls (9197.60 μg/uL ± 2939.2 μg/uL vs. 6405.15 μg/uL ± 2018.91 μg/uL vs. 2790.33 μg/uL ± 833.49 μg/uL) respectively (p-values < 0.001). DKK-1 concentration was significantly higher among SLE patients with positive as compared with negative anti-double-stranded DNA (dsDNA) antibodies (p-value < 0.001). According to receiver operating characteristic (ROC) curve analysis, serum DKK-1 level diagnosed the SLE at a statistically significant level with a 98% sensitivity and 70% specificity and serum DKK-1 level also diagnosed active lupus nephritis at a 90% sensitivity and 63% specificity. Conclusion DKK-1 could diagnose SLE and lupus nephritis with high sensitivity and specificity. Serum DKK-1 is a reliable biomarker for the identification of SLE and patients with LN and could be used as a key molecule for the diagnosis of SLE and as a prognostic indicator of LN