Elementi managementa okoline u jednom integriranom sustavu upravljanja

Un dem Artikel wurde, auf dem Beispiel der Gusseisengießerei, die Bedeutung von Umweltmanagement beim Einführen des integrierten Managementsystems und sein Einfluss auf das Unternehmensfunktionieren vorgestellt. Man zeigte, wie Umweltaspekt Unternehmensmanagement und seine Ergebnisse beeinflusst. Es wurden auch Handlungen, die zwecks der Einleitung des Umweltmanagementsystems durchgeführt wurden, und Änderungen, die sie sowohl in Unternehmensmanagement als auch in Betriebsgliederung hervorgerufen haben, dargestellt. Man zeigte auch Faktoren, welche den Bedarf der Berücksichtigung des ökologischen Aspektes im Unternehmensfunktionieren hervorrufen und von den Normen ISO 14000 und der TQEM - Philosophie erfolgen. Es wurden auch alternative Messungsmöglichkeiten von Erfüllungsgrad ökologischer Anforderungen gekennzeichnet.U članku je na primjeru ljevaonice sivog željeza predstavljeno značenje upravljanja okolišem putem uvođenja integriranog sistema managementa i njegov utjecaj na funkcioniranje poduzeća. Pokazano je kako se na management poduzeća i njegove rezultate utječe sa aspekta okoliša. Predstavljene su i radnje koje se provode radi uvođenja sistema managementa okoliša i promjene koje su izazvale u managementu poduzeća i u strukturi pogona. Također su prikazani i čimbenici koji izazivaju potrebu da se vodi računa o ekološkom aspektu poduzeća i o normama ISO 14000 i TQEM - filozofiji. Naznačene su i alternativne mogućnosti mjerenja ispunjavanja ekoloških zahtjeva

Sex hormones drive changes in lipoprotein metabolism

Summary Women have a reduced cardiovascular disease (CVD) risk compared to men which could be partially driven by sex hormones influencing lipid levels post-puberty. The interrelationship between sex hormones and lipids was explored in pre-pubertal children, young post-pubertal cis-men/women, and transgender individuals on cross-sex-hormone treatment (trans-men/women) using serum metabolomics assessing 149 lipids. High-density lipoproteins (HDL, typically atheroprotective) were significantly increased and very-low- and low-density lipoproteins (typically atherogenic) were significantly decreased in post-pubertal cis-women compared to cis-men. These differences were not observed pre-puberty and were induced appropriately by cross-sex-hormone treatment in transgender individuals, supporting that sex hormones regulate lipid metabolism in vivo. Only atheroprotective apolipoprotein (Apo)A1 expressing lipoproteins (HDL) were differentially expressed between all hormonally unique comparisons. Thus, oestradiol drives a typically atheroprotective lipid profile through upregulation of HDL/ApoA1 which could contribute to the sexual dimorphism observed in CVD risk post-puberty. Together, this could inform sex-specific therapeutic strategies for CVD management

Sex-bias in COVID-19: a meta-analysis and review of sex differences in disease and immunity

A striking anecdotal feature of the Coronavirus disease 2019 (COVID-19) outbreak is the difference in morbidity and mortality between the sexes. Here, we present a meta-analysis of 206, 128 reported cases to demonstrate that whilst there is no difference in the proportion of males and females with confirmed COVID-19, male patients have more than double the odds of requiring intensive treatment unit admission (OR 2.5) and higher odds of death (OR 1.60) when compared to females. We review data revealing how previous Coronavirus outbreaks have demonstrated a similar pattern. Important differences in the immune response to infection exist between sexes, which are likely to contribute to this observation. In this review, we discuss these differences highlighting that females have a more robust innate antiviral response and a better adaptive immune response to infection. An appreciation of how sex is influencing COVID-19 outcomes will have important implications for clinical management and mitigation strategies for this disease

Increased apolipoprotein-B:A1 ratio predicts cardiometabolic risk in patients with juvenile onset SLE

Background: Cardiovascular disease is a leading cause of mortality in patients with juvenile-onset systemic lupus erythematosus (JSLE). Traditional factors for cardiovascular risk (CVR) prediction are less robust in younger patients. More reliable CVR biomarkers are needed for JSLE patient stratification and to identify therapeutic approaches to reduce cardiovascular morbidity and mortality in JSLE. Methods: Serum metabolomic analysis (including >200 lipoprotein measures) was performed on a discovery (n=31, median age 19) and validation (n=31, median age 19) cohort of JSLE patients. Data was analysed using cluster, receiver operating characteristic analysis and logistic regression. RNA-sequencing assessed gene expression in matched patient samples. Findings: Hierarchical clustering of lipoprotein measures identified and validated two unique JSLE groups. Group-1 had an atherogenic and Group-2 had an atheroprotective lipoprotien profile. Apolipoprotein(Apo)B:ApoA1 distinguished the two groups with high specificity (96.2%) and sensitivity (96.7%). JSLE patients with high ApoB:ApoA1 ratio had increased CD8+ T-cell frequencies and a CD8+ T-cell transcriptomic profile enriched in genes associated with atherogenic processes including interferon signaling. These metabolic and immune signatures overlapped statistically significantly with lipid biomarkers associated with sub-clinical atherosclerosis in adult SLE patients and with genes overexpressed in T-cells from human atherosclerotic plaque respectively. Finally, baseline ApoB:ApoA1 ratio correlated positively with SLE disease activity index (r=0.43, p=0.0009) and negatively with Lupus Low Disease Activity State (r=-0.43, p=0.0009) over 5-year follow-up. Interpretation: Multi-omic analysis identified high ApoB:ApoA1 as a potential biomarker of increased cardiometabolic risk and worse clinical outcomes in JSLE. ApoB:ApoA1 could help identify patients that require increased disease monitoring, lipid modification or lifestyle changes. Funding: Lupus UK, The Rosetrees Trust, British Heart Foundation, UCL & Birkbeck MRC Doctoral Training Programme and Versus Arthritis

Sex and Pubertal Differences in the Type 1 Interferon Pathway Associate With Both X Chromosome Number and Serum Sex Hormone Concentration

Type 1 interferons (IFN) are an antiviral cytokine family, important in juvenile onset systemic lupus erythematosus (jSLE) which is more common in females, around puberty. We report that plasmacytoid dendritic cells (pDC) from healthy females produced more type 1 IFN after toll like receptor (TLR) 7 signaling than males, even before puberty, but that puberty itself associated with increased production of type 1 IFN. A unique human model allows us to show that this was related to X chromosome number, and serum testosterone concentration, in a manner which differed depending on the number of X chromosomes present. In addition, we have showed that pDC were more activated in females overall, and immune cell TLR7 gene expression was higher in females after puberty. Therefore, sex hormones and X chromosome number were associated individually and interactively with the type 1 IFN response, which contributes to our understanding of why females are more likely to develop an IFN mediated disease like jSLE after puberty

Favourable antibody responses to human coronaviruses in children and adolescents with autoimmune rheumatic diseases

Background: Differences in humoral immunity to coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), between children and adults remain unexplained and the impact of underlying immune dysfunction or suppression unknown. Here, we sought to examine the antibody immune competence of children and adolescents with prevalent inflammatory rheumatic diseases, juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM) and juvenile systemic lupus erythematosus (JSLE), against the seasonal human coronavirus (HCoV)-OC43 that frequently infects this age group. // Methods: Sera were collected from JIA (n=118), JDM (n=49) and JSLE (n=30) patients, and from healthy control (n=54) children and adolescents, prior to the coronavirus disease-19 (COVID-19) pandemic. We employed sensitive flow cytometry-based assays to determine titres of antibodies that reacted with the spike and nucleoprotein of HCoV-OC43 and cross-reacted with the spike and nucleoprotein of SARS-CoV-2, and compared with respective titres in sera from patients with multisystem inflammatory syndrome in children and adolescents (MIS-C). // Findings: Despite immune dysfunction and immunosuppressive treatment, JIA, JDM and JSLE patients maintained comparable or stronger humoral responses than healthier peers, dominated by IgG antibodies to HCoV-OC43 spike, and harboured IgG antibodies that cross-reacted with SARS-CoV-2 spike. In contrast, responses to HCoV-OC43 and SARS-CoV-2 nucleoproteins exhibited delayed age-dependent class-switching and were not elevated in JIA, JDM and JSLE patients, arguing against increased exposure. // Conclusions: Consequently, autoimmune rheumatic diseases and their treatment were associated with a favourable ratio of spike to nucleoprotein antibodies