In Safety Management System (SMS), the risk management plays a key role for the prevention of accidents. The aim of this paper is to propose a Safety Management model using a system dynamic approach to update conventional industrial safety into the new industrial safety 4.0 that is time to developed. This study analyzes some safety 4.0 aspects lacked in the Bhopal incidental event by considering different data detected in the industrial Plant. The model proposed in this paper discusses the relationships among the main causes that have contributed to the occurrence of the incidental event studied, such as broken safety devices, inadequate personnel experience, operator decisions, manager production strategy, policy decision, as deduced from the relevant literature about Bhopal incidental dynamic.

The immunization of healthcare workers in the early stages of the rollout of COVID-19 vaccines was prioritized in order to ensure uninterrupted medical care provision. At the same time the increasing number of available COVID-19 vaccines may trigger hesitancy towards the decision to get vaccinated. Thus, accumulating reliable information on the adverse events following immunization may educate and urge the general population to receive a COVID-19 vaccine. The present study aimed to evaluate the adverse events (AEs) following immunization with any of the available COVID-19 vaccine among Bulgarian healthcare workers (HCWs). A cross-sectional study among HCWs in Plovdiv, Bulgaria was conducted in the period March – September 2021. Through a semi-structured online questionnaire, the participants reported the adverse events following the administration of the first and second dose of a COVID-19 vaccine. A total of 253 respondents, vaccinated with one of the available vaccines against COVID-19 took part in the study. Of them 71.9% were females, and 75.9% received mRNA-based vaccines, while 24.1% received a viral-vector based vaccine. Overall 91.6% and 82.6% of all participants reported at least one local AE after the first and second dose of a COVID-19 vaccine. The share of respondents reporting at least one systemic AE after the first and second dose of a COVID-19 vaccine was 59.7% and 62.4% respectively. The most common local AE was pain at the injection spot (84.0%), while the most common systemic AEs were fatigue (54.9%), chills (43.2%), and headache (41.7%). The mRNA-based vaccines versions seem to cause higher prevalence of local AEs, while the vector-based vaccines were linked with increased prevalence of systemic AEs. Female HCWs and the younger age group were associated with an increased risk of adverse events generally. Our results added more evidence that mRNA-based and viral-vector based vaccines are generally safe. The reported adverse events were mild, although they occurred in a high share of the respondents. No serious AEs attributable to the vaccines were reported.

This work reviews three frameworks for responding to economic disruption: risk mitigation, systemic recovery, and economic resilience. Specifically, by reviewing extant literature in economics, communication, and other disciplines, we argue that current approaches to understanding resilience in economics largely fail to address ongoing and emergent disruptions to the economic and social world. In response to these issues, we work to synthesize economic frameworks and the communication theory of resilience to forward a new way of examining the overlapping questions of economic resilience related to metatheoretical commitments, analytic contexts, and implications for theory, method, and practice.

The concept of sustainability and sustainable development, especially systemic sustainable development, still raises controversy in literature. The article makes an attempt to re-examine these concepts from a systems perspective, seeking foundations and applications in the selected sector. It is becoming increasingly clear that sustainability and sustainable development are aimed at integrated economic, social, cultural, political, and ecological factors [1[,[2] (pp.641-642). This causes that the constructive approach to the issue is required, taking into account all the actors, areas and dimensions involved in the pursuit of systemic sustainable development. As a result, both local and global dimensions and the way they interact must be explored in a multi-faceted manner in order to offer a perspective more useful than other analytical approaches, because the systems view is a way of thinking in terms of connectedness, relationships, and context [3]. The article aims to review selected publications and studies so as to form the general idea of systemic sustainable development and define the systemic development of sustainable transport, including in particular the perspective of the actors of the sector, transport providers (passenger, urban) and transport development program, implemented both by local governments and on the European scale. An attempt was made to identify elements of the systemic sustainable development model, setting it in the reality of the following subcategories: “Society”, “Economy” and “Environment” in sectoral terms. It is supposed that, systemic sustainable development is a conglomerate of public administration entities, companies operating in the sector, individual and corporate customers, acting in certain conditions for economic, social and environmental well-being, and a number of their initiatives of major or minor significance, grouped in six sub-areas, undertaken to achieve systemic value in the examined sector, with a positive or negative business/economic, social and environmental impact.

Background: Migraine is the commonest complex neurological disorder affecting over a billion people worldwide. Neuroinflammation has long been considered to play an important role in the pathophysiology of migraine. The main aim of this single-centre, proof of concept, retrospective study was to determine the possible clinical utility of systemic immune-inflammatory response in migraine with and without aura in a hospitalized cohort. We measured the role of universally available serial white blood cell counts to calculate the serial systemic immune-inflammatory indices (SSIIi) and the potential association between aura and SSIIi changes in a cohort of migraine patients admitted to tertiary care center in Melbourne Australia.Main body: We retrospectively assessed patients' medical records presenting to Western Health with migraine over an 18 month period. Patients were classified as either having migraine with aura (MA) or without aura (MO) based on ICHD-3 criteria. Baseline demographics and brain imaging findings in each group were evaluated. Patients with two sets of white blood cell counts during the admission were included in the analysis. SSIIi were calculated as, neutrophil counts x platelet counts / lymphocyte counts. Correlation between SSIIi and MA and MO were assessed using SPSS27.Conclusion: SSIIi were elevated in MA and MO followed by a downward trend in both groups, with MA being statistically significant. This proof-of-concept study suggests the potential role of systemic inflammation in pathobiology of migraine. SSIIi appear to show clinical utility. Further comprehensive ,controlled , multicenter studies are required to clarify the exact role of systemic inflammatory response and the clinical utility of SSIIi in a subset of migraine in the Emergency department setting.

Introduction: The gastrointestinal tract (GI) is the second most affected organ system in systemic sclerosis or systemic/localized scleroderma (SSc) and is an important topic for research. Approximately 90% of patients with scleroderma exhibit pathology of the GI tract. The systemic scleroderma has the potential to impact any part of the gastrointestinal tract, between the oral cavity and anorectum. The pathological complications of scleroderma adversely impact the health-related quality of life of the affected patients and increase the treatment burden of patients and medical professionals. Study Aim: We summarized the epidemiology, commonly reported clinical manifestations, complications, and available therapies for treating the GI pathology in systemic scleroderma patients. Methodology: We performed a literature review using the keywords "systemic sclerosis," "scleroderma," "GI manifestations in scleroderma," and "GI complications of scleroderma" across databases, including Google Scholar, Medline, Embase, and PubMed. We also analyzed a range of case reports concerning scleroderma manifestations and treatment modalities. Results: Our research revealed the annual incidence of SSc attributing to19.3 cases per million adults in the United States. We found the highest incidence of systemic scleroderma in patients within the age range of 44-55 years. Our results affirmed 5:1 incidence of systemic scleroderma that confirmed the higher impact of this disease condition in females than male populations. We found that the gastrointestinal manifestations of systemic scleroderma predominantly elevate the morbidity and mortality incidence among the affected patients. Esophageal and intestinal manifestations impact 90% and 40-70% of patients with systemic scleroderma. The small bowel hypomotility and small intestinal bacterial overgrowth (SIBO) in systemic scleroderma cases trigger the episodes of malabsorption and malnutrition that eventually add to 50% of the mortality rate. Systemic sclerosis is associated with the high incidence of fecal incontinence that triggers depression and its deleterious mental health manifestations in many clinical scenarios. Conclusion: The gastrointestinal complications in systemic sclerosis potentially deteriorate the daily living activities of the affected patients. The systematic management of the gastrointestinal complications of systemic scleroderma warrants multidisciplinary approaches. Prospective studies should focus on developing targeted therapies for improving the recovery patterns and prognostic outcomes in systemic scleroderma cases.

In the wake of the 2008 financial crisis, the Financial Stability Board (FSB) and the Basel Committee on Banking Supervision (BCBS) created a list of Systemically Important Financial Institutions (SIFIs) with the intention of determining which financial institutions were important enough to the global market that their failure would result in systemic collapse. In this work we create a model that modifies the BCBS's five indicators of size, interconnectedness, cross-jurisdictional activities, complexity, and substitutability and applies these measures of systemic stress to governments. The original application of the model is to track the systemic interdependence of the Eurozone, with particular emphasis on the case of Greece. We anticipate this model can be used in regional fiscal situations beyond the Eurozone.

Plant-based alternative medicine is normally grounded on empiric cultural perception, as the main objective, these practices intent to either maintain good health or to provide a route to turn-the-tide on a specific disease or ailment. Amongst the thousands of plants that have been used and studied, Neem (Azadirachta indica) seems to have a very interesting tale to tell, since its properties to ward-off certain diseases have overtime, and in a rigorous way, been proven. The preceding concise review is a collection of some of the most relevant studies today, not only focusing on the health benefits obtained by its use, but digging into the molecular mechanisms of how the properties come about. In particular, we take a look over antioxidant properties and how these mediate and mitigate important molecules such as IL-6 and TNF-, leading the way in reducing systematic damage by oxidative stress. Further, we relate this oxidative reduction to other systemic diseases such as cancer and diabetes, as these are currently becoming the most rampant killers. As of yet not all is known about the different ways of extracting or the total composition of an extract, as these may be from different parts of the plant. Therefore, we also allude to an important cautionary view where toxicological effects and conflicting outcomes arise. Overall, presented results show a great potential for the different extracts of Neem as their antioxidant activity can be taken advantage off, and potentially used in modern medicine.

The research reported on this paper was aimed at improving the overall efficiency of a PDO certified artisanal cheese production process. Being a PDO certified foodstuff by the EU, it is considered to have properties and qualities determined by the geographical environment in which is made, with its production taking place in a specific and determined geographical location, in this case the Serra da Estrela region. In that sense, the authors conducted a mapping according to a systemic perspective of the processes involved in the context of manufacturing and distribution of certified Serra da Estrela cheese. Numerous methods were used throughout the process, such as a systemic design analysis, and techniques derived from ethnographic methods, which led to the collection of data in the field and consequently provided the immersion of the researcher in genuine work situations. Critical points were identified and emphasized in the systemic map with the purpose of encouraging initiatives to address and overcome the gaps and inefficiencies detected. The systemic design analysis triggered the development of design work. Observations following an ethnographic approach identified ergonomic risks in cheese making during the process of cutting excess chips, fostering the emergence of musculoskeletal disorders at the wrist. A tool that fits best to the task at hand was developed. A prototype of the new tool enabled collecting feedback from use in the work context, in order to inform product development. The domains of agricultural production and microbiology, considering the specific microorganisms developed trough the ripening process of the cheese, turned out to be aspects of high importance for the issue under focus, contributing to a broader understanding of the ripening process and its risks, simultaneously improving the efficiency and success of cheese production. If it were not for the systemic analysis, which served as a link between the boundaries of distinct domains such as the risk of microorganism contamination, ergonomics, energy efficiency, legislation and regulation policies, transportation challenges and economic viability, approached throughout the research. Simultaneously creating bridges between them, the various problems might not have been detected in the first place, as they are usually addressed in specialized disciplines, predetermined by the restrictions of each specific area of knowledge. As a consequence of the development of this research, which was based on an analysis that sought to establish possible connections between various disciplines and tried to constantly maintain a holistic perspective, making new connections and observing the issues from a new angle, apart from the already established methodologies. All this allowed to lay out the seeds for the development of a plan to tackle the critical points identified by the systemic analysis reported in this paper.

The aims of this study are to determine the oral health status of a rare sample of 19th-century migrant settlers to South Australia, how oral conditions may have influenced their general health, and how the oral health of this group compares with contemporaneous samples in Australia, New Zealand, and Britain. Dentitions of 18 adults and 22 subadults were investigated using non-destructive methods (micro-CT, macroscopic, radiographic). Extensive carious lesions were identified in 17 adults and 4 subadults, from this group 1 subadult and 16 adults had antemortem tooth loss. Sixteen adults showed evidence of periodontal disease. Enamel hypoplastic (EH) defects were identified in 14 adults and 9 subadults. Many individuals with dental defects also had skeletal signs of co-morbidities. South Australian individuals had the same percentage of carious lesions as the British sample (53%), more than other historic Australian samples, but less than a contemporary New Zealand sample. Over 50% of individuals from all the historic cemeteries had EH defects suggesting systemic health insults during dental development were common during the 19th century. The overall oral health of the South Australian settlers was poor but, in some categories, (tooth wear, periapical abscess, periodontal disease), better than the other historic samples.

Although man is still rapidly evolving, he has not co-evolved with all of the modern chemicals made by man, including those in cosmetic products. Care must be taken when formulating products so that commonly used ingredients, such as polyethylene glycol, can be substituted with safer ingredients to which man has adapted and that will not cause irritation and inflammation. This is especially important given that induction of skin inflammation will cause systemic inflammation. A review of the literature and of commercially available products was made to highlight techniques and products that remediate inflammation or induce inflammation. Many skin care products contain chemicals that induce irritation and inflammation that may lead to chronic, systemic inflammation. Well studied natural products, especially skin identical chemicals, may offer an advantage compared to recent man-made chemicals in cosmetic and topical formulations and help to reduce skin inflammation as well as skin derived systemic chronic inflammation.

The use of fluoride (F^-) for decreasing the prevalence and incidence of tooth decay was the greatest worldwide preventive public health measure of the 20th century. There have been controversial reports about the benefits of the use of F^-, because in small amounts it helps prevent dental caries, but in high concentrations it can be potentially toxic and harmful to dental and systemic health. Since the mid-20th century, F^- has been studied by toxicologists, looking at its deleterious effects in human populations. During the last decade, the interest on the undesirable effects has resurfaced because of the knowledge that it interacts with the cellular system, even in low doses, with a very small safety margin. Acute ingestion of toxic amounts of fluoride can cause corrosive gastric mucosa injury. Also respiratory effects such as bleeding, pulmonary edema, tracheostomy and shortness of breath, have been observed in individuals who inhale hydrogen fluoride. Some researchers had shown that F^- is an oxidizing agent and a well-known reversible enzymatic inhibitor that interferes with the enzyme activity of at least 80 proteins, can altered the intracellular redox equilibrium, lipid peroxidation, as well as, alteration in the gene expression and apoptosis induction. The primary purpose of this review is to examine findings of the action of inorganic F^-, and an overview of hard and soft tissue disturbances, known as fluorosis. The goal of this review is to enhance understanding of the mechanisms by which F^- affects cells with an emphasis on human tissue-specific events.

Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease, and organ manifestations, such as lupus nephritis (LN) or skin disease, may be refractory to standard treatment. Therefore, new agents are required to allow for a more personalized therapeutic approach. Recently, several new therapies have been approved internationally, including voclosporine for LN and anifrolumab for moderately to severely active SLE. Here, we report a case of SLE with a predominant and refractory cutaneous manifestation despite treatment with glucocorticoids, hydroxychloroquine, mycophenolate mofetil, and belimumab. Belimumab was switched to anifrolumab, and the patient responded quickly after two infusions (eight weeks) with a reduction of the Cutaneous Lupus Assessment and Severity Index (CLASI) from 17 to 7. In addition, we review the available clinical trial data for anifrolumab with a focus on cutaneous outcomes. Based on phase II and III clinical trials investigating the intravenous administration, a consistent CLASI improvement was observed at 12 weeks. Interestingly, in a phase II trial of subcutaneous anifrolumab application, CLASI response was not different from placebo at 12 weeks but numerically different at 24 and 52 weeks, respectively. Thus, anifrolumab emerges as an attractive new therapeutic option suggesting a possible domain-based approach.

Background: We previously developed a refined, tumor selective adenovirus, Ad5NULL-A20, har-boring tropism ablating mutations in each major capsid protein, to ablate all native means of infection. We incorporated a 20mer peptide (A20) in the fiber knob for selective infection via αvβ6 integrin, a marker of aggressive epithelial cancers. Methods: To ascertain the selectivity of Ad5NULL-A20 for αvβ6 positive tumor cell lines of pancreatic and breast cancer origin, we performed reporter gene and cell viability assays. Biodistribution of viral vectors in mice harboring xenografts with low, medium, and high αvβ6 levels was quantified by qPCR for viral genomes 48 hours post intravenous administration. Results: Ad5NULL-A20 vector transduced cells in an αvβ6 selective manner, whilst cell killing me-diated by oncolytic Ad5NULL-A20 was αvβ6 selective. Biodistribution analysis following intrave-nous administration into mice bearing breast cancer xenografts demonstrated that Ad5NULL-A20 resulted in significantly reduced liver accumulation coupled with increased tumor accumulation compared to Ad5 in all three models, with tumor: liver ratios improved as a function of αvβ6 expression. Conclusions: Ad5NULL-A20 based virotherapies efficiently target αvβ6 integrin positive tumors following intravenous administration, validating the potential of Ad5NULL-A20 for systemic ap-plications, enabling tumor selective overexpression of virally encoded therapeutic transgenes.

Psoriasis is a chronic, multisystem, inflammatory disease. The typical clinical cutaneous manifestation of psoriasis is scaly erythema or plaque, limited or widely distributed. However, psoriasis is far beyond the skin involvement and provides many challenges, including associated comorbidities. In this review, we classify psoriasis as cutaneous and systemic psoriasis, according to the clinical diversity and associated comorbid diseases, and recommend classification criteria for psoriasis. The key objective of this novel classification is to raise awareness of the complexity of this multifaceted disease and help to better understand and manage this complex disease comprehensively.

Background: To assess the prevalence of Hypertension (HTN) in Burning Mouth Syndrome (BMS) patients and to investigate its relationship with sociodemographic factors, pain and the psychological profile. Methods: A case-control study was conducted by enrolling 242 BMS patients and 242 controls matched for age and gender. Sociodemographic and clinical characteristics were recorded, and all the participants completed the numeric rating scale (NRS), the short-form of the McGill pain questionnaire (SF-MPQ), the Hamilton rating scale for anxiety and depression (HAM-A, HAM-D), the Pittsburgh sleep quality index (PSQI) and the Epworth sleepiness scale (ESS). Results: The BMS patients presented a statistically significant higher prevalence of HTN compared to the controls (55% versus 33.5%; p-value: <.001**) and higher median scores of the NRS, SF-MPQ, HAM-A, HAM-D, PSQI and ESS (p < .001**). Multivariate regression analysis in the BMS patients indicated positive correlations between HTN and age, systemic diseases, drug consumption and anxiety (p-value: <.001**) and these predictors were responsible for 11.3% of the HTN variance in the BMS patients, when considered together. Conclusions: The prevalence of HTN was significantly higher in the BMS patients, since ageing, the presence of comorbidities, drug consumption and anxiety were potential predictors. Further studies are needed to better investigate the relationship between BMS and HTN.

Systemic sclerosis is an autoimmune disease characterized by organ fibrosis and vasculopathy. Almost all patients suffer from Raynaud’s phenomenon (RP). Currently, several imaging techniques are available; nailfold video capillaroscopy (NVC) is the most widely available, but flow quantification is not possible with NVC. Novel imaging techniques are of interest in this population. We performed a single-center feasibility study using Micro Vascular Imaging (MVI) as a novel imaging technique for flow quantification of small fingertip vessels. We compared a group of 20 healthy controls (HCs) with 20 Systemic Sclerosis (SSc) patients. In HCs, flow measurements assessed with MVI were statistically significantly higher in individual fingers and combined for all fingers (p<0.0001). As a cut-off value to discriminate HCs from SSc, a peak systolic (PS) flow velocity of <6.9 cm/s and an end-diastolic (ED) flow velocity of <2.68 cm/s was determined. Test characteristics for PS flow velocity showed moderate sensitivity (0.69, 95% CI 0.58-0.78) but high specificity (0.88, 95% CI 0.79-0.93). Similar test characteristics for ED flow velocity were obtained. The optimal cut-off point was estimated at <2.68 cm/s, sensitivity was moderate (0.65, 95% CI 0.53-0.75), specificity was 0.80 (95% CI 0.70-0.87). Here, we present the first study on the use of MVI to assess blood flow in the fingertips with high specificity in SSc patients. Future studies need to investigate correlations with the risk for organ complications, such as digital ulcers or pulmonary arterial hypertension.

Various studies have addressed the role of neutrophils in cancer wherein the focus has been drawn on the elevated neutrophil count in blood or at tumor loci. However, cancer has a systemic impact which targets various organs thus challenging the overall physiology of the host. So, it is worthwhile to explore whether and how neutrophils contribute to systemic deterioration in cancer. To discern the systemic role of neutrophils, we monitored their number and function at different stages of tumor growth in Dalton’s lymphoma mice model. Notably, we observed a gradual increase in neutrophil count in blood and their infiltration in vital organs of tumor bearing mice. In parallel, we observed damaged histoarchitecture with significant alterations in biochemical parameters that aggravated with tumor progression. We next examined systemic impact of neutrophil by assessing neutrophil elastase, myeloperoxidase, and matrix metalloproteinases (MMP-8 and MMP-9) wherein we found their upregulated expression and activity in tumor condition. Taken together, our results demonstrate high infiltration and hyperactivation of neutrophils which possibly account for gradual systemic deterioration during cancer progression. Our findings thus implicate neutrophils as a potential therapeutic target that may help to reduce the overall fatality rate of cancer.

The human oral microbiome refers to an ecological community of symbiotic and pathogenic microorganisms found in the oral cavity. The oral cavity is a suitable environment that provides various kinds of biological niches such as teeth, tongue, and oral mucosa. The oral cavity is the gateway between the external environment and the human body, maintaining oral homeostasis, protecting the mouth, and preventing disease. On the flip side, the oral microbiome plays an important role in triggering, development, and progression of oral and systemic diseases. Currently, disease diagnosis through the analysis of the human oral microbiome has been realized with the recent development of innovative detection technology, and is overwhelmingly promising compared to the previous era. It has been found that patients with oral diseases and systemic diseases have variations in the oral microbiome compared to normal subjects. This narrative review provides insight into the pathophysiological role that oral microbiome plays in influencing oral and systemic diseases, and updates the knowledge related to the oral microbiome over the past 30 years. A wide range of updates was provided with the latest knowledge of the oral microbiome to help researchers and clinicians in both academic and clinical aspects. The microbial community information can be utilized in non-invasive diagnosis and help develop a new paradigm in precision medicine, which will benefit human health in the era of post-metagenomics.

The standard care for metastatic breast cancer (MBC) is systemic therapies with imbrication of focal treatment for symptoms. Recently, thanks to implementation of radiological and metabolic exams and development of new target therapies, oligometastatic and oligoprogressive settings are even more common, paving the way to a paradigm change of focal treatments role. In fact, according to immunophenotype, radiotherapy can be considered with radical intent in these settings of patients. The aim of this literature review is to analyse available clinical data on prognosis of bone metastases from breast cancer and benefits of available treatments for developing a practical guide for clinicians.

Focusing on the implementation of the 2003 UNESCO Convention for the Safeguarding of the Intangible Cultural Heritage (ICH), this article highlights the fact that the cataloging procedures, the way records are stored, and the metadata models used during recording, visualization, and storage of ICH expression elements, vary from country to country. Especially in these days of great uncertainty, war conflicts, and the systemic risks that may arise, it is vital to clarify what techniques will be used in the storage of ICH to ensure its unhindered preservation and dissemination over time across the globe. Using the systems thinking approach indicated for cases of great complexity, the process followed in Greece for depositing a new element in its local repository is described to demonstrate the need for a well-defined process by UNESCO, which must be followed worldwide and which has not been defined so far. What are the potential challenges not only in determining the type of data but also in choosing the best metadata model to use in each case when capturing this data? What technologies must be used for storing digital cultural heritage in such a way that will preserve it over time, defying physical and technological hazards? The article finally suggests how Blockchain Technologies (BT) can be effectively used to store the global ICH and ensure its continuity in future generations by creating a decentralized worldwide network between the heritage stakeholders.

Background: Neuroendocrine tumors (NET) are a rare group of epithelial neoplasm present in gastrointestinal tract (GI) (67.5%), bronchopulmonary tree (25.3-30%), and in 15% of cases, the primary sites cannot be identified. Although endoscopic screening, improvement in pathological techniques, and early detection have shown improvement in NET survival rates, the prognosis of advanced, metastatic, and poorly differentiated NET is very poor. In this study, we aimed to evaluate the effect of Gastrointestinal and pancreatic (GEPs) NETs grade on overall survival. Method: We searched observational studies describing the overall survival or prognostic factors of primary GEP NETs from May 2011 -May 2021 following PRISMA guidelines. Studies describing the effect of primary grade 3 GEP NETs on overall survival were included. Meta-analysis was performed, and pooled hazard ratio and their 95% confidence interval (95% CI) were obtained. The forest plots were created using random-effects models and sensitivity analysis was performed to account for the heterogeneity. Results: Seven studies with 7692 confirmed patients were included. In our meta-analysis grade 3 GEP NET were associated with higher odds of poor survival (pooled HR: 2.73; 95% CI: 1.36–5.47; p = 0.005), with 92% heterogeneity between studies (p < 0.0001). To account for heterogeneity, sensitivity analysis was performed by removing two outlying studies (Fathi et al. and Foubert et al.) on funnel plots. The results after sensitivity analysis did not change and still showed significant association of grade 3 with poor survival (pooled HR: 4.53; 95% CI: 3.54–5.78; p < 0.00001), with no heterogeneity between studies (p = 0.72; I2 = 0%). Conclusion: Our meta-analysis found that grade 3 GEP NETs are associated with poor survival and additional future studies are needed to identify other risk factors associated with poor survival in GEP NETs to improve mortality.

Cancer has emerged as a systemic disease which targets various organs thus challenging the overall physiology of the host. Recently, we have shown that hyperactive neutrophils infiltrate various organs of tumor bearing host and contribute significantly to gradual systemic deterioration. Therefore, taming neutrophils via potent immunomodulators could be an appropriate therapeutic approach in regulating systemic damage. Tinospora cordifolia (TC), an Ayurvedic panacea, is known for its immense medicinal values in traditional literature and recent reports have also documented its strong immunomodulatory potential. However, whether TC can regulate neutrophils to exert its therapeutic effectiveness has not been deciphered so far. To discern this, we utilized murine model of Dalton’s Lymphoma (DL) wherein, we have earlier reported heightened infiltration of neutrophils and their hyperactivation. Our findings showed that TC treatment significantly reduced neutrophil count in peripheral blood and their infiltration in vital organs of tumor bearing host. Further, it ameliorated neutrophil hyperactivation by down regulating the expression of its key cargoes including neutrophil elastase (NE), myeloperoxidase (MPO), MMP-8, MMP-9 and cathepsin G (CSTG) at early and mid stage of tumor growth. In addition, TC treatment prevented histopathological alterations and restored the normal serum enzyme levels at different stages of tumor growth. Importantly, TC treatment also showed significant reduction in tumor burden which was accompanied by a remarkable increase in survival of the tumor-bearing mice. We conclude that Tinospora cordifolia could limit systemic damage via regulating neutrophil infiltration and hyperactivation which can further lead to cancer control at both prophylactic and therapeutic level.

Objectives: To determine the prevalence of controlled systemic hypertension and its associated risk factors among the hypertensive patients who attended the clinic at Mbeya Zonal Referral Hospital in Tanzania. Methods: A descriptive cross-sectional quantitative study was used determine the prevalence of co to 252 hypertensive patients were recruited during clinic visit from September to November 2020 and participant was randomly selected interviews using structured self-administered questionnaires. Data was analyzed using chi square test to find the risk factors associated with controlled hypertension. Results: Among 252 participants, 94(39.7%) individuals with controlled hypertension giving the prevalence of controlled hypertension. The proportion of females with controlled hypertension was slightly higher than male (49 females to 45 males). The prevalence of uncontrolled hypertension was 152(60.3%) participants. The prevalence of controlled hypertension was higher among patients who have regular clinic visit (p< .05) and have daily adherence to their anti-hypertensive medication. A similar trend was observed among participants without financial challenges to attend clinic, short duration of illness, higher level of education and there was no association between age, sex, marital status, smoking, alcohol consumption, having health insurance and having chronic illness. Conclusion: Prevalence of controlled hypertension is higher among patients who have regular clinic visit and have daily adherence to their anti-hypertensive medication. Also, it is higher among participants without financial challenges to attend clinic so they can have regular clinic visit and checkup. Reinforcement on regular drug intake and clinic visit, good nutrition and reduced salt intake and modifying lifestyles of patient with hypertension is important.

In this study, a dynamic mixture copula is used to estimate the marginal expected shortfall in the South African insurance sector. While other studies assumed nonlinear dependence to be static over time, our model capture time-varying nonlinear dependence between institutions and the market. In order to capture time-varying nonlinear dependence, the generalized autoregressive score (GAS) is used to model the dynamic copula parameters. Furthermore, our study implements a ranking that expresses to what degree individual insurers are systemically important in South Africa. We use daily stock return of five South African insurers listed in the Johannesburg Stock Exchange (JSE) from November 13, 2007 to June 15, 2020. We find that Sanlam and Discovery contribute the most to systemic risk, while Santam is found to be the least contributor to the overall systemic risk in the South African insurance sector. Our findings would be of paramount importance for the South African regulators as they would be informed that not only banks are systemically important, but some insurers also are systemically important financial institutions. Hence, stricter regulation of these institutions in the form of higher capital and loss absorbency requirements could be required based on the individual business activities undertaken by the company.

The subject of this article is the dynamics of water in a soil pedostructure sample whose internal environment is subjected to a potential gradient created by the departure of water through surface evaporation. This work refers entirely to the results and conclusions of a fundamental theoretical study focused on the molecular thermodynamic equilibrium of the two aqueous phases of the soil pedostructure. The new concepts and descriptive variables of the hydro-thermodynamic equilibrium state of the soil medium, which have been established at the molecular level of the fluid phases of the pedostructure (water and air) in a previous article, are recalled here in the systemic paradigm of hydrostructural pedology. They allow access to the molecular description of water migration in the soil and go beyond the classical mono-scale description of soil water dynamics. We obtain a hydro-thermodynamic description of the soil's pedostructure at different hydro-functional scale levels including those relating to the water molecule and its atoms. The experimental results show a perfect agreement with the theory, validating at the same time the systemic approach which was the framework.

The La Oroya metallurgical complex reveals a process of structural or power pathology, where economic and environmental social policies lead to a citizenry without systemic freedom, characterized by environmental contamination (PAMA executed on average 67%, some processes with 0%) and sanitary (plumbosis 8.39 to 10.28 μg / dL), the economic dependence of this industry is also observed, which caused the weakening of the communities to maintain autonomy over their own destinies.The Doe Run Peru, operated the metallurgical complex, creating added value to the extractive-export chain of mineral concentrate, but also took advantage of the legal loopholes, the little coordination between the State institutions and the little authority of the supervisory institutions to get the most out of it, complying with the law in some cases, but without moral quality in some others, such as health in the oroinos.Government institutions must have strong links that provide a normative framework with prospects with sustainable development, where the beneficiary is society and not only certain interest groups. The economic benefits of the metallurgical complex operation are multiple, which begin with labor, the purchase and sale of materials and services, the collection of taxes and energy.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by a broad array of clinical signs. In this study, we aimed to use intravenous immunoglobulins (IVIG), called intacglobin, as a monotherapy to manage SLE in three patients. Laboratory investigations for SLE diagnosis were performed, including the detection of anti-nuclear antibodies (ANA) and SLE confirmation by detecting high titers of anti-dsDNA antibodies. C3 and C4 serum levels were assessed, as well as the determination of immunoglobulins. The SLEDAI score was measured to determine whether a significant degree of disease activity existed and as a prognostic value. The evaluation of any chest infection was performed by chest-X-ray. The patients were treated with five–ten g/day of IVIG for six consecutive days, followed by five–ten g/month. Immunological evaluation demonstrated that patients presented with a flare of SLE with high titers of ANA and anti-dsDNA antibodies, low C3 and C4, and elevated immunoglobulin levels. The SLEDAI score falls from 10 to below 3, and chest infections in some patients are cleared up. The postulated mechanisms of action of IVIG demonstrated that it could be used as an immunosuppressor, immunomodulator, and antimicrobial agent in patients with SLE.

Stroke is one of the leading cause of adult disability and the second leading cause of death worldwide. The immune system actively participates in the pathobiological process of AIS, during the index event and during the repair process despite the limited attention drawn to this aspect in the existing stroke guidelines globally. The similar clinical course and similar circulating innate and adaptive immune cell counts in AIS and COVID-19 has created a renewed interest in these easily available biomarkers innate and adaptive immunological changes in AIS with potential diagnostic, prognostic, and therapeutic implications. The current scoping review aimed to assess the significance of circulating neutrophil and lymphocyte counts and their ratio (NLR) in AIS and explore their association with post-stroke recovery trajectory. The Arksey and O'Malley methodological framework was employed to review the published papers on the neutrophil-lymphocyte ratio (NLR) and AIS in late November 2020. Only studies published in English from 2000-2020 were included in this scoping review. Fifty-three published papers were reviewed. This review's key finding is that a canonical inflammatory response occurs in AIS just as in the case of COVID-19 and neurological involvements well described in the recent literature. An excessive circulating innate immune cells (neutrophils) and reduced circulating adaptive immune cells (lymphocytes ) are associated with poorer outcomes during the acute interventions ( reperfusion therapies) as well as the recovery trajectory. Main representatives of innate and adaptive immunity follow a canonical course in AIS and COVID-19. Exaggerated circulating innate ( elevated neutrophils and elevated NLR) and reduced adaptive immune response (lymphopenia) correlate with the worse outcome in AIS and COVID-19. This scoping review's findings make the strongest case for a systems biology-based approach to the standard operating procedures in stroke care urgently.

Interleukin-33 (IL-33), a member of the IL-1 cytokine family has been recently associated with the development of autoimmune diseases, including SLE. IL-33 is an alarmin and a pleiotropic cytokine that affects various types of immune cells via binding to its receptor, ST2. In this study, we determine the impact of intraperitoneal IL-33 treatments in young lupus, NZB/W F1 mice. Mice were treated from the age of 6 to 11 weeks. We then assessed the proteinuria level, renal damage, survival rate, and anti-dsDNA antibodies. The induction of regulatory B (Breg) cells and changes in gene expression were also examined. In comparison to the control group, young NZB/W F1 mice administered with IL-33 had a better survival rate as well as reduced proteinuria level and lupus nephritis. IL-33 treatments significantly induced IgM anti-dsDNA antibody, IL-10 expressing Breg cells, and alternatively induced M2 macrophage gene signatures. These results imply that IL-33 exhibit regulatory roles during lupus onset via the expansion of protective IgM anti-dsDNA as well as regulatory cells such as Bregs and M2 macrophages.

Pre-diabetes is a serious health condition where blood sugar levels are higher than normal, but not high enough yet to be diagnosed as type 2 diabetes. Pre-diabetes puts one at an increased risk of developing type 2 diabetes and heart disease Methodology: A cross-sectional study was carried out on 384 patients aged 20-70 years old, attending the dental clinics to assess the risk for diabetes, using the FINDRISC questionnaire, HbA1c blood test and a periodontal examination. Results: The mean age of participants was 38.90±10.74. 32.3% were categorized as no risk, 46.6% low risk, while 19% and 2.1% moderate and high risk of developing diabetes respectively. Tests for serum HbA1c Level showed 46.1 % had normal HbA1c followed by 18.0% and 3.6 % were pre-diabetic and diabetic respectively. 19.3% of participants had periodontal pockets measuring more than 4mm and 15.9% measuring more than 6mm. Conclusion: The study has proven to be useful in identifying patients at high-risk of developing diabetes. Controlling and managing periodontal disease could be a new aspect to include in the standards for diabetes care. Dental settings could be a successful platform to carry out the screening and risk stratification of pre-diabetic patients.

Background: To evaluate the effect of systemic erythropoietin, as well as oral steroids, in the management of recent onset non-arteritic anterior ischemic optic neuropathy (NAION). Method: Ninety-nine eyes of 99 patients diagnosed with NAION within 5 days of onset were included in this single masked randomized clinical trial. Thirty-four patients were randomized into group 1 (systemic erythropoietin), group 2 (oral steroids), and group 3 (control). Group A received 10,000 units of erythropoietin twice a day for three days. Group B received oral prednisone 75 mg daily for two weeks followed by a tapering dose (70 mg for 5 days, 60 mg for 5 days, and 5 mg reductions thereafter every 5 days). Functional and structural outcomes were analyzed at 3 and 6 months following treatment. Best corrected visual acuity (BCVA) was the main outcome measure, and mean deviation (MD) of visual field (VF) test and peripapillary retinal nerve fiber layer thickness (PRNFLT) were secondary outcome measures. Results:The mean BCVA (±SD) at the time of presentation was 1 ± 0.56, 1.01 ± 0.6, and 0.94 ± 0.47 logMAR in groups A, B, and C, respectively (P = 0.140); corresponding values were 0.72 ± 0.45, 0.83 ± 0.46, and 0.78 ± 0.4 logMAR (P = 0.417), and at 6-month follow-up, they were 0.70 ± 0.44, 0.73 ± 0.35, and 0.75 ± 0.39 logMAR, respectively (P = 0.597). Fifty-five percent of patients in group A vesus 34.3% in group B, and 31.2% in group C had an improvement of at least 3 lines in the BCVA values at the 6th-month follow-up visit. (P= 0.04) The mean deviation (MD) at the time of presentation was 19.67 ± 6.2, 20.83 ± 4.83, and 18.94 ± 6.92 decibels (db), respectively (P= 0.483).The corresponding values at month 3 were 18.22 ± 7.5, 19.82 ± 7.15, and 17.65 ± 7.22 db, (P = 0.848); and at month 6 they were 16.56 ± 7.08, 18.15 ± 6.57, and 15.9 ± 5.97 db, respectively. (P = 0.699) PRNFLT at presentation was 189 ± 58, 193 ± 64, and 199 ± 62 micrometers, respectively (P = 0.779), which decreased to 110 ± 45, 127 ± 37, and 119 ± 37 at month 3 (P = 0.423). The corresponding values for month 6 were 88 ± 12, 74 ± 25, and 71 ± 18, respectively (P = 0.041). Conclusion: The findings of our study indicate the beneficial effects of systemic erythropoietin in preserving the function and structure of the optic nerve in recent onset NAION.

The human body supports the growth of a wide array of microbial communities in various niches, such as the oral cavity, gastro-intestinal and urogenital tracts and on the surface of the skin. These host associated microbial communities include yet-un-cultivable bacteria and are influenced by various factors. Together, these communities of bacteria are referred to as the human microbiome. Human oral microbiome consists of both symbionts and pathobionts. Deviation from symbiosis among the bacterial community leads to “dysbiosis”—a state of community disturbance. Dysbiosis occurs due to many confounding factors that predispose to a shift in the composition and relative abundance of microbial communities. Dysbiotic communities have been a major cause for many microbiomes related systemic infections. Such dysbiosis is directed by certain important pathogens called the “keystone pathogens” that could modulate community microbiome variations. One such persistent infection is oral infection, mainly periodontitis, where a wide array of causal organisms has been implied to systemic infections such as cardio vascular disease, diabetes mellitus, rheumatoid arthritis and Alzheimer’s disease. The keystone pathogens co-occur with many yet-cultivable bacteria and their interactions lead to dysbiosis. This has been the focus of recent research. While immune evasion is one of the major modes that lead to dysbiosis, new processes and new virulence factors of bacteria have been shown to be involved in this important process of that determine disease or health state. This review focuses on such dysbiotic communities, their interactions and their virulence factors that predispose the host to other systemic implications.

Disruptive technologies can be conceptualized in different ways. Depending on how they are conceptualized, different ethical issues come into play. This article contributes to a general framework to navigate the ethics of disruptive technologies. It proposes three basic distinctions to be included in such a framework. First, emerging technologies may instigate localized “first-order” disruptions, or systemic “second-order” disruptions. The ethical significance of these disruptions differs: first-order disruptions tend to be of modest ethical significance, whereas second-order disruptions are highly significant. Secondly, technologies may be classified as disruptive based on their technological features or based on their societal impact. Depending on which of these classifications one adopts and takes as the starting point of ethical inquiry, different ethical questions are foregrounded. Thirdly, the ethics of disruptive technology raises concerns at four different levels of technology assessment: the technology level, the artifact level, the application level, and the society level. The respective suitability of approaches in technology ethics to address concerns about disruptive technologies co-varies with the respective level of analysis. The article clarifies these distinctions, thereby laying some of the groundwork for an ethical framework tailored for assessing disruptive technologies.

Background. Neoplastic diseases and infections have become the leading causes of death in SLE in recent decades. Cancers and infections were also precipitating factors in the development of catastrophic APS. Case summary. We describe two patients: one of them had definite antiphospholipid syndrome (APS) and melanoma and the other had definite systemic lupus erythematosus (SLE) with APS, melanoma, infiltrative tuberculosis and severe Herpes Zoster (HZ). Management of patients with SLE concurrent with APS is a rather difficult task in rheumatology practice. In addition to kidney damage and cardiovascular disease, infections and malignancies are a significant cause of death in this cohort. The risk of malignancy in SLE is of considerable interest, since the immune and genetic pathways underlying the pathogenesis of this disease, as well as the immunosuppressive therapy, can significantly alter the risk. Both patients still had reliable APS, confirmed by triple-positive aPL. Both were at high risk of thrombosis. Patients ' adherence to treatment with direct oral anticoagulants and relapse of thrombosis on the background of rivaroxaban were noted. Conclusion. The cases where cancer or tuberculosis develops in the presence of rheumatic diseases are not so common and complicate the possibilities of therapeutic approaches, limiting the use of drugs that are not regulated by clinical recommendations.

Systemic lupus erythematosus (SLE) is a heterogenous autoimmune disease. While its etiology remains elusive, current understanding suggests a multifactorial process with contributions by genetic, immunologic, hormonal, and environmental factors. A hypothesis that combines several of these factors proposes that genomic elements, the L1 retrotransposons, are instrumental in SLE pathogenesis. L1 retroelements are transcriptionally activated in SLE and produce two proteins, ORF1p and ORF2p, which are immunogenic and can drive type I interferon (IFN) production by producing DNA species that activate cytosolic DNA sensors. In addition, these two proteins reside in RNA-rich macromolecular assemblies that also contain well-known SLE autoantigens like Ro60. We surmise that cells expressing L1 will exhibit all the hallmarks of cells infected by a virus, resulting in a cellular and humoral immune response similar to those in chronic viral infections. However, unlike exogenous viruses, L1 retroelements cannot be eliminated from the host genome. Hence, dysregulated L1 will cause a chronic, but perhaps episodic, challenge for the immune system. The clinical and immunological features of SLE can be largely explained by this model. Here we review the support for, and the gaps in, this hypothesis of SLE and its potential for new diagnostic, prognostic, and therapeutic options in SLE.

RNA interference (RNAi) has become a widely utilised method to study gene function, yet despite this, many of the mechanisms surrounding RNAi remain elusive. The core RNAi machinery is relatively well understood, however many of the systemic mechanisms, particularly double stranded RNA (dsRNA) transport, are not. Here, we demonstrate that dsRNA binding proteins in the serum contribute to systemic RNAi, and may be the limiting factor in RNAi capacity for species such as spiny lobsters where gene silencing is not functional. Incubating serum from a variety of species across phyla with dsRNA led to a gel mobility shift in species where systemic RNAi has been observed, with this response being absent in species where systemic RNAi has never been observed. Proteomic analysis suggested lipoproteins may be responsible for this phenomenon, and may transport dsRNA to spread the RNAi signal systemically. Following this, we identified the same gel shift in the slipper lobster Thenus australiensis and subsequently silenced the insulin androgenic gland hormone, marking the first time RNAi has been performed in any lobster species. These results pave the way for inducing RNAi in spiny lobsters, and better understanding the mechanisms of systemic RNAi in Crustacea, as well as across phyla.

Cryptocurrencies like Bitcoin rely on a proof-of-work system to validate transactions and prevent attacks or double-spending. A new proof-of-work is introduced which seems to be the first number theoretic proof-of-work unrelated to primes: it is based on a new metric associated to the Collatz algorithm whose natural generalization is algorithmically undecidable: the inflation propensity is defined as the cardinality of new maxima in a developing Collatz orbit. It is numerically verified that the distribution of inflation propensity slowly converges to a geometric distribution of parameter $0.714 \approx \frac{(\pi - 1)}{3}$ as the sample size increases. This pseudo-randomness opens the door to a new class of proofs-of-work based on congruential graphs.

Stroke represents one of the most important causes of morbidity ( eighty million patients with disabling of ongoing effects of stroke at a given time, globally) and mortality (the second leading cause of death) worldwide. Innovative systems biology-based approach is likely to increase the understanding of the underpinning of acute stroke promise to enhance stroke prevention, acute treatment, and neurorehabilitation. Recent growing body of evidence with shared pathobiology with COVID-19 and the critically important role of inflammation in the context of stroke points to far-reaching consequences of acute stroke, just as in the case of COVID-19 ( post-acute event issues as well as long term issues ) . So far, stroke typically defined by late-appearing disease manifestation by the range of stroke subtypes as defined by the WHO or American Stroke Association. This definition neglects the underlying pathobiological mechanisms such as low-grade chronic inflammation and already compromised vascular system. Diseases such as stroke is hardly a simple result of a single problem, but rather a complex cascade of pathobiological processes and interactions in a complex biochemical environment. The evidence of changes in innate immunity and adaptive immunity during the index event of acute stroke and recovery over next 3-12 months can be easily elicited with simple bedside blood tests such as neutrophil-lymphocyte ratio (NLR) with well over 300 published papers including several systematic reviews and meta-analyses confirming this. Global standard operating procedures (SOP) of stroke care dictated by the national and international stroke guidelines at present. It is imperative to explore the evidence of systems biology approach in current stroke guidelines. This is likely to be a key turning point in managing stroke across the continuum (prevention, management of acute event and rehabilitation).

The oral cavity is the gateway for microorganisms into your body where they disseminate not only to the directly connected respiratory and digestive tracts, but also to the many remote organs. Oral microbiota, traveling to the end of the intestine and circulating our body through blood vessels, not only affect a gut microbiome profile, but also many systemic diseases. By gathering information accumulated from the era of focal infection theory to the age of revolution in microbiome research, we propose a pivotal role of “leaky gum”, as an analogy of “leaky gut”, to underscore the importance of the oral cavity in systemic health. The oral cavity has unique structures, the gingival sulcus (GS) and the junctional epithelium (JE) below the GS, which are rarely found anywhere else in our body. The JE is attached to the tooth enamel and cementum by hemidesmosome (HD), which is structurally weaker than desmosome and is thus vulnerable to microbial infiltration. In the GS, microbial biofilms can build up for life, unlike the biofilms on the skin and intestinal mucosa that fall off by natural process. Thus, we emphasize that the GS and the JE are the weakest leaky point for microbes to invade human body, making the leaky gum just as important as, or even more important than, the leaky gut.

The nature of the sustainability crisis is characterized by high levels of complexity, thus it is not amenable to be approached from the linearity or reductionist paradigm. Emergence is a multilevel phenomenon that is characterized by qualitative novelty and is recognized as an important attribute of complex systems produced by self-organized processes, unveiled from a holistic stance. This conceptual-analytical article explores the emergence phenomenon and questions whether it can be a way of enhancing the solution process to meet the sustainability challenges. Emergent properties or behaviors emerge only when the system parts interact in a wider whole. Moreover, a systemic approach is proposed as an intermediary component in the process of emergence of creative and wise solutions to the wicked problems of unsustainability. This requires observation and entails analyzing open systems as a whole and recognizing the impact of traversing macro- and micro- scales on causal and creative emergence. The study also emphasizes synergies between emergence and creativity aimed at sustainability. Sustainable development requires leapfrogging past conventional practices, in an accelerated way, and the emergence phenomenon at play between systems levels, coupled with purposefully structured creative processes, holds the potential for catalyzing sustainable development efforts.

Systemic lupus erythematosus (SLE) myocarditis is presumed to be rare but associated with ad-verse outcomes. If SLE diagnosis has not previously been established, its clinical presentation is often unspecific and difficult to recognize. Furthermore, there is a lack of data in the scientific literature regarding myocarditis and its treatment in systemic immune-mediated diseases, leading to its late recognition and undertreatment. We present the case of a young woman whose first lupus manifestations included acute perimyocarditis, among other symptoms and signs that provided clues to the diagnosis of SLE. Transthoracic and speckle tracking echocardiography were helpful in detecting early abnormalities in myocardial wall thickness and contractility while waiting for cardiac magnetic resonance (CMR). Since the patient presented with acute decompensated heart failure (HF), HF treatment was promptly started in parallel with immunosuppressive therapy, with a good response. In the treatment of myocarditis with heart failure, we were guided by the echocardiographic findings, biomarkers for myocardial injury N-terminal pro b-type natriuretic peptide (NT-proBNP) and hs-troponin I, biomarkers for systemic inflammation erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and biomarkers for SLE disease activity (Complement C)3, C4, and anti-dsDNA levels.

In this study, we wanted to discuss the acute coronary syndromes in the pregnant womens which are very important for life ofthe fetus. Spontaneous coronary artery dissection and management, which is the most common cause of acute coronary syndrome in pregnant women is also discussed. About 300 articles were examined and 35 articles which published in high quality journals with high level of evidence were chosen and this review was prepared.

Washing hands, social distancing and staying at home are the preventive measures set in place to contain the spread of the COVID-19, a disease caused by SARS-CoV-2. These measures, although straightforward to follow, highlight the tip of an imbalanced socio-economic and socio-technological iceberg. Here, a System Dynamic (SD) model of COVID-19 preventive measures and their correlation with the 17 Sustainable Development Goals (SDGs) is presented. The result demonstrates a better informed view of the COVID-19 vulnerability landscape. This novel qualitative approach refreshes debates on the future of SDGS amid the crisis and provides a powerful mental representation for decision makers to find leverage points that aid in preventing long-term disruptive impacts of this health crisis on people, planet and economy. There is a need for further tailor-made and real-time qualitative and quantitative scientific research to calibrate the criticality of meeting the SDGS targets in different countries according to ongoing lessons learned from this health crisis.

We examine the global legal entity identifier (LEI) system for the identification of participants in financial markets. Semi-structured interviews with data professionals reveal the many ways in which the LEI can improve both business process efficiency and counterparty and credit risk management. Larger social benefits, including monitoring of systemic financial risk, are achievable if it becomes the accepted universal standard for legal entity identification. Our interviews also review the substantial co-ordination and investment barriers to LEI adoption. To address these, a clear regulatory-led road map is needed for its future development with widespread application in regulatory reporting.

Maternal intake of the polyunsaturated fatty acids omega-3 (n-3 PUFA) and omega-6 (n-6 PUFA) impacts hippocampal neurogenesis during development, an effect that may extend to adulthood by altering adult hippocampal neurogenesis (AHN). n-3 PUFA and n-6 PUFA are precursors of inflammatory regulators that potentially affect AHN and glia. Additionally, n-3 PUFA dietary supplementation may present a sexually dimorphic action in the brain. Therefore, we postulated that dietary n-6/n-3 PUFA balance shapes the adult DG in a sex-dependent manner influencing AHN and glia. We test our hypothesis by feeding adult female and male mice with n-3 PUFA balanced or deficient diets. To analyze the immunomodulatory potential of the diets, we injected mice with the bacterial endotoxin lipopolysaccharide (LPS). LPS reduced neuroblast number, and its effect was exacerbated by the n-3 PUFA deficient diet. The n-3 PUFA deficient diet reduced the DG volume, AHN, microglia number and surveilled volume. Diet effect on most mature neuroblasts was exclusively significant in female mice. Colocalization and multivariate analysis revealed an association between microglia and AHN, and the sexual dimorphic effect of diet. Our study reveals that female mice are more susceptible than males to the effect of dietary n-6/n-3 PUFA ratio on AHN and microglia.

Inhibition of amyloid fibril formation could benefit patients with systemic amyloidosis. In this group of diseases, deposition of amyloid fibrils derived from normally soluble proteins leads to progressive tissue damage and organ failure. Although many small molecules have been proposed as inhibitors of amyloid formation, few have been successful in clinical trials. Amyloid formation is complex and several individual steps could be targeted by small molecules. However, the exact mechanism of action for a molecule is often not known, which impedes medicinal chemistry efforts to develop more potent molecules. Furthermore, commonly used assays are prone to artifacts that must be controlled for. Here, potential mechanisms by which small molecules could inhibit aggregation of immunoglobulin light chain dimers, the precursor proteins for AL amyloidosis are studied in assays that recapitulate different aspects of amyloidogenesis in vitro. One molecule reduced unfolding-coupled proteolysis of light chains, but no molecules inhibited aggregation of light chains or disrupted pre-formed amyloid fibrils. This work demonstrates the challenges associated with drug development for amyloidosis, but also highlights the potential to combine therapies that target different aspects of amyloidogenesis.

Nutrition support is increasingly recognized as a clinically relevant aspect of the intensive care treatment of cardiac surgery patients. However, evidence from adequate large-scale studies evaluating its clinical significance for patients’ mid- to long-term outcome remains sparse. Considering nutrition support as a key component in the perioperative treatment of these critically ill patients, led us to review and discuss our understanding of the metabolic response to the inflammatory burst induced by cardiac surgery. In addition, we discuss how to identify patients who may benefit from nutrition therapy, when to start nutritional interventions, present evidence about the use of enteral and parenteral nutrition and the potential role of pharmaconutrition in cardiac surgery patients. Although the clinical setting of cardiac surgery provides advantages due to its scheduled insult and predictable inflammatory response, researchers and clinicians face lack of evidence and several limitations in the clinical routine, which are critically considered and discussed in this paper.

Vitamin D plays an important role in maintaining healthy mineralized skeleton. It is also consid-ered an immunomodulatory agent that regulate the innate and adaptive immune systems. Multi-ple observational studies have demonstrated the association between low level of serum 25-hydroxyvitamin D [25(OH)D] and presence and severity of several rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), spondyloarthropathies and oste-oarthritis (OA). Nevertheless, the specific benefits of vitamin D supplement for treatment and prevention of rheumatic diseases are less accepted as the results from randomized clinical trials are inconsistent, although some conceivable benefits of vitamin D for improvement of disease ac-tivity of RA, SLE and OA have been demonstrated in meta-analyses. It is also possible that some individuals might benefit from vitamin D differently from others since inter-individual difference in responsiveness to vitamin D supplementation has been observed in genomic studies. Although the optimal level of serum 25(OH)D is still debatable, it is advisable it is advisable that patients with rheumatic diseases should maintain serum 25(OH)D level at least 30 ng/mL (75 nmol/L) to prevent osteomalacia, secondary osteoporosis and fracture, and possibly 40 – 60 ng/mL (100 – 150 nmol/L) to achieve maximal benefit from vitamin D for immune health and overall health.

The aim was to study alterations of bacterial communities in patients undergoing hip or knee arthroplasty to assess the impact of chlorhexidine gluconate soap decolonisation and systemic antibiotic prophylaxis. A Swedish multicentre, prospective collection of samples obtained from elective arthroplasty patients (n=83) by swabbing anterior nares, skin sites in the groin and the site of planned surgery, before and after arthroplasty surgery, was analysed by 16S rRNA (V3-V4) gene sequencing and a complementary targeted tuf gene sequencing approach to comprehensively characterise alterations in staphylococcal communities. Significant reductions in alpha diversity was detected for both bacterial (p=0.04) and staphylococcal (p=0.03) groin communities after arthroplasty surgery with significant reductions in relative Corynebacterium (p=0.001) abundance and S. hominis (p=0.01) relative staphylococcal abundance. In nares, significant reductions occurred for S. hominis (p=0.02), S. haemolyticus (p=0.02), and S. pasteuri (p=0.003) relative to other staphylococci. S. aureus colonised 35% of anterior nares before and 26% after arthroplasty surgery. S. epidermidis was the most abundant staphylococcal species at all sampling sites. No bacterial genus or staphylococcal species increased significantly after arthroplasty surgery. Application of a targeted tuf gene sequencing approach provided auxiliary staphylococcal community profiles and allowed species-level characterisation directly from low biomass clinical samples.

To examine the role of RNA silencing in defense against viroid, a Dicer-like 2 and 4 (DCL2&4)—double knockdown transgenic tomato line 72E was created. The expression of endogenous DCL2 and DCL4 in line 72E decreased to about a half of the empty cassette line EC. When challenged with potato spindle tuber viroid (PSTVd), 72E allowed significantly higher level of PSTVd accumulation early in infection and showed lethal systemic necrosis. The size distribution of PSTVd-derived small RNA was significantly changed: the numbers of 21 and 22 nucleotides (nt) species in line 72E was approximately 66.7% and 5% of those in line EC, respectively. Conversely, the numbers of 24-nt species increased by 1100%. Furthermore, expression of miR398a-3p and miR398 increased 770–868% in the PSTVd-infected 72E, compared to the PSTVd-infected EC. In parallel, superoxide dismutase (SOD1) in PSTVd-infected 72E showed higher expression levels. In concert with miR398a-3p, SOD1 controls detoxification of reactive oxygen species (ROS) generated in cells. Since high levels of ROS production and its scavenging activity were observed in PSTVd-infected 72E, the lack of full-activity of DCLs was thought to have made the plant incapable to control excessive ROS production and thus resulted in to develop lethal systemic necrosis.

Most mature companies have started some kind of “transformation”, either digital, or agile transformations, to cope with changes in the environment, yet most fail, ending up delivering nothing or just one more reorganization. We postulate that considering the Organization as a self-aware Complex Adaptative System (CAS) is paramount, as the common conception (Industrial: mechanistic and predictive) results in bringing the systems in a frozen or defensive mode. Stimulating the system enables us to use its adaptative power to develop new capabilities, and all layers should be tackled simultaneously, to prevent the system from collapsing back into its original state. To ensure this, it is necessary to create a seed per level, and a mechanism to propagate the transformation, with a focus on development instead of growth, that is qualitative change rather than quantitative. A common vocabulary should also be provided, so conversations can occur at every level. Finally, changing mindsets is key, and both concepts and techniques should be provided as enablers to the adequate mindset level. We detail one such transformation that resulted in distributed leadership and more intrinsic motivation, providing both an account of the transformation itself and a model to read it.

The Estimation of systemic risk in India is still in its infancy stage. There are several methods which are available but none of the methods are fully compatible to forecast the systemic risk since under different circumstances the factors responsible for the risk differs. In this paper the systemic risk estimation in India being carried out based on spread in daily stock market price(Difference between the bid and ask price of a share) of the top 100 firms in India according to market capitalization for the period of July2007 to March 2016. The results were compared with the Financial Stability Report published by Reserve Bank Of India for the period of March 2010 to June 2016.The results clearly indicates that there exits relationship between market illiquidity represented by spread and risks associated with the Financial System. In most of the cases the Z score (deviation from the mean/Standard Deviation) of the spread has become negative which provides the spread which is farther from the mean, also a good indicator of volatility in market and risk to financial system. It is also seen that the Systemic Risk Survey conducted by Reserve Bank of India which started during October 2011 has supported the results.