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The Covid-19 pandemic has ushered in a new age in the world. We are still grappling with the implications in various areas of our everyday lives. The impulsive buying habits of consumers, the supply chain, and the whole industry are not exceptions. Consumers and supply chains were both unprepared during the early stages of the novel coronavirus pandemic. The procurement of utilitarian products was referred to as panic buying. The study examined using exploratory studies on several individuals in the eight selected Islamic countries who have been panic buying in coronavirus-affected areas and have faced regional constraints. The data apply on exploratory factor analysis (EFA) in eight selected Islamic countries, three hundred sample finally selected, and a good number of volunteers supported in this study. The results have shown that a drastic financial effect on the economy where purchasing power and remittance inflow declined, inflation goes up and precaution for lockdown, whereas impulsive buying goods tendency increased due to misinformation, and panic buying immensely impact in the economy. The decision-making process has shifted, preventing financial burdening, rising saving patterns, and unwelcoming unhealthy consumption. Moreover, visible psychological distress, depression, anxiety, and post-traumatic stress. These studies concluded with a policy recommendation providing the results.

BackgroundAppropriately modulating inflammation after traumatic brain injury (TBI) may prevent disabilities for the millions of those inflicted annually. In TBI, cellular mediators of inflammation, including macrophages and microglia, possess a range of phenotypes relevant for an immunomodulatory therapeutic approach. It is thought that early phenotypic modulation of these cells will have a cascading healing effect. In fact, an anti-inflammatory, “M2-like” macrophage phenotype after TBI has been associated with neurogenesis, axonal regeneration, and improved white matter integrity (WMI). There already exist clinical trials seeking an M2-like bias through mesenchymal stem/stromal cells (MSCs). However, MSCs do not endogenously synthesize key signals that induce robust M2-like phenotypes such as interleukin-4 (IL-4).MethodsTo enrich M2-like macrophages in a clinically relevant manner, we augmented MSCs with synthetic IL-4 mRNA to transiently express IL-4. These IL-4 expressing MSCs (IL-4 MSCs) were characterized for expression and functionality and then delivered in a modified mouse TBI model of closed head injury. Groups were assessed for functional deficits and MR imaging. Brain tissue was analyzed through flow cytometry, multi-plex ELISA, qPCR, histology, and RNA sequencing.ResultsWe observed that IL-4 MSCs indeed induce a robust M2-like macrophage phenotype and promote anti-inflammatory gene expression after TBI. However, here we demonstrate that acute enrichment of M2-like macrophages did not translate to improved functional or histological outcomes, or improvements in WMI on MR imaging. To further understand whether dysfunctional pathways underlie the lack of therapeutic effect, we report transcriptomic analysis of injured and treated brains. Through this, we discovered that inflammation persists despite acute enrichment of M2-like macrophages in the brain.ConclusionThe results demonstrate that MSCs can be engineered to induce a stronger M2-like macrophage response in vivo. However, they also suggest that acute enrichment of only M2-like macrophages after diffuse TBI cannot orchestrate neurogenesis, axonal regeneration, or improve WMI. Here, we also discuss our modified TBI model and methods to assess severity, behavioral studies, and propose that IL-4 expressing MSCs may also have relevance in other cavitary diseases or in improving biomaterial integration into tissues.

Background Pulmonary oedema (PE) is a serious complication of Plasmodium falciparum malaria which can lead to acute lung injury in severe cases. Lung macrophages are activated during malaria infection due to a complex host-immune response. The molecular basis for macrophage polarization is still unclear but understanding the predominant subtypes could lead to new therapeutic strategies where the diseases present with lung involvement. The present study was designed to study the polarization of lung macrophages, as M1 or M2 macrophages, in the lungs of severe P. falciparum malaria patients, with and without evidence of PE. Methods Lung tissue samples, taken from patients who died from severe P. falciparum malaria, were categorized into severe malaria with PE and without PE (non-PE). Expression of surface markers (CD68+, all macrophages; CD40+, M1 macrophage; and CD163+, M2 macrophage) on activated lung macrophages was used to quantify M1/M2 macrophage subtypes. Results Lung injury was demonstrated in malaria patients with PE. The expression of CD40 (M1 macrophage) was prominent in the group of severe P. falciparum malaria patients with PE (63.44 ± 1.98%), compared to non-PE group (53.22 ± 3.85%, p Conclusions The study demonstrates M1 polarization in lung tissues from severe P. falciparum malaria infections with PE. Understanding the nature of macrophage characterization in malaria infection may provide new insights into therapeutic approaches that could be deployed to reduce lung damage in severe P. falciparum malaria.

Consider an agent who can costlessly add mean‐preserving noise to his output. To deter such risk‐taking, the principal optimally offers a contract that makes the agent's utility concave in output. If the agent is risk‐neutral and protected by limited liability, this concavity constraint binds and so linear contracts maximize profit. If the agent is risk averse, the concavity constraint might bind for some outputs but not others. We characterize the unique profit‐maximizing contract and show how deterring risk‐taking affects the insurance‐incentive trade‐off. Our logic extends to costly risk‐taking and to dynamic settings where the agent can shift output over time.

The purpose of this paper is to explore the relationship between market orientation, innovation resources and companies’ financial performance. Focus is put on the mediator role of proactive market orientation (PMO) in the relationship between reactive market orientation (RMO), innovation resources and financial performance in the context of Central and Eastern European (CEE) countries. Research builds on reliable scales. Four hundred and fifteen usable questionnaires were collected from companies in Slovenia with more than 20 employees. The results show a strong and positive relationship between RMO and PMO. The impact of RMO on innovativeness as an element of organisational culture is both positive and stronger than the impact of PMO. PMO proved to have a significant positive influence on the capacity to innovate. While innovativeness alone does not directly influence financial performance, the results do confirm the positive impact of an organisational capacity to innovate on financial performance. The finding of our paper is that when PMO was included as a mediator between RMO and the capacity to innovate, the result was that this indirect impact proved to be one of the strongest in the model. Also, it proves that in CEE countries, it is important to stress the influence of market and market orientation in building innovation resources and consequently financial performance. The limitation of the current study is that we considered the relationship only among few marketing resources and organisational performance. In future research, additional measures of market performance may be introduced as mediators between innovation resources and financial performance.

Immune Thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibodies-mediated platelet destruction, a prevalence of M1 pro-inflammatory macrophage phenotype and an elevated T helper 1 and T helper 2 lymphocytes (Th1/Th2) ratio, resulting in impairment of inflammatory profile and immune response. Macrophages are immune cells, present as pro-inflammatory classically activated macrophages (M1) or as anti-inflammatory alternatively activated macrophages (M2). They have a key role in ITP, acting both as effector cells, phagocytizing platelets, and, as antigen presenting cells, stimulating auto-antibodies against platelets production. Eltrombopag (ELT) is a thrombopoietin receptor agonist licensed for chronic ITP to stimulate platelet production. Moreover, it improves T and B regulatory cells functions, suppresses T-cells activity, and inhibits monocytes activation. We analyzed the effect of ELT on macrophage phenotype polarization, proposing a new possible mechanism of action. We suggest it as a mediator of macrophage phenotype switch from the M1 pro-inflammatory type to the M2 anti-inflammatory one in paediatric patients with ITP, in order to reduce inflammatory state and restore the immune system function. Our results provide new insights into the therapy and the management of ITP, suggesting ELT also as immune-modulating drug.

Diabetes mellitus type II and obesity are two important causes of death in modern society. They are characterized by low-grade chronic inflammation and metabolic dysfunction (meta-inflammation), which is observed in all tissues involved in energy homeostasis. A substantial body of evidence has established an important role for macrophages in these tissues during the development of diabetes mellitus type II and obesity. Macrophages can activate into specialized subsets by cues from their microenvironment to handle a variety of tasks. Many different subsets have been described and in diabetes/obesity literature two main classifications are widely used that are also defined by differential metabolic reprogramming taking place to fuel their main functions. Classically activated, pro-inflammatory macrophages (often referred to as M1) favor glycolysis, produce lactate instead of metabolizing pyruvate to acetyl-CoA, and have a tricarboxylic acid cycle that is interrupted at two points. Alternatively activated macrophages (often referred to as M2) mainly use beta-oxidation of fatty acids and oxidative phosphorylation to create energy-rich molecules such as ATP and are involved in tissue repair and downregulation of inflammation. Since diabetes type II and obesity are characterized by metabolic alterations at the organism level, these alterations may also induce changes in macrophage metabolism resulting in unique macrophage activation patterns in diabetes and obesity. This review describes the interactions between metabolic reprogramming of macrophages and conditions of metabolic dysfunction like diabetes and obesity. We also focus on different possibilities of measuring a range of metabolites intra-and extracellularly in a precise and comprehensive manner to better identify the subsets of polarized macrophages that are unique to diabetes and obesity. Advantages and disadvantages of the currently most widely used metabolite analysis approaches are highlighted. We further describe how their combined use may serve to provide a comprehensive overview of the metabolic changes that take place intracellularly during macrophage activation in conditions like diabetes and obesity.

A good prediction model is useful to accurately predict patient prognosis. Tumor–node–metastasis (TNM) staging often cannot accurately predict prognosis when used alone. Some researchers have shown that the infiltration of M2 macrophages in many tumors indicates poor prognosis. This approach has the potential to predict prognosis more accurately when used in combination with TNM staging, but there is less research in gastric cancer. A multivariate analysis demonstrated that CD163 expression, TNM staging, age, and gender were independent risk factors for overall survival. Thus, these parameters were assessed to develop the nomogram in the training data set, which was tested in the validation and whole data sets. The model showed a high degree of discrimination, calibration, and good clinical benefit in the training, validation, and whole data sets. In conclusion, we combined CD163 expression in macrophages, TNM staging, age, and gender to develop a nomogram to predict 3- and 5-year overall survivals after curative resection for gastric cancer. This model has the potential to provide further diagnostic and prognostic value for patients with gastric cancer.

Background: To analyze the course of microglial and macroglial activation in injured and contralateral retinas after unilateral optic nerve crush (ONC). Methods: The left optic nerve of adult pigmented C57Bl/6 female mice was intraorbitally crushed and injured, and contralateral retinas were analyzed from 1 to 45 days post-lesion (dpl) in cross-sections and flat mounts. As controls, intact retinas were studied. Iba1+ microglial cells (MCs), activated phagocytic CD68+MCs and M2 CD206+MCs were quantified. Macroglial cell changes were analyzed by GFAP and vimentin signal intensity. Results: After ONC, MC density increased significantly from 5 to 21 dpl in the inner layers of injured retinas, remaining within intact values in the contralateral ones. However, in both retinas there was a significant and long-lasting increase of CD68+MCs. Constitutive CD206+MCs were rare and mostly found in the ciliary body and around the optic-nerve head. While in the injured retinas their number increased in the retina and ciliary body, in the contralateral retinas decreased. Astrocytes and Müller cells transiently hypertrophied in the injured retinas and to a lesser extent in the contralateral ones. Conclusions: Unilateral ONC triggers a bilateral and persistent activation of MCs and an opposed response of M2 MCs between both retinas. Macroglial hypertrophy is transient.

This paper argues that provision of industrial commons (IC), might be considered as a crucial factor of a cluster’s attractiveness in digital transformation, e.g. in Industry 4.0 (I4.0) time. By drawing on the qualitative case study method of Hamburg Aviation cluster (HAv), it aims at exploring the nature of IC in the leading German I4.0 cluster. Proximity emerges, even if sometimes not explicitly, as the recurring topic facilitating the provision of IC, along with the advancement of I4.0. As Industry 4.0 stipulates much uncertainty, the closeness featuring in clusters, seems to bring various benefits, which can help address challenges associated with I4.0, and faced mainly by small and medium firms (SMEs). The vicinity to key actors and the gains of networking, reflect the importance of (un)articulated proximity.3

Purpose Respiratory syncytial virus (RSV) can cause serious respiratory illnesses such as pneumonia, asthma, and bronchiolitis in infants and elderly or immunocompromised individuals. An RSV vaccine has yet to be developed; only prophylactic anti-RSV antibody is commercially available. So, we investigated whether our vaccine candidate is able to induce type 1 CD4+ T helper (Th1), CD8+ T-cell responses, and protective immunity without vaccine-enhanced disease (VED) against RSV. Materials and methods We used RSV G protein fragment (Gcf A) with recombinant baculovirus capable of expressing the RSV M2 protein (Bac M2) as a vaccine candidate, and injected this vaccine (Gcf A/Bac M2) intramuscularly, and challenged with RSV intranasally into mice. Enzyme-linked immunosorbent assay, flow cytometry, plaque assay, and weight measurement were performed to confirm humoral immunity, cellular immunity, and protective immunity. Results The Gcf A/Bac M2 formulation induced a stronger IgG response to Gcf A than Gcf A inoculation alone, and the ratio of IgG1/IgG2a indicated that the responses shifted predominantly to Th1. In addition, both RSV G-specific Th1 responses and RSV M2-specific CD8+ T-cell responses were induced, and G protein-associated eosinophilic infiltration was suppressed compared to the control group. Moreover, the Gcf A/Bac M2 group showed effective protection after an RSV challenge. Conclusion Bac M2 could serve as a vaccine with intrinsic adjuvant activity, and the Gcf A/Bac M2 shows promise as a vaccine candidate for inducing protective immunity without inciting VED.

The main goal of the study was to examine or investigate the impact of strategic management practices on the growth of SMEs in Ghana. Purposive sampling technique was employed to sample 190 SMEs in Accra, though 150 SMEs responded to the questionnaire. With the help of SPSS version 22, Multiple regression analysis was conducted to assess the impact of strategic management practices on the performance and hence growth of SMEs in Ghana. The study revealed a significant positive relationship between strategy formulation and growth of SMEs in Ghana. The study also found a significant positive relationship between strategy implementation and the growth of SMEs in Ghana, but found a negative relationship between strategy evaluation and growth of SMEs in Ghana. However, overall, the study found a positive relationship between effective and efficient application of strategic management practices and the growth of SMEs in Ghana. As a contribution to policy and practice, the study recommended among others that policy makers, managers and owners of Small and Medium Enterprises (SMEs) should employ strategic management experts especially in the field of strategy evaluation to enhance the quality of their strategy evaluation process so as to positively influence the performance and growth of SMEs.

Activated microglia involved in the development of orofacial pain hypersensitivity have two major polarization states. The aim of this study was to assess the involvement of the aging-related phenotypic conversion of medullary microglia in the enhancement of intraoral pain sensitivity using senescence-accelerated mice (SAM)-prone/8 (SAMP8) and SAM-resistant/1 (SAMR1) mice. Mechanical head-withdrawal threshold (MHWT) was measured for 21 days post palatal mucosal incision. The number of CD11c-immunoreactive (IR) cells [affective microglia (M1)] and CD163-IR cells [protective microglia (M2)], and tumor-necrosis-factor-&alpha, (TNF-&alpha, )-IR M1 and interleukin (IL)-10-IR M2 were analyzed via immunohistochemistry on days 3 and 11 following incision. The decrease in MHWT observed following incision was enhanced in SAMP8 mice. M1 levels and the number of TNF-&alpha, IR M1 were increased on day 3 in SAMP8 mice compared with those in SAMR1 mice. On day 11, M1 and M2 activation was observed in both groups, whereas IL-10-IR M2 levels were attenuated in SAMP8 mice, and the number of TNF-&alpha, IR M1 cells increased, compared to those in SAMR1 mice. These results suggest that the mechanical allodynia observed following intraoral injury is potentiated and sustained in SAMP8 mice due to enhancement of TNF-&alpha, signaling, M1 activation, and an attenuation of M2 activation accompanying IL-10 release.

The digital-based start-up industry in Indonesia has developed, but with a high failure rate. This research aims at elaborating the relationship between business model, entrepreneurial orientation, innovation, and sustainable performance on the digital start-up companies in Indonesia. The data were collected using offline and online surveys to 206 leaders or founders of digital start-up companies spread throughout Indonesia. Then, the data were then analysed using the structural equation model. The research results revealed that a business model had a significant role in achieving sustainable performance. A business model needs to be supported by customer participation and innovation. Innovation was more influential compared to customer participation in achieving companies’ sustainable performance. The indirect effect of customer participation and innovation on sustainable performance through the business model was greater than the direct effect not through the business model. The novelty of this research is the examination and analysis of the relationship between innovation, customer participation, business model, and sustainable performance in one model, and the use of digital start-up companies in Indonesia as the research analysis unit.

The role of the innate immune system in ovarian cancer is gaining importance. The relevance of tumor-associated macrophages (TAM) is insufficiently understood. In this pilot project, comprising the immunofluorescent staining of 30 biopsies taken from 24 patients with ovarian cancer, we evaluated the presence of total TAM (cluster of differentiation (CD) 68 expression), M1 (major histocompatibility complex (MHC) II expression), and M2 (anti-mannose receptor C type 1 (MRC1) expression), and the blood vessel diameter. We observed a high M1/M2 ratio in low-grade ovarian cancer compared to high-grade tumors, more total TAM and M2 in metastatic biopsies, and a further increase in total TAM and M2 at interval debulking, without beneficial effects of bevacizumab. The blood vessel diameter was indicative for M2 tumor infiltration (Spearman correlation coefficient of 0.65). These data mainly reveal an immune beneficial environment in low-grade ovarian cancer in contrast to high-grade serous ovarian cancer, where immune suppression is not altered by neoadjuvant therapy. ispartof: CELLS vol:9 issue:2 ispartof: location:Switzerland status: published

In high power regimes, broad area semiconductor lasers usually suffer from poor beam quality due to their asymmetric beam divergence, large beam quality factor (M2) and from the absence of any intrinsic filtering mechanism that can be integrated inside the cavity. In this work, we present a compact photonic crystal spatial filter, fabricated by periodically modulating refractive index media on a glass substrate using tightly focused femtoseconds laser. This filter work by deflecting the higher angular field components in a given frequency range. We demonstrate the spatial filtering effect when placed in an extended cavity configuration for a single BAS emitter, with transverse width of 400-µm and cavity length 1500-µm. We report a decrease of the laser M2 value along the slow axis with the introduction of the photonic crystal inside the cavity, together with a brightness enhancement by a factor of 1.5 compared to that of an unfiltered case. These results were compared with those obtained in the far field domain, with a conventional spatial filter consisting of an intra-cavity slit.

Tumor-associated macrophages (TAMs) as immune cells within the tumor microenvironment have gained much interests as basic science regarding their roles in tumor progression unfolds. Better understanding of their polarization into pro-tumoral phenotype to promote tumor growth, tumor angiogenesis, immune evasion, and tumor metastasis has prompted various studies to investigate their clinical significance as a biomarker of predictive and prognostic value across different cancer types. Yet, the methodologies to investigate the polarization phenomena in solid tumor tissue vary. Nonetheless, quantifying the ratio of M1 to M2 TAMs has emerged to be a prevailing parameter to evaluate this polarization phenomena for clinical application. This mini-review focuses on recent studies exploring clinical significance of M1/M2 TAM ratio in human cancer tissue and critically evaluates the technicalities and challenges in quantifying this parameter for routine clinical practice. Immunohistochemistry appears to be the preferred methodology for M1/M2 TAM evaluation as it is readily available in clinical laboratories, albeit with certain limitations. Recommendations are made to standardize the quantification of TAMs for better transition into clinical practice and for better comparison among studies in various populations of patients and cancer types.

The aim of this research was determining the factors of growth in the textile and food sector of Pakistan. The research study analyzed data from the financial statements of textile and food sector companies of Pakistan for the period 2013-17. A fixed effect regression model was used for regression analysis after the conformation of (Hausman, 1970) specification test. The results of the study indicated that there was a significant and positive impact of profitability and negative impact of leverage on firm growth in textiles as well as the food sector of Pakistan. The results also indicated that firm growth was not significantly affected by innovation, liquidity or solvency. Growth of assets was used to measure firm growth. The findings of the study are applicable to textile as well as food sector companies in Pakistan. This research study suggested that management and policymakers in the textile as well as in the food sector of Pakistan should consider profitability as a driving factor for enhancing growth in both sectors. A small number of research studies could be found for the driving factors of growth especially in the textile as well as for the food sector of Pakistan. The present research study contributed to the existing literature by providing fresh evidence from Pakistan as a developing market. It allows the research community to explore the differences and similarities for the driving factors of growth in both sectors of Pakistan.

In this paper, I study the short-run effect of social distancing due to the COVID-19 outbreak on movie demand and box-office revenue. Using longitudinal data on the Korean movie theater industry, I first estimate a nested logit model of movie demand, and then quantify the revenue loss in the industry. Estimation results reveal that the revenue loss due to the decrease in underlying movie demand is approximately 52 million dollars nationwide during the first five weeks after the outbreak, implying a 34 percent decrease in sales. The results also suggest an additional 42 million dollars were lost as the delay of some major movies lowered the overall quality of available movies in the market.

After spinal cord injury (SCI), macrophages infiltrate into the lesion and can adopt a wide spectrum of activation states. However, the pro-inflammatory, pathological macrophage activation state predominates and contributes to progressive neurodegeneration. Azithromycin (AZM), an FDA approved macrolide antibiotic, has been demonstrated to have immunomodulatory properties in a variety of inflammatory conditions. Indeed, we previously observed that post-SCI AZM treatment reduces pro-inflammatory macrophage activation. Further, a combined pre- and post-injury treatment paradigm improved functional recovery from SCI. Therefore, for the current study, we hypothesize that post-injury AZM treatment will improve recovery from SCI. To test this hypothesis, we examined the therapeutic potential of delayed AZM treatment on locomotor, sensory, and anatomical recovery. We administered AZM beginning 30-min, 3-h, or 24-h following contusion SCI in female mice, and then daily for 7 days. AZM administration beginning 30-min and 3-h post-injury improved locomotor recovery with increased stepping function relative to vehicle controls. Further, delaying treatment for 30-min after SCI significantly reduced lesion pathology. Initiating AZM treatment 24-h post-injury was not therapeutically effective. Regardless of the timing of the initial treatment, AZM did not statistically reduce the development of neuropathic pain (mechanical allodynia) nor increase neuron survival. Collectively, these results add to a growing body of evidence supporting AZM’s translational potential as a therapeutic agent for SCI and other neuroinflammatory conditions in which patients currently have very few options.

Purpose Over time, technological intensity has been used as a proxy for innovation capability of firms in an industrial sector. However, not only firms belonging to the stratum of high technological intensity are able to innovate. Therefore, this study aims to explore a potential association between technological intensity and innovation capability in firms from different industrial sectors, using the Organization for Economic Cooperation and Development (OECD)’s classification and the components of innovation capability proposed by Zawislak et al. (2012, 2013). Design/methodology/approach The authors conducted an exploratory research with four case studies focusing on the innovation capability of Brazilian firms. Findings The results show that the four firms, each belonging to one stratum of technological intensity, have innovation capability, and the differences regarding this feature can be explained by the balance and development of all firms’ capabilities (technological, operational, managerial and transactional). Originality/value In the literature, studies that relate technological intensity and innovation capability are scarce. Therefore, the originality of this research is to relate these two concepts. The most important is that firms can be innovative regardless of their stratum of technological intensity, which shows the importance of other capabilities to ensure the innovation’s success.

Gross margin, as a measure of profitability has been associated with an enterprise and for a single product. The determinants of the gross margin have also been investigated using multiple regression. Whilst attempts have been made to model joint production, this has not been the case for gross margin for joint production. Further, multiple regression analysis is inadequate in modelling the gross margins of joint production. In this paper, we contribute to the literature by estimating gross margin for a joint product, decomposed the gross margin into the respective joint products and investigated the drivers (and constraints) of the joint product gross margins by use of multivariate multiple regression. Using data on smallholder palm fruit processing in Ghana, collected using a pretested questionnaire, we have shown that, attention must not be on the gross margin of the major product alone, in a joint production environment. Gender (being female), number of years of formal education, experience in palm oil processing and credit explained the joint product gross margin. Government, NGOs and other development partners should encourage females to stay longer in the formal school system and enhance credit opportunities to smallholder palm oil processors. The gross margin of the complete set of the joint product must be considered. We showed that failure to account for the minor product would underestimate the gross margin. The outcome is useful for computing profit margins in a joint production environment. Also, it assists the manager in identifying what factors to tweak to increase the profit margin for the joint product.

BackgroundM2 occlusions may result in poor outcomes and potentially benefit from endovascular therapy. Data on the rate of M2 strokes is lacking.MethodologyPatients with acute ischemic stroke discharged over a period of 3 years from a tertiary level hospital in the ‘stroke belt’ were evaluated for M2 occlusions on baseline vascular imaging. Regional and national incidence was calculated from discharge and multicounty data.ResultsThere were 2739 ICD-9 based AIS discharges. M2 occlusions in 116 (4%, 95% CI 3.5% to 5%) patients constituted the second most common occlusion site. The median National Institute of Health Stroke Scale (NIHSS) score was 12 (IQR 5–18). Good outcomes were observed in 43% (95% CI 34% to 53%), poor outcomes in 57% (95% CI 47% to 66%), and death occurred in 27% (95% CI 19% to 37%) of patients. Receiver operating characteristics curves showed the NIHSS to be predictive of outcomes (area under the curve 0.829, 95% CI 0.745 to 0.913, p3 for NIHSS score ≥9 versus 30 (±34)cm3 for NIHSS score ConclusionM2 occlusions can present with serious neurological deficits and cause significant morbidity and mortality. Patients with M2 occlusions and higher baseline deficits (NIHSS score ≥9) may benefit from endovascular therapy, thus potentially expanding the category of acute ischemic strokes amenable to intervention.

// Lei Tu 1,* , Jie Chen 2,* , Dandan Xu 2 , Zhongming Xie 2 , Bing Yu 3 , Ying Tao 3 , Guixiu Shi 3 and Lihua Duan 3 1 Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China 2 College of Medicine, Xiamen University, Fujian, China 3 Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China * These authors have contributed equally to this work Correspondence to: Lihua Duan, email: // Guixiu Shi, email: // Keywords : IL-33, inflammatory bowel disease, macrophage, M2, Arginase-1, Immunology and Microbiology Section, Immune response, Immunity Received : January 17, 2017 Accepted : February 28, 2017 Published : March 07, 2017 Abstract Accumulated data have shown that alternatively activated macrophage exerts a modulatory role in many diseases, including colitis. Interleukin-33 (IL-33), a critical modulator in adaptive and innate immune, has been implicated in autoimmunity and inflammation. Previously, we have reported that IL-33 functions as a protective modulator in TNBS-induced colitis, which is closely related to a Th1-to-Th2/Treg switch. Here, we present novel evidence suggesting that IL-33 primes macrophage into alternatively activated macrophages (AAM) in TNBS-induced colitis. The strong polarized effect of IL-33 was tightly associated with the markedly increased induction of Th2-type cytokines. To confirm the beneficial effects of AAM induced by IL-33, peritoneal AAMs isolated from IL-33-treated mice were transferred to recipient mice with TNBS colitis. The adoptive transfer resulted in prominent inhibition of disease activity and inflammatory cytokines in the TNBS-treated mice. In conclusion, our data provide clear evidence that IL-33 plays a protective role in TNBS-induced colitis, which is closely related to AAM polarization.

Background: Craniofacial osteosarcomas (COS) and extracranial osteosarcomas (EOS) show distinct clinical differences. COS show a remarkably lower incidence of metastases and a better survival. However, in contrast to EOS, they show a poor response to neoadjuvant chemotherapy. Tumor-associated macrophages and their polarization as well as developmental biological signaling pathways are possible candidates for explaining the clinical differences between COS and EOS. The aim of the study was to analyze differential expression of macrophage markers and important regulators of these pathways.Methods: Twenty osteosarcoma cases (10 COS and 10 EOS) were immunohistochemically stained to assess CD68, CD11c, CD163, MRC1, Gli1, and Gli2 expression. Statistical differences between COS and EOS were tested using the Mann–Whitney U test. Additionally, the paper describes an example of multidisciplinary treatment of a patient suffering from COS and discusses the surgical challenges in treatment and rehabilitation of COS.Results: COS showed a significantly (p < 0.05) increased infiltration of CD11c-positive M1 macrophages and a shift toward M1 polarization compared to EOS. Additionally, COS revealed a significantly (p < 0.05) lower Gli1 expression than EOS.Conclusion: The reduced Gli1 expression in COS can be interpreted as reduced activation of the Hedgehog (Hh) signaling pathway. The increased M1 polarization and reduced Hh activation in COS could explain the low incidence of metastases in these osteosarcomas.

The benefits of moderate aerobic physical exercise for allergic asthma are well-known, particularly that of the anti-inflammatory effect that occurs by reducing Th2 responses and lung remodeling. However, the mechanisms of this immunoregulation are still under investigation. In this study, we investigated the possible immunoregulatory mechanisms of lung inflammation induced by moderate aerobic exercise in an experimental asthma model. BALB/c mice were distributed into Control, Exercise (EX), OVA, and OEX groups. OVA and OEX groups were sensitized with ovalbumin (OVA) on days 0, 14, 21, 28, and 42 and were challenged with OVA aerosol three times a week from days 21 to 51. The EX and OEX groups underwent moderate aerobic physical exercise from days 21 to 51 (5 d/w, 1 h/d). The mice were euthanized on day 52. We evaluated pulmonary cytokine production, serum immunoglobulin levels, and the inflammatory cell profile in lung and mediastinal lymph nodes. OVA mice showed increased expression of IL-4, IL-6, IL-10, and TGF-β and decreased macrophage type 2 (M2) recruitment. Physical exercise did not affect the increased antibody production of IgG2a, IgG1, or IgE induced by OVA. Of note, physical exercise alone markedly increased production of anti-inflammatory cytokines such as IL-10 and TGF-β. Physical exercise in OVA-mice also increased the recruitment of M2 in the lungs, as well as the influx and activation of regulatory T cells (Tregs) and CD4 and CD8 lymphocytes. In the draining lymph nodes, it was also observed that physical exercise increased the activation of CD4 T cells, regardless of the presence of OVA. Notably, physical exercise decreased common dendritic cells' (cDCs; pro-inflammatory) expression of co-stimulatory molecules such as CD80, CD86, and ICOSL in the draining lymph nodes, as well as increased ICOSL in plasmacytoid dendritic cells (pDCs; anti-inflammatory). Together, these findings show that physical exercise modulates pulmonary allergic inflammation by increasing Treg and M2 recruitment, as well as pDCs activation, which leads to an increase in anti-inflammatory cytokines and a decrease in pro-inflammatory cells and mediators.

The corporate headquarters (CHQ) is an important part of the organization of large firms; yet, it is neglected in organization design theory. In this brief essay, I argue that we need a better understanding of the CHQ to further our understanding of the link between the top-management team and the rest of the organization, and to improve our understanding of the costs and benefits of hierarchical organization in general. I outline a number of organizational economics ideas that may help addressing these challenges.

A profound review of the literature on entrepreneurship reveals that it does not exist a specific information tool to measure the individuals’ readiness for entrepreneurship. The purpose of this research has been building such kind of instrument to estimate the individuals’ readiness for entrepreneurship. Its design takes in consideration the inclusion of the main variables identified by the literature as those most associated with entrepreneurial profiles. These variables have been grouped into three categories: sociological, psychological and managerial-entrepreneurial. Each group provides batteries of items which are evaluated thanks to a specific scoring system. The final objective is to provide a system to calculate individual scores of readiness for entrepreneurship and, at the same time, partial scores on concrete aspects of it. The information tool is presented at this paper and will be tested and refined in the near future.

The introduction of mobile number portability (MNP) in the Nigerian telecommunications industry has brought a new challenge for mobile operators. This study investigates the use of Analytic Hierarchy Process (AHP) in customer retention decisions in the Nigerian telecommunication industry using a cross-sectional survey design. Primary data were obtained through questionnaires administered to 480 mobile telecommunications subscribers in six tertiary institutions located in Lagos State, Nigeria. These educational institutions were chosen using a multistage sampling technique. Of 438 questionnaires received from subscribers, 408 were valid. Based on this sample data an AHP model was built to assess the determinants of customer retention decisions. Next, eigen values, an eigen vector and maximum lambda (λMax) were obtained using the AHP analysis for the matrices. This analysis shows that customers considered call quality as the important in the retention decision. We conclude that AHP is a meaningful tool for determining what motivates retention decisions, that can help network operators formulate effective customer retention strategies.

Background Macrophage heterogeneity is the main feature of the tumour microenvironment. Breast cancer is one of the most life-threatening cancers. However, macrophage polarization patterns in different tumour stages and the importance of its relationship to human epidermal growth factor receptor 2 (HER2) in breast cancer remains highly unclear. The present study investigated the patterns of monocyte differentiation and macrophage polarization in breast cancer. Methods Patients with breast cancer (n = 48) and healthy controls (n = 39) were prospectively recruited. The percentages and subsets of circulating macrophage-like cells were analysed by flow cytometry, and the polarization patterns of these cells in the peripheral blood of patients with breast cancer were compared with those of healthy controls. In addition, macrophage polarization patterns in different stages and HER2 status in breast cancer were investigated. Results The percentages of circulating macrophages, which are defined as PM-2 K+ cells in the peripheral blood, were significantly higher in patients with breast cancer than in healthy controls. The percentages of M1-like macrophages were significantly lower, but those of M2-like macrophages were significantly higher in patients with breast cancer than in healthy controls. The percentage of M2c-like macrophages was significantly higher in advanced (stages II and III) breast cancer. However, the patterns of macrophage polarization were not associated with HER2 status in breast cancer. Conclusions Aberrant macrophage polarization was observed in breast cancer and was correlated with breast cancer stage. These quantitative data may provide new molecular biomarkers and potential therapeutic targets in breast cancer. Electronic supplementary material The online version of this article (10.1186/s12885-018-4284-y) contains supplementary material, which is available to authorized users.

Background: Systemic sclerosis (SSc) is a disorder characterized by immune system alterations, vasculopathy and fibrosis. SSc-related interstitial lung disease (ILD) represents a common and early complication, being the leading cause of mortality. Monocytes/macrophages seem to have a key role in SSc-related ILD. Interestingly, the classically (M1) and alternatively (M2) activated monocyte/macrophage phenotype categorization is currently under revision. Our aim was to evaluate if circulating monocyte/macrophage phenotype could be used as biomarker for lung involvement in SSc. To this purpose we developed a wide phenotype characterization of circulating monocyte/macrophage subsets in SSc patients and we evaluated possible relations with lung involvement parameter values. Methods: A single centre cross-sectional study was performed in fifty-five consecutive SSc patients, during the year 2017. All clinical and instrumental tests requested for SSc follow up and in particular, lung computed tomography (CT) scan, pulmonary function tests (PFTs), Doppler echocardiography with systolic pulmonary artery pressure (sPAP) measurement, blood pro-hormone of brain natriuretic peptide (pro-BNP) evaluation, were performed in each patient in a maximum one-month period. Flow cytometry characterization of circulating cells belonging to the monocyte/macrophage lineage was performed using specific M1 (CD80, CD86, TLR2 and TLR4) and M2 surface markers (CD204, CD163 and CD206). Non-parametric tests were used for statistical analysis. Results: A higher percentage of circulating CD204(+)CD163(+)CD206(+)TLR4(+)CD80(+)CD86(+) and CD14(+)CD206(+)CD163(+)CD204(+)TLR4(+)CD80(+)CD86(+) mixed M1/M2 monocyte/macrophage subsets, was identified to characterize patients affected by SSc-related ILD and higher systolic pulmonary artery pressure. Mixed M1/M2 monocyte/macrophage subset showed higher percentages in patients positive for anti-topoisomerase antibody, a known lung involvement predictor. Conclusions: The present study shows for the first time, through a wide flow cytometry surface marker analysis, that higher circulating mixed M1/M2 monocyte/macrophage cell percentages are associated with ILD, sPAP and anti-topoisomerase antibody positivity in SSc, opening the path for research on their possible role as pathogenic or biomarker elements for SSc lung involvement.

Background: The prognosis of solid malignancies has been shown to depend on immunological parameters, such as macrophage polarisation (M1/M2). Recently, it was reported that preoperative oral surgery leads to a worsening of oral squamous cell carcinomas (OSCC) prognosis. Diagnostic incision biopsies are oral surgery procedures that might lead to healing-associated M2 macrophage polarisation with a potential negative influence on tumour biology. No studies have compared macrophage polarisation in OSCC biopsies and tumour specimens. Methods: Preoperative diagnostic incision biopsies (n=25) and tumour resection specimens (n=34) of T1/T2 OSCC were processed for immunohistochemistry to detect CD68-, CD11c-, CD163- and MRC1-positive cells. Samples were digitised using whole-slide imaging, and the expression of macrophage markers was quantitatively analysed. Results: Carcinoma tissues obtained during OSCC tumour resections showed a significantly (P

This research seeks to study the factors that enhance or preclude owners of SMEs in Ghana in making risk management decisions. The study was conducted with managers of SMEs in four regions in Ghana. The researchers adopted a quantitative approach and employed STATA 10 and SPSS version 20 in the analysis. Stratified and simple random sampling techniques were used to select the sample units. The probit model was used in the analysis of data. A total of 447 SMEs were sampled for the study, with at least 111 from each of the selected regions. The probit results show that the demographic factors indicate a positive influence on the likelihood that managers will take risk management decisions. All of the business related demographic factors are significant at various levels and positive, except for risk-loving. The economically related factors, such as the estimated amount at risk, the estimated cost of risk management and the estimated total monthly income after tax all have a positive influence on risk management decision making. However, government and tax policies are perceived to negatively influence risk management decisions by managers. We recommend that institutions working closely with SMEs acquire the expertise to train the managers of SMEs on risk management practices.

Background It is known that tissue macrophages derive not only from blood monocytes but also from yolk sac or fetal liver, and the tissue of residence guides their function. When isolated, they lose tissue specific signatures, hence studies of human macrophages should be ideally done directly in the tissue. The aim of this study was to investigate directly in human lung tissue the polarization of alveolar macrophage (AM), classic (M1) or alternative (M2), in health and disease, using COPD as a model. Methods Surgical lungs from 53 subjects were studied: 36 smokers whose FEV1 varied from normal to severe COPD, 11 non-smokers and 6 normal donors. iNOS and CD206 immunohistochemistry was used to quantify the percentage of AM polarized as M1 or M2 in lung sections. Results and Discussion The percentage of M1 and M2 increased progressively with smoking and COPD severity, from 26% to 84% for M1 and from 7% to 78% for M2. In donors 74% of AM were negative for M1 and 93% for M2. Confocal microscopy showed co-localization of M1 and M2 in the same AM in severe COPD. Conclusion In normal lungs alveolar macrophages were mostly non-polarized. With smoking and COPD severity, M1 and M2 polarization increased significantly and so did the co-expression of M1 and M2 in the same alveolar macrophage. Electronic supplementary material The online version of this article (doi:10.1186/s12931-017-0522-0) contains supplementary material, which is available to authorized users.

This paper reviews the definitions of Corporate Social Responsibility (CSR) as they have evolve over time. It traces the origins of the concept and creates a theoretical framework for international use, thus having the benefit of applicability in both developing as well as developed economies. The models of Carroll and Visser are integrated to produce The International Pyramid Model of CSR, which acknowledges the relative importance of economic, glocal, legal and ethical, and philanthropic aspects of the CSR concept. The primary innovation in the International Pyramid is the development of ‘glocal’ responsibilities, relating to the environment, socio-cultural matters, technology users, and political rights. Additionally, the International Pyramid condenses Carroll (Business Horizons 34(4):39–48, 1991) pyramid such that the separate legal and ethical responsibilities are merged into one ‘legal and ethical’ obligation. Furthermore, it offers flexibility by acknowledging that the various responsibilities it embodies can shift up or down the pyramid as priorities change, which is inevitable as businesses and economies differ cross-sectionally, and over time.

An excessive foreign body response (FBR) has contributed to the adverse events associated with polypropylene mesh usage for augmenting pelvic organ prolapse surgery. Consequently, current biomaterial research considers the critical role of the FBR and now focuses on developing better biocompatible biomaterials rather than using inert implants to improve the clinical outcomes of their use. Tissue engineering approaches using mesenchymal stem cells (MSCs) have improved outcomes over traditional implants in other biological systems through their interaction with macrophages, the main cellular player in the FBR. The unique angiogenic, immunomodulatory and regenerative properties of MSCs have a direct impact on the FBR following biomaterial implantation. In this review, we focus on key aspects of the FBR to tissue-engineered MSC-based implants for supporting pelvic organs and beyond. We also discuss the immunomodulatory effects of the recently discovered endometrial MSCs on the macrophage response to new biomaterials designed for use in pelvic floor reconstructive surgery. We conclude with a focus on considerations in biomaterial design that take into account the FBR and will likely influence the development of the next generation of biomaterials for gynaecological applications.

8 p.-4 fig.-4 tab. Herrera, Mercedes et al., Tumor epithelial cells within a tumor coexist with a complex microenvironment in which a variety of interactions between its various components determine the behavior of the primary tumors. Cancer-associated fibroblasts (CAF) and M2 macrophages, characterized by high expression of different markers, including a-SMA, FSP1 and FAP, or CD163 and DCSIGN, respectively, are involved in the malignancy of different tumors. In the present study, expression of the above markers in CAF and M2 macrophages was analyzed using RT-PCR and immunohistochemistry in the normal mucosa and tumor tissue from a cohort of 289 colorectal cancer patients. Expression of CAF and M2 markers is associated with the clinical outcome of colorectal cancer patients. Moreover, the combination of CAF and M2 markers identifies three groups of patients with clear differences in the progression of the disease. This combined variable could be a decisive factor in the survival of advanced-stage patients. Taken together, these analyses demonstrate the prognostic involvement of interrelationships between DCSIGN, CD163, a-SMA, FSP1 and FAP markers in the survival of colon cancer patients., This work has been supported by Fundaci on Cient ıfica AECC, SAF2010-20750, S2010 ⁄BMD-2344, RTICC-RD06 ⁄ 0020 ⁄ 0020, PI12 ⁄ 02037 and Fundaci on Banco Santander. A.G.H. laboratory was supported by RD06 ⁄ 0020 ⁄ 0040. C.P. is the recipient of a Miguel Servet Contract from the Instituto de Salud Carlos III (CP09 ⁄ 00294) and V.G. is the recipient of a Fundaci on Científica AECC fellowship.

// Alessandra Ciucci 1, * , Gian Franco Zannoni 2, * , Marianna Buttarelli 1 , Enrica Martinelli 1 , Floriana Mascilini 3 , Marco Petrillo 3 , Gabriella Ferrandina 3, 4 , Giovanni Scambia 3 , Daniela Gallo 1 1 Unit of Translational Medicine for Women and Children Health, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy 2 Department of Pathology, Catholic University of the Sacred Heart, Rome, Italy 3 Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy 4 Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy * These authors contributed equally to this work Correspondence to: Daniela Gallo, email: daniela.gallo@unicatt.it Keywords: ovary, tumor-associated macrophages, TAM, M1, M2 Received: May 26, 2016 Accepted: July 13, 2016 Published: July 23, 2016 ABSTRACT Only recently low-grade serous carcinoma (LGSOC) of the ovary has been recognized as a disease entity distinct from the more common high-grade serous carcinoma (HGSOC), with significant differences in pathogenesis and clinical and pathologic features. The present study aimed at evaluating whether the different natural histories and patterns of response to therapy demonstrated for LGSOC and HGSOC, along with a diverse genomic landscape, may also reside in the supporting tumor stroma, specifically in the state of differentiation and activation of tumor associated macrophages (TAMs). TAMs play complex roles in tumorigenesis since they are believed to possess both tumor rejecting (M1 macrophages) and tumor promoting (M2 macrophages) activities. Here we showed that, when compared to HGSOC ( n = 55), LGSOC patients ( n = 25) exhibited lower density of tumor-infiltrating CD68+ macrophage, along with an attenuated M2-skewed (CD163+) phenotype. Accordingly, assessment of intratumoral vascularization and of matrix metalloproteinase 9 expression (a key protein involved in tumor invasion and metastasis) revealed lower expression in LGSOC compared to HGSOC patients, in line with emerging evidence supporting a role for TAMs in all aspects of tumor initiation, growth, and development. In conclusion, results from the present study demonstrate that microenvironmental factors contribute greatly to determine clinical and pathological features that differentiate low and high grade serous ovarian carcinomas. This understanding may increase possibilities and opportunities to improve disease control and design new therapeutic strategies.

A vital activity is the issue of creating a knowledge society, which can only be solved by involving all the forces of intellectual, academic, all generators of ideas. The paper is intended as a contribution, along with attempts by other specialists in finding operational solutions and their implementation in estimating the risk of bankruptcy and predicting its occurrence so through research and development, education and innovation can bring prosperity, development sustainable and personal development of every citizen. Scientific novelty and originality of research and of the results obtained is to formulate proposals of rates in the score function of economic models to estimate the risk of bankruptcy of firms. This rate takes into account intangible assets predominant factor in the evolution of the company and the market value of the company. On the basis of an analysis made it demonstrated that score function for models Altman, Conan-Holder and Rating suffered a pretty significant change if we took into account the intangible assets of the company. Entering this rate into the mentioned models was made using expert systems and neural networks. The analysis, arguments, mathematical models, principles, goals can all be made based on the methodology of scientific research in the creation of knowledge society, scientific elaborations. The results of the work can be applied to all firms in the EU countries' national economies. The mathematical model could have other economic interpretations and therefore can be used in formulating and solving a number of problems in the national economies. This work is licensed under aCreative Commons Attribution-NonCommercial 4.0 International License.