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PurposeAlthough grounded theory (GT) was introduced in 1967, GT remains widely misunderstood as scholars incorporate a limited spectrum of the GT techniques and fail to integrate GT's full potential into academic research. The purpose of this article is, therefore, to discuss divergences between four GT strategies and by doing so to provide criteria for making an informed choice between one GT approach or another.Design/methodology/approachThe study offers a comparative analysis of four GT approaches by relying on a recently completed empirical work focused on the practice and perception of corporate social responsibility (CSR) in non-Western context conducted by the author.FindingsAs a result, the study outlines the main points of divergence between the four GT strategies and discusses how their differences impact the research outcomes, theoretical products and application of the proposed theories in organisational and management research.Research limitations/implicationsAs a result of the comparative analysis, the study will help researchers make an informed choice when selecting one GT approach or another.Originality/valueThe study demonstrates the potential of GT in organisational and management research by utilising a practical example of GT's implementation from a recently completed empirical study.

Several studies have addressed the challenges faced by cultural and creative professionals and businesses since the emergence of the global COVID-19 pandemic. Some success stories have surfaced around larger organizations that managed to adapt quickly because they had been preparing for the digital era. The focus of the study presented here adds the much-needed viewpoint of those individuals who form the target audiences and are vital for the future of any CCI organization. These are the results of a public survey aimed at informing directly cultural organizations that experiment with new creative approaches and are adjusting to the transformations that have taken place. Findings are vital for organizations from smaller cultural markets while key conclusions shed light on the new disposition of the public towards existing and future formats of cultural offers online that are valid for contemporary audiences in general. These cover several key observations regarding the most popular type of cultural content and events online; the engagement rate of different audience groups; the most preferred duration of culture in video format; gender affinities influencing the engagement with cultural content online; the motivations and barriers for attending cultural events online, ways to keep the audiences informed, and finally, which new forms of cultural and creative offers would the public be willing to attend online in the recent future. The article demonstrates that knowing the target audience and using data analytics on public dispositions while creating new content can empower CCI organizations. This claim is also based on the successful experience of pilot offers created by CCIs that have benefited directly from the research results of Intercultura Consult’s 2021 project. Work continues in a new project empowering cultural organizations to incubate experimental offers (digital dimension including). The goal is to enhance their connection with key audiences.

The sizeable theoretical and empirical literature on corporate social responsibility (CSR) and business ethics in Western, developed economies indicates that the topic has attracted significant interest from academics and practitioners. There is, however, less evidence of the practice of CSR and business ethics in non-Western, transition economies, as insufficient attention is paid to the contextual specifications and underlying processes that may lead to different versions of CSR. Therefore, this paper examines the practice and sense-making of CSR and business ethics from the perspective of the fertile and under researched post-communist context of Central and Eastern Europe (CEE), to join the growing academic debate about the impact of cultural and historical traditions on the practice and sense-making of CSR and business ethics in non-Western contexts. The study adopts a particular focus on the post-communist and under researched context of Bulgaria where CSR is still a relatively new phenomenon. By following an exploratory research design and by collecting qualitative data from 34 executives employed by public and private sector organisations in Bulgaria, the study finds that the local business environment is composed of a complex mix of various institutionalised pressures and challenges that predispose organisations to adopt a particular approach to CSR, ethical misconduct and CSR-washing. Apart from the significant contributions related to the practice, understanding and contextualisation of CSR in non-Western countries, the study also identifies challenges of business ethics in transition economies and adds depth to the emerging literature on CSR-washing by proposing a model for neo-communist CSR-washing. The study also offers contributions for practitioners and policy-makers.

BackgroundImmune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer. However, only a portion of patients respond to such treatments. Therefore, it remains a prevailing clinical need to identify factors associated with acquired resistance or lack of response to ICIs. We hypothesized that the immunosuppressive CD71+erythroid cells (CECs) within the tumor and/or distant ‘out-of-field’ may impair antitumor response.MethodsWe studied 38 patients with cancer through a phase II clinical trial investigating the effects of oral valproate combined with avelumab (anti-programmed death-ligand 1 (PD-L1)) in virus-associated solid tumors (VASTs). We quantified the frequency/functionality of CECs in blood and biopsies of patients. Also, we established an animal model of melanoma (B16-F10) to investigate the possible effects of erythropoietin (EPO) treatment on anti-PD-L1 therapy.ResultsWe found a substantial expansion of CECs in the blood of patients with VAST compared with healthy controls. We noted that the frequency of CECs in circulation was significantly higher at the baseline and throughout the study in non-responders versus responders to PD-L1 therapy. Moreover, we observed that CECs in a dose-dependent manner suppress effector functions of autologous T cells in vitro. The subpopulation of CD45+CECs appears to have a more robust immunosuppressive property compared with their CD45−counterparts. This was illustrated by a stronger expression of reactive oxygen species, PD-L1/PD-L2, and V-domain Ig suppressor of T-cell activation in this subpopulation. Lastly, we found a higher frequency of CECs in the blood circulation at the later cancer stage and their abundance was associated with anemia, and a poor response to immunotherapy. Finally, we report the expansion of CECs in the spleen and tumor microenvironment of mice with melanoma. We found that although CECs in tumor-bearing mice secret artemin, this was not the case for VAST-derived CECs in humans. Notably, our results imply that EPO, a frequently used drug for anemia treatment in patients with cancer, may promote the generation of CECs and subsequently abrogates the therapeutic effects of ICIs (eg, anti-PD-L1).ConclusionsOur results demonstrate that anemia by the expansion of CECs may enhance cancer progression. Notably, measuring the frequency of CECs may serve as a valuable biomarker to predict immunotherapy outcomes.

Jason Wicks, The Price of Profit: Rethinking Corporate Social Responsibility. Independently Published, 2018. $72.99, 171pp., (Paperback). ISBN-10: 1980349053; ISBN-13: 978-1980349051

We report significant upregulation of Galectin-9 (Gal-9) and VISTA on both CD4+ and CD8+ T cells in HIV-infected human patients. Gal-9 and VISTA expression was associated with impaired T cells effector functions. Although Gal-9 was coexpressed with other coinhibitory receptors such as TIGIT, CD160, CD39, and VISTA, it was simultaneously coexpressed with PD-1. Coexpression of Gal-9 with PD-1 was associated with a more terminally exhausted T cell phenotype in HIV-1 patients. This was marked by higher expression of EOMES, blimp1, and Glut1 in Gal-9+ versus Gal-9− T cells, which is consistent with an exhausted T cell phenotype. Gal-9+ T cells exhibited the phenotype characteristics of effector T cells (CD45RA+, CD45RO-/lo, CD62L−, CD27lo) with higher T-bet expression. A positive correlation between the plasma viral load with the plasma Gal-9 levels in treatment-naive HIV patients and an inverse correlation between CD4 count with the frequency of CD4+Gal-9+ T cells were observed. Increased percentages of Gal-9+ T cells was evident in HIV-treated patients. Enhanced expression of Gal-9 on T cells following PMA stimulation via protein kinase C suggests persistent TCR stimulation as a potential contributing factor in Gal-9 upregulation in HIV patients. This was supported by the constant degranulation of Gal-9+ T cells. Moreover, CD44 clustering by Gal-9 may influence cytoskeleton rearrangement and coclustering of CD3, which likely impact initiation of signal transduction via TCR. Our preliminary data also confirm upregulation of Gal-9 on T cells in hepatitis B virus and HPV infections. These results demonstrate a novel role for Gal-9 and VISTA in HIV pathogenesis.

Academic research suggests that variances in contextual dynamics, and more specifically religion, may lead to disparate perceptions and practices of corporate social responsibility (CSR). Driven by the increased geopolitical and economic importance of the Middle East and identified gaps in knowledge, the study aims to examine if indeed there is a divergent form of CSR exercised in the region. The study identifies unique CSR dimensions and constructs presented through an empirical framework in order to outline the practice and perception of CSR in a context with strong Islamic beliefs. The framework goes beyond the platform of mere Islamic philanthropy and is based on CSR-stakeholder management practices. Following an exploratory research design and collecting interview data from representatives of 63 organisations from Saudi Arabia, the United Arab Emirates and Oman, the study offers a snapshot of the CSR reality from the perspective of those living the phenomenon. The results suggest that the practice and perception of CSR in the examined context are largely grounded in the areas of social and altruistic actions but they cannot be examined in isolation from the religious context of CSR operation. This focus is mainly attributed to the dominant role of Islam in the examined sample, which leads to forms of non-structured or semi-structured approaches to CSR. Apart from the theoretical advancements offered to the CSR literature, the study also provides contributions for practitioners and policy makers.

BACKGROUND Maternal pre-postnatal psychosocial distress increases the risk for childhood allergic disease. This may occur through a host immunity pathway that involves intestinal secretory immunoglobulin A (sIgA). Experimental animal models show changes in the gut microbiome and immunity of offspring when exposed to direct or prenatal maternal stress, but little is known in humans. OBJECTIVE We determined the association between maternal depression and stress symptom trajectories and infant fecal sIgA concentrations. METHODS 1043 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort were studied. Trajectories of maternal perceived stress and depression were based on scored scales administered in pregnancy and postpartum. sIgA was quantified in infant stool (mean age 3.7 months) with Immundiagnostik ELISA. Linear regression and logistic regression were employed to test associations. RESULTS Very low fecal sIgA concentrations were more common in infants of mothers in the antepartum and persistent depression trajectories (6% and 2% of women, respectively). Independent of breastfeeding status at fecal sampling, infant antibiotic exposure or other covariates, the antepartum depressive symptom trajectory was associated with reduced mean infant sIgA concentrations (β=-0.07, P

The intestinal microbiota is involved in ulcerative colitis (UC) pathogenesis. Prebiotics are hypothesized to improve health through alterations to gut microbiota composition and/or activity. Our aim was therefore to determine if inulin-type fructans induce clinical benefits in UC, and identify if benefits are linked to compositional and/or functional shifts of the luminal (fecal) and mucosal (biopsy) bacterial communities. Patients (n = 25) with mild/moderately active UC received 7.5 g (n = 12) or 15 g (n = 13) daily oral oligofructose-enriched inulin (Orafti®Synergy1) for 9 weeks. Total Mayo score, endoscopic activity and fecal calprotectin were assessed. Fecal and mucosal bacterial communities were characterized by 16S rRNA tag sequencing, and short chain fatty acids (SCFA) production were measured in fecal samples. Fructans significantly reduced colitis in the high-dose group, with 77% of patients showing a clinical response versus 33% in the low-dose group (P = 0.04). Fructans increased colonic butyrate production in the 15 g/d dose, and fecal butyrate levels were negatively correlated with Mayo score (r = −0.50; P = 0.036). The high fructan dose led to an increased Bifidobacteriaceae and Lachnospiraceae abundance but these shifts were not correlated with improved disease scores. In summary, this pilot study revealed that 15 g/d dose inulin type fructans in UC produced functional but not compositional shifts of the gut microbiota, suggesting that prebiotic-induced alterations of gut microbiota metabolism are more important than compositional changes for the benefits in UC. The findings warrant future well-powered controlled studies for the use of β-fructans as adjunct therapy in patients with active UC.

AIM To understand the effects of delivery mode on the immune cells frequency and function in cord blood and placenta. METHODS We evaluated immunological differences in cord blood and placental tissues for a case of twins one of which delivered vaginally while the other delivered by caesarian section (C-section). Cord blood mononuclear cells were isolated and placenta tissues were processed for cell isolation. Immune phenotyping was performed by flow cytometry methods following staining for T cells, natural killer (NK) cells, monocytes, neutrophils and CD71+ erythroid cells in both cord blood and placenta tissues. In addition, fetal calprotectin of twins was measured 12 wk after birth. RESULTS We found lower percentages of immune cells (e.g. T cells, monocytes and neutrophils) in the cord blood of C-section delivered compared to vaginally delivered newborn. In contrast, percentages of monocytes and neutrophils were > 2 folds higher in the placental tissues of C-section delivered newborn. More importantly, we observed lower percentages of CD71+ erythroid cells in both cord blood and placental tissues of C-section delivered case. Lower CD71+ erythroid cells were associated with a more pro-inflammatory milieu at the fetomaternal interface reflected by higher expression of inhibitory receptors on CD4+ T cells, higher frequency of monocytes and neutrophils. Furthermore, type of delivery impacted the gene expression profile in CD71+ erythroid cells. Finally, we found that C-section delivered child had > 20-fold higher FCP in his fecal sample at 12 wk of age. CONCLUSION Mode of delivery impacted immune cells profile in cord blood/placenta. In particular frequency of immunosuppressive CD71+ erythroid cells was reduced in C-section delivered newborn.

Introduction: The functional role of milk for the developing neonate is an area of great interest, and a significant amount of research has been done. However, a lot of work remains to fully understand the complexities of milk, and the variations imposed through genetics. It has previously been shown that both secretor (Se) and Lewis blood type (Le) status impacts the human milk oligosaccharide (HMO) content of human milk. While some studies have compared the non-HMO milk metabolome of Se+ and Se− women, none have reported on the non-HMO milk metabolome of Se− and Le– mothers.Method and Results: To determine the differences in the non-HMO milk metabolome between Se–Le– mothers and other HMO phenotypes (Se+Le+, Se+Le–, and Se–Le+), 10 milk samples from 10 lactating mothers were analyzed using nuclear magnetic resonance (NMR) spectroscopy. Se or Le HMO phenotypes were assigned based on the presence and absence of 6 HMOs generated by the Se and Le genes. After classification, 58 milk metabolites were compared among the HMO phenotypes. Principal component analysis (PCA) identified clear separation between Se–Le– milk and the other milks. Fold change analysis demonstrated that the Se–Le– milk had major differences in free fatty acids, free amino acids, and metabolites related to energy metabolism.Conclusion: The results of this brief research report suggest that the milk metabolome of mothers with the Se–Le– phenotype differs in its non-HMO metabolite composition from mothers with other HMO phenotypes.

Immature red blood cells (erythroid precursors or CD71+ erythroid cells) have a wide range of immunomodulatory properties. In this study, we found that these erythroid precursors are abundant in the human cord blood/placental tissues, in the blood of HIV-infected and anemic individuals. We observed that these cells exacerbate HIV-1 replication/infection in target cells and even make HIV target cells more permissible to HIV infection. In addition, we found that HIV gets a free ride by binding on the surface of these cells and thus can travel to different parts of the body. In agreement, we noticed a positive correlation between the plasma viral load and the frequency of these cells in HIV patients. More importantly, we observed that infective HIV particles reside inside these erythroid precursors but not mature red blood cells. Therefore, these cells by harboring HIV can play an important role in HIV pathogenesis., CD71+ erythroid cells (CECs) have a wide range of immunomodulatory properties. Here, we show that CECs are expanded in the peripheral blood of HIV patients, with a positive correlation between their frequency and the plasma viral load. CECs from HIV patients and human cord blood/placenta exacerbate HIV-1 infection/replication when cocultured with CD4+ T cells, and that preexposure of CD4+ T cells to CECs enhances their permissibility to HIV infection. However, mature red blood cells (RBCs) do not enhance HIV replication when cocultured with CD4+ T cells. We also found CECs express substantial levels of the NOX2 gene and via a mitochondrial reactive oxygen species (ROS)-dependent mechanism possibly upregulate NF-κB in CD4+ T cells once cocultured, which affects the cell cycle machinery to facilitate HIV-1 replication. The complement receptor-1 (CD35) and the Duffy antigen receptor for chemokines (DARC) as potential HIV target molecules are expressed significantly higher on CECs compared to mature red blood cells. Blocking CD35 or DARC substantially abolishes HIV-1 transmission by RBCs to uninfected CD4+ T cells but not by CECs. In contrast, we observed CECs bind to HIV-1 via CD235a and subsequently transfer the virus to uninfected CD4+ T cells, which can be partially blocked by the anti-CD235a antibody. More importantly, we found that CECs from HIV-infected individuals in the presence of antiretroviral therapy harbor infective viral particles, which mediate HIV-1 trans-infection of CD4+ T cells. Therefore, our findings provide a novel insight into the role of CECs in HIV pathogenesis as potential contributing cells in viral persistence and transmission.

Survival of the allogeneic pregnancy depends on the maintenance of immune tolerance to paternal alloantigens at the fetomaternal interface. Multiple localized mechanisms contribute to the fetal evasion from the mother’s immune rejection as the fetus is exposed to a wide range of stimulatory substances such as maternal alloantigens, microbes and amniotic fluids. In this article, we demonstrate that CD71+ erythroid cells are expanded at the fetomaternal interface and in the periphery during pregnancy in both humans and mice. These cells exhibit immunosuppressive properties, and their abundance is associated with a Th2 skewed immune response, as their depletion results in a proinflammatory immune response at the fetomaternal interface. In addition to their function in suppressing proinflammatory responses in vitro, maternal CD71+ erythroid cells inhibit an aggressive allogeneic response directed against the fetus such as reduction in TNF-α and IFN-γ production through arginase-2 activity and PD-1/programmed death ligand-1 (PDL-1) interactions. Their depletion leads to the failure of gestation due to the immunological rejection of the fetus. Similarly, fetal liver CD71+ erythroid cells exhibit immunosuppressive activity. Therefore, immunosuppression mediated by CD71+ erythroid cells on both sides (mother/fetus) is crucial for fetomaternal tolerance. Thus, our results reveal a previously unappreciated role for CD71+ erythroid cells in pregnancy and indicate that these cells mediate homeostatic immunosuppressive/immunoregulatory responses during pregnancy.

Establishing optimal growth conditions for secondary metabolites production in vitro is vital for the biotechnological development of medicinal plants. In the present work we investigate the relations between the supplementation of plant growth regulators (benzyl adenine and indole-3-butyric acid) to in vitro shoot cultures of the medicinal plant Artemisia alba Turra, the productivity of antioxidant polyphenolic compounds and the structural and functional characteristics of the photosynthetic apparatus. We assayed the structural characteristics of isolated thylakoid membranes from the aerial parts by means of circular dichroism spectroscopy and atomic force microscopy, and the photosynthetic performance by pulse amplitude fluorescence modulated imaging. Although a complex relationship between benzyl adenine and indole-3-butyric acid supplementation, the polyphenolic levels and the architecture and functionality of the photosynthetic thylakoid membranes was revealed, a clear correlation was established between the concentration of the produced polyphenolic compounds and the quantum yield of photosystem II. Our data demonstrate that there is an optimal combination of the applied plant growth regulators that triggers efficient photosynthesis and high phenolics production.

The impact of institutional environment and institutional entrepreneurs for corporate social responsibility (CSR) uptake, practice and process in the context of Western countries has been extensive...

Newborns are highly susceptible to infection. The underlying mechanism of neonatal infection susceptibility has generally been associated with neonatal immune cell immaturity. In this study, we challenged this notion and built upon our recent discovery that neonates are physiologically enriched with erythroid TER119+CD71+ cells (Elahi et al. 2013. Nature 504: 158–162). We have used Bordetella pertussis, a common neonatal respiratory tract infection, as a proof of concept to investigate the role of these cells in newborns. We found that CD71+ cells have distinctive immune-suppressive properties and suppress innate immune responses against B. pertussis infection. CD71+ cell ablation unleashed innate immune response and restored resistance to B. pertussis infection. In contrast, adoptive transfer of neonatal CD71+ cells into adult recipients impaired their innate immune response to B. pertussis infection. Enhanced innate immune response to B. pertussis was characterized by increased production of protective cytokines IFN-γ, TNF-α, and IL-12, as well as recruitment of NK cells, CD11b+, and CD11c+ cells in the lung. Neonatal and human cord blood CD71+ cells express arginase II, and this enzymatic activity inhibits phagocytosis of B. pertussis in vitro. Thus, our study challenges the notion that neonatal infection susceptibility is due to immune cell–intrinsic defects and instead highlights active immune suppression mediated by abundant CD71+ cells in the newborn. Our findings provide additional support for the novel theme in neonatal immunology that immunosuppression is essential to dampen robust immune responses in the neonate. We anticipate that our results will spark renewed investigation in modulating the function of these cells and developing novel strategies for enhancing host defense to infections in newborns.

CD71+erythroid cells (CECs) have a wide range of immunomodulatory properties but their potential role in HIV has never been investigated before. Here, we demonstrate that CECs are abundant in the human cord blood, placental tissue and peripheral blood of pregnant mothers. We found that CECs exacerbate HIV-1 infection/replication when co-cultured with CD4+T cells; and that pre-exposure of CD4+T cells to CECs make them more permissible to HIV-infection. Our observations indicate how interactions of CECs with CD4+T cells via reactive oxygen species (ROS)-dependent mechanism results in the upregulation of NF-kB, which affects the cell cycle machinery to facilitate HIV-1 replication. We found the complement receptor-1 (CD35) and the Duffy antigen receptor for chemokines (DARC) as potential HIV-target molecules are expressed significantly higher on CECs compared to mature red blood cells. However, blocking CD35 or DARC did not inhibit HIV-1 trans-infection to uninfected CD4+T cells. We demonstrate that CECs bind to HIV-1 via CD235a and subsequently trans-infect the virus to uninfected CD4+T cells. In addition, we found significant abundance of CECs in the blood of HIV-1 infected and anemic subjects, which enhanced HIV infection/replication in autologous CD4+T cells similar to what we observed for the cord blood and placenta-derived CECs. In agreement, a positive correlation between the frequency of CECs with the plasma viral load in HIV-1 infected antiretroviral therapy naïve individuals was observed. In addition, we found that CECs even in the presence of Tenofovir, can trans-infect HIV-1 to CD4+T cells. Our studies provide a novel insight into the role of CECs in HIV pathogenesis as potential contributing cells for viral persistence in the presence of antiretroviral therapy.Author summaryDespite current antiretroviral therapy, HIV-1 persists in a small pool of infected cells. A better understanding of HIV-reservoirs and influence of other non-immune cells on HIV-1 replication and transmission is a pre-requisite to the development of HIV-eradication strategies. Immature red blood cells (CD71+erythroid cells) are physiologically abundant in newborns, cord blood, placenta and blood of pregnant women, with a wide range of immunological properties. This study demonstrates that these cells not only enhance HIV-1 infection/replication by reactive oxygen species in HIV-target cells (CD4+T cells) but also bind to HIV and trans-infect the virus to the target cells in the presence of Tenofovir, an HIV drug.We found that these immature red blood cells are abundant in the blood of HIV-patients and anemic individuals. In addition, we observed a positive correlation between the levels of plasma viral load with the frequency of immature red blood cells in HIV-infected individuals. Therefore, our studies discover a novel role for these immature red blood in HIV pathogenesis, which encourages efforts to target these cells as adjuncts of current treatment strategies.

Cell-surface transferrin receptor (CD71+) erythroid cells are abundant in newborns with immunomodulatory properties. Here, we show that neonatal CD71+ erythroid cells express significant levels of V-domain Immunoglobulin (Ig) Suppressor of T Cell Activation (VISTA) and, via constitutive production of transforming growth factor (TGF)- β, play a pivotal role in promotion of naïve CD4+ T cells into regulatory T cells (Tregs). Interestingly, we discovered that CD71+VISTA+ erythroid cells produce significantly higher levels of TGF-β compared to CD71+VISTA− erythroid cells and CD71+ erythroid cells from the VISTA knock-out (KO) mice. As a result, CD71+VISTA+ erythroid cells—compared to CD71+VISTA− and CD71+ erythroid cells from the VISTA KO mice—significantly exceed promotion of naïve CD4+ T cells into induced Tregs (iTreg) via TGF-β in vitro. However, depletion of CD71+ erythroid cells had no significant effects on the frequency of Tregs in vivo. Surprisingly, we observed that the remaining and/or newly generated CD71+ erythroid cells following anti-CD71 antibody administration exhibit a different gene expression profile, evidenced by the up-regulation of VISTA, TGF-β1, TGF-β2, and program death ligand-1 (PDL-1), which may account as a compensatory mechanism for the maintenance of Treg population. We also observed that iTreg development by CD71+ erythroid cells is mediated through the inhibition of key signaling molecules phosphorylated protein kinase B (phospho-Akt) and phosphorylated mechanistic target of rapamycin (phospho-mTOR). Finally, we found that elimination of Tregs using forkhead box P3 (FOXP3)-diptheria toxin receptor (DTR) mice resulted in a significant expansion in the frequency of CD71+ erythroid cells in vivo. Collectively, these studies provide a novel, to our knowledge, insight into the cross-talk between CD71+ erythroid cells and Tregs in newborns. Our results highlight the biological role of CD71+ erythroid cells in the neonatal period and possibly beyond., Author summary The primary role of the red blood cells is to transport oxygen, but we know relatively little about the other functions they perform. Following maturation, red blood cells exit the bone marrow and enter blood circulation. Their immature counterparts are normally absent or in very low frequency in the blood of healthy adults. However, we showed previously that immature red blood cells are abundant in the spleens of neonatal mice and in human umbilical cord blood and that these cells possess immunological properties. In this report, we studied a subset of neonatal immature red blood cells that express a protein called V-domain Immunoglobulin (Ig) Suppressor of T Cell Activation (VISTA) on their surface. We found that the presence of VISTA enables the cells to repeatedly produce the regulatory cytokine TGF-β. TGF-β induces a subset of naïve lymphocytes—the CD4+ T cells—and converts them into regulatory T cells, also known as Tregs. Tregs modulate and suppress other immune cells. Our studies provide novel insights, to our knowledge, into the immunological role of immature red blood cells in newborns.

Background and aims For women with inflammatory bowel disease [IBD], it is not very well known how IBD or IBD treatment affects their breast milk components. We aimed to investigate whether breast milk composition differs in healthy control [HC] versus IBD mothers in terms of antibodies, cytokines, and metabolite,s to identify potential impact of IBD breast milk on neonatal immune system. Methods Breast milk specimens from HC [n = 17] and IBD [n = 31 for Crohn's disease [CD]; and n = 41 for ulcerative colitis [UC]; were collected at 3 and 6 months postpartum [PP3] and [PP6], respectively. Faecal samples were also collected. Cytokines and immunoglobulins [IgA/IgG/IgE] were analysed by multiplex Meso Scale Discovery [MSD] and commercial kits. Moreover, breast milk metabolites were analysed by 1H nuclear magnetic resonance [NMR]. Results We found that breast milk from IBD mothers showed significantly lower levels of IgA, sugar metabolite [lactose], and 2-aminobutyrate. In contrast, we observed that breast milk from mothers with IBD had increased levels of pro-inflammatory cytokines and higher energy metabolites [lactate and succinate] than milk from healthy mothers. In addition, we noticed that the type of treatment [5-aminosalicylic acid versus biologics] influenced the milk cytokines and metabolites profile. Conclusions The reduction in immunoprotective components of IBD breast milk such as sIgA and lactose theoretically may modulate the potential protective effects of breastfeeding. On the other hand, presence of higher levels of pro-inflammatory cytokines, lactate, and succinate may predispose the offspring to an inflammatory condition or impact on the gut microbiome. Better understanding of the role of succinate in infants and its potential effects on microbiome or mucosal immunity merits further investigations.

The pioneer microbiota of the neonatal gut are essential for gut maturation, and metabolic and immunologic programming. Recent research has shown that early bacterial colonization may impact the occurrence of disease later in life (microbial programming). Despite early conflicting evidence, it has long been considered that the womb is a sterile environment and human microbial colonization begins at birth. In the last few years, several findings have reiterated the presence of microbes in infant first stool (meconium) and pointed to the existence of in utero microbial colonization of the infant gut. The dominant bacterial taxa detected in meconium specimens belong to the Enterobacteriaceae family (Escherichia genus) and lactic acid bacteria (notably members of the genera Leuconostoc, Enterococcus, and Lactococcus). Maternal atopy promotes dominance of Enterobacteriaceae in newborn meconium, which in turn may lead to respiratory problems in the infant. This microbial interaction with the host immune system may in fact, originate during fetal life. Our review evaluates the evidence for an intrauterine origin of meconium microbiota, their composition and influences, and potential clinical implications on infant health.

The sizeable theoretical and empirical literature on corporate social responsibility (CSR) and business ethics in developed economies and Western countries indicates that the topic has attracted si...

BACKGROUND AND AIMS: CD71(+) erythroid cells are enriched during pregnancy with immuno suppressive properties. We investigated the frequency and functionality of CD71(+) erythroid cells in peripheral blood, cord blood, and placenta of inflammatory bowel disease [IBD] patients versus healthy controls [HCs]. We aimed to determine their role in IBD pathogenesis during pregnancy. METHODS: Peripheral blood was collected at preconception, the first, second and third trimesters, and postpartum. Cord blood and placental tissues were collected at the time of birth. Cells from different specimens were subjected to immune-phenotyping and functional assays. CD71(+) erythroid cells were purified for quantitative polymerase chain reaction [qPCR] analysis. Using an allogeneic mouse model of pregnancy, the effects of CD71(+) erythroid cells depletion on intestinal homeostasis and dysbiosis was studied. RESULTS: IBD patients had lower CD71(+) erythroid cells during pregnancy compared with HCs. Placenta and cord blood CD71(+) erythroid cells from IBD patients exhibited impaired functionality and expressed lower inhibitory molecules including VISTA, TGF-β, and reactive oxygen species [ROS]. Lower CD71(+) erythroid cells were correlated with reduced regulatory T cells and increased immune-activation in IBD patients. Depletion of CD71(+) erythroid cells in an allogeneic pregnancy model resulted in upregulation of TLRs, IL-6, and CXCL-1, and enhanced production of TNF-α, in intestinal tissues. In contrast, TGF-β gene expression was reduced. Excessive inflammatory response in the gut [e.g. TNF-α] affects intestinal integrity and CD71(+) erythroid cells impact on the gut’s bacterial composition. CONCLUSIONS: Reduced frequency and/or impaired functionality of CD71(+) erythroid cells during pregnancy may predispose IBD patients to a more pro-inflammatory milieu in their gastrointestinal tract, characterised by lower Tregs, higher IL-6, and TNF-α, and dysbiosis.

Survival of the allogeneic pregnancy depends on the maintenance of immune tolerance to paternal alloantigens at the fetomaternal interface. Multiple localized mechanisms contribute to the fetal evasion from the mother's immune rejection as the fetus is exposed to a wide range of stimulatory substances such as maternal alloantigens, microbes and amniotic fluids. In this article, we demonstrate that CD71

Corporate Social Responsibility (CSR) is a research area of burgeoning focus for international business and yet it is mostly dominated by its Western perspectives. However, the CSR movement can have global ramifications and thus it is important to examine its potential variations in different socio-cultural contexts. This paper chooses to examine the status of CSR in the Middle East by utilising extant secondary sources in the field. The results highlight two interconnected yet contradictory issues: (a) CSR as a concept does not appear to be well-researched or well-developed in the Middle Eastern context however it is highly possible that (b) the CSR movement as understood in the Western context may not be particularly relevant in this socio-cultural context and maybe alternative interpretations of CSR are needed. The review identifies gaps in the literature, discusses possible research directions that can enrich our knowledge of CSR by developing unique nuances that will augment the knowledge domain with new theoretical insights for the phenomenon.

Grounded Theory strategy (GT) has been introduced almost 50 years ago as the approach developed significantly since that time and contributed to emergence of variety of GT strategies. One of these variations is the constructive turn of Kathy Charmaz. In this paper we demonstrate (1) the potential of Constructive Grounded Theory (CGT) into scientific inquiry on CSR and (2) how the approach was implemented in order to build a substantive theory for CSR by utilising a practical example from a recently completed doctoral study by the lead author.

Purpose – The authors are reviewing Social Intrapreneurism and All That Jazz: How business innovators are helping to build a more sustainable world – the last book of the scholarly team David Grayson, Melody McLaren and Heiko Spitzeck issued in March 2014 that aims to demonstrate how business can become an active participant in building a sustainable future by utilizing its capacity and resources. Design/methodology/approach – By reviewing their book in perspective through the literature, the authors discuss its potential and significance for academic and business society. Findings – By doing so, the book was identified as a quite beneficial and a valuable source of information for business students with interest in corporate social responsibility and sustainability, individuals having career aspirations in the field of social intrapreneurship, and managers aiming to introduce social intrapreneurism in their organisations. Originality/value – The paper adds some further insights into the topic of social intrapreneurship and the relevance of this practice to well-known and established concepts focused on the relationship between business and society.

Maternal and childhood obesity in pregnancy are worrisome public health issues facing our world today. New gene sequencing methods have advanced our knowledge of the disruptive effect of birth interventions and postnatal exposures on the maturation of gut microbiota and immunity during infancy. Yet, little is known about the impact of maternal pregnancy overweight on gut microbes and related processes, and how this may affect overweight risk in offspring. To address this gap in knowledge, we surveyed human studies for evidence in children, infants and pregnant women to piece together the limited literature and generate hypotheses for future investigation. From this literature, we learned that higher Lactobacillus yet lower Bacteroides spp. colonization of gut microbiota within 3 months of birth predicted risk for infant and child overweight. The abundance of bifidobacteria and staphylococci also appeared to play a role in the association with overweight, as did infant fecal immunoglobulin A levels, glycoproteins of the gut immune system that are acquired from breast milk and produced by the infant. We proposed that pregnancy overweight influences the compositional structure of gut microbiota in infants through vertical transfer of microbiota and/or their metabolites during pregnancy, delivery and breastfeeding. Finally, we brought forward emerging evidence on sex dimorphism, as well as ethnic and geographic variation, in reported associations between maternal overweight-induced gut microbiota dysbiosis and overweight risk.

Increasing globally, particularly in children, obesity is a serious public health issue and risk factor for overweight and metabolic disease in later life. Both in experimental animal and human studies, advances in gene sequencing technologies have yielded intriguing possibilities for the role of the gut microbiome in later development of overweight status. Before translating study findings into practice, we must first reconcile inconsistencies between animal experimentation, and human adult and infant studies. Recent evidence for associations with gut microbiota and infant weight gain or child weight status, implicate Bacteroides and Lactobacillus species. Dietary manipulation with human milk and pre/probiotic formulations holds promise for preventing obesity.

Lamium album L. is a perennial herb widely used in folk medicine. It possesses a wide spectrum of therapeutic activities (anti-inflammatory, astringent, antiseptic, antibiotic, antispasmodic, antioxidant and anti-proliferative). Preservation of medicinal plant could be done by in vitro propagation to avoid depletion from their natural habitat. It is important to know whether extracts from L. album plants grown in vitro possess similar properties as extracts from plants grown in vivo. For these reasons, it is important to examine changes in the composition of secondary metabolites during in vitro cultivation of the plant and how they affect the biological activity. We used A549 human cancer cell line and normal kidney epithelial cells MDCKII (Madin–Darby canine kidney cells II) as controls in assessing the anti-cancer effect of plant extracts. To elucidate changes in some key functional characteristics, adhesion test, MTT (3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyl tetrazolium bromide), transepithelial resistance (TER), immunofluorescence staining and trypan blue exclusion test were performed. Methanol and chloroform extracts of in vivo and in vitro propagated plants affected differently cancerous and non-cancerous cells. The most pronounced differences were observed in the morphological analysis and in the cell adhesive properties. We also detected suppressed epithelial transmembrane electrical resistance of MDCK II cells, by treatment with plant extracts, compared to non-treated MDCK II cells. A549 cells did not polarize under the same conditions. Altered organization of actin filaments in both cell types were noticed suggesting that extracts from L. album L. change TER and actin filaments, and somehow may block cell mechanisms, leading to the polarization of MDCK II cells.

In vitro culture of Balkan endemic medicinal plant Sideritis scardica was previously initiated and different approaches for influencing the productivity of polyphenolics have been applied [1]. The present work discusses the spectrophotometric and HPTLC phenolics and flavonoids phytochemical profiling, DPPH radical scavenging activity and lipase and acetylcholinesterase inhibition assay of total methanol extract of plant material of the in vitro cultured plant. The following plant growth regulators were added to the control medium: 0.2 mg/L benzyl adenine (BA) + 0.02 mg/L 1-Naphthaleneacetic acid (NAA) (Sm); 0.2 mg/L BA + 0.5 mg/L NAA (Sr_1), 0.2 mg/L BA + 1.0 mg/L NAA (Sr_2), 0.5 mg/L BA + 0.5 mg/L NAA (Sr_3) and 0.5 mg/L BA + 1.0 mg/L NAA (Sr_4). As a general observation all treatments increased significantly the survival rate of explants, as well as polyphenolics productions as compared with the non-treated control. Strong relation between polyphenolic content and radical scavenging capacity were recorded and one probable lipase and and 2-4 components with acetylcholinesterase inhibition activity were identified. As a result of the work in vitro culture systems for optimal biomass production and secondary metabolites yield were selected. This work was financed by the PhytoBalk project (BSRP, grant No. IZEBZ0_142989). [1] Koleva P, Petrova N, Krumova S, Velikova V, Aneva I, Evstatieva L, Wolfram E, Danova K (2016) Planta Med 2016; 82(S 01): S1-S381

Secretory Immunoglobulin A (sIgA) plays a critical role to infant gut mucosal immunity. Delayed IgA production is associated with greater risk of allergic disease. Murine models of stressful events during pregnancy and infancy show alterations in gut immunity and microbial composition in offspring, but little is known about the stress-microbiome-immunity pathways in humans. We investigated differences in infant fecal sIgA concentrations according to the presence of maternal depressive symptoms during and after pregnancy. A subsample of 403 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) cohort were studied. Their mothers completed the Center of Epidemiologic Studies Depression Scale when enrolled prenatally and again postpartum. Quantified by Immundiagnostik sIgA ELISA kit, sIgA from infant stool was compared across maternal depressive symptom categories using Mann-Whitney U-tests and logistic regression models that controlled for various covariates. Twelve percent of women reported clinically significant depressive symptoms only prenatally, 8.7% had only postpartum symptoms and 9.2% had symptoms both pre and postnatally. Infants born to mothers with pre and postnatal symptoms had significantly lower median sIgA concentrations than those in the reference group (4.4 mg/g feces vs. 6.3 mg/g feces; p = 0.033). The odds for sIgA concentrations in the lowest quartile was threefold higher (95% CI: 1.25–7.55) when mothers had pre and postnatal symptoms, after controlling for breastfeeding status, infant age, antibiotics exposure and other covariates. Postnatal symptoms were not associated with fecal sIgA, independently of breastfeeding status. Infants born to mothers with depressive symptoms appear to have lower fecal sIgA concentrations, predisposing them to higher risk for allergic disease.

Infant’s immune system cannot control infection or respond to vaccination as efficiently as older individuals, a phenomenon that has been attributed to immunological immaturity. Recently, we challenged this notion and proposed the presence of actively immunosuppressive and physiologically enriched CD71+ erythroid cells in neonates. Here we utilized Bordetella pertussis, a common neonatal respiratory tract pathogen, as a proof of concept to investigate the role of these cells in adaptive immunity. We observed that CD71+ cells have distinctive immunosuppressive properties and prevent recruitment of immune cells to the mucosal site of infection. CD71+ cells ablation unleashed induction of B. pertussis-specific protective cytokines (IL-17 and IFN-γ) in the lungs and spleen upon re-infection or vaccination. We also found that CD71+ cells suppress systemic and mucosal B. pertussis-specific antibody responses. Enhanced antigen-specific adaptive immunity following CD71+ cells depletion increased resistance of mice to B. pertussis infection. Furthermore, we found that human cord blood CD71+ cells also suppress T and B cell functions in vitro. Collectively, these data provide important insight into the role of CD71+ erythroid cells in adaptive immunity. We anticipate our results will spark renewed investigation in modulating the function of these cells to enhance host defense to infections in newborns.

Newborns are highly susceptible to infection. The underlying mechanism of neonatal infection susceptibility has generally been associated with neonatal immune cell immaturity. In this study, we challenged this notion and built upon our recent discovery that neonates are physiologically enriched with erythroid TER119