Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th) 1 responses and ...show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a suitable tool for the characterisation of macrophage polarisation in situ. Furthermore, CD163 cannot be considered a reliable M2 marker when used on its own.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Reveals what factors influence the use of a range of appropriability mechanisms in a less developed economy (LDE).•Shows how innovative firms in an LDE combine pairs of appropriability ...mechanisms.•Discloses that despite fragile patenting conditions, firms do use patents with neighbouring mechanisms.•Uncovers the role of design, lead-time and trademarks for appropriation in LDEs.•Reveals that firms in LDEs make extensive use of appropriability mechanisms that are not technology based.
Despite increased focus on understanding how firms appropriate the returns from innovation, our knowledge regarding firms' behaviour in less developed economies (LDEs) is still scant. This paper provides a nuanced view as to how firms that are not at the technological frontier attempt to capture value when they encounter fragile patenting conditions. I analyse a unique dataset on innovative activities in Brazil. My findings reveal the effects (if any) of a number of factors on the use of a wide range of appropriability mechanisms. These factors include measures of knowledge intensity, novelty of products and processes, firm size, degree of competition, innovation cooperation, government support for innovation, and type of ownership. In addition, my empirical exercise provides evidence of the extent to which firms in an LDE adopt different appropriability mechanisms in pairs. Overall, this paper indicates that even in the absence of an effective patent system, firms do use patents. However, there are other patterns of appropriability in which firms use design (being registered or not registered accordingly), lead-time or trademarks in association with other means of appropriation.
Most observations of the patent behavior of firms are derived from institutional environments in which relatively strong protection can be obtained, even if patents per se are imperfect protection ...mechanisms. As a result, the determinants of a firm's propensity to patent in a weak appropriability regime are still unclear. This paper advances our current understanding of patent behavior by exploring the effects of manufacturing firms’ innovation partnerships, foreign ownership, and adoption of new management practices on the likelihood of patenting. Our analysis is based on the responses of firms to questions in the Brazilian Industrial Survey of Technological Innovation (Pintec). The findings presented here indicate that, despite the weaknesses of the patent system, firms engaged in innovation-oriented collaborations are more likely to patent than firms not involved in these partnerships. Additionally, the results reveal that domestic and foreign firms in a weak institutional environment are similar in their inclination to patent. Finally, the empirical exercise shows that when a patent system is characterized by high levels of formalism and low levels of safeguarding against infringements of property rights firms adopt novel management practices as substitutes for patents.
•I examine firms’ propensity to patent in a weak institutional environment.•Firms in this context adopt new management practices as substitutes for patents.•Firms that cooperate are more likely to patent even if the patent system is weak.•Foreign firms are no different from domestic ones in their likelihood of patenting.
Despite recognizing the detrimental impact of parental violence on children’s mental and physical health throughout their lives, violence remains an all-too-real part of life for many children around ...the globe. However, data on the child-reported prevalence of experienced family violence are scarce and primarily based on parental reports. This study aimed to broaden the body of evidence and measure the lifetime prevalence of child-reported experience of violent disciplinary practices perpetrated by parents and to identify its associated sociodemographic and economic factors. We conducted a cross-sectional study using data from 5,281 Generation XXI participants recruited from 2005 to 2006 in Porto, Portugal. Parental disciplinary practices were reported by 7-year-old children using the Parent-Child Conflict Tactics Scale. Pearson’s Chi-squared test was used to compare differences in child-reported frequencies of violent disciplinary practices by sociodemographic variables. We observed statistically significant differences in rates of violent disciplinary practices according to the child’s and parent’s gender. Specifically, fathers exhibited a higher likelihood than mothers to engage in psychological aggression and corporal punishment, while mothers were more prone to engage in severe and very severe physical assault. When fathers were the perpetrators, boys were more inclined than girls to report all forms of violent disciplinary measures, and when mothers were the perpetrators, boys were particularly susceptible to severe and very severe physical assault compared to girls. In our study, children reported being frequently subjected to violent parental disciplinary practices, independently of family socioeconomic background. Children were more likely to experience psychological aggression and corporal punishment if they were born into high-income families, while severe and very severe physical assaults were more common among children whose parents had lower educational levels. National public awareness of the negative effects of violent disciplinary practices is urgently needed, promoting child-friendly and nonviolent approaches to discipline.
There is considerable literature on the psychological and behavioural benefits of green space. However, less is known about its health-promoting effects, as expressed on biological markers. ...Additionally, incorporating biomarkers into pediatric research may help elucidate the links between exposures to environmental stressors and lifelong health.
To measure the association between geographical accessibility to green spaces and allostatic load (AL), a measure of biological multi-system dysregulation.
We used data from 3108 7-year old children enrolled in Generation XXI, a population-based birth cohort from the Porto Metropolitan Area (Portugal). We computed an AL index based on seven biomarkers representing four regulatory systems: immune/inflammatory system (high sensitivity C-reactive protein); metabolic system (high density lipoprotein; total cholesterol; glycated hemoglobin; waist-hip ratio) and cardiovascular system (systolic and diastolic blood pressure). Accessibility to green spaces was calculated using a Geographic Information System and crude and adjusted associations were estimated using mixed-effects regression models.
Among the 3108 children (51.7% male; mean age 87.3 months), the mean AL index was 0.00 (standard deviation 2.94). Adjusted models showed that having a green space within 400 m and 800 m from the child's school was inversely associated with AL (400 m: beta −0.29 95% CI −0.54 to −0.02; 800 m: −0.29 95% CI −0.51 to −0.07). Also, there was a 12% (0%; 23%) increase in the AL index for every 1 km increase in distance to the nearest green space. No significant associations with AL were observed with residential accessibility to green space or with the presence of a garden at home.
We found a cross-sectional negative association between accessibility to green space near schools and AL in children, suggesting that the provision of green space may contribute to improvements in population health beginning early in life.
•Little is known about the health-promoting effects of green space on biomarkers.•We studied the association between green space accessibility and allostatic load.•Green space around schools lowers allostatic load in urban children.
Abstract
Commonly attributed to the prevalence of M2 macrophages, tumor-associated macrophages (TAM) are linked to poor outcome in Hodgkin lymphoma (HL). MYC is supposed to control the expression of ...M2-specific genes in macrophages, and deficiency in MYC-positive macrophages inhibits tumor growth in mouse models. To verify this hypothesis for HL, seventy-six samples were subjected to immunohistochemical double staining using CD68 or CD163 macrophage-specific antibodies and a reagent detecting MYC. For each cell population, labelled cells were grouped according to low, intermediate and high numbers and related to disease-free survival (DFS) and overall survival (OS). MYC+ cells accounted for 21% and 18% of CD68+ and CD163+ cells, respectively. Numbers of MYC− macrophages were significantly higher in EBV+ cases while no differences were observed for MYC+ macrophages between EBV+ and EBV− cases. Cases with highest numbers of macrophages usually showed worst DFS and OS. In most scenarios, intermediate numbers of macrophages were associated with better outcome than very low or very high numbers. Our observations are reminiscent of the “hormesis hypothesis” and suggest that a relative lack of TAM may allow HL growth while macrophages display an inhibitory effect with increasing numbers. Above a certain threshold, TAM may again support tumor growth.
AbstractObjectiveTo assess the association of low socioeconomic status and risk factors for non-communicable diseases (diabetes, high alcohol intake, high blood pressure, obesity, physical ...inactivity, smoking) with loss of physical functioning at older ages.DesignMulti-cohort population based study.Setting37 cohort studies from 24 countries in Europe, the United States, Latin America, Africa, and Asia, 1990-2017.Participants109 107 men and women aged 45-90 years.Main outcome measurePhysical functioning assessed using the walking speed test, a valid index of overall functional capacity. Years of functioning lost was computed as a metric to quantify the difference in walking speed between those exposed and unexposed to low socioeconomic status and risk factors.ResultsAccording to mixed model estimations, men aged 60 and of low socioeconomic status had the same walking speed as men aged 66.6 of high socioeconomic status (years of functioning lost 6.6 years, 95% confidence interval 5.0 to 9.4). The years of functioning lost for women were 4.6 (3.6 to 6.2). In men and women, respectively, 5.7 (4.4 to 8.1) and 5.4 (4.3 to 7.3) years of functioning were lost by age 60 due to insufficient physical activity, 5.1 (3.9 to 7.0) and 7.5 (6.1 to 9.5) due to obesity, 2.3 (1.6 to 3.4) and 3.0 (2.3 to 4.0) due to hypertension, 5.6 (4.2 to 8.0) and 6.3 (4.9 to 8.4) due to diabetes, and 3.0 (2.2 to 4.3) and 0.7 (0.1 to 1.5) due to tobacco use. In analyses restricted to high income countries, the number of years of functioning lost attributable to low socioeconomic status by age 60 was 8.0 (5.7 to 13.1) for men and 5.4 (4.0 to 8.0) for women, whereas in low and middle income countries it was 2.6 (0.2 to 6.8) for men and 2.7 (1.0 to 5.5) for women. Within high income countries, the number of years of functioning lost attributable to low socioeconomic status by age 60 was greater in the United States than in Europe. Physical functioning continued to decline as a function of unfavourable risk factors between ages 60 and 85. Years of functioning lost were greater than years of life lost due to low socioeconomic status and non-communicable disease risk factors.ConclusionsThe independent association between socioeconomic status and physical functioning in old age is comparable in strength and consistency with those for established non-communicable disease risk factors. The results of this study suggest that tackling all these risk factors might substantially increase life years spent in good physical functioning.
Despite the potentially significant impact of women-prenatal care provider communication quality (WPCQ) on women's perinatal health, evidence on the determinants of those perceptions is still ...lacking, particularly among migrant women.
We aimed to examine the effect of women's host-country language proficiency on their perceived WPCQ. We analyzed the data of 1210 migrant and 1400 native women who gave birth at Portuguese public hospitals between 2017 and 2019 and participated in the baMBINO cohort study. Migrants' language proficiency was self-rated. Perceived WPCQ was measured as a composite score of 9 different aspects of self-reported communication quality and ranged from 0 (optimal) to 27.
A high percentage of women (29%) rated communication quality as "optimal". Zero-inflated regression models were fitted to estimate the association between language proficiency and perceived WPCQ. Women with full (aIRR 1.35; 95% CI 1.22,1.50), intermediate (aIRR 1.41; 95% CI 1.23,1.61), and limited (aIRR 1.72; 95% CI 1.45,2.05) language proficiencies were increasingly more likely to have lower WPCQ when compared to natives.
Facilitating communication with migrant women experiencing language barriers in prenatal care could provide an important contribution to improving prenatal care quality and addressing potential subsequent disparities in perinatal health outcomes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tumor-infiltrating macrophages are associated with adverse outcome in adult classical Hodgkin lymphoma (cHL). We have previously shown age-related changes in the lymphocyte composition of pediatric ...cHL. We therefore hypothesized that the number, function, and prognostic impact of macrophages in pediatric cHL would be different from adult cases.
We analyzed the number of macrophages and dendritic cells (DC) in the tumor microenvironment of pediatric cHL by immunohistochemistry. Results were analyzed in context of age, histologic characteristics, Epstein-Barr virus (EBV) status, clinical follow-up, and our previous study of T-cell populations in these cases.
One hundred cHL cases were studied, including 69% nodular sclerosis and 23% mixed cellularity cases. A total of 44.8% of cases were EBV-positive. Patients ≤10 years displayed more CD14(+) cells (P = 0.025). In comparison with nodular sclerosis, mixed cellularity was characterized by higher numbers of CD14(+), (P = 0.003) and CD163(+) cells (P = 0.027). EBV(+) cases exhibited higher numbers of CD14(+) (P < 0.0005), CD68(+) (P = 0.005), and CD163(+) cells (P = 0.02). CD68-positive cells did not display an effect on outcome. Worse overall survival was observed in cases with CD163/CD8 ratio ≥2 (P = 0.007). High numbers of CD163(+) cells were associated with worse progression-free survival (PFS; P = 0.015). Furthermore, high numbers of CD163(+) and granzyme B(+) cells were associated with worse PFS in EBV-negative (P = 0.005) but not in EBV-positive cases.
Our results suggest that macrophage composition in pediatric cHL is distinct from adults. Functional status of macrophages and their value as prognostic indicators in pediatric cHL may depend on EBV status.
PDF
