Access to recreational physical activities by car and bus : an assessment of socio-spatial inequalities in mainland Scotland

Obesity and other chronic conditions linked with low levels of physical activity (PA) are associated with deprivation. One reason for this could be that it is more difficult for low-income groups to access recreational PA facilities such as swimming pools and sports centres than high-income groups. In this paper, we explore the distribution of access to PA facilities by car and bus across mainland Scotland by income deprivation at datazone level. GIS car and bus networks were created to determine the number of PA facilities accessible within travel times of 10, 20 and 30 minutes. Multilevel negative binomial regression models were then used to investigate the distribution of the number of accessible facilities, adjusting for datazone population size and local authority. Access to PA facilities by car was significantly (p<0.01) higher for the most affluent quintile of area-based income deprivation than for most other quintiles in small towns and all other quintiles in rural areas. Accessibility by bus was significantly lower for the most affluent quintile than for other quintiles in urban areas and small towns, but not in rural areas. Overall, we found that the most disadvantaged groups were those without access to a car and living in the most affluent areas or in rural areas

Using Growth Factors in Human Extraction Sockets: A Histologic and Histomorphometric Evaluation of Short-Term Healing

Purpose: Ridge preservation protocols reduce crestal remodeling after tooth extraction. There is insufficient evidence on bone grafting in combination with platelet-rich plasma (PRP) or recombinant human platelet-derived growth factor (rhPDGF-BB). The aim of this study is to evaluate healing of grafted and nongrafted sockets and the effect of PRP and rhPDGF-BB on early remodeling. Materials and Methods: Forty-one patients whose treatment plan included extraction of anterior or premolar teeth were randomized into four groups. Group 1: collagen plug (control). Group 2: mineralized freeze-dried bone allograft (FDBA)/β-tricalcium phosphate (β-TCP)/collagen plug. Group 3: FDBA/β-TCP/PRP/collagen plug. Group 4: FDBA/β-TCP/rhPDGF-BB/collagen plug. At 8 weeks, a core was harvested from the center of 41 sockets. Histomorphometric analysis took place. Differences were analyzed using one-way analysis of variance (ANOVA) or chi-square tests for continuous and categorical data. Pairwise comparisons were tested using least squares means. Spearman correlation coefficients were used to evaluate the relationship of bone growth with potential confounders. A P value < .05 was considered statistically significant. Results: ANOVA did not indicate statistical significance in age, gender, smoking, ethnicity, or race distribution. Significant differences in tissue distribution were identified between groups and between different thirds of harvested core. More new bone and amorphous organic matrix was noted in the control group. In sites where bone graft was combined with growth factors, the amount of residual particles was less than in sites where bone graft was used alone. Conclusions: Inclusion of bone replacement graft suppressed new bone formation during early healing. Inclusion of PRP and rhPDGF-BB produced less residual bone graft material, indicating more rapid turnover of bone graft. All treatment modalities achieved a significant amount of new vital bone at 8 weeks postextraction

Identification of enhanced IFN-γ signaling in polyarticular juvenile idiopathic arthritis with mass cytometry

Polyarticular juvenile idiopathic arthritis (JIA) is among the most challenging of the JIA subtypes to treat. Even with current biologic therapies, the disease remains difficult to control in a substantial subset of patients, highlighting the need for new therapies. The aim of this study was to use the high dimensionality afforded by mass cytometry with phospho-specific antibodies to delineate signaling abnormalities in immune cells from treatment-naive polyarticular JIA patients. Peripheral blood mononuclear cells were isolated from 17 treatment-naive polyarticular JIA patients, 10 of the patients after achieving clinical remission, and 19 healthy controls. Samples were stimulated for 15 minutes with IL-6 or IFN-γ and analyzed by mass cytometry. Following IFN-γ stimulation, increased STAT1 and/or STAT3 phosphorylation was observed in subsets of CD4 T cells and classical monocytes from treatment-naive patients. The enhanced IFN-γ signaling was associated with increased expression of JAK1 and SOCS1 in CD4 T cells. Furthermore, substantial heterogeneity in surface marker expression was observed among the subsets of CD4 T cells and classical monocytes with increased IFN-γ responsiveness. The identification of enhanced IFN-γ signaling in CD4 T cells and classical monocytes from treatment-naive polyarticular JIA patients provides mechanistic support for investigations into therapies that attenuate IFN-γ signaling in this disease

Mechanistic model of natural killer cell proliferative response to IL-15 receptor stimulation

Natural killer (NK) cells are innate lymphocytes that provide early host defense against intracellular pathogens, such as viruses. Although NK cell development, homeostasis, and proliferation are regulated by IL-15, the influence of IL-15 receptor (IL-15R)-mediated signaling at the cellular level has not been quantitatively characterized. We developed a mathematical model to analyze the kinetic interactions that control the formation and localization of IL-15/IL-15R complexes. Our computational results demonstrated that IL-15/IL-15R complexes on the cell surface were a key determinant of the magnitude of the IL-15 proliferative signal and that IL-15R occupancy functioned as an effective surrogate measure of receptor signaling. Ligand binding and receptor internalization modulated IL-15R occupancy. Our work supports the hypothesis that the total number and duration of IL-15/IL-15R complexes on the cell surface crosses a quantitative threshold prior to the initiation of NK cell division. Furthermore, our model predicted that the upregulation of IL-15Rα on NK cells substantially increased IL-15R complex formation and accelerated the expansion of dividing NK cells with the greatest impact at low IL-15 concentrations. Model predictions of the threshold requirement for NK cell recruitment to the cell cycle and the subsequent exponential proliferation correlated well with experimental data. In summary, our modeling analysis provides quantitative insight into the regulation of NK cell proliferation at the receptor level and provides a framework for the development of IL-15 based immunotherapies to modulate NK cell proliferation

A method to evaluate equitable accessibility: combining ethical theories and accessibility-based approaches

In this paper, we present the case that traditional transport appraisal methods do not sufficiently capture the social dimensions of mobility and accessibility. However, understanding this is highly relevant for policymakers to understand the impacts of their transport decisions. These dimensions include the distribution of mobility and accessibility levels over particular areas or for specific population groups, as well as how this may affect various social outcomes, including their levels of participation, social inclusion and community cohesion. In response, we propose a method to assess the socially relevant accessibility impacts (SRAIs) of policies in some of these key dimensions. The method combines the use of underlying ethics principles, more specifically the theories of egalitarianism and sufficientarianism, in combination with accessibility-based analysis and the Lorenz curve and Gini index. We then demonstrate the method in a case study example. Our suggestion is that policymakers can use these ethical perspectives to determine the equity of their policies decisions and to set minimum standards for local transport delivery. This will help them to become more confident in the development and adoption of new decision frameworks that promote accessibility over mobility and which also disaggregate the costs and benefits of transport policies over particular areas or for specific under-served population groups

Dual requirement of cytokine and activation receptor triggering for cytotoxic control of murine cytomegalovirus by NK cells

Natural killer (NK) cells play a critical role in controlling murine cytomegalovirus (MCMV) and can mediate both cytokine production and direct cytotoxicity. The NK cell activation receptor, Ly49H, is responsible for genetic resistance to MCMV in C57BL/6 mice. Recognition of the viral m157 protein by Ly49H is sufficient for effective control of MCMV infection. Additionally, during the host response to infection, distinct immune and non-immune cells elaborate a variety of pleiotropic cytokines which have the potential to impact viral pathogenesis, NK cells, and other immune functions, both directly and indirectly. While the effects of various immune deficiencies have been examined for general antiviral phenotypes, their direct effects on Ly49H-dependent MCMV control are poorly understood. To specifically interrogate Ly49H-dependent functions, herein we employed an in vivo viral competition approach to show Ly49H-dependent MCMV control is specifically mediated through cytotoxicity but not IFNγ production. Whereas m157 induced Ly49H-dependent degranulation, efficient cytotoxicity also required either IL-12 or type I interferon (IFN-I) which acted directly on NK cells to produce granzyme B. These studies demonstrate that both of these distinct NK cell-intrinsic mechanisms are integrated for optimal viral control by NK cells

Type I IFN promotes NK cell expansion during viral infection by protecting NK cells against fratricide

Type I interferon (IFN) is crucial in host antiviral defense. Previous studies have described the pleiotropic role of type I IFNs on innate and adaptive immune cells during viral infection. Here, we demonstrate that natural killer (NK) cells from mice lacking the type I IFN-α receptor (Ifnar(−/−)) or STAT1 (which signals downstream of IFNAR) are defective in expansion and memory cell formation after mouse cytomegalovirus (MCMV) infection. Despite comparable proliferation, Ifnar(−/−) NK cells showed diminished protection against MCMV infection and exhibited more apoptosis compared with wild-type NK cells. Furthermore, we show that Ifnar(−/−) NK cells express increased levels of NK group 2 member D (NKG2D) ligands during viral infection and are susceptible to NK cell–mediated fratricide in a perforin- and NKG2D-dependent manner. Adoptive transfer of Ifnar(−/−) NK cells into NK cell–deficient mice reverses the defect in survival and expansion. Our study reveals a novel type I IFN–dependent mechanism by which NK cells evade mechanisms of cell death after viral infection

Periodontal manifestations of systemic diseases and developmental and acquired conditions:consensus report of workgroup 3 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions

BACKGROUND A variety of systemic diseases and conditions can affect the course of periodontitis or have a negative impact on the periodontal attachment apparatus. Gingival recessions are highly prevalent and often associated with hypersensitivity, the development of caries and non-carious cervical lesions on the exposed root surface and impaired esthetics. Occlusal forces can result in injury of teeth and periodontal attachment apparatus. Several developmental or acquired conditions associated with teeth or prostheses may predispose to diseases of the periodontium. The aim of this working group was to review and update the 1999 classification with regard to these diseases and conditions, and to develop case definitions and diagnostic considerations. METHODS Discussions were informed by four reviews on 1) periodontal manifestions of systemic diseases and conditions; 2) mucogingival conditions around natural teeth; 3) traumatic occlusal forces and occlusal trauma; and 4) dental prostheses and tooth related factors. This consensus report is based on the results of these reviews and on expert opinion of the participants. RESULTS Key findings included the following: 1) there are mainly rare systemic conditions (such as Papillon-Lefevre Syndrome, leucocyte adhesion deficiency, and others) with a major effect on the course of periodontitis and more common conditions (such as diabetes mellitus) with variable effects, as well as conditions affecting the periodontal apparatus independently of dental plaque biofilm-induced inflammation (such as neoplastic diseases); 2) diabetes-associated periodontitis should not be regarded as a distinct diagnosis, but diabetes should be recognized as an important modifying factor and included in a clinical diagnosis of periodontitis as a descriptor; 3) likewise, tobacco smoking - now considered a dependence to nicotine and a chronic relapsing medical disorder with major adverse effects on the periodontal supporting tissues - is an important modifier to be included in a clinical diagnosis of periodontitis as a descriptor; 4) the importance of the gingival phenotype, encompassing gingival thickness and width in the context of mucogingival conditions, is recognized and a novel classification for gingival recessions is introduced; 5) there is no evidence that traumatic occlusal forces lead to periodontal attachment loss, non-carious cervical lesions, or gingival recessions; 6) traumatic occlusal forces lead to adaptive mobility in teeth with normal support, whereas they lead to progressive mobility in teeth with reduced support, usually requiring splinting; 7) the term biologic width is replaced by supracrestal tissue attachment consisting of junctional epithelium and supracrestal connective tissue; 8) infringement of restorative margins within the supracrestal connective tissue attachment is associated with inflammation and/or loss of periodontal supporting tissue. However, it is not evident whether the negative effects on the periodontium are caused by dental plaque biofilm, trauma, toxicity of dental materials or a combination of these factors; 9) tooth anatomical factors are related to dental plaque biofilm-induced gingival inflammation and loss of periodontal supporting tissues. CONCLUSION An updated classification of the periodontal manifestations and conditions affecting the course of periodontitis and the periodontal attachment apparatus, as well as of developmental and acquired conditions, is introduced. Case definitions and diagnostic considerations are also presented