Miracle-dz/UniFAR-FTUs huggingface dataset:
The Immunoregulatory Roles of Natural Killer T Cells in Cyclophosphamide-Induced Tolerance

Background. Recent studies have indicated that natural killer T (NKT) cells are essential for the establishment of transplantation tolerance. In the present study, we have elucidated the role of recipient and donor NKT cells in cyclophosphamide (CP)-induced tolerance. Method. DBA/2 (DBA; H-2d) mice were used as donors and BALB/c (BALB; H-2d) wild-type (WT) or V&agr;14 NKT-knockout (KO, BALB/c background) mice were used as recipients. Recipients were treated with CP-induced tolerance regimen, which consists of donor spleen cells (SC) on day 0 and CP on day 2. In some experiments, NKT KO mice, which received NKT cells from either WT, inferon-&ggr; KO, or interleukin-4 KO mice, were treated with tolerant regimen. To deplete Ly49 inhibitory receptors on NKT cells in the recipient mice, anti-Ly49 monoclonal antibody cocktails were injected on day −1 when indicated. Results. Donor skin graft was permanently accepted in recipient BALB WT mice with induction of donor mixed chimerism. On the contrary, donor DBA skin allografts were chronically rejected in NKT KO recipient. Lower levels of mixed chimerism were observed in NKT KO recipients comparing to the WT recipients. The production of interferon-&ggr; or interleukin-4 from NKT cells did not affect the induction of tolerance. Depletion of Ly49 positive NKT cells abrogated the induction of skin graft tolerance. Conclusion. Recipient NKT cells, but not donor NKT cells, were dominantly required for the induction of allograft tolerance. Our results indicated that the single cytokine produced by NKT cells did not mediate the regulatory function in the induction of allograft tolerance.
Incidence of Selected Opportunistic Infections Among Children with Juvenile Idiopathic Arthritis

Objective— To compare incidence rates of selected opportunistic infections (OI) among children with and without juvenile idiopathic arthritis (JIA). Methods— Using United States national Medicaid administrative claims data from 2000 through 2005, we identified a cohort of children with JIA based on physician diagnosis codes and dispensed medications. We defined a non-JIA comparator cohort of children diagnosed with attention deficit hyperactivity disorder (ADHD). We defined 15 types of OI using physician diagnosis or hospital discharge codes, and 7 of these types also required evidence of treatment with specific antimicrobials. We calculated infection incidence rates (IR). The rates in the ADHD comparator cohort were standardized to the age, sex, and race distribution of the JIA cohort. We calculated incidence rate ratios (IRR) to compare infection rates. Results— The JIA cohort included 8,503 children with 13,990 person-years (p-y) of follow-up. The ADHD comparator cohort included 360,362 children with 477,050 p-y of follow-up. When all OI were considered together as a single outcome, there were 42 infections in the JIA cohort (IR 300 per 100,000 p-y; IRR 2.4 [1.7–3.3] versus ADHD). The most common OI among children with JIA were 3 Coccidioides (IR 21 per 100,000 p-y; IRR 101 [8.1–5319] versus ADHD); 5 Salmonella (IR 35 per 100,000 p-y; IRR 3.8 [1.2–9.5]); and 32 herpes zoster (IR 225 per 100,000 p-y; IRR 2.1 [1.4–3.0]). Conclusions— OI are rare among children with JIA. Nevertheless, children with JIA had a higher rate of OI, including Coccidioides, Salmonella, and herpes zoster, than children with ADHD.
A comparison of multiparametric MRI modalities to discriminate prostate cancer tumours

Using multiparametric MRI (mpMRI) protocols to monitor prostate cancer could provide new insights into the biological mechanisms of developing tumours. Automatically discriminating tumour regions active area of research due to the complexity and plurality of cancer behaviour. This work evaluates four different Magnetic Resonance Imaging (MRI) image modalities, namely: Diffusion-Weighted Imaging evaluated at b = {0, 100, 1000}, Apparent Diffusion Coefficient and Dynamic Contrast Enhanced MRI, by extracting texture and functional features and then selecting the optimal ones to discriminate anatomical prostate regions in each modality. The images used were taken prior to radiotherapy from eight patients previously diagnosed with moderate risk of recurrent cancer. Finally, we compared the relevance of each modality to discriminate between healthy tissue and tumour cells.
An evaluation of a community health intervention programme aimed at improving health and wellbeing

Objective The objective of this evaluation was to examine the extent to which participants in the Tailor Made Leisure Package programme experienced any improvement in their health and wellbeing. Design A quantitative survey. Setting The Healthy Living Centre initiative is an example of a community-based intervention which was formalized as part of the British government's health policy. The purpose of this initiative is to reduce inequalities in health and promote good health and wellbeing. The programme was offered by a Healthy Living Centre located in Scotland. Method The benefits of the initiative were investigated through the use of a postal questionnaire which was used to examine the perceived benefits of the Tailor Made Leisure Package programme. This was distributed to a total of 177 people who had applied to take part in the programme during the period February 2004 to February 2005. Results Of the 177 people surveyed 90 returned completed questionnaires giving a response rate of 51 per cent. Of these, 70 people started the programme. Those who started the programme took part in a variety of activities including the gym, GP Referral programme and complementary therapies. The reported benefits were that individuals felt fitter and healthier, they were taking part in additional leisure activities and that they were socializing more frequently. Those participants who had complementary therapy reported a relief of symptoms associated with their particular health condition. All of these benefits are important in the process of improving health and wellbeing. The 20 individuals who did not start their programme reported that personal circumstances, health reasons, transport problems, financial difficulties and the activities/programme being inappropriate were the main reasons for not starting the programme. Conclusion The results of the evaluation suggest that an initiative such as this is worthwhile in promoting positive health and wellbeing.
Anti-tumor necrosis factor α targets protein kinase B/c-Akt-induced resistance of effector cells to suppression in juvenile idiopathic arthritis.

OBJECTIVE To determine whether therapeutic strategies that block interleukin-6 (IL-6) or tumor necrosis factor α (TNFα) can improve the responsiveness of Teff cells to suppression in patients with juvenile idiopathic arthritis (JIA). METHODS Synovial fluid mononuclear cells (SFMCs) from the inflamed joints of patients with JIA were cultured in the presence of etanercept or anti-IL-6 in vitro, and protein kinase B (PKB)/c-Akt activation and responsiveness to suppression were measured. In addition, the in vivo effects of TNFα blockade were investigated using peripheral blood mononuclear cells obtained from patients before and after the start of etanercept therapy. RESULTS In vitro treatment of SFMCs with anti-IL-6 led to improved Treg cell-mediated suppression of cell proliferation in some but not all patients. Blocking TNFα with etanercept, however, clearly enhanced suppression, especially that of CD8+ T cells. In the presence of etanercept, PKB/c-Akt activation of Teff cells was reduced, and cells became more susceptible to transforming growth factor β-mediated suppression, indicating that anti-TNFα directly targets resistant Teff cells. CONCLUSION This study is the first to show that anti-TNFα targets the resistance of Teff cells to suppression, resulting in improved regulation of inflammatory effector cells.
Distributed formation output regulation of switching heterogeneous multi-agent systems

In this article, the distributed formation output regulation problem of linear heterogeneous multi-agent systems with uncertainty under switching topology is considered. It is a generalised framework for multi-agent coordination problems, which contains or concerns a variety of important multi-agent problems in a quite unified way. Its background includes active leader following formation for the agents to maintain desired relative distances and orientations to the leader with a predefined trajectory, and multi-agent formation with environmental inputs. With the help of canonical internal model we design a distributed dynamic output feedback to handle the distributed formation output regulation problem.
Palmitate Has Proapoptotic and Proinflammatory Effects on Articular Cartilage and Synergizes With Interleukin‐1

Obesity is a major risk factor for the development of osteoarthritis (OA) that is associated with a state of low‐grade inflammation and increased circulating levels of adipokines and free fatty acids (FFAs). The aim of this study was to analyze the effects of saturated (palmitate) and monounsaturated (oleate) FFAs on articular chondrocytes, synoviocytes, and cartilage.
Xenon and isoflurane improved biventricular function during right ventricular ischemia and reperfusion

Background: Although anesthetics have some cardioprotective properties, these benefits are often counterbalanced by their negative inotropic effects. Xenon, on the other hand, does not influence myocardial contractility. Thus, xenon may be a superior treatment for the maintenance of global hemodynamics, especially during right ventricular ischemia, which is generally characterized by a high acute complication rate.
Utilização e cobertura do Sistema de Vigilância Alimentar e Nutricional no Estado do Rio Grande do Sul, Brasil

This article seeks to describe the utilization and coverage percentage of the Nutritional and Food Surveillance System (SISVAN-Web) in the Regional Health Offices of Rio Grande do Sul in 2010 and to assess its correlation with socio-economic, demographic and health system organization variables at the time. It is an ecological study that used secondary data from the SISVAN-Web, the Department of Primary Health Care, the IT Department of the Unified Health System and the Brazilian Institute of Geography and Statistics. The evaluation of utilization and coverage data was restricted to nutritional status. The percentage of utilization of SISVAN-Web refers to the number of cities that fed the system. Total coverage was defined as the percentage of individuals in all stages of the life cycle monitored by SISVAN-Web. It was found that 324 cities fed the application, corresponding to a utilization percentage of 65.3%. Greater system coverage was observed in all Regional Health Coordination (RHC) Units for ages 0 to 5 years and 5-10 years. There was a significant association between the percentage of utilization of SISVAN-Web and Family Health Strategy coverage in each RHC Unit. The results of this study indicated low percentages of utilization and coverage of SISVAN-Web in Rio Grande do Sul.
Off Side! A Simple Modification to the Parasagittal In-Plane Approach for Paravertebral Block

Abstract The use of thoracic paravertebral blocks (PVBs) for breast cancer surgery confers important analgesic benefits. Several ultrasound (US)-guided PVB approaches have been described, but still elusive is the ideal technique that (1) permits continuous visualization of the entire needle shaft and tip, (2) avoids aiming the needle tip and injectate directly toward the neuraxis, and (3) is easy to perform. Although the parasagittal view in-plane PVB approach satisfies the former 2 criteria, maneuvering the needle to reach the targeted paravertebral space can be difficult as its trajectory is often obstructed by the bony transverse processes. This brief technical report describes the “off-side” technique—a simple solution to the technical challenge posed by the double-fulcrum effect exerted first by the transducer and then by the adjacent inferior transverse process. Our “off-side” technique marks a departure from conventional US-guided regional anesthesia teaching that recommends positioning the target in the middle of the US field and may be useful in similar types of US-guided regional anesthesia procedures such as neuraxial blockade.
Transforaminal Epidural Steroid Injections: Anatomical and Imaging Analysis Trumps Other Agendas

The issue of safety regarding therapeutic epidural injections has recently come to the forefront of the attention of health care providers and the media after the US Food and Drug Administration (FDA) distributed a warning about the risks of major morbidity or mortality from epidural corticosteroids. The warning, unfortunately, preceded the anticipated publication of the FDA’s Safe Use Initiative report on that topic. In this issue of Regional Anesthesia and Pain Medicine, Nishio writes a Daring Discourse article that demonstrates the importance of the angle of introduction of the needle for cervical transforaminal injection, informed by preprocedural planning and review of the magnetic resonance images. He appropriately shows that, in some cases, the vertebral artery may be insinuated in the path of the needle if the preprocedural approach has not adequately taken anatomical factors and variations into account. Nishio discusses the role of aberrantly located or hypoplastic vertebral arteries and other arteries (ascending cervical and deep cervical) that contribute to the segmental medullary blood supply to the spinal cord and brainstem. Other recent literature has also suggested that the vertebral artery is often displaced into the foramen in advanced cervical degenerative disease, further underscoring the importance of both advanced imaging analysis and an advanced understanding of the implication of degenerative changes around the foraminal opening. The authors of that study found, under computed tomography fluoroscopy conditions, that the foraminal opening was either completely or nearly
Channel characteristics and coordination in three-echelon dual-channel supply chain

We explore the impact of channel structure on the manufacturer, the distributer, the retailer and the entire supply chain by considering three different channel structures in radiance of with and without coordination. These structures include a traditional retail channel and two manufacturer direct channels with and without consistent pricing. By comparing the performance of the manufacturer, the distributer and the retailer, and the entire supply chain in three different supply chain structures, it is established analytically that, under some conditions, a dual channel can outperform a single retail channel; as a consequence, a coordination mechanism is developed that not only coordinates the dual channel but also outperforms the non-cooperative single retail channel. All the analytical results are further analysed through numerical examples.
KCa1.1 Inhibition Attenuates Fibroblast‐like Synoviocyte Invasiveness and Ameliorates Disease in Rat Models of Rheumatoid Arthritis

Fibroblast‐like synoviocytes (FLS) participate in joint inflammation and damage in rheumatoid arthritis (RA) and its animal models. The purpose of this study was to define the importance of KCa1.1 (BK, Maxi‐K, Slo1, KCNMA1) channel expression and function in FLS and to establish these channels as potential new targets for RA therapy.
Intermittent observer-based consensus control for multi-agent systems with switching topologies

In this paper, we focus on the consensus problem for leaderless and leader–followers multi-agent systems with periodically intermittent control. The dynamics of each agent in the system is a linear system, and the interconnection topology among the agents is assumed to be switching. We assume that each agent can only share the outputs with its neighbours. Therefore, a class of distributed intermittent observer-based consensus protocols are proposed for each agent. First, in order to solve this problem, a parameter-dependent common Lyapunov function is constructed. Using this function, we prove that all agents can access a prescribed value, under the designed intermittent controller and observer, if there are suitable conditions on communication. Second, based on the investigation of the leader-following consensus problem, we design a new distributed intermittent observer-based protocol for each following agent. Finally, we provide an illustrative example to verify the effectiveness of the proposed approach.
Effects of nitroglycerin on left ventricular function in patients with ischemic heart disease

To evaluate the effects of nitroglycerin on left ventricular function in 27 patients with ischemic heart disease, ejection fraction (EF) was measured every 1 to 5 min by a nuclear stethoscope after sublingual administration of nitroglycerin (0.3 mg). There was a good correlation between EF determined by the nuclear stethoscope and EF by left ventriculography (r = 0.80, p less than 0.001). EF showed a rise after sublingual nitroglycerin, which was most marked at 4 to 7 min and returned to the control level in 20 to 25 min. There were no significant differences in the maximum percent increase in EF among patients with 0, 1, 2 and 3 vessel disease. The maximum percent increases in EF were 34.0 +/- 10.0% in the normal contraction group, 24.0 +/- 8.5% in the hypokinesis group (p less than 0.05 vs the normal contraction group) and 15.2 +/- 8.5% in the akinesis group (p less than 0.01 vs the normal contraction group, p less than 0.05 vs the hypokinesis group). There was a weak correlation between the maximum percent increase in EF and the changes in heart rate (r = 0.49, p less than 0.05) and there was an inverse correlation between the maximum percent increase in EF and the changes in systolic blood pressure (r = -0.65, p less than 0.01). It was shown that the improvement in EF by sublingual nitroglycerin was greatest in the normal contraction group, somewhat less in the hypokinesis group and least in the akinesis group. The nuclear stethoscope is useful in monitoring changes in left ventricular function during intervention.
Glucocorticoid‐Induced Leucine Zipper Governs the Therapeutic Potential of Mesenchymal Stem Cells by Inducing a Switch From Pathogenic to Regulatory Th17 Cells in a Mouse Model of Collagen‐Induced Arthritis

Mesenchymal stem cells (MSCs) are potent immunosuppressive cells that have shown promise in the treatment of rheumatoid arthritis (RA). Deciphering the intrinsic characteristics of MSCs that correlate with their biologic activity will facilitate their clinical use. Recently, the role of glucocorticoid‐induced leucine zipper (GILZ) in the development of RA has been documented. The aim of this study was to evaluate whether GILZ expression by MSCs may contribute to their therapeutic effect.
Interleukin‐21 Receptor Blockade Inhibits Secondary Humoral Responses and Halts the Progression of Preestablished Disease in the (NZB × NZW)F1 Systemic Lupus Erythematosus Model

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is driven in part by chronic B and T lymphocyte hyperresponsiveness to self antigens. A deficiency of interleukin‐21 (IL‐21) or IL‐21 receptor (IL‐21R) in mice dramatically reduces inflammation and B and T cell activation in models of autoimmunity, including SLE. However, whether IL‐21 is essential for the maintenance and amplification of preestablished inflammation has not been widely examined in various animal models. The purpose of this study was to examine the impact of novel mouse IL‐21R neutralizing antibodies on recall responses to antigen challenge and on disease progression in the (NZB × NZW)F1 (NZB/NZW) mouse model of SLE.
QTL mapping of inbreeding‐related cold sensitivity and conditional lethality in Drosophila melanogaster

Inbreeding depression is a central theme within genetics, and is of specific interest for researchers within evolutionary and conservation genetics and animal and plant breeding. Inbreeding effects are thought to be caused by the joint expression of conditional and unconditional deleterious alleles. Whenever the expression of deleterious alleles is conditional, this can result in extreme environmental sensitivity in certain inbred lineages. Analysis of conditional lethal effects can reveal some of the loci that are sensitive to inbreeding. We performed a QTL (quantitative trait locus) mapping study of inbreeding‐related and conditionally expressed lethality in Drosophila melanogaster. The lethal effect was triggered by exposure to a cold shock. We used a North Carolina crossing Design 3 to establish the mapping population, as well as to estimate the average dominance ratio and heritability. We found two QTL on the major autosomes carrying recessive lethals that caused male mortality, one of which also affected female mortality. More detailed study of these loci will provide information on the mechanistic basis and environmental sensitivity of inbreeding depression.
Hemiclonal analysis reveals significant genetic, environmental and genotype × environment effects on sperm size in Drosophila melanogaster

Spermatozoa are the most diverse of all animal cells. Variation in size alone is enormous and yet there are still no clear evolutionary explanations that can account for such diversity. The basic genetics of sperm form is also poorly understood, although sperm size is known to have a strong genetic component. Here, using hemiclonal analysis of Drosophila melanogaster, we demonstrate that there is not only a significant additive genetic component contributing to phenotypic variation in sperm length but also a significant environmental effect. Furthermore, the plasticity of sperm size has a significant genetic component to it (a genotype × environment interaction). A genotype × environment interaction could contribute to the maintenance of the substantial genetic variation in this trait and thereby explain the persistent inter‐male differences in sperm size seen in numerous taxa. We suggest that the low conditional dependence and high heritability but low evolvability (the coefficient of additive genetic variation) of sperm length is more consistent with a history of stabilizing selection rather than either sexual selection or strong directional selection.
Macroevolutionary patterns in the origin of mutualisms involving ants

Ants are a diverse and abundant insect group that form mutualistic associations with a number of different organisms from fungi to insects and plants. Here, we use a phylogenetic approach to identify ecological factors that explain macroevolutionary trends in the mutualism between ants and honeydew‐producing Homoptera. We also consider association between ant–Homoptera, ant–fungi and ant–plant mutualisms. Homoptera‐tending ants are more likely to be forest dwelling, polygynous, ecologically dominant and arboreal nesting with large colonies of 104–105 individuals. Mutualistic ants (including those that garden fungi and inhabit ant‐plants) are found in under half of the formicid subfamilies. At the genus level, however, we find a negative association between ant–Homoptera and ant–fungi mutualisms, whereas there is a positive association between ant–Homoptera and ant–plant mutualisms. We suggest that species can only specialize in multiple mutualisms simultaneously when there is no trade‐off in requirements from the different partners and no redundancy of rewards.
Association of Joint Inflammation With Pain Sensitization in Knee Osteoarthritis: The Multicenter Osteoarthritis Study

Pain sensitization is associated with pain severity in knee osteoarthritis (OA), but its cause in humans is not well understood. We examined whether inflammation, assessed as synovitis and effusion on magnetic resonance imaging (MRI), or mechanical load, assessed as bone marrow lesions (BMLs), was associated with sensitization in knee OA.