A systemic granulomatous response to Schistosoma mansoni eggs alters responsiveness of bone marrow‐derived macrophages to Toll‐like receptor agonists

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141008/1/jlb0314.pd

Efeitos do uso tópico do óleo de andiroba puro e ozonizado em feridas induzidas em cavalos

Este trabalho realizou uma avaliação clínica e histopatológica da aplicação tópica do óleo de andiroba (Carapa guianensis Aublet), puro e ozonizado, no processo de cicatrização de feridas em cinco equinos saudáveis. Oito feridas de 6,25 cm2 foram induzidas cirurgicamente, quatro de cada lado da região lombar, craniais em relação à região sacral. Em três animais, o lado esquerdo foi destinado à avaliação macroscópica e mensuração de área, enquanto o lado direito foi destinado à análise histopatológica. Nos outros dois animais, as avaliações foram invertidas. O tratamento tópico foi iniciado 12 horas após a indução cirúrgica e foi mantido diariamente até a completa cicatrização das feridas. Foram usados, sequencialmente e bilateralmente, no sentido craniocaudal: solução salina (GC), solução salina ozonizada (GO), óleo de andiroba puro (GAP) e óleo de andiroba ozonizado (GAO). Aleatoriamente, a sequência de tratamentos foi modificada. As análises macroscópicas e microscópicas foram realizadas 3, 7, 14 e 21 dias após a cirurgia, e o tempo total para cicatrização registrado. A contração da ferida foi de 67,75% para GC, 65,26% para GO, 67,91% para GAP, e 69,84% para GAO. A avaliação histopatológica demonstrou que as feridas tratadas com GAO e GAP apresentaram uma avançada epitelização, proliferação fibroblástica e deposição de colágeno, moderada proliferação vascular e presença de infiltrados de células polimorfonucleares (PMN) e discreta proliferação de células mononucleares (MN). Foi possível concluir que todos os tratamentos usados foram benéficos perante o grupo de controle, mostrando que as versões pura e ozonizada do óleo de andiroba representam alternativas terapêuticas ao tratamento de feridas em equinos.The aim of this study was to evaluate clinical and histopathological aspects of topical application of pure and ozonized andiroba oil (Carapa guianensis Aublet.) on the healing process of wounds of healthy horses. Eight 6.25-cm2 wounds were surgically produced on each horse, cranial to the sacrum, being four wounds on each side of the lumbar region. In three animals, left side was used for macroscopic observations and area measurement and right side was used for histopathological analysis. For the other two animals, evaluations were inverted. Beginning of the topical treatment occurred 12 hours after surgical induction of the injuries and was maintained daily until complete healing of the wounds, using sequentially and bilaterally in the craniocaudal direction saline solution (GC), ozonized saline solution (GO), pure andiroba oil (GAP) and ozonized andiroba oil (GAO). Randomly, sequence of the treatments was modified. Macroscopic and histopathological analyses were performed at 3, 7, 14, and 21 days after surgery. Completed healing time for all wounds were recorded. A wound contraction of 67.75% for GC, 65.26% for GO, 67.91% for GAP, and 69.84% for GAO were recorded. Histopathologic evaluation revealed that wounds from the GAO and GAP had an advanced epithelialization, fibroblast proliferation and collagen deposition, moderate vascular proliferation, and presence of PMN infiltrate and discrete viewing of MN. It was possible to conclude that all treatments had benefits when comparing to control group and both pure and ozonized andiroba oil can be good options for wound treatment in horses

Cross-cultural adaptation of the NoMAD questionnaire to Brazilian Portuguese

BACKGROUND: The Normalization Measure Development (NoMAD) tool is used to determine the contextual determinants in the process of implementing complex health interventions. The aim of this study is to translate and culturally adapt NoMAD to Brazilian Portuguese. METHODS: The cross-cultural adaptation was performed in five steps: 1) translation of the questionnaire into Portuguese; 2) synthesis and creation of the first version; 3) back-translation of the instrument into the source language; 4) review of the instrument by a group of experts and target professionals; and 5) pretesting. A final version of the questionnaire was answered by users of a clinical monitoring system in specialist care services for people living with HIV/AIDS, and the internal consistency of the questionnaire was assessed using Cronbach's alpha. RESULTS: The questionnaire was answered by 188 health professionals, of which 87.7% were female, and the average age was 45.2 years. For the final version of the questionnaire, Cronbach's alpha was over 0.70 for the construct's coherence (0.74), collective action (0.70), cognitive participation (0.71), and reflexive monitoring (0.81). CONCLUSION: The NoMAD questionnaire was cross-culturally adapted and can be used to evaluate the implementation of complex health care interventions

Exome analysis of rare and common variants within the NOD signaling pathway

Pediatric inflammatory bowel disease (pIBD) is a chronic heterogeneous disorder. This study looks at the burden of common and rare coding mutations within 41 genes comprising the NOD signaling pathway in pIBD patients. 136 pIBD and 106 control samples underwent whole-exome sequencing. We compared the burden of common, rare and private mutation between these two groups using the SKAT-O test. An independent replication cohort of 33 cases and 111 controls was used to validate significant findings. We observed variation in 40 of 41 genes comprising the NOD signaling pathway. Four genes were significantly associated with disease in the discovery cohort (BIRC2 p = 0.004, NFKB1 p =  0.005, NOD2 p = 0.029 and SUGT1 p = 0.047). Statistical significance was replicated for BIRC2 (p = 0.041) and NOD2 (p = 0.045) in an independent validation cohort. A gene based test on the combined discovery and replication cohort confirmed association for BIRC2 (p = 0.030). We successfully applied burden of mutation testing that jointly assesses common and rare variants, identifying two previously implicated genes (NFKB1 and NOD2) and confirmed a possible role in disease risk in a previously unreported gene (BIRC2). The identification of this novel gene provides a wider role for the inhibitor of apoptosis gene family in IBD pathogenesis

Exome analysis of patients with concurrent pediatric inflammatory bowel disease (PIBD) and autoimmune disease

BACKGROUND: Pediatric Inflammatory Bowel Disease (PIBD) is a chronic condition seen in genetically predisposed individuals. Genome-wide association studies have implicated >160 genomic loci in IBD with many genes coding for proteins in key immune pathways. This study looks at autoimmune disease burden in patients diagnosed with PIBD and interrogates exome data of a subset of patients. METHODS: Patients were recruited from the Southampton Genetics of PIBD cohort. Clinical diagnosis of autoimmune disease in these individuals was ascertained from medical records. For a subset of patients with PIBD and concurrent asthma, exome data was interrogated to ascertain the burden of pathogenic variants within genes implicated in asthma. Association testing was conducted between cases and population controls using the SKAT-O test. RESULTS: Forty-nine (28.3%) PIBD children (18.49% CD, 8.6% UC, and 21.15% IBDU patients) had a concurrent clinical diagnosis of at least one other autoimmune disorder; asthma was the most prevalent, affecting 16.2% of the PIBD cohort. Rare and common variant association testing revealed 6 significant genes (P < 0.05) before Bonferroni adjustment. Three of these genes were previously implicated in both asthma and IBD (ZPBP2 IL1R1, and IL18R1) and 3 in asthma only (PYHIN1, IL2RB, and GSTP1). CONCLUSIONS: One-third of our cohort had a concurrent autoimmune condition. We observed higher incidence of asthma compared with the overall pediatric prevalence. Despite a small sample size, SKAT-O evaluated a significant burden of rare and common mutations in 6 genes. Variant burden suggests that a systemic immune dysregulation rather than organ-specific could underpin immune dysfunction for a subset of patients

16S sequencing and functional analysis of the fecal microbiome during treatment of newly diagnosed pediatric inflammatory bowel disease

JJA is funded by a National Institute of Health Research Academic Clinical Fellowship and has received an Action Medical Research training fellowship. TC is funded by a Crohn’s in Childhood research association fellowship. CMC received a PhD studentship from SULSA Spirit industrial studentship. The NGS analysis was made possible by the award of a grant from the Source Bioscience 110th year anniversary promotion to CMC. The Rowett Institute receives funding from the Scottish Government (RESAS).Peer reviewedPublisher PD

Effects of topical application of pure and ozonized andiroba oil on experimentally induced wounds in horses

The aim of this study was to evaluate clinical and histopathological aspects of topical application of pure and ozonized andiroba oil (Carapa guianensis Aublet.) on the healing process of wounds of healthy horses. Eight 6.25-cm2 wounds were surgically produced on each horse, cranial to the sacrum, being four wounds on each side of the lumbar region. In three animals, left side was used for macroscopic observations and area measurement and right side was used for histopathological analysis. For the other two animals, evaluations were inverted. Beginning of the topical treatment occurred 12 hours after surgical induction of the injuries and was maintained daily until complete healing of the wounds, using sequentially and bilaterally in the craniocaudal direction saline solution (GC), ozonized saline solution (GO), pure andiroba oil (GAP) and ozonized andiroba oil (GAO). Randomly, sequence of the treatments was modified. Macroscopic and histopathological analyses were performed at 3, 7, 14, and 21 days after surgery. Completed healing time for all wounds were recorded. A wound contraction of 67.75% for GC, 65.26% for GO, 67.91% for GAP, and 69.84% for GAO were recorded. Histopathologic evaluation revealed that wounds from the GAO and GAP had an advanced epithelialization, fibroblast proliferation and collagen deposition, moderate vascular proliferation, and presence of PMN infiltrate and discrete viewing of MN. It was possible to conclude that all treatments had benefits when comparing to control group and both pure and ozonized andiroba oil can be good options for wound treatment in horses

Evidence-based medicine in primary care: qualitative study of family physicians

BACKGROUND: The objectives of this study were: a) to examine physician attitudes to and experience of the practice of evidence-based medicine (EBM) in primary care; b) to investigate the influence of patient preferences on clinical decision-making; and c) to explore the role of intuition in family practice. METHOD: Qualitative analysis of semi-structured interviews of 15 family physicians purposively selected from respondents to a national survey on EBM mailed to a random sample of Canadian family physicians. RESULTS: Participants mainly welcomed the promotion of EBM in the primary care setting. A significant number of barriers and limitations to the implementation of EBM were identified. EBM is perceived by some physicians as a devaluation of the 'art of medicine' and a threat to their professional/clinical autonomy. Issues regarding the trustworthiness and credibility of evidence were of great concern, especially with respect to the influence of the pharmaceutical industry. Attempts to become more evidence-based often result in the experience of conflicts. Patient factors exert a powerful influence on clinical decision-making and can serve as trumps to research evidence. A widespread belief that intuition plays a vital role in primary care reinforced views that research evidence must be considered alongside other factors such as patient preferences and the clinical judgement and experience of the physician. DISCUSSION: Primary care physicians are increasingly keen to consider research evidence in clinical decision-making, but there are significant concerns about the current model of EBM. Our findings support the proposed revisions to EBM wherein greater emphasis is placed on clinical expertise and patient preferences, both of which remain powerful influences on physician behaviour

Patients' perspectives on taking warfarin: qualitative study in family practice

BACKGROUND: Despite the well-documented benefits of using warfarin to prevent stroke, physicians remain reluctant to initiate therapy, and especially so with the elderly owing to the higher risk of hemorrhage. Prior research suggests that patients are more accepting of the risk of bleeding than are physicians, although there have been few qualitative studies. The aim of this study was to employ qualitative methods to investigate the experience and perspective of individuals taking warfarin. METHODS: We conducted face-to-face interviews with 21 older patients (12 male, 9 female) who had been taking warfarin for a minimum of six months. Participants were patients at a family practice clinic situated in a large, tertiary care teaching hospital. We used a semistructured interview guide with four main thematic areas: decision-making, knowledge/education, impact, and satisfaction. Data were analysed according to the principles of content analysis. RESULTS AND DISCUSSION: Participants tended to have minimal input into the decision to initiate warfarin therapy, instead relying in great part on physicians' expertise. There appeared to be low retention of information received regarding the therapy; half the patients in our sample possessed only a superficial level of understanding of the risks and benefits. This notwithstanding, participants reported a high level of satisfaction with the care provided and a low level of impact on their day-to-day lives. CONCLUSIONS: Minimal patient involvement in the initial decision and modest knowledge did not appear to diminish satisfaction with warfarin management. At the same time, care providers exert a tremendous influence on the initiation of warfarin therapy and should strive to incorporate patient preferences and expectations into the decision-making process

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure