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1.
J Sci Med Sport ; 26(11): 566-573, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37777396

ABSTRACT

OBJECTIVES: To assess how biomarkers indicating central nervous system insult (neurobiomarkers) vary in peripheral blood with exertional-heat stress from prolonged endurance exercise. DESIGN: Observational study of changes in neuron specific enolase (NSE), S100 calcium-binding protein B (S100ß), Glial Fibrillary Acid Protein (GFAP) and Ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) at Brighton Marathon 2022. METHODS: In 38 marathoners with in-race core temperature (Tc) monitoring, exposure (High, Intermediate or Low) was classified by cumulative hyperthermia - calculated as area under curve of Time × Tc > 38 °C - and also by running duration (finishing time). Blood was sampled for neurobiomarkers, cortisol and fluid-regulatory stress surrogates, including copeptin and creatinine (at rested baseline; within 30 min of finishing; and at 24 h). RESULTS: Finishing in 236 ±â€¯40 min, runners showed stable GFAP and UCH-L1 across the marathon and next-day. Significant (P < 0.05) increases from baseline were shown post-marathon and at 24 h for S100ß (8.52 [3.65, 22.95] vs 39.0 [26.48, 52.33] vs 80.3 [49.1, 99.7] ng·L-1) and post-marathon only for NSE (3.73 [3.30, 4.32] vs 4.85 [4.45, 5.80] µg·L-1, P < 0.0001). Whilst differential response to hyperthermia was observed for cortisol, copeptin and creatinine, neurobiomarker responses did not vary. Post-marathon, only NSE differed by exercise duration (High vs Low, 5.81 ±â€¯1.77 vs. 4.69 ±â€¯0.73 µg·L-1, adjusted P = 0.0358). CONCLUSIONS: Successful marathon performance did not associate with evidence for substantial neuronal insult. To account for variation in neurobiomarkers with prolonged endurance exercise, factors additional to hyperthermia, such as exercise duration and intensity, should be further investigated.


Subject(s)
Body Temperature , Running , Humans , Marathon Running , Creatinine , Hydrocortisone , Running/physiology , Biomarkers
2.
Syst Rev ; 10(1): 148, 2021 05 12.
Article in English | MEDLINE | ID: mdl-33980324

ABSTRACT

BACKGROUND: Venous leg ulcers (VLUs) are chronic wounds characterized by slow healing and high recurrence. Information on prevalence and incidence is essential for ascertaining the burden of VLU on the health care system and to inform epidemiological research, priority setting, and health care planning. The objective of this protocol is to present a transparent process for how we plan to review the existing international literature on the prevalence and incidence of VLU as well as the characteristics of the population reported within these studies. METHODS: An exploratory search was performed using MEDLINE via PubMed and CINHAL via Ebsco to identify concepts, keywords, MeSH terms, and headings to identify study types looking at data of VLU prevalence and/or incidence and related patient characteristics. The findings of this exploratory search will determine the final search strategy. The titles and abstracts of the identified articles will be screened independently be two authors for relevance. Study which pass the quality assessment will be included. Data extraction will be performed independently by two authors and in accordance with a pre-designed data extraction form. If the data allows, a meta-analysis will be performed otherwise a descriptive summary of the findings will be conducted. DISCUSSION: The results of this review will contribute to the evidence base on VLU occurrence and may inform the decision making of healthcare professionals, policy-makers, and consumers. It will also inform future research in this area of VLU care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020205855.


Subject(s)
Varicose Ulcer , Epidemiologic Studies , Humans , Incidence , Meta-Analysis as Topic , Prevalence , Systematic Reviews as Topic , Varicose Ulcer/epidemiology , Wound Healing
3.
BMJ Open ; 11(5): e044604, 2021 05 11.
Article in English | MEDLINE | ID: mdl-33980525

ABSTRACT

INTRODUCTION: Chronic venous leg ulcer (VLU) healing is a complex clinical problem. It requires intervention from skilled, costly, multidisciplinary wound-care teams, working with patients to manage their care. Compression therapy has been shown to help heal venous ulcers and to reduce recurrence, with some evidence suggesting the value of exercise as well. These activities require health education and health literacy (HL) as patients must process, understand and consistently apply health information for successful self-management. Research suggests that those most vulnerable to VLUs also tend to have limited HL, but there have been no reviews examining the state of HL in patients with previous or active VLUs. This scoping review aims to examine the level of HL in VLU patients and how HL may link to self-management behaviours (particularly exercise and compression adherence), and their VLU healing generally. METHODS AND ANALYSIS: We will use Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review guidelines and the Levac methodology framework to explore eligible papers that examine the effect of HL on their exercise and compression adherence. Electronic databases will be searched (MEDLINE, EMBASE, the Cochrane Library, PsycInfo and Health, OpenGray), examining for all papers on these subjects published between 2000 and 2020. All studies describing compression and or exercise during VLU management will be included. Study characteristics will be recorded; qualitative data will be extracted and evaluated. Quantitative data will be extracted and summarised. ETHICS AND DISSEMINATION: We will disseminate results through peer-reviewed publications. We will use data (ie, journal articles) from publicly available platforms; so, this study does not require ethical review. The consultation step will be carried out with patients, carers and health professionals as part of an established wound consumer group.


Subject(s)
Health Literacy , Varicose Ulcer , Exercise , Humans , Recurrence , Review Literature as Topic , Systematic Reviews as Topic , Varicose Ulcer/therapy , Wound Healing
4.
Int J Nurs Stud ; 113: 103774, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33080480

ABSTRACT

BACKGROUND: Venous leg ulcers are the most common chronic wound seen in Australian primary care. Healing outcomes are protracted due to suboptimal use of clinical practice guideline recommendations. A better understanding of the differences between patients and clinicians may optimise management in primary care and improve healing and health outcomes for patients and healthcare spend in society. OBJECTIVE: We explored venous leg ulcer management from patients' and primary care clinicians' perspective, including assessment, diagnosis, treatment, referral, and health education as outlined in the clinical practice guidelines. DESIGN: We conducted a qualitative secondary analysis of data obtained from the qualitative face-to-face and telephone interviews with the primary care clinicians and telephone interviews with patients with venous leg ulcers. SETTING: Clinicians were recruited from urban and rural primary health practices across Victoria, Australia. Patients were recruited from two specialist care wound clinics in Victoria. PARTICIPANTS: We analysed data from interviews with 66 participants, including 31 patients with venous leg ulcers, 15 general practitioners and 20 practice nurses. METHODS: Secondary analysis of qualitative data was carried out using thematic analysis. Interview transcripts were coded and analysed for common themes. RESULTS: We found patients and clinicians reported differing perspectives related to venous leg ulcer management. Patients reported the need for earlier referral to specialist wound care clinics from primary care, emphasizing the need for vascular assessment and compression therapy. Clinicians discussed clinical judgements about when to refer rather than follow guideline recommendations. Clinicians frequently discussed managing venous leg ulcers using only topical dressing treatments, without compression therapy. Patients reported inadequate pain management for wound pain. Meanwhile, clinicians reported that they generally did not discuss wound pain management as part of overall venous leg ulcer management. Clinicians reported patients lacked an understanding about the role of compression in management of and subsequent healing outcomes. Patients stated they wanted more information about how to care for venous leg ulcers and how best to prevent recurrence, and needed more information than was already provided by clinicians. Conversely, clinicians reported less information is given to ensure patients were not overwhelmed with health information. CONCLUSION: There are discrepancies between what patients want and what clinicians do. These data suggest that patients' preferences are aligned with venous leg ulcer clinical practice guideline recommendations. Greater awareness of the guidelines by health professional may not only reduce discrepancies they may improve health and healing outcomes. Tweetable abstract: Patients and primary care clinicians have different perspectives about venous leg ulcer management.


Subject(s)
Leg Ulcer , Varicose Ulcer , Bandages , Humans , Leg Ulcer/therapy , Primary Health Care , Varicose Ulcer/therapy , Victoria , Wound Healing
5.
Midwifery ; 90: 102818, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32827841

ABSTRACT

OBJECTIVE: To critically appraise and synthesize the best available evidence on the effectiveness of massage to reduce antenatal women's anxiety and/ or depression. DESIGN: Systematic review with meta-analysis PARTICIPANTS, INTERVENTIONS: Pregnant women over the age of 18 years who receive massage interventions. MEASUREMENTS AND FINDINGS: Eight studies were included in the review; seven were randomized controlled trials. Data were collected via pregnant women's self-reported ratings of anxiety or depression using validated tools. Meta-analysis of four studies revealed a moderate effect of massage therapy on women's depressive symptoms as measured by the Center for Epidemiologic Studies Depression Scale (CES-D) (MD = -5.95, 95%CI = -8.11 to -3.80, I2 = 0%) compared with usual care. A moderate effect of massage interventions on women's anxiety were also found based on five studies using various measures (SMD = -0.59, 95%CI = -1.06 to -0.12, I2 = 75%) when compared with usual care. However, none of the trials had a low risk of bias. KEY CONCLUSIONS: Non-pharmacologic treatments for mental health symptoms are an important option for women to use during pregnancy. As shown in meta-analysed data, massage therapy might be more effective in reducing pregnant women's anxiety and depression than usual care, although the current results may be prone to bias. Further high-quality research is required to fully evaluate the impact of massage therapy on pregnant women's mental health symptoms in the immediate and also longer term. IMPLICATIONS FOR PRACTICE: Massage therapy may be an acceptable and feasible approach for pregnant women to employ to reduce their anxiety and depressive symptoms. More research evidence examining the safety and effectiveness of massage is required before practice recommendations can be made.


Subject(s)
Anxiety/therapy , Depression/therapy , Massage/standards , Pregnant Women/psychology , Adult , Anxiety/psychology , Depression/psychology , Female , Humans , Massage/methods , Middle Aged , Pregnancy
6.
Int J Nurs Stud ; 103: 103503, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31931442

ABSTRACT

BACKGROUND: Venous leg ulcers represent the most common chronic wound problem managed in Australian primary care. Despite the prevalence of the condition, there is an evidence-practice gap in both diagnosis and management of venous leg ulcers. OBJECTIVE: We used the Theoretical Domains Framework to identify barriers and enablers perceived by primary care practitioners in implementing venous leg ulcer guidelines in clinical practice. DESIGN: We collected data to explore the experiences of practice nurses and general practitioners related to their use of clinical practice guidelines in management of venous leg ulcers. SETTING(S): We recruited participants from primary care settings located in metropolitan and rural areas across Victoria, Australia. PARTICIPANTS: We recruited general practitioners (15) and practice nurses (20). METHODS: We conducted 35 semi-structured face-to-face and telephone interviews. Content analysis of health practitioners' statements was performed and barriers to implementing clinical practice guidelines were mapped across the Theoretical Domains Framework theoretical domains. RESULTS: Six main domains from the Theoretical Domains Framework (Environmental context and resources, Knowledge, Skills, Social influences, Social/Professional Role and Identity and Belief about Capabilities) best explained these barriers and enablers. Many participants were not aware of venous leg ulcer clinical practice guidelines. Those that were aware, stated that finding and accessing guidelines was challenging and most participants relied on other sources of information. Venous leg ulcer management was greatly influenced by professional experience and suggestions from colleagues. Other barriers included busy clinical practice, absence of handheld Doppler ultrasonography, insufficient skills and a lack of confidence related to the use of technology to rule out arterial involvement prior to compression application, a particular skill related to venous leg ulcer management that will impact on healing outcomes. CONCLUSIONS: We identified a number of barriers and the lack of enablers that influence the uptake of venous leg ulcer clinical practice guidelines in primary care. This paper adds a theoretically sound, systematic approach for understanding and addressing the behaviour change required to improve translation of venous leg ulcer clinical practice guidelines in clinical practice. Tweetable abstract: The need to optimise venous leg ulcer clinical practice guidelines (CPG) has never been greater as the current estimate of health cost is AUD3billion and increasing due to rising epidemics of diabetes and obesity. We found most primary care health practitioners are unaware of CPG and this will impact on health and healing outcomes in Australian primary care.


Subject(s)
Leg/blood supply , Practice Guidelines as Topic , Varicose Ulcer/therapy , Australia , Female , Humans , Male , Varicose Ulcer/diagnosis
7.
Methods Enzymol ; 574: 149-165, 2016.
Article in English | MEDLINE | ID: mdl-27423861

ABSTRACT

The density and diversity of posttranslational modifications (PTMs) observed in histone proteins typically limit their purification to homogeneity from biological sources. Access to quantities of uniformly modified histones is, however, critical for investigating the downstream effects of histone PTMs on chromatin-templated processes. Therefore, a number of semisynthetic methodologies have been developed to generate histones bearing precisely defined PTMs or close analogs thereof. In this chapter, we present two optimized and rapid strategies for generating functional analogs of site-specifically acetylated and sumoylated histones. First, we describe a convergent strategy to site-specifically attach the small ubiquitin-like modifier-3 (SUMO-3) protein to the site of Lys12 in histone H4 by means of a disulfide linkage. We then describe the generation of thialysine analogs of histone H3 acetylated at Lys14 or Lys56, using thiol-ene coupling chemistry. Both strategies afford multimilligram quantities of uniformly modified histones that are easily incorporated into mononucleosomes and nucleosome arrays for biophysical and biochemical investigations. These methods are readily extendable to any desired sites in the four core nucleosomal histones and their variant forms.


Subject(s)
Histones/chemistry , Protein Processing, Post-Translational , Small Ubiquitin-Related Modifier Proteins/chemistry , Acetylation , Animals , Cloning, Molecular/methods , Cysteine/analogs & derivatives , Cysteine/chemistry , Disulfides/chemistry , Histones/genetics , Humans , Lysine/analogs & derivatives , Lysine/chemistry , Models, Molecular , Mutagenesis, Site-Directed/methods , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Small Ubiquitin-Related Modifier Proteins/genetics , Sumoylation , Ubiquitins/chemical synthesis , Ubiquitins/chemistry , Ubiquitins/genetics
8.
J Vet Intern Med ; 28(6): 1853-9, 2014.
Article in English | MEDLINE | ID: mdl-25312330

ABSTRACT

BACKGROUND: Salmonella enterica can significantly impact management of animal facilities. Comprehensive screening is essential for effective control in high-risk populations. Availability of reliable point-of-care diagnostic tests would facilitate these efforts. HYPOTHESIS/OBJECTIVES: Compare the ability of commercially available rapid diagnostic assays (2 lateral flow immunoassays [LFIs], DNA hybridization [DNAH], real-time PCR [qPCR]), and culture to detect common serotypes of S. enterica in feces. ANIMALS: n/a. METHODS: In an experimental study, 112 S. enterica isolates were randomly selected from the 10 most common serotypes recovered at a veterinary hospital. Archived isolates were amplified in broth and standardized inocula (100 colony forming units) were incubated with equine feces in tetrathionate broth (TET). Cultures were tested in a blinded fashion by using LFIs, DNAH, qPCR, and culture. RESULTS: The LFIs detected 84% and 67% of isolates, respectively, but reactivity varied among serotypes. Both reacted poorly with serotype Cerro (Group K) isolates, and 1 LFI did not react with any serotype Mbandaka (Group C1) or Montevideo (Group C1) isolates. DNAH detected 94% of isolates, whereas culture and qPCR most reliably detected all serotypes. False-positive results were obtained for 4 negative controls by using DNAH and 1 negative control by using qPCR, but LFIs and culture had no false-positive results. CONCLUSIONS AND CLINICAL IMPORTANCE: Culture, qPCR, and DNAH were effective in detecting most Salmonella isolates, but have limited application at point-of-care settings. LFIs are appealing as point-of-care tests because of low cost and ease of use, but limited detection of some serotypes needs to be evaluated with samples obtained from naturally infected animals.


Subject(s)
Feces/microbiology , Horse Diseases/microbiology , Salmonella Infections, Animal/microbiology , Salmonella enterica , Animals , Bacteriological Techniques/veterinary , Horse Diseases/diagnosis , Horses , Immunoassay/veterinary , Nucleic Acid Hybridization , Point-of-Care Systems , Reagent Kits, Diagnostic/veterinary , Real-Time Polymerase Chain Reaction/veterinary , Salmonella Infections, Animal/diagnosis , Salmonella enterica/classification , Serotyping/methods , Serotyping/veterinary
9.
Aliment Pharmacol Ther ; 38(11-12): 1347-53, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24117797

ABSTRACT

BACKGROUND: There is increased proportional mortality from Parkinson's disease amongst livestock farmers. The hypokinesia of Parkinson's disease has been linked to Helicobacter pylori. H. suis is the most common zoonotic helicobacter in man. AIM: To compare the frequency of H. suis, relative to H. pylori, in gastric biopsies of patients with idiopathic parkinsonism (IP) and controls from gastroenterology services. METHODS: DNA extracts, archived at a Helicobacter Reference Laboratory, from IP patient and gastroenterology service biopsies were examined anonymously for H. suis, using species-specific RT-PCR. RESULTS: Relative risk of having H. suis in 60 IP patients compared with 256 controls was 10 times greater than that of having H. pylori. In patients with IP and controls, respectively, frequencies of H. suis were 27 (exact binomial 95% C.I. 15, 38) and 2 (0, 3)%, and of H. pylori, 28 (17, 40) and 16 (12, 21)%. Excess of H. suis in IP held when only the antral or corporal biopsy was considered. Of 16 IP patients with H. suis, 11 were from 19 with proven H. pylori eradication, 3 from 17 pre-H. pylori eradication, 2 from 24 H. pylori culture/PCR-negative. Frequency was different between groups (P = 0.001), greatest where H. pylori had been eradicated. Even without known exposure to anti-H. pylori therapy, H. suis was more frequent in IP patients (5/41) than in controls (1/155) (P = 0.002). Partial multilocus sequence typing confirmed that strains from IP patients (6) and control (1) differed from RT-PCR standard strain. CONCLUSIONS: Greater frequency of H. suis in idiopathic parkinsonism appears exaggerated following H. pylori eradication. Multilocus sequence testing comparison with porcine strains may clarify whether transmission is from pigs/porcine products or of human-adapted, H. suis-like, bacteria.


Subject(s)
Helicobacter Infections/microbiology , Helicobacter heilmannii/isolation & purification , Helicobacter pylori/isolation & purification , Parkinsonian Disorders/microbiology , Adult , Aged , Aged, 80 and over , Case-Control Studies , DNA, Bacterial/analysis , Female , Helicobacter Infections/epidemiology , Humans , Male , Middle Aged , Parkinsonian Disorders/epidemiology , Reverse Transcriptase Polymerase Chain Reaction , Risk , Young Adult
10.
J Wound Care ; 22(2): 83-4, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23687661
11.
Cephalalgia ; 31(13): 1359-67, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21914734

ABSTRACT

OBJECTIVE: To assess validity of a self-administered web-based migraine-questionnaire in diagnosing migraine aura for the use of epidemiological and genetic studies. METHODS: Self-reported migraineurs enrolled via the LUMINA website and completed a web-based questionnaire on headache and aura symptoms, after fulfilling screening criteria. Diagnoses were calculated using an algorithm based on the International Classification of Headache Disorders (ICHD-2), and semi-structured telephone-interviews were performed for final diagnoses. Logistic regression generated a prediction rule for aura. Algorithm-based diagnoses and predicted diagnoses were subsequently compared to the interview-derived diagnoses. RESULTS: In 1 year, we recruited 2397 migraineurs, of which 1067 were included in the validation. A seven-question subset provided higher sensitivity (86% vs. 45%), slightly lower specificity (75% vs. 95%), and similar positive predictive value (86% vs. 88%) in assessing aura when comparing with the ICHD-2-based algorithm. CONCLUSIONS: This questionnaire is accurate and reliable in diagnosing migraine aura among self-reported migraineurs and enables detection of more aura cases with low false-positive rate.


Subject(s)
Internet , Migraine with Aura/diagnosis , Patient Selection , Surveys and Questionnaires , Adolescent , Adult , Aged , Algorithms , Area Under Curve , Cohort Studies , Female , Humans , International Classification of Diseases , Interviews as Topic , Male , Middle Aged , Models, Theoretical , Netherlands , Predictive Value of Tests , ROC Curve , Reproducibility of Results , Sampling Studies , Self Report , Young Adult
12.
J Wound Care ; 19(10): 417, 420-3, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20948489

ABSTRACT

OBJECTIVE: To estimate the difference between mean interface sub-bandage pressures of two multilayer compression bandage systems in healthy volunteers when supine, standing, exercising and during recovery. METHOD: Inelastic and elastic compression bandages were randomised to opposite limbs of each participant. Sub-bandage interface pressures for both bandages were compared within person. Participants and study staff were aware of the treatment. A pressure transducer measured sub-bandage pressures on the medial aspect of the lower leg, at the transition of the gastrocnemius muscle into the Achilles tendon (B1). The difference in interface pressure for the two different compression bandages was measured at level B1 during supine resting, standing, exercise and recovery. We defined the pressure difference between active standing and lying as a measure of stiffness, and amplitude as the range of pressures during plantar flexion while standing. The two bandage systems (inelastic and elastic) were applied from the base of the toes to just below knee and remained in place for the duration of the experiment. Elastic bandage consisted of three layers of graduated tubular bandage (83% cotton, 9% Lycra, 8% polyamide). Inelastic or short-stretch bandage consisted of 100% cotton crepe bandage. RESULTS: Interface sub-bandage pressures varied during different activities, but the mean difference in interface pressures between inelastic and elastic bandages was consistently at least 13 mm Hg. Stiffness was 7.3 mm Hg higher in the inelastic group (95% CI 5.1-9.5). The estimated difference in amplitude of sub-bandage pressure between the bandages during exercise was 15.5 mm Hg (95% CI 12.2-18.9). CONCLUSION: We found in vivo interface sub-bandage pressures varied with the type of bandage and activity phase. Inelastic bandages resulted in an increased mean interface sub-bandage pressure when resting and recovering, which was further increased when standing or exercising. Bandage stiffness and amplitude were also greater for inelastic compared with elastic bandages. CONFLICT OF INTEREST: None.


Subject(s)
Elasticity , Pressure , Stockings, Compression/standards , Adult , Aged , Elasticity/physiology , Equipment Design , Exercise/physiology , Female , Humans , Male , Materials Testing , Middle Aged , Pressure/adverse effects , Rest/physiology , Sex Characteristics , Stockings, Compression/adverse effects , Supine Position/physiology
13.
J Wound Care ; 19(8): 347-53, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20852507

ABSTRACT

There is a growing need to add to the evidence base in wound care. Randomised controlled trials (RCTs) are one methodological approach for this. The CONSORT statement, which provides guidance on how to conduct a rigorous RCT, was updated earlier this year. Implementation of the Consort statement will clarify to the reader what exactly was done in the RCT, to whom and when. In this way, practitioners and health-care providers can determine its validity. The Consort statement has the potential to play a crucial role in influencing the quality of research and clinical practice, and so to improve wound care. The benefits of Consort 2010 are clear; the challenge is for clinicians and researchers to use it.


Subject(s)
Guidelines as Topic , Randomized Controlled Trials as Topic , Research Design/standards , Wounds and Injuries/therapy , Bias , Checklist , Data Interpretation, Statistical , Editorial Policies , Evidence-Based Practice , Humans , Outcome Assessment, Health Care , Periodicals as Topic/standards , Publishing/standards , Quality of Health Care , Randomized Controlled Trials as Topic/methods , Randomized Controlled Trials as Topic/standards , Sample Size , Stockings, Compression/standards
14.
Vis Neurosci ; 26(2): 215-26, 2009.
Article in English | MEDLINE | ID: mdl-19439107

ABSTRACT

The visual system of birds includes an efferent projection from a visual area, the isthmo-optic nucleus in the midbrain, back to the retina. Using a combination of anterograde labeling of efferent fibers, reconstruction of dye-filled neurons, NADPH-diaphorase staining, and transmission electron microscopy, we have examined the distribution of efferent fibers and their synaptic structures in the chicken retina. We show that efferent fibers terminate strictly within the ventral retina. In two completely mapped retinas, only 2 fibers from a total of 15,359 terminated in the dorsal retina. The major synapse made by each efferent fiber is with a single efferent target amacrine cell (TC). This synapse consists of 5-25 boutons of 2 microm diameter, each with multiple active zones, pressed into the TC soma or synapsing with a basketwork of rudimentary TC dendrites in the inner nuclear layer (INL). This basketwork, which is sheathed by Muller cell processes, defines a private neuropil in the INL within which TCs were also seen to receive input from retinal neurons. In addition to the major synapse, efferent fibers typically produce several very thin processes that terminate nearby in single small boutons and for which the soma of a local amacrine cell is one of the likely postsynaptic partners. A minority of efferent fibers also give rise to a thicker process, terminating in a strongly diaphorase-positive ball about 5 microm in diameter.


Subject(s)
Neurons, Efferent/ultrastructure , Retina/ultrastructure , Synapses/ultrastructure , Amacrine Cells/metabolism , Amacrine Cells/ultrastructure , Animals , Cell Count , Chickens , Dendrites/ultrastructure , Dextrans , Fluorescent Dyes , Isoquinolines , Microscopy, Fluorescence , NADPH Dehydrogenase/biosynthesis , Neurons, Efferent/metabolism , Neuropil/ultrastructure , Retina/metabolism , Rhodamines , Staining and Labeling
15.
Br J Cancer ; 97(4): 523-30, 2007 Aug 20.
Article in English | MEDLINE | ID: mdl-17622249

ABSTRACT

Activation of nuclear factor-kappaB (NF-kappaB) signaling was observed in pancreatic adenocarcinoma cell lines and tumours. However, information on the expression of RelA/p65, the major transcription activating NF-kappaB subunit, in these carcinomas and possible correlations thereof with NF-kappaB activation and patient survival is not available. To provide this missing translational link, we analysed expression of RelA/p65 in 82 pancreatic adenocarcinomas by immunohistochemistry. Moreover, we measured activation of the NF-kappaB pathway in 11 tumours by quantitative PCR for NF-kappaB target genes. We observed strong cytoplasmic or nuclear expression of RelA/p65 in 42 and 37 carcinomas, respectively. High cytoplasmic and nuclear expression of RelA/p65 had negative prognostic impact with 2-year survival rates for patients without cytoplasmic or nuclear RelA/p65 positivity of 41 and 40% and rates for patients with strong cytoplasmic or nuclear RelA/p65 expression of 22 and 20%, respectively. High RelA/p65 expression was correlated to increased expression of NF-kappaB target genes. The observation that high expression of RelA/p65 is correlated to an activation of the NF-kappaB pathway and indicates poor patient survival identifies a patient subgroup that might particularly benefit from NF-kappaB-inhibiting agents in the treatment of pancreatic cancer. Based on our findings, this subgroup could be identified by applying simple immunohistochemical techniques.


Subject(s)
Adenocarcinoma/diagnosis , Adenocarcinoma/genetics , NF-kappa B/metabolism , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/genetics , Transcription Factor RelA/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/mortality , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Humans , Middle Aged , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/mortality , Prognosis , Signal Transduction , Survival Analysis , Transcription Factor RelA/metabolism
16.
Novartis Found Symp ; 279: 142-50; discussion 151-4, 216-9, 2006.
Article in English | MEDLINE | ID: mdl-17278392

ABSTRACT

Mast cells are tissue-resident cells that are localized particularly in the skin, gastrointestinal tract and respiratory tract. They are mainly recognised for their role in adaptive immunity and allergy where cross-linking of surface-bound IgE results in acute mediator release giving early symptoms, and cytokine production contributing to chronic changes. The mast cell is now also increasingly recognized for its role in innate immunity conferred by its repertoire of complement and Toll receptors. Thus, mast cell deletion has been shown to suppress certain innate immune responses in murine models. Our interest is in the mechanisms involved in population of tissues by mast cells, particularly the airways. Mast cells are released from the bone marrow into the blood as committed precursors. These cells circulate in very low numbers and accumulate in tissues where they proliferate and mature under the influence of local cytokines and growth factors that define the mature phenotype appropriate for their location. Chemoattraction is important at critical phases in the life history of the mast cell, i.e. movement towards and through the bone marrow sinus endothelium, recruitment to tissues and movement within the tissues to the location of the mature cell. These phases are dependent on chemoattractants generated at specific locations acting on cell surface receptors whose repertoire evolves as the mast cell matures.


Subject(s)
Lung/cytology , Lung/immunology , Mast Cells/cytology , Mast Cells/immunology , Animals , Humans
17.
Mem Inst Oswaldo Cruz ; 100 Suppl 1: 153-60, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15962115

ABSTRACT

Allergic diseases result in a considerable socioeconomic burden. The incidence of allergic diseases, notably allergic asthma, has risen to high levels for reasons that are not entirely understood. With an increasing knowledge of underlying mechanisms, there is now more potential to target the inflammatory process rather than the overt symptoms. This focuses attention on the role of leukocytes especially Th2 lymphocytes that regulate allergic inflammation and effector cells where eosinophils have received much attention. Eosinophils are thought to be important based on the high numbers that are recruited to sites of allergic inflammation and the potential of these cells to effect both tissue injury and remodelling. It is hoped that future therapy will be directed towards specific leukocyte types, without overtly compromising essential host defence responses. One obvious target is leukocyte recruitment. This necessitates a detailed understanding of underlying mechanisms, particularly those involving soluble chemoattractants signals and cell-cell adhesion molecules.


Subject(s)
Chemokines/immunology , Chemotactic Factors, Eosinophil/immunology , Eosinophils/immunology , Inflammation/immunology , Respiratory Hypersensitivity/immunology , Animals , Chemokines/biosynthesis , Humans , Th2 Cells/immunology
18.
Int J Food Microbiol ; 101(2): 123-44, 2005 May 25.
Article in English | MEDLINE | ID: mdl-15862875

ABSTRACT

Numerous small meat processors in the United States have difficulties complying with the stabilization performance standards for preventing growth of Clostridium perfringens by 1 log10 cycle during cooling of ready-to-eat (RTE) products. These standards were established by the Food Safety and Inspection Service (FSIS) of the US Department of Agriculture in 1999. In recent years, several attempts have been made to develop predictive models for growth of C. perfringens within the range of cooling temperatures included in the FSIS standards. Those studies mainly focused on microbiological aspects, using hypothesized cooling rates. Conversely, studies dealing with heat transfer models to predict cooling rates in meat products do not address microbial growth. Integration of heat transfer relationships with C. perfringens growth relationships during cooling of meat products has been very limited. Therefore, a computer simulation scheme was developed to analyze heat transfer phenomena and temperature-dependent C. perfringens growth during cooling of cooked boneless cured ham. The temperature history of ham was predicted using a finite element heat diffusion model. Validation of heat transfer predictions used experimental data collected in commercial meat-processing facilities. For C. perfringens growth, a dynamic model was developed using Baranyi's nonautonomous differential equation. The bacterium's growth model was integrated into the computer program using predicted temperature histories as input values. For cooling cooked hams from 66.6 degrees C to 4.4 degrees C using forced air, the maximum deviation between predicted and experimental core temperature data was 2.54 degrees C. Predicted C. perfringens growth curves obtained from dynamic modeling showed good agreement with validated results for three different cooling scenarios. Mean absolute values of relative errors were below 6%, and deviations between predicted and experimental cell counts were within 0.37 log10 CFU/g. For a cooling process which was in exact compliance with the FSIS stabilization performance standards, a mean net growth of 1.37 log10 CFU/g was predicted. This study introduced the combination of engineering modeling and microbiological modeling as a useful quantitative tool for general food safety applications, such as risk assessment and hazard analysis and critical control points (HACCP) plans.


Subject(s)
Clostridium perfringens/growth & development , Food Handling/methods , Meat Products/microbiology , Models, Biological , Temperature , Animals , Computer Simulation , Consumer Product Safety , Finite Element Analysis , Food Microbiology , Hot Temperature , Mathematics , Predictive Value of Tests , Risk Assessment , Stem Cells , Swine
19.
Mem. Inst. Oswaldo Cruz ; 100(supl.1): 153-160, Mar. 2005.
Article in English | LILACS | ID: lil-402192

ABSTRACT

Allergic diseases result in a considerable socioeconomic burden. The incidence of allergic diseases, notably allergic asthma, has risen to high levels for reasons that are not entirely understood. With an increasing knowledge of underlying mechanisms, there is now more potential to target the inflammatory process rather than the overt symptoms. This focuses attention on the role of leukocytes especially Th2 lymphocytes that regulate allergic inflammation and effector cells where eosinophils have received much attention. Eosinophils are thought to be important based on the high numbers that are recruited to sites of allergic inflammation and the potential of these cells to effect both tissue injury and remodelling. It is hoped that future therapy will be directed towards specific leukocyte types, without overtly compromising essential host defence responses. One obvious target is leukocyte recruitment. This necessitates a detailed understanding of underlying mechanisms, particularly those involving soluble che-moattractants signals and cell-cell adhesion molecules.


Subject(s)
Animals , Humans , Chemokines/immunology , Chemotactic Factors, Eosinophil/immunology , Eosinophils/immunology , Inflammation/immunology , Respiratory Hypersensitivity/immunology , Chemokines/biosynthesis , /immunology
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