Summary
The contact system is a plasma protease cascade initiated by factor XII (FXII) that activates the proinflammatory kallikrein‐kinin system and the procoagulant intrinsic coagulation pathway. ...Anionic surfaces induce FXII zymogen activation to form proteolytically active FXIIa. Bacterial surfaces also have the ability to activate contact system proteins, indicating an important role for host defense using the cooperation of the inflammatory and coagulation pathways. Recent research has shown that inorganic polyphosphate found in platelets activates FXII in vivo and can induce coagulation in pathological thrombus formation. Experimental studies have shown that interference with FXII provides thromboprotection without a therapy‐associated increase in bleeding, renewing interest in the FXIIa‐driven intrinsic pathway of coagulation as a therapeutic target. This review summarizes how the contact system acts as the cross‐road of inflammation, coagulation, and innate immunity.
For regular parametric problems, we show how median centring of the maximum likelihood estimate can be achieved by a simple modification of the score equation. For a scalar parameter of interest, the ...estimator is equivariant under interest-respecting reparameterizations and is third-order median unbiased. With a vector parameter of interest, componentwise equivariance and third-order median centring are obtained. Like the implicit method of Firth (1993) for bias reduction, the new method does not require finiteness of the maximum likelihood estimate and is effective in preventing infinite estimates. Simulation results for continuous and discrete models, including binary and beta regression, confirm that the method succeeds in achieving componentwise median centring and in solving the boundary estimate problem, while keeping comparable dispersion and the same approximate distribution as its main competitors.
Plasma protein factor XII (FXII) activates the procoagulant and proinflammatory contact system that drives both the kallikrein–kinin system and the intrinsic pathway of coagulation. When zymogen FXII ...comes into contact with negatively charged surfaces, it auto‐activates to the serine proteaseactivated FXII (FXIIa). Recently, various in vivo activators of FXII have been identified including heparin, misfolded protein aggregates, polyphosphate and nucleic acids. Murine models have established a central role of FXII in arterial and venous thrombosis. Despite its central function in thrombosis, deficiency in FXII does not impair haemostasis in animals and humans. In a preclinical cardiopulmonary bypass system in large animals, the FXIIa‐blocking antibody 3F7 prevented thrombosis; however, in contrast to traditional anticoagulants, bleeding was not increased. In addition to its function in thrombosis, FXIIa initiates formation of the inflammatory mediator bradykinin. This mediator increases vascular leak, causes vasodilation, and induces chemotaxis with implications for septic, anaphylactic and allergic disease states. Therefore, targeting FXIIa appears to be a promising strategy for thromboprotection without associated bleeding risks but with anti‐inflammatory properties.
The objective of this study was to describe bacterial culture and antibiotic susceptibility results in 476 dogs presenting with suspected bacterial keratitis in Iowa and surrounding Midwestern ...states, further detailing trends in patient characteristics, seasonality, and antimicrobial resistance. Corneal swabs yielded 465 bacterial isolates and 220 cultures (46.2%) with no apparent growth (0-5 isolates per culture). The most frequent bacterial genera were
(32.3%),
(19.1%), and
(12.5%), while the most common bacterial species were
(26.7%),
(12%), and
(7.5%). Compared to mixed-breed dogs, canine breeds most likely to be examined for ulcerative keratitis included Boston terrier, Cavalier King Charles spaniel, miniature pinscher, pug, rat terrier, Saint Bernard, shih tzu, and silky terriers. In summer, the likelihood to yield a negative culture was reduced while the likelihood to culture
species was increased. Bacteria considered multidrug resistant (MDR, resistant to ≥ 3 antibiotic classes) represented 20% of all canine isolates and were most prevalent for
species (33%). An alarming, escalating trend of MDR prevalence was noted between 2016 (5%) and 2020 (34%). Individual ophthalmic preparations (i.e., single antibiotics or commercially available antibiotic combinations) with highest efficacy against all bacterial isolates included chloramphenicol (83%), ceftiofur (79%), amikacin (77%), neomycin-polymyxin B-bacitracin (77%), and gentamicin (74%). Efficacy of systemic antibiotics and combinations of ophthalmic preparations was also evaluated. Based on the present findings, triple antibiotic (Neo-Poly-Bac) is recommended as empirical monotherapy for prophylactic antibiotic therapy in dogs with simple corneal ulcers, while a chloramphenicol-ciprofloxacin combination is empirically recommended for therapeutic management of infected corneal ulcers. Pending culture and susceptibility results, appropriate selection of empiric antibiotic therapy is important to enhance therapeutic outcome and reduce antibacterial resistance in dogs with corneal ulceration.
Chronic inflammation is a component of many disease conditions that affect a large group of individuals worldwide. Chronic inflammation is characterized by persistent, low-grade inflammation and is ...increased in the aging population. Neutrophils are normally the first responders to acute inflammation and contribute to the resolution of inflammation. However, in chronic inflammation, the role of neutrophils is less well understood and has been described as either beneficial or detrimental, causing tissue damage and enhancing the immune response. Emerging evidence suggests that neutrophils are important players in several chronic diseases, such as atherosclerosis, diabetes mellitus, nonalcoholic fatty liver disease and autoimmune disorders. This review will highlight the interaction of neutrophils with other cells in the context of chronic inflammation, the contribution of neutrophils to selected chronic inflammatory diseases, and possible future therapeutic strategies.
Bacterial keratitis is a serious and vision-threatening condition in veterinary and human patients, one that often requires culture and susceptibility testing to adjust therapy and improve clinical ...outcomes. The present study challenges the antimicrobial susceptibility testing (AST) paradigm in ophthalmology, enabling more accurate
-to-
translation by incorporating factors normally present during host-pathogen interactions in clinical patients. Thirty bacteria (10
, 10
, 10
) were isolated from canine patients with infectious keratitis. For each isolate, commercial plates (Sensititre™ JOEYE2) were used to assess the minimal inhibitory concentration (MIC) of 17 different antibiotics in the absence (0% albumin, control) or presence of canine albumin (0.01-2%). For
, the experiment was repeated with actual tear fluid collected from canine eyes with ocular surface inflammation. Kruskal-Wallis, Wilcoxon signed rank test and Spearman's correlation tests were used for statistical analysis. Clinical outcomes were unfavorable in selected canine patients with bacterial keratitis (e.g., globe perforation, graft dehiscence) despite standard AST (i.e., 0% albumin in test medium) confirming that most corneal infections (93%) were susceptible to ≥1 topical antibiotics used at the initial visit. Albumin levels ≥0.05% increased MICs in a dose-dependent, bacteria-specific, and antibiotic-specific manner. No significant differences (
= 1.000) were noted in MICs of any antibiotic whether albumin or tear fluid was added to the Mueller-Hinton broth. Percent protein binding inherent to each antibiotic was associated with clinical interpretations (Spearman's rho = -0.53,
= 0.034) but not changes in MICs. Albumin in tears impacted the efficacy of selected ophthalmic antibiotics as only the unbound portion of an antibiotic is microbiologically active. The present findings could improve decision making of clinicians managing bacterial keratitis, reduce development of antimicrobial resistance, influence current guidelines set by the Clinical and Laboratory Standards Institute, and serve as a reference for bacteriological evaluations across medical fields and across species.
Increased vascular permeability and consequent plasma leakage from postcapillary venules is a cardinal sign of inflammation. Although the movement of plasma constituents from the vasculature to the ...affected tissue aids in clearing the inflammatory stimulus, excessive plasma extravasation can lead to hospitalisation or death in cases such as influenza-induced pneumonia, burns or brain injury. The use of intravital imaging has significantly contributed to the understanding of the mechanisms controlling the vascular permeability alterations that occur during inflammation. Today, intravital imaging can be performed using optical and non-optical techniques. Optical techniques, which are generally used in experimental settings, include traditional intravital fluorescence microscopy and near-infrared fluorescence imaging. Magnetic resonance (MRI) and radioisotopic imaging are used mainly in the clinical setting, but are increasingly used in experimental work, and can detect plasma leakage without optics. Although these methods are all able to visualise inflammatory plasma leakage in vivo, the spatial and temporal resolution differs between the techniques. In addition, they vary with regards to invasiveness and availability. This overview discusses the use of imaging techniques in the visualisation of inflammatory plasma leakage.
To achieve quality in medical education, peer teaching, understood as students taking on roles as educators for peers, is frequently used as a teaching intervention. While the benefits of peer ...teaching for learners and faculty are described in detail in the literature, less attention is given to the learning outputs for the student-teachers. This systematic review focuses on the learning outputs for medical undergraduates acting as student-teachers in the last decade (2012-2022).
Our aim is to describe what learning outputs student-teachers have from peer teaching, and map what research methods are used to assess the outputs. We defined learning outputs in a broad sense, including all types of learning experiences, intended and non-intended, associated with being a peer teacher.
A literature search was conducted in four electronic databases. Title, abstract and full text were screened by 8 independent reviewers and selection was based on predefined eligibility criteria. We excluded papers not describing structured peer teaching interventions with student-teachers in a formalized role. From the included articles we extracted information about the learning outputs of being a student-teacher as medical undergraduate.
From 668 potential titles, 100 were obtained as full-texts, and 45 selected after close examination, group deliberation, updated search and quality assessment using MERSQI score (average score 10/18). Most articles reported learning outputs using mixed methods (67%). Student-teachers reported an increase in subject-specific learning (62%), pedagogical knowledge and skills (49%), personal outputs (31%) and generic skills (38%). Most articles reported outputs using self-reported data (91%).
Although there are few studies that systematically investigate student-teachers learning outputs, evidence suggests that peer teaching offers learning outputs for the student-teachers and helps them become better physicians. Further research is needed to enhance learning outputs for student-teachers and systematically investigate student-teachers' learning outputs and its impact on student-teachers.
The present study describes the prevalence of bacterial cross-contamination in a veterinary ophthalmology setting, a serious issue that can result in healthcare-associated (or nosocomial) infections ...among patients and staff. Retrospective (
= 5 patients) and prospective (
= 23 patients) studies evaluated bacterial isolates in companion animals presenting with ulcerative keratitis, sampling the patients' cornea and surrounding examination room, including the environment (exam table, countertop, floor) and ophthalmic equipment (slit lamp, transilluminator, direct ophthalmoscope, indirect headset, tonometer). Results of bacterial culture and antibiotic susceptibility testing were recorded, and degree of genetic relatedness was evaluated in six pairs of isolates (cornea + environment or equipment) using pulse-field gel electrophoresis (PFGE). Overall contamination rate of ophthalmic equipment, environment, and examination rooms (equipment + environment) was 42.9% (15/35 samples), 23.7% (9/38 samples) and 32.9% (24/73 samples), respectively. Methicillin-resistant
(MRSP), a multi-drug resistant (MDR) pathogen with zoonotic potential, was isolated in 8.2% (6/73) of samples. The patient's cornea was likely the source of cross-contamination in 50% (3/6) of MRSP pairs as evaluated by PFGE; notably, two of the three similar bacterial strains did not have an exact match of their antibiotic susceptibility profiles, highlighting the importance of advanced diagnostics such as PFGE to assess cross-contamination in healthcare facilities. Future work could examine the contamination prevalence of specific equipment or the efficacy of cleaning protocols to mitigate cross-contamination in veterinary practice.
The objective of this paper was to explore what stressful events post‐menopausal women with primary or recurrent breast cancer experience, how bothersome these events were and which coping strategies ...these women used. Data were collected from 131 patients diagnosed with primary or recurrent breast cancer. The Daily Coping Assessment was used. Thematic analysis was applied to form themes of stressful events. Six types of stressful events were extracted. The most frequently experienced events for women with primary cancer and those with recurrent cancer were ‘distressing bodily symptoms’. The most bothersome event among primary cancer was ‘everyday concerns’ and in the recurrent group, ‘distressing psychological reactions’. The most commonly used strategies were ‘acceptance’, ‘distraction’ and ‘relaxation’. This study shows that women in different parts of the cancer trajectory differ in what they perceive to be stressful events when reporting them in their own words in a diary. The differences have an impact on the subsequent coping strategies they used.
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