Neutrophils enhance the clearance of systemic amyloid deposits in a murine amyloidoma model.

Introduction: Amyloid-specific antibodies have been shown to opsonize and enhance amyloid clearance in systemic amyloidosis mouse models. However, the immunological mechanisms by which amyloid is removed have not been clearly defined. Previous reports from preclinical studies suggest polymorphonuclear cells (, neutrophils) can affect amyloid removal.

Lunar-linked biological rhythms in the immune system of freshwater three-spined stickleback.

Immune responses are widely accepted to be under circadian regulation via a molecular clock, with many practical consequences, but much less is known of how other biological rhythms could affect the immune system. In this study, we search for lunar rhythms (circalunar, circasemilunar, and circatidal cycles) in the immune expression of the recently marine-derived freshwater fish, the low-plate morph of the three-spined stickleback. We employed time series of immune expression (mRNA) measurements for 14 immune-associated genes, representing a variety of immunological pathways.

Human platelet concentrates treated with microbicidal 405 nm light retain hemostasis activity.

Chemical and UV light-based pathogen reduction technologies are currently in use for human platelet concentrates (PCs) to enhance safety from transfusion-transmitted infections. Relative to UV light, 405 nm violet-blue light in the visible spectrum is known to be less harmful. Hence, in this report for the first time, we have assessed the global hemostasis activity of PCs stored in plasma and the activities of six plasma coagulation factors (CFs) as a measure of in vitro hemostatic activity following exposure to the microbicidal 405 nm light.

Preclinical evaluation of Tc-99m p5+14 peptide for SPECT detection of cardiac amyloidosis.

Introduction: Amyloid deposition is a cause of restrictive cardiomyopathy. Patients who present with cardiac disease can be evaluated for transthyretin (TTR)-associated cardiac amyloidosis using nuclear imaging with 99mTc-labeled pyrophosphate (PYP); however, light chain-associated (AL) cardiac amyloid is generally not detected using this tracer. As an alternative, the amyloid-binding peptide p5+14 radiolabeled with iodine-124 has been shown to be an effective pan-amyloid radiotracer for PET/CT imaging.

Promotion Criteria for Medical Educators: Are We Climbing a Ladder with Invisible Rungs?

Objective: In 2006 the Association of American Medical Colleges recommended standardization of documentation of the contributions of medical educators and guidelines for their academic promotion. The authors characterized current United States (US) medical school promotion guidelines for medical educators.

Methods: Authors collected publicly available data from medical school promotion websites from March through July 2022 after determining categories by traditional-set domains as well as peer-reviewed standards.

Development and characterization of a prototypic pan-amyloid clearing agent - a novel murine peptide-immunoglobulin fusion.

Introduction: Systemic amyloidosis is a progressive disorder characterized by the extracellular deposition of amyloid fibrils and accessory proteins in visceral organs and tissues. Amyloid accumulation causes organ dysfunction and is not generally cleared by the immune system. Current treatment focuses on reducing amyloid precursor protein synthesis and slowing amyloid deposition.

Sources of bias and limitations of thrombinography: inner filter effect and substrate depletion at the edge of failure algorithm.

Background: Fluorogenic thrombin generation (TG) is a global hemostasis assay that provides an overall representation of hemostasis potential. However, the accurate detection of thrombin activity in plasma may be affected by artifacts inherent to the assay-associated fluorogenic substrate. The significance of the fluorogenic artifacts or their corrections has not been studied in hemophilia treatment applications.

Remotely sensed localised primary production anomalies predict the burden and community structure of infection in long-term rodent datasets.

The increasing frequency and cost of zoonotic disease emergence due to global change have led to calls for the primary surveillance of wildlife. This should be facilitated by the ready availability of remotely sensed environmental data, given the importance of the environment in determining infectious disease dynamics. However, there has been little evaluation of the temporal predictiveness of remotely sensed environmental data for infection reservoirs in vertebrate hosts due to a deficit of corresponding high-quality long-term infection datasets.

Early-life immune expression profiles predict later-life health and fitness in a wild rodent.

Individuals differ in the nature of the immune responses they produce, affecting disease susceptibility and ultimately health and fitness. These differences have been hypothesized to have an origin in events experienced early in life that then affect trajectories of immune development and responsiveness. Here, we investigate how early-life immune expression profiles influence life history outcomes in a natural population of field voles, Microtus agrestis, in which we are able to monitor variation between and within individuals through time by repeat sampling of individually marked animals.

Shame at the Gates of Medicine: A Hermeneutic Exploration of Premedical Students' Experiences of Shame.

Purpose: Little is known about the nature of shame in students attempting to enter medical school, despite its potential to impact well-being and professional identity formation during training. In this study, the authors used hermeneutic phenomenology to ask: How do premedical students experience shame as they apply to medical school?

Method: From September 2020 to March 2021, the authors recruited 12 students from a U.S.

Effects of an IgE receptor polymorphism acting on immunity, susceptibility to infection, and reproduction in a wild rodent.

The genotype of an individual is an important predictor of their immune function, and subsequently, their ability to control or avoid infection and ultimately contribute offspring to the next generation. However, the same genotype, subjected to different intrinsic and/or extrinsic environments, can also result in different phenotypic outcomes, which can be missed in controlled laboratory studies. Natural wildlife populations, which capture both genotypic and environmental variability, provide an opportunity to more fully understand the phenotypic expression of genetic variation.

Collagen inhibits phagocytosis of amyloid and and may act as a 'don't eat me' signal.

Background: Systemic amyloidosis refers to a group of protein misfolding disorders characterized by the extracellular deposition of amyloid fibrils in organs and tissues. For reasons heretofore unknown, amyloid deposits are not recognized by the immune system, and progressive deposition leads to organ dysfunction.

Methods: and phagocytosis assays were performed to elucidate the impact of collagen and other amyloid associated proteins (eg serum amyloid p component and apolipoprotein E) had on amyloid phagocytosis.

Living with chronic infection: Persistent immunomodulation during avirulent haemoparasitic infection in a wild rodent.

Apicomplexans are a protozoan phylum of obligate parasites which may be highly virulent during acute infections, but may also persist as chronic infections which appear to have little fitness cost. Babesia microti is an apicomplexan haemoparasite that, in immunocompromised individuals, can cause severe, potentially fatal disease. However, in its natural host, wild field voles (Microtus agrestis), it exhibits chronic infections that have no detectable impact on survival or female fecundity.

Some observations on meaningful and objective inference in radioecological field studies.

Anthropogenic releases of radiation are of ongoing importance for environmental protection, but the radiation doses at which natural systems begin to show effects are controversial. More certainty is required in this area to achieve optimal regulation for radioactive substances. We recently carried out a large survey (268 sampled animals and 20 sites) of the association between environmental radiation exposures and small mammal gut-associated microbiomes (fungal and bacterial) in the Chornobyl Exclusion zone (CEZ).

Can We Ensure That Workshops Are Effective in Their Goal? Impact of a National Education Workshop on Participants' Subsequent Scholarship.

Medical education conferences offer practical workshops to facilitate physicians' lifelong learning. Little is known about integration of workshop material after conferences. We sought to evaluate the application of workshop content focused on scholarly publication preparation.

Management of transitions to adult services for young people with eating disorders: survey of current practice in England.

Aims And Method: The Royal College of Psychiatrists has published recommendations for managing transitions between child and adolescent mental health services (CAMHS) and adult services for eating disorders. A self-report questionnaire was designed to establish how many CAMHS teams meet these recommendations and was distributed to 70 teams providing eating disorders treatment in England.

Results: Of the 38 services that participated, 31 (81.

Treatment of glioblastoma with current oHSV variants reveals differences in efficacy and immune cell recruitment.

Oncolytic herpes simplex viruses (oHSVs) have demonstrated efficient lytic replication in human glioblastoma tumors using immunodeficient mouse models, but early-phase clinical trials have reported few complete responses. Potential reasons for the lack of efficacy are limited vector potency and the suppressive glioma tumor microenvironment (TME). Here we compare the oncolytic activity of two HSV-1 vectors, a KOS-strain derivative KG4:T124 and an F-strain derivative rQNestin34.

Fungal microbiomes are determined by host phylogeny and exhibit widespread associations with the bacterial microbiome.

Interactions between hosts and their resident microbial communities are a fundamental component of fitness for both agents. Though recent research has highlighted the importance of interactions between animals and their bacterial communities, comparative evidence for fungi is lacking, especially in natural populations. Using data from 49 species, we present novel evidence of strong covariation between fungal and bacterial communities across the host phylogeny, indicative of recruitment by hosts for specific suites of microbes.

Considerations on activity assay discrepancies in factor VIII and factor IX products.

New modified coagulation factor VIII (FVIII) and factor IX (FIX) products have been designed to improve the treatment of individuals with hemophilia A and B by increasing the interval between dosing. Although these FVIII and FIX molecules have been structurally modified to improve the circulation time, the changes have also influenced their behavior in functional assays in comparison with traditional plasma-derived or recombinant coagulation factors. The assignment of potencies for these products can be problematic because discordance in factor activity values between the commonly used one-stage clotting and chromogenic substrate assays is often observed.

Impacts of radiation exposure on the bacterial and fungal microbiome of small mammals in the Chernobyl Exclusion Zone.

Environmental impacts of the 1986 Chernobyl Nuclear Power Plant accident are much debated, but the effects of radiation on host microbiomes have received little attention to date. We present the first analysis of small mammal gut microbiomes from the Chernobyl Exclusion Zone in relation to total absorbed dose rate, including both caecum and faeces samples. We provide novel evidence that host species determines fungal community composition, and that associations between microbiome (both bacterial and fungal) communities and radiation exposure vary between host species.

Fluorescence artifact correction in the thrombin generation assay: Necessity for correction algorithms in procoagulant samples.

Introduction: The thrombin generation (TG) test is a global hemostasis assay sensitive to procoagulant conditions. However, some TG assays may underestimate elevated TG when the thrombin fluorogenic substrate is depleted or fluorescence is attenuated by the inner filter effect (IFE).

Objectives: We sought to elucidate the extent to which procoagulant conditions require correcting for fluorogenic substrate depletion and/or IFE.

Detecting factor XIa in immune globulin products: Commutability of international reference materials for traditional and global hemostasis assays.

Background: Activated coagulation factor XIa (FXIa) is an impurity and primary source of procoagulant activity in thrombosis-implicated immune globulin (IG) products. Several assays, of varying quality and precision are used to assess FXIa-like procoagulant activity in units relevant to their respective principles.

Objectives: To advance unified reporting, we sought to employ the World Health Organization reference reagents (RRs) to present the results of differing methodologies in units of FXIa activity and rank the sensitivity and robustness of these methodologies.