Cross-sectional study of approaches to diagnosis and management of dogs with immune-mediated haemolytic anaemia in primary care and referral veterinary practices in the United Kingdom.

ObjectivesTo determine whether veterinarians in primary care practices (PCPs) and board-certified clinicians (BCCs) approach treatment of dogs with immune-mediated haemolytic anaemia (IMHA) similarly, and whether practitioners with more experience treat similarly to those with less experience. We hypothesised those in PCPs would show more variation in their approach to similar cases than BCCs.MethodsA cross-sectional study was conducted by distributing a questionnaire to BCCs and veterinarians in PCPs. The questionnaire included direct questions and a number of clinical scenarios intended to capture approaches to common treatment problems.ResultsQuestionnaire responses were received from 241 veterinarians, including 216 in PCPs and 25 BCCs. Veterinarians in both settings used similar tests for diagnosis of IMHA, but BCCs performed more tests to exclude underlying causes of 'associative' disease. All veterinarians reported use of similar initial dosages of glucocorticoids (median 2 mg/kg per day in both groups, p = 0.92) but those used by more experienced practitioners were higher than those with less experience. Most veterinarians made allowances for the weight of dogs, using lower prednisolone dosages in a clinical scenario involving a 40 kg dog compared to a 9 kg dog (p = 0.025 for PCP, p = 0.002 for BCC). BCCs reported greater use of combinations of immunosuppressive drugs (pConclusionsApproaches to treatment of dogs with IMHA differ between BCCs and those in PCP. These differences may affect design and implementation of future research studies and clinical guidelines

Histotripsy of the Prostate in a Canine Model: Characterization of Post-Therapy Inflammation and Fibrosis

Introduction: Histotripsy is a nonthermal, noninvasive, pulsed ultrasound technology that homogenizes tissue within the targeted volume. From previous experiments, it appeared that the resultant fibrotic response from histotripsy was limited compared with the typical tissue response seen after thermoablation. The objective of this study was to characterize the inflammatory response and quantify patterns of collagen deposition 6 weeks after in vivo canine prostate histotripsy. Methods: Histotripsy was applied to the left half of eight canine prostates to produce an intraparenchymal zone of tissue homogenization. Six weeks after treatment, prostates were harvested, sectioned, and stained with hematoxylin and eosin for histologic evaluation, CD3, CD20, and Mac387 immunohistochemistry to characterize the inflammatory components, and picrosirius red staining to identify collagen. Results: Seven of eight treated prostates exhibited only minimal residual inflammation. Visual microscopic analysis of picrosirius red slides revealed a band of dense collagen (0.5?mm wide) immediately adjacent to the cavity produced by histotripsy. This was surrounded by a second band (1?mm wide) of less dense collagen interspersed among glandular architecture. A lobar distribution of epithelial atrophy and basal cell hyperplasia reminiscent of periurethral glands and ducts was apparent surrounding the margin of the treatment cavities. Tissue loss (-31%) was apparent on the treated side of all prostates while four demonstrated a net decrease in collagen content. Conclusions: In vivo histotripsy of canine prostate produced a decrease in prostate volume coupled with a limited inflammatory and fibrotic response. A narrow (1.5?mm) band of fibrosis around the empty, reepithelialized treatment cavity was observed 6 weeks after treatment. In four cases, an overall reduction in collagen content was measured. Further studies are planned to correlate these histologic findings with alteration in mechanical tissue properties and to explore histotripsy strategies for treatment of benign prostatic hyperplasia that optimize tissue volume removal with minimization of fibrosis.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140079/1/end.2014.0585.pd

Septic arthritis in an in vivo murine model induced by Staphylococcus aureus:a comparison between actions of the haemolysin toxin and the effects of the host immune response

AIMS: Staphylococcus aureus is a major cause of septic arthritis, and in vitro studies suggest α haemolysin (Hla) is responsible for chondrocyte death. We used an in vivo murine joint model to compare inoculation with wild type S. aureus 8325-4 with a Hla-deficient strain DU1090 on chondrocyte viability, tissue histology, and joint biomechanics. The aim was to compare the actions of S. aureus Hla alone with those of the animal’s immune response to infection. METHODS: Adult male C57Bl/6 mice (n = 75) were randomized into three groups to receive 1.0 to 1.4 × 10(7) colony-forming units (CFUs)/ml of 8325-4, DU1090, or saline into the right stifle joint. Chondrocyte death was assessed by confocal microscopy. Histological changes to inoculated joints were graded for inflammatory responses along with gait, weight changes, and limb swelling. RESULTS: Chondrocyte death was greater with 8325-4 (96.2% (SD 5.5%); p < 0.001) than DU1090 (28.9% (SD 16.0%); p = 0.009) and both were higher than controls (3.8% (SD 1.2%)). Histology revealed cartilage/bone damage with 8325-4 or DU1090 compared to controls (p = 0.010). Both infected groups lost weight (p = 0.006 for both) and experienced limb swelling (p = 0.043 and p = 0.018, respectively). Joints inoculated with bacteria showed significant alterations in gait cycle with a decreased stance phase, increased swing phase, and a corresponding decrease in swing speed. CONCLUSION: Murine joints inoculated with Hla-producing 8325-4 experienced significantly more chondrocyte death than those with DU1090, which lack the toxin. This was despite similar immune responses, indicating that Hla was the major cause of chondrocyte death. Hla-deficient DU1090 also elevated chondrocyte death compared to controls, suggesting a smaller additional deleterious role of the immune system on cartilage. Cite this article: Bone Joint Res 2022;11(9):669–678

Evaluating the communication within fire and rescue services and the NHS on the fire risk of emollients in accordance of the MHRA safety update

The Medicines and Healthcare products Regulatory Agency update in 2018 reported 50 fatal fires linked with emollient use. It detailed the fire risk and new advice aimed at fire service and health care professionals in reporting of such fire incidents and educating the public on safer use of emollients. This study investigates how this has been communicated internally and publicly, with 52 Fire and Rescue Services (FRSs) websites and, 191 Clinical Commissioning Groups (CCGs), and 21 Local Health Boards (LHBs) formularies accessed. A Freedom of Information Request (FOIR) was also made, giving further details of implementations. Our study revealed that 63% of FRSs, 32% of CCGs and, 72% of LHBs gave no safety advice within their website or formularies. Of the 37% of FRSs and 68% of CCGs that did, only 5% and 4% were sufficiently up to date. 27% of FRSs and 28% of CCGs/LHBs revealed that they had no warning/advice internally in their FOIR responses and 25% of FRSs and, 35% of CCG/LHBs had not disseminated advice on using emollient safely to the public. We suggest improvements in safety campaigns using a multiagency and national approach and recommend organizations to educate professionals to improve reporting and effective dissemination

Frog nest foams exhibit pharmaceutical foam-like properties

Foams have frequently been used as systems for the delivery of cosmetic and therapeutic molecules; however, there is high variability in the foamability and long-term stability of synthetic foams. The development of pharmaceutical foams that exhibit desirable foaming properties, delivering appropriate amounts of the active pharmaceutical ingredient (API) and that have excellent biocompatibility is of great interest. The production of stable foams is rare in the natural world; however, certain species of frogs have adopted foam production as a means of providing a protective environment for their eggs and larvae from predators and parasites, to prevent desiccation, to control gaseous exchange, to buffer temperature extremes, and to reduce UV damage. These foams show great stability (up to 10 days in tropical environments) and are highly biocompatible due to the sensitive nature of amphibian skin. This work demonstrates for the first time that nests of the túngara frog ( Engystomops pustulosus ) are stable ex situ with useful physiochemical and biocompatible properties and are capable of encapsulating a range of compounds, including antibiotics. These protein foam mixtures share some properties with pharmaceutical foams and may find utility in a range of pharmaceutical applications such as topical drug delivery systems

A Population of X-ray Weak Quasars: PHL 1811 Analogs at High Redshift

We report the results from Chandra and XMM-Newton observations of a sample of 10 type 1 quasars selected to have unusual UV emission-line properties (weak and blueshifted high-ionization lines; strong UV Fe emission) similar to those of PHL 1811, a confirmed intrinsically X-ray weak quasar. These quasars were identified by the Sloan Digital Sky Survey at high redshift (z~2.2); eight are radio quiet while two are radio intermediate. All of the radio-quiet PHL 1811 analogs are notably X-ray weak by a mean factor of ~13. These sources lack broad absorption lines and have blue UV/optical continua, suggesting they are intrinsically X-ray weak. However, their average X-ray spectrum appears to be harder than those of typical quasars, which may indicate the presence of heavy intrinsic X-ray absorption. Our radio-quiet PHL 1811 analogs support a connection between an X-ray weak spectral energy distribution and PHL 1811-like UV emission lines; this connection provides an economical way to identify X-ray weak type 1 quasars. The fraction of radio-quiet PHL 1811 analogs in the radio-quiet quasar population is estimated to be < 1.2%. We have investigated correlations between relative X-ray brightness and UV emission-line properties for a sample combining radio-quiet PHL 1811 analogs, PHL 1811, and typical type 1 quasars. These correlation analyses suggest that PHL 1811 analogs may have extreme wind-dominated broad emission-line regions. Observationally, radio-quiet PHL 1811 analogs appear to be a subset (~30%) of radio-quiet weak-line quasars. The existence of a subset of quasars in which high-ionization "shielding gas" covers most of the BELR, but little more than the BELR, could potentially unify the PHL 1811 analogs and WLQs. The two radio-intermediate PHL 1811 analogs are X-ray bright. One of them appears to have jet-dominated X-ray emission, while the nature of the other remains unclear.Comment: ApJ accepted; 25 pages, 11 figures and 8 table

The Sloan Digital Sky Survey Reverberation Mapping Project: Technical Overview

The Sloan Digital Sky Survey Reverberation Mapping project (SDSS-RM) is a dedicated multi-object RM experiment that has spectroscopically monitored a sample of 849 broad-line quasars in a single 7 deg$^2$ field with the SDSS-III BOSS spectrograph. The RM quasar sample is flux-limited to i_psf=21.7 mag, and covers a redshift range of 0.1<z<4.5. Optical spectroscopy was performed during 2014 Jan-Jul dark/grey time, with an average cadence of ~4 days, totaling more than 30 epochs. Supporting photometric monitoring in the g and i bands was conducted at multiple facilities including the CFHT and the Steward Observatory Bok telescopes in 2014, with a cadence of ~2 days and covering all lunar phases. The RM field (RA, DEC=14:14:49.00, +53:05:00.0) lies within the CFHT-LS W3 field, and coincides with the Pan-STARRS 1 (PS1) Medium Deep Field MD07, with three prior years of multi-band PS1 light curves. The SDSS-RM 6-month baseline program aims to detect time lags between the quasar continuum and broad line region (BLR) variability on timescales of up to several months (in the observed frame) for ~10% of the sample, and to anchor the time baseline for continued monitoring in the future to detect lags on longer timescales and at higher redshift. SDSS-RM is the first major program to systematically explore the potential of RM for broad-line quasars at z>0.3, and will investigate the prospects of RM with all major broad lines covered in optical spectroscopy. SDSS-RM will provide guidance on future multi-object RM campaigns on larger scales, and is aiming to deliver more than tens of BLR lag detections for a homogeneous sample of quasars. We describe the motivation, design and implementation of this program, and outline the science impact expected from the resulting data for RM and general quasar science.Comment: 25 pages, submitted to ApJS; project website at http://www.sdssrm.or