The Impact of Setons on Perianal Fistula Outcomes in Patients With Crohn's Disease Treated With Anti-TNF Therapy: A Multicentre Study.

Background And Aims: We aimed to assess the impact of setons on perianal fistula outcomes in patients with perianal fistulising Crohn's disease (PFCD) treated with anti-TNF therapy.

Methods: We included patients treated with their first anti-TNF therapy for PFCD after undergoing a pelvic MRI between 2005 and 2022 from 6 North American centres. Our exposure was one or more setons at the time of anti-TNF therapy.

Measuring the effect of the anti-nerve growth factor antibodies bedinvetmab and frunevetmab on quality of life in dogs and cats with osteoarthritis using a validated health-related quality of life outcome measure: an observational real-world study.

Background: Osteoarthritis causes chronic pain, impaired joint function, decreased mobility and negatively impacts quality of life (QOL). Anti-nerve growth factor antibodies bedinvetmab for dogs and frunevetmab for cats are licensed for the alleviation of osteoarthritis pain but their QOL impact is unreported. Our aim was to determine if these therapeutics improve QOL using a validated health-related QOL measure that generates scores in four domains of QOL-energetic and enthusiastic (E/E), happy and content (H/C), active and comfortable (A/C) and calm and relaxed (C/R)-in the dog and three in the cat-vitality, comfort and emotional wellbeing (EWB).

Outcomes of a mandatory non-medical switch of infliximab to a biosimilar for inflammatory bowel disease in British Columbia, Canada.

Background: Despite infliximab biosimilars becoming widely used in inflammatory bowel disease (IBD) patients, real-world non-medical switching is sparse. A biosimilar non-medical switch was launched in British Columbia in 2019, the first Canadian province to do so, from Remicade to an approved biosimilar (CT-P13 or SB2).

Aims: This study aims to obtain real-world evidence evaluating the clinical outcomes of non-medical switching from Remicade to the infliximab biosimilars.

CRYAB plays a role in terminating the presence of pro-inflammatory macrophages in the older, injured mouse peripheral nervous system.

Evidence indicates that dysfunction of older Schwann cells and macrophages contributes to poor regeneration of more mature peripheral nervous system (PNS) neurons after damage. Since the underlying molecular factors are largely unknown, we investigated if CRYAB, a small heat shock protein that is expressed by Schwann cells and axons and whose expression declines with age, impacts prominent deficits in the injured, older PNS including down-regulation of cholesterol biosynthesis enzyme genes, Schwann cell dysfunction, and macrophage persistence. Following sciatic nerve transection injury in 3- and 12-month-old wildtype and CRYAB knockout mice, we found by bulk RNA sequencing and RT-PCR, that while gene expression of cholesterol biosynthesis enzymes is markedly dysregulated in the aging, injured PNS, CRYAB is not involved.

Regulatory T cells use heparanase to access IL-2 bound to extracellular matrix in inflamed tissue.

Although FOXP3 regulatory T cells (Treg) depend on IL-2 produced by other cells for their survival and function, the levels of IL-2 in inflamed tissue are low, making it unclear how Treg access this critical resource. Here, we show that Treg use heparanase (HPSE) to access IL-2 sequestered by heparan sulfate (HS) within the extracellular matrix (ECM) of inflamed central nervous system tissue. HPSE expression distinguishes human and murine Treg from conventional T cells and is regulated by the availability of IL-2.

FOXP3 regulatory T cells use heparanase to access IL-2 bound to ECM in inflamed tissues.

FOXP3 regulatory T cells (Treg) depend on exogenous IL-2 for their survival and function, but circulating levels of IL-2 are low, making it unclear how Treg access this critical resource . Here, we show that Treg use heparanase (HPSE) to access IL-2 sequestered by heparan sulfate (HS) within the extracellular matrix (ECM) of inflamed central nervous system tissue. HPSE expression distinguishes human and murine Treg from conventional T cells and is regulated by the availability of IL-2.

Efficacy of autologous mesenchymal stromal cell treatment for chronic degenerative musculoskeletal conditions in dogs: A retrospective study.

Introduction: The objective of this study was to retrospectively analyze clinical data from a referral regenerative medicine practice, to investigate the efficacy of autologous mesenchymal stromal cells (MSC) in 245 dogs deemed unresponsive to conventional treatment by their referring vet.

Methods: Diagnostic imaging [radiology and musculoskeletal ultrasound (MSK-US)] identified musculoskeletal pathology holistically. MSCs, produced according to current guidelines, were initially administered with PRP by targeted injection to joints and/or tendons, with a second MSC monotherapy administered 12 weeks later to dogs with severe pathology and/or previous elbow arthroscopic interventions.

Time resolved growth of (N)-polycyclic aromatic hydrocarbons in engine deposits uncovered with OrbiSIMS depth profiling.

Carbonaceous deposits are ubiquitous, being formed on surfaces in engines, fuel systems and on catalysts operating at high temperatures for hydrocarbon transformations. In internal combustion engines, their formation negatively affects worldwide vehicle emissions and fuel economy, leading to premature deaths and environmental damage. Deposit composition and formation pathways are poorly understood due to their insolubility and the intrinsic complexity of their layered carbonaceous matrix.

Molecular Formula Prediction for Chemical Filtering of 3D OrbiSIMS Datasets.

Modern mass spectrometry techniques produce a wealth of spectral data, and although this is an advantage in terms of the richness of the information available, the volume and complexity of data can prevent a thorough interpretation to reach useful conclusions. Application of molecular formula prediction (MFP) to produce annotated lists of ions that have been filtered by their elemental composition and considering structural double bond equivalence are widely used on high resolving power mass spectrometry datasets. However, this has not been applied to secondary ion mass spectrometry data.

The Short Form of the Glasgow Composite Measure Pain Scale in Post-operative Analgesia Studies in Dogs: A Scoping Review.

The measurement and treatment of acute pain in animals is essential from a welfare perspective. Valid pain-related outcome measures are also crucial for ensuring reliable and translatable findings in veterinary clinical trials. The short form of the Glasgow Composite Measure Pain Scale (CMPS-SF) is a multi-item behavioral pain assessment tool, developed and validated using a psychometric approach, to measure acute pain in the dog.

Validity and Responsiveness of the Generic Health-Related Quality of Life Instrument (VetMetrica™) in Cats With Osteoarthritis. Comparison of Vet and Owner Impressions of Quality of Life Impact.

Validity is not an inherent property of a measurement scale and so evidence for validity relating to its use for particular purposes, with defined populations and in specified contexts must be accumulated. We have published the development of a web-based, generic health-related quality of life instrument (VetMetrica™) to measure the affective impact of chronic disease in cats and provided evidence for its validity in a mixed population of cats, some of which, according to veterinary judgement, were healthy and others of which were suffering from chronic conditions likely to affect their quality of life, often with multiple co-morbidities present. The first aim of the current study was to demonstrate the construct validity of the VetMetrica™ generic instrument when used with cats suffering from osteoarthritis, by testing the hypothesis that the health-related quality of life profile of cats with different severities of osteoarthritis would differ and by demonstrating convergent validity between the health-related quality of life profile scores and independently quantified vet-assessed pain and quality of life impact scores.

She Doesn't Even Go Here: The Role of Inflammatory Astrocytes in CNS Disorders.

Astrocyte heterogeneity is a rapidly evolving field driven by innovative techniques. Inflammatory astrocytes, one of the first described subtypes of reactive astrocytes, are present in a variety of neurodegenerative diseases and may play a role in their pathogenesis. Moreover, genetic and therapeutic targeting of these astrocytes ameliorates disease in several models, providing support for advancing the development of astrocyte-specific disease modifying therapies.

Fecal Diversion for Perianal Crohn Disease in the Era of Biologic Therapies: A Multicenter Study.

Background: The natural history of perianal Crohn disease (PCD) after fecal diversion in the era of biologics is poorly understood. We assessed clinical and surgical outcomes after fecal diversion for medically refractory PCD and determined the impact of biologics.

Methods: We performed a retrospective, multicenter study from 1999 to 2020.

Corrigendum: Development of an Early Warning System for Owners Using a Validated Health-Related Quality of Life (HRQL) Instrument for Companion Animals and Its Use in a Large Cohort of Dogs.

[This corrects the article DOI: 10.3389/fvets.2020.

Expected and Unexpected Reactivities of Homoleptic LiNacNac and Heteroleptic NacNacMg(TMP) β-Diketiminates toward Various Small Unsaturated Organic Molecules.

Homoleptic LiNacNac forms simple donor-acceptor complexes with ,'-dicyclohexylcarbodiimide (CyN═C═NCy), triphenylphosphine oxide (PhP═O), and benzophenone (PhCO). These crystallographically characterized compounds could be regarded as model intermediates en route to reducing the N═C, P═O, and C═O bonds of unsaturated substrates. Heteroleptic NacNacMg(TMP) intriguingly functions as a TMP nucleophile both with -BuNCO and -BuNCS, producing a urea or thiourea derivative respectively attached to Mg, though the NacNac ligand in the former reaction also engages noninnocently with a second -BuNCO molecule via insertion at the reactive NacNac backbone γ-carbon site.

Effect of Age, Breed, and Sex on the Health-Related Quality of Life of Owner Assessed Healthy Dogs.

Using an app, this exploratory study generated information on HRQL in a large cohort of dogs deemed healthy according to the owner. It forms the basis for further studies investigating the natural history of HRQL of dogs to inform the interpretation of interventional studies, but highlights the risks of relying on owner impression of health status. A previously published health-related quality of life (HRQL) instrument (VetMetrica™) that generates scores in four domains of quality of life in dogs - Energetic and Enthusiastic (E/E), Happy and Content (H/C), Active and Comfortable (A/C), and Calm and Relaxed (C/R), generated information on HRQL in 4,217 dogs (3 months-21 years).

Optimisation of Scores Generated by an Online Feline Health-Related Quality of Life (HRQL) Instrument to Assist the Veterinary User Interpret Its Results.

Using methodology previously described for the dog health-related quality of life (HRQL) tool (VetMetrica™), the aim was to optimize the scores profile of a comparable feline online HRQL instrument for monitoring HRQL in cats, to assist in its interpretation. Measuring HRQL helps quantify the impact of disease and its treatment on well-being, aids clinical decision making and provides information in clinical trials. In Study 1, using data collected from previous studies, scores generated for three domains of HRQL (Vitality, Comfort, Emotional Well-being) in healthy cats were normalized using standard statistical techniques of logit transformation and -scores, such that the average healthy cat has a score of 50 in all three HRQL domains.

Development of an Early Warning System for Owners Using a Validated Health-Related Quality of Life (HRQL) Instrument for Companion Animals and Its Use in a Large Cohort of Dogs.

Preventive measures in human healthcare are recognized as a means of providing early detection of disease, however, the veterinary profession has not been as effective in communicating the benefits of preventive measures to pet owners. Readily available pet healthcare information on the internet, owners not understanding that regular health evaluations can ensure the well-being of their pets and owners confusing the signs of chronic disease with normal aging have contributed to declining numbers of veterinary visits. The use of web-based generic health-related quality of life (HRQL) measures to evaluate health status (wellness) remotely could facilitate veterinary preventive medicine.

Spatially Resolved Molecular Compositions of Insoluble Multilayer Deposits Responsible for Increased Pollution from Internal Combustion Engines.

Internal combustion engines are used heavily in diverse applications worldwide. Achieving the most efficient operation is key to improving air quality as society moves to a decarbonized energy system. Insoluble deposits that form within internal combustion engine components including fuel injectors and filters negatively impact CO and pollutant emissions.

Using deep learning for a diffusion-based segmentation of the dentate nucleus and its benefits over atlas-based methods.

The dentate nucleus (DN) is a gray matter structure deep in the cerebellum involved in motor coordination, sensory input integration, executive planning, language, and visuospatial function. The DN is an emerging biomarker of disease, informing studies that advance pathophysiologic understanding of neurodegenerative and related disorders. The main challenge in defining the DN radiologically is that, like many deep gray matter structures, it has poor contrast in T1-weighted magnetic resonance (MR) images and therefore requires specialized MR acquisitions for visualization.

Backbone Reactivity of Lithium β-Diketiminate (NacNac) Complexes with CO , tBuNCO and iPrNCO.

Though alkali metal NacNac (β-diketiminate) complexes have been utilised in synthesis as NacNac-transfer agents, studies of them in their own right with small molecules are exceptionally rare. Here, the lithium compound of the common 2,6-diisopropylphenyl-β-methyldiketiminate [NacNac(Dipp, Me)] ligand is investigated with carbon dioxide and isocyanates. In all four cases reaction occurs at the backbone γ-C atom of the NacNac ligand, which redistributes electronically into a diimine.

Optimising outputs from a validated online instrument to measure health-related quality of life (HRQL) in dogs.

Measurement of health-related quality of life (HRQL) is becoming increasingly valuable within veterinary preventative health care and chronic disease management, as well as in outcomes research. Initial reliability and validation of a 22 item shortened version of VetMetrica (VM), structured questionnaire instrument to measure HRQL in dogs via a mobile application was reported previously. Meaningful interpretation and presentation of the 4 domain scores comprising the HRQL profile generated by VM is key to its successful use in clinical practice and research.

Structural and functional connectivity of the nondecussating dentato-rubro-thalamic tract.

The dentato-rubro-thalamic tract (DRTT) regulates motor control, connecting the cerebellum to the thalamus. This tract is modulated by deep-brain stimulation in the surgical treatment of medically refractory tremor, especially in essential tremor, where high-frequency stimulation of the thalamus can improve symptoms. The DRTT is classically described as a decussating pathway, ascending to the contralateral thalamus.