Open-mouth jaw locking in cats:a literature review and use of CT in three cases

Case series summary This report summarises and reviews the published cases of open-mouth jaw locking in cats and describes three further cases. Case 1 was a 5-year-old, 5.3 kg male neutered domestic shorthair cat. CT identified changes consistent with temporomandibular joint (TMJ) dysplasia with osseous degenerative changes, and the cat subsequently underwent bilateral partial zygomectomy with bilateral partial coronoidectomy. Case 2 was a 10-year-old, 6.0 kg male neutered Exotic Shorthair. Aside from a fracture of the left maxillary canine tooth crown and absence of the left maxillary fourth premolar tooth, no abnormalities were found on CT scan. The cat also underwent bilateral partial zygomectomy with bilateral partial coronoidectomy. The third case was a 1-year-old, 4.0 kg male neutered Persian cat. Changes on CT were consistent with bilateral TMJ dysplasia, and the cat underwent staged bilateral partial zygomectomy with bilateral partial coronoidectomy. There was no recurrence of open-mouth jaw locking in any of the cases on long-term follow-up. Relevance and novel information Open-mouth jaw locking has been reported in cats of a wide range of ages, from 1–10 years. Cats with all skull types (brachycephalic, mesaticephalic and dolichocephalic) may be affected, but brachycephalic breeds seem to be over-represented. A CT scan with the jaw locked in place is recommended for diagnosis and surgical planning purposes; two of the cases reported here document the first cases of TMJ dysplasia in cats to be definitively diagnosed using CT. Trauma and symphyseal or TMJ laxity may also predispose to development of the condition. Partial coronoidectomy and partial zygomatic arch resection performed alone or in combination are generally successful at preventing recurrence. Bilateral partial zygomectomy with bilateral partial coronoidectomy has not previously been reported as a surgical treatment, and is recommended when open-mouth jaw locking occurs bilaterally. </jats:sec

Blunted endogenous opioid release following an oral amphetamine challenge in pathological gamblers

Pathological gambling is a psychiatric disorder and the first recognized behavioral addiction, with similarities to substance use disorders but without the confounding effects of drug-related brain changes. Pathophysiology within the opioid receptor system is increasingly recognized in substance dependence, with higher mu-opioid receptor (MOR) availability reported in alcohol, cocaine and opiate addiction. Impulsivity, a risk factor across the addictions, has also been found to be associated with higher MOR availability. The aim of this study was to characterize baseline MOR availability and endogenous opioid release in pathological gamblers (PG) using [(11)C]carfentanil PET with an oral amphetamine challenge. Fourteen PG and 15 healthy volunteers (HV) underwent two [(11)C]carfentanil PET scans, before and after an oral administration of 0.5 mg/kg of d-amphetamine. The change in [(11)C]carfentanil binding between baseline and post-amphetamine scans (ΔBPND) was assessed in 10 regions of interest (ROI). MOR availability did not differ between PG and HV groups. As seen previously, oral amphetamine challenge led to significant reductions in [(11)C]carfentanil BPND in 8/10 ROI in HV. PG demonstrated significant blunting of opioid release compared with HV. PG also showed blunted amphetamine-induced euphoria and alertness compared with HV. Exploratory analysis revealed that impulsivity positively correlated with caudate baseline BPND in PG only. This study provides the first evidence of blunted endogenous opioid release in PG. Our findings are consistent with growing evidence that dysregulation of endogenous opioids may have an important role in the pathophysiology of addictions

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Tyrosine kinase Flt3/Flt3-ligand signaling in the modulation of immune responses in experimental arthritis

Rheumatoid arthritis (RA) is an autoimmune, chronic systemic inflammatory disorder that primarily affects flexible joints resulting in severe joint destruction and disability if left untreated. Today, advances in treatment have significantly improved the outcome for patients, although the pathogenesis of RA remains relatively unknown. Signaling through the tyrosine kinase receptor fms-like tyrosine kinase 3 (Flt3) has been suggested to play a part in the RA pathogenesis. Flt3 is primarily expressed on hematopoietic stem cells and lymphoid progenitors in the bone marrow and has an important role in early B-cell development and formation of dendritic cells (DC). Furthermore, the ligand for Flt3 (Flt3L) serves as a regulator of regulatory T-cell (Treg) homeostasis and has been suggested to support differentiation of bone-resorbing osteoclasts. This thesis aimed to investigate the effect of Flt3/Flt3L signaling on the immune system during development of arthritis using an experimental animal model of human RA. Our study shows that Flt3 signaling supports formation of DCs and Treg cells during arthritis development. Treg expansion associated with Flt3L treatment resulted in a reduced production of inflammatory cytokines, reduced levels of antigen-specific antibodies and reduced bone destruction. On the contrary, lack of Flt3L was associated with reduced Treg formation resulting in loss of control over T-cell proliferation, and bone destruction during arthritis. Flt3L was found to positively influence the transcription of the osteoclast-regulating factor IRF8, and could by this mechanism influence osteoclast formation. Impaired signaling through Flt3 resulted in low IRF8 expression, accumulation of osteoclasts in the arthritic joint and an increased loss of femoral trabecular bone. Conversely, Flt3L treatment was associated with increased IRF8 expression, reduced osteoclast formation and restoration of trabecular bone formation in mice lacking Flt3L (Flt3LKO). Finally, we could identify a previously unacknowledged role for Flt3 in peripheral B-cell responses. We demonstrated that Flt3 was re-expressed on activated B-cells following LPS stimulation in vitro and on a population of germinal center B-cells in vivo. By using Flt3LKO mice we could identify an important role for Flt3L in class switch recombination (CSR) to IgG1. B-cells from Flt3LKO mice were found have reduced activation of Stat6 after IL-4 stimulation, resulting in impaired initiation of CSR to IgG1 and highly reduced formation of IgG1+ B-cells and IgG1 production. In summary this thesis shows that Flt3L has an important function in regulating DC and Treg homeostasis and function during arthritis. Furthermore, Flt3L has a regulatory role on osteoclast development and on trabecular bone formation. Finally, signaling through the Flt3 receptor on activated B-cells has an important role in the CSR process and deficiency of Flt3L leads to a skewed antibody response towards the more potent IgG subclasses IgG2b and IgG2c. Together, these results suggest that Flt3L might play a protective role during arthritis by reduction of bone destruction, induction of regulatory T-cells and regulation of antibody effector functions. The conclusion of this thesis is that signaling through the tyrosine kinase Flt3 plays an important role in modulating immune responses during experimental arthritis