The Role of Dental Occlusion Ties to Achieve Stable Maxillomandibular Fixation During Temporomandibular Joint Replacement.

Dental occlusion ties (Minne Ties®) are a new example of the concept of an oral zip tie used to establish maxillomandibular fixation (MMF). Each tie uses a blunt introducer that is easily passed between embrasures and fed through a self-locking, unidirectional clasp. Five to six ties are used to establish MMF. They are fast, easy to use, and relatively safe because there are no sharps or wires associated with their use. The authors report their experience using this MMF method for temporomandibular joint replacement surgery, where over the last 2 years, over 65 collective cases have been completed using this method.

Acute pain pathways: protocol for a prospective cohort study.

INTRODUCTION: Opioid analgesics are often used to treat moderate-to-severe acute non-cancer pain; however, there is little high-quality evidence to guide clinician prescribing. An essential element to developing evidence-based guidelines is a better understanding of pain management and pain control among individuals experiencing acute pain for various common diagnoses. METHODS AND ANALYSIS: This multicentre prospective observational study will recruit 1550 opioid-naïve participants with acute pain seen in diverse clinical settings including primary/urgent care, emergency departments and dental clinics. Participants will be followed for 6 months with the aid of a patient-centred health data aggregating platform that consolidates data from study questionnaires, electronic health record data on healthcare services received, prescription fill data from pharmacies, and activity and sleep data from a Fitbit activity tracker. Participants will be enrolled to represent diverse races and ethnicities and pain conditions, as well as geographical diversity. Data analysis will focus on assessing patients' patterns of pain and opioid analgesic use, along with other pain treatments; associations between patient and condition characteristics and patient-centred outcomes including resolution of pain, satisfaction with care and long-term use of opioid analgesics; and descriptive analyses of patient management of leftover opioids. ETHICS AND DISSEMINATION: This study has received approval from IRBs at each site. Results will be made available to participants, funders, the research community and the public. TRIAL REGISTRATION NUMBER: NCT04509115.

Discordance Rate Among Bilateral Simultaneous and Sequential Temporal Artery Biopsies in Giant Cell Arteritis: Role of Frozen Sectioning Based on the Mayo Clinic Experience.

IMPORTANCE: Frozen section temporal artery biopsy (TAB) may prevent a contralateral biopsy from being performed. OBJECTIVE: To evaluate the sensitivity and specificity of TAB frozen vs permanent section pathology results for giant cell arteritis (GCA) and determine the discordance rate of bilateral TABs. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort study, medical records were reviewed from 795 patients 40 years or older who underwent TAB from January 1, 2010, to December 1, 2018, treated at a single tertiary care center with the ability to perform both frozen and permanent histologic sections. Data were analyzed from January 2019 to December 2020. MAIN OUTCOMES AND MEASURES: Sensitivity and specificity of frozen section TAB for detecting GCA, and discordance rates of bilateral permanent section TAB. RESULTS: Of the 795 included participants, 329 (41.4%) were male, and the mean (SD) age was 72 (10) years. From the 795 patients with 1162 TABs, 119 patients (15.0%) and 138 TABs had positive findings on permanent section. Of these 119 patients, 103 (86.6%) also had positive results on the frozen section, with 4 false-positives (0.6%) and 20 false-negatives (16.8%). Frozen section had a specificity of 99.4% (95% CI, 98.5-99.8), sensitivity of 83.2% (95% CI, 75.2-89.4), positive predictive value of 96.1% (95% CI, 90.4-98.9), negative predictive value of 96.6% (95% CI, 94.9-97.8), positive likelihood ratio of 140.6 (95% CI, 72.7-374.8), and a negative likelihood ratio of 0.17 (95% CI, 0.11-0.25). Simultaneous bilateral TABs were performed in 60 patients (7.5%) with a 5% discordance rate on permanent section. In comparison, bilateral frozen section-guided sequential TABs were performed in 307 patients (38.6%) with 5.5% discordance based on permanent section. In multivariate models, there was a greater odds of positive findings with age (odds ratio [OR], 1.04; 95% CI, 1.01-1.07; P = .008), vision loss (OR, 2.72; 95% CI, 1.25-5.75; P = .01), diplopia (OR, 3.33; 95% CI, 1.00-10.29; P = .04), headache (OR, 2.32; 95% CI, 1.25-4.53; P = .01), weight loss (OR, 2.37; 95% CI, 1.26-4.43; P = .007), and anorexia (OR, 5.65; 95% CI, 2.70-11.89; P < .001). CONCLUSIONS AND RELEVANCE: These results support the hypothesis that negative findings from frozen sections should not be solely relied on to refute the diagnosis of GCA, whereas positive findings from frozen sections can be reliably used to defer a contralateral biopsy pending the permanent section results.

Overexpression of uncoupling protein 3 in skeletal muscle protects against fat-induced insulin resistance.

Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and is strongly associated with obesity. Increased concentrations of intracellular fatty acid metabolites have been postulated to interfere with insulin signaling by activation of a serine kinase cascade involving PKCtheta in skeletal muscle. Uncoupling protein 3 (UCP3) has been postulated to dissipate the mitochondrial proton gradient and cause metabolic inefficiency. We therefore hypothesized that overexpression of UCP3 in skeletal muscle might protect against fat-induced insulin resistance in muscle by conversion of intramyocellular fat into thermal energy. Wild-type mice fed a high-fat diet were markedly insulin resistant, a result of defects in insulin-stimulated glucose uptake in skeletal muscle and hepatic insulin resistance. Insulin resistance in these tissues was associated with reduced insulin-stimulated insulin receptor substrate 1- (IRS-1-) and IRS-2-associated PI3K activity in muscle and liver, respectively. In contrast, UCP3-overexpressing mice were completely protected against fat-induced defects in insulin signaling and action in these tissues. Furthermore, these changes were associated with a lower membrane-to-cytosolic ratio of diacylglycerol and reduced PKCtheta activity in whole-body fat-matched UCP3 transgenic mice. These results suggest that increasing mitochondrial uncoupling in skeletal muscle may be an excellent therapeutic target for type 2 diabetes mellitus.

PKC-theta knockout mice are protected from fat-induced insulin resistance.

Insulin resistance plays a primary role in the development of type 2 diabetes and may be related to alterations in fat metabolism. Recent studies have suggested that local accumulation of fat metabolites inside skeletal muscle may activate a serine kinase cascade involving protein kinase C-theta (PKC-theta), leading to defects in insulin signaling and glucose transport in skeletal muscle. To test this hypothesis, we examined whether mice with inactivation of PKC-theta are protected from fat-induced insulin resistance in skeletal muscle. Skeletal muscle and hepatic insulin action as assessed during hyperinsulinemic-euglycemic clamps did not differ between WT and PKC-theta KO mice following saline infusion. A 5-hour lipid infusion decreased insulin-stimulated skeletal muscle glucose uptake in the WT mice that was associated with 40-50% decreases in insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-1-associated PI3K activity. In contrast, PKC-theta inactivation prevented fat-induced defects in insulin signaling and glucose transport in skeletal muscle. In conclusion, our findings demonstrate that PKC-theta is a crucial component mediating fat-induced insulin resistance in skeletal muscle and suggest that PKC-theta is a potential therapeutic target for the treatment of type 2 diabetes.

Inactivation of fatty acid transport protein 1 prevents fat-induced insulin resistance in skeletal muscle.

Insulin resistance in skeletal muscle plays a major role in the development of type 2 diabetes and may be causally associated with increases in intramuscular fatty acid metabolites. Fatty acid transport protein 1 (FATP1) is an acyl-CoA synthetase highly expressed in skeletal muscle and modulates fatty acid uptake and metabolism by converting fatty acids into fatty acyl-CoA. To investigate the role of FATP1 in glucose homeostasis and in the pathogenesis of insulin resistance, we examined the effect of acute lipid infusion or chronic high-fat feeding on insulin action in FATP1 KO mice. Whole-body adiposity, adipose tissue expression of adiponectin, intramuscular fatty acid metabolites, and insulin sensitivity were not altered in FATP1 KO mice fed a regular chow diet. In contrast, FATP1 deletion protected the KO mice from fat-induced insulin resistance and intramuscular accumulation of fatty acyl-CoA without alteration in whole-body adiposity. These findings demonstrate an important role of intramuscular fatty acid metabolites in causing insulin resistance and suggest that FATP1 may be a novel therapeutic target for the treatment of insulin resistance and type 2 diabetes.

Differential effects of rosiglitazone on skeletal muscle and liver insulin resistance in A-ZIP/F-1 fatless mice.

To determine the role of adipocytes and the tissue-specific nature in the insulin sensitizing action of rosiglitazone, we examined the effects of 3 weeks of rosiglitazone treatment on insulin signaling and action during hyperinsulinemic-euglycemic clamps in awake A-ZIP/F-1 (fatless), fat-transplanted fatless, and wild-type littermate mice. We found that 53 and 66% decreases in insulin-stimulated glucose uptake and insulin receptor substrate (IRS)-1-associated phosphatidylinositol (PI) 3-kinase activity in skeletal muscle of fatless mice were normalized after rosiglitazone treatment. These effects of rosiglitazone treatment were associated with 50% decreases in triglyceride and fatty acyl-CoA contents in the skeletal muscle of rosiglitazone-treated fatless mice. In contrast, rosiglitazone treatment exacerbated hepatic insulin resistance in the fatless mice and did not affect already reduced IRS-2-associated PI 3-kinase activity in liver. The worsening of insulin action in liver was associated with 30% increases in triglyceride and fatty acyl-CoA contents in the liver of rosiglitazone-treated fatless mice. In conclusion, these data support the hypothesis that rosiglitazone treatment enhanced insulin action in skeletal muscle mostly by its ability to repartition fat away from skeletal muscle.