Macrophage LRP1 Promotes Diet-Induced Hepatic Inflammation and Metabolic Dysfunction by Modulating Wnt Signaling

Hepatic inflammation is associated with the development of insulin resistance, which can perpetuate the disease state and may increase the risk of metabolic syndrome and diabetes. Despite recent advances, mechanisms linking hepatic inflammation and insulin resistance are still unclear. The low-density lipoprotein receptor-related protein 1 (LRP1) is a large endocytic and signaling receptor that is highly expressed in macrophages, adipocytes, hepatocytes, and vascular smooth muscle cells. To investigate the potential role of macrophage LRP1 in hepatic inflammation and insulin resistance, we conducted experiments using macrophage-specific LRP1-deficient mice (macLRP1−/−) generated on a low-density lipoprotein receptor knockout (LDLR−/−) background and fed a Western diet. LDLR−/−; macLRP1−/− mice gained less body weight and had improved glucose tolerance compared to LDLR−/− mice. Livers from LDLR−/−; macLRP1−/− mice displayed lower levels of gene expression for several inflammatory cytokines, including Ccl3, Ccl4, Ccl8, Ccr1, Ccr2, Cxcl9, and Tnf, and reduced phosphorylation of GSK3α and p38 MAPK proteins. Furthermore, LRP1-deficient peritoneal macrophages displayed altered cholesterol metabolism. Finally, circulating levels of sFRP-5, a potent anti-inflammatory adipokine that functions as a decoy receptor for Wnt5a, were elevated in LDLR−/−; macLRP1−/− mice. Surface plasmon resonance experiments revealed that sFRP-5 is a novel high affinity ligand for LRP1, revealing that LRP1 regulates levels of this inhibitor of Wnt5a-mediated signaling. Collectively, our results suggest that LRP1 expression in macrophages promotes hepatic inflammation and the development of glucose intolerance and insulin resistance by modulating Wnt signaling.

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Voice Disorders are Associated With Stress Among Teachers: A Cross-Sectional Study in Finland

Voice disorders are considered to be more common among teachers than other occupations. However, epidemiological data are scarce and only a few researchers have studied stress as a risk factor in voice disorders in teachers. This paper presents data from a study on Finnish school teachers which investigated the prevalence of voice disorders and evaluated the risk factors for voice disorders, especially stress.

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Predicting Patient Needs for Interdisciplinary Services in a Voice and Swallowing Center

In a subspecialty interdisciplinary voice and swallowing clinic, patient referrals come from a wide variety of disciplines for various reasons, which can make scheduling their initial evaluations challenging. Depending on the nature of complaints and symptoms, patients may best be evaluated either by a single provider (a laryngologist) or by an interdisciplinary team that includes a speech-language pathologist. If not scheduled appropriately, the provider and the patient may lose valuable time, resources, and money.

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Susceptibility-weighted imaging of retinal hemorrhages in abusive head trauma

Abstract

Background

Retinal hemorrhages are one of the most important supportive evidences for abusive head trauma (AHT). Susceptibility-weighted imaging (SWI) is highly suited to identify various forms of intracranial hemorrhage in AHT. However its utility in imaging retinal hemorrhage is not well established.

Objective

SWI is a sensitive sequence for identifying retinal hemorrhage on MRI.

Materials and methods

In this retrospective analysis, 26 consecutive infants and young children with a suspected admission diagnosis of AHT underwent indirect ophthalmoscopy and brain MRI protocol for AHT along with SWI. Brain susceptibility-weighted images of 14 age-matched children were used as controls. For detecting retinal hemorrhage, susceptibility-weighted images of patients and controls were reviewed randomly and independently by two neuroradiologists who were blinded to the history and ophthalmology findings. A pediatric ophthalmologist graded the indirect ophthalmoscopy images.

Results

A diagnosis of AHT was confirmed in all 26 cases from a multidisciplinary meeting. Indirect ophthalmoscopy images were available in 21 cases. Ophthalmoscopy was positive for retinal hemorrhage in the right eye in 18 cases (85.7%) and in the left eye in 16 cases (76.2%). On SWI, retinal hemorrhage was identified in the right eye in 9/21 cases (42.8%) and in the left eye in 8/21 cases (38.1%) of AHT. Analysis of SWI in 21 cases of AHT demonstrated a sensitivity of 50%, specificity of 100%, positive predictive value of 100% and negative predictive value of 32% for detecting retinal hemorrhage.

Conclusion

SWI is moderately sensitive and highly specific for identifying retinal hemorrhage in AHT. Further studies are needed to identify steps to improve the efficiency of SWI in detecting retinal hemorrhage.

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Clinical immunotherapeutic approaches for the treatment of head and neck cancer

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, accounting for more than 550,000 cases and 380,000 deaths annually. The primary risk factors associated with HNSCC are tobacco use and alcohol consumption; nevertheless genetic predisposition and oncogenic viruses also play important roles in the development of these malignancies. The current treatments for HNSCC patients include surgery, chemotherapy, radiotherapy, and cetuximab, and combinations of these.

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Should we fear direct oral anticoagulants more than vitamin K antagonists in simple single tooth extraction? A prospective comparative study

Abstract

Objectives

The aim of this prospective comparative clinical study was to evaluate the effect of oral anticoagulants on peri- and post-operative bleeding during simple single tooth extractions, comparing patients in treatment with vitamin K antagonists (VKAs) and patients assuming direct oral anticoagulants (DOACs).

Materials and methods

Patients under oral anticoagulant therapy needing dental extraction were eligible for entering the study; patients were enrolled following inclusion and exclusion criteria and divided into VKAs and DOAC group according to the anticoagulation therapy. Included patients underwent a simple single dental extraction with elevators and forceps with a maximum surgical time of 15 minutes, without anticoagulation therapy discontinuation. All participants were assessed pre-operatively, during surgery, 30 min minutes and 7 days after surgery. Biological complications were registered and post-extraction bleeding was clinically defined according to Iwabuchi classification. Parametric and non-parametric tests were used to evaluate the variables between the groups.

Results

Sixty-five patients per group were enrolled and 130 teeth were extracted. The two groups were comparable for pre-, peri-, and post-operative variables. Only 1 patient of DOAC group and 2 patients for VKA group needed medical evaluation for post-extractive bleeding. No statistically significant difference resulted in post-operative bleeding events between the groups (p = 0.425).

Conclusions

DOAC and VKA patients showed the same incidence of bleeding complications after simple single tooth extraction. Bleeding events were not statistically significant and not clinically relevant.

Clinical relevance

Patients assuming DOACs can be treated similarly to patients in VKAs therapy with INR index between 2 and 3. Non-ceasing of DOAC therapy seems to be appropriate for simple single dental extractions.

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Antimicrobial photodynamic therapy as adjunct to non-surgical periodontal treatment in smokers: a randomized clinical trial

Abstract

Objectives

This study aims to investigate the additional influence of multiple applications of antimicrobial photodynamic therapy (aPDT) in smokers with chronic periodontitis.

Materials and methods

Twenty smokers with chronic periodontitis were treated in a split-mouth design study with aPDT adjunct to Scaling and Root Planing (SRP) or SRP. aPDT was performed by using a laser light source with 660 nm wavelength associated with a photosensitizer. The applications were performed in four episodes (at days 0, 2, 7, and 14). All patients were monitored for 90 days. Plaque index, probing depth, clinical attachment level, and bleeding on probing were performed at baseline, 30, and 90 days after the SRP. Gingival crevicular fluid and subgingival plaque samples were collected for immunological and microbiological analysis, respectively. Data obtained were statistically analyzed.

Results

aPDT as an adjunct to SRP did not demonstrate statistically significant advantages on clinical parameters when compared with SRP alone. No statistic significant differences between groups were observed (p < 0.05). Levels of anti-inflammatory cytokines and bacterial species were comparable in both groups at day 90 after treatment.

Conclusion

Periodontal treatment with SRP + aPDT in multiples episodes was not able to promote additional clinical, immunological, and microbiological benefits in smokers when compared SRP alone in patients with chronic periodontitis.

Clinical relevance

Multiple episodes of aPDT adjunctive to non-surgical treatment did not improve significantly the clinical, immunological, and microbiological parameters when compared with SRP alone. More randomized clinical trials are needed to evaluate adjuvant therapies for scaling and root planning in smokers with chronic periodontitis. ClinicalTrials.gov Identifier: NCT03039244

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