The difficulty in obtaining as well as maintaining weight loss, together with the impairment of metabolic control in conditions like diabetes and cardiovascular disease, may represent pathological situations of inadequate neural communication between the brain and peripheral organs and tissues. Innervation of adipose tissues by peripheral nerves provides a means of communication between the master metabolic regulator in the brain (chiefly the hypothalamus), and energy-expending and energy-storing cells in the body (primarily adipocytes). Although chemical and surgical denervation studies have clearly demonstrated how crucial adipose tissue neural innervation is for maintaining proper metabolic health, we have uncovered that adipose tissue becomes neuropathic (ie: reduction in neurites) in various conditions of metabolic dysregulation. Here, utilizing both human and mouse adipose tissues, we present evidence of adipose tissue neuropathy, or loss of proper innervation, under pathophysiological conditions such as obesity, diabetes, and aging, all of which are concomitant with insult to the adipose organ as well as metabolic dysfunction. Neuropathy is indicated by loss of nerve fiber protein expression, reduction in synaptic markers, and lower neurotrophic factor expression in adipose tissue. Aging-related adipose neuropathy particularly results in loss of innervation around the tissue vasculature, which cannot be reversed by exercise. Together with indications of neuropathy in muscle and bone, these findings underscore that peripheral neuropathy is not restricted to classic tissues like the skin of distal extremities, and that loss of innervation to adipose may trigger or exacerbate metabolic diseases. In addition, we have demonstrated stimulation of adipose tissue neural plasticity with cold exposure, which may ameliorate adipose neuropathy and be a potential therapeutic option to re-innervate adipose and restore metabolic health.

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Molar incisor hypomineralization (MIH) is an enamel condition characterized by lesions ranging in color from white to brown which present rapid caries progression, and mainly affects permanent first molars and incisors. These enamel defects usually occur when there are disturbances during the mineralization or maturation stage of amelogenesis. Both genetic and environmental factors have been suggested to play roles in MIH’s development, but no conclusive risk factors have shown the source of the disease. During head and neck development, the interferon regulatory factor 6 (IRF6) gene is involved in the structure formation of the oral and maxillofacial regions, and the transforming growth factor alpha (TGFA) is an essential cell regulator, acting during proliferation, differentiation, migration and apoptosis. In this present study, it was hypothesized that these genes interact and contribute to predisposition of MIH. Environmental factors affecting children that were 3 years of age or older were also hypothesized to play a role in the disease etiology. Those factors included respiratory issues, malnutrition, food intolerance, infection of any sort and medication intake. A total of 1,065 salivary samples from four different cohorts were obtained, and DNA was extracted from each sample and genotyped for nine different single nucleotide polymorphisms. Association tests and logistic regression implemented in PLINK were used for analyses. A potential interaction between TGFA rs930655 with all markers tested in the cohort from Turkey was identified. These interactions were not identified in the remaining cohorts. Associations (p<0.05) between the use of medication after three years of age and MIH were also found, suggesting that conditions acquired at the age children start to socialize might contribute to the development of MIH.

The difficulty in obtaining as well as maintaining weight loss, together with the loss of metabolic control in conditions like diabetes and cardiovascular disease, may represent pathological situations of inadequate neural communication between the brain and peripheral organs and tissues. Innervation of adipose tissues by peripheral nerves provides a means of communication between the master metabolic regulator in the brain (chiefly the hypothalamus), and energy-expending and energy-storing cells in the body (primarily adipocytes). Although chemical and surgical denervation studies have clearly demonstrated how crucial adipose tissue neural innervation is for maintaining proper metabolic health, we have uncovered that adipose tissue becomes neuropathic in various conditions of metabolic dysregulation. Here, utilizing both human and mouse adipose tissues, we present evidence of adipose tissue neuropathy, or loss of innervation, under pathophysiological conditions such as obesity, diabetes, and aging, all of which are concomitant with insult to the adipose organ and metabolic dysfunction. Neuropathy is indicated by loss of nerve fiber protein expression, reduction in synaptic markers, and less neurotrophic factor expression in adipose tissue. Aging-related adipose neuropathy particularly results in loss of innervation around the tissue vasculature. These findings underscore that peripheral neuropathy is not restricted to classic tissues like the skin of distal extremities, and that loss of innervation to adipose may trigger or exacerbate metabolic diseases. In addition, we have demonstrated stimulation of adipose tissue neural plasticity with exercise, cold exposure or neurotrophic factor treatment, which may ameliorate adipose neuropathy and be a potential therapeutic option to re-innervate adipose and restore metabolic health.

cancer is a disease caused by a process that drives the transformation of normal cells into malignant cells. the late diagnosis of cancer has a negative impact on the health care system due to high treatment cost and decreased chances of favorable prognosis. Here, we aimed to identify orofacial conditions that can serve as potential risk markers for cancers by performing a phenome-wide scan (PheWAS). From a pool of 6,100 individuals, both genetic and epidemiological data of 1,671 individuals were selected: 350 because they were previously diagnosed with cancer and 1,321 to match to those individuals that had cancer, based on age, sex, and ethnicity serving as a comparison group. Results of this study showed that when analyzing the individuals affected by cancer separately, tooth loss/ edentulism is associated with Snps in AXIN2 (rs11867417 p = 0.02 and rs2240308 p = 0.02), and leukoplakia of oral mucosa is associated with both AXIN2 (rs2240308 p = 0.03) and RHEB (rs2374261 p = 0.03). These phenotypes did not show the same trends in patients that were not diagnosed with cancer, allowing for the conclusion that these phenotypes are unique to cases with higher cancer risk. Cancer is a complex disease based on a process that drives the transformation of normal cells into their malignant derivatives 1. Approximately 38.4% of people will be diagnosed with some form of cancer in their lifetime 2. According to the American Cancer Society estimate for 2018, 1,735,350 people would be diagnosed with cancer in the United States, and an estimated 609,640 people would die of cancer 3. However, survival rates vary depending on the type of cancer and the stage at diagnosis. Earlier stage diagnosis increases the likelihood of successful treatment and survival rates 2. Nevertheless, because early cancers can be difficult to detect, much focus has been placed on the identification of more easily detectable cancer risk markers. A risk marker is a physiologic or anatomical characteristic that indicates a genetic tendency of developing the disease in question. The BRCA1 and BRCA2 genes are examples of genetic risk markers whose pathogenic variants can cause a significant increased risk of breast and ovarian cancer 4. Additionally, several phenotypic risk markers (i.e., clinical traits), such as anatomical craniofacial abnormalities, have also been associated with an increased likelihood of developing cancers 5-12. For example, cleft lip/palate has been found to be associated with diffuse gastric cancer 5 , breast cancer 6 , squamous cell carcinoma of the skin and others 7. Additional studies reported associations between periodontitis and colorectal cancer 8 , breast cancer 9 or any type of cancer 10. Lastly, hypodontia (a disorder of tooth development) has been correlated with risk for epithelial ovarian cancer 11 and colorectal cancer 12. These previous reports point towards the hypothesis that orofacial phenotypes are related to cancer risk independent to cancer type. In other words, we can predict risk for cancer through the prese...

Background and Purpose: To determine intra-session test-retest reliability, agreement and minimum detectable change (MDC) of the 30 CST across three tests in people with knee osteoarthritis (OA). Methods:A test-retest reliability study was performed with 93 people with mild radiological knee OA. Participants were asked to complete three attempts of the 30 CST 1-2 min apart according to a standardised protocol. Participants completed three attempts on two occasions: baseline and 6 months later. Change between tests within each session was assessed with ANOVA's and post-hoc t-tests. Reliability was assessed with intra-class correlation coefficients (ICC [2,1] ). Measurement error was expressed as MDC for an individual (MDC ind ) and a group (MDC group ).Floor effects were considered present if more than 15% of participants scored zero for a test.Results: Scores increased by 0.5 and 0.8 stands between the first and second test (p < 0.05) at the baseline and 6-month assessments respectively, and then stabilised between the second the third tests at the baseline assessment (p > 0.05) or decreased (0.3 stands) at the 6-month assessment (p < 0.05). Scores demonstrated excellent reliability (ICCs >0.9). MDC ind was approximately 2.5 stands and MDC group was 0.3-0.4 stands. No floor effects were apparent.Discussion: The 30CST demonstrated a practice effect between the first and second tests, which was no longer apparent by the third test. Despite this, scores demonstrated excellent intra-session reliability. MDC estimates provide clinicians and researchers with the smallest change that can be detected by the instrument beyond measurement error for individuals and groups in community-dwelling adults with knee OA.

Background and study aims  Endoscopic mucosal resection (EMR) of large sessile or laterally spreading colonic lesions is a safe alternative to surgery. We assessed reductions in Surgical Resection (SR) rates and associated clinical and financial benefits following the introduction of an EMR service to a large regional center. Patients and methods  Ongoing prospective intention-to-treat analysis of EMR was undertaken from time of service inception in 2009 to 2017. Retrospective data for SR of large sessile/laterally spreading colonic lesions were collected for the period 4 years before commencement of the EMR service (2005 – 2008) and 9 years after its introduction (2009 – 2017). Results  From 2005 to 2008, 32 surgical procedures were performed for non-malignant colonic neoplasia (50 % male, median age 68 years, median Length of Stay (LoS) 10 days). Following the introduction of the EMR service, there was a 56 % reduction in the number of patients referred for surgery (32 surgical procedures, 47 % male, median age 70 years, median LoS 8.5 days). During this period, EMR was successfully performed in 183 patients with 216 lesions resected (60 % male, median age 68 years, median LoS 1 day). Compared to the SR group, the EMR cohort had a lower peri-procedural complication rate (7.7 % vs 54.7 %, P  < 0.0001), and shorter average LoS (1 vs 9 days, P  < 0.0001). A cost saving of AUD $ 19 543.5 was seen per lesion removed with EMR compared to SR. Conclusions  The introduction of a dedicated EMR service into a large regional center as an alternative to SR can lead to a substantial decrease in unnecessary surgery with subsequent clinical and financial benefits.

IntroductionSymptomatic knee osteoarthritis (OA) is common. Advanced knee OA is successfully treated with joint replacement surgery, but effectively managing mild to moderate knee OA can be difficult. Angiogenesis increases with OA and might contribute to pain and structural damage. Modifying angiogenesis is a potential treatment pathway for OA. The aim of the current study is to determine whether transcatheter arterial embolisation of abnormal neovasculature arising from the genicular arterial branches improves knee pain, physical function and quality of life in people with mild to moderate symptomatic knee OA.Methods and analysisThe study is a single centre, parallel-arm, double-blinded (participant and assessor), randomised controlled superiority trial with 1:1 random block allocation. Eligible participants have mild to moderate symptomatic knee OA and will be randomly assigned to receive either embolisation of aberrant knee neovasculature of genicular arterial branches or a placebo intervention. Outcome measures will be collected prior to the intervention and again 1, 6 and 12 months postintervention. The primary outcome is change in knee pain between baseline and 12 month assessment as measured by the Knee Injury and Osteoarthritis Outcome Score (KOOS). Secondary outcomes include change in self-reported physical function (KOOS), self-reported quality of life (KOOS, EuroQol: EQ-5D-5L), self-reported knee joint stiffness (KOOS), self-reported global change, 6 min walk test performance, and 30 s chair-stand test performance. Intention-to-treat analysis will be performed including all participants as randomised. To detect a mean between group difference in change pain of 20% at the one year reassessment with a two-sided significance level of α=0.05 and power of 80% using a two-sample t-test, we require 29 participants per arm which allows for 20% of participants to drop out.Ethics and disseminationBarwon Health Human Research Ethics Committee, 30 May 2016, (ref:15/101). Study results will be disseminated via peer-reviewed publications and conference presentations.Trial registration numberUniversal trial number U1111-1183-8503, Australian New Zealand Clinical Trials Registry, ACTRN12616001184460, approved 29 August 2016.