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Background: Eating disorders are relatively common mental health disorders in Western European and North American populations. The peak incidence occurs within the adolescent years, which correlates with the largest orthodontic patient population. The morbidity associated with these psychological conditions is significant, and has a direct impact upon patient well-being, orthodontic outcomes and the success of treatment. Therefore, it is of relevance to the orthodontist to be aware of potential presenting features of these conditions, when and where to seek advice, and how such disorders may impact upon orthodontic outcomes., Methods: Articles published on PUBMED and MEDLINE relevant to orthodontics and eating disorders were reviewed. Key information was extracted, and the relevant evidence for the orthodontist summarised., Results: Eating disorders may present to the orthodontist in specialist or hospital practice, either undiagnosed or as a co-morbidity. Orthodontists may benefit from an appreciation of these potential diagnoses, the orthodontic implications and to have the confidence to refer their patients to the necessary services., Limitations: There is little existing research in this area., Conclusions: These conditions have a significant impact on patient morbidity and mortality. This cohort of patients is not suitable for orthodontic treatment while their disease is active. The impact of a developing eating disorder can adversely affect orthodontic treatment.

Background: Infective endocarditis (IE) is a recognized complication of central line-associated bloodstream infection (CLABSI). Central venous access devices (CVADs) are essential for the delivery of long-term parenteral nutrition (PN), yet there are no published data as to the prevalence, characteristics and outcomes of IE in this population., Methods: A prospectively maintained database of patients with intestinal failure (IF) types 2 and 3, managed by a national intestinal failure center between January 2010 and December 2018, was analyzed retrospectively and relevant factors extracted from case records., Results: A total of 745 patients with IF and CVADs in situ on admission, or placed during their stay, were admitted over the duration of this study, 640 with type 2 IF and 105 with type 3 IF. Two hundred eighty-two echocardiograms were performed to investigate potential IE associated with a CLABSI event. Four cases of IE were identified in the entire cohort of 782,666 catheter days (IE incidence rate: 0.005 per 1000 catheter days and 187 per 100,000 person-years for the entire cohort; 0.048 per 1000 inpatient catheter days for acute type 2 IF, 0.0026 per 1000 outpatient catheter days [ie, 99 per 100,000 person-years for outpatients with type 3 IF])., Conclusion: IE is rare in the type 3 IF population and a rare consequence of CLABSI in inpatient acute type 2 IF. However, mortality and morbidity are high. Routine echocardiography may not be warranted for investigation of CLABSI unless there is a high risk of IE or a virulent organism is involved., (© 2020 American Society for Parenteral and Enteral Nutrition.)

A wide variety of patients with medical co-morbidities may present to general orthodontic practice. It is important for the treating clinician to have a general understanding of key medical conditions that may impact upon the treatment and management options. This clinical supplement provides a treatment-focused summative update for the orthodontist regarding significant medical co-morbidities, their general prevalence and an exploration of potential impacts upon orthodontic treatment. This review also discusses the significance of key medications and provides suggestions for the safe provision of orthodontic treatment.

Competing Interests: Competing interests: None declared.

Background and Aims: Colorectal cancer screening programmes that target detection and excision of adenomatous colonic polyps have been shown to reduce colorectal cancer related mortality. Many screening programmes include an initial faecal occult blood test (FOBt) prior to colonoscopy. To refine the selection of patients for colonoscopy other faecal-based diagnostic tools have been proposed, including tumour M2-pyruvate kinase (tM2-PK). To determine whether tM2-PK quantification may have a role in diverse settings we have assessed the assay in a cohort of patients derived from both the England bowel cancer screening programme (BCSP) and symptomatic individuals presenting to secondary care., Method: Patients undergoing colonoscopy provided faecal samples prior to bowel preparation. Faecal tM2-PK concentrations were measured by ELISA. Sensitivity, specificity, positive predictive value, negative predictive value and ROC analyses were calculated., Results: Ninety-six patients returned faecal samples: 50 of these with adenomas and 7 with cancer. Median age was 68. Median faecal tM2-PK concentration was 3.8 U/mL for individuals without neoplastic findings at colonoscopy, 7.7 U/mL in those with adenomas and 24.4 U/mL in subjects with colorectal cancer (both, p=0.01). ROC analysis demonstrated an AUROC of 0.66 (sensitivity 72.4%, specificity 48.7%, positive predictive value 67.7%, negative predictive value 36.7%). Amongst BCSP patients with a prior positive FOBt faecal tM2-PK was more abundant (median 6.4 U/mL, p=0.03) and its diagnostic accuracy was greater (AUROC 0.82)., Conclusion: Our findings confirm that faecal tM2-PK ELISA may have utility as an adjunct to FOBt in a screening context, but do not support its use in symptomatic patients.

Background & Aims: Colorectal cancer (CRC) is the second most common form of malignancy in Europe and North America, and is one of the major causes of cancer death, with a 50.7% 5 year mortality rate. The majority of cases are of a sporadic nature and develop from a pre-cancerous lesion. Screening programmes have been introduced in many countries to detect and treat the condition. These mostly rely on a combination of faecal occult blood tests and endoscopy to guide diagnosis. They are expensive to establish and run, have a potential for false negatives (especially for high risk adenomas and right sided cancers) and they are often unacceptable to a significant percentage of the at-risk population. Consequently many groups have sought sensitive and specific diagnostic biomarkers for CRC and adenomas. These biomarkers form three broad categories: cytogenetic, enzymatic/protein and metabolomic., Methods: Pubmed and Medline databases were searched to identify relevant articles concerning colorectal cancer screening., Conclusion: Here we provide a review of the current population-based screening possibilities and faecal biomarkers currently under investigation, an assessment of their cost-effectiveness, their efficacy and suggestions for the future of large scale screening in CRC.

There is a considerable stigma associated with obesity, among healthcare professionals as well as the general population, which often leads to discrimination and weight bias. But why is there a stigma attached to obesity? The origin of this stigma has been identified in the 18th century but its roots lie much further back in history. There is some debate about how this negative perception of obesity arose and the role of medical professionals in its creation. This paper examines both positive and negative conceptions by following three major aspects of the modern stigma through from Palaeolithic statues to the medical texts of ancient Greece and Rome, finishing with the medical and literary sources of the 18th century 'Enlightenment'. The modern perception of obesity originated in the social and scientific climate of the Enlightenment through the combination of three key themes; obesity as conspicuous consumption, associations with suspect morals and excess, and as an outward representation of the soul. The evolution of each of these themes can be clearly identfied in pre-Enlightenment sources. By the eighteenth century, these perceptions became amplified by, and disseminated through, the literary and media boom to create a recognisably modern stigma against the obese.

Chronic cocaine exposure is associated with severe cardiac complications, but the mechanisms of cocaine cardiotoxicity remain unclear, and current therapies are unsatisfactory. We investigated the hypothesis of oxidative stress-mediated cardiotoxicity and the role of NADPH oxidase in this process in a mouse model of chronic escalating "binge" cocaine administration (milligrams per kilogram): days 1 to 4 at 3 x 15 mg, days 5 to 8 at 3 x 20 mg, days 9 to 12 at 3 x 25 mg, and days 13 to 14 at 3 x 30 mg. Compared with vehicle controls, chronic binge cocaine administration significantly increased the cardiac NADPH-dependent O(2)(.) production (1.96- +/- 0.4-fold) as detected by tiron (an O(2)(.) scavenger)-inhibitable lucigenin chemiluminescence and dihydroethidium fluorescence. Cocaine-induced reactive oxygen species (ROS) production was associated with significant increases ( approximately 2-fold) in the protein expressions of Nox2 (an isoform of NADPH oxidase) and its regulatory subunits: p22(phox), p67(phox), p47(phox), p40(phox), and Rac1, and in p47(phox) phosphorylation as detected by immunoblotting (all p < 0.03). Increased Nox2 activity was accompanied by the activation of extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase (MAPK), and c-Jun NH(2)-terminal kinase, notably in the cardiomyocytes. Cell culture experiments revealed that cocaine-induced ROS production was primarily a direct action of cocaine on cardiac myocytes, which caused severe oxidative damage to myocytes and cell death as detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. These could be inhibited by inhibitors to protein kinase C (bisindolymaleimide) or by depletion of Nox2 using small interfering RNA. In conclusion, chronic cocaine administration directly causes severe myocardial oxidative stress through the activation of Nox2 oxidase. Increased ROS production contributes to MAPK activation and the subsequent myocyte damage. Inhibitors to NADPH oxidase or antioxidants may have therapeutic potential in the treatment of cocaine cardiotoxicity.

Cardiac tissues express constitutively an NADPH oxidase, which generates reactive oxygen species (ROS) and is involved in redox signaling. Myocardial metabolism generates abundant adenosine, which binds to its receptors and plays important roles in cardiac function. The adenosine A2A receptor (A2AR) has been found to be expressed in cardiac myocytes and coronary endothelial cells. However, the role of the A2AR in the regulation of cardiac ROS production remains unknown. We found that knockout of A2AR significantly decreased (39+/-8%) NADPH-dependent O2- production in mouse hearts compared to age (10 weeks)-matched wild-type controls. This was accompanied by a significant decrease in Nox2 (a catalytic subunit of NADPH oxidase) protein expression, and down-regulation of ERK1/2, p38MAPK, and JNK phosphorylation (all P<0.05). In wild-type mice, intraperitoneal injection of the selective A2AR antagonist SCH58261 (3-10 mg/kg body weight for 90 min) inhibited phosphorylation of p47phox (a regulatory subunit of Nox2), which was accompanied by a down-regulated cardiac ROS production (48+/-8%), and decreased JNK and ERK1/2 activation by 54+/-28% (all P<0.05). In conclusion, A2AR through MAPK signaling regulates p47phox phosphorylation and cardiac ROS production by NADPH oxidase. Modulation of A2AR activity may have potential therapeutic applications in controlling ROS production by NADPH oxidase in the heart.