Relative Deficiency of Anti-Inflammatory N-Acylethanolamines Compared to Prostaglandins in Oral Lichen Planus.

Oral lichen planus (OLP) is a chronic inflammatory oromucosal disease. The N-acylethanolamines (NAEs), are a family of endogenous biologically active lipid mediators, with palmitoylethanolamide (PEA) being of particular interest here due to its anti-inflammatory and analgesic properties. In this study using oral mucosa biopsies from OLP patients and healthy controls, we investigated whether NAE synthesis was mobilized in response to the inflammation associated with OLP. PTGS2 levels, coding for cyclooxygenase-2 (COX-2), were increased approximately 4-fold in OLP compared to controls and a significant increase in the ratio of PTGS2 to NAPEPLD, the latter coding for a key enzyme in NAE synthesis, was seen. This was matched by an increased ratio of COX-2-derived prostaglandins to PEA in a second patient cohort. We conclude that there is an imbalance between prostaglandins and PEA in OLP, opening up the possibility that PEA might be a useful treatment for this disorder.

The Basal Pharmacology of Palmitoylethanolamide.

Palmitoylethanolamide (PEA, N-hexadecanoylethanolamide) is an endogenous compound belonging to the family of N-acylethanolamines. PEA has anti-inflammatory and analgesic properties and is very well tolerated in humans. In the present article, the basal pharmacology of PEA is reviewed. In terms of its pharmacokinetic properties, most work has been undertaken upon designing formulations for its absorption and upon characterising the enzymes involved in its metabolism, but little is known about its bioavailability, tissue distribution, and excretion pathways. PEA exerts most of its biological effects in the body secondary to the activation of peroxisome proliferator-activated receptor-α (PPAR-α), but PPAR-α-independent pathways involving other receptors (Transient Receptor Potential Vanilloid 1 (TRPV1), GPR55) have also been identified. Given the potential clinical utility of PEA, not least for the treatment of pain where there is a clear need for new well-tolerated drugs, we conclude that the gaps in our knowledge, in particular those relating to the pharmacokinetic properties of the compound, need to be filled.

What influences chronic pain management? A best-worst scaling experiment with final year medical students and general practitioners.

BACKGROUND: Chronic pain education is an essential determinant for optimal chronic pain management. Given that attitudes and preferences are involved in making treatment decisions, identifying which factors are most influential to final year medical students' and general practitioners' (GPs) chronic pain management choices is of importance. This study investigates Swedish and Australian students' preferences with respect to a chronic pain condition, using a best-worst scaling (BWS) experiment, which is designed to rank alternatives. METHODS: BWS, a stated-preference method grounded in random utility theory, was used to explore the importance of factors influencing chronic pain management. RESULTS: All three cohorts considered the patients' pain description and previous treatment experience as the most important factors in making treatment decisions, whereas their demographics and voices or facial expressions while describing their pain were considered least important. Factors such as social support, patient preferences and treatment adherence were, however, disregarded by all cohorts in favour of pain assessment factors such as pain ratings, description and history. Swedish medical students and GPs show very high correlation in their choices, although the GPs consider their professional experience as more important compared to the students. CONCLUSION: This study suggests that the relative importance of treatment factors is cemented early and thus underline the critical importance of improving pain curricula during undergraduate medical education.

Interferon γ treatment increases endocannabinoid and related N-acylethanolamine levels in T84 human colon carcinoma cells.

BACKGROUND AND PURPOSE: Endocannabinoids and related N-acylethanolamines (NAEs) are involved in regulation of gut function, but relatively little is known as to whether inflammatory cytokines such as IFNγ affect their levels. We have investigated this in vitro using cultures of T84 colon cancer cells. EXPERIMENTAL APPROACH: T84 cells, when cultured in monolayers, differentiate to form adult colonic crypt-like cells with excellent permeability barrier properties. The integrity of the permeability barrier in these monolayers was measured using transepithelial electrical resistance (TEER). NAE levels were determined by ultra-performance liquid chromatography-tandem mass spectrometric analysis. Expression of the enzymes involved in NAE and 2-arachidonoylglycerol (2-AG) turnover were assessed with qPCR. KEY RESULTS: IFNγ treatment for 8 or 24 h increased levels of both endocannabinoids (anandamide and 2-AG) and the related NAEs. The treatment did not affect the rate of hydrolysis of either anandamide or palmitoylethanolamide by intact cells, and in both cases, fatty acid amide hydrolase (FAAH) rather than NAE-hydrolysing acid amidase (NAAA) was mainly responsible for the hydrolysis of these NAEs. IFNγ treatment reduced the TEER of the cells in a manner that was not prevented by inhibition of either FAAH or NAAA but was partially reversed by apical administration of the NAE palmitoylethanolamide. CONCLUSION AND IMPLICATIONS: IFNγ treatment mobilized endocannabinoid and related NAE levels in T84 cells. However, blockade of anandamide or NAE hydrolysis was insufficient to negate the deleterious effects of this cytokine upon the permeability barrier of the cell monolayers. LINKED ARTICLES: This article is part of a themed section on 8th European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc.

Differences in Swedish and Australian medical student attitudes and beliefs about chronic pain, its management, and the way it is taught.

Background and aims Medical students receive training in the management of chronic pain, but the training is often suboptimal. Considering that the basis for physician's knowledge is their medical education, it is important to explore the attitudes and beliefs of medical students with respect both to chronic pain management and to their views on current pain education. Therefore, the aim of this study was to compare Swedish and Australian medical student's attitudes and beliefs about patients with chronic pain, and their perceptions regarding their chronic pain management education. Methods An online survey was conducted with final year Australian and Swedish medical students from two different universities between December 2016 and February 2017. Attitudes and beliefs towards chronic pain patients were measured using the Health Care Providers' Pain and Impairment Scale (HC-PAIRS). A thematic analysis was conducted on open end questions regarding their views on their education and important skills for chronic pain management. Results A total of 57 Swedish and 26 Australian medical students completed the HC-PAIRS scale. The Swedish medical students showed statistically significantly lower total mean HC-PAIRS scores compared to Australian medical students (46 and 51, respectively). Australian students had statistically significantly higher scores than the Swedish students for two of four factors: functional expectations and need for cure, whereas no significant differences were seen for the factors social expectations or for projected cognition. From the open end questions it was evident that final year medical students are knowledgeable about key chronic pain items described in clinical guidelines. However, both cohorts described their chronic pain training as poor and in need of improvement in several areas such as more focus on the biopsychosocial model, working in multidisciplinary teams, seeing chronic pain patients and pharmacological training. Conclusions Attitudes and beliefs are formed during medical education, and our study exploring attitudes of medical students towards chronic pain and how it is taught have provided valuable information. Our survey provided detailed and cohesive suggestions for education improvement that also are in line with current clinical guidelines. This study indicates that the Swedish final year students have a more positive attitude towards chronic pain patients compared to their Australian counterparts. The majority of students in both cohorts perceived chronic pain management education in need of improvement. Implications This study highlights several areas of interest that warrant further investigation, for example, the impact of a changed medical curriculum in alignment with these clinical guidelines requested by students in this survey, and correspondingly if their attitudes towards chronic pain patients can be improved through education. Further, we conclude that it would be valuable to align the implementation of the HC-PAIRS instrument in order to achieve comparable results between future studies.

Resolution of superimposed pre-eclampsia, and improvement in umbilical artery flow in a surviving twin after intrauterine demise of its co-twin.

Pre-eclampsia has a progressive clinical course, and is only cured by delivery of the placenta. We report a 30-year-old G1P0 with dichorionic twins, discordant growth and chronic hypertension who developed superimposed pre-eclampsia in her 21st week of gestation. After intrauterine demise of the severely growth-restricted twin, the superimposed pre-eclampsia resolved. The surviving twin initially had absent end diastolic flow, which resolved after the demise. A healthy 1935-g neonate with Apgar 9/9 was delivered at 34 weeks. Antenatal resolution of pre-eclampsia is extremely rare and resolution of superimposed pre-eclampsia has not, to our knowledge, been reported.

Intention to change nutrition-related behaviors in adult participants of a Supplemental Nutrition Assistance Program-Education.

OBJECTIVE: To determine whether participation in selected Supplemental Nutrition Assistance Program-Education (SNAP-Ed) lessons had an impact on the intent to improve nutrition-related behaviors of participants. METHODS: A quantitative study using a retrospective post-then-pre design to measure SNAP-Ed outcomes of 203 adult participants after selected nutrition lessons in 14 counties across the state of Utah. After the intervention participants completed a retrospective post-then-pre survey evaluating intent to improve nutrition behaviors related to the SNAP-Ed lessons. Wilcoxon signed rank test with Bonferroni correction and paired t test were used. RESULTS: Participants reported sometimes engaging in nutrition related behaviors before attending SNAP-Ed lessons and intent to usually engage in these behaviors after attending SNAP-Ed lessons. CONCLUSION AND IMPLICATIONS: This study demonstrated that participation in selected SNAP-Ed lessons was positively related to the intent of participants to improve nutrition-related behaviors.

Non-necrotizing Granulomatous Pulmonary Vasculitis Mimicking Lung Cancer on PET/CT.

Fluorodeoxyglucose positron emission tomography ((18)FDG-PET) scan has become a valuable resource in the staging of lung cancer. Inflammation is known to cause false positives on (18)FDG-PET scan. In the absence of symptoms suggesting a diagnosis of an inflammatory condition, (18)FDG-avid lung masses on PET/CT scan is strongly suggestive of a diagnosis of lung cancer, rather than an inflammatory condition. We report the case of a 57-year-old man, with a history of heavy smoking and working in the sandblasting industry, with two suspicious (18)FDG-avid nodules in the left lung. Surgical specimens of these nodules revealed findings suspecting giant cell arteritis rather than malignancy.

'Hop the skip' with extended segment intestinal biopsy in Hirschsprung's disease.

INTRODUCTION: Skip segment Hirschsprung's is an extremely rare condition, with only 25 reported cases in the English language literature. Diagnosis of skip segment Hirschsprung's may be missed as it is rarely suspected at initial surgery. PRESENTATION OF CASE: A case report of an infant with total colonic aganglionosis and a skip segment Hirschsprung's in the cecum is presented. A review of literature on current surgical practice is presented along with our suggested modification to the diagnostic and therapeutic algorithm of this rare condition. DISCUSSION: In our patient the initial leveling colostomy was incorrectly sited at the level of the first detected ganglionated segment. Subsequent recurrent episodes of enterocolitis led to a diagnosis of a long skip segment involving the ascending colon, cecum and terminal ileum. Correct leveling colostomy and a subsequent Duhamel procedure led to a good outcome. CONCLUSION: Determination of the transition zone in Hirschsprung's may be incorrect if intestinal biopsies are terminated at the first evidence of ganglion cells. Extended segment intestinal biopsies should be included in the algorithm for management of long segment Hirschsprung's disease and will enable the surgeon to correctly detect rare manifestations such as skip segment disease at the initial procedure.

Rape-accepting attitudes of university undergraduate students.

The College Date Rape Attitudes Survey and the Attitudes Toward Women Scale were used in a cross-sectional study to assess rape-accepting attitudes of a convenience sample of 1602 university undergraduate students using a survey distributed online. The findings evidenced that males and individuals with more traditional gender role beliefs had attitudes more accepting of rape than the females and individuals who had more egalitarian gender role beliefs. Respondents who personally knew a rape survivor had attitudes less accepting of rape than those respondents who did not know a survivor. These findings support a continuing need to address rape myths in sexual violence prevention programming. The sexual assault nurse examiner (SANE-A) has an important role in prevention services to educate and build awareness of rape myths both on campus and through community-based efforts to reach this high risk population. Further, the SANE can build important linkages between the college campus and the healthcare setting to support the provision of effective intervention services and improved outcomes in victims of sexual violence.

Escherichia coli NsrR regulates a pathway for the oxidation of 3-nitrotyramine to 4-hydroxy-3-nitrophenylacetate.

Chromatin immunoprecipitation and microarray (ChIP-chip) analysis showed that the nitric oxide (NO)-sensitive repressor NsrR from Escherichia coli binds in vivo to the promoters of the tynA and feaB genes. These genes encode the first two enzymes of a pathway that is required for the catabolism of phenylethylamine (PEA) and its hydroxylated derivatives tyramine and dopamine. Deletion of nsrR caused small increases in the activities of the tynA and feaB promoters in cultures grown on PEA. Overexpression of nsrR severely retarded growth on PEA and caused a marked repression of the tynA and feaB promoters. Both the growth defect and the promoter repression were reversed in the presence of a source of NO. These results are consistent with NsrR mediating repression of the tynA and feaB genes by binding (in an NO-sensitive fashion) to the sites identified by ChIP-chip. E. coli was shown to use 3-nitrotyramine as a nitrogen source for growth, conditions which partially induce the tynA and feaB promoters. Mutation of tynA (but not feaB) prevented growth on 3-nitrotyramine. Growth yields, mutant phenotypes, and analyses of culture supernatants suggested that 3-nitrotyramine is oxidized to 4-hydroxy-3-nitrophenylacetate, with growth occurring at the expense of the amino group of 3-nitrotyramine. Accordingly, enzyme assays showed that 3-nitrotyramine and its oxidation product (4-hydroxy-3-nitrophenylacetaldehyde) could be oxidized by the enzymes encoded by tynA and feaB, respectively. The results suggest that an additional physiological role of the PEA catabolic pathway is to metabolize nitroaromatic compounds that may accumulate in cells exposed to NO.

Garden-based nutrition education affects fruit and vegetable consumption in sixth-grade adolescents.

Schoolyard gardens are emerging as a nutrition education tool in academic settings. The purpose of this study was to investigate the effects of garden-based nutrition education on adolescents' fruit and vegetable consumption using a nonequivalent control group design. Sixth-grade students (n=99) at three different elementary schools made up a control and two treatment groups. Students in the treatment groups participated in a 12-week nutrition education program, and one treatment group also participated in garden-based activities. Students in all three groups completed three 24-hour food-recall workbooks before and after the intervention. A repeated-measures analysis of variance showed that adolescents who participated in the garden-based nutrition intervention increased their servings of fruits and vegetables more than students in the two other groups. Significant increases were also found in vitamin A, vitamin C, and fiber intake. Although further research is needed, the results of this study seem to indicate the efficacy of using garden-based nutrition education to increase adolescents' consumption of fruits and vegetables.

Neonatal extracorporeal life support: impact of new therapies on survival.

OBJECTIVE: To evaluate the effects of pre-extracorporeal life support (ECLS) management with nitric oxide (NO), high frequency ventilation (HFV), and surfactant on mortality among neonates supported with ECLS. STUDY DESIGN: Extracorporeal Life Support Organization (ELSO) data on 7017 neonates cannulated for respiratory reasons between 1996 and 2003 were analyzed using chi2, analysis of variance, and logistic regression. RESULTS: The use of ECLS declined by 26.6% over the study period with no significant change in mortality. Unadjusted ECLS mortality for NO-treated patients was lower than for infants not treated with NO (25.1% vs 28.6%, P = .0012) and for infants treated with surfactant than for infants not treated with surfactant (18.7% vs 30.3%, p <.0001.) Unadjusted mortality for HFV-treated patients was no different than for non-HFV-treated patients (26.0% vs 26.6%, P = .56). After adjusting for confounders (primary diagnosis, age at cannulation, ECMO year 1996-1999 vs 2000-2003), surfactant use was associated with decreased mortality. NO-treated neonates were less likely to have a pre-ECLS cardiopulmonary arrest than infants not treated with NO. NO, HFV, and surfactant were not associated with prolongation of ECLS or mechanical ventilation. CONCLUSIONS: NO, HFV, and surfactant were not associated with increased mortality in neonates who require ECLS for hypoxic respiratory failure.

Extensive stage small cell lung cancer presenting as an acute perforated appendix: case report and review of the literature.

Malignancies of the appendix are uncommon; a small subset of these lesions are actually metastatic cancers. In some rare cases, these lesions can cause obstruction, appendicitis, and perforation. M.K. is a 54-year-old man who presented to our institution with a 1-day history of right lower quadrant pain and a past medical history significant only for a 75-pack-year smoking history. CT scan revealed a perforated appendix, and the patient was taken to the operating room where a gangrenous appendix was removed uneventfully. Two days post-procedure, the patient was found to have acute mental status changes, requiring intubation and transfer to the surgical intensive care unit. As part of a workup, a CT scan of the head revealed multiple lesions compatible with metastatic disease. At that point, the pathology from the appendix came back as small cell lung cancer. Chest CT revealed hilar adenopathy and a hilar mass. The patient received emergent whole-brain irradiation therapy with improvement in his mental status, allowing him to be extubated and discharged from the hospital within 10 days of admission. Surgeons should remember that an underlying oncologic process may be the etiology of appendicitis in a small but important subgroup of patients.

Sweat gland carcinoma.

Sweat gland carcinoma is a rare malignant tumor of the skin adnexa that can occur in a variety of locations. It is a slow-growing tumor that metastasizes early and often. The rarity of this tumor has led to a relative lack of adequate evidence with regard to treating this entity. Recent advances in immunohistochemical staining have better defined this tumor and have aided in diagnosing its subtypes though histologic grade and presence of regional lymph nodes at the time of diagnosis. These are the best indicators for prognosis and management currently available. Indications for sentinel node biopsy are currently not well defined. Because of the poor prognosis of high-grade sweat gland carcinoma, clinicians should be aware of this entity and be prepared to treat aggressively. Management of sweat gland carcinoma is difficult because extensive study into both surgical and nonsurgical treatment has not been done. We present a case of sweat gland carcinoma of the lower extremity and a review of the clinicopathologic literature of these rare neoplasms, including diagnosis and surgical management.