A novel candidate gene in autosomal dominant facial pruritus.

In the clinical investigation of a family with debilitating centrofacial pruritus by exome sequencing, we have observed a clear segregation of the TRPM3 variant outlined, which is highly suggestive of a causal relationship.

Feed-derived iodine overrides environmental contribution to cow milk.

Diets worldwide are deficient in iodine, leading to a range of undesirable health effects at the population level. Dairy products are a primary source of iodine in diets for those populations in which iodized salt is not systematically used or available. However, the flows of iodine through dairy agroecosystems are not well understood. The aim of this research was to investigate iodine flows though the dairy agroecosystem, including the influence of atmospheric depositional inputs, environmental variables, season, husbandry, and diet. Three farm-based sampling campaigns were carried out in this investigation, with milk, soil, silage, grass, and feed iodine determined by inductively coupled plasma mass spectroscopy, and nonparametric statistical analysis tests were conducted on data sets obtained. Natural iodine inputs into the environment are dominated by atmospheric deposition, which mainly from sea spray, and thus the location of farms relative to the coast and prevailing wind direction. Herbage and silage produced from grass-based systems strongly correlated with soil iodine, yet there was a strong disconnect between soil, forage, and feed and the milk that results. This was due to the levels of iodine in supplemental feeds being approximately 10-fold higher than those in forage-derived feeds. The practice of feed supplementation, accentuated by summer housing of cows, led to elevated milk iodine.

Characterizing membrane phospholipid hydrolysis of pork loins throughout three aging periods.

Three chops from 20 pork carcasses were aged for 1, 8, and 21 days. Electrospray ionization-tandem mass spectrometry was used to comprehensively analyze profiles of phospholipids from each sample (n = 60). Total phospholipid quantity decreased 4-folds (P < .01) from 1 to 21 days of aging in pork loins. Phosphatidylinositol (PI) and phosphatidylserine (PS) increased by 30% and 73%, respectively, from 1 to 21 days of aging in pork loins (P < .01). This increase was mainly due to relative percentage increase from PI 38:4 (18:0-20:4) and PS 36:2 (18:0-18:2; P < .01). The results also showed that the relative percentage of lysophosphatidylcholine increased by 35% after short term aging (8d), and phosphatidic acid increased by 10-folds after extended aging (21d; P < .01). These results documented that phospholipids undergo enzymatic hydrolysis during aging, but also indicated that lipid species containing 18:2 or 20:4 within PI and PS were slightly more resistant to enzymatic hydrolysis compared with the other phospholipids.

Experience of menopause in women with inflammatory bowel disease: pilot study.

OBJECTIVE: Inflammatory bowel diseases (IBD) are debilitating chronic intestinal diseases requiring extensive medical intervention. Little is known how IBD symptoms and treatments affect menopause experience and quality of life. The study's goal was to investigate the relationship between IBD and menopause. METHOD: Women with IBD, between the ages of 30 and 65 years, were recruited from an outpatient IBD clinic. They completed surveys on obstetric, medical, and IBD history and clinical disease activity. Quality of life was assessed using the validated menopause-specific quality of life (MENQOL) questionnaire. RESULTS: Seventy-one women (47 Crohn's disease, 22 ulcerative colitis, and two indeterminate colitis, median age 45 years) enrolled into the study. Younger age of IBD diagnosis was correlated with younger age of last menstrual period (r = 0.697). IBD severity affected menopause-related quality of life in three MENQOL domains (psychosocial, physical, and sexual); the fourth domain (vasomotor) did not appear to be affected by the severity of IBD clinical disease. CONCLUSION: Women with IBD may experience additional challenges when going through the menopause transition. Our findings support the need for further studies to better inform patients and clinicians on the relationship between IBD and menopause to optimize patient care.

Forest floor lead, copper and zinc concentrations across the northeastern United States: synthesizing spatial and temporal responses.

Understanding how metal concentrations in soil have responded to reductions of anthropogenic emissions is essential for predicting potential ecosystem impacts and evaluating the effectiveness of pollution control legislation. The objectives of this study were to present new data and synthesize existing literature to document decreases in Pb, Cu, and Zn concentrations in forest soils across the northeastern US. From measurements at 16 sites, we observed that forest floor Pb, Cu, and Zn concentrations have decreased between 1980 and 2011 at an overall mean rate of 1.3 ± 0.5% yr(-1). E-folding times, a concentration exponential decay rate (1/k), for Pb, Cu and Zn at the 16 sites were estimated to be 46 ± 7, 76 ± 20 and 81 ± 19 yr, respectively. Mineral soil concentrations were correlated with forest floor concentrations for Pb, but not for Cu and Zn, suggesting an accumulation in one pool does not strongly influence accumulation in the other. Forest floor Pb, Cu and Zn concentrations from our sites and 17 other studies conducted from 1970-2014 in remote forests across the northeastern US were compiled into pooled data sets. Significant decreasing trends existed for pooled forest floor Pb, Cu, and Zn concentrations. The pooled forest floor Pb e-folding time was determined to be 33 ± 9 yrs, but the explanatory power of pooled Cu and Zn regressions were inadequate for calculating e-folding times (r(2)<0.25). Pooled Pb, Cu, and Zn concentrations in forest floor were multiple-regressed with latitude, longitude, elevation, and year of sampling, cumulatively explaining 55, 38, and 28% of the variation across compiled studies. Our study suggests anthropogenic Pb in the forest floor will continue to decrease, but decreases in forest floor Cu and Zn concentrations may be masked by spatial heterogeneity or are at a new steady state.

Quality and safety impact on the provision of parenteral nutrition through introduction of a nutrition support team.

BACKGROUND/OBJECTIVES: Parenteral nutrition (PN) should be provided to the malnourished patient if enteral feeding is insufficient or unsafe. A nutrition support team (NST) may improve PN services. We compared the use and complications of hospital PN before and after the implementation of an NST. SUBJECTS/METHODS: All inpatients referred for PN outside of the intensive care unit and the intestinal failure unit were prospectively included from 2009 to 2012. The NST was introduced in 2010. Quality improvement methodology was applied. RESULTS: In 2009, a mean of 16 (limits of normal variation 4-28) patients were referred for PN each month. After introduction of the NST, this rose to 26 (10-42) referrals per month. The percentage of referrals where PN was not initiated increased from 5.3% in 2009 to 10.1% in 2012 (P=0.03). This increase was restricted to teams that infrequently referred for PN, and enteral nutrition could replace PN in 31 of 51 patients (61%) as compared with 8 of 32 (25%) patients referred from teams that frequently referred for PN (P=0.001). The frequency of PN started owing to an insufficient oral or enteral intake decreased from 11% to 3% (P=0.01). The catheter-related bloodstream infection rate dropped from 6.7 to 0.7 episodes per 1000 catheter days (P<0.001). CONCLUSIONS: Introduction of an NST increased both the total PN use and the percentage of referrals where enteral nutrition could replace PN. Medical specialty influenced the referral pattern and the likelihood that a referral resulted in PN being initiated. Safety of PN catheters improved significantly following NST introduction.

Quantification of hepatic FOXP3+ T-lymphocytes in HIV/hepatitis C coinfection.

Coinfection with HIV adversely impacts every stage of hepatitis C (HCV) infection. Liver damage in HCV infection results from host antiviral responses rather than direct viral pathogenesis. Despite depressed cellular immunity, coinfected patients show accelerated hepatic fibrosis compared with HCV monoinfected patients. This paradox is poorly understood. T-regulatory (Treg) cells (CD4+ and FOXP3+) are hypothesized to limit hepatic damage in HCV. Our hypothesis was that reduced frequency of hepatic Treg in HIV/HCV coinfection compared with HCV monoinfection may explain poorer outcomes. We quantified FOXP3+, CD4+, CD8+ and CD20+ cells in liver biopsies of 35 male subjects matched by age and ISHAK fibrosis score, 12 HIV monoinfected, 11 HCV monoinfected and 12 HIV/HCV coinfected. Cell counts were performed using indirect immunohistochemical staining and light microscopy. HIV/HCV coinfected subjects had fewer hepatic FOXP3+ (P = 0.031) and CD4+ cells (P = 0.001) than HCV monoinfected subjects. Coinfected subjects had more hepatic CD8+ cells compared with HCV monoinfected (P = 0.023), and a lower ratio of FOXP3+ to CD8+ cells (0.08 vs 0.27, P < 0.001). Multivariate analysis showed number of CD4+ cells controlled for differences in number of FOXP3+ cells. Fewer hepatic FOXP3+ and CD4+ cells in HIV/HCV coinfection compared with HCV monoinfection suggests lower Treg activity, driven by an overall loss of CD4+ cells. Higher number of CD8+ cells in HIV/HCV coinfection suggests higher cytotoxic activity. This may explain poorer outcomes in HIV/HCV coinfected patients and suggests a potential mechanism by which highly active antiretroviral therapy may benefit these patients.

A text message based weight management intervention for overweight adults.

BACKGROUND: Weight management interventions can be extended using mobile telephone technology to deliver support in real-time, real-world settings. The present study aimed to determine whether text messaging helped patients maintain or lose weight following a weight-loss programme. METHODS: In this controlled study, overweight and obese [body mass index (BMI) >30 kg m(-2) or >28 kg m(-2) with co-morbidities] adults who completed a weight-loss programme participated in an additional 12-week text message intervention [Lifestyle, Eating and Activity Programme (LEAP) Beep]. Patients were allocated goals for steps, fruit, vegetable and breakfast consumption. Patients regularly 'texted' their progress and received tailored practitioner feedback. Pre/post-intervention body weight, waist circumference (WC), BMI, quality of life (QOL), anxiety and depression measurements were compared retrospectively with a control group offered weight checks only. RESULTS: Compared to control (n = 17), the intervention group's (n = 17) body weight, WC and BMI reduced significantly (-1.6 versus 0.7 kg, P = 0.006; -2.2 versus 1.5 cm, P = 0.0005; -0.6 versus 0.7 kg m(-2) , P = 0.03, respectively). QOL and depression scores also improved (-6.8 versus 1 point, P = 0.134; -0.2 versus 0.2 points, P = 0.228). No difference was observed in anxiety scores between the groups. Intervention versus control group follow-up attendance improved significantly (4.4 versus 1.7 attendances, P = 0.0005). CONCLUSIONS: LEAP Beep promoted losses in weight, WC and BMI, and improved QOL parameters and follow-up attendance. Text messaging is a cheap, portable, convenient and innovative medium facilitating goal setting, self-monitoring and information exchange. Further improvements to automation at the same time as maintaining individual support are necessary to ease practitioner burden. Text messaging offers cost-efficient dietetic input, opening up possibilities for practitioner-to-patient support and yields positive weight outcomes following initial weight loss.

Nutritional screening of elderly patients: a health improvement approach to practice.

INTRODUCTION: Almost 60% of elderly care in-patients are at risk of malnutrition. Malnourished patients have poorer clinical outcomes and this is a key factor with respect to prolonging the length of stay. Since 2003, the Malnutrition Universal Screening Tool (MUST) has been advocated as a method for identifying these at-risk patients. Screening should take place on admission; however, the Trust has set a stretch target of aiming to document the score accurately within 6 h of admission. METHODS: Three 'care of the elderly' wards participated in the project. Each month, the timeliness (within 6 h of admission) and accuracy (compared to a dietician assessment) of the MUST scores on the wards were reviewed. Plan-Do-Study-Act cycles were used to rapidly test changes in the ward areas. Tests included a study day, one-to-one ward-based nutrition training, a focus on the use of alternative anthropometric measurements, the development of a training pack and the identification of the challenges for undertaking accurate and timely assessments. RESULTS: Baseline data identified that a MUST was documented in <60% of patients within 6 h of admission and that only 70% were accurate. After implementation of the change package, all the wards achieved an improvement and documented MUST within 6 h of admission; one ward achieved 90% accuracy in the scores. CONCLUSIONS: Ward teams receiving training and monthly feedback of their results creates ownership, momentum and maintains enthusiasm for striving to reach stretch targets. The team continues to work on improving accurate nutritional screening across the Trust by using quality improvement methodologies.

Effect of chloride on nitrite-induced methaemoglobinemia in Atlantic sturgeon, Acipenser oxyrinchus oxyrinchus (Mitchill).

We evaluated the effects of chloride concentration on the clinical pathology in juvenile Atlantic sturgeon, Acipenser oxyrinchus oxyrinchus (Mitchill), following semi-static exposures to 1 mg L(-1) nitrite for 96 h. In spring water naturally low in chloride (5 mg L(-1)), plasma nitrite concentrated to more than 40× environmental levels resulting in a severe methaemoglobinemia characterized by torpid behaviour, 30-fold increase in methaemoglobin fraction, anaemia, leucopenia and hyperkalaemia. Loss of intracellular water and potassium to extracellular space may have resulted in hyperkalaemia and haemodilution. Fish survived nitrite exposure, but 60% of torpid fish died following capture and tissue sampling. Fish acclimated to 10-fold higher chloride content (55 mg L(-1)) did not concentrate nitrite in the plasma above environmental levels or develop methaemoglobinemia, but did exhibit similar haematology and plasma chemistry changes. Plasma nitrite returned to preexposure levels by 14 days following nitrite exposures, but severity of clinical pathology changes persisted or increased, suggesting that Atlantic sturgeon have reduced capacity to recover from methaemoglobinemia. Fish that survive methaemoglobinemia may be susceptible to mortality from the cumulative effects of intoxication, handling and other stresses for two or more weeks following nitrite remediation. Chloride buffering in aquaculture systems reduces the toxic effects of nitrite accumulation.

Interactions between methylating and pyridyloxobutylating agents in A/J mouse lungs: implications for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis.

The tobacco-specific nitrosamine, 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone, is activated to lung DNA methylating and pyridyloxobutylating intermediates. It is likely that both pathways play a role in lung tumor initiation by this nitrosamine. Previous studies indicated that O(6)-methylguanine (O(6)-mG) persistence is critical for lung tumor formation in A/J mice. The model pyridyloxobutylating agent, 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (NNKOAc), enhanced the tumorigenic activity of a model methylating agent, acetoxymethylmethylnitrosamine (AMMN), presumably by increasing O(6)-mG persistence in lung DNA. We have been testing the hypothesis that the pyridyloxobutylation pathway increases the mutagenic activity of the DNA methylation pathway by preventing the repair of O(6)-mG by O(6)-alkylguanine-DNA alkyltransferase (AGT). In this study, we report that NNKOAc depletes AGT in lungs but not livers of A/J mice. The consequences of AGT depletion by NNKOAc were then compared with those observed with a known AGT inhibitor, O(6)-benzylguanine (O(6)-bG). NNKOAc and O(6)-bG had similar effects on the levels of AMMN-derived O(6)-mG at 4 and 96 h postinjection. This increase in O(6)-mG levels correlated to increased lung tumor multiplicity in animals simultaneously treated with AMMN (0.75 or 1 micromol) and NNKOAc or O(6)-bG. Only NNKOAc significantly increased lung tumor multiplicity at doses of 0.25 or 0.5 micromol AMMN. The results from these studies indicate that the pyridyloxobutylating agent, NNKOAc, can influence the tumorigenic activity of methylating agents in two ways. At low AMMN doses, the increase in tumor multiplicity is dominated by the additive tumorigenic properties of AMMN and NNKOAc. At higher AMMN doses, NNKOAc appears to enhance the tumorigenic activity of AMMN through enhanced depletion of the repair protein, AGT, leading to increased O(6)-mG persistence. It is likely that similar interactions are important for the organospecific effects of 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone.

First steps: approaching The Discipline based, outcome oriented ministry model.

This article describes how a new staff chaplain is approaching and applying a discipline based, outcome oriented ministry model. He describes his move from being a lone, geriatric chaplain in a long term care facility to becoming a member of a team of staff chaplains in a teaching hospital who have disciplined themselves to an outcome oriented ministry model. The writer gives his perspective on The Discipline, and denotes ways in which his ministry has been impacted. Though the author has been involved with this process for only six months, both he and those in his care are experiencing some of the benefits of making tangible contributions and developing measurable outcomes in ministry.

Cutaneous histiocytic lymphangitis: an unusual manifestation of rheumatoid arthritis.

Two cases are presented of unusual cutaneous lesions associated with rheumatoid arthritis in underlying joints. The lesions were evanescent, erythematous and violaceous partly macular and partly indurated plaques, with a livedo-like pattern of erythema at the edge in one case. Histological changes were identical in the two cases. The major features were dilated, dermal lymphatics containing aggregates of inflammatory cells, mainly histiocytes, with adjacent perivascular lymphoid aggregates. An appropriate name for this reaction would appear to be cutaneous histiocytic lymphangitis.

The expression of membrane-associated 67-kDa laminin receptor (67LR) is modulated in vitro by cell-contact inhibition.

The interaction of cells with their substratum is an important determinant of cell behaviour, influencing attachment, proliferation, and motility. Such interactions are mediated by cell surface receptors which bind to attachment factors, like the glycoprotein laminin in basement membranes. We have previously shown that expression of the 67-kDa laminin receptor (67LR) is elevated in proliferating retinal microvasculature compared with mature, quiescent vessels. Here, we examined 67LR mRNA and protein expression in primary cultures of retinal microvascular endothelial cells (RMEC) and in the breast cancer cell-line T47D during stages of contact inhibition. In both cell types, the expression levels of 67LR mRNA and membrane-associated 67LR protein were significantly increased during the proliferative phases of monolayer formation. As the cells achieved contact inhibition, 67LR expression was reduced to comparatively low levels. Thus, the differential expression of 67LR between dividing and contact-inhibited cells may indicate a role for this receptor during proliferative processes.