Helping the healer: population-informed workplace wellness recommendations for physician well-being.

Background: The need to keep physicians healthy and in practice is critical as demand for doctors grows faster than the supply. Workplace wellness programmes can improve employee health and retain skilled workers. Aims: To broaden our understanding about ways to help doctors coping with mental health problems and to develop population-informed workplace wellness recommendations for physician populations. Methods: Researchers surveyed physicians to document potential warning signs and prevention strategies. A survey was issued to doctors who presented to a physician health programme with mental health complaints. The survey captured respondents' feedback about how to identify and prevent mental health problems. Data were analyzed using simple descriptive statistics. Results: There were 185 participants. Half of respondents believed their problems could have been recognized sooner and 60% said they exhibited signs that could aid in earlier detection. Potential warnings included fluctuations in mood (67%), increased comments about stress/burnout (49%) and behavioural changes (32%). To improve detection, prevention and care-seeking for mental health problems, doctors endorsed multiple items related to the use of interpersonal supports, personal factors and organizational dynamics throughout the survey. Conclusions: The findings confirmed earlier work demonstrating the value of social and organizational support in maintaining physician health. It further indicated that earlier identification and/or prevention of mental health problems is not only possible, but that medical organizations are uniquely situated to carry out this work.

Dietary guidance normalizes large intestinal endocrine cell densities in patients with irritable bowel syndrome.

BACKGROUND/OBJECTIVES: To determine the large intestinal endocrine cell types affected following dietary guidance in patients with irritable bowel syndrome (IBS). SUBJECTS/METHODS: The study included 13 IBS patients and 13 control subjects. The patients received three sessions of individualized dietary guidance. Both the control subjects and the patients were scheduled for colonoscopies at baseline and again for the patients at 3-9 months after dietary guidance. Biopsy samples were taken from the colon and rectum and were immunostained for all types of large intestinal endocrine cells. The endocrine cells were quantified using computerized image analysis. RESULTS: The daily total consumption (mean±s.e.m. values) of fruits and vegetables rich in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) decreased significantly from 16.2±5.3 g before receiving dietary guidance to 9.2±3.2 g after receiving dietary guidance (P=0.02). In the total colon, the densities of serotonin cells were 46.8±8.9, 10.5±2.1 and 22.6±3.2 cells/mm(2) in control subjects and in IBS patients before and after receiving dietary guidance, respectively (P=0.007); the corresponding densities of peptide YY cells were 11.6±1.8, 10.8±1.7 and 16.8±2.1 cells/mm(2), respectively (P=0.06). The cell densities for both serotonin and peptide YY did not change significantly in the rectum. The densities of somatostatin cells in the rectum were 13.5±3.0, 13.2±3.0, and 22.3±3.2 cells/mm(2) for control subjects and for IBS patients before and after receiving dietary guidance, respectively (P=0.01). CONCLUSIONS: The densities of the large intestinal endocrine cells tend to normalize following dietary guidance that may have contributed to the improvement of the patients with IBS symptoms.

Discrimination and Romani health: a validation study of discrimination scales among Romani women in Macedonia and Serbia.

OBJECTIVES: Scales used to assess discrimination in public health research have rarely been validated outside of high income countries. Our objective was to validate the Experiences of Discrimination (EOD) scale and the Everyday Discrimination Scale (EDS) among 410 Romani women in Macedonia and Serbia. METHODS: Romani female interviewers conducted interviews in 2012-2013. We used a multiple indicator multiple cause approach to test a one-factor model for each scale and to assess differential item functioning (DIF) by age, wealth, country, and education. We also measured associations between the EOD and EDS with smoking in the past year and psychological distress. RESULTS: Three items of the EOD were conceptually irrelevant. Two items of the EDS were not conditionally independent. DIF was found by country for one item in each scale. After excluding these items, all scales exhibited good model fit and were associated with smoking (EOD beta = 0.40, 95% CI = 0.18, 0.63; EDS beta = 0.33, 95% CI = 0.12, 0.54) and psychological distress (EOD beta = 0.26, 95% CI = 0.15, 0.37; EDS beta = 0.26, 95% CI = 0.04, 0.47). CONCLUSIONS: Discrimination scales can be adapted for use among Romani women and are associated with both smoking and psychological distress.

Effect of dietary management on the gastric endocrine cells in patients with irritable bowel syndrome.

BACKGROUND/OBJECTIVES: The gastric endocrine cells in patients with irritable bowel syndrome (IBS) tend to normalize following dietary guidance. The aim of the present study was to identify the gastric endocrine cell types that are changed following such dietary guidance. SUBJECTS/METHODS: Fourteen IBS patients and 14 healthy subjects were included in the study. Patients received three sessions of individual dietary management guidance. Gastroscopy was performed on both the controls and the patients at baseline and then again for the patients at 3-9 months after dietary guidance. Biopsy samples from the corpus and antrum were immunostained for all gastric endocrine cell types. Endocrine cells were quantified by computerized image analysis. RESULTS: The densities of the ghrelin cells for the controls and IBS patients before and after dietary guidance were 149.6 ± 36.2 (mean ± s.e.m.; 95% confidence interval (CI) 71.3-227.8), 114.5 ± 32.7 and 161.8 ± 37.8 cells/mm(2), respectively. The densities of the gastrin cells in these groups were 155.8 ± 21.0 (95% CI 110.3-201.2), 159.4 ± 24.3 and 211.6 ± 28.0 cells/mm(2), respectively; the corresponding densities of serotonin cells in the corpus were 18.2 ± 3.9 (95% CI 9.8-26.6), 10.6 ± 3.4 and 14 ± 2.0 cells/mm(2) and in the antrum were 44.6 ± 12.2 (95% CI 18.1-71.1), 1.7 ± 0.5 and 14.7 ± 6.3 cells/mm(2). The densities of the somatostatin cells in the corpus were 40.0 ± 7.7 (95% CI 23.5-56.5), 23.0 ± 3.0 and 37.3 ± 4.2 cells/mm(2), respectively, and in the antrum were 138.9 ± 22.0 (95% CI 91.4-186.3), 95.6 ± 15.9 and 86.0 ± 16.9 cells/mm(2), respectively. CONCLUSIONS: The densities of all of the gastric endocrine cell types changed towards the healthy control values in the IBS patients following a change in food intake.

Physician health programmes and malpractice claims: reducing risk through monitoring.

BACKGROUND: Physician health programmes (PHPs) are peer-assistance organizations that provide support to physicians struggling with addiction or with physical or mental health challenges. While the services they offer are setting new standards for recovery and care, they are not immune to public debate and criticism since some have concerns about those who are enrolled in, or have completed, such programmes and their subsequent ability to practice medicine safely. AIMS: To examine whether medical malpractice claims were associated with monitoring by a PHP using a retrospective examination of administrative data. METHODS: Data on PHP clients who were insured by the largest malpractice carrier in the state were examined. First, a business-model analysis of malpractice risk examined relative risk ratings between programme clients and a matched physician cohort. Second, Wilcoxon analysis examined differences in annual rates of pre- and post-monitoring claims for PHP clients only. RESULTS: Data on 818 clients was available for analysis. After monitoring, those enrolled in the programme showed a 20% lower malpractice risk than the matched cohort. Furthermore physicians' annual rate of claims were significantly lower after programme monitoring among PHP clients (P < 0.01). CONCLUSIONS: This is the only study examining this issue to date. While there are a variety of reasons why physicians present to PHPs, this study demonstrates that treatment and monitoring is associated with a lowered risk of malpractice claims and suggests that patient care may be improved by PHP monitoring.

Chromogranin A cell density in the rectum of patients with irritable bowel syndrome.

In a previous study, chromogranin A (CgA) cell density in the colon of patients with irritable bowel syndrome (IBS) was found to be reduced. It has been suggested that intestinal CgA cell density may be used as a marker for the diagnosis of IBS. The rectum harbours a larger number of large intestinal endocrine cells and is more accessible for biopsies than the colon. The present study aimed at determining the CgA cell density in the rectum of IBS patients. A total of 47 patients with IBS that fulfilled the Rome Criteria III (39 females and 8 males; average age, 38 years) were included. A total of 28 patients had diarrhea (IBS-D) and 19 had constipation (IBS-C) as the predominant symptom. A total of 27 subjects that underwent colonoscopy with rectal biopsies were used as the controls. These subjects underwent colonoscopy due to gastrointestinal bleeding (the source of which was identified as haemorrhoids or angiodysplasia; 19 females and 8 males; average age, 49 years), or health worries. The rectal biopsies were immunostained for CgA and quantified by computer image analysis. The CgA density in the controls was 206.3±22.2 (mean ± SEM), in all IBS patients 190.2±14.3, in IBS-D patients 188.8±14.7 and in IBS-C patients 195.3±34.1. There was no statistically significant difference between the controls, IBS, IBS-D or IBS-C patients (P=0.5, 0.5 and 0.7, respectively). The present study showed that although the rectum comprises the same endocrine cell types as the colon, attention must be paid when drawing conclusions regarding the whole large intestine from studies carried out on the rectum. This particularly applies when endocrine cells are investigated. As CgA cell density represents the total endocrine cell content of the rectum, changes in specific endocrine cells in IBS patients cannot be excluded.

The role of diet in the pathogenesis and management of irritable bowel syndrome (Review).

Most patients with irritable bowel syndrome (IBS) believe that diet plays a significant role in inducing IBS symptoms and desire to know what foods to avoid. It has been found that the intake of calories, carbohydrates, proteins and fat by IBS patients does not differ from that of the background population. IBS patients were found to avoid certain food items that are rich in fermentable oligo-, di- and monosacharides and polyols (FODMAPs), but they did have a high consumption of many other FODMAP-rich food items. The diet of IBS patients was found to consist of a low calcium, magnesium, phosphorus, vitamin B2 and vitamin A content. There is no consistent evidence that IBS patients suffer from food allergy, nor is there documented evidence that food intolerance plays a role in IBS symptoms. Abnormalities in gut hormones have been reported in IBS patients. As gut hormones control and regulate gastrointestinal motility and sensation, this may explain the abnormal gastrointestinal motility and visceral hypersensitivity reported in these patients. Guidance concerning food management which includes individually based restrictions of FODMAP-rich food items and individual evaluation of the effects of protein-, fat- and carbohydrate-rich/poor diets may reduce IBS symptoms.

Low densities of serotonin and peptide YY cells in the colon of patients with irritable bowel syndrome.

BACKGROUND: The gut hormones are important in regulating gastrointestinal motility. Disturbances in gastrointestinal motility have been reported in patients with irritable bowel syndrome (IBS). Reduced endocrine cell density, as revealed by chromogranin A, has been reported in the colon of IBS patients. AIMS: To investigate a possible abnormality in the colonic endocrine cells of IBS patients. METHODS: A total of 41 patients with IBS according to Rome Criteria III and 20 controls were included in the study. Biopsies from the right and left colon were obtained from both patients and controls during colonoscopy. The biopsies were immunostained for serotonin, peptide YY (PYY), pancreatic polypeptide (PP), entroglucagon, and somatostatin cells. Cell densities were quantified by computerized image analysis. RESULTS: Serotonin and PYY cell densities were reduced in the colon of IBS patients. PP, entroglucagon, and somatostatin-immunoreactive cells were too few to enable reliable quantification. CONCLUSION: The cause of these observations could be primary genetic defect(s), secondary to altered serotonin and/or PYY signaling systems and/or subclinical inflammation. Serotonin activates the submucosal sensory branch of the enteric nervous system and controls gastrointestinal motility and chloride secretion via interneurons and motor neurons. PYY stimulates absorption of water and electrolytes, and inhibits prostaglandin (PG) E2, and vasoactive intestinal peptide, which stimulates intestinal fluid secretion and is a major regulator of the "ileal brake". Although the cause and effect relationship of these findings is difficult to elucidate, the abnormalities reported here might contribute to the symptoms associated with IBS.

The prevalence of celiac disease in patients with irritable bowel syndrome.

The diagnosis of irritable bowel syndrome (IBS) is based on symptom assessment such as the Rome III criteria. It is sometimes difficult to clinically distinguish IBS from adult-onset celiac disease (CD). Individuals with CD presenting with relatively vague abdominal symptoms are at risk of been dismissed as having IBS. This study aimed to investigate the prevalence of patients with CD among those that fulfill the Rome III criteria for IBS from among patients referred to the gastroenterology section of our hospital over the last 5 years. The study included a total of 968 patients with an average age of 32 years (range 18-59 years). Females constituted 95% of all patients. Duodenal biopsies were obtained during standard gastroscopy. Sections from these biopsies were stained with haematoxylin and eosin and immunostained for human leucocytes CD45 using the avidin-biotin complex (ABC) method. The sections were then histopathologically examined. Four patients had CD: one with Marsh type 3b, and 3 with Marsh type 1. All four of these patients were positive for tissue transglutminase antibodies (anti-t-TG) IgA and were females aged 24, 20, 36 and 38 years. These 4 patients fulfilled the Rome III criteria for the sub-type IBS-diarrhea. This amounts to a prevalence of 0.4% of CD in IBS patients. The present findings support the notion that IBS patients should be routinely examined for CD. This applies to all subtypes of IBS.

Using blood plasma for monitoring organochlorine contaminants in juvenile white sturgeon, Acipenser transmontanus, from the lower Columbia River.

Organochlorine (OC) pesticide concentrations in blood plasma samples from 88 juvenile white sturgeon collected from the lower Columbia River were measured and compared to plasma sex steroid and OC tissue levels previously measured in corresponding fish. Significant squared correlation coefficients between summation operator DDT concentrations in sturgeon plasma and gonads and livers were 0.37 and 0.32, respectively. Significant negative correlations between plasma testosterone concentration and plasma Sigma DDT concentration in male fish (r(2)=0.26), plasma 17beta estradiol concentration and plasma Sigma DDT concentration in female fish (r(2)=0.38) and condition factor and plasma Sigma DDT concentration in all fish were found (r(2)=0.17). These results suggest that blood plasma may be a suitable nondestructive method for monitoring adult sturgeon population for persistent OC contaminants.

Mercury concentrations in gonad, liver, and muscle of white sturgeon Acipenser transmontanus in the lower Columbia River.

This study determined the partitioning of total mercury in liver, gonad, and cheek muscle of white sturgeon (Acipenser transmonatus) in the lower Columbia River. The relationship between tissue mercury concentrations and various physiologic parameters was assessed. White sturgeon were captured in commercial fisheries in the estuary and Bonneville, The Dalles, and John Day Reservoirs. Condition factor (CF), relative weight (Wr), and gonadosomatic index (GSI) were determined for each fish (n = 57). Gonadal tissue was examined histologically to determine sex and stage of maturity. Liver (n = 49), gonad (n = 49), and cheek muscle (n = 57) were analyzed for total mercury using cold-vapor atomic fluorescence spectrophotometry. Tissue protein concentrations were measured by ultraviolet-visible spectroscopy. Plasma was analyzed for testosterone (T), 11-ketotestosterone (KT), and 17ss-estradiol (E2) using radioimmunoassay. Mean tissue mercury concentrations were higher in muscle compared with liver and gonad at all sampling locations, except Bonneville Reservoir where mean liver mercury content was the highest tissue concentration observed in the study. Significant negative correlations between plasma androgens (T and KT) and muscle mercury content and plasma E2 and liver mercury content were found. A significant positive linear relationship between white sturgeon age and liver mercury concentrations was evident. Significant negative correlations between CF and relative weight and gonad and liver mercury content were found. In addition, immature male sturgeon with increased gonad mercury content had decreased GSIs. These results suggest that mercury, in the form of methylmercury, may have an effect on the reproductive potential of white sturgeon.

Tenascin-C inhibits beta1 integrin-dependent T lymphocyte adhesion to fibronectin through the binding of its fnIII 1-5 repeats to fibronectin.

The extracellular matrix consists of different proteins interacting to form a meshwork-like structure. T lymphocyte adhesion to individual matrix proteins is mainly regulated at the adhesion receptor level, but it is conceivable that the composition of the matrix itself may affect T lymphocyte adhesion to individual proteins. We have addressed the latter point by studying the effect of the matrix protein tenascin-C (TN-C) on T lymphocyte adhesion to fibronectin. Here we report that TN-C inhibits adhesion of T lymphocytes and MOLT-4 lymphoma cells to fibronectin. We demonstrate that a TN-C fragment consisting of fibronectin type III repeats 1-5 (TNfnIII 1-5) but not TNfnIII A-D and TNfnIII 6-8 inhibited alpha5beta1 and alpha4beta1 integrin-mediated T lymphocyte and MOLT-4 adhesion to fibronectin. At concentrations that did not inhibit adhesion, TNfnIII 1-5 still prevented MOLT-4 cells from spreading on fibronectin. Preincubation and co-immobilization of TNfnIII 1-5 with fibronectin was more effective in inhibiting MOLT-4 adhesion to fibronectin than soluble TNfnIII 1-5 present during the adhesion test. Using an enzyme-linked immunosorbent assay we could demonstrate binding of TNfnIII 1-5 to fibronectin and fibronectin fragments. Taken together, these data demonstrate that the TNfnIII 1-5 domain is implicated in the inhibition of T lymphocyte adhesion to fibronectin caused by TN-C, and indicate that this effect involves the binding of TN-C repeats TNfnIII 1-5 to fibronectin.

Characterization of human fibroleukin, a fibrinogen-like protein secreted by T lymphocytes.

We have recently cloned the human homologue of the murine pT49 cDNA (hpT49h), a transcript encoding a protein homologous to the beta- and gamma-chains of fibrinogen. Here, we report the identification of the hpT49h gene product using mAbs generated against a peptide corresponding to the carboxyl-terminal end of the deduced protein and a recombinant protein fragment expressed in Escherichia coli. mAbs 23A6, 7B12, and 3F4 specifically recognized a protein of 70 kDa in reducing SDS-PAGE in the culture supernatant of 293T cells transiently transfected with the full length hpT49h cDNA and freshly isolated PBMC. Under nonreducing conditions, the material migrated with a molecular mass of 250 to 300 kDa, indicating that the 70-kDa protein forms a disulfide bonded complex. Because of its homology with fibrinogen, we have termed this protein fibroleukin. Fibroleukin is spontaneously secreted in vitro by freshly isolated CD4+ and CD8+ T lymphocytes. RT-PCR analysis revealed preferential expression of fibroleukin mRNA in memory T lymphocytes (CD3+/CD45R0+) compared with naive T lymphocytes (CD3+/CD45RA+). Fibroleukin production by PBMC was rapidly lost in culture. Production could be partially maintained in the presence of IFN-gamma, while T lymphocyte activation had no effect. To demonstrate fibroleukin production in vivo, we analyzed colon mucosa by immunohistology. Fibroleukin staining was detected in the extracellular matrix of the T lymphocyte-rich upper portion of the lamina propria mucosa. While the exact function of fibroleukin remains to be defined, these data suggest that fibroleukin may play a role in physiologic lymphocyte functions at mucosal sites.

Nested PCR for ultrasensitive detection of the potato ring rot bacterium, Clavibacter michiganensis subsp. sepedonicus.

Oligonucleotide primers derived from sequences of the 16S rRNA gene (CMR16F1, CMR16R1, CMR16F2, and CMR16R2) and insertion element IS1121 of Clavibacter michiganensis subsp. sepedonicus (CMSIF1, CMSIR1, CMSIF2, and CMISR2) were used in nested PCR to detect the potato ring rot bacterium C. michiganensis subsp. sepedonicus. Nested PCR with primer pair CMSIF1-CMSIR1 followed by primer pair CMSIF2-CMSIR2 specifically detected C. michiganensis subsp. sepedonicus, while nested PCR with CMR16F1-CMR16R1 followed by CMR16F2-CMR16R2 detected C. michiganensis subsp. sepedonicus and the other C. michiganensis subspecies. In the latter case, C. michiganensis subsp. sepedonicus can be differentiated from the other subspecies by restriction fragment length polymorphism (RFLP) analyses of the nested PCR products (16S rDNA sequences). The nested PCR assays developed in this work allow ultrasensitive detection of very low titers of C. michiganensis subsp. sepedonicus which may be present in symptomiess potato plants or tubers and which cannot be readily detected by direct PCR (single PCR amplification). RFLP analysis of PCR products provides for an unambiguous confirmation of the identify of C. michiganensis subsp. sepedonicus.

"Candidatus phytoplasma australiense," a new phytoplasma taxon associated with Australian grapevine yellows.

A phytoplasma was detected in naturally diseased 'Chardonnay' grapevines exhibiting symptoms of Australian grapevine yellows disease. The use of PCR designed to amplify phytoplasma DNA resulted in detection of phytoplasma DNA in all of the diseased plants examined; no phytoplasma DNA was detected in healthy seedling grapevines. The collective restriction fragment length polymorphism (RFLP) patterns of amplified 16S ribosomal DNA differed from the patterns described previously for other phytoplamas. On the basis of the RFLP patterns, Australian grapevine yellows phytoplasma was classified as a representative of a new subgroup, designated subgroup 16SrI-J, in phytoplasma 16S rRNA group 16SrI (aster yellows and related phytoplasmas). A phylogenetic analysis in which parsimony of 16S rRNA gene sequences from this and other group 16SrI phytoplasmas was used identified the Australian grapevine yellows phytoplasma as a member of a distinct subclade (subclade xii) in the phytoplasma clade of the class Mollicutes. A phylogenetic tree constructed on the basis of 16S rRNA gene sequences was consistent with the hypothesis that there was divergent evolution of Australian grapevine yellows phytoplasma and its closet known relative, European stolbur phytoplasma (subgroup 16SrI-G), from a common ancestor. The unique properties of the DNA from the Australian grapevine yellows phytoplasma clearly establish that it represents a new taxon, "Candidatus Phytoplasma australiense."

Plasmin-induced proteolysis of tenascin-C: modulation by T lymphocyte-derived urokinase-type plasminogen activator and effect on T lymphocyte adhesion, activation, and cell clustering.

Proteolysis and remodeling of the extracellular matrix occur physiologically in processes such as tissue morphogenesis and repair and may participate in the regulation of complex cell functions, including proliferation and differentiation. While matrix degradation appears to be relevant to T lymphocyte migration through tissues, little is known about whether degraded matrix affects T lymphocyte function. We have studied the interaction between T lymphocytes and tenascin-C (TN-C), a matrix protein we have previously reported to inhibit T lymphocyte activation, in the context of plasmin-induced degradation. Here we report that plasmin efficiently cleaves TN-C. Peripheral blood T lymphocytes stimulated with phorbol ester, anti-CD28, or anti-CD3 Ab, induce, within 24 to 48 h, a strong plasminogen-dependent proteolysis of TN-C. We demonstrate that stimulated T lymphocytes activate plasminogen by secreting the urokinase-type plasminogen activator (u-PA). Plasminogen activation by T lymphocyte-derived u-PA occurs efficiently in fluid phase in the absence of cells. We investigate the consequences of plasmin-induced proteolysis on three of the effects of TN-C in relation to lymphocyte functions. Plasmin proteolysis converts TN-C from a nonadhesive into an adhesive substrate for T lymphocytes and abolishes its aggregating activity on PBMC. In contrast, the inhibitory effect of TN-C on T lymphocyte activation remains unaffected. These observations demonstrate that stimulated T lymphocytes induce plasminogen-dependent proteolysis of TN-C by secreting u-PA and suggest that proteolysis of TN-C may represent a mechanism by which to regulate some of its effects on T lymphocyte functions.