A Pilot Integrative Analysis of Colonic Gene Expression, Gut Microbiota, and Immune Infiltration in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease: Association of Disease With Bile Acid Pathways.

BACKGROUND: Although a majority of patients with PSC have colitis [PSC-IBD; primary sclerosing cholangitis-inflammatory bowel disease], this is phenotypically different from ulcerative colitis [UC]. We sought to define further the pathophysiological differences between PSC-IBD and UC, by applying a comparative and integrative approach to colonic gene expression, gut microbiota and immune infiltration data. METHODS: Colonic biopsies were collected from patients with PSC-IBD [n = 10], UC [n = 10], and healthy controls [HC; n = 10]. Shotgun RNA-sequencing for differentially expressed colonic mucosal genes [DEGs], 16S rRNA analysis for microbial profiling, and immunophenotyping were performed followed by multi-omic integration. RESULTS: The colonic transcriptome differed significantly between groups [p = 0.01]. Colonic transcriptomes from HC were different from both UC [1343 DEGs] and PSC-IBD [4312 DEGs]. Of these genes, only 939 had shared differential gene expression in both UC and PSC-IBD compared with HC. Imputed pathways were predominantly associated with upregulation of immune response and microbial defense in both disease cohorts compared with HC. There were 1692 DEGs between PSC-IBD and UC. Bile acid signalling pathways were upregulated in PSC-IBD compared with UC [p = 0.02]. Microbiota profiles were different between the three groups [p = 0.01]; with inferred function in PSC-IBD also being consistent with dysregulation of bile acid metabolism. Th17 cells and IL17-producing CD4 cells were increased in both PSC-IBD and UC when compared with HC [p < 0.05]. Multi-omic integration revealed networks involved in bile acid homeostasis and cancer regulation in PSC-IBD. CONCLUSIONS: Colonic transcriptomic and microbiota analysis in PSC-IBD point toward dysregulation of colonic bile acid homeostasis compared with UC. This highlights important mechanisms and suggests the possibility of novel approaches in treating PSC-IBD.

Seasonal Influenza Vaccine Uptake in a Respiratory Outpatients Clinic.

Influenza is an acute viral respiratory illness that continues to cause significant morbidity and mortality in Ireland. Despite well-established national and international guidelines1 and increased public awareness campaigns, vaccine uptake rates are well below target worldwide2. We performed an audit of influenza vaccine uptake at a Respiratory outpatient clinic in a tertiary referral centre. 54% (n=41) of patients received the annual vaccine, well below the target of 75% set by the European Centre for Disease Prevention and Control (ECDC).

Fatal Prevotella oralis meningitis.

Prevotella oralis, an obligate Gram-negative anaerobe, was detected as the cause of acute meningitis in a four-year-old cocker spaniel. Clinical signs included acute onset collapse and severe depression. Despite treatment, the animal died. A post-mortem examination was performed which revealed a fibrinosuppurative meningitis with no significant inflammation of the brain or spinal parenchyma. The aetiological diagnosis was confirmed by anaerobic bacterial culture. This report discusses the nature and extent of the lesions and possible routes of infection of the causative organism.

The American College of Medical Practice Executives' competency study.

This article is the first of two studies conducted by the American College of Medical Practice Executives (ACMPE) that examines the perceived roles of medical practice executives. (Founded in 1956, the American College of Medical Practice Executives is the professional development and credentialing arm of the Medical Group Management Association (MGMA)). This study asked groups of physicians and nonphysician administrators to identify the competencies and associated skills and knowledge for administering group practices in today's changing environment. Those surveyed included administrators who are Fellows in ACMPE and 795 physicians who comprise the Society of Physician Administrators of the Medical Group Management Association. The responses were examined through a framework provided by the Managed Care Process Model. In this model, the focus is on the administrative and clinical processes required by different levels of managed care market penetration. The model progresses from a focus on relatively traditional practice management functions to those activities that are more complex with a greater focus on the integration of both clinical and business processes aimed at the health of populations. The analysis of the perceived competencies indicated that while both executive types perceived the importance of managing the health of populations, that task is not yet being incorporated into their professional roles.

The professional is political: an interpretation of the problem of the past in solution-focused therapy.

This paper proposes that therapists subject their work to radical doubt designed to uncover and interpret the micro-politics that in here in professional knowledge and practice. Using Orlie's notion of trespass, the approach to the past employed by solution-focused therapies is examined. These trespasses involve the therapy's silence about the meaning of injustice; its role in relation to social movements; and its potential to reproduce relations of domination. A new conception of ethics is proposed that takes into account the inevitable presence of the political as it fashions the history that conditions us as human beings.

Occupational otitis externa in chicken catchers.

Otitis externa is only occasionally occupational in origin and infestations of the ear are even less common. Two cases of occupational otitis externa due to infestation with Dermanyssus gallinae, the red poultry mite, are reported occurring in poultry workers.

This is what we're all about. American College of Medical Group Administrators.

This MGM Journal spotlights the College, its members, their quest for professionalism and some of their ideas for managing medical group practices effectively, writes Andrea Rossiter, College director. This article profiles who they are, what's important to them and what they expect to get out of their pursuit.

The effect of vasoactive intestinal polypeptide on the lower esophageal sphincter in achalasia.

Vasoactive intestinal polypeptide (VIP) is one of the main neurotransmitters implicated in the relaxation of the lower esophageal sphincter (LES). The effect of exogenous VIP on LES motor activity was determined by esophageal manometry. LES pressure (LESP) and LES relaxation were compared in four healthy volunteers and in six patients with achalasia. The effects of intravenous doses of 1.5, 3, and 5 pmol.kg-1.min-1 of VIP were compared with placebo. Neither placebo nor 3 and 5 pmol.kg-1.min-1 of VIP produced any effect on esophageal motility in healthy volunteers. In achalasia the three doses of VIP caused a dose-dependent decrease in LESP with a significant improvement in LES relaxation. A dose of 5 pmol.kg-1.min-1 produced a maximal decrease of 51% in LESP. A beta-adrenergic agonist, isoproterenol, caused a decrease in LESP both in healthy volunteers and in patients with achalasia without improving LES relaxation. In summary, intravenous VIP improved LES relaxation and caused a decrease in LESP in patients with achalasia without affecting LESP in healthy volunteers, indicating that the LES muscle in achalasia is supersensitive to VIP. The current study suggests that a selective damage in the noncholinergic nonadrenergic innervation of the esophagus is in part responsible for the motor alteration seen in these patients. The findings and the inability of isoproterenol to improve LES relaxation despite decreasing LESP support a role in VIP as a indicator of LES relaxation.

Transcutaneous electrical nerve stimulation decreases lower esophageal sphincter pressure in patients with achalasia.

Vasoactive intestinal peptide (VIP) is believed to be an inhibitory neurotransmitter responsible for lower esophageal sphincter (LES) relaxation. In patients with achalasia the concentration of VIP and the number of VIP-containing nerve fibers are reduced or absent. It has been suggested that the response to low-frequency transcutaneous electrical nerve stimulation (TENS) may be mediated by a nonadrenergic noncholinergic pathway in which the release of VIP is responsible for the smooth muscle relaxation. The present study was designed to evaluate the effect of TENS on LES pressure and on VIP plasma concentrations in six patients with achalasia (five female, one male). TENS was performed daily during one week for 45-min sessions with a pocket stimulator that delivered low-frequency pulses (6.5 Hz), at 10 pulses/sec of 0.1-msec duration at intensities of 10-20 mA until rhythmic flexion of the fingers was obtained without producing pain. LES pressure and VIP levels were obtained before TENS, after the first 45-min session, and after a week of daily stimulation. After 45-min, TENS produced a significant reduction (P less than 0.01) in LES resting pressure from the mean value 56 +/- 6.4 mm Hg to 42.3 +/- 6.4 mm Hg; with LES relaxation improvement from 50.6 +/- 3% to 63.1 +/- 3.2% (P less than 0.01). After one week of daily TENS, an additional reduction in LES resting pressure (40.3 +/- 4 mm Hg) was observed (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of local instillation of alcohol on sphincter of Oddi motor activity: combined ERCP and manometry study.

The effect of local instillation of alcohol on sphincter of Oddi motor activity was determined by endoscopic manometry. Sphincter of Oddi pressures and motor function were compared in eight cholecystectomized subjects with normal sphincter of Oddi motor function and in four patients with chronic alcoholic pancreatitis. The effect of local instillation of 3 ml of 40% alcohol was compared with water instillation. In cholecystectomized subjects, alcohol produced a significant increase of basal sphincter of Oddi pressure from 21.0 +/- 2.8 mm Hg to 95.8 +/- 83 mm Hg (p less than 0.01) without significant changes in the amplitude, duration, and frequency of phasic contractions. In patients with alcoholic chronic pancreatitis, alcohol instillation resulted in a significant increase of basal sphincter of Oddi pressure from 32.5 +/- 4.8 mm Hg to 225.1 +/- 105 mm Hg without changes in amplitude, duration, and frequency of phasic contractions. Two patients with chronic alcoholic pancreatitis had a tonic contraction of the sphincter of Oddi with transitory and mild epigastric pain. Local instillation of alcohol increases sphincter of Oddi motor activity which may play a role in the pathogenesis of alcoholic pancreatitis.

The effect of transcutaneous nerve stimulation on sphincter of Oddi pressure in patients with biliary dyskinesia.

Vasoactive intestinal polypeptide (VIP) has been postulated as a neuropeptide with inhibitory neurotransmitter activity in nonadrenergic noncholinergic pathways. Transcutaneous electric nerve stimulation (TENS) relaxes the lower esophageal sphincter in patients with achalasia. Such response is accompanied by a 30% increase in VIP concentrations in the systemic circulation. Since the sphincter of Oddi (SO) receives a very dense VIP nerve supply, we evaluate the effect of TENS on SO motor activity and on VIP plasma concentrations in patients with biliary dyskinesia and in healthy volunteers. TENS was performed with a pocket stimulator for 45 min. SO pressure and VIP levels were obtained before and after 45 min of TENS. In patients with SO dyskinesia, TENS produced a significant decrease in SO pressure from 80.1 +/- 11.9 mm Hg to 58.3 +/- 9.7 mm Hg p less than 0.01); this was accompanied by a significant increase in VIP plasma levels from 21.1 +/- 0.5 pg/ml to 32.6 +/- 1.5 pg/ml (p less than 0.01). In healthy volunteers, TENS did not produce significant changes in SO pressure. However, a significant increase in VIP plasma values was observed (p less than 0.01). No significant changes in amplitude, duration and frequency of SO phasic contractions were observed in either of the two groups evaluated. We conclude that, in patients with SO dyskinesia, TENS decreases SO basal pressure, possibly by a direct action of the released VIP in the systemic circulation. In healthy volunteers, TENS increases VIP plasma values without significant effect on SO basal pressure. These findings suggest that the response to TENS may be mediated by VIP. It is also possible that the alterations seen in patients with biliary dyskinesia may be due to impairment of the VIP nerve supply at the level of the SO.

High vasoactive intestinal polypeptide plasma levels in patients with Barrett's esophagus.

We have evaluated the correlation between vasoactive intestinal polypeptide (VIP) plasma concentration and severity of gastroesophageal reflux in patients with Barrett's esophagus and the possible differences in the VIP values of these patients compared with healthy volunteers. We also evaluated the relation between VIP plasma concentration and lower esophageal sphincter (LES) pressure in 24 patients with Barrett's esophagus. The mean VIP plasma concentration in 14 patients with severe gastroesophageal reflux was 25.6 +/- 0.75 pg/ml, significantly higher than the mean value observed in 10 patients with moderate reflux (18.9 +/- 0.67 pg/ml) (p less than 0.01). The mean LES resting pressure was significantly lower in the group of patients with severe gastroesophageal reflux than that observed in patients with moderate reflux (3 +/- 0.64 and 10.3 +/- 0.69 mm Hg, respectively; p less than 0.01). The mean VIP plasma concentration in 11 healthy volunteers (20.6 +/- 0.65 pg/ml) was significantly lower than the mean value observed in the subgroup of patients with severe gastroesophageal reflux (p less than 0.01). VIP values in patients with moderate reflux were not significantly different from those observed in our volunteers. There was a significant correlation between LES pressure and VIP plasma level (r = -0.9253; p less than 0.01). In conclusion, it is possible that the decreased LES resting pressure observed in patients with Barrett's esophagus and severe gastroesophageal reflux may be due to impairment of the VIPergic innervation, resulting in an increased local VIP release with possible overflow to peripheral plasma.

A model for group intervention with preschool children experiencing separation and divorce.

A six-session group program model is described. It is designed to facilitate the adjustment of preschoolers to separation and divorce of parents. Goals are specified and the plan of each group session outlined. Some preliminary observations regarding outcome are discussed.

Cloning in Bacillus subtilis of an extremely thermostable alpha amylase: comparison with other cloned heatstable alpha amylases.

A heatstable alpha amylase gene was shotgun cloned from Bacillus licheniformis RPO1 into Bacillus subtilis. Restriction endonuclease analysis of the recombinant plasmid revealed a map which was identical to a previously cloned alpha amylase from B. licheniformis FDO2 and very similar to the restriction map of a high temperature amylase from Bacillus coagulans. The thermostability and temperature optimum of the cloned alpha amylase was measureably different from those of the previously reported cloned alpha amylases.