Baseline characteristics and comorbidities in the CAnadian REgistry for Pulmonary Fibrosis.

BACKGROUND: The CAnadian REgistry for Pulmonary Fibrosis (CARE-PF) is a multi-center, prospective registry designed to study the natural history of fibrotic interstitial lung disease (ILD) in adults. The aim of this cross-sectional sub-study was to describe the baseline characteristics, risk factors, and comorbidities of patients enrolled in CARE-PF to date. METHODS: Patients completed study questionnaires and clinical measurements at enrollment and each follow-up visit. Environmental exposures were assessed by patient self-report and comorbidities by the Charlson Comorbidity Index (CCI). Baseline characteristics, exposures, and comorbidities were described for the overall study population and for incident cases, and were compared across ILD subtypes. RESULTS: The full cohort included 1285 patients with ILD (961 incident cases (74.8%)). Diagnoses included connective tissue disease-associated ILD (33.3%), idiopathic pulmonary fibrosis (IPF) (24.7%), unclassifiable ILD (22.3%), chronic hypersensitivity pneumonitis (HP) (7.5%), sarcoidosis (3.2%), non-IPF idiopathic interstitial pneumonias (3.0%, including idiopathic nonspecific interstitial pneumonia (NSIP) in 0.9%), and other ILDs (6.0%). Patient-reported exposures were most frequent amongst chronic HP, but common across all ILD subtypes. The CCI was ≤2 in 81% of patients, with a narrow distribution and range of values. CONCLUSIONS: CTD-ILD, IPF, and unclassifiable ILD made up 80% of ILD diagnoses at ILD referral centers in Canada, while idiopathic NSIP was rare when adhering to recommended diagnostic criteria. CCI had a very narrow distribution across our cohort suggesting it may be a poor discriminator in assessing the impact of comorbidities on patients with ILD.

Paediatric dentistry education of atraumatic restorative treatment (ART) in Brazilian dental schools.

AIM: To evaluate the degree of knowledge, use and teaching of atraumatic restorative treatment (ART) of paediatric dentistry lecturers in dental schools throughout Brazil. METHODS: A structured questionnaire was applied, containing questions regarding the use of ART, socio-demographic characteristics and academic degree background. Descriptive analysis and Poisson's regression were conducted in order to verify the association between exploratory variables and ART teaching (α=5%). RESULTS: Of the 721 questionnaires sent to dental schools, approximately 40% were returned (n=285). Some 98.2% of the participants teach ART. STATISTICS: Concerning dental lecturers who teach ART, in multiple regression model, considering ART indication (emergency versus restorative treatment) the lecturers residents of the Mid-West (PR=1.66; CI:1.13-2.45) and Northeast region (PR=1.33; CI:1.02-1.72) and lecturers who use ART regularly (PR=3.73; CI:2.11-5.59) teach ART as restorative treatment. When the question was about reason for using ART (conservative technique versus other techniques failures/fast treatment), lecturers with a longer period of TG (time elapsed since graduation) (PR=1.30; CI:1.08- 1.56) and also lecturers who use ART regularly (PR=2.87; CI:1.95-4.22), teach it as being a conservative technique. Regarding the patients' age covered by ART (versus without limitation), women (PR=1.26; CI:1.06-1.50) and lecturers who use ART regularly (PR=1.28; CI:1.06-1.54), teach that there is no age restriction. CONCLUSIONS: ART has been widely taught in Brazilian dental schools, is regularly used in lecturer's clinical practices and has positively influenced the appropriate teaching of this technique.

5-hydroxytryptamine signalling in irritable bowel syndrome with diarrhoea: effects of gender and menstrual status.

BACKGROUND: Symptomatology and physiology differ between men and women and across the menstrual cycle in irritable bowel syndrome (IBS). Ovarian hormones influence 5-hydroxytryptamine (5-HT), an amine known to play a role in gut motor-sensory function. AIM: To assess the effects of gender and menstrual status on platelet-depleted plasma (PDP) 5-HT concentration in IBS patients with diarrhoea (IBS-D) patients compared with healthy volunteers (HV). METHODS: Platelet-depleted plasma 5-HT concentrations were assessed under fasting and fed conditions in 73 IBS-D patients (aged 18-58 years; 18 men) and 64 HV (aged 18-50 years; 24 men). Women were divided into those with low or high progesterone/oestrogen (P/O) levels. RESULTS: Irritable bowel syndrome patients with diarrhoea had higher PDP 5-HT concentrations than HV under fasting (P = 0.002) and fed (P = 0.049) conditions. This was particularly related to IBS-D men having higher PDP 5-HT concentrations than healthy controls (P = 0.002). Moreover, PDP 5-HT concentrations in IBS-D women with low P/O levels were similar to healthy controls. CONCLUSIONS: Similar to IBS-D women with high P/O levels, IBS-D men also have raised PDP 5-HT concentrations. 5-HT concentration normalizes at menses in IBS-D women, suggesting a shift in the mechanisms responsible for abnormal 5-HT signalling in these patients.

Sex differences in physiological progression of idiopathic pulmonary fibrosis.

In idiopathic pulmonary fibrosis, incidence is higher in males, and females may have better survival. The aim of the present study was to determine whether the rate of increase in desaturation during serial 6-min walk testing would be greater, and survival worse, for males versus females. Serial changes in the percentage of maximum desaturation area (DA) over 1 yr were estimated using mixed models in 215 patients. DA was defined as the total area above the curve created using desaturation percentage values observed during each minute of the 6-min walk test. Multivariate Cox regression assessed survival differences. Adjusting for baseline DA, 6-min walk distance, change in 6-min walk distance over time and smoking history, the percentage of maximum DA increased by an average of 2.83 and 1.37% per month for males and females, respectively. Females demonstrated better survival overall, which was more pronounced in patients who did not desaturate below 88% on ambulation at baseline and after additionally adjusting for 6-month relative changes in DA and forced vital capacity. These data suggest that differences in disease progression contribute to, but do not completely explain, better survival of females with idiopathic pulmonary fibrosis.

Effect of the NK(3) receptor antagonist, talnetant, on rectal sensory function and compliance in healthy humans.

Visceral hypersensitivity is important in the pathophysiology of irritable bowel syndrome and thus a target for modulation in drug development. Neurokinin (NK) receptors, including NK(3) receptors, are expressed in the motor and sensory systems of the digestive tract. The aim of this study was to compare the effects of two different doses (25 and 100 mg) of the NK(3) receptor antagonist, talnetant (SB223412) with placebo on rectal sensory function and compliance in healthy volunteers studied at two centres. Rectal barostat tests were performed on 102 healthy volunteers, randomized to receive either oral talnetant 25 or 100 mg or placebo over 14-17 days. Studies were performed on three occasions: day 1 immediately prior to 1st dose, day 1 4 h postdose, and after 14- to17-day therapy. Compliance, and pressure thresholds for first sensation, urgency, discomfort and pain were measured using ascending method of limits, and sensory intensity ratings for gas, urgency, discomfort and pain determined during four random phasic distensions (12, 24, 36 and 48 mmHg). Talnetant had no effect on rectal compliance, sensory thresholds or intensity ratings compared with placebo. In general, the results obtained at the two centres differed minimally, with intensity scores at one centre consistently somewhat lower. At the doses tested, talnetant has no effect on rectal compliance or distension-induced rectal sensation in healthy participants.

Investigation of the photochemistry of the poly{p-phenylenevinylene} precursor system: implications for nanolithography.

The photochemistry of poly{p-phenylene[1-(tetrahydrothiophen-1-io)ethylene chloride]} (PPTEC), a water soluble precursor of the semiconducting polymer, poly{p-phenylenevinylene} (PPV), has been studied both under atmospheric conditions and in environments devoid of oxygen. UV-visible spectroscopy and photoluminescence data has been used to provide a picture of the mechanistic pathways involved in UV irradiation of the PPTEC material. A new quantitative model for the effect of UV irradiation upon film morphology is presented, which leads to insights for the improved control of the characteristics of PPV nanostructures produced via near-field scanning optical lithography.

Effect of a second-generation alpha2delta ligand (pregabalin) on visceral sensation in hypersensitive patients with irritable bowel syndrome.

BACKGROUND: Visceral hypersensitivity is an important pathophysiological factor in irritable bowel syndrome (IBS). Pre-clinical studies suggest that the alpha(2)delta ligand pregabalin reduces both visceral allodynia and hyperalgesia, but is inactive on basal sensitivity. AIM: To assess the effect of pregabalin on the perception of rectal distension in hypersensitive IBS patients. METHODS: Twenty-six patients with Rome-II-defined IBS (aged 18-46 years, 7 male) were included in a randomized, double-blind, placebo-controlled, parallel-group study in which they received either 3 weeks oral pregabalin (titrated: 50 mg tid days 1-3, 100 mg tid days 4-7, 150 mg tid days 8-11; fixed 200 mg tid days 12-21 +/-4) or placebo control. Rectal sensitivity was assessed using a barostat technique, in which sensory thresholds were determined using the ascending method of limits, followed by tracking both before and after treatment. Only patients with a pain threshold of

Barostat testing of rectal sensation and compliance in humans: comparison of results across two centres and overall reproducibility.

We assessed reproducibility of measurements of rectal compliance and sensation in health in studies conducted at two centres. We estimated samples size necessary to show clinically meaningful changes in future studies. We performed rectal barostat tests three times (day 1, day 1 after 4 h and 14-17 days later) in 34 healthy participants. We measured compliance and pressure thresholds for first sensation, urgency, discomfort and pain using ascending method of limits and symptom ratings for gas, urgency, discomfort and pain during four phasic distensions (12, 24, 36 and 48 mmHg) in random order. Results obtained at the two centres differed minimally. Reproducibility of sensory end points varies with type of sensation, pressure level and method of distension. Pressure threshold for pain and sensory ratings for non-painful sensations at 36 and 48 mmHg distension were most reproducible in the two centres. Sample size calculations suggested that crossover design is preferable in therapeutic trials: for each dose of medication tested, a sample of 21 should be sufficient to demonstrate 30% changes in all sensory thresholds and almost all sensory ratings. We conclude that reproducibility varies with sensation type, pressure level and distension method, but in a two-centre study, differences in observed results of sensation are minimal and pressure threshold for pain and sensory ratings at 36-48 mmHg of distension are reproducible.

Hand washing. Simple, cost effective, evidence based ... lip service!

Hand washing is so simple that we teach our toddlers to do it. It's so important in our every day lives that facilities for hand washing can be found in every conceivable environment. Scientists, literature and the media give evidence on the benefits and in the art of good techniques. So why, in an environment where the management of infection is a matter of health and safety for all, is hand washing so low on our ever-growing list of priorities? This article examines the legal and moral issues of hand washing in relation to health and safety, concentrating on possible reasons for non-compliance and how these can be addressed.

Structural aspects of survivors' thinking about the Holocaust.

Videotaped interviews of 30 Holocaust survivors were scored for integrative complexity, the recognition of alternate perspectives or dimensions of a topic ("differentiation") and the joint consideration of several perspectives or dimensions ("integration"). Memories showed decreased differentiation and integration as they moved from pre-war life to the shock and upheaval when organized persecution began. High complexity levels reflected survivors mustering their resources to enhance their chances of survival and successful postwar adaptation. These findings demonstrate the usefulness of quantitative, objective content analytic methods in Holocaust survivor research, add a cognitive dimension to the study of survival during and after extreme situations, and confirm theoretical propositions about decision making and information processing under stress.

Glucose-dependent insulinotropic polypeptide stimulated insulin release from a tumor-derived beta-cell line (beta TC3).

The beta TC3 tumor cell line was examined for the presence of functional glucose-dependent insulinotropic polypeptide (GIP) receptors. Increasing amounts of natural porcine GIP decreased the binding of HPLC-purified [125I]GIP to beta TC3 cells in a concentration-dependent manner. Displacement of GIP was significant at concentrations as low as 500 pM, and the radioligand was fully displaced at 100 nM. GIP(1-30) produced a displacement of [125I]GIP comparable with that produced by GIP(1-42), and glucagon yielded 20% displacement at a concentration of 1 microM but was without effect at 100 mM. Incubation of beta TC3 cells in the presence of glucose concentrations of 2-20 mM yielded a concentration-dependent stimulation of immunoreactive insulin (IRI) release. GIP and glucagon-like peptide-I(7-36) amide (tGLP-I) at concentrations of 1 nM or greater significantly stimulated IRI release in the presence of 2 mM glucose. The threshold glucose concentration for GIP-stimulated IRI release from beta TC3 cells was 0.5 mM, and maximal potentiation of IRI release by GIP occurred at 5 mM glucose. Somatostatin significantly inhibited GIP-stimulated IRI release in the presence of 5 mM glucose. It is concluded that beta TC3 cells have functional GIP receptors and may provide a useful model for the study of IRI secretion at the cellular level.

Blockade by phentolamine of induced inotropic responses in the canine heart in vivo.

Positive inotropic responses, measured as increases in the maximum derivative of left ventricular pressure (dP/dt), were induced by carotid artery occlusion (CAR), intravenous norepinephrine (NOR), or intravenous isoproterenol (ISO) in the canine heart in vivo. NOR and ISO also increased peak ascending flow velocity (V max). ISO increased heart rat (HR), while NOR and CAR produced comparatively little chronotropic response. Phentolamine (1 mg/kg) considerably reduced induced increases in dP/dt, Vmax and HR, while the same dose of propranolol almost completely abolished such increases. The results indicate that phentolamine, and alpha-adrenergic blocking drug, does have and ability to partially block induced positive inotropic responses in the canine heart, and perhaps chronotropic responses as well, although propranolol, a beta-blocker, is more effective. the results are in accord with the view that the principal cardiac adrenergic receptors are not adequately described either as classical beta- or alpha-adrenergic receptors.