"I must do this!": A latent profile analysis approach to understanding the role of irrational beliefs and motivation regulation in mental and physical health.

In the research concerning rational emotive behaviour therapy (REBT) in sport and exercise, irrational beliefs are proposed as a risk factor for health. Concurrent to this, researchers have also indicated that autonomous and controlled motivation, as proposed in organismic integration theory could, together with irrational beliefs, determine individual health. However, research is yet to align irrational beliefs and motivation, and explore how this alignment relates to mental health. The present two study paper identifies individual subgroups, drawn from data concerning irrational beliefs, motivation, and health (psychological distress, and physical health), in a sample of exercisers (study 1) and student athletes (study 2). We examined the latent profile structure of irrational beliefs and motivation, and how these latent profiles relate to psychological distress (studies 1 and 2), and physical health (study 2). Results indicate a two class profile whereby class 1 is characterised by high irrational beliefs, low self-determined motivation, and poor health outcomes. Class 2 is characterised by low irrational beliefs, high self-determined motivation, and better health outcomes. The findings are discussed in relation to the theoretical implications for REBT and organismic integration theory, and the practical implications for key stakeholders in the health of exercise participants and athletes.

The Protective Role of 1,8-Dihydroxynaphthalene-Melanin on Conidia of the Opportunistic Human Pathogen Aspergillus fumigatus Revisited: No Role in Protection against Hydrogen Peroxide and Superoxides.

Previously, 1,8-dihydroxynaphthalene (DHN)-melanin was described to protect Aspergillus fumigatus against hydrogen peroxide (H2O2), thereby protecting this opportunistic human pathogen from reactive oxygen species generated by the immune system. This was based on the finding that the ATCC 46645 mutant with mutations in the pksP gene of the DHN-melanin synthesis pathway showed increased sensitivity to reactive oxygen species compared to the wild type. Here, it is shown that deletion of the pksP gene in A. fumigatus strain CEA10 did not affect sensitivity for H2O2 and superoxide in a plate stress assay. In addition, direct exposure of the dormant white conidia of the pksP deletion strains to H2O2 did not result in increased sensitivity. Moreover, complementation of the ATCC 46645 pksP mutant strain with the wild-type pksP gene did result in pigmented conidia but did not rescue the H2O2-sensitive phenotype observed in the plate stress assay. Genome sequencing of the ATCC 46645 pksP mutant strain and its complemented strain revealed a mutation in the cat1 gene, likely due to the UV mutagenesis procedure used previously, which could explain the increased sensitivity toward H2O2. In summary, DHN-melanin is not involved in protection against H2O2 or superoxide and, thus, has no role in survival of conidia when attacked by these reactive oxygen species. IMPORTANCE Opportunistic pathogens like Aspergillus fumigatus have strategies to protect themselves against reactive oxygen species like hydrogen peroxides and superoxides that are produced by immune cells. DHN-melanin is the green pigment on conidia of Aspergillus fumigatus and more than 2 decades ago was reported to protect conidia against hydrogen peroxide. Here, we correct this misinterpretation by showing that DHN-melanin actually is not involved in protection of conidia against hydrogen peroxide. We show that UV mutagenesis that was previously used to select a pksP mutant generated many more genome-wide mutations. We discovered that a mutation in the mycelial catalase gene cat1 could explain the observed phenotype of increased hydrogen peroxide sensitivity. Our work shows that UV mutagenesis is not the preferred methodology to be used for generating mutants. It requires genome sequencing with single-nucleotide polymorphism analysis as well as additional validations to discard unwanted and confirm correct phenotypes.

Differential localization of A-Raf regulates MST2-mediated apoptosis during epithelial differentiation.

A-Raf belongs to the family of oncogenic Raf kinases that are involved in mitogenic signaling by activating the MEK-ERK pathway. Low kinase activity of A-Raf toward MEK suggested that A-Raf might have alternative functions. We recently identified A-Raf as a potent inhibitor of the proapoptotic mammalian sterile 20-like kinase (MST2) tumor suppressor pathway in several cancer entities including head and neck, colon, and breast. Independent of kinase activity, A-Raf binds to MST2 thereby efficiently inhibiting apoptosis. Here, we show that the interaction of A-Raf with the MST2 pathway is regulated by subcellular compartmentalization. Although in proliferating normal cells and tumor cells A-Raf localizes to the mitochondria, differentiated non-carcinogenic cells of head and neck epithelia, which express A-Raf at the plasma membrane. The constitutive or induced re-localization of A-Raf to the plasma membrane compromises its ability to efficiently sequester and inactivate MST2, thus rendering cells susceptible to apoptosis. Physiologically, A-Raf re-localizes to the plasma membrane upon epithelial differentiation in vivo. This re-distribution is regulated by the scaffold protein kinase suppressor of Ras 2 (KSR2). Downregulation of KSR2 during mammary epithelial cell differentiation or siRNA-mediated knockdown re-localizes A-Raf to the plasma membrane causing the release of MST2. By using the MCF7 cell differentiation system, we could demonstrate that overexpression of A-Raf in MCF7 cells, which induces differentiation. Our findings offer a new paradigm to understand how differential localization of Raf complexes affects diverse signaling functions in normal cells and carcinomas.

Basis for the development of sustainable optimisation indicators for activated sludge wastewater treatment plants in the Republic of Ireland.

This paper describes the basis of a stakeholder-based sustainable optimisation indicator (SOI) system to be developed for small-to-medium sized activated sludge (AS) wastewater treatment plants (WwTPs) in the Republic of Ireland (ROI). Key technical publications relating to best practice plant operation, performance audits and optimisation, and indicator and benchmarking systems for wastewater services are identified. Optimisation studies were developed at a number of Irish AS WwTPs and key findings are presented. A national AS WwTP manager/operator survey was carried out to verify the applied operational findings and identify the key operator stakeholder requirements for this proposed SOI system. It was found that most plants require more consistent operational data-based decision-making, monitoring and communication structures to facilitate optimised, sustainable and continuous performance improvement. The applied optimisation and stakeholder consultation phases form the basis of the proposed stakeholder-based SOI system. This system will allow for continuous monitoring and rating of plant performance, facilitate optimised operation and encourage the prioritisation of performance improvement through tracking key operational metrics. Plant optimisation has become a major focus due to the transfer of all ROI water services to a national water utility from individual local authorities and the implementation of the EU Water Framework Directive.

Changes in sexual inhibition and excitation during PDE5I therapy.

The aim of this longitudinal study was to assess possible changes in sexual inhibition and excitation (measured using the Sexual Inhibition and Sexual Excitation Scales (SIS/SES)) in men being treated with PDE5 inhibitors (PDE5I) for ED. Established PDE5I users diagnosed with psychogenic ED completed the SES/SIS questionnaire at recruitment and 3 months later. On the basis of International Index of Erectile Function scores at recruitment, subjects were divided into two groups - mildly affected (M) and mild-to-moderately affected (MM). SES scores were significantly lower, and SIS1 scores were significantly higher in Group MM at recruitment and at 3 months (P<0.001). In Group M, SES scores increased (P<0.005) and SIS1 (P<0.001) and SIS2 (P=0.01) scores decreased over the 3 months of the study. In Group MM, ongoing decreases in SES and increases in SIS1 scores were observed (P<0.001). The results of multiple linear regression showed that SIS/SES variables were of little value in predicting erectile function (EF) at recruitment, or changes in EF during the study period. The results for Group M showed that men whose EF scores increased were more likely to experience increased SIS2 and decreased SES scores.

Identification of patients with low-risk pulmonary embolism suitable for outpatient treatment using the pulmonary embolism severity index (PESI).

BACKGROUND: There is increasing evidence that outpatient treatment of patients with low-risk stable pulmonary embolism (PE) is safe, effective and potentially reduces costs. It is not clear how many patients presenting to an Irish Emergency Department (ED) are potentially suitable for outpatient management. AIMS: To identify how many patients presenting to our ED over a 1-year period who were diagnosed with acute PE are potentially suitable for outpatient treatment. METHODS: A retrospective observational study was conducted over a 1-year period. Clinical notes for patients who had a positive computed tomographic pulmonary angiogram (CTPA) within 24 h of presentation to the ED were examined to risk stratify the patients according to the pulmonary embolism severity index (PESI). RESULTS: Forty-seven patients who presented to our ED were diagnosed with a PE. Clinical notes were missing for 3 cases, and 44 cases were analysed further. The mean age was 64.3 (±16.8 SD) years and 24 (54.5 %, 95 % CI 40-68.3 %) were males. Six patients (13.6 %, 95 % CI 6.4-26.7 %) had a background of cancer. Fifteen cases (34.1 %, 95 % CI 21.9-48.7 %) were deemed to be low risk as they were categorised as PESI risk class I or II. Our study found that 61/420 (14.5 %, 95 % CI 11.5-18.2) of CTPAs done were positive for PE. CONCLUSION: This study suggests that a significant percentage of patients diagnosed with acute PE are low risk as per PESI and therefore potentially suitable for outpatient management.

4-Methylumbelliferone inhibits tumour cell growth and the activation of stromal hyaluronan synthesis by melanoma cell-derived factors.

BACKGROUND: There is a close correlation between tumour progression and hyaluronan production, either by tumour cells or by stromal cells that are stimulated by tumour-derived factors. Inhibition of tumour stimulation of fibroblast hyaluronan may suppress tumour growth and invasion. OBJECTIVES: To examine the effect of the hyaluronan synthesis inhibitor 4-methylumbelliferone (4-MU) on the growth of and hyaluronan synthesis by fibroblasts and C8161 and MV3 melanoma cell lines, invasion, and inhibition of tumour cell-derived factor activation of fibroblasts. METHODS: Effects of 4-MU on growth and hyaluronan synthesis by fibroblasts and melanoma cells were examined in monolayer culture and fibroblast-contracted collagen lattices, and their effects on the growth and invasion of tumour cells into collagen lattices were also studied. RESULTS: 4-MU caused a dose-dependent growth inhibition of fibroblast and melanoma cells with maximum inhibition at 0·5 mmol L(-1) 4-MU. At this dose, 4-MU inhibited (3) H-glucosamine incorporation into fibroblast glycosaminoglycans by 52%, and hyaluronan synthesis by 64%. The relative inhibition was more pronounced when fibroblasts were stimulated with C8161 melanoma cell-conditioned medium. 4-MU reduced the level of hyaluronan in fibroblast-contracted collagen lattices, and inhibited both the growth on and invasion into the lattices by melanoma cells. This growth inhibition appears to be predominantly independent of inhibition of hyaluronan synthesis. The effect on growth inhibition was reversible, and 4-MU had no effect on apoptosis. CONCLUSIONS: 4-MU is a potent inhibitor of hyaluronan synthesis, induction of stromal hyaluronan accumulation by tumour cells, and fibroblast and melanoma cell proliferation, and results suggest that 4-MU may have potential as a tumour cell anti-invasive and antiproliferative agent.

Expression of p16, CD95, CD95L and Helix pomatia agglutinin in relapsing and nonrelapsing very thin melanoma.

BACKGROUND: The incidence of malignant melanoma is increasing worldwide and patients are being diagnosed earlier with thinner primary lesions. Most patients with very thin melanoma (Breslow thickness < 0.76 mm) are cured by surgery but 2-18% relapse locally or with distant metastases. OBJECTIVES: The objective of this study was to establish potential new prognostic markers in very thin melanoma. METHODS: We identified a group of subjects with relapsing very thin primary cutaneous melanoma and a matched control group who had not relapsed. We investigated the expression of p16, Helix pomatia agglutinin (HPA), CD95 and CD95 ligand (CD95L) by immunohistochemistry on paraffin-embedded tissue sections from the subject group, their subsequent metastases and the control group. RESULTS: Reduced p16 expression was significantly associated with relapse in very thin melanoma (P = 0.0129). Loss of p16 expression was also found in 76% of metastases. There was no significant association between HPA, CD95 or CD95L expression and subsequent relapse. CONCLUSIONS: This work is the first to show a significant loss of p16 in relapsing very thin melanoma.

Outbreak of Legionnaires' disease on a cruise ship: lessons for international surveillance and control.

A sporadic case of Legionnaires' disease was linked to travel on a cruise ship. Investigation identified two further cases of Legionnaires' Disease and one case of non-pneumonic Legionella infection. An Incident Team confirmed the source to be the ship's water system and control measures were instituted that included pasteurisation, super chlorination and chlorine dioxide dosing. The Public Health Laboratory Service (PHLS) Communicable Disease Surveillance Centre (CDSC), through the European Surveillance Scheme for Travel Associated Legionnaires' Disease, identified three previous cases associated with the same ship's water system including one fatality. Lessons for the international surveillance and control of Legionnaires' disease on cruise ships are discussed.

Expression of respiratory mucins in fatal status asthmaticus and mild asthma.

AIMS: The airways of patients with asthma are characterized by chronic inflammatory changes comprising mainly T-cells and eosinophils, and airway remodelling with goblet cell metaplasia and submucosal gland hyperplasia. Mucus hypersecretion is often a marked feature, particularly in status asthmaticus. The matrix of airway sputum consists of high molecular glycoproteins and mucins. In this study, the expression and distribution of the major gel-forming mucins MUC5AC and MUC5B were studied in fatal status asthmaticus tissues and bronchial biopsies of mild asthmatic patients. The effect of inhaled corticosteroids on the expression of these mucins was also investigated. METHODS AND RESULTS: Polyclonal antibodies specific for MUC5AC and MUC5B, and a monoclonal antibody for MUC5B were used to stain lung tissues and airway mucosal biopsies obtained from patients who died of status asthmaticus (n=5) and from mild asthmatics (n=4), respectively. Immunohistochemistry for MUC5AC revealed abundant staining of goblet cells situated in the epithelial surface lining and glandular ducts of tissues from patients with fatal asthma. MUC5B immunoreactivity was restricted to mucous cells of submucosal glands and to epithelial cells. In mild asthmatics, large amounts of MUC5B, but not MUC5AC, positive extracellular mucus was found in the airway lumen as plugs, adjacent to the epithelial lining and in the necks of glandular secretory ducts of mild asthmatics. The distribution of MUC5AC and MUC5B in bronchial biopsies of mild asthmatics was similar before and after inhaled steroid treatment. CONCLUSIONS: The expression of MUC5AC and MUC5B shares a similar distribution to normal airways in different states of asthma. The distribution is not affected by topical corticosteroid therapy.

Cocaine/heroin induced rhabdomyolysis and ventricular fibrillation.

A case of cardiorespiratory arrest in a 28 year old man after cocaine and heroin ingestion is described. The arrest is attributed primarily to hyperkalaemia/rhabdomyolysis-a recognised consequence of each of these drugs. The administration of naloxone may have been contributory. He developed acute renal failure, disseminated intravascular coagulopathy with consequent lower limb compartment syndrome requiring fasciotomy. Ventricular fibrillation was identified at thoracotomy.

Specialist alcohol liaison services in general hospitals improve engagement in alcohol rehabilitation and treatment outcome.

OBJECTIVE: To examine the impact of providing a specialist addictions trained psychiatric nurse on outcome of alcohol treatment in patients presenting to general medical and surgical wards of a district general hospital. Before introducing the specialist alcohol liaison service, a range of staff including a consultant liaison psychiatrist, junior psychiatrists and community psychiatric nurses trained in liaison psychiatry assessed this patient group. METHOD: A retrospective review of all alcohol liaison referrals with ICD-10 defined alcohol misuse was performed for one year. Comparison data for the first 100 referrals to the specialist alcohol liaison service were obtained prospectively. Indicators included diagnosis at referral, and engagement in and completion of alcohol rehabilitation. RESULTS: The rates of completion of a four to six week period of alcohol rehabilitation were significantly better after introduction of the Specialist Alcohol Liaison Service. Of those who commenced alcohol rehabilitation, 88% completed, compared to 40% in the traditional assessment service (p < 0.0001). CONCLUSION: Specialist addictions trained staff in the assessment and management of alcohol dependent patients in medical and surgical wards produce a better immediate outcome than their non-specialist colleagues. This may have implications for service design.

One-year effects of increasingly fat-restricted, carbohydrate-enriched diets on lipoprotein levels in free-living subjects.

Restriction of all dietary fat is a popular strategy for restricting saturated fat intake to lower LDL cholesterol. Some authorities advise the restriction of fat intake to the extreme of less than 10% of daily energy on the assumption that more fat restriction is better. The two studies described herein address questions relating to whether increasing fat restriction produces proportionally increasing benefit on cardiovascular risk factors in hyperlipidemic subjects. The first study is the Dietary Alternatives Study (DAS). The DAS was conducted in 531 male Boeing employees over a 2-year period. Subjects were defined as hypercholesterolemic (HC) or combined hyperlipidemic (CHL) based on age-specific 75th percentiles for plasma LDL-C and triglyceride levels. Hypothesis test analyses were performed at 1 year. HC subjects were randomized to diets taught to attain fat intakes of 30, 26, 22, and 18% (Diets levels 1-4, respectively). CHL subjects (slightly fewer in number) were randomized to Diets 1-3. After 1 year, subjects' total fat intakes were 27, 26, 25, and 22% of energy (en%), resulting in saturated fat intakes of 8, 7, 7, and 6%, respectively. In HC subjects the greatest LDL-C decrease was with Diet 2 (mean of 13.4%) and in CHL subjects with Diet 1 (7.0%). Surprisingly, plasma triglyceride concentrations rose in HC subjects 20% and 40% above baseline on Diets 3 and 4, respectively, with reciprocal reductions in HDL cholesterol of 2.5% and 3%, respectively. Furthermore, apo B reductions were attenuated below Diet 2 in HC subjects and Diet 1 in CHL subjects, and no further reductions were seen in plasma glucose and insulin concentrations, blood pressure, or body weight. Measurements of plasma total fatty acid composition showed a slight increase in plasma palmitate, whereas stearate decreased slightly, supporting the idea that de novo synthesis of palmitic acid was increased in the chronic high-carbohydrate feeding condition. The second study asked if the most effective diet in HC subjects, Diet 2, has an equivalent effect in women and men. To answer this question, men and women Boeing employees were taught the closely similar National Cholesterol Education Program (NCEP) Step II diet. After 6 and 12 months, equivalent reductions in LDL cholesterol were observed in women compared with men. HDL cholesterol levels in men were unchanged from baseline at 6 and 12 months, but were reduced 8% in HC women, with accompanying decreases of 18% in HDL2-cholesterol and 5% in apoprotein A-I (all P < 0.01). These data indicate that intakes of fat below about 25 en% and carbohydrate intake above approximately 60 en% yield no further LDL-C lowering in HC and CHL male subjects and can be counterproductive to triglyceride, HDL-C, and apo B levels. This lack of benefit appears to be explained by an enhanced endogenous synthesis of palmitic acid, which negates the benefit of further saturated fat restriction. The HDL-C decrease in HC women may have a similar cause and points to an underlying male-female difference. Alternative dietary approaches to limit saturated fat intake deserve intensive study.

Discriminant validity of the Wender Utah Rating Scale for attention-deficit/hyperactivity disorder in adults.

The authors examined the factor structure and discriminant validity of the Wender Utah Rating Scale (WURS) in adults seeking evaluation for attention-deficit/hyperactivity disorder (ADHD). Three factors (Dysthymia, Oppositional/Defiant Behavior, and School Problems) accounted for 59.4% of the variance. In a stepwise discriminant function analysis, age and childhood school problems emerged as significant variables. The classification procedure correctly classified 64.5% of patients. Among those who did not have ADHD, only 57.5% were correctly classified compared with 72.1% among those with ADHD. The WURS is sensitive in detecting ADHD, but it misclassifies approximately half of those who do not have ADHD.

Motherhood in the teens and twenties: some surprises.

We report a study of the association of health and social support variables with motherhood in teenagers and older mothers. Both teenage and older mothers reported poorer physical and mental health and fewer and less frequent social contacts than their nulliparous peers. Contrary to expectation, however, older mothers reported less extensive and less adequate social support networks than did teenagers.

Reliability and validity of screening instruments for drug and alcohol abuse in adults seeking evaluation for attention-deficit/hyperactivity disorder.

A growing number of adults are seeking evaluation for Attention-Deficit/Hyperactivity Disorder (ADHD). Screening for substance use disorders should be included as part of any comprehensive ADHD evaluation. We describe the validity and reliability of the Drug Abuse Screening Test (DAST) and the Alcohol Use Disorders Identification Test (AUDIT) in adults seeking evaluation for ADHD. Internal reliability estimates were excellent for both instruments. Scores on the DAST and AUDIT were higher among patients with a DSM-IV diagnosis of current drug abuse or dependence or current alcohol abuse or dependence, respectively. A cutoff score of 6 or above appears to be optimal for identifying individuals who are current drug abusers. A cutoff score of 6 or above on the AUDIT is suggested for detection of current alcohol abuse in this population. Comparable rates of substance use disorders were observed in ADHD and non-ADHD patients. Both measures are valid and reliable instruments for screening for alcohol and drug abuse among adults seeking evaluation for ADHD.

Differential effect of National Cholesterol Education Program (NCEP) Step II diet on HDL cholesterol, its subfractions, and apoprotein A-I levels in hypercholesterolemic women and men after 1 year: the beFIT Study.

We previously reported that high density lipoprotein cholesterol (HDL-C) decreases more in hypercholesterolemic (HC) women than in HC men ingesting an National Cholesterol Education Program (NCEP) Step II diet for 6 months. We examined these subjects to determine whether the differential HDL-C reduction persists after 12 months and whether it is associated with decreased HDL(2)-C and apoprotein A-I. Subjects were screened from an industrial workforce and were defined as HC if 2 low density lipoprotein cholesterol measurements were >/=75th percentile or defined as combined hyperlipidemic (CHL) if triglycerides were also >/=75th percentile. The subjects were then taught the NCEP Step II diet in 8 weekly classes and counseled quarterly. Seventy-three HC and 92 CHL women (mean ages 43 and 44 years, respectively) and 112 HC and 106 CHL men (ages 45 and 41 years, respectively) were studied. All groups reported similar total fat (24% to 26% kcal) and saturated fat (7.1% to 7.9% kcal) intakes at 1 year. HDL-C decreased 7.6% in HC women (P<0.01), exceeding the nonsignificant 1.3% decrease in HC men (P=0.000). HDL(2)-C decreased 16.7% in HC women (P<0.01) compared with the nonsignificant 0.5% increase in HC men (P=0.000). In CHL women and men, HDL-C decreased 3.5% and 3.9% (both P<0.01); HDL(2)-C decreased more in women (7.1%, P<0.01) than in men (4.3%, a nonsignificant difference). Apoprotein A-I decreased significantly (5.3%, P<0.01) in HC women only. Plasma triglycerides were unchanged. Low density lipoprotein cholesterol and weight changes were not different among the 4 groups. HDL-C, HDL(2)-C, and apoprotein A-I levels decreased more in HC women than in HC men after following the NCEP Step II diet for 1 year, continuing a trend observed with HDL-C at 6 months. The total HDL-C and HDL(2)-C reductions narrow the baseline differences between men and women by 50%. Whether this reduction impacts women's protection from cardiovascular disease deserves future study. Nonetheless, the results point to sex-based differences in intrahepatic glucose and fatty acid metabolism linked to alterations in HDL formation and removal.