PUM1 and PGK1 are Favorable Housekeeping Genes over Established Biodosimetry-related Housekeeping Genes such as HPRT1, ITFG1, DPM1, MRPS5, 18S rRNA and Others after Radiation Exposure.

In gene expression (GE) studies, housekeeping genes (HKGs) are required for normalization purposes. In large-scale inter-laboratory comparison studies, significant differences in dose estimates are reported and divergent HKGs are employed by the teams. Among them, the 18S rRNA HKG is known for its robustness. However, the high abundance of 18S rRNA copy numbers requires dilution, which is time-consuming and a possible source of errors. This study was conducted to identify the most promising HKGs showing the least radiation-induced GE variance after radiation exposure. In the screening stage of this study, 35 HKGs were analyzed. This included selected HKGs (ITFG1, MRPS5, and DPM1) used in large-scale biodosimetry studies which were not covered on an additionally employed pre-designed 96-well platform comprising another 32 HKGs used for different exposures. Altogether 41 samples were examined, including 27 ex vivo X-ray irradiated blood samples (0, 0.5, 4 Gy), six X-irradiated samples (0, 0.5, 5 Gy) from two cell lines (U118, A549), as well as eight non-irradiated tissue samples to encompass multiple biological entities. In the independent validation stage, the most suitable candidate genes were examined from another 257 blood samples, taking advantage of already stored material originating from three studies. These comprise 100 blood samples from ex vivo X-ray irradiated (0-4 Gy) healthy donors, 68 blood samples from 5.8 Gy irradiated (cobalt-60) Rhesus macaques (RM) (LD29/60) collected 0-60 days postirradiation, and 89 blood samples from chemotherapy-(CTx) treated breast tumor patients. CTx and radiation-induced GE changes in previous studies appeared comparable. RNA was isolated, converted into cDNA, and GE was quantified employing TaqMan assays and quantitative RT-PCR. We calculated the standard deviation (SD) and the interquartile range (IQR) as measures of GE variance using raw cycle threshold (Ct) values and ranked the HKGs accordingly. Dose, time, age, and sex-dependent GE changes were examined employing the parametrical t-test and non-parametrical Kruskal Wallis test, as well as linear regression analysis. Generally, similar ranking results evolved using either SD or IQR GE measures of variance, indicating a tight distribution of GE values. PUM1 and PGK1 showed the lowest variance among the first ten most suitable genes in the screening phase. MRPL19 revealed low variance among the first ten most suitable genes in the screening phase only for blood and cells, but certain comparisons indicated a weak association of MRPL19 with dose (P = 0.02-0.09). In the validation phase, these results could be confirmed. Here, IQR Ct values from, e.g., X-irradiated blood samples were 0.6 raw Ct values for PUM1 and PGK1, which is considered to represent GE differences as expected due to methodological variance. Overall, when compared, the GE variance of both genes was either comparable or lower compared to 18S rRNA. Compared with the IQR GE values of PUM1 and PGKI, twofold-fivefold increased values were calculated for the biodosimetry HKG HPRT1, and comparable values were calculated for biodosimetry HKGs ITFG1, MRPS5, and DPM1. Significant dose-dependent associations were found for ITFG1 and MRPS5 (P = 0.001-0.07) and widely absent or weak (P = 0.02-0.07) for HPRT1 and DPM1. In summary, PUM1 and PGK1 appeared most promising for radiation exposure studies among the 35 HKGs examined, considering GE variance and adverse associations of GE with dose.

Survey of dental clinic patients: smoking and preferences for cessation support.

BACKGROUND: Smoking cessation interventions delivered by dental practitioners can be as effective as those delivered by general medical practitioners. However, concern that addressing smoking may cause offence to their patients is a reason cited by dental practitioners for not regularly addressing patient smoking behaviours, despite believing they should play a role in smoking cessation. This study aimed to elicit the smoking behaviour and smoking cessation preferences of dental patients to determine if these concerns accurately reflect patient attitudes. METHODS: We surveyed 726 adult dental patients attending The University of Queensland's School of Dentistry dental clinics, Brisbane Dental Hospital and four private dental practices in South-East Queensland. RESULTS: Most (80%) current daily smokers had tried to quit smoking. Smokers and non-smokers both agreed that dentists should screen for smoking behaviour and are qualified to offer smoking cessation advice (99% and 96% respectively). Almost all participants (96%) said they would be comfortable with their dentist asking about their smoking and that if their smoking was affecting their oral health their dentist should advise them to quit. CONCLUSIONS: Patients are receptive to dental practitioners inquiring about smoking behaviour and offering advice on quitting. Smoking patients showed considerable motivation and interest in quitting smoking, particularly in the context of health problems related to smoking being identified. These results should encourage dentists to raise the issue with their patients.

Survey of Australian oral health practitioners and their smoking cessation practices.

BACKGROUND: Smoking is a significant health and economic burden in Australia. Studies of smoking cessation practices in dental settings have primarily concentrated on dentists rather than other oral health practitioner (OHP) groups (dental hygienists, dental therapists and oral health therapists). The aim of this study was to measure Australian OHPs' attitudes, behaviours, interest and barriers to delivering smoking cessation interventions. METHODS: Members of the two peak professional bodies representing Australian OHPs were invited to participate in an anonymous online questionnaire. RESULTS: There were discrepancies between practitioner attitudes and current smoking cessation practices. While the majority of practitioners (90.1%) frequently screened for smoking behaviour, fewer (51.1%) assisted patients to quit smoking. The principal form of assistance was referral to Quitline (45.7%) or to a general medical practitioner (44.4%). The most prevalent barriers identified were lack of knowledge of pharmacological treatments (45.8%) and lack of access to smoking cessation resources (44.2%). Contrary to international studies, time and financial incentive were not commonly cited barriers to delivering smoking cessation interventions. CONCLUSIONS: This survey identifies a need for continuing education in smoking cessation practice. Dissemination of policies, guidelines and resources may assist OHPs to become more engaged and confident in delivering smoking cessation interventions as part of their routine practice.

[Chronic knee pain in children and adolescents: review of anatomical and overload-related knee pain]. / Chronische Knieschmerzen bei Kindern und Jugendlichen : Eine Übersicht über anlage- und überlastungsbedingte Knieschmerzen.

BACKGROUND: Knee pain in children and adolescents is a common reason for presentation in pediatric orthopedic consultation. The causes are manifold and require a thorough patient history, detailed physical examination and extensive diagnostics. DIAGNOSTICS: Chronic knee pain in children and adolescents is a diagnosis by exclusion. An extensive patient history including training habits, pain localization and clinical examination provide indications vital for the diagnosis. Overuse is often the trigger. In dynamic investigations consideration should be given to muscle imbalance. Imaging techniques have a high sensitivity and specificity only in combination with the anamnesis and clinical findings. THERAPY: With pain therapy, targeted physiotherapy, a break in active sport or training modifications, the prognosis is good for overload syndromes. An operative therapy after unsuccessful conservative therapy is necessary in only a few cases. Among the anatomy-related types of knee pain primary popliteal cysts mostly require no therapy and for plica syndrome arthroscopic resection should only be necessary if conservative treatment is unsuccessful. Operative therapy is necessary for symptomatic discoid meniscus.

A longitudinal study of the bi-directional relationship between tobacco smoking and psychological distress in a community sample of young Australian women.

BACKGROUND: Tobacco smoking and poor mental health are both prevalent and detrimental health problems in young women. The temporal relationship between the two variables is unclear. We investigated the prospective bi-directional relationship between smoking and mental health over 13 years. METHOD: Participants were a randomly selected community sample of 10 012 young women with no experience of pregnancy, aged 18-23 years at baseline (1996) from the Australian Longitudinal Study on Women's Health. Follow-up surveys over 13 years were completed in 2000, 2003, 2006 and 2009, allowing for five waves of data. Measures included self-reported smoking and mental health measured by the Mental Health Index from the 36-item short-form health questionnaire and the 10-item Center for Epidemiologic Studies Depression Scale. Sociodemographic control variables included marital status, education level and employment status. RESULTS: A strong cross-sectional dose-response relationship between smoking and poor mental health was found at each wave [odds ratio (OR) 1.41, 95% confidence intervals (CI) 1.17-1.70 to OR 2.27, 95% CI 1.82-2.81]. Longitudinal results showed that women who smoked had 1.21 (95% CI 1.06-1.39) to 1.62 (95% CI 1.24-2.11) times higher odds of having poor mental health at subsequent waves. Women with poor mental health had 1.12 (95% CI 1.17-1.20) to 2.11 (95% CI 1.68-2.65) times higher odds of smoking at subsequent waves. These results held after adjusting for mental health history and smoking history and sociodemographic factors. Correlation analysis and structural equation modelling results were consistent in showing that both directions of the relationship were statistically significant. CONCLUSIONS: The association between poor mental health and smoking in young women appeared to be bi-directional.

Are Australian smokers interested in using low-nitrosamine smokeless tobacco for harm reduction?

AIMS: To determine (1) whether Australian smokers are aware of low-nitrosamine smokeless tobacco (LNSLT) products and (2) whether they would be interested in using LNSLT either as a long-term substitute for smoking or as an aid to quitting, if these products were to become legally available. METHODS: 401 daily smokers were recruited by a market research company to complete an internet questionnaire about their smoking history, knowledge of smokeless tobacco and intentions to purchase LNSLT under different scenarios. FINDINGS: Just under half (48%) indicated they were willing to buy an LNSLT product. Predictors of an interest in purchasing LNSLT were low income, poorer health, prior SLT use, belief that SLT is less harmful than cigarettes, switching to a lower tar cigarette in the past year, ever using nicotine replacement therapy products for quitting or other reasons, having made a failed cessation attempt in the previous year and not planning to quit smoking. Analysis of quitting and LNSLT purchasing intentions under different scenarios suggest that making LNSLT available at a much lower cost than smoked cigarettes while increasing taxes on cigarettes could provide a greater reduction in the number of smokers than the same tax increase alone. These results support further examination of the potential for LNSLT to reduce smoking-related harm in Australia.

Supping with the devil? The role of law in promoting tobacco harm reduction using low nitrosamine smokeless tobacco products.

In Sweden, male cigarette smoking has declined as snus, a smokeless tobacco product which is low in carcinogenic nitrosamines, has gained popularity among male tobacco users. Epidemiological modelling based on the Swedish experience indicates that there would be major public health gains if a substantial number of current smokers in other countries could also be persuaded to switch to this product. This form of 'tobacco harm reduction' is very controversial in the public health community for many reasons. These include: objections in principle to the use of less harmful but still addictive nicotine products; uncertainties about the long-term effects of these products on health; doubts about the likely interest in and uptake of these products among existing smokers; concerns that increasing the availability of these products will increase the number of new tobacco users and eventually the number of smokers in the population; and anxiety about how the tobacco industry may use these products to undermine current tobacco control policies. This paper concludes with suggestions for a graduated series of policies that may allow exploration of the public health costs and benefits of encouraging smokers to switch to snus.

Predicting the future prevalence of cigarette smoking in Australia: how low can we go and by when?

BACKGROUND: In Australia, smoking prevalence has declined in men since the 1950s and in women since the 1980s. Future smoking prevalence in Australia is predicted from estimates of previous and current age-specific and sex-specific cessation rates and smoking uptake in young people derived from national survey data on the prevalence of smoking between 1980 and 2007. METHODS: A dynamic forecasting model was used to estimate future smoking prevalence in the Australian population based on a continuation of these current trends in smoking uptake and cessation. RESULTS: The results suggest that Australia's smoking prevalence will continue to fall while current rates of initiation and cessation are maintained. But a continuation of current smoking cessation and initiation patterns will see around 14% of adults still smoking in 2020. CONCLUSIONS: Smoking cessation rates will need to double for Australian smoking prevalence to reach a policy target of 10% by 2020.

[Case report of Ito-syndrome associated with congenital hemihypertrophy from the orthopaedic point of view]. / Fallbericht über das Ito-Syndrom mit angeborener Hemihypertrophie aus orthopädischer Sicht.

We report on the orthopaedic treatment of a patient with the very rare Ito syndrome and congenital hemihypertrophy. The leading symptom is the lamellar depigmentation of the skin for which it is synonymously called incontinantia pigmenti acromians. Further anomalies are found in the central nervous system, as well as the ocular and the musculoskeletal systems. The treatment of the hemihypertrophy and the coexistent dysplasia of the hip with a combination of intertrochanteric shortening osteotomy and a triple osteotomy are specified and further methods are discussed.

[Limited efficacy of opioids in chronic musculoskeletal pain]. / Eingeschränkte Wirksamkeit von Opioiden bei chronischen muskuloskelettalen Schmerzen. Eine Ursachenanalyse.

After excluding malignant disease in 21 patients with unremitting strong pain of the musculoskeletal system despite long-term opioid medication, the opioids were withdrawn to search for reasons of the limited effectiveness of the opioids. The opioid withdrawal was integrated in multimodal pain coping therapy. Besides the somatic diagnoses, pain-relevant psychosomatic diagnoses were evaluated with the structured clinical interview for DSM-IV (SCID). At the time of admission and discharge pain medication, physical functions, mood, and pain intensity were recorded. In the SCID interview, all patients were diagnosed with a relevant comorbid psychiatric condition (pain disorder, anxiety, depression). Despite reduction of the opioid medication, there was no increase of pain, but an improvement of the physical functions. In patients with chronic pain of the musculoskeletal system and limited effectiveness of opioid medication, psychosomatic comorbidities should be evaluated. Instead of continued and increased opioid medication, pain coping strategies and opioid withdrawal should be tested.

[Bronchial rupture combined with luxation fracture of the thoracic spine following direct trauma]. / Bronchusruptur kombiniert mit Brustwirbelsäulenluxationsfraktur durch direktes Trauma.

Tracheobronchial injuries in blunt thoracic trauma are very rare (incidence: under 1%), with potentially devastating consequences. Appropriate pre-, intra-, and postoperative management is mandatory to ensure the patient's survival and maintain lung function. We report the case of a 62-year-old male patient hit by a tree over the chest while cutting down trees, suffering a rupture of the right bronchus and a tear of the trachea combined with a luxation fracture of the thoracic spine between Th2 and Th3 (without neurological deficit). With immediate suture of the torn bronchus and trachea and stabilization of the spine fracture on the following day, we achieved a successful outcome in this patient. To our knowledge, this is the first description in the literature of the combination of both injuries.

Particulate matter and lung function growth in children: a 3-yr follow-up study in Austrian schoolchildren.

The effects of particulate matter <10 microm in diameter (PM10) and other air pollutants on lung function were assessed in 975 schoolchildren, from eight communities in Lower Austria between 1994-1997. In each community, air pollution data were collected. Spirometry was performed twice a year. PM10 concentration (mean concentration between two subsequent lung-function measures in spring and autumn (summer interval) or between autumn and spring (winter interval)) showed a mean value of 17.36 microg x m(-3) in the summer interval and 21.03 microg m(-3) in the winter interval. A slower increase in the forced expiratory volume in one second (FEV1) and midexpiratory flow between 25 and 75% of the forced vital capacity (MEF25-75) with age in children exposed to higher summer PM10 was observed in the 3-yr study period. After adjusting for potential confounders (sex, atopy, passive smoking, initial height, height difference, site, initial lung function) an increase of summer PM10 by 10 microg x m(-3) was associated with a decrease in FEV1 growth of 84 mL x yr(-1) and 329 mL x s(-1) x yr(-1) for MEF25-75. Nitrogen dioxide and ozone also showed a negative effect on lung-function growth, confirming previous work. The authors concluded that long-term exposure to particulate matter <10 microm in diameter had a significant negative effect on lung-function proxy for the development of large (forced expiratory volume in one second) and small (midexpiratory flow between 25 and 75% of the forced vital capacity) airways, respectively, with strong evidence for a further effect of ozone and nitrogen dioxide on the development of forced vital capacity and forced expiratory volume in one second.

Co-purification of mitochondrial HSP70 and mature protein disulfide isomerase with a functional rat kidney high-M(r) cysteine S-conjugate beta-lyase.

S-(1,1,2,2-Tetrafluoroethyl)-L-cysteine (TFEC, the cysteine S-conjugate of tetrafluoroethylene) is an example of a nephrotoxic, halogenated cysteine S-conjugate. Toxicity results in part from the cysteine S-conjugate beta-lyase(s)-catalyzed conversion of TFEC to a thioacylating fragment with the associated production of pyruvate and ammonia. In the present study, we have demonstrated that rat kidney homogenates contain at least three enzyme fractions that are capable of catalyzing a cysteine S-conjugate beta-lyase reaction with TFEC. One of these fractions contains a high-M(r) lyase. At least two proteins co-purify with this high-M(r) complex. N-Terminal analysis (15 cycles) revealed that the smaller species was mature protein disulfide isomerase (M(r) approximately 54,200) from which the 24 amino acid endoplasmic reticulum signal peptide had been removed. Internal amino acid sequencing (15 cycles) revealed that the larger species was mitochondrial HSP70 (mtHSP70; M(r) approximately 75,000). The present findings offer an explanation for the previous observation that mtHSP70 in kidney mitochondria is heavily thioacylated when rats are injected with TFEC (Bruschi et al., J Biol Chem 1993;268:23157-61).

[The effect of inhalable dust particles (PN10) on lung function and respiratory symptoms of school children in Lower Austria]. / Der Einfluss von inhalierbaren Staubpartikeln (PM10) auf Lungenfunktion und respiratorische Symptome bei niederösterreichischen Volksschulkindern.

The effect of PM10 (particulate matter less than 10 microns in diameter) on respiratory symptoms and lung function was evaluated in 881 children (aged 8 to 11 years) in 8 communities in Lower Austria. In each community, air pollution data (PM10, SO2, NO2, O3) were collected. The examination of each child included a questionnaire (spring 1996), and two lung function tests (autumn 1995, spring 1996). Statistically significant relationships were observed between PM10 levels (annual mean, 15.8-26.9 micrograms/m3) and parameters of lung function (adjusted for sex, height, atopy, passive smoking, altitude, temperature). A 10 micrograms/m3 increase in the last two weeks' mean PM10 in spring 1996 was associated with a 0.05% decrease in FVC, a 0.05% decrease in FEV1, a 0.15% decrease in MEF50, and a 0.13% decrease in MEF75-25. Furthermore, a 10 micrograms/m3 increase in last year's mean PM10 was associated with a 0.07% decrease in FVC. No association between the prevalence of respiratory symptoms and the last year's mean PM10-exposure was found. Our study demonstrates a small effect of low-level particulate air pollution on lung function of healthy school children.

Comparison of the bioavailability of natural palm oil carotenoids and synthetic beta-carotene in humans.

Palm oil carotenoids are a mixture of alpha- and beta-carotenes, which are used as food colorants. They may also be applied as a functional food ingredient because of the provitamin A activity of alpha- and beta-carotenes and their proposed beneficial roles in the prevention of chronic diseases. This paper discusses the results of an incomplete balanced crossover study with 69 healthy adult volunteers to compare palm oil carotenoids with synthetic beta-carotene in their efficacies to increase plasma levels of carotenoids. Four days of supplementation with natural palm oil carotenoids (7.6 mg/day of alpha-carotene, 11.9 mg/day of all-trans-beta-carotene, 7.5 mg/day of cis-beta-carotene) or synthetic beta-carotene (23.8 mg/day of all-trans-beta-carotene, 4.4 mg/day of cis-beta-carotene), added to a mixed meal, resulted in significant increases in plasma levels of the supplied carotenoids as compared to consumption of a low-carotenoid meal (i.e., 7.2-fold increase in alpha-carotene and 3.5-fold increase in all-trans-beta-carotene following palm oil carotenoids; 6.9-fold increase in all-trans beta-carotene following synthetic beta-carotene). As the carotenoid content differed between the treatments, the relative plasma responses were calculated per milligram of beta-carotene intake. These were similar for the two supplements, suggesting that the presence of alpha-carotene does not affect the bioavailability of beta-carotene from palm oil. It was concluded that 4 days of supplementation with palm oil carotenoids or synthetic beta-carotene improves the plasma beta-carotene status substantially, whereas alpha-carotene is additionally delivered by the palm oil supplement.

Lung function growth and ambient ozone: a three-year population study in school children.

We followed a cohort of 1,150 children for 3 yr to investigate long-term effects of ambient ozone. Nine study sites were selected on the basis of air-quality data to represent a broad range of ozone exposure. In 1994, 1995, and 1996 lung function was recorded biannually, always before and after summertime. The effect of ozone was analyzed with regression analyses and study-site, a child's sex, atopy, passive smoking, baseline lung function, and increase in height were considered as confounding variables. A negative effect of summertime ozone on the pre- to post-summer-time change in FEV(1) (ml/d) was present in 1994 (beta = -0.019 ml/d/ppb; p < 0.01) and in 1995 (beta = -0.017 ml/d/ ppb; p < 0.05), but not in 1996 (beta = 0. 004 ml/d/ppb; p = 0.6); corresponding estimates for FVC were in 1994: beta = -0.022 ml/d/ppb, p < 0.005; 1995: beta = -0.018 ml/d/ppb, p < 0.05; and 1996: beta = 0.006 ml/d/ppb, p = 0.46. When all three study years were considered simultaneously, i.e., the changes in lung function between each of two subsequent surveys being the dependent variable, summertime ozone was associated with a lesser increase in FEV(1) (beta = -0.029 ml/d/ppb; p < 0.001), FVC (beta = -0.018 ml/d/ppb; p < 0.001), and MEF(50) (beta = -0.076 ml/s/d; p = 0.001). No consistent associations were observed for lung function and NO(2), SO(2) and PM(10). Long-term ambient ozone exposure might negatively influence lung function growth.

Protein and nonprotein cysteinyl thiol modification by N-acetyl-p-benzoquinone imine via a novel ipso adduct.

N-acetyl-p-benzoquinone imine (NAPQI), a reactive metabolite of acetaminophen (APAP), can arylate and oxidize protein and nonprotein thiols in the pathogenesis of APAP-induced hepatotoxicity. We report the first direct evidence for the formation of a labile ipso adduct between glutathione (GSH) and NAPQI using a combination of techniques including liquid chromatography/tandem mass spectrometry and liquid chromatography/NMR spectroscopy. Decomposition kinetics of the GSH-NAPQI ipso adduct and product ratios suggested that the ipso adduct was readily reversible back to NAPQI under neutral and basic conditions. The significance of the ipso adduct is that it may migrate from its site of formation to other cell compartments where it can either oxidize protein thiols or covalently modify them. Ipso adduct formation with protein thiols was demonstrated with a cysteine protease, papain, whose catalytic activity relies on the presence of an active site cysteinyl thiol. The formation and reactions of cysteinyl thiol ipso adducts of NAPQI provides significant new insights into possible reactions of quinone imines with cellular peptides and proteins.

Potential of vegetable processing to increase the delivery of carotenoids to man.

It has been suggested that carotenoids contribute to the inverse association between vegetable consumption and risk for coronary heart disease and cancer. However, there are indications that the bioavailability of beta-carotene from vegetables is less than previously thought. Therefore, it is of interest to explore whether the bioavailability of carotenoids from vegetables can be improved. We have reviewed data on the effect of vegetable processing on carotenoid bioavailability. Based on this analysis, we conclude that processing of vegetables by mechanical homogenization or heat treatment has the potential of increasing the bioavailability of carotenoids. Addition of fat during processing may also have an effect.