Smoking exposure trajectories and pulmonary function in early adulthood in a Brazilian cohort.

OBJECTIVES: To investigate smoking trajectories and their association with pulmonary function (PF) and respiratory symptoms at age 22. METHODS: Data from a population-based cohort study of 3350 individuals and their spirometries were analysed. The outcomes were: forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), forced expiratory flow at the mid expiratory phase (FEF25-75 %), FEV1/FVC and FEF25-75/FVC ratio. Smoking data were collected at perinatal follow-up (gestational exposure) and 15, 18 and 22 years. Group-based trajectory model was applied. RESULTS: Four groups were identified: no exposure (NE), gestational (GE), gestational and adulthood (GAE) and continuous (CE) exposure. Both CE and GAE trajectories were associated with lower values of FEV1/FVC (-1.77pp; p = 0.01 and -1.58 pp; p<0.001 respectively) and FEF25-75/FVC ratio (-7.27pp; p = 0.019 and -6.04pp; p<0.001 respectively) compared to the NE trajectory. Lower FEV1 and FEF25-75 % values were also related to the GAE trajectory (-68 ml; p = 0.03 and -253 ml/s;p<0.001 respectively). Compared to those who never smoked, individuals who smoked 10 or more cigarettes daily presented a reduction in the FEV1/FVC ratio by 1.37pp (p<0.001), FEF25-75 % by 126 ml (p = 0.012) and FEF25-75 %/FVC ratio by 3.62pp (p = 0.011). CE trajectory showed higher odds of wheezing (OR 4.14; p<0.001) and cough (OR 2.39; p = 0.002) compared to the non-exposed group. CONCLUSIONS: The in-uterus exposure to maternal smoking reduces PF later in life. However, the perpetuation of smoking behaviour throughout adolescence and early adulthood is determinant for PF main reduction and the emergence of respiratory-related symptoms.

Elucidating in vitro and in vivo phenotypic behaviour of L. infantum/L. major natural hybrids.

The clinical manifestation and course of Leishmania infections depend on factors such as species, virulence and host-immunity. Although trypanosomatids are considered to have clonal propagation, genetic hybridization has produced successful natural hybrid lineages. Hybrids displaying strong selective advantages may have an impact on pathogenesis and the eco-epidemiology of leishmaniasis. Thus, characterization of phenotypic properties of Leishmania hybrids could bring significant insight into the biology, infectivity, pathogenicity and transmission dynamics of these atypical strains. The present study focuses on phenotypic features and survival capacity of Leishmania infantum/Leishmania major hybrid isolates as compared with representative putative parental species, L. infantum and L. major. In vitro assays (growth kinetics, susceptibility to different conditions) and in vivo infection (parasite detection and histopathological alterations) showed that hybrids present higher growth capacity and decreased susceptibility to reactive oxygen species. Furthermore, evaluation of infected spleen tissue suggests that hybrids induce a stronger immune reaction than their putative parents, leading to the development of white pulp hyperplasia in B-lymphocyte compartments. Overall, these hybrids have shown high plasticity in terms of their general behaviour within the different phenotypic parameters, suggesting that they might have acquired genetic features conferring different mechanisms to evade host cells.

Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes.

Type 2 diabetes (T2D) is characterized by insulin resistance and impaired insulin secretion, but the mechanisms underlying insulin secretion failure are not completely understood. Here, we show that a set of co-expressed genes, which is enriched for genes with islet-selective open chromatin, is associated with T2D. These genes are perturbed in T2D and have a similar expression pattern to that of dedifferentiated islets. We identify Sox5 as a regulator of the module. Sox5 knockdown induces gene expression changes similar to those observed in T2D and diabetic animals and has profound effects on insulin secretion, including reduced depolarization-evoked Ca2+-influx and ß-cell exocytosis. SOX5 overexpression reverses the expression perturbations observed in a mouse model of T2D, increases the expression of key ß-cell genes and improves glucose-stimulated insulin secretion in human islets from donors with T2D. We suggest that human islets in T2D display changes reminiscent of dedifferentiation and highlight SOX5 as a regulator of ß-cell phenotype and function.

Impact of maxillary sinus augmentation on oral health-related quality of life.

BACKGROUND: The aim of this study was to measure the oral health-related quality of life (OHRQoL) after maxillary sinus augmentation to determine the physical and psychological impact of this procedure for the patient. METHODS: Three hundred sixteen patients treated with an external or internal maxillary sinus augmentation and a total of 863 implants in the Department of Oral and Maxillofacial Surgery, Johannes Gutenberg University, Mainz, Germany, between July 2002 and December 2007 were included in this retrospective study. Total implant survival was assessed. Completion of a modified 26-item version of the Oral Health Impact Profile (OHIP-G) for assessing the oral health-related quality of life before and after the treatment was asked for. Subcategories were (1) functional limitations, (2) physical and psychological disabilities, and (3) complaints due to the surgical procedure. In 53 patients available for clinical follow-up examination, assessment of soft tissue parameters was performed. RESULTS: After an average time in situ of 41.2 ± 27 months (3.4 years), the in situ rate was 95.4%. One-year survival rate and five-year survival rate according to Kaplan Meier were 95.4 and 94.4%. Concerning functional limitations, significant better values for OHRQoL after sinus augmentation procedure than before the treatment (p < 0.001) were seen. In the subcategory physical and psychological disabilities, all questions had significant better values after the sinus lift (p < 0.001). Concerning complaints due to the surgical procedure, mean total scores were 5.1 ± 5.4 pre-operative, 6.9 ± 6.1 (0-31) post-operative, and 2.4 ± 3.7 recently. This meant a significant difference between "pre-operative" vs. "post-operative" (p = 0.003), "pre-operative" vs. "recently" (p < 0.001), and "post-operative" vs. "recently" (p < 0.001). Concerning the influence of implant indication, edentulous patients showed the most distinct improvement after the procedure. Clinical assessment showed stable soft tissue parameters. CONCLUSIONS: Evaluation of OHRQoL after sinus augmentation showed a significant improvement indicating a remarkable benefit for the patients through this procedure.

Joint use of Disparate Data for the Surveillance of Zoonoses: A Feasibility Study for a One Health Approach in Germany.

Zoonotic diseases concern human and animal populations and are transmitted between both humans and animals. Nevertheless, surveillance data on zoonoses are collected separately for the most part in different databases for either humans or animals. Bearing in mind the concept of One Health, it is assumed that a global view of these data might help to prevent and control zoonotic diseases. In following this approach, we wanted to determine which zoonotic data are routinely collected in Germany and whether these data could be integrated in a useful way to improve surveillance. Therefore, we conducted an inventory of the existing data collections and gathered information on possible One Health surveillance areas in Germany by approaching experts through a scoping survey, personal interviews and during a workshop. In matching the information between the status quo for existing data collections and the possible use cases for One Health surveillance, this study revealed that data integration is currently hindered by missing data, missing pathogen information or a lack of timeliness, depending on the surveillance purpose. Therefore, integrating the existing data would require substantial efforts and changes to adapt the collection procedures for routine databases. Nevertheless, during this study, we observed a need for different stakeholders from the human and animal health sectors to share information to improve the surveillance of zoonoses. Therefore, our findings suggest that before the data sets from different databases are integrated for joint analyses, the surveillance could be improved by the sharing of information and knowledge through a collaboration of stakeholders from different sectors and institutions.

Modulation of microRNA-375 expression alters voltage-gated Na(+) channel properties and exocytosis in insulin-secreting cells.

AIM: MiR-375 has been implicated in insulin secretion and exocytosis through incompletely understood mechanisms. Here we aimed to investigate the role of miR-375 in the regulation of voltage-gated Na(+) channel properties and glucose-stimulated insulin secretion in insulin-secreting cells. METHODS: MiR-375 was overexpressed using double-stranded mature miR-375 in INS-1 832/13 cells (OE375) or downregulated using locked nucleic acid (LNA)-based anti-miR against miR-375 (LNA375). Insulin secretion was determined using RIA. Exocytosis and ion channel properties were measured using the patch-clamp technique in INS-1 832/13 cells and beta-cells from miR-375KO mice. Gene expression was analysed by RT-qPCR, and protein levels were determined by Western blot. RESULTS: Voltage-gated Na(+) channels were found to be regulated by miR-375. In INS-1 832/13 cells, steady-state inactivation of the voltage-gated Na(+) channels was shifted by approx. 6 mV to a more negative membrane potential upon down-regulation of miR-375. In the miR-375 KO mouse, voltage-gated Na(+) channel inactivation was instead shifted by approx. 14 mV to a more positive membrane potential. Potential targets differed among species and expression of suggested targets Scn3a and Scn3b in INS-1 832/13 cells was only slightly moderated by miR-375. Modulation of miR-375 levels in INS-1-832/13 cells did not significantly affect insulin release. However, Ca(2+) dependent exocytosis was significantly reduced in OE375 cells. CONCLUSION: We conclude that voltage-gated Na(+) channels are regulated by miR-375 in insulin-secreting cells, and validate that the exocytotic machinery is controlled by miR-375 also in INS-1 832/13 cells. Altogether we suggest miR-375 to be involved in a complex multifaceted network controlling insulin secretion and its different components.

Zoonotic disease surveillance--inventory of systems integrating human and animal disease information.

Although 65% of recent major disease outbreaks throughout the world have a zoonotic origin, there is still a sharp division among the disciplines into the human and animal health sectors. In the last few decades, a global integrative concept, often referred to as 'One Health', has been strongly endorsed. Surveillance and monitoring efforts are major components for effective disease prevention and control. As human health and animal health are inextricably linked, it is assumed that a cross-sectoral data interpretation of zoonotic disease information will improve their prevention, prediction and control. To provide an overview of existing systems throughout the world which integrate information from humans and animals on zoonotic diseases, a literature review was conducted. Twenty projects were identified and described regarding their concepts and realization. They all vary widely depending on their surveillance purpose, their structure and the source of information they use. What they have in common is that they quite often use data which have already been collected for another purpose. Therefore, the challenges of how to make use of such secondary data are of great interest.

Vitamin D binding protein and vitamin D in human allergen-induced endobronchial inflammation.

Allergic asthma is a chronic disease of the airways associated with airway hyperresponsiveness, a variable degree of airflow obstruction, airway remodelling and a characteristic airway inflammation. Factors of the vitamin D axis, which include vitamin D metabolites and vitamin D binding protein (VDBP), have been linked to asthma, but only few data exist about their regulation in the lung during acute allergen-induced airway inflammation. Therefore, we analysed the regulation of factors of the vitamin D axis during the early- and late-phase reaction of allergic asthma. Fifteen patients with mild allergic asthma underwent segmental allergen challenge. VDBP was analysed in bronchoalveolar lavage fluid (BALF) and serum using the enzyme-linked immunosorbent assay (ELISA) technique. 25-hydroxyvitamin D(3)[25(OH)D(3)] and 1,25-dihydroxyvitamin D(3)[1,25(OH)(2)D(3)] were analysed by a commercial laboratory using the liquid chromatography-mass spectrometry (LC/MS) technique. VDBP (median 2·3, range 0·2-7·1 µg/ml), 25(OH)D(3) (median 0·060, range < 0·002-3·210 ng/ml) and 1,25(OH)(2)D(3) (median < 0·1, range < 0·1-2·8 pg/ml) were significantly elevated in BALF 24 h but not 10 min after allergen challenge. After correction for plasma leakage using the plasma marker protein albumin, VDBP and 25(OH)D(3) were still increased significantly while 1,25(OH)(2)D(3) was not. VDBP and 25(OH)D(3) were correlated with each other and with the inflammatory response 24 h after allergen challenge. Serum concentrations of all three factors were not influenced by allergen challenge. In conclusion, we report a significant increase in VDBP and 25(OH)D(3) in human BALF 24 h after allergen challenge, suggesting a role for these factors in the asthmatic late-phase reaction.

[Lifting capacity with low back pain : Discrepancy between self-rated and real lifting capacity in patients with back pain and pain-free controls]. / Hebefähigkeit bei Rückenschmerzen : Diskrepanz zwischen Selbsteinschätzung und tatsächlich gezeigter Hebefähigkeit bei Rückengesunden und Patienten mit Rückenschmerzen.

BACKGROUND: The fear-avoidance model implies that in situations with physical demands patients with back pain will overestimate the demand and underestimate their own capacities. PATIENTS AND METHODS: A total of 71 patients with back pain and 48 pain-free control subjects carried out a standardized lifting test with a preceding estimation of their lifting capacity. RESULTS: In both groups the self-estimation and real lifting capacity were in concordance for most group members with patients showing less disconcordance than controls. In the control group 35% of the subjects even underestimated their lifting capacity, which was the case in only 14% of the patients. Patients more frequently overestimated their capacity than pain-free controls (14% vs. 2%). Within the patients subgroups could be identified where patients in general either underestimated or overestimated their own capacity. A comparison between the groups demonstrated significant differences in pain intensity, fear avoidance beliefs and effort. CONCLUSION: As an explanation for these unexpected results it can be hypothesized that in cases of back pain, patients' attention is focused on pain-relevant issues which enables a more realistic estimation of their lifting capacity.

Cross-sectional study discloses a positive family history for Parkinson's disease and male gender as epidemiological risk factors for substantia nigra hyperechogenicity.

Hyperechogenicity of the substantia nigra (SN) has been proposed to be a typical finding in Parkinson's disease (PD) and a marker of vulnerability to nigrostriatal dysfunction in healthy subjects. This large cross-sectional study including 1120 subjects older than 50 years without any signs of PD was performed to evaluate the association of SN hyperechogenicity and other proposed epidemiological risk factors for PD. Among all variables assessed only family history of PD and male gender proved to be significantly associated with SN hyperechogenicity, indicating a genetic predisposition for the ultrasound marker.

Determination of patulin by online-SPE-LC.

The mycotoxin patulin mainly occurs in fruits and fruit-derived products. For its determination a newly developed method employing a simplified liquid-liquid partitioning step followed by an online-SPE-LC analysis with UV detection is presented. The sample is diluted with phosphate buffer and extracted with ethyl acetate. The extract is evaporated and re-dissolved. The online-SPE-LC analysis employs a styrene-divinylbenzene copolymere phase for the SPE step, on which the carbonate washing step is carried out as well. The final LC analysis with UV detection uses a Polaris C18A column. This method reaches a limit of quantification of 15 µg/kg (clear apple juice), with a standard deviation of 10.7% (matrix calibration, n=5; c (patulin)=50 µg/kg).

Dynamic autoregulation testing in the posterior cerebral artery.

BACKGROUND AND PURPOSE: Dynamic autoregulation has been studied predominantly in the middle cerebral artery (MCA). Because certain clinical conditions, ie, presyncopal symptoms or hypertensive encephalopathy, suggest a higher vulnerability of autoregulation within posterior parts of the brain, we investigated whether the cerebral blood flow velocity (CBFV) is modulated differently within the posterior cerebral artery (PCA). METHODS: Spontaneous oscillations of CBFV and arterial blood pressure (ABP) in the frequency range of 0.5 to 20 cycles per minute were studied in 30 volunteers (supine and tilted positions). Analysis was based on the "high-pass filter model," which predicts a specific frequency-dependent phase and amplitude relationship between oscillations in CBFV to ABP. These parameters, characterized as phase shift angles and transfer function gains, were calculated from simultaneously recorded beat-to-beat blood pressure and transcranial Doppler signals of the PCA and MCA by means of cross-spectrum analysis. RESULTS: In the MCA and PCA, phase shift angles were decreased, and gains were elevated with increasing oscillation frequency. The PCA gain values in supine and tilted positions were significantly higher than in the MCA. CONCLUSIONS: The phase and amplitude relationship between CBFV and ABP showed a frequency dependence in the PCA similar to that in the MCA. The study therefore suggests that the high-pass filter model of dynamic cerebral autoregulation can be applied to the PCA. In this model the generally higher gain values in the PCA indicate a lower damping of ABP oscillations, which are transmitted to the posterior part of cerebral circulation.

Three-dimensional power Doppler ultrasound of the subendometrial blood flow under the administration of a contrast agent (Levovist).

METHODS: Based on the results from 42 IVF patients on the day of oocyte aspiration, our study tested the hypothesis that 3-D Doppler ultrasound of the endometrium supported by a contrast agent possesses advantages over a conventional 3-D Doppler ultrasound examination. We also determined whether the subendometrial blood flow indices measured under continuous infusion of Levovist (Schering, Berlin, Germany) were an indicator of a successful implantation. RESULTS: It was demonstrated that, after the administration of Levovist, all subendometrial blood flow parameters (e.g., vascularization index [VI: 8.82+/-16.64], flow index [FI: 35.67+/-9.33], and vascularization flow index [VFI: 3.99+/-8.80]) were significantly higher than without the contrast agent ( p<0.001; VI: 3.09+/-7.11; FI: 29.13+/-14.26; VFI: 1.35+/-3.31). However, no significant differences between blood flow with contrast agent and pregnancy rate were found. CONCLUSION: In summary, quantitative 3-D Doppler ultrasound employing Levovist (Schering, Berlin, Germany) is significantly more sensitive when compared to conventional 3-D Doppler examination. For the first time this was demonstrated on 42 IVF patients on the day of oocyte aspiration. However, no correlation with outcome of the IVF-treatment could be found.

End-of-life competencies and the NCLEX-RN examination.

With the aging of the population, health care workers must be prepared to deal with clients and families facing end-of-life (EOL) issues. Nurses, as one of the primary providers of care and the largest professional group to provide care, can make a significant impact on EOL care. This article uses 15 nursing competencies that have been identified as important in providing high-quality care to clients and the families of clients at the end of life and delineates where these competencies are addressed in the 1998 NCLEX-RN Test Plan. Available resources that provide information on EOL content are mentioned as well as how to become involved in the NCLEX item development process.

Importance of the 3' untranslated region of ornithine decarboxylase mRNA in the translational regulation of the enzyme.

Translational regulation of ornithine decarboxylase (ODC), which catalyses the first step in the biosynthesis of polyamines, appears to be an important mechanism in the strong feedback control as well as in the hypotonic induction of the enzyme. However, the exact mechanisms are not yet understood. The ODC mRNA has long 5' and 3' untranslated regions (UTRs) which may be involved in the translational control of the enzyme. In the present study we have used a series of stable transfectants of Chinese Hamster ovary cells expressing ODC mRNAs with various truncations in the 5' and 3' UTRs to investigate the importance of these regions. It is demonstrated that neither the 5' UTR nor the 3' UTR appears to be involved in the polyamine-mediated feedback control of ODC synthesis. The hypotonic induction of ODC, on the other hand, was shown to be highly dependent on the presence of the 3' UTR, but not on the 5' UTR, of ODC mRNA. Cells expressing ODC mRNAs lacking the 3' UTR showed no, or only a very slight, induction of ODC whether the 5' UTR was present or not, whereas the cell lines expressing ODC mRNAs containing the 3' UTR (with or without the 5' UTR) markedly induced ODC after a hypotonic shock. The present finding of a role for the ODC mRNA 3' UTR in the hypotonic induction of ODC is the first demonstration of a specific effect of the 3' UTR in the regulation of ODC.

Expression of tissue factor in high-grade carotid artery stenosis: association with plaque destabilization.

BACKGROUND AND PURPOSE: The procoagulant protein tissue factor (TF) has been implicated in thromboembolic complications associated with advanced atherosclerosis. In this study, we investigated whether TF expression in high-grade stenoses of the internal carotid artery (ICA) is associated with clinical features of plaque destabilization and addressed the relationship between TF expression and plaque inflammation. METHODS: In 36 consecutive patients undergoing surgery for high-grade ICA stenosis, clinical evidence of plaque instability was provided by the recent occurrence of ischemic symptoms attributable to the stenosis and the detection of cerebral microembolism by means of transcranial Doppler ultrasound monitoring of the ipsilateral middle cerebral artery. Endarterectomy specimens were stained immunocytochemically for TF expression as well as macrophage (CD68) and T cell (CD3) infiltration. RESULTS: Morphologically, TF immunoreactivity was codistributed with plaque inflammation and predominantly localized to CD68+ macrophages. Accordingly, statistical analysis revealed a significant association of TF expression with plaque infiltration by macrophages (P<0.0001) and T cells (P=0.013). Plaques extensively stained for TF (median of TF+ total section area >40% in semiquantitative assessment) were more frequent in symptomatic (12/27) than in asymptomatic patients (1/9). Conversely, plaques exhibiting little TF expression (median of TF+ section area <20%) were more frequent in asymptomatic (3/9) than in symptomatic (1/27) patients (P=0.016). Likewise, we found a highly significant association of TF expression with the occurrence of cerebral microembolism (P=0.008). CONCLUSIONS: Induction of TF at sites of plaque inflammation may play an important role in the destabilization of high-grade ICA stenosis.