[Consensus statement of the Austrian Sleep Medicine Society on the management of residual excessive daytime sleepiness in obstructive sleep apnea]. / Konsensus-Statement der Österreichischen Gesellschaft für Schlafmedizin (ÖGSM/ASRA) zum Management der residualen exzessiven Tagesschläfrigkeit (rETS) bei obstruktiver Schlafapnoe: Die SPAIN-Checkliste für den klinischen Alltag.

Background: Six to ten percent of patients with obstructive sleep apnea suffer from residual excessive daytime sleepiness (rEDS) despite adequate nocturnal positive airway pressure therapy or effective alternative treatment. The differential diagnosis of rEDS is an interdisciplinary challenge in clinical practice. Objectives: Development of a clear guideline for the detection, differential diagnostic considerations, and options for the continuing treatment of rEDS in clinical practice. Methods: MeSH analysis-based research and interdisciplinary consensus among specialists in internal medicine and pneumology, neurology, as well as psychiatry and psychotherapy. Results: The SPAIN checklist for systematic differential diagnostic exploration of rEDS with the parameters: S leep behavior, P sychological causes, A namesis of medication, I nternal causes and N eurological causes. Conclusions: rEDS should be recognized as a symptom worthy of treatment. It requires an interdisciplinary assessment and the individual adaptation of the treatment to the needs of the affected person.

14GHz longitudinally detected electron spin resonance using microHall sensors.

In this work we developed a home-made LOngitudinally Detected Electron Spin Resonance (LODESR) spectrometer based on a microsize Hall sensor. A coplanar waveguide (CPW)-resonator is used to induce microwave-excitation on the sample at 14GHz. We used InSb cross-shaped Hall devices with active areas of (10µm×10µm) and (5µm×5µm). Signal intensities of the longitudinal magnetization component of DPPH and YIG samples of volumes about (10µm)3 and (5µm)3, are measured under amplitude and frequency modulated microwave magnetic field generated by the CPW-resonator. At room temperature, 109spins/G√Hz sensitivity is achieved for 0.2mT linewidth, a result which is still better than most of inductive detected LODESR sensitivities.

Successful conservative treatment of a cervical ectopic pregnancy at 13 weeks.

BACKGROUND: Cervical ectopic pregnancy is a potentially life-threatening condition due to the unexpected occurrence of uncontrollable bleeding from the cervix. CASE REPORT: A 39-year-old secundigravida was admitted with amenorrhea of 12 weeks and four days due to suspected cervical pregnancy, without bleeding. The ultrasonography revealed a gestational sac at the anterior wall of the isthmic-cervical part with a single viable fetus, with crown-rump length (CRL) of 59 mm and regular heart rate. The serum ß-human chorionic gonadotropin (ß-hCG) level on admission was 143.416 mIU/l. Two possible therapeutic options were considered, (1) systemic methotrexate treatment and (2) uterine artery embolization with gelatine sponge. The first was rejected due to gestational age, viable fetus, high ß-hCG level, and CRL, and the later was rejected by the vascular surgeons due to lack of experience. The curettage was performed. After the evacuation, prostin was administered into cervix accompanied with tamponade. On the next day ß-hCG level was 44.342 mIU/l and the following day ultrasonography revealed the oval non-homogenous formation in the cervical cavity (blood clots or residual trophoblastic tissue); ß-hCG level was 36.501 mIU/l. The reintervention was performed on the fifth day after the curettage and 200 ml of coagulated blood was aspirated; ß-hCG level was 16.432 mlU/l. Since the isthmic-cervical part was slightly dilated (23 mm) seven days after the curettage, systemic methotrexate treatment (100 mg intramuscular) was initiated. Serum ß-hCG level on the second and fourth day after methotrexate were 12.553 mIU/l and 8.900 mIU/l, respectively. The second dose of 100 mg of methotrexate was administered intramuscular seven days after the first dose. Three days after, ß-hCG level was 2.329 U/l and ultrasound scan revealed normal isthmic-cervical finding. CONCLUSION: The present case report showed efficient fertility sparing conservative treatment, dilatation and curettage, of 13 week cervical pregnancy followed by systemic methotrexate.

MMSET/WHSC1 enhances DNA damage repair leading to an increase in resistance to chemotherapeutic agents.

MMSET/WHSC1 is a histone methyltransferase (HMT) overexpressed in t(4;14)+ multiple myeloma (MM) patients, believed to be the driving factor in the pathogenesis of this MM subtype. MMSET overexpression in MM leads to an increase in histone 3 lysine 36 dimethylation (H3K36me2), and a decrease in histone 3 lysine 27 trimethylation (H3K27me3), as well as changes in proliferation, gene expression and chromatin accessibility. Prior work linked methylation of histones to the ability of cells to undergo DNA damage repair. In addition, t(4;14)+ patients frequently relapse after regimens that include DNA damage-inducing agents, suggesting that MMSET may play a role in DNA damage repair and response. In U2OS cells, we found that MMSET is required for efficient non-homologous end joining as well as homologous recombination. Loss of MMSET led to loss of expression of several DNA repair proteins, as well as decreased recruitment of DNA repair proteins to sites of DNA double-strand breaks (DSBs). By using genetically matched MM cell lines that had either high (pathological) or low (physiological) expression of MMSET, we found that MMSET-high cells had increased damage at baseline. Upon addition of a DNA-damaging agent, MMSET-high cells repaired DNA damage at an enhanced rate and continued to proliferate, whereas MMSET-low cells accumulated DNA damage and entered cell cycle arrest. In a murine xenograft model using t(4;14)+ KMS11 MM cells harboring an inducible MMSET shRNA, depletion of MMSET enhanced the efficacy of chemotherapy, inhibiting tumor growth and extending survival. These findings help explain the poorer prognosis of t(4;14) MM and further validate MMSET as a potential therapeutic target in MM and other cancers.

MMSET stimulates myeloma cell growth through microRNA-mediated modulation of c-MYC.

Multiple myeloma (MM) represents the malignant proliferation of terminally differentiated B cells, which, in many cases, is associated with the maintenance of high levels of the oncoprotein c-MYC. Overexpression of the histone methyltransferase MMSET (WHSC1/NSD2), due to t(4;14) chromosomal translocation, promotes the proliferation of MM cells along with global changes in chromatin; nevertheless, the precise mechanisms by which MMSET stimulates neoplasia remain incompletely understood. We found that MMSET enhances the proliferation of MM cells by stimulating the expression of c-MYC at the post-transcriptional level. A microRNA (miRNA) profiling experiment in t(4;14) MM cells identified miR-126* as an MMSET-regulated miRNA predicted to target c-MYC mRNA. We show that miR-126* specifically targets the 3'-untranslated region (3'-UTR) of c-MYC, inhibiting its translation and leading to decreased c-MYC protein levels. Moreover, the expression of this miRNA was sufficient to decrease the proliferation rate of t(4;14) MM cells. Chromatin immunoprecipitation analysis showed that MMSET binds to the miR-126* promoter along with the KAP1 corepressor and histone deacetylases, and is associated with heterochromatic modifications, characterized by increased trimethylation of H3K9 and decreased H3 acetylation, leading to miR-126* repression. Collectively, this study shows a novel mechanism that leads to increased c-MYC levels and enhanced proliferation of t(4;14) MM, and potentially other cancers with high MMSET expression.

The histone methyltransferase MMSET/WHSC1 activates TWIST1 to promote an epithelial-mesenchymal transition and invasive properties of prostate cancer.

Epigenetic deregulation of gene expression has a role in the initiation and progression of prostate cancer (PCa). The histone methyltransferase MMSET/WHSC1 (Multiple Myeloma SET domain) is overexpressed in a number of metastatic tumors, but its mechanism of action has not been defined. In this work, we found that PCa cell lines expressed significantly higher levels of MMSET compared with immortalized, non-transformed prostate cells. Knockdown experiments showed that, in metastatic PCa cell lines, dimethylation of lysine 36 and trimethylation of lysine 27 on histone H3 (H3K36me2 and H3K27me3, respectively) depended on MMSET expression, whereas depletion of MMSET in benign prostatic cells did not affect chromatin modifications. Knockdown of MMSET in DU145 and PC-3 tumor cells decreased cell proliferation, colony formation in soft agar and strikingly diminished cell migration and invasion. Conversely, overexpression of MMSET in immortalized, non-transformed RWPE-1 cells promoted cell migration and invasion, accompanied by an epithelial-mesenchymal transition (EMT). Among a panel of EMT-promoting genes analyzed, TWIST1 expression was strongly activated in response to MMSET. Chromatin immunoprecipitation analysis demonstrated that MMSET binds to the TWIST1 locus and leads to an increase in H3K36me2, suggesting a direct role of MMSET in the regulation of this gene. Depletion of TWIST1 in MMSET-overexpressing RWPE-1 cells blocked cell invasion and EMT, indicating that TWIST1 was a critical target of MMSET, responsible for the acquisition of an invasive phenotype. Collectively, these data suggest that MMSET has a role in PCa pathogenesis and progression through epigenetic regulation of metastasis-related genes.

Sleep habits and sleep complaints in Austria: current self-reported data on sleep behaviour, sleep disturbances and their treatment.

OBJECTIVES: To acquire current information on sleep habits, disturbances and treatment options in the adult population of Austria and compare results with previously collected data. MATERIALS AND METHODS: A representative sample of the Austrian population (women: n = 522, men: n = 478). RESULTS: Seventy-five percent reported daily sleep-duration between 6 and 8 h. In 76%, sleep latency was <30 min, 15% described difficulties in sleep maintenance. Longer sleep on weekends was prevalent in 54%, 23% took a nap. Concerning sleep environment, 31% reported sleeping alone; the rest had a constant or occasional bed partner. Sleep disturbances such as sleep disruption or prolonged sleep latency were reported by 18%. Predominant symptoms included snoring/apneas (22%), nightmares (22%) and restless legs (21%). Daytime tiredness was reported by 17% and sleepiness by 20%. Twenty-four percent did not take treatment. Only 7% asked for medical help: 96% consulted their physician; 47% tried to change their way of living. Sleep promoting drugs were taken by 7%. Sleep improving measures were: sleep promoters (45%), general measures (20%), consultation of general practitioner (20%), psychotherapy (6%), and technical tools (3%). Comparison with a dataset of 1993 revealed only a slight increase in short sleepers and a slight decrease in long sleepers. CONCLUSIONS: Subjectively reported sleep disorders proved to be relatively stable between 1993 and 2007.

The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide.

OBJECTIVE: To update the follow-up of the Euro-Lupus Nephritis Trial (ELNT), a randomised prospective trial comparing low-dose (LD) and high-dose (HD) intravenous (IV) cyclophosphamide (CY) followed by azathioprine (AZA) as treatment for proliferative lupus nephritis. PATIENTS AND METHODS: Data for survival and kidney function were prospectively collected during a 10-year period for the 90 patients randomised in the ELNT, except in 6 lost to follow-up. RESULTS: Death, sustained doubling of serum creatinine and end-stage renal disease rates did not differ between the LD and HD group (5/44 (11%) vs 2/46 (4%), 6/44 (14%) vs 5/46 (11%) and 2/44 (5%) vs 4/46 (9%), respectively) nor did mean serum creatinine, 24 h proteinuria and damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressant agents and blood pressure lowering drugs. After 10 years of follow-up, the positive predictive value for a good outcome of an early drop in proteinuria in response to initial immunosuppressive therapy was confirmed. CONCLUSION: The data confirm that a LD IVCY regimen followed by AZA-the "Euro-Lupus regimen"-achieves good clinical results in the very long term.

Rapid chlorophyll a fluorescence transients of Lemna minor leaves as indication of light and exogenous electron carriers effect on photosystem II activity.

By using saturating flash, we investigated the change in the rapid fluorescence rise when Lemna minor leaf was exposed to different light conditions and treated with exogenous electron acceptors (methyl viologen and duroquinone) and electron donor (hydroxylamine). Investigation was carried out by using combined pulse amplitude modulated fluorometer and plant efficiency analyzer system, which were employed simultaneously to provide different light conditions and to induce rapid fluorescence rise respectively. We have shown that when leaf of L. minor was exposed to different conditions of illumination, rapid fluorescence rise was greatly influenced by the electron transport functions beyond quinone A-plastoquinone reduction. This was indicated by the change in both fluorescence yield and appearance time of the different transients. When exogenous electron donor (hydroxylamine) and acceptors (methyl viologen and duroquinone) were applied in in vivo condition, we showed that rapid fluorescence rise represented a reliable indicator of PSII-PSI electron transport state and energy dissipation process.

Sample patterning on NMR surface microcoils.

Aligned microcontact printing for patterning the sample in areas of homogeneous RF-field on the highly sensitive surface of planar NMR microprobes is presented. We experimentally demonstrate that sample patterning allows drastic improvement of the spin excitation uniformity. The NMR microprobes are designed for cell analysis and characterized using lipid vesicles as cell substitutes. Lipid vesicles are advantageous as composition and concentration of the confined solution are precisely controlled and because of their similarity to living cells. Using aligned microcontact printing, a monolayer of lipid vesicles is immobilized on the surface of the planar NMR microprobe in a patterned way. 1H NMR spectra and CPMG spin echoes of sucrose solution confined within the lipid vesicles are successfully recorded. Nutation curves of the sample structured in different patterns demonstrate the impact of patterning on the spin excitation uniformity. The total detection volumes are between 1 and 2 nL and derived with help of a theoretic model based on 3D finite element simulation. This model predicts the signal-to-noise ratio and the progression of the nutation curves.

Effects of socio-demographic variables on health-related quality of life determined by the quality of life index--German version.

STUDY OBJECTIVE: The purpose of this study was to determine subjective health-related quality of life (HRQoL) in a sample of the Austrian population over 14 years of age in order to evaluate the effect of socio-demographic variables on HRQoL. DESIGN/SETTING: HRQoL was determined by means of the quality of life index-German version (QLI-Ge). The influence of socio-demographic variables on HRQoL was assessed by statistical analysis using the Kruskal-Wallis test and an analysis of variance. PARTICIPANTS: A random-quota procedure was used to get balanced representation from regions and demographic groups of the Austrian population. The sample consisted of 1049 participants, 493 men and 556 women. MAIN RESULTS: Age was found to influence the QLI-Ge total score (index score) and most individual items, with increasing age resulting in a decrease in HRQoL. Differences between the sexes were observed in three dimensions: males scored higher in 'physical well-being', 'psychological well-being' and 'occupational functioning'. Marital status impacted most items with married persons showing better values than divorced persons or singles. Profession had only a minor effect on HRQoL, the level of education showed no influence at all. CONCLUSIONS: The socio-demographic variables age, sex and objective living conditions had a major influence on subjectively rated HRQoL, whereas profession and education were found to play a minor role in this context. It is recommended that in the interpretation of studies assessing HRQoL the above-mentioned objective factors be considered. This will be of particular importance when determining the effect of a pharmacotherapy on HRQoL in patients.

Planar microcoil-based microfluidic NMR probes.

Microfabricated small-volume NMR probes consisting of electroplated planar microcoils integrated on a glass substrate with etched microfluidic channels are fabricated and tested. 1H NMR spectra are acquired at 300 MHz with three different probes having observed sample volumes of respectively 30, 120, and 470 nL. The achieved sensitivity enables acquisition of an 1H spectrum of 160 microg sucrose in D2O, corresponding to a proof-of-concept for on-chip NMR spectroscopy. Increase of mass-sensitivity with coil diameter reduction is demonstrated experimentally for planar microcoils. Models that enable quantitative prediction of the signal-to-noise ratio and of the influence of microfluidic channel geometry on spectral resolution are presented and successfully compared to the experimental data. The main factor presently limiting sensitivity for high-resolution applications is identified as being probe-induced static magnetic field distortions. Finally, based on the presented model and measured data, future performance of planar microcoil-based microfluidic NMR probes is extrapolated and discussed.

Oxyfluorfen toxic effect on S. obliquus evaluated by different photosynthetic and enzymatic biomarkers.

The effect of oxyfluorfen was investigated when alga Scenedesmus obliquus has been exposed to different concentrations (7.5, 15, and 22.5 microg x L(-1)) at 12, 24, and 48 hours of exposure. Toxicity test was done by using 13 biomarkers concerning growth rate, chlorophyll content and indicators of photosynthetic and antioxidant enzyme activities. The change of the 13 parameters showed a great variation of sensitivity indicating differences in parameters' suitability to be used as biomarkers when alga culture was exposed to oxyfluorfen toxicity. The order of sensitivity between those biomarkers was: Antenna size (ABS/RC) > Chlorophyll content > Catalase (CAT) > Operational PSII quantum yield (phiS(PSII)) > Glutathione S-transferase (GST) > Functional plastoquinone pool (Q(PQ)) > Glutathione reductase (GR) > Growth rate > Nonphotochemical quenching (QN) > Proton gradient quenching (Q(Emax)) > Ascorbate peroxidase (APX) > Photochemical quenching (Q(p)) > Maximum PSII quantum yield (Phi(PSII)). The effect of oxyfluorfen on the changes of those parameters was interpreted as a result of herbicide mode of action at molecular level of alga cellular system. This study indicated for some photosynthetic and enzymatic biomarkers to be useful indicators of toxicity effect induced in non-target alga species. Determination of biomarkers' sensitivity order may facilitate their selection to be used in environmental risk assessment of polluted water.

PAM fluorometry in the determination of the sensitivity of Chlorella vulgaris, Selenastrum capricornutum, and Chlamydomonas reinhardtii to copper.

The pulse-amplitude-modulation (PAM) fluorometric method was used in the past as a sensitive and rapid method for assessing toxic effect of pollutants in plants. Here, we used the advantages of this method to evaluate the difference in sensitivity of Chlorella vulgaris, Selenastrum capricornutum, and Chlamydomonas reinhardtii to copper toxicity. We found by using the PAM-fluorescence parameters (phiM, phi'M, QP, and QN), that C. reinhardtii is the most sensitive species, followed by S. capricornutum and C. vulgaris. Indeed, the copper 5-, 48-, and 96-h EC50 for phiM, phi'M, and QP vary between 11 and 34 microg/L for C. reinhardtii, while for S. capricornutum this value is between 25 and 50 microg/L. However, the same parameters obtained from C. vulgaris did not show susceptibility to copper, even at very high concentrations (100 microg/L). In this study, the estimated 5-h EC50 for C. reinhardtii and S. capricornutum are lower than the 24-h EC50 reported earlier for these species with other bioassays, indicating that the use of PAM fluorometry in copper bioassay provides a more sensitive method than the other biotests in aquatic toxicology.

Sleeping habits in the Austrian population.

OBJECTIVES: To gain reliable data on sleeping habits and sleep disturbances of the Austrian population. BACKGROUND: Exact data on sleeping habits are of interest in relation to assessment of sleep disturbance-related illnesses and general social processes. METHODS: A prospective, cross-sectional study was performed with recruitment of a representative sample of 1049 Austrians (aged 15-82 years), according to the Federal Statistics population characteristics. Interviews were conducted in the households of the participants by specially trained interviewers of an institute for empirical research. RESULTS: Men consider their quality of sleep to be significantly better than women (P=0.00234), and younger persons consider their quality of sleep to be significantly better than older persons (P=0.00001). In comparison, women and people over the age of 50 report worse subjective sleep quality, worse sleep efficiency, more difficulty in falling asleep and sleep maintenance, more apneic events, more pathologic limb movements, more daytime dysfunction, and more intake of sleeping medication. Other sociodemographic factors influence sleep reports to a lesser extent. CONCLUSIONS: Subjectively disturbed sleep (prevalence in the total population 24.9%), excessive hypnotic drug intake (prevalence 13.0%), and daytime dysfunction (prevalence 17.4%) are a widespread problem, especially in women and older people. With increasing life expectancy in Western societies, the prevalence of sleep disturbances will increase.

Evaluation of different algal species sensitivity to mercury and metolachlor by PAM-fluorometry.

In this study, the pulse-amplitude-modulation (PAM)-fluorometric method was used to evaluate the difference in the sensitivity to mercury (Hg) and metolachlor of six algal species: Ankistrodesmus falcatus, Selenastrum capricornutum, Chlorella vulgaris, Nannoplankton (PLS), Microcystis aeruginosa and Pediastrum biwae. We found that the fluorescence parameters (phiM, the maximal photosystem II (PSII) quantum yield, phi'M, the operational PSII quantum yield at steady state of electron transport, Q(P), the photochemical quenching value, and Q(N), the non-photochemical quenching value) were appropriate indicators for inhibitory effects of mercury but only phi'M and Q(N) were useful for metolachlor. The examined algal species showed very different levels of sensitivity to the effect of Hg and of metolachlor. The most sensitive species to Hg and metolachlor were respectively M. aeruginosa and A. falcatus, while the least sensitive were C. vulgaris and P. biwae. We interpreted these differences by the action mode of pollutants and by the different metabolism properties and morphological characteristics between algal species. These results related to fluorescence parameters may offer useful tool to be used in bioassay for different pollutants. Heterogeneous algal sensitivity to the same pollutant suggests the need to use a battery of species to evaluate the effects of mixtures of pollutants in aquatic systems.

Spectroscopic analysis of desiccation-induced alterations of the chlorophyllide transformation pathway in etiolated barley leaves.

Effects of water deficit on the chlorophyllide (Chlide) transformation pathway were studied in etiolated barley (Hordeum vulgare) leaves by analyzing absorption spectra and 77-K fluorescence spectra deconvoluted in components. Chlide transformations were examined in dehydrated leaves exposed to a 35-ms saturating flash triggering protochlorophyllide (Pchlide) and Chlide transformation processes. During the 90 min following the flash, we found that dehydration induced modifications of Chlide transformations, but no effect on Pchlide phototransformation into Chlide was observed. During this time, content of NADPH-Pchlide oxydoreductase in leaves did not change. Chlide transformation process in dehydrated leaves was characterized by the alteration of the Shibata shift process, by the appearance of a new Chlide species emitting at 692 nm, and by the favored formation of Chl(ide) A(668)F(676). The formation of Chl(ide) A(668)F(676), so-called "free Chlide," was probably induced by disaggregation of highly aggregated Chlide complexes. Here, we offer evidence for the alteration of photoactive Pchlide regeneration process, which may be caused by the desiccation-induced inhibition of Pchlide synthesis.

Effects of neuroprotective cocktails on hippocampal neuron death in an in vitro model of cerebral ischemia.

Cocktails of neuroprotectants acting at different parts of the ischemic injury cascade may have advantages over single agents. This study investigated, singly and in combination, the neuroprotective efficacy of an energy substrate (3.5 mM fructose 1,6-bisphosphate, FBP), an antagonist of NMDA receptors (1 and 10 microM MK-801), a free-radical scavenger (100 microM ascorbate), an adenosine A1 receptor agonist (10 microM 2-chloroadenosine), and an inhibitor of neurotransmission (2% isoflurane). These agents were evaluated for their ability to prevent loss and morphologic damage of CA1 neurons in rat hippocampal slices when these agents were administered during 30 minutes in vitro ischemia (combined oxygen/glucose deprivation at 37 degrees C) followed by 5 hours of recovery. Ten microM MK-801, alone or in combination with the other compounds, prevented loss of CA1 neurons and preserved their histologic appearance. Isoflurane, which prevents glutamate receptor-dependent cell death in this model, was also protective. Protection against neuron loss was also found when a subtherapeutic concentration of MK-801 (1 microM) was combined with 2-chloroadenosine (which indirectly causes NMDA receptor suppression), but not FBP or ascorbate. The authors conclude that in this model, the strategy of antagonizing NMDA receptors appears more protective than fructose-1,6-bisphosphate, 2-chloroadenosine or ascorbate.