Accelerometer-measured physical activity and its impact on sleep quality in patients suffering from restless legs syndrome.

BACKGROUND: The primary symptoms of restless legs syndrome (RLS) are sleep onset insomnia and difficulty to maintain sleep. Previous studies have shown that regular physical activity can reduce the risk of developing RLS. However, the relationship between physical activity and sleep quality parameters in individuals suffering from RLS has not yet been investigated by applying accelerometry. Thus, the present study investigates the impact of physical activity (measuring both intensity levels and duration of physical activity) during the day (7-12 h, 12-18 h, 18-23 h) on sleep quality in patients suffering from idiopathic RLS by applying a real-time approach. METHODS: In a sample of 47 participants suffering from idiopathic RLS, physical activity and sleep quality were measured over one week using accelerometers. For data analysis, physical activity levels and step counts during three periods of the day (morning, afternoon, evening) were correlated with sleep quality parameters of the subsequent night. RESULTS: This observational study revealed that in most instances physical activity was not correlated with sleep parameters (two exceptions exist: steps taken in the morning were negatively correlated with periodic leg movements during sleep, and physical activity in the evening was negatively correlated with total sleep time). The physical activity levels of the participants in this study, however, were unexpectedly high compared to population-level data and variance in physical activity was low. The average activity was 13,817 (SD = 4086) steps and 347 (SD = 117) minutes of moderate physical activity per day in females, and 10,636 (SD = 3748) steps and 269 (SD = 69) minutes of moderate physical activity in males, respectively. Participants did not engage in any vigorous physical activity. CONCLUSIONS: Further interventional studies are needed to investigate the daily effects of different intensities of physical activity on RLS symptoms.

[Physical training for neurological and mental diseases]. / Körperliches Training bei neurologischen und psychischen Erkrankungen.

BACKGROUND: Physical activity has beneficial effects on somatic and mental health factors; therefore, regular exercise has preventive and therapeutic capabilities to improve neurological and mental dysfunction. OBJECTIVES: In this overview of the current literature, the evidence of the effects of exercise on such disorders is summarized. Physical exercise interventions for stroke, Parkinson's disease, dementia, depression, psychoses, anxiety disorders, and chronic pain syndromes are considered in detail. RESULTS: Physical activity reduces the risk of suffering from stroke, dementia and Parkinson's disease. Furthermore, it is negatively correlated with dysthymia and other depressive symptoms and various anxiety and pain disorders as well as headache syndromes. A therapeutic effect of systematic physical exercise was revealed for depression, some symptoms of psychosis and multiple sclerosis, addiction, eating disorders, the fibromyalgia syndrome as well as short-term interventions for anxiety disorders. CONCLUSION: The concerted integration of physical exercise into prophylactic and therapeutic interventions can lower the burden of neurological and mental diseases; however, scientific evidence is still lacking concerning the optimal duration, type, and intensity as well as potential risks of physical exercise.

A collimated, high-speed outflow from the dying star V Hydrae.

Stars with masses in the range 1-8 solar masses (M(\circ)) live ordinary lives for approximately 10(9)-10(10) years, but die extraordinary deaths. First, during their death throes as asymptotic giant branch (AGB) stars they eject, over 10(4)-10(5) years, half or more of their mass in slowly expanding, spherical winds, and then, in a short (a few 100-1,000 years) and poorly understood phase, they are transformed into aspherical planetary nebula. Recent studies support the idea that high-speed, jet-like flows play a crucial role in this transformation. Evidence for such outflows is indirect, however; this phase is so short that few nearby stars are likely to be caught in the act. Here we report the discovery of a newly launched, high-speed jet-like outflow in the nearby AGB star, V Hydrae. We have detected both proper motions and ongoing evolution in the jet. These results support a model in which the jet is driven by an accretion disk around an unseen, compact companion. We also find a central, dense equatorial disk-like structure which may enable and/or enhance the formation of the accretion disk.

Physical activity and all-cause mortality: an updated meta-analysis with different intensity categories.

In a meta-analysis we investigated the effect of physical activity with different intensity categories on all-cause mortality. Many studies have reported positive effects of regular physical activity on primary prevention. This recent meta-analysis analyzed all-cause mortality with special reference to intensity categories. A computerized systematic literature search was performed in EMBASE, PUBMED, and MEDLINE data bases (1990-2006) for prospective cohort studies on physical leisure activity. Thirty-eight studies were identified and evaluated. The presentation refers to studies with 3 or 4 different intensities of regular physical activity according to a standard questionnaire. There was a significant association of lower all-cause mortality for active individuals compared with sedentary persons. For studies with three activity categories (mildly, moderately, and highly active) and multivariate-adjusted models, highly active men had a 22% lower risk of all-cause mortality (RR=0.78; 95% CI: 0.72 to 0.84) compared to mildly active men. For women, the relative risk was 0.69 (95% CI: 0.53 to 0.90). We observed similar results in moderately active persons compared to mildly active individuals (RR=0.81 for men and RR=0.76 for women). This association of activity to all-cause mortality was similar and significant in older subjects. Regular physical activity over longer time is strongly associated with a reduction in all-cause mortality in active subjects compared to sedentary persons. There is a dose-response curve especially from sedentary subjects to those with mild and moderate exercise with only a minor additional reduction with further increase in activity level.

Strontium-modified premixed calcium phosphate cements for the therapy of osteoporotic bone defects.

In this study a premixed strontium-containing calcium phosphate bone cement for the application in osteoporotic bone defects has been developed and characterised regarding its material and in vitro properties as well as minimally invasive applicability in balloon kyphoplasty. Strontium was introduced into the cement by substitution of one precursor component, CaCO3, with its strontium analogue, SrCO3. Using a biocompatible oil phase as carrier liquid, a cement paste that only set upon contact with aqueous environment was obtained. Strontium modification resulted in an increased strength of set cements and radiographic contrast; and the cements released biologically relevant doses of Sr2+-ions that were shown to enhance osteoprogenitor cell proliferation and osteogenic differentiation. Finally, applicability of strontium-containing cement pastes in balloon kyphoplasty was demonstrated in a human cadaver spine procedure. The cement developed in this study may therefore be well suited for minimally invasive, osteoporosis-related bone defect treatment. STATEMENT OF SIGNIFICANCE: Strontium-releasing calcium phosphate bone cements are promising materials for the clinical regeneration of osteoporosis-related bone defects since they have been shown to stimulate bone formation and at the same time limit osteoclastic bone resorption. Today clinical practice favours minimally invasive surgical techniques, e.g. for vertebral fracture treatment, posing special demands on such cements. We have therefore developed a premixed, strontium-releasing bone cement with enhanced mechanical properties and high radiographic visibility that releases biologically relevant strontium concentrations and thus stimulates cells of the osteogenic lineage. In a pilot experiment we also exemplify its excellent suitability for minimally invasive balloon kyphoplasty procedures.

Frameshift suppressor mutations outside the anticodon in yeast proline tRNAs containing an intervening sequence.

Extragenic suppressors of +1 frameshift mutations in proline codons map in genes encoding two major proline tRNA isoacceptors. We have shown previously that one isoacceptor encoded by the SUF2 gene (chromosome 3) contains no intervening sequence. SUF2 suppressor mutations result from the base insertion of a G within a 3'-GGA-5' anticodon, allowing the tRNA to read a 4-base code word. In this communication we describe suppressor mutations in genes encoding a second proline tRNA isoacceptor (wild-type anticodon 3'-GGU-5') that result in a novel mechanism for translation of a 4-base genetic code word. The genes that encode this isoacceptor include SUF7 (chromosome 13), SUF8 (chromosome 8), trn1 (chromosome 1), and at least two additional unmapped genes, all of which contain an intervening sequence. We show that suppressor mutations in the SUF7 and SUF8 genes result in G-to-U base substitutions at position 39 that disrupted the normal G . C base pairing in the last base pair of the anticodon stem adjacent to the anticodon loop. These anticodon stem mutations might alter the size of the anticodon loop and permit the use of a 3'-GGGU-5' sequence within the loop to read 4-base proline codons. Uncertainty regarding the exact structure of the mature suppressor tRNAs results from the possibility that anticodon stem mutations might affect sites of intervening sequence removal. The possible role of the intervening sequence in the generation of mature suppressor tRNA is discussed. Besides an analysis of suppressor tRNA genes, we have extended previous observations of the apparent relationship between tRNA genes and repetitive delta sequences found as solo elements or in association with the transposable element TY1. Hybridization studies and a computer analysis of the DNA sequence surrounding the SUF7 gene revealed two incomplete, inverted delta sequences that form a stem and loop structure located 165 base pairs from the 5' end of the tRNA gene. In addition, sequences beginning 164 base pairs from the 5' end of the trn1 gene also exhibit partial homology to delta. These observations provide further evidence for a nonrandom association between tRNA genes and delta sequences.

Mutations in the anticodon stem affect removal of introns from pre-tRNA in Saccharomyces cerevisiae.

To evaluate the role of exon domains in tRNA splicing, the anti-codon stem of proline pre-tRNAUGG from Saccharomyces cerevisiae was altered by site-directed mutagenesis of the suf8 gene. Sixteen alleles were constructed that encode mutant pre-tRNAs containing all possible base combinations in the last base pair of the anticodon stem adjacent to the anticodon loop (positions 31 and 39). The altered pre-tRNAs were screened by using an in vitro endonucleolytic cleavage assay to determine whether perturbations in secondary structure affect the intron excision reaction. The pre-tRNAs were cleaved efficiently whenever secondary structure in the anticodon stem was maintained through standard base pairing or G.U interactions. However, most of the pre-tRNAs with disrupted secondary structure were poor substrates for intron excision. We also determined the extent to which the suf8 alleles produce functional products in vivo. Each allele was integrated in one to three copies into a yeast chromosome or introduced on a high-copy-number plasmid by transformation. The formation of a functional product was assayed by the ability of each allele to suppress the +1 frameshift mutation his4-713 through four-base codon reading, as shown previously for the SUF8-1 suppressor allele. We found that alleles containing any standard base pair or G.U pair at position 31/39 in the anticodon stem failed to suppress his4-713. We could not assess in vivo splicing with these alleles because the tRNA products, even if they are made, would be expected to read a normal triplet rather than a quadruplet codon. However, all of the alleles that contained a disrupted base pair at position 31/ 39 in the anticodon stem altered the structure of the tRNA in a manner that caused frameshift suppression. Suppression indicated that splicing must have occurred to some extent in vivo even though most of the suppression alleles produced pre-tRNAs that were cleaved with low efficiency or not at all in vitro. These results have important implications for the interpretation of in vitro cleavage assays in general and for the potential use of suppressors to select mutations that affects tRNA splicing.

Splicing of a yeast proline tRNA containing a novel suppressor mutation in the anticodon stem.

The intron-containing proline tRNAUGG genes in Saccharomyces cerevisiae can mutate to suppress +1 frameshift mutations in proline codons via a G to U base substitution mutation at position 39. The mutation alters the 3' splice junction and disrupts the bottom base-pair of the anticodon stem which presumably allows the tRNA to read a four-base codon. In order to understand the mechanism of suppression and to study the splicing of suppressor pre-tRNA, we determined the sequences of the mature wild-type and mutant suppressor gene products in vivo and analyzed splicing of the corresponding pre-tRNAs in vitro. We show that a novel tRNA isolated from suppressor strains is the product of frameshift suppressor genes. Sequence analysis indicated that suppressor pre-tRNA is spliced at the same sites as wild-type pre-tRNA. The tRNA therefore contains a four-base anticodon stem and nine-base anticodon loop. Analysis of suppressor pre-tRNA in vitro revealed that endonuclease cleavage at the 3' splice junction occurred with reduced efficiency compared to wild-type. In addition, reduced accumulation of mature suppressor tRNA was observed in a combined cleavage and ligation reaction. These results suggest that cleavage at the 3' splice junction is inefficient but not abolished. The novel tRNA from suppressor strains was shown to be the functional agent of suppression by deleting the intron from a suppressor gene. The tRNA produced in vivo from this gene is identical to that of the product of an intron+ gene, indicating that the intron is not required for proper base modification. The product of the intron- gene is a more efficient suppressor than the product of an intron+ gene. One interpretation of this result is that inefficient splicing in vivo may be limiting the steady-state level of mature suppressor tRNA.

Long-term survival and neurologic status after resuscitation from out-of-hospital cardiac arrest.

Thirty-eight survivors from among 117 patients hospitalized after out-of-hospital cardiac arrest were evaluated approximately 3 1/2 years later. Twenty patients were living; 18 had died. Fifty-three percent had resumed independent social activities, but only 32% had returned to work. Eight of 14 patients tested were normal on limited neuropsychologic tests. Satisfactory long-term outcome was associated statistically with the patient's being awake on admission or awakening to follow simple commands within 2 days, and with good neurologic status at the time of discharge from the hospital. None of nine patients with poor neurologic function at discharge subsequently resumed working or independent living.

Enzymatic approaches to probing of RNA secondary and tertiary structure.

To make strong statements about possible tertiary structure or the relative stability of regions of secondary structure, the structure-probing experiments must go further than single-hit reactions. Some elements of the environment of the RNA molecule must be altered systematically. Knowledge of the effects of ions or other interacting factors on the activity or physical parameters (e.g., NMR and melting cooperativity) of the RNA help in experimental design. For example, the copious work on tRNA(Phe) compared the crystal and solution structures and allowed the direct correlation of Mg2+ stabilization of the tertiary structure of that molecule. Figure 3 demonstrates that pre-tRNA(Leu-3) responds to Mg2+ depletion in the same manner as detected by the appearance of highly sensitive RNase cleavage sites in the D and T psi C loops. Similar experiments titrating polyamine concentrations suggested that secondary structure was more efficiently stabilized by polyamines than by Mg2+. The variation of Mg2+ concentrations has been used to gain additional information about other RNA structures. Others have used protein-RNA interactions to approach the question of the functional structure of a RNA (for examples, see Ref. 3). Thus, the ideal parameters to choose would be those known to affect the function of the RNA. The variation of Mg2+ and polyamine concentrations would minimally suggest regions of greater or lesser secondary or tertiary structure stability.

Microglial/macrophage accumulation during cuprizone-induced demyelination in C57BL/6 mice.

To study microglial/macrophage infiltration, a cuprizone-induced model for demyelination in C57BL/6 mice was established. Cuprizone is known to cause demyelination in Swiss mice, however, cuprizone-induced demyelination in C57BL/6 mice has not been previously described. Induction of demyelination in C57BL/6 mice enables examination of the function of microglia/macrophage through comparative analyses of syngeneic mice with various targeted genetic mutations. In this report, cuprizone-induced demyelination is easily inducible, localized, and predictable. Concurrent with the initiation of demyelination, we noted microglial/macrophage accumulation and changes in astrocyte morphology. Astrogliosis promptly followed microglia/macrophage recruitment. These observations suggested that microglia/macrophage actively contribute to the demyelination process.

Identification and quantification of 6 beta-hydroxydexamethasone as a major urinary metabolite of dexamethasone in man.

Identification of 6 beta-hydroxydexamethasone as a major urinary metabolite of dexamethasone in man has been accomplished by nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry. Mass fragmentographic measurements revealed that more than 30% of the intravenously or orally administered dexamethasone dose was excreted in the 24-h urine as 6 beta-hydroxydexamethasone, while only a small fraction of the dose was excreted as unchanged dexamethasone and its glucuronic acid conjugate.

Total digestion of silicate containing matrices (plants, soil, sludges) using a pressure ashing device with PFA-vessels.

A digestion procedure for silicate containing matrices like soil, sludge, etc. by using a commercially available pressure ashing device (Seif-Aufschlubetatechnik, Germany) with PFA (perfluoroalkoxy) sample vessels is described at the results for different matrix- and trace elements in different suitable certified standard reference materials. The advantages of this technique compared with the use of Teflon(R)-(PTFE, polytetrafluoroethylene) vessels and the open treatment in Pt-crucibles will be discussed.

Stable-isotope methodology in the bioavailability study of 17 alpha-methyltestosterone using gas chromatography-mass spectrometry.

The application of a stable-isotope coadministration technique for estimating the relative bioavailability of 17 alpha-methyltestosterone is described. Eight healthy male subjects were administered orally a single 10-mg 17 alpha-methyltestosterone tablet together with a 10-mg 17 alpha-methyltestosterone-d3 solution. The serum concentrations of 17 alpha-methyltestosterone and 17 alpha-methyltestosterone-d3 were determined by gas chromatography-mass spectrometry with selected ion monitoring using 17 alpha-methyltestosterone-d6 as an internal standard. The extent of absorption from the tablet formulation was comparable to that from the oral solution. The stable-isotope methodology was compared with the conventional cross-over method for evaluating the bioavailability of 17 alpha-methyltestosterone.

The frequency of illegitimate V(D)J recombinase-mediated mutations in children treated with etoposide-containing antileukemic therapy.

Etoposide is among the most widely used anti-cancer drugs. Its use, however, has been associated with increased risk of secondary acute myeloid leukemia (AML) which is characterized by chromosomal translocations suggesting involvement of recombination-associated motifs at the breakpoints. A PCR-based assay was developed to quantitate the frequency of two illegitimate V(D)J recombinase-mediated genomic rearrangements-a 20-kb deletion in the hprt gene and the bcl2/IgH translocation (t(14;18)) found in non-Hodgkin's lymphoma. We examined both lymphocyte and non-lymphocyte blood cell DNA of children with acute lymphoblastic leukemia (ALL) for changes in the frequencies of these biomarkers during etoposide therapy to determine the level of illegitimate V(D)J recombination changes during therapy. A low level of t(14;18) was found in the lymphocytes before etoposide treatment, which was significantly reduced during etoposide therapy. In before-etoposide samples, no t(14;18) were found among 7.72x107 non-lymphocytes; during treatment none were found among 1.87x108 non-lymphocytes. Deletions were not found before etoposide treatment in either the lymphocytes (6.67x107) or non-lymphocytes (5.43x107) and were non-significantly elevated during etoposide therapy (1 in 1.4x108 lymphocytes and 1 in 1.39x108 non-lymphocytes). It is interesting to note the one patient with an hprt deletion mutation in non-lymphocytes; V(D)J recombination is not normally found in this cell type, but is the cell type from which AML derives. Several patients had clones of t(14;18)-bearing cells as determined by DNA sequence analysis. These results suggest that this etoposide-based chemotherapy was ineffective in producing genomic rearrangements mediated by illegitimate V(D)J recombination in these patients.

Quantification of illegitimate V(D)J recombinase-mediated mutations in lymphocytes of newborns and adults.

We used a direct polymerase chain reaction (PCR) method for quantification of HPRT exons 2 + 3 deletions and t(14;18) translocations as a measure of illegitimate V(D)J recombination. We determined the baseline frequencies of these two mutations in mononuclear leukocyte DNA from the umbilical cord blood of newborns and from the peripheral blood of adults. In an initial group of 21 newborns, no t(14;18) translocations were detected (< 0.049 x 10(-7)). The frequency of HPRT exons 2 + 3 deletions was 0.10 x 10(-7) per mononuclear leukocyte, lower than expected based on the T-cell proportion of this cell fraction (55%-70%) and previous results using the T-cell cloning assay (approximately 2-3 x 10(-7) per clonable T-cell). Phytohemagglutinin (PHA), as used in the T-cell cloning assay, was examined for its effect on the frequencies of these mutation events in mononuclear leukocytes from an additional 11 newborns and from 12 adults. There was no significant effect of PHA on t(14;18) translocations which were rare among the newborns (1 detected among 2.7 x 10(8) leukocytes analyzed), and which occurred at frequencies from < 1 x 10(-7) (undetected) to 1.6 x 10(-4) among the adults. The extremely high frequencies of t(14;18)-bearing cells in three adults were due mainly to in vivo expansion of two to six clones. However, PHA appeared to stimulate a modest (although not significant) increase in the frequency of HPRT exons 2 + 3 deletions in the leukocytes of the newborns, from 0.07 x 10(-7) to 0.23 x 10(-7). We show that both the direct PCR assay and the T-cell cloning assay detect similar frequencies of HPRT exons 2 + 3 deletions when calculations are normalized to blood volume, indicating that the apparent discrepancy is probably due to the different population of cells used in the assays. This direct PCR assay may have utility in characterizing the effects of environmental genotoxic agents on this clinically important recombination mechanism.

Sequential testing as an efficient screening method for interferences in routine analysis as applied to atomic-absorption spectrometry with flame and graphite furnace atomization.

Reliable standardization is a serious problem for most analytical methods. In spite of extensive work on interferences, the results are not suited for prediction of gross errors in any particular case. This paper is intended to show the power of sequential testing in practical atomic-absorption spectrometric analyses for the efficient detection of interferences causing changes in sensitivity; this test is carried out by comparing the sensitivity of the standard with the sensitivity for the sample, as determined by the difference between the signals for the spiked and unspiked samples. The simple computations can be carried out instantly and experimentation is terminated as soon as a conclusion can be drawn. The major advantage over the traditional tests lies in the smaller number of independent measurements, requiring less time and sample. Three separate cases are discussed: with the mean sensitivity of the standard known and the deviation expected to occur in one direction only (single-sided alternative hypothesis); with the standard deviation of the determination known and the deviation possibly occurring in both directions (double-sided alternative hypothesis); and with the mean and the standard deviation unknown but estimated during the test (sequential t-test). It is shown that assumptions about the normal distribution of the data do not impose serious restrictions in practical AAS work.

A sensitive atomic-absorption spectrometric method for the determination of tin with atomization from impregnated graphite surfaces.

The atomization of Sn from graphite surfaces is potentially hindered by reactions with the surface. The impregnation of graphite tubes with other carbide-forming elements (W, Zr, Ta, Mo) favourably alters the surface characteristics of the graphite furnace for the atomization of Sn. At the acid concentrations needed to prevent the hydrolysis of Sn, these surfaces are considerably more stable (even after more than 100 atomization cycles) than those of pyrolytic graphite. Two graphite furnaces of different design, the HGA 72 and the HGA 76, were tested. With impregnated graphite tubes the determination of Sn is possible in the HGA 72 with a detection limit of approximately 15 pg. In the HGA 76 the tin determination is vastly improved with respect to prolonged lifetime of the furnaces and stable signals over much longer periods of time. Detailed interference studies reveal that the use of the "gas stop" mode minimizes the influence of many ions that are frequently either introduced by the decomposition reagents or present in the sample itself. The practical potential of this method is demonstrated for the determination of Sn in a slag material and in copper- and aluminium-based alloys.