The impact of different health dimensions on overall quality of life related to kyphoplasty and non-surgical management.

UNLABELLED: This study uses data from a previously published randomised trial where balloon kyphoplasty was compared to non-surgical management. Of the improved overall quality of life, 60 % was caused by decreased pain. However, ignoring other dimensions of quality of life would underestimate the procedure's effect. INTRODUCTION: Acute back pain has been viewed as the most important factor lowering quality of life (QoL) for patients suffering vertebral fractures. The objective of this study was to quantify the impact of different health dimensions on overall QoL using patient-reported outcome measurements (PROMs) collected in Fracture Reduction Evaluation (FREE) trial. METHODS: The analysis was based on patients included in the 2-year-long randomised controlled FREE trial studying the efficacy and safety of balloon kyphoplasty procedure (BKP) compared to non-surgical management (NSM). The PROMs included were EQ-5D, Short Form (SF)-36, visual analogue scale (VAS) pain and the Roland-Morris Disability Questionnaire (RMDQ). The health dimensional contribution to the overall QoL improvements was analysed by isolating the impact of each dimension on QoL in the SF-36 and EQ-5D, respectively. A correlation analysis of the QoL improvement was performed to investigate the relationships between the four instruments. RESULTS: Changes in pain explained 60 % of the quality-adjusted life years (QALY) gained in BKP vs. NSM followed by self-care (17 %), mobility (16 %) and usual activities (10 %) (EQ-5D). Health dimensions capturing the mental state had little impact on the QALY gained. The SF-36 dimensional analysis showed similar results. The correlation analysis showed that the correlation between VAS pain, RMDQ and QALY improvement was fairly weak. CONCLUSIONS: Changes in the pain dimension of health are the most important drivers for changes of overall QoL in patients treated with BKP or NSM. However, ignoring the impact of other dimensions would lead to an underestimation of the actual improvement in overall QoL.

Eastern geothermal resources: should we pursue them?

A geothermal resource that consists of hot water at moderate temperatures (below 125 degrees C) underlies many areas in the central and eastern United States. Programs funded by the Department of Energy have revealed that this resource is definable and economically competitive with conventional fuels for use in direct heat applications. The resource, therefore, has the potential for reducing our dependence on the imported oil used for space heating. However, front-end costs and risks to explore, drill, test, and evaluate the magnitude of the resource have inhibited development. The question is, therefore, how much federal stimulation will be needed to convince private capital to exploit this widespread low-quality energy source.

Three Mars years: viking lander 1 imaging observations.

The Mutch Memorial Station (Viking Lander 1) on Mars acquired imaging and meteorological data over a period of 2245 martian days (3:3 martian years). This article discusses the deposition and erosion of thin deposits (ten to hundreds of micrometers) of bright red dust associated with global dust storms, and the removal of centimeter amounts of material in selected areas during a dust storm late in the third winter. Atmospheric pressure data acquired during the period of intense erosion imply that baroclinic disturbances and strong diurnal solar tidal heating combined to produce strong winds. Erosion occurred principally in areas where soil cohesion was reduced by earlier surface sampler activities. Except for redistribution of thin layers of materials, the surface appears to be remarkably stable, perhaps because of cohesion of the undisturbed surface material.

Early meteorological results from the viking 2 lander.

Early results from the meteorological instruments on the Viking 2 lander are presented. As on lander 1, the daily patterns of temperature, wind, and pressure have been highly repetitive during the early summer period. The average daily maximum temperature was 241 degrees K and the diurnal minimum was 191 degrees K. The wind has a vector mean of 0.7 meter per second from the southeast with a diurnal amplitude of 3 meters per second. Pressure exhibits both diurnal and semidiurnal oscillations, although of substantially smaller amplitude than those of lander 1. Departures from the repetitive diurnal patterns begin to appear on sol 37.

Preliminary meteorological results on Mars from the viking 1 lander.

The results from the meteorology instruments on the Viking 1 lander are presented for the first 4 sols of operation. The instruments are working satisfactorily. Temperatures fluctuated from a low of 188 degrees K to an estimated maximum of 244 degrees K. The mean pressure is 7.65 millibars with a diurnal variation of amplitude 0.1 millibar. Wind speeds averaged over several minutes have ranged from essentially calm to 9 meters per second. Wind directions have exhibited a remarkable regularity which may be associated with nocturnal downslope winds and gravitational oscillations, or to tidal effects of the diurnal pressure wave, or to both.

Mars climatology from viking 1 after 20 sols.

The results from the meteorology instruments on the Viking 1 lander are presented for the first 20 sols of operation. The daily patterns of temperature, wind, and pressure have been highly consistent during the period. Hence, these have been assembled into 20-sol composites and analyzed harmonically. Maximum temperature was 241.8 degrees K and minimum 187.2 degrees K. The composite wind vector has a mean diurnal magnitude of 2.4 meters per second with prevailing wind from the south and counterclockwise diurnal rotation. Pressure exhibits diurnal and semidiurnal oscillations. The diurnal is ascribed to a combination of effects, and the semidiurnal appears to be the solar semidiurnal tide. Similarities to Earth are discussed. A major finding is a continual secular decrease in diurnal mean pressure. This is ascribed to carbon dioxide deposition at the south polar cap.

DJ-1 binds androgen receptor directly and mediates its activity in hormonally treated prostate cancer cells.

The oncogene DJ-1 has been associated with multiple cancers, including prostate cancer, where it can be stabilized by androgens and antiandrogens. However, little data exist on the expression pattern and function of DJ-1 in prostate cancer. To address the function of DJ-1 in prostate, a yeast two-hybrid screen was done to identify novel DJ-1 binding proteins. The androgen receptor (AR) was identified and confirmed as a DJ-1 binding partner. This is the first evidence that DJ-1 directly interacts with AR. We also show that modulation of DJ-1 expression regulated AR transcriptional activity. Importantly, both the subcellular localization of DJ-1 and the interaction with AR are regulated by androgens and antiandrogens. Additionally, immunohistochemical staining on two human prostate cancer tissue arrays was done providing the first large-scale expression analysis of DJ-1 in prostate. DJ-1 expression did not change with Gleason pattern but increased after androgen deprivation therapy, indicating that it may be involved in the development of androgen independence. These data provide a novel mechanism where DJ-1-mediated regulation of AR may promote the progression of prostate cancer to androgen independence.

Description of International Caenorhabditis elegans Experiment first flight (ICE-FIRST).

Traveling, living and working in space is now a reality. The number of people and length of time in space is increasing. With new horizons for exploration it becomes more important to fully understand and provide countermeasures to the effects of the space environment on the human body. In addition, space provides a unique laboratory to study how life and physiologic functions adapt from the cellular level to that of the entire organism. Caenorhabditis elegans is a genetic model organism used to study physiology on Earth. Here we provide a description of the rationale, design, methods, and space culture validation of the ICE-FIRST payload, which engaged C. elegans researchers from four nations. Here we also show C. elegans growth and development proceeds essentially normally in a chemically defined liquid medium on board the International Space Station (10.9 day round trip). By setting flight constraints first and bringing together established C. elegans researchers second, we were able to use minimal stowage space to successfully return a total of 53 independent samples, each containing more than a hundred individual animals, to investigators within one year of experiment concept. We believe that in the future, bringing together individuals with knowledge of flight experiment operations, flight hardware, space biology, and genetic model organisms should yield similarly successful payloads.

Positive and negative thyroid hormone response elements are composed of strong and weak half-sites 10 nucleotides in length.

The steroid-thyroid hormone receptors bind to imperfect repeats of two or more half-sites. It is generally accepted that a T3 response element (TRE) half-site consists of a six-nucleotide core motif (5'-AGGT(C/A)A-3'). It is less widely appreciated that the nucleotides flanking this core motif also have a major influence on the affinity of T3 receptor (TR) for its response element. We analyzed TR-DNA interactions under conditions in which the affinity of receptor monomers for individual TRE half-sites of the rat GH (rGH) gene was measured. These studies avoided the effects of half-site spacing and orientation on receptor binding. Variations in the nucleotides flanking the core sequence can modulate receptor binding by more than 15-fold. Systematic mutational analysis of TRE half-site structure demonstrated that at least two nucleotides flanking either side of the half-site core motif strongly influence TR binding affinity and activity, indicating that half-sites are approximately 10 nucleotides long. Thus, the half-sites of most TREs overlap, and mutations in one half-site may affect the activity of its partner. The TRE half-site sequence 5'-CTGAGGTAACG-3' was bound with highest affinity by TRs. The negatively T3-responsive promoter of the rGH gene was used to investigate the functional significance of the nucleotides flanking the core motif in vivo. A promoter consisting of only 22 rGH nucleotides, containing two functional TRE half-sites which overlap the rGH TATA box, directed T3-inhibited transcription. Mutation of nucleotides flanking the core sequence of the weaker half-site dramatically reduced the activity of the element, demonstrating that the flanking sequences of the half-sites can profoundly affect TRE activity.

Structure and regulation of the mouse GRP78 (BiP) promoter by glucose and calcium ionophore.

Dietary calorie restriction, also termed energy restriction, increases mean and maximum life span, reduces the incidence of tumors and increases the mean age of onset of diseases and tumors in every animal tested. Because life-span is genetically determined, we are studying the mechanisms by which energy restriction regulates the expression of genes. We found that energy restriction reduces hepatic glucose-regulated protein-78 (GRP78) and protein-94 mRNA levels by 2-3-fold in mice [Spindler et al., J. Nutr. 20 (1990) 1412-1417]. To investigate this down-regulation, we have cloned the mouse GRP78 promoter (pGRP78) and studied its regulation by glucose. The mouse pGRP78 and the previously cloned rat promoter mediate responsiveness to glucose deprivation, as well as to the calcium ionophore A23187. These studies are the first demonstration that cis-elements in the pGRP78 mediate responsiveness to glucose deprivation.

Glucose regulation of GRP78 gene expression.

The endoplasmic reticulum chaperone glucose-regulated protein 78 (GRP78) is essential for the proper glycosylation, folding and assembly of many membrane bound and secreted proteins. GRP78 mRNA is well known to be induced in cultured cells by lowering medium glucose concentrations from 4.5 to 0 mg/ml. Here we report a study designed to determine the effects of intermediate concentrations of glucose on GRP78 mRNA abundance. Progressive reduction in culture medium glucose from 4.5 to 1.0 mg/ml progressively reduced GRP78 mRNA to approximately 30% of the initial level. Induction of GRP78 mRNA by glucose starvation was observed in medium containing less than 1 mg/ml glucose. Determination of the amount of glucose consumed in these cultures showed that reduction of glucose concentrations led first to repression of GRP78 mRNA abundance, followed by induction of the mRNA only when glucose is nearly exhausted. Caloric restriction in mice both reduces fasting and mean 24 h glucose blood concentrations and GRP78 mRNA abundance in the liver. Thus, it is possible that negative regulation of GRP78 mRNA in the liver is due directly to reduced blood glucose concentrations.

Investigation of the role of calcium in the supersensitivity produced by cocaine in cat spleen strips.

1. Cocaine (2 x 10(-6) M and 10(-5) M) produced 2 and 7 fold shifts to the left of the dose-response curve to (-)-noradrenaline recorded isotonically in isolated splenic capsular strips of the cat. 2. The same concentrations of cocaine also produced increases in the maximum response of the tissue to 117% and 126.7% of control. 3. Desmethylimipramine (DMI, 10(-7) to 10(-6) M) produced no significant potentiation of the response of cat spleen strips to (-)-noradrenaline. At 10(-5) M DMI decreased the maximum response. 4. Cocaine (10(-5) M) produced a 3.3 fold shift to the left of the dose-response curve whereas DMI (10(-6) M) had no effect on the dose-response curve to oxymetazoline in cat splenic capsular strips. 5. Cocaine (10(-5) M) in the presence of phentolamine (10(-6) M) produced a shift to the left and an increase in the maximum response to K+, an agonist which is believed to produce muscle contraction by increasing the membrane calcium flux. 6. Cocaine (10(-5 M) had no effect on the dose-response curve to angiotensin which is believed to contract vascular muscle by releasing calcium from intracellular storage sites. 7. The potentiating effect of cocaine (10(-5) M) on responses of spleen strips to (-)-noradrenaline was blocked by the calcium flux inhibitor SKF 525A (2.65 x 10(-5) M). 8. It is concluded that the results are compatible with the view that cocaine enhances the influx of calcium across the cell membrane during responses to agonists that utilize the extracellular pool of calcium and that this effect is responsible for a large part of the potentiation of the response.

Promoter independent down-regulation of the firefly luciferase gene by T3 and T3 receptor in CV1 cells.

We report that the activity of the firefly luciferase (LUC) reporter gene is down-regulated by T3 and T3 receptor (TR) in the CV1 mammalian cell line, which is widely used for studies of TR action. Repression was highly reproducible, T3 and TR dependent, promoter independent, and observed regardless of whether an internal control for transfection efficiency was used. Cotransfections with normal and mutant TRs indicate that the negative T3 response is mediated by sequences within the LUC gene coding region, and is not due to the interaction of TR with a limiting transcription factor. Negative regulation of the LUC reporter was overcome by a strong, cis-linked T3 response element (TRE), but continued in the presence of a TRE of moderate strength. The results described here demonstrate that conclusions drawn from studies of TRE structure and activity performed using the LUC reporter in CV1 cells should be interpreted with caution.

Insect pheromones--an overview of biosynthesis and endocrine regulation.

This overview describes, compares, and attempts to unify major themes related to the biosynthetic pathways and endocrine regulation of insect pheromone production. Rather than developing and dedicating an entirely unique set of enzymes for pheromone biosynthesis, insects appear to have evolved to add one or a few tissue-specific auxiliary or modified enzymes that transform the products of "normal" metabolism to pheromone compounds of high stereochemical and quantitative specificity. This general understanding is derived from research on model species from one exopterygote insect order (Blattodea) and three endopterygote insect orders (Coleoptera, Diptera, and Lepidoptera). For instance, the ketone hydrocarbon contact sex pheromone of the female German cockroach, Blattella germanica, derives its origins from fatty acid biosynthesis, arising from elongation of a methyl-branched fatty acyl-CoA moiety followed by decarboxylation, hydroxylation, and oxidation. Coleopteran sex and aggregation pheromones also arise from modifications of fatty acid biosynthesis or other biosynthetic pathways, such as the isoprenoid pathway (e.g. Cucujidae, Curculionidae, and Scolytidae), or from simple transformations of amino acids or other highly elaborated host precursors (e.g. Scarabaeidae and Scolytidae). Like the sex pheromone of B. germanica, female-produced dipteran (e.g. Drosophilidae and Muscidae) sex pheromone components originate from elongation of fatty acyl-CoA moieties followed by loss of the carbonyl carbon and the formation of the corresponding hydrocarbon. Female-produced lepidopteran sex pheromones are also derived from fatty acids, but many moths utilize a species-specific combination of desaturation and chain-shortening reactions followed by reductive modification of the carbonyl carbon. Carbon skeletons derived from amino acids can also be used as chain initiating units and elongated to lepidopteran pheromones by this pathway (e.g. Arctiidae and Noctuidae). Insects utilize at least three hormonal messengers to regulate pheromone biosynthesis. Blattodean and coleopteran pheromone production is induced by juvenile hormone III (JH III). In the female common house fly, Musca domestica, and possibly other species of Diptera, it appears that during hydrocarbon sex pheromone biosynthesis, ovarian-produced ecdysteroids regulate synthesis by affecting the activities of one or more fatty acyl-CoA elongation enzyme(s) (elongases). Lepidopteran sex pheromone biosynthesis is often mediated by a 33 or 34 amino acid pheromone biosynthesis activating neuropeptide (PBAN) through alteration of enzyme activities at one or more steps prior to or during fatty acid synthesis or during modification of the carbonyl group. Although a molecular level understanding of the regulation of insect pheromone biosynthesis is in its infancy, in the male California fivespined ips, Ips paraconfusus (Coleoptera: Scolytidae), JH III acts at the transcriptional level by increasing the abundance of mRNA for 3-hydroxy-3-methylglutaryl-CoA reductase, a key enzyme in de novo isoprenoid aggregation pheromone biosynthesis.

Regulation of enzymatic activity involved in sex pheromone production in the housefly, Musca domestica.

Ovarian produced ecdysteroids regulate sex pheromone production in the female housefly, inducing the synthesis of (Z)-9-tricosene (Z9-23:Hy), cis-9,10-epoxytricosane, (Z)-14-tricosen-10-one and methylalkanes. Experiments were performed to gain a detailed understanding of the processes affected by 20-hydroxyecdysone (20-HE) that result in sex pheromone production as the female becomes reproductively mature. A novel microsomal fatty acid synthetase (FAS) is present in the epidermal tissue and plays a role in producing the methyl-branched fatty acid precursors to the methylalkanes. This FAS is released from the microsomes in the presence of 3 M KCl. A major enzyme activity influenced by 20-HE is the fatty acyl-CoA elongation system. A shift in the chain length specificity of the products of the elongation system causes the change in the chain lengths of the alkenes produced to switch from C27 and longer in the previtellogenic female to C23 in the mature female. Data is presented indicating that it is the condensation activity of the elongation system that is affected. Z9-23:Hy arises from a 24 carbon acyl group which is reduced to an aldehyde, and then converted to the hydrocarbon. Data is presented demonstrating that it is the fatty acyl-CoA derivative and not the free fatty acid that is the substrate. There does not appear to be a chain length specificity which regulates the conversion of fatty acyl-CoAs to hydrocarbons as both 24 and 28 carbon fatty acyl-CoAs are converted to hydrocarbon by both males and females of all ages.

Assessing the need for anaerobic medium for the recovery of clinically significant blood culture isolates in children.

We examined the sensitivity of several BACTEC media options for the detection of bacteremia and fungemia in children at two pediatric health care facilities. At one institution a single aerobic bottle containing PEDS Plus medium was as sensitive in identifying positive blood cultures as the combination of aerobic and anaerobic media (77% vs. 80%; P = 1.0). When data from both facilities were combined, a blood culture set containing both aerobic and anaerobic media detected significantly more positive blood cultures than any single aerobic medium. However, the aerobic/anaerobic bottle combination was not significantly better than a blood culture set containing two aerobic media and, in absolute terms, the latter identified more cases of bacteremia. Of the 116 clinically significant episodes of bacteremia identified in this study, only 1 was caused by an anaerobic bacterium. We conclude that the routine use of anaerobic media for blood cultures of pediatric patients might be unnecessary but that the use of two different aerobic media could increase the sensitivity of the BACTEC blood culture system.

Caloric intake alters the efficiency of catalase mRNA translation in the liver of old female mice.

The free radical theory of aging predicts that calorie restriction, which extends life span, should reduce oxidant damage. In mammals, the oxidative processes centered in the liver are a major source of free radicals. Liver catalase has the dominant role in the intracellular detoxification of hydrogen peroxide. In male rodents, published studies indicate that aging decreases catalase gene transcription and that calorie restriction obviates this effect. In females, published studies are inconsistent, and no molecular mechanisms have been identified. Here we report that, in female mice, aging can lead to an increase in the translational efficiency of hepatic catalase mRNA, and that calorie restriction obviates this effect. Consideration of these results and published studies leads us to propose that the variability in catalase results in females may arise from the small number of studies or from unique aspects of female physiology, perhaps the estrous cycle and its cessation with age.

The microcomputer and basic peripheral equipment.

This article has presented the basic information needed for setting up a microcomputer work station. The four basic components are the central processing unit (CPU), the monitor (CRT), the keyboard, and the disk drive. A brief overview of how the microcomputer works was presented, including the concepts of random-access memory (RAM) and read-only memory (ROM). The use of peripheral devices to enhance the operating capabilities of the microcomputer has allowed this technology to become practical and useful both at home and in business and research. Special furniture is available to assure a comfortable and practical environment. Perhaps one of the most important concepts presented in this article is the necessity of backing up data on a regular basis. Finally, computer equipment must be cleaned and maintained on a regular basis.

Changes in the bone and liver isoenzymes of alkaline phosphatase in postmenopausal women being treated with norethisterone.

The effects of norethisterone therapy on alkaline phosphatase isoenzyme activities were studied in a group of postmenopausal women. There was a significant fall in total alkaline phosphatase activity after 8 wk which was still in evidence after 24 wk. Both bone and liver alkaline phosphatase isoenzyme activities were decreased during the first 16 wk on treatment, but after 24 wk only the bone phosphatase activity was significantly lower than the pretreatment level. The other biochemical indices of bone metabolism and liver function were also measured during the study. The results indicate that bone specific alkaline phosphatase activity is a more sensitive index of bone activity than total alkaline phosphatase and that monitoring of total activity may in some instances be misleading.

Effect of fenoprofen on thyroid function tests.

We observed that a few patients taking the anti-inflammatory drug fenoprofen showed increases in total and free T3 serum levels without convincing evidence of an associated thyrotoxicosis. To confirm these findings, two volunteers were given fenoprofen for two weeks. Within this time total T3 levels almost doubled and free T3 levels increased threefold. Administration of fenoprofen did not have any measurable effect on T4 or TSH estimations. Cross-reactivities of fenoprofen and 4'-hydroxyfenoprofen were studied with antisera from various total and free T3 assays. Results show that the metabolite cross-reacts with the antisera from Amerlex total and free T3 assay kits. A lesser degree of interference was observed with the Corning total and free T3 assays. 4'-hydroxyfenoprofen had no effect on an 'in house' total T3 assay. Laboratories should therefore be aware of the possibility that their assay may be subject to interference by fenoprofen or its metabolites while clinicians should be aware of this interference in order that they may avoid unnecessary and harmful treatment.