Self-management and adherence in childhood-onset systemic lupus erythematosus: what are we missing?

OBJECTIVES: The aims of this study are (1) to characterize factors influencing self-management behaviors and quality of life in adolescent and young adult (AYA) patients with childhood-onset systemic lupus erythematosus (cSLE) and (2) to identify barriers and facilitators of treatment adherence via focus groups. METHODS: AYAs with cSLE ages 12-24 years and primary caregivers of the adolescents participated in this study. Recruitment occurred during pediatric rheumatology clinic visits at a Midwestern children's hospital or the hospital's cSLE active clinic registry. Information about disease severity was obtained from patient health records. Pain and fatigue questionnaires were administered. Descriptive statistics were used to analyze data. RESULTS: Thirty-one AYA patients and caregivers participated in six focus groups. Ten major themes emerged from sessions; four were expressed both by the AYA and caregiver groups: knowledge deficits about cSLE, symptoms limiting daily function, specifically mood and cognition/learning, barriers and facilitators of adherence, and worry about the future. Themes unique to AYA participants included symptoms limiting daily functioning-pain/fatigue, self-care and management, impact on personal relationships, and health care provider communication/relationship. For caregiver groups unique themes included need for school advocacy, disruption of family schedule, and sense of normalcy for their adolescent. CONCLUSION: AYAs with cSLE face a lifelong disease characterized by pervasive pain, fatigue, organ damage, isolation-social and/or physical-and psycho-socioeducational challenges. This study confirmed that continued psychosocial support, health information education, adherence interventions, and personalized treatment plans are necessary to increase self-management and autonomy in AYAs with cSLE.

The membrane estrogen receptor ligand STX rapidly enhances GABAergic signaling in NPY/AgRP neurons: role in mediating the anorexigenic effects of 17ß-estradiol.

Besides its quintessential role in reproduction, 17ß-estradiol (E2) is a potent anorexigenic hormone. E2 and the selective Gq-coupled membrane estrogen receptor (Gq-mER) ligand STX rapidly increase membrane excitability in proopiomelanocortin (POMC) neurons by desensitizing the coupling of GABAB receptors to G protein-coupled inwardly rectifying K(+) channels (GIRKs), which upon activation elicit a hyperpolarizing outward current. However, it is unknown whether E2 and STX can modulate GABAB signaling in neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons. We used single-cell RT-PCR and whole cell patch clamping with selective pharmacological reagents to show that NPY/AgRP cells of mice express the GABAB-R1 and -R2 receptors and are hyperpolarized by the GABAB agonist baclofen in an E2-dependent manner. In males, E2 rapidly attenuated the coupling of GABAB receptors to GIRKs, which was blocked by the general PI3K inhibitors wortmannin and LY-294002 or the selective p110ß subunit inhibitor TGX-221. The ERα-selective agonist propyl pyrazole triol mimicked the effects of E2. STX, in contrast, enhanced the GABAB response in males, which was abrogated by the estrogen receptor (ER) antagonist ICI 182,780. In gonadectomized mice of both sexes, E2 enhanced or attenuated the GABAB response in different NPY/AgRP cells. Coperfusing wortmannin with E2 or simply applying STX always enhanced the GABAB response. Thus, in NPY/AgRP neurons, activation of the Gq-mER by E2 or STX enhances the GABAergic postsynaptic response, whereas activation of ERα by E2 attenuates it. These findings demonstrate a clear functional dichotomy of rapid E2 membrane-initiated signaling via ERα vs. Gq-mER in a CNS neuron vital for regulating energy homeostasis.

Precise Measurement of Lunar Spectral Irradiance at Visible Wavelengths.

We report a measurement of lunar spectral irradiance with an uncertainty below 1 % from 420 nm to 1000 nm. This measurement uncertainty meets the stability requirement for many climate data records derived from satellite images, including those for vegetation, aerosols, and snow and ice albedo. It therefore opens the possibility of using the Moon as a calibration standard to bridge gaps in satellite coverage and validate atmospheric retrieval algorithms. Our measurement technique also yields detailed information about the atmosphere at the measurement site, suggesting that lunar observations are a possible solution for aerosol monitoring during the polar winter and can provide nighttime measurements to complement aerosol data collected with sun photometers. Our measurement, made with a novel apparatus, is an order of magnitude more accurate than the previous state-of-the-art and has continuous spectral coverage, removing the need to interpolate between filter passbands.

Serotonin 5-HT2C receptor-mediated inhibition of the M-current in hypothalamic POMC neurons.

Hypothalamic proopiomelanocortin (POMC) neurons are controlled by many central signals, including serotonin. Serotonin increases POMC activity and reduces feeding behavior via serotonion [5-hydroxytryptamine (5-HT)] receptors by modulating K(+) currents. A potential K(+) current is the M-current, a noninactivating, subthreshold outward K(+) current. Previously, we found that M-current activity was highly reduced in fasted vs. fed states in neuropeptide Y neurons. Because POMC neurons also respond to energy states, we hypothesized that fasting may alter the M-current and/or its modulation by serotonergic input to POMC neurons. Using visualized-patch recording in neurons from fed male enhanced green fluorescent protein-POMC transgenic mice, we established that POMC neurons expressed a robust M-current (102.1 ± 6.7 pA) that was antagonized by the selective KCNQ channel blocker XE-991 (40 µM). However, the XE-991-sensitive current in POMC neurons did not differ between fed and fasted states. To determine if serotonin suppresses the M-current via the 5-HT(2C) receptor, we examined the effects of the 5-HT(2A)/5-HT(2C) receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) on the M-current. Indeed, DOI attenuated the M-current by 34.5 ± 6.9% and 42.0 ± 5.3% in POMC neurons from fed and fasted male mice, respectively. In addition, the 5-HT(1B)/5-HT(2C) receptor agonist m-chlorophenylpiperazine attenuated the M-current by 42.4 ± 5.4% in POMC neurons from fed male mice. Moreover, the selective 5-HT(2C) receptor antagonist RS-102221 abrogated the actions of DOI in suppressing the M-current. Collectively, these data suggest that although M-current expression does not differ between fed and fasted states in POMC neurons, serotonin inhibits the M-current via activation of 5-HT(2C) receptors to increase POMC neuronal excitability and, subsequently, reduce food intake.

Comparison of ground reaction forces and contact times between 2 lateral plyometric exercises in professional soccer players.

There are no studies which have examined the differences in kinetics between lateral plyometric exercises and the selection of these exercises is largely based on the experience and observation of coaches. This study aimed to compare ground reaction forces (GRF) and contact times (GCT) between 2 lateral plyometric exercises: lateral alternative leg hopping (HOP), and speed lateral footwork (SPEED). 16 professional male soccer players (age: 24.6±5.5 years; and BMI: 21.7±2.2 kg.m - 2) participated in this within-participant repeated measures study. 3-dimensional GRF data were measured by force platform. Our study revealed significant differences between the 2 lateral plyometric exercises in all kinetics parameters (F=573.7, P<0.01). HOP produced significantly longer GCT (0.45 s vs. 0.23 s, P<0.01, large effect), significantly higher values (P<0.05, large effect) in peak force (3.31 vs. 2.47 Body Weight [BW]), peak rate of force development (0.94 vs. 0.29 BW/s), and impulse (0.76 vs. 0.31 BW.s) except for peak force in the medial-lateral (P<0.05, medium effect) and impulse in the anterio-posterior direction (not significant, small effect). Therefore, SPEED is an exercise that aims to increase step frequency because of its short GCT (< 0.25 s) while HOP increases leg strength and power.

Calicivirus pathogenic for swine: a new serotype isolated from opaleye Girella nigricans, an ocean fish.

A new calicivirus, designated San Miguel sea lion virus type 7 (SMSV-7), was isolated from fish and produced a disease condition identical to vesicular exanthema in experimentally infected swine. Serotype SMSV-7 was also isolated from four elephant seals and one sea lion trematode, whereas a second calicivirus serotype isolated from fish proved to be SMSV-6.

Leptospirosis epizootic among California sea lions.

A Leptospira species is suspected of being the etiological agenit in a recent epizootic among California sea lions. The disease was confined to subadult males of the species Zalophus c. californianus.

Calicivirus isolation and persistence in a pygmy chimpanzee (Pan paniscus).

What may be the first calicivirus isolate from any primate species, including man, was recovered from a herpesvirus-like lip lesion on a pygmy chimpanzee and then, 6 months later, from the throat of the same animal. The infected individual and its cage mates had circulating antibodies that were type-specific for this calicivirus. The agent was antigenically different from 30 other calicivirus serotypes and is tentatively designated primate calicivirus Pan paniscus type 1 (PCV-Pan 1).

Cefixime-tellurite rhamnose MacConkey agar for isolation of Vero cytotoxin-producing Escherichia coli serogroup O26 from Scottish cattle and sheep faeces.

AIMS: To compare rhamnose MacConkey agar supplemented with cefixime and tellurite (CT-RMac) and tryptone bile X-glucuronide (TBX) agars as isolation media for Vero cytotoxin-producing Escherichia coli (VTEC) serogroup O26 from animal faeces. METHODS AND RESULTS: Nine VTEC O26 were isolated from sheep faeces; out of which six were isolated only on CT-RMac and one was isolated only on TBX. One hundred and twelve VTEC O26 were isolated from calf faeces; out of which 97% were from CT-RMac and 52% were from TBX. In a study of E. coli O26 strains, 84% of VT-positive O26 did not ferment rhamnose when compared with 16% of VT-negative O26. VT-positive (19%) and VT-negative (39%) E. coli O26 strains did not grow on CT-RMac agar. CONCLUSIONS: It is important to consider that VTEC O26 strains either may ferment rhamnose or may be sensitive to the CT supplement of CT-RMac agar. SIGNIFICANCE AND IMPACT OF THE STUDY: This work compares CT-RMac and TBX agars as isolation medium for VTEC O26 from Scottish animal faeces and highlights that VTEC O26 may be missed if only CT-RMac agar is used.

Evaluating Single-Spacecraft Observations of Planetary Magnetotails With Simple Monte Carlo Simulations: 1. Spatial Distributions of the Neutral Line.

A simple Monte Carlo model is presented that considers the effects of spacecraft orbital sampling on the inferred distribution of magnetic flux ropes, generated through magnetic reconnection in the magnetotail current sheet. When generalized, the model allows the determination of the number of orbits required to constrain the underlying population of structures: It is able to quantify this as a function of the physical parameters of the structures (e.g., azimuthal extent and probability of generation). The model is shown adapted to the Hermean magnetotail, where the outputs are compared to the results of a recent survey. This comparison suggests that the center of Mercury's neutral line is located dawnward of midnight by 0 . 3 7 - 1 . 02 + 1 . 21 R M and that the flux ropes are most likely to be wide azimuthally (∼50% of the width of the Hermean tail). The downtail location of the neutral line is not self-consistent or in agreement with previous (independent) studies unless dissipation terms are included planetward of the reconnection site; potential physical explanations are discussed. In the future the model could be adapted to other environments, for example, the dayside magnetopause or other planetary magnetotails.

Evaluating Single Spacecraft Observations of Planetary Magnetotails With Simple Monte Carlo Simulations: 2. Magnetic Flux Rope Signature Selection Effects.

A Monte Carlo method of investigating the effects of placing selection criteria on the magnetic signature of in situ encounters with flux ropes is presented. The technique is applied to two recent flux rope surveys of MESSENGER data within the Hermean magnetotail. It is found that the different criteria placed upon the signatures will preferentially identify slightly different subsets of the underlying population. Quantifying the selection biases first allows the distributions of flux rope parameters to be corrected, allowing a more accurate estimation of the intrinsic distributions. This is shown with regard to the distribution of flux rope radii observed. When accounting for the selection criteria, the mean radius of Hermean magnetotail quasi-force-free flux ropes is found to be 58 9 - 269 + 273  km. Second, it is possible to weight the known identifications in order to determine a rate of recurrence that accounts for the presence of the structures that will not be identified. In the case of the Hermean magnetotail, the average rate of quasi-force-free flux ropes is found to 0.12 min-1 when selection effects are accounted for (up from 0.05 min-1 previously inferred from observations).

Magnetic reconnection in Saturn's magnetotail: A comprehensive magnetic field survey.

Reconnection within planetary magnetotails is responsible for locally energizing particles and changing the magnetic topology. Its role in terms of global magnetospheric dynamics can involve changing the mass and flux content of the magnetosphere. We have identified reconnection related events in spacecraft magnetometer data recorded during Cassini's exploration of Saturn's magnetotail. The events are identified from deflections in the north-south component of the magnetic field, significant above a background level. Data were selected to provide full tail coverage, encompassing the dawn and dusk flanks as well as the deepest midnight orbits. Overall 2094 reconnection related events were identified, with an average rate of 5.0 events per day. The majority of events occur in clusters (within 3 h of other events). We examine changes in this rate in terms of local time and latitude coverage, taking seasonal effects into account. The observed reconnection rate peaks postmidnight with more infrequent but steady loss seen on the dusk flank. We estimate the mass loss from the event catalog and find it to be insufficient to balance the input from the moon Enceladus. Several reasons for this discrepancy are discussed. The reconnection X line location appears to be highly variable, though a statistical separation between events tailward and planetward of the X line is observed at a radial distance of between 20 and 30RS downtail. The small sample size at dawn prevents comprehensive statistical comparison with the dusk flank observations in terms of flux closure.

Three-dimensional structure of calicivirus.

The Caliciviridae comprise a new family of single-stranded RNA viruses. While human caliciviruses cause gastroenteritis, the animal caliciviruses cause a wide range of diseases. We have determined the three-dimensional structure of a primate calicivirus using electron cryomicroscopy and computer image-processing techniques. Calicivirus is one of the rare animal viruses whose capsid is made of a single structural protein. The three-dimensional structure of the virus is distinct from that of any other animal virus. However, there are several architectural similarities with plant viruses such as tomato bushy stunt virus and turnip crinkle virus. The calicivirions are 405 A in diameter and exhibit T = 3 icosahedral symmetry. The main features of the three-dimensional structure are the 32 large surface hollows, 50 A deep and 90 A wide, at the icosahedral 5-fold and 3-fold axes, and the 90 distinctive arch-like capsomeres surrounding these hollows at the local and strict 2-fold axes. Each capsomere is a dimer of the capsid protein. Despite noticeable differences, the three quasi-equivalent subunits show common structural features: the upper bilobed domain, the central stem domain, and the lower shell domain. The 2-fold related capsid proteins interact through the bilobed domains to form the top of the arch. The structural differences between the connectors of the stem and the shell domain among the three subunits suggest the presence of a hinge region that may facilitate the capsid protein to adapt to the three quasi-equivalent environments of the T = 3 icosahedral structure. The shell domains of the pentavalent and hexavalent capsid proteins associate to form a continuous shell between the radii of 115 and 150 A. A beta-barrel structure has been suggested for the shell domain. The mass density in the inner shell between the radius of 85 and 110 A may contain a portion of the capsid protein interacting with the RNA. The features between the 45 and 85 A radius are suggestive of ordered RNA.

Gender differences in balance performance at the time of retirement.

BACKGROUND: Impairments in balance performance are a commonly accepted risk factor for falling in older people. Since there is a higher reported incidence of falling in women, it is of interest to test whether this correlates with poorer balance performance in women than men at the time of retirement in order to plan health promotional strategies. The purpose of this study was to investigate whether any gender differences exist in balance performance in people approaching retirement age. METHODS: Ninety-seven healthy volunteers (44 males, 53 females) planning to retire shortly were enrolled in the study (age range 50-67 years). Balance assessments during quiet standing were performed under various conditions; feet together eyes open, feet together eyes closed and single limb stance eyes open. The range of centre of pressure displacement in both the anterior-posterior and medial-lateral planes was collected for each task using a force platform. FINDINGS: For several of the balance tasks the men exhibited a statistically significant larger range of centre of pressure displacement than the women (P<0.01). However, after normalising the data for height, no gender differences were seen. Over half of the group failed to complete all three single limb stance trials on both limbs. INTERPRETATION: When the data was normalised for height, no differences were found in static balance performance between men and women of retirement age. A number of participants demonstrated balance impairments whilst performing the single limb stance likely to affect functional activities. Health promotional messages should be targeted equally at men and women.

High-gain cryogenic amplifier assembly employing a commercial CMOS operational amplifier.

We have developed a cryogenic amplifier for the measurement of small current signals (10 fA-100 nA) from cryogenic optical detectors. Typically operated with gain near 10(7) V/A, the amplifier performs well from DC to greater than 30 kHz and exhibits noise level near the Johnson limit. Care has been taken in the design and materials to control heat flow and temperatures throughout the entire detector-amplifier assembly. A simple one-board version of the amplifier assembly dissipates 8 mW to our detector cryostat cold stage, and a two-board version can dissipate as little as 17 µW to the detector cold stage. With current noise baseline of about 10 fA/(Hz)(1/2), the cryogenic amplifier is generally useful for cooled infrared detectors, and using blocked impurity band detectors operated at 10 K, the amplifier enables noise power levels of 2.5 fW/(Hz)(1/2) for detection of optical wavelengths near 10 µm.

Field dipolarization in Saturn's magnetotail with planetward ion flows and energetic particle flow bursts: Evidence of quasi-steady reconnection.

We present a case study of an event from 20 August (day 232) of 2006, when the Cassini spacecraft was sampling the region near 32 RS and 22 h LT in Saturn's magnetotail. Cassini observed a strong northward-to-southward turning of the magnetic field, which is interpreted as the signature of dipolarization of the field as seen by the spacecraft planetward of the reconnection X line. This event was accompanied by very rapid (up to ~1500 km s-1) thermal plasma flow toward the planet. At energies above 28 keV, energetic hydrogen and oxygen ion flow bursts were observed to stream planetward from a reconnection site downtail of the spacecraft. Meanwhile, a strong field-aligned beam of energetic hydrogen was also observed to stream tailward, likely from an ionospheric source. Saturn kilometric radiation emissions were stimulated shortly after the observation of the dipolarization. We discuss the field, plasma, energetic particle, and radio observations in the context of the impact this reconnection event had on global magnetospheric dynamics.

Analysis of promoter activity by transformation of Acremonium chrysogenum.

Promoter activity was examined in the beta-lactam-producing fungus, Acremonium chrysogenum, by assessment of the properties of transformant isolates. Transformation was achieved using plasmid constructs specifying hygromycin B resistance (HyR) linked to the promoter elements of gpdA (the glucose-6-phosphate dehydrogenase-encoding gene of Aspergillus nidulans), and pcbC [the gene encoding the isopenicillin N synthetase (IPNS) enzyme of A. chrysogenum]. Transformation frequency, HyR levels, and Hy phosphotransferase (HPT) levels suggested that the transformants of constructs using the gpdA promoter showed a higher level of expression of the HyR gene than in transformants obtained using the pcbC promoter. The patterns of integration of the transforming DNA also differed in that pcbC promoter construct transformants appeared to have tandem repeats. All integrations of plasmid DNA occurred on a single chromosome which was different in four out of five transformants studied. Multiple copy transformants of constructs using the pcbC promoter did not show the regulated pattern of expression of HPT activity observed with IPNS in untransformed strains.

Specific photoaffinity labelling of a ferripyoverdin outer membrane receptor of Pseudomonas aeruginosa.

In order to identify and characterize the receptors involved in pyoverdin-mediated iron transport in Pseudomonas aeruginosa ATCC 15692, a photoactivatable siderophore has been synthesized. In the dark, this probe is stable and is able to promote iron transport at the same rate as the native pyoverdin. Under irradiation at 312 nm, the molecule is photodecomposed and a clear inhibition of the iron transport is observed. With the radioactive form of this photoactivatable probe, we were able to visualize on a SDS-PAGE gel a labelled protein of approximately 90 kDa molecular mass, which is very likely the FpvA receptor or a yet unknown pyoverdin receptor.

Iron uptake in Pseudomonas aeruginosa mediated by N-(2,3-dihydroxybenzoyl)-L-serine and 2,3-dihydroxybenzoic acid.

Pseudomonas aeruginosa is known to have an inducible uptake system for the enterobacterial siderophore enterobactin. In this work we have examined iron transport mediated by the biosynthetic precursor 2,3-dihydroxybenzoic acid and N-(2,3-dihydroxybenzoyl)-L-serine, a breakdown product of enterobactin. Iron complexed with 2,3-dihydroxybenzoyl-L-serine was transported into P. aeruginosa IA1 via a transport system which is energy-dependent and iron-repressible. The rate of transport was not altered by growing the cells in the presence of either pyoverdin or pyochelin, which have been shown previously to induce transport via that system. Growth of the cells in the presence of enterobactin did cause an increase in the rate of transport, indicating that the complex can be transported by the inducible enterobactin uptake system, but also that a separate system must exist. In contrast, transport of iron complexed with 2,3-dihydroxybenzoic acid was neither iron-repressible nor strongly energy-dependent, from which we conclude that there must be a novel mode of transport not characteristic of iron-siderophore transport systems.

Genetic diversity of the Helicobacter pylori haemagglutinin/protease (hap) gene.

Helicobacter pylori has been associated with the etiology of gastritis, gastric and duodenal ulcers and gastric cancer in man. In this study we confirm the presence of the haemagglutinin/protease (hap) gene in ten geographically diverse strains of H. pylori, but the Southern analysis of genomic DNA suggested that the location of the hap gene was different in each strain. We suggest that the hap gene is subject to a high rate of mutation and subsequent polymorphisms by virtue of a mobile, genetic element located upstream of the hap gene in the H. pylori genome. Simple transformation experiments suggested that this polymorphism may be mediated by a transposon-like element.