HIV and SARS-CoV-2 co-infection: cross-sectional findings from a German 'hotspot'.

PURPOSE: This study aimed to determine the proportion of people living with HIV with anti-SARS-CoV-2 IgG antibodies in a sample from a large single HIV center in Munich, Germany, after the first phase of the coronavirus pandemic and to infer the prevalence of SARS-CoV-2 co-infection in people living with HIV. METHODS: Prospective sub-study of the ongoing ArcHIV cohort between May and July 2020. Anti-SARS-CoV-2 IgG antibodies were measured using the recomWell SARS-CoV-2 IgG ELISA (Mikrogen, Neuried, Germany); positive and borderline results were re-tested using the recomLine SARS-CoV-2 IgG immunoassay (Mikrogen, Neuried, Germany). Demographic and medical data were extracted from the electronic patient files. RESULTS: Overall, 500 people living with HIV were included in the study (83% male, median age 51 years). Three participants had been diagnosed with COVID-19 prior to study inclusion. Of those, nine were confirmed positive for SARS-CoV-2 IgG antibodies, resulting in an estimated seroprevalence (accounting for sensitivity and specificity of the test) of 1.5% (CI 95%: 0.69; 3.13) for the entire study sample, and 2.2% (CI 95%: 1.1; 3.9) for the subset of the Munich citizens. There were no marked differences for people living with HIV with and without SARS-CoV-2 co-infection. CONCLUSION: The seroprevalence of SARS-CoV-2 co-infection in people living with HIV as found in our study does not seem to exceed previous reports from general populations of 'hot-sport' areas; comparative data from the Munich population can be expected to be published soon. Our data also highlight, once more, the need to do confirmatory testing on positive samples to minimize the impact of false-positive results.

Standardizing 25-hydroxyvitamin D data from the HunMen cohort.

Standardization of 25-hydroxyvitamin D (25OHD) values is still a challenge. We propose standardization by correction of the measured 25OHD values using the linear regression bias from the National Institute of Standards and Technology (NIST) 'total' target values reported by Vitamin D External Quality Assessment Scheme (DEQAS). Our approach could perhaps be a practical solution to the anomaly surrounding non-standardized 25OHD values. INTRODUCTION: Standardization of 25OHD values is still a challenge. We propose standardization by correction of the measured 25OHD values using the linear regression equation derived from the analysis of relationship between total 25OHD values measured by the methodology used by the laboratory and the NIST total target values (TV) reported by the DEQAS for all 5 of the DEQAS samples in a given survey. METHODS: We applied our approach to standardize total 25OHD values of the HunMen cohort. RESULTS: All 206 samples for the HunMen cohort were evaluated using the automated Liaison DiaSorin total 25OHD chemiluminescence immunoassay (CLIA). The timing of these measurements coincided with that of the October 2015 DEQAS survey using samples 481 to 485. Following standardization, the mean total 25OHD changed from 53 to 62 nmol/L and the prevalence of hypovitaminosis D (<75 nmol/L) decreased significantly from 84 to 72%. CONCLUSION: A simple approach readily applicable at the routine diagnostic laboratory could perhaps be a practical solution to the anomaly surrounding non-standardized 25OHD values.

Investigation of Deteriorated Dissolution of Amorphous Itraconazole: Description of Incompatibility with Magnesium Stearate and Possible Solutions.

Disadvantageous crystallization phenomenon of amorphous itraconazole (ITR) occurring in the course of dissolution process was investigated in this work. A perfectly amorphous form (solid dispersion) of the drug was generated by the electroblowing method (with vinylpyrrolidone-vinyl acetate copolymer), and the obtained fibers were formulated into tablets. Incomplete dissolution of the tablets was noticed under the circumstances of the standard dissolution test, after which a precipitated material could be filtered. The filtrate consisted of ITR and stearic acid since no magnesium content was detectable in it. In parallel with dissolution, ITR forms an insoluble associate, stabilized by hydrogen bonding, with stearic acid deriving from magnesium stearate. This is why dissolution curves do not have the plateaus at 100%. Two ways are viable to tackle this issue: change the lubricant (with sodium stearyl fumarate >95% dissolution can be accomplished) or alter the polymer in the solid dispersion to a type being able to form hydrogen bonds with ITR (e.g., hydroxypropyl methylcellulose). This work draws attention to one possible phenomenon that can lead to a deterioration of originally good dissolution of an amorphous solid dispersion.

Capnogram slope and ventilation dead space parameters: comparison of mainstream and sidestream techniques.

BACKGROUND: Capnography may provide useful non-invasive bedside information concerning heterogeneity in lung ventilation, ventilation-perfusion mismatching and metabolic status. Although the capnogram may be recorded by mainstream and sidestream techniques, the capnogram indices furnished by these approaches have not previously been compared systematically. METHODS: Simultaneous mainstream and sidestream time and volumetric capnography was performed in anaesthetized, mechanically ventilated patients undergoing elective heart surgery. Time capnography was used to assess the phase II (SII,T) and III slopes (SIII,T). The volumetric method was applied to estimate phase II (SII,V) and III slopes (SIII,V), together with the dead space values according to the Fowler (VDF), Bohr (VDB), and Enghoff (VDE) methods and the volume of CO2 eliminated per breath ([Formula: see text]). The partial pressure of end-tidal CO2 ([Formula: see text]) was registered. RESULTS: Excellent correlation and good agreement were observed in SIII,T measured by the mainstream and sidestream techniques [ratio=1.05 (sem 0.16), R(2)=0.92, P<0.0001]. Although the sidestream technique significantly underestimated [Formula: see text] and overestimated SIII,V [1.32 (0.28), R(2)=0.93, P<0.0001], VDF, VDB, and VDE, the agreement between the mainstream and sidestream techniques in the difference between VDE and VDB, reflecting the intrapulmonary shunt, was excellent [0.97 (0.004), R(2)=0.92, P<0.0001]. The [Formula: see text] exhibited good correlation and mild differences between the mainstream and sidestream approaches [0.025 (0.005) kPa]. CONCLUSIONS: Sidestream capnography provides adequate quantitative bedside information about uneven alveolar emptying and ventilation-perfusion mismatching, because it allows reliable assessments of the phase III slope, [Formula: see text] and intrapulmonary shunt. Reliable measurement of volumetric parameters (phase II slope, dead spaces, and eliminated CO2 volumes) requires the application of a mainstream device.

Vitamin D status in men with psoriatic arthritis: a case-control study.

UNLABELLED: We determined hypovitaminosis D prevalence in men with psoriatic arthritis. This is a cross-sectional, analyst blinded, age- and sex-matched, case-control study. Men with psoriatic arthritis have significantly lower 25-hydroxyvitamin D levels. Men with psoriatic arthritis are at increased odds of suffering from hypovitaminosis D. INTRODUCTION: Skeletal manifestations as a result of abrupted bone metabolism may be predominant in psoriatic arthritis (PsA). Vitamin D plays a vital role in maintenance of skeletal health and is known to modulate the immune system in various autoimmune diseases including PsA. The aim of the present study was to determine the prevalence of hypovitaminosis D in a treatment naïve, de novo psoriatic arthritis male cohort in a cross-sectional, analyst blinded, age- and sex-matched, case-control study. METHODS: 25 hydroxyvitamin D (25OHD), parathyroid (PTH), osteocalcin (OC) and C-terminal telopeptides of type-I collagen (CTx) levels, and lumbar spine and femoral neck bone mineral density were compared between 53 PsA and controls. RESULTS: The prevalence of hypovitaminosis D (25 hydroxyvitamin D (25OHD) levels <75 nmol/L) was 81 and 57 % in the PsA and control groups, respectively. Compared to the healthy controls, 25OHD (67.2 (12-137) nmol/L vs. 51.9 (15-95) nmol/L; p = 0.001) was significantly lower, and osteocalcin (13.6 (5-33) µg/L vs. 18.2 (6-35) µg/L; p = 0.003) and C-terminal telopeptides of type-I collagen (0.20 (0.01-0.71) µg/L vs. 0.28 (0.06-0.69) µg/L; p = 0.008) were significantly higher in the PsA group. A significant association was found between hypovitaminosis D and PsA; the odds for patients with PsA of having hypovitaminosis D was 3.297 (95 % confidence interval 1.372 to 7.922). CONCLUSION: The results of this study suggest that men with PsA have significantly lower 25-hydroxyvitamin D levels, and furthermore, men with PsA are at statistically significant increased odds of suffering from hypovitaminosis D.

Prevalence and seasonal variation of hypovitaminosis D and its relationship to bone metabolism in healthy Hungarian men over 50 years of age: the HunMen Study.

UNLABELLED: This study reports a high prevalence of hypovitaminosis D and low bone mineral density (BMD) in a healthy Hungarian male cohort over 50 years of age. Men with 25-hydroxyvitamin D levels of <75 nmol/L had a significantly higher 10-year hip and major osteoporotic fracture probability using the country-specific fracture risk assessment (FRAX) algorithm. INTRODUCTION: The aim of this study is to characterize the prevalence and seasonal variation of hypovitaminosis D and its relationship to bone metabolism in healthy Hungarian men over 50 years of age. METHODS: We determined levels of 25-hydroxyvitamin D (25-OH-D), PTH, osteocalcin (OC), C-terminal telopeptides of type-I collagen (CTX-I), procollagen type 1 amino-terminal propeptide (PINP), BMD at L1-L4 (LS) and femur neck (FN), daily dietary calcium intake, and the 10-year probability of hip fracture and a major osteoporotic fracture using the country-specific FRAX algorithm in 206 randomly selected ambulatory men. RESULTS: The mean (range) age of the volunteers was 60 (51-81) years. The prevalence of hypovitaminosis D (25-OH-D, <75 nmol/L) was 52.9%. The prevalence of low (T-score < -1.0) BMD at the FN and LS was 45% and 35.4%, respectively. The mean (range) FRAX hip fracture and FRAX major osteoporotic fracture was 0.8% (0-9.4%) and 3.8% (1.7-16%), respectively. On comparing the vitamin D sufficient to the insufficient group, there was a statistically significant difference between the FRAX hip fracture and FRAX major osteoporotic fracture indexes. There was significant seasonal variation in the vitamin D levels; the lowest levels were measured in winter and the highest in summer. CONCLUSIONS: A high prevalence of hypovitaminosis D and low BMD were observed in the studied Hungarian male population. This is the first study reporting higher 10-year hip and major osteoporotic fracture probability using the country-specific FRAX algorithm in individuals with hypovitaminosis D.

Little or no solar wind enters Venus' atmosphere at solar minimum.

Venus has no significant internal magnetic field, which allows the solar wind to interact directly with its atmosphere. A field is induced in this interaction, which partially shields the atmosphere, but we have no knowledge of how effective that shield is at solar minimum. (Our current knowledge of the solar wind interaction with Venus is derived from measurements at solar maximum.) The bow shock is close to the planet, meaning that it is possible that some solar wind could be absorbed by the atmosphere and contribute to the evolution of the atmosphere. Here we report magnetic field measurements from the Venus Express spacecraft in the plasma environment surrounding Venus. The bow shock under low solar activity conditions seems to be in the position that would be expected from a complete deflection by a magnetized ionosphere. Therefore little solar wind enters the Venus ionosphere even at solar minimum.

Maintenance of antifracture efficacy over 10 years with strontium ranelate in postmenopausal osteoporosis.

UNLABELLED: In an open-label extension study, BMD increased continuously with strontium ranelate over 10 years in osteoporotic women (P < 0.01). Vertebral and nonvertebral fracture incidence was lower between 5 and 10 years than in a matched placebo group over 5 years (P < 0.05). Strontium ranelate's antifracture efficacy appears to be maintained long term. INTRODUCTION: Strontium ranelate has proven efficacy against vertebral and nonvertebral fractures, including hip, over 5 years in postmenopausal osteoporosis. We explored long-term efficacy and safety of strontium ranelate over 10 years. METHODS: Postmenopausal osteoporotic women participating in the double-blind, placebo-controlled phase 3 studies SOTI and TROPOS to 5 years were invited to enter a 5-year open-label extension, during which they received strontium ranelate 2 g/day (n = 237, 10-year population). Bone mineral density (BMD) and fracture incidence were recorded, and FRAX® scores were calculated. The effect of strontium ranelate on fracture incidence was evaluated by comparison with a FRAX®-matched placebo group identified in the TROPOS placebo arm. RESULTS: The patients in the 10-year population had baseline characteristics comparable to those of the total SOTI/TROPOS population. Over 10 years, lumbar BMD increased continuously and significantly (P < 0.01 versus previous year) with 34.5 ± 20.2% relative change from baseline to 10 years. The incidence of vertebral and nonvertebral fracture with strontium ranelate in the 10-year population in years 6 to 10 was comparable to the incidence between years 0 and 5, but was significantly lower than the incidence observed in the FRAX®-matched placebo group over 5 years (P < 0.05); relative risk reductions for vertebral and nonvertebral fractures were 35% and 38%, respectively. Strontium ranelate was safe and well tolerated over 10 years. CONCLUSIONS: Long-term treatment with strontium ranelate is associated with sustained increases in BMD over 10 years, with a good safety profile. Our results also support the maintenance of antifracture efficacy over 10 years with strontium ranelate.

Effects of erythropoietin on glucose metabolism.

We purposed to determine the impact of erythropoietin on altering glucose metabolism in the settings of in vitro and in vivo experiments. The acute effect of erythropoietin on lowering blood glucose levels was studied in animal experiments. In [³H]-deoxy-D-glucose isotope studies we measured glucose uptake with insulin and erythropoietin using 3T3-L1 cells cultured under normal or high glucose conditions. Altered activation of Akt and ERK pathways was evaluated in immunoblot analyses. Immunocytochemistry was conducted to determine the glucose transporter 4 translocation to the plasma membrane. Addition of erythropoietin significantly lowered blood glucose levels in vivo in rats. The glucose uptake was markedly increased by erythropoietin treatment (at concentrations 0.15, 0.3, and 0.625 ng/ml) in adipocytes grown in high glucose medium (p<0.05), but it remained unaltered in cells under normal glucose conditions. Significant increase of phosphorylation of ERK and Akt was detected due to erythropoietin (p<0.05). Co-administration of erythropoietin and insulin resulted in higher phosphorylation of Akt and [³H]-deoxy-D-glucose uptake in adipocytes than insulin treatment alone. We found that erythropoietin induced the trafficking of glucose transporter 4 to the plasma membrane. Our data showed that erythropoietin significantly decreased blood glucose levels both in vivo and in vitro, in part, by increasing glucose uptake via the activation of Akt pathway. Preliminary data revealed that adipocytes most likely exhibit a specific receptor for erythropoietin.

A magnetic reconnection X-line extending more than 390 Earth radii in the solar wind.

Magnetic reconnection in a current sheet converts magnetic energy into particle energy, a process that is important in many laboratory, space and astrophysical contexts. It is not known at present whether reconnection is fundamentally a process that can occur over an extended region in space or whether it is patchy and unpredictable in nature. Frequent reports of small-scale flux ropes and flow channels associated with reconnection in the Earth's magnetosphere raise the possibility that reconnection is intrinsically patchy, with each reconnection X-line (the line along which oppositely directed magnetic field lines reconnect) extending at most a few Earth radii (R(E)), even though the associated current sheets span many tens or hundreds of R(E). Here we report three-spacecraft observations of accelerated flow associated with reconnection in a current sheet embedded in the solar wind flow, where the reconnection X-line extended at least 390R(E) (or 2.5 x 10(6) km). Observations of this and 27 similar events imply that reconnection is fundamentally a large-scale process. Patchy reconnection observed in the Earth's magnetosphere is therefore likely to be a geophysical effect associated with fluctuating boundary conditions, rather than a fundamental property of reconnection. Our observations also reveal, surprisingly, that reconnection can operate in a quasi-steady-state manner even when undriven by the external flow.

In vitro and in vivo evaluation of drug release from semisolid dosage forms.

This study presents the in vitro and in vivo testing of anti-inflammatory drug containing creams, hydrogels and organogels for dermal use. In vitro penetration studies were performed with products by measuring the diffused drug amount through synthetic membranes soaked in isopropyl myristate (IPM). Our developed preparations were investigated under in vitro conditions together with two marketed medicinal products used as reference preparations. In vivo studies were carried out on anaesthetized male Wistar rats; the carrageenan-induced paw oedema decreasing effect of twelve different formulations and the reference products were measured in comparison with a control group. All - previously in vitro screened - selected products reduced paw oedema in rats. Significant differences were found among the developed products both in vitro and in vivo. Correlation between the in vitro penetration studies and in vivo results were found in the case of o/w creams, organogels and hydrogels.

Identification of comet Hyakutake's extremely long ion tail from magnetic field signatures

Observations of the varying orientations of comet tails led to the suggestion of the existence of the solar wind--a continuous outflow of ionized material from the Sun. It is now well established that gas from comets is ionized by several processes and joins the solar wind, forming an ion (plasma) tail that points away from the Sun. The plasma environments of three comets have been measured in situ, but only in the upstream direction or less than 8,000 km downstream of the nucleus. Here we report a fortuitous crossing by a spacecraft of the plasma tail of comet Hyakutake (C/1996 B2), at a distance of more than 3.8 astronomical units (550 million kilometres) from its nucleus. This surpasses the tail length of 2 AU determined for the Great March Comet of 1843 (C/1843 D1). Our measurements reveal that, at this distance, the tail of comet Hyakutake was a structured entity at least 7 million kilometres in diameter.

Transport of solar wind into Earth's magnetosphere through rolled-up Kelvin-Helmholtz vortices.

Establishing the mechanisms by which the solar wind enters Earth's magnetosphere is one of the biggest goals of magnetospheric physics, as it forms the basis of space weather phenomena such as magnetic storms and aurorae. It is generally believed that magnetic reconnection is the dominant process, especially during southward solar-wind magnetic field conditions when the solar-wind and geomagnetic fields are antiparallel at the low-latitude magnetopause. But the plasma content in the outer magnetosphere increases during northward solar-wind magnetic field conditions, contrary to expectation if reconnection is dominant. Here we show that during northward solar-wind magnetic field conditions-in the absence of active reconnection at low latitudes-there is a solar-wind transport mechanism associated with the nonlinear phase of the Kelvin-Helmholtz instability. This can supply plasma sources for various space weather phenomena.

Author Correction: Proteomic and Transcriptomic Changes in Hibernating Grizzly Bears Reveal Metabolic and Signaling Pathways that Protect against Muscle Atrophy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The heliospheric magnetic field over the South polar region of the sun.

Magnetic field measurements from the Ulysses space mission overthe south polar regions of the sun showed that the structure and properties of the three-dimensional heliosphere were determined by the fast solar wind flow and magnetic fields from the large coronal holes in the polar regions of the sun. This conclusion applies at the current, minimum phase of the 11-year solar activity cycle. Unexpectedly, the radial component of the magnetic field was independent of latitude. The high-latitude magnetic field deviated significantly from the expected Parker geometry, probably because of large amplitude transverse fluctuations. Low-frequency fluctuations had a high level of variance. The rate of occurrence of discontinuities also increased significantly at high latitudes.

Magnetic field observations during the ulysses flyby of jupiter.

The Jovian flyby of the Ulysses spacecraft presented the opportunity to confirm and complement the findings of the four previous missions that investigated the structure and dynamics of the Jovian magnetosphere and magnetic field, as well as to explore for the first time the high-latitude dusk side of the magnetosphere and its boundary regions. In addition to confirming the general structure of the dayside magnetosphere, the Ulysses magnetic field measurements also showed that the importance of the current sheet dynamics extends well into the middle and outer magnetosphere. On the dusk side, the magnetic field is swept back significantly toward the magnetotail. The importance of current systems, both azimuthal and field-aligned, in determining the configuration of the field has been strongly highlighted by the Ulysses data. No significant changes have been found in the internal planetary field; however, the need to modify the external current densities with respect to previous observations on the inbound pass shows that Jovian magnetic and magnetospheric models are highly sensitive to both the intensity and the structure assumed for the current sheet and to any time dependence that may be assigned to these. The observations show that all boundaries and boundary layers in the magnetosphere have a very complex microstructure. Waves and wave-like structures were observed throughout the magnetosphere; these included the longest lasting mirror-mode wave trains observed in space.

Energetic Charged-Particle Phenomena in the Jovian Magnetosphere: First Results from the Ulysses COSPIN Collaboration.

The Ulysses spacecraft made the first exploration of the region of Jupiter's magnetosphere at high Jovigraphic latitudes ( approximately 37 degrees south) on the dusk side and reached higher magnetic latitudes ( approximately 49 degrees north) on the day side than any previous mission to Jupiter. The cosmic and solar particle investigations (COSPIN) instrumentation achieved a remarkably well integrated set of observations of energetic charged particles in the energy ranges of approximately 1 to 170 megaelectron volts for electrons and 0.3 to 20 megaelectron volts for protons and heavier nuclei. The new findings include (i) an apparent polar cap region in the northern hemisphere in which energetic charged particles following Jovian magnetic field lines may have direct access to the interplanetary medium, (ii) high-energy electron bursts (rise times approximately 17 megaelectron volts) on the dusk side that are apparently associated with field-aligned currents and radio burst emissions, (iii) persistence of the global 10-hour relativistic electron "clock" phenomenon throughout Jupiter's magnetosphere, (iv) on the basis of charged-particle measurements, apparent dragging of magnetic field lines at large radii in the dusk sector toward the tail, and (v) consistent outflow of megaelectron volt electrons and large-scale departures from corotation for nucleons.

Proteomic and Transcriptomic Changes in Hibernating Grizzly Bears Reveal Metabolic and Signaling Pathways that Protect against Muscle Atrophy.

Muscle atrophy is a physiological response to disuse and malnutrition, but hibernating bears are largely resistant to this phenomenon. Unlike other mammals, they efficiently reabsorb amino acids from urine, periodically activate muscle contraction, and their adipocytes differentially responds to insulin. The contribution of myocytes to the reduced atrophy remains largely unknown. Here we show how metabolism and atrophy signaling are regulated in skeletal muscle of hibernating grizzly bear. Metabolic modeling of proteomic changes suggests an autonomous increase of non-essential amino acids (NEAA) in muscle and treatment of differentiated myoblasts with NEAA is sufficient to induce hypertrophy. Our comparison of gene expression in hibernation versus muscle atrophy identified several genes differentially regulated during hibernation, including Pdk4 and Serpinf1. Their trophic effects extend to myoblasts from non-hibernating species (including C. elegans), as documented by a knockdown approach. Together, these changes reflect evolutionary favored adaptations that, once translated to the clinics, could help improve atrophy treatment.

Alterations in the SMARCB1 (INI1) tumor suppressor gene in familial schwannomatosis.

Schwannomatosis is a third major form of neurofibromatosis that has recently been linked to mutations in the SMARCB1 (hSnf5/INI1) tumor suppressor gene. We analyzed the coding region of SMARCB1 by direct sequencing and multiplex ligation-dependent probe amplification (MLPA) in genomic DNA from 19 schwannomatosis kindreds. Microsatellite markers in the SMARCB1 region were developed to determine loss of heterozygosity (LOH) in associated tumors. We detected four alterations in conserved splice acceptor or donor sequences of exons 3, 4 and 6. Two alterations that likely affect splicing were seen in introns 4 and 5. An additional four alterations of unclear pathogenicity were found to segregate on the affected allele in eight families including two non-conservative missense alterations in three families. No constitutional deletions or duplications were detected by MLPA. Nine of 13 tumors examined showed partial LOH of the SMARCB1 region consistent with 'second hits.' Alterations were detected in tumors both with and without somatic NF2 gene changes. These findings support the hypothesis that SMARCB1 is a tumor suppressor for schwannomas in the context of familial disease. Further work is needed to determine its role in other multiple and single tumor syndromes.

Childhood-onset mild cutaneous porphyria with compound heterozygotic mutations in the uroporphyrinogen decarboxylase gene.

Three children (two boys and one girl) from the same family presented with photosensitivity, hyperpigmentation, hypertrichosis, mild skin fragility, blistering and scarring in childhood. On examination, the cutaneous lesions were found to have improved since their previous examinations. Laboratory tests showed raised plasma and urine carboxyporphyrins and decreased uroporphyrinogen decarboxylase enzyme activity in red blood cells. Triggering factors for porphyria were not detected except for a hepatitis C virus infection in the younger boy. The girl's clinical symptoms recurred in late adolescence, after iron and oestrogen treatments. Mutation analysis of the UROD gene detected two missense mutations, 19 A-->G M1V (novel) and 703C-->T P235S (previously reported), in an uncommon compound heterozygous manner in the three siblings.