Deep far infrared ISOPHOT survey in "Selected Area 57", I. Observations and source counts

We present here the results of a deep survey in a 0.4 sq.deg. blank field in Selected Area 57 conducted with the ISOPHOT instrument aboard ESAs Infrared Space Observatory (ISO) at both 60 um and 90 um. The resulting sky maps have a spatial resolution of 15 x 23 sq.arcsec. per pixel which is much higher than the 90 x 90 sq.arcsec. pixels of the IRAS All Sky Survey. We describe the main instrumental effects encountered in our data, outline our data reduction and analysis scheme and present astrometry and photometry of the detected point sources. With a formal signal to noise ratio of 6.75 we have source detection limits of 90 mJy at 60 um and 50 mJy at 90 um. To these limits we find cumulated number densities of 5+-3.5 per sq.deg. at 60 um and 14.8+-5.0 per sq.deg.at 90 um. These number densities of sources are found to be lower than previously reported results from ISO but the data do not allow us to discriminate between no-evolution scenarios and various evolutionary models.Comment: 15 pages, 11 figures, accepted by Astronomy & Astrophysic

Spatio-temporal trends in stock mixing of eastern and western Baltic cod in the Arkona Basin and the implications for recruitment

In the Baltic Sea, two genetically distinct cod populations occur, the eastern and the western Baltic cod. Since 2006, cod abundance has increased substantially in the Arkona Basin (SD 24), the potential mixing area between the two stocks management areas, presumably due to spill-over from the eastern stock. In this study, the spatio-temporal dynamics of stock mixing were analysed using shape analysis of archived otoliths. Further, the impact of eastern cod immigration on recruitment in the western Baltic Sea was investigated using hydrographic drift modelling. The percentage of eastern Baltic cod in the Arkona Basin increased from ca. 30% before 2005 to >80% in recent years. Geographic patterns in stock mixing with a pronounced east–west trend suggest that immigration occurs north of Bornholm, but propagates throughout the Arkona Basin. The immigration cannot be attributed to spawning migration, as no seasonal trend in stock mixing was observed. Based on environmental threshold levels for egg survival and time-series of hydrography data, the habitat suitable for successful spawning of eastern cod was estimated to range between 20 and 50% of the maximum possible habitat size, limited by primarily low salinity. Best conditions occurred irregularly in May–end June, interspersed with years where successful spawning was virtually impossible. Using a coupled hydrodynamic modelling and particle-tracking approach, the drift and survival of drifters representing eastern cod eggs was estimated. On average, 19% of the drifters in the Arkona Basin survive to the end of the yolk-sac stage, with mortality primarily after bottom contact due to low salinity. The general drift direction of the surviving larvae was towards the east. Therefore, it is the immigration of eastern cod, rather than larval transport, that contributes to cod recruitment in the western Baltic Sea

Intermittent mild negative pressure applied to the lower limb in patients with spinal cord injury and chronic lower limb ulcers: a crossover pilot study

Study design Randomized, assessor-blinded crossover pilot study. Objectives To explore the use of an intermittent negative pressure (INP) device for home use in addition to standard wound care (SWC) for patients with spinal cord injury (SCI) and chronic leg and foot ulcers before conducting a superiority trial. Setting Patient homes and outpatient clinic. Methods A 16-week crossover trial on 9 SCI patients (median age: 57 years, interquartile range [IQR] 52–66), with leg ulcers for 52 of weeks (IQR: 12–82) duration. At baseline, patients were allocated to treatment with INP + SWC or SWC alone. After 8 weeks, the ulcers were evaluated. To assess protocol adherence, the patients were then crossed over to the other group and were evaluated again after another 8 weeks. Lower limb INP treatment consisted of an airtight pressure chamber connected to an INP generator (alternating 10 s −40mmHg/7 s atmospheric pressure) used 2 h/day at home. Ulcer healing was assessed using a photographic wound assessment tool (PWAT) and by measuring changes in wound surface area (WSA). Results Seven of nine recruited patients adhered to a median of 90% (IQR: 80–96) of the prescribed 8-week INP-protocol, and completed the study without side effects. PWAT improvement was observed in 4/4 patients for INP + SWC vs. 2/5 patients for SWC alone (P = 0.13). WSA improved in 3/4 patients allocated to INP + SWC vs. 3/5 patients in SWC alone (P = 0.72). Conclusions INP can be used as a home-based treatment for patients with SCI, and its efficacy should be tested in an adequately sized, preferably multicenter randomized trial.måsjekke

The effect of general anaesthetics on brain lactate release

The effects of anaesthetic agents on brain energy metabolism may explain their shared neurophysiological actions but remain poorly understood. The brain lactate shuttle hypothesis proposes that lactate, provided by astrocytes, is an important neuronal energy substrate. Here we tested the hypothesis that anaesthetic agents impair the brain lactate shuttle by interfering with astrocytic glycolysis. Lactate biosensors were used to record changes in lactate release by adult rat brainstem and cortical slices in response to thiopental, propofol and etomidate. Changes in cytosolic nicotinamide adenine dinucleotide reduced (NADH) and oxidized (NAD+) ratio as a measure of glycolytic rate were recorded in cultured astrocytes. It was found that in brainstem slices thiopental, propofol and etomidate reduced lactate release by 7.4 ± 3.6% (P < 0.001), 9.7 ± 6.6% (P < 0.001) and 8.0 ± 7.8% (P = 0.04), respectively. In cortical slices, thiopental reduced lactate release by 8.2 ± 5.6% (P = 0.002) and propofol by 6.0 ± 4.5% (P = 0.009). Lactate release in cortical slices measured during the light phase (period of sleep/low activity) was ~25% lower than that measured during the dark phase (period of wakefulness) (326 ± 83 μM vs 430 ± 118 μM, n = 10; P = 0.04). Thiopental and etomidate induced proportionally similar decreases in cytosolic [NADH]:[NAD+] ratio in astrocytes, indicative of a reduction in glycolytic rate. These data suggest that anaesthetic agents inhibit astrocytic glycolysis and reduce the level of extracellular lactate in the brain. Similar reductions in brain lactate release occur during natural state of sleep, suggesting that general anaesthesia may recapitulate some of the effects of sleep on brain energy metabolism

Vesicular glutamate release from central axons contributes to myelin damage

Neuronal activity can lead to vesicular release of glutamate. Here the authors demonstrate that vesicular release of glutamate occurs in axons during ischemic conditions, and that an allosteric modulator of GluN2C/D is protective in models of ischemic injury

Working Group on Biological Parameters (WGBIOP) 2021

The main objective of the Working Group on Biological Parameters (WGBIOP) is to review the status, issues, developments, and quality assurance of biological parameters used in assessment and management. WGBIOP (1) plans workshops, exchanges, and validation studies on a range of biological varia-bles to review the quality of information supplied for stock assessment and improve quality as-surance and training; (2) investigates data availability and develops documentation and methods to improve communication between data collectors and end-users; (3) delivers new and im-proved functionality for the SmartDots platform. Four otolith exchanges and two workshops were completed in 2020–2021 using SmartDots— eight further exchanges are ongoing. Proposed future exchanges and workshops were reviewed and approved. The development of the SmartDots platform proceeded with the inclusion of the maturity, eggs, atresia, fecundity, and larval identification modules into the software version. A live SmartDots tutorial for event coordinators was conducted. Work to further develop quality assurance guidelines—and review national applications of these—progressed. Age and maturity validation studies were reviewed and a new method for prioritizing future validation work was proposed. Progress with the Stock Identification Database (SID) was reviewed, and the potential for creating a WGBIOP library collection and active involvement of WGBIOP in updating FishBase.org data were evaluated. The importance of identifying and documenting links be-tween all relevant databases and document repositories was identified, and a task to address this was initiated. Work on improving the feedback loop between data collectors and stock assessors on the usage and quality of biological parameters in stock assessment continued. Moving forward, WGBIOP aims to continue collaboration with WGALES and WGSMART on the development of the SmartDots platform, encouraging cross-group sharing of skills and ex-perience to optimize results. WGBIOP aims to improve accessibility to its outputs through up-dates to SID and FishBase.org, and the potential creation of a WGBIOP library collection. WGBIOP hopes to improve two-way communication between data collectors and end-users around the quality and utility of biological parameters used in assessment. WGBIOP also aims to amalgamate all validation activities into one coherent workstream.ICE

Cellular Growth Kinetics Distinguish a Cyclophilin Inhibitor from an HSP90 Inhibitor as a Selective Inhibitor of Hepatitis C Virus

During antiviral drug discovery, it is critical to distinguish molecules that selectively interrupt viral replication from those that reduce virus replication by adversely affecting host cell viability. In this report we investigate the selectivity of inhibitors of the host chaperone proteins cyclophilin A (CypA) and heat-shock protein 90 (HSP90) which have each been reported to inhibit replication of hepatitis C virus (HCV). By comparing the toxicity of the HSP90 inhibitor, 17-(Allylamino)-17-demethoxygeldanamycin (17-AAG) to two known cytostatic compounds, colchicine and gemcitabine, we provide evidence that 17-AAG exerts its antiviral effects indirectly through slowing cell growth. In contrast, a cyclophilin inhibitor, cyclosporin A (CsA), exhibited selective antiviral activity without slowing cell proliferation. Furthermore, we observed that 17-AAG had little antiviral effect in a non-dividing cell-culture model of HCV replication, while CsA reduced HCV titer by more than two orders of magnitude in the same model. The assays we describe here are useful for discriminating selective antivirals from compounds that indirectly affect virus replication by reducing host cell viability or slowing cell growth

The lancet weight determines wheal diameter in response to skin prick testing with histamine

BACKGROUND:Skin prick test (SPT) is a common test for diagnosing immunoglobulin E-mediated allergies. In clinical routine, technicalities, human errors or patient-related biases, occasionally results in suboptimal diagnosis of sensitization. OBJECTIVE:Although not previously assessed qualitatively, lancet weight is hypothesized to be important when performing SPT to minimize the frequency of false positives, false negatives, and unwanted discomfort. METHODS:Accurate weight-controlled SPT was performed on the volar forearms and backs of 20 healthy subjects. Four predetermined lancet weights were applied (25 g, 85 g, 135 g and 265 g) using two positive control histamine solutions (1 mg/mL and 10 mg/mL) and one negative control (saline). A total of 400 SPTs were conducted. The outcome parameters were: wheal size, neurogenic inflammation (measured by superficial blood perfusion), frequency of bleeding, and the lancet provoked pain response. RESULTS:The mean wheal diameter increased significantly as higher weights were applied to the SPT lancet, e.g. from 3.2 ± 0.28 mm at 25 g to 5.4 ± 1.7 mm at 265 g (p<0.01). Similarly, the frequency of bleeding, the provoked pain, and the neurogenic inflammatory response increased significantly. At 265 g saline evoked two wheal responses (/160 pricks) below 3 mm. CONCLUSION AND CLINICAL RELEVANCE:The applied weight of the lancet during the SPT-procedure is an important factor. Higher lancet weights precipitate significantly larger wheal reactions with potential diagnostic implications. This warrants additional research of the optimal lancet weight in relation to SPT-guidelines to improve the specificity and sensitivity of the procedure

Discovery of drug-omics associations in type 2 diabetes with generative deep-learning models.

The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug-omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug-drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities. [Abstract copyright: © 2023. The Author(s).