The longitudinal behavioral effects of acute exposure to galactic cosmic radiation in female C57BL/6J mice: implications for deep space missions, female crews, and potential antioxidant countermeasures.

Galactic cosmic radiation (GCR) is an unavoidable risk to astronauts that may affect mission success. Male rodents exposed to 33-beam-GCR (33-GCR) show short-term cognitive deficits but reports on female rodents and long-term assessment is lacking. Here we asked: What are the longitudinal behavioral effects of 33-GCR on female mice? Also, can an antioxidant/anti-inflammatory compound mitigate the impact of 33-GCR? Mature (6-month-old) C57BL/6J female mice received the antioxidant CDDO-EA (400 µg/g of food) or a control diet (vehicle, Veh) for 5 days and either Sham-irradiation (IRR) or whole-body 33-GCR (0.75Gy) on the 4th day. Three-months post-IRR, mice underwent two touchscreen-platform tests: 1) location discrimination reversal (which tests behavior pattern separation and cognitive flexibility, two abilities reliant on the dentate gyrus) and 2) stimulus-response learning/extinction. Mice then underwent arena-based behavior tests (e.g. open field, 3-chamber social interaction). At the experiment end (14.25-month post-IRR), neurogenesis was assessed (doublecortin-immunoreactive [DCX+] dentate gyrus neurons). Female mice exposed to Veh/Sham vs. Veh/33-GCR had similar pattern separation (% correct to 1st reversal). There were two effects of diet: CDDO-EA/Sham and CDDO-EA/33-GCR mice had better pattern separation vs. their respective control groups (Veh/Sham, Veh/33-GCR), and CDDO-EA/33-GCR mice had better cognitive flexibility (reversal number) vs. Veh/33-GCR mice. Notably, one radiation effect/CDDO-EA countereffect also emerged: Veh/33-GCR mice had worse stimulus-response learning (days to completion) vs. all other groups, including CDDO-EA/33-GCR mice. In general, all mice show normal anxiety-like behavior, exploration, and habituation to novel environments. There was also a change in neurogenesis: Veh/33-GCR mice had fewer DCX+ dentate gyrus immature neurons vs. Veh/Sham mice. Our study implies space radiation is a risk to a female crew's longitudinal mission-relevant cognitive processes and CDDO-EA is a potential dietary countermeasure for space-radiation CNS risks.

Tachykinins amplify the action of capsaicin on central histaminergic neurons.

Substance P (SP), a product of the tachykinin 1 (Tac1) gene, is expressed in many hypothalamic neurons. Its wake-promoting potential could be mediated through histaminergic (HA) neurons of the tuberomamillary nucleus (TMN), where functional expression of neurokinin receptors (NKRs) waits to be characterized. As in the process of nociception in the peripheral nervous system (PNS) capsaicin-receptor (transient potential vanilloid 1: TRPV1) signalling is amplified by local release of histamine and SP, we tested the involvement of tachykinins in the capsaicin-induced long-lasting enhancement (LLEcaps) of HA neurons firing by investigating selective neurokinin receptor ligands in the hypothalamic mouse brain slice preparation using patch-clamp recordings in cell-attached mode combined with single-cell RT-PCR. We report that the majority of HA neurons respond to SP (EC50 3 nM), express the SP precursor tachykinin 1 (Tac1) gene and at least one of the neurokinin receptors. Responses to selective agonists of three known neurokinin receptors were sensitive to corresponding antagonists. LLEcaps was significantly impaired by the neurokinin receptor antagonists, indicating that in hypothalamus, as in the PNS, release of tachykinins downstream to TRPV1 activation is able to boost the release of histamine. The excitatory action of SP on histaminergic neurons adds another pathway to the noradrenergic and orexinergic ones to synergistically enhance cortical arousal. We show NK1R to play a prominent role on HA neurons and thus the control of wakefulness.

Familiarity influences social networks in dairy cows after regrouping.

Regrouping is common practice when managing dairy cow groups, and it is known to have disruptive effects on behavior and production. The presence of a small group of familiar cows upon regrouping may provide social support and mitigate some of the negative effects. In this study we investigated (1) how regrouping affects social relationships among familiar cows and (2) if cows prefer familiar individuals over unfamiliar ones as social partners after regrouping. We used 3 established groups of cows to create 2 new groups, each containing 14 cows, using subgroups of familiar animals (i.e., 4, 6, and 4 cows) from the original groups. The new groups were similar in respect to the age, parity, and sire of cows. The frequencies of grooming and displacements were determined in the walking alley, lying stalls, and feed bunk by observing 48 h of continuous video before regrouping, directly after regrouping, and 1 wk later. First, social network analysis was applied to investigate the effects of regrouping on the relationships within the subgroups of familiar cows. Second, we determined if familiar cows were more or less connected than would be expected by chance (i.e., assortment), considering displacement, grooming, and feed bunk neighbor networks (derived from electronic feeder data) after regrouping. Regrouping increased the number of displacements, especially in the walking alley. Within the subgroups of familiar cows, regrouping resulted in slightly more displacements, but the network structure did not change. The frequency of grooming among familiar cows remained stable across all observation periods, and the network structure was not affected by regrouping. We found positive assortment in grooming and feed bunk neighbor networks, thereby suggesting that cows preferred familiar individuals as grooming partners and feeding neighbors directly after regrouping and, to a smaller extent, 1 wk later. The effect of familiarity on displacements depended on the pen area. The weak assortment directly after regrouping at the feed bunk indicated that familiar cows displaced each other more than unfamiliar ones, possibly because they were neighbors more often. Our results indicated that a small group of familiar cows may provide ongoing social buffering after regrouping. Further research with multiple groups and larger group sizes is needed to determine whether similar effects are consistently present when groups of familiar cows are subjected to regrouping.

A copper(II)-binding triazole derivative with ionophore properties is active against Candida spp.

Invasive fungal infections (IFIs) are life threatening and existing antifungal drugs are not completely effective due to undesirable side effects and resistance emergence. Azoles are often the treatment of choice for IFIs and growing evidence suggests that copper can act synergistically with these drugs. In this work, we designed a compound bringing together azole and copper(II)-binding groups and studied the molecular mechanisms underlying its biological toxicity. Our results show that both the compound, 4, and its copper(II) complex, Cu.4, are active against Candida spp. We found that Cu.4 acts as a copper(II) ionophore, which results in the intracellular accumulation of reactive oxygen species (ROS), whereas compound 4 is an iron chelator and exerts its toxicity by decreasing iron bioavailability. Interestingly, while 4 is not very toxic to macrophages or HeLa cells, Cu.4 significantly affects their viability. Overall, this work provides evidence of how copper can be combined with azoles to deregulate copper homeostasis, opening new horizons for the development of bifunctional antifungals.

Gigabit per second visible light communication based on AlGaInP red micro-LED micro-transfer printed onto diamond and glass.

Full-color smart displays, which act both as a display and as a high-speed visible light communication (VLC) transmitter, can be realized by the integration of red-green-blue micron-sized light emitting diodes (micro-LEDs) onto a common platform. In this work, we report on the integration of aluminum gallium indium phosphide red micro-LEDs onto diamond and glass substrates by micro-transfer printing and their application in VLC. The device on-diamond exhibits high current density and bandwidth operation, enabled by diamond's superior thermal properties. Employing an orthogonal frequency division multiplexing modulation scheme, error-free data rates of 2.6 Gbps and 5 Gbps are demonstrated for a single micro-LED printed on-glass and on-diamond, respectively. In a parallel configuration, a 2x1 micro-LED array achieves error-free data rates of 3 Gbps and 6.6 Gbps, on-glass and on-diamond, respectively.

[Urology in the corona-virus pandemic-a guideline 4/20]. / Urologie in der Corona-Virus-Pandemie ­ Leitfaden 4/20.

The coronavirus pandemic is a major challenge for healthcare systems worldwide. For urology, the expansion of the health-care structures for the treatment of patients suffering from COVID-19 should be supported as best as possible. At the same time, one should aim to ensure adequate care for urological emergencies and urgent urological treatments as far as possible, even during the pandemic. For this, patients must be prioritized individually, alternative therapy concepts must be considered and regional and supraregional cooperation must be used. Outpatient departments are of great importance in the care, examination and coordination of urological emergencies and urgent treatment. Urological clinics must prepare themselves to perform urgent operations and interventions on SARS-CoV­2-positive patients. Here, the creation of a separate, appropriately equipped emergency operating room to perform operations and interventions on SARS-CoV­2 patients should be considered. Furthermore strictly defined hygiene measures to protect employees in various clinical scenarios should be set up.

Optical spatial modulation design.

Visible light communication (VLC) systems are inherently signal-to-noise ratio (SNR) limited due to link budget constraints. One favourable method to overcome this limitation is to focus on the pre-log factors of the channel capacity. Multiple-input multiple-output (MIMO) techniques are therefore a promising avenue of research. However, inter-channel interference in MIMO limits the achievable capacity. Spatial modulation (SM) avoids this limitation. Furthermore, the performance of MIMO systems in VLC is limited by the similarities among spatial channels. This limitation becomes particularly severe in intensity modulation/direct detection (IM/DD) systems because of the lack of phase information. The motivation of this paper is to propose a system that results in a multi-channel transmission system that enables reliable multi-user optical MIMO SM transmission without the need for a precoder, power allocation algorithm or additional optics at the receiver. A general bit error performance model for the SM system is developed for an arbitrary number of light-emitting diodes (LEDs) in conjunction with pulse amplitude modulation. Based on this model, an LED array structure is designed to result in spatially separated multiple channels by manipulating the transmitter geometry. This article is part of the theme issue 'Optical wireless communication'.

Evaluation of bladder stimulation as a non-invasive technique for urine collection to diagnose urinary tract infection in infants under 6 months: a randomized multicenter study ("EE-Sti.Ve.N").

BACKGROUND: Febrile urinary tract infection (UTI) is common in infants and needs to be diagnosed quickly. However, the symptoms are non-specific, and diagnosis can only be confirmed after high quality urinalysis. The American Academy of Pediatrics recommends suprapubic aspiration (1-9% contamination) and urinary catheterization (8-14% contamination) for urine collection but both these procedures are invasive. Recent studies have shown a new non-invasive method of collecting urine, bladder stimulation, to be quick and safe. However, few data about bacterial contamination rates have been published for this technique. We hypothesize that the contamination rate of urine collection by bladder stimulation to diagnose febrile UTI in infants under 6 months is equivalent to that of urinary catheterization. METHODS/DESIGN: This trial aims to assess equivalence in terms of bacterial contamination of urinary samples collected by urinary catheterization and bladder stimulation to diagnose UTI. Seven hundred seventy infants under 6 months presenting with unexplained fever in one of four Pediatric Emergency Departments in France will be enrolled. Each child will be randomized into a bladder stimulation or urinary catheterization group. The primary endpoints will be the validity of the urine sample assessed by the presence of contamination on bacterial culture. CONCLUSION: A high recruitment rate is achievable due to the high prevalence of suspected UTIs in infants. The medical risk is the same as that for routine clinical care as we analyze patients with isolated fever. If our hypothesis holds true and the rate of urine contamination collected by bladder stimulation is acceptable, the infants included in the study will have benefited from a non-invasive and reliable means of collecting urine. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03801213. Registered on 11 January 2019.

On-chip GaN-based dual-color micro-LED arrays and their application in visible light communication.

Integrated multi-color micron-sized light emitting diode (micro-LED) arrays have been demonstrated in recent years for display applications; however, their potential as visible light communication (VLC) transmitters is yet to be fully explored. In this work, we report on the fabrication and characterization of on-chip dual-color micro-LED arrays and their application in VLC. For this purpose, blue-green and blue-violet micro-LED arrays were fabricated by transfer printing blue-emitting micro-LEDs onto the substrate of green and violet micro-LEDs, respectively. The potential of these dual-color micro-LED arrays as VLC transmitters is demonstrated with respective error-free data rates of 1.79 and 3.35 Gbps, achieved by the blue-green and blue-violet devices in a dual wavelength multiplexing scheme.

Guidelines of the French Society of Otorhinolaryngology (SFORL): Nonsteroidal anti-inflammatory drugs (NSAIDs) and pediatric ENT infections. Short version.

OBJECTIVES: To present the guidelines of the French Society of Otolaryngology-Head and Neck Surgery concerning the use of non-steroidal anti-inflammatory drugs (NSAIDs) in pediatric ENT infections. METHODS: Based on a critical analysis of the medical literature up to November 2016, a multidisciplinary workgroup of 11 practitioners wrote clinical practice guidelines. Levels of evidence were classified according to the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) system: GRADE A, B, C or "expert opinion". The first version of the text was reworked by the workgroup following comments by the 22 members of the reading group. RESULTS: The main recommendations are: NSAIDs are indicated at analgesic doses (e.g. 20-30 mg/kg/day for ibuprofen) in combination with paracetamol (acetaminophen) in uncomplicated pediatric ENT infections (acute otitis media, tonsillitis, upper respiratory infections, and maxillary sinusitis) if: o pain is of medium intensity (visual analogue scale (VAS) score 3-5 or "Evaluation Enfant Douleur" (EVENDOL) child pain score 4-7) and insufficiently relieved by first-line paracetamol (residual VAS≥3 or EVENDOL≥4); o pain is moderate to intense (VAS 5-7 or EVENDOL 7-10). When combined, paracetamol and ibuprofen are ideally taken simultaneously every 6h. It is recommended: (1) o not to prescribe NSAIDs in severe or complicated pediatric ENT infections; (2) o to suspend NSAIDs treatment in case of unusual clinical presentation of the infection (duration or symptoms); (3) o not to prescribe NSAIDs for more than 72h.

Investigation of charge ratio variation in mRNA - DEAE-dextran polyplex delivery systems.

mRNA pharmaceuticals represent a new class of therapeutics, with applications, in cancer vaccination, tumour therapy and protein substitution. Formulations are required to deliver messenger RNA (mRNA) to the target sites where induction of genetic transfection following receptor mediated cell uptake & translation is required. In the current study, the cationic polysaccharide diethylaminoethylen (DEAE) - Dextran was selected as a model system carrier for the investigation of polyplex nanoparticle formation together with mRNA as a function of the molar ratio of the components. The structure of the mRNA/Dextran colloids was investigated as a function of the polymer-to-mRNA ratio and correlated with the biological activity determined by cellular transfection with luciferase coding mRNA. Dynamic light scattering (DLS), small angle x-ray scattering (SAXS), and small angle neutron scattering (SANS) with deuterium contrast variation were used to achieve structural insight into the systems. Similarly to previously investigated lipid based systems, colloidally stable particles with confined size were obtained with either excess of positive or negative charge. Highest activity was obtained with positive charge excess. From the scattering experiments information on the internal organization inside the polymer/mRNA systems was derived. Indication for the presence of structural elements in the length scale of ten to 20 nm were found in the excess of dextran, which could be due to either excess or particulate polymer. Information on the molecular organization of the mRNA nanoparticle products may provide a valuable basis for defining critical quality attributes of drug products for pharmaceutical application.

Infant botulism: Two case reports and electroneuromyogram findings.

Botulism is an uncommon severe neuromuscular disorder. We report two recent cases of confirmed infant botulism diagnosed in an 11-week and a 5-month-old infant along with electroneuromyogram (ENMG) findings. Then, we discuss the EMG features of infant botulism. In severe forms of infant botulism, presence of these features might help decide to use botulinum immune globulin. To our knowledge, case 1 is the first case reported in France based on confirmed dust contamination.

[Handling of retrieved implants in orthopedic surgery : Results of a survey within the framework of the EndoCert initiative]. / Bestandsaufnahme zum Umgang mit ausgebauten Implantaten in der orthopädischen Chirurgie : Ergebnisse einer Umfrage im Rahmen der EndoCert-Initiative.

BACKGROUND: Although investigations of retrieved medical implants can provide valuable information about the cause of the revision, there is a lack of information, which could be avoided by consequent failure analyses. In the framework of the EndoCert certification system it is obligatory to record and report incidents. OBJECTIVES: The present work examines how the willingness to report has developed in certified arthroplasty centers and which method of handling retrievals is preferred and actually used. MATERIALS AND METHODS: On the basis of a questionnaire for handling retrievals, all 508 arthroplasty centers that were certified till June 1, 2016, were included (return rate = 97.2%). RESULTS: A total of 93.3% of the centers have established an algorithm for handling of retrievals and 83.0% of the centers prefer to hand out the retrieval to the patient, while only 25.7% wish to store it in the center for research purposes. In the case of a potential incident as the cause of revision, centers prefer to forward the retrieval to damage analysis, whereby the centers act in different ways, depending on the case. An implant fracture is, e.g., considered a reportable event in most cases without temporal limitation. On the other hand, breakage or failure of surgical instruments is considered not to be reported in the case of more than half of the centers. In 2014 and 2015, approximately 71% of EPZs reported no incidents. CONCLUSIONS: According to our survey, many certified arthroplasty centers are sensitized to careful handling of retrievals. The treatment of the explanted components is conducted in different ways. The assessment of whether an incident is to be reported shows large differences. In view of the relatively high number of revision surgeries, the number of reports to the authorities appears to be low.

Transfer-printed micro-LED and polymer-based transceiver for visible light communications.

Visible light communications (VLC) is an emerging technology that uses LEDs, such as found in lighting fixtures and displays, to transmit data wirelessly. Research has so far focused on LED transmitters and on photoreceivers as separate, discrete components. Combining both types of devices into a single transceiver format will enable bi-directional VLC and offer flexibility for the development of future advanced VLC systems. Here, a proof of concept for an integrated optical transceiver is demonstrated by transfer printing a microsize LED, the transmitter, directly onto a fluorescent optical concentrator edge-coupled to a photodiode, the receiver. This integrated device can simultaneously receive (downlink) and transmit (uplink) data at rates of 416 Mbps and 165 Mbps, respectively. Its capability to operate in optical relay mode at 337 Mbps is experimentally demonstrated.

InGaN µLEDs integrated onto colloidal quantum dot functionalized ultra-thin glass.

Red-, orange-, and green-emitting integrated optoelectronic sources are demonstrated by transfer printing blue InGaN µLEDs onto ultra-thin glass platforms functionally enhanced with II-VI colloidal quantum dots (CQDs). The forward optical power conversion efficiency of these heterogeneously integrated devices is, respectively, 9%, 15%, and 14% for a blue light absorption over 95%. The sources are demonstrated in an orthogonal frequency division multiplexed (OFDM) visible light communication link reaching respective data transmission rates of 46 Mbps, 44 Mbps and 61 Mbps.

Human basophils are a source of - and are differentially activated by - IL-31.

BACKGROUND: Basophils are important effector cells involved in the pathogenesis of inflammatory skin diseases including chronic urticaria which is associated by increased IL-31 serum levels. So far the effects of IL-31 on human basophils are unknown. OBJECTIVE: To analyse the functional role of IL-31 in basophil biology. METHODS: IL-31 expression was evaluated in skin samples derived from chronic spontaneous urticaria patients. Oncostatin M receptor (OSMR), IL-31 receptor A (RA) and IL-31 protein expressions were analysed on human basophils from healthy donors. Basophil responses to IL-31 were assessed for chemotaxis, externalization of CD63 and CD203c as well as the release of histamine, IL-4 and IL-13. RESULTS: IL-31RA and OSMR were expressed on human basophils. IL-31 was strongly expressed in the skin of patients with chronic spontaneous urticaria and was released from isolated basophils following either anti-IgE, IL-3 or fMLP stimulation. IL-31 induced chemotaxis and the release of IL-4 and IL-13 which was specifically inhibited by anti-IL-31RA and anti-OSMR. Conversely, IL-31 had no effect on CD63 and CD203c externalization or histamine release. CONCLUSIONS AND CLINICAL RELEVANCE: Human basophils are a source of -and are activated by - IL-31 with the release of pro-inflammatory cytokines and the induction of chemotaxis indicating an important novel function of IL-31 in basophil biology.