A previously unrecognized superfamily of macro-conotoxins includes an inhibitor of the sensory neuron calcium channel Cav2.3.

Animal venom peptides represent valuable compounds for biomedical exploration. The venoms of marine cone snails constitute a particularly rich source of peptide toxins, known as conotoxins. Here, we identify the sequence of an unusually large conotoxin, Mu8.1, which defines a new class of conotoxins evolutionarily related to the well-known con-ikot-ikots and 2 additional conotoxin classes not previously described. The crystal structure of recombinant Mu8.1 displays a saposin-like fold and shows structural similarity with con-ikot-ikot. Functional studies demonstrate that Mu8.1 curtails calcium influx in defined classes of murine somatosensory dorsal root ganglion (DRG) neurons. When tested on a variety of recombinantly expressed voltage-gated ion channels, Mu8.1 displayed the highest potency against the R-type (Cav2.3) calcium channel. Ca2+ signals from Mu8.1-sensitive DRG neurons were also inhibited by SNX-482, a known spider peptide modulator of Cav2.3 and voltage-gated K+ (Kv4) channels. Our findings highlight the potential of Mu8.1 as a molecular tool to identify and study neuronal subclasses expressing Cav2.3. Importantly, this multidisciplinary study showcases the potential of uncovering novel structures and bioactivities within the largely unexplored group of macro-conotoxins.

From Unregulated Networks to Designed Microstructures: Introducing Heterogeneity at Different Length Scales in Photopolymers for Additive Manufacturing.

Photopolymers have been optimized as protective and decorative coating materials for decades. However, with the rise of additive manufacturing technologies, vat photopolymerization has unlocked the use of photopolymers for three-dimensional objects with new material requirements. Thus, the originally highly cross-linked, amorphous architecture of photopolymers cannot match the expectations for modern materials anymore, revealing the largely unanswered question of how diverse properties can be achieved in photopolymers. Herein, we review how microstructural features in soft matter materials should be designed and implemented to obtain high performance materials. We then translate these findings into chemical design suggestions for enhanced printable photopolymers. Based on this analysis, we have found microstructural heterogenization to be the most powerful tool to tune photopolymer performance. By combining the chemical toolbox for photopolymerization and the analytical toolbox for microstructural characterization, we examine current strategies for physical heterogenization (fillers, inkjet printing) and chemical heterogenization (semicrystalline polymers, block copolymers, interpenetrating networks, photopolymerization induced phase separation) of photopolymers and put them into a material scientific context to develop a roadmap for improving and diversifying photopolymers' performance.

Prey Shifts Drive Venom Evolution in Cone Snails.

Venom systems are complex traits that have independently emerged multiple times in diverse plant and animal phyla. Within each venomous lineage there typically exists interspecific variation in venom composition where several factors have been proposed as drivers of variation, including phylogeny and diet. Understanding these factors is of broad biological interest and has implications for the development of anti-venom therapies and venom-based drug discovery. Because of their high species richness and the presence of several major evolutionary prey shifts, venomous marine cone snails (genus Conus) provide an ideal system to investigate drivers of interspecific venom variation. Here, by analyzing the venom gland expression profiles of ∼3,000 toxin genes from 42 species of cone snail, we elucidate the role of prey-specific selection pressures in shaping venom variation. By analyzing overall venom composition and individual toxin structures, we demonstrate that the shifts from vermivory to piscivory in Conus are complemented by distinct changes in venom composition independent of phylogeny. In vivo injections of venom from piscivorous cone snails in fish further showed a higher potency compared to venom of non-piscivores demonstrating a selective advantage. Together, our findings provide compelling evidence for the role of prey shifts in directing the venom composition of cone snails and expand our understanding of the mechanisms of venom variation and diversification.

Bioprocess development for cord blood mesenchymal stromal cells on microcarriers in Vertical-Wheel bioreactors.

Equine mesenchymal stromal cells (MSCs) have been found to be beneficial for the treatment of many ailments, including orthopedic injuries, due to their superior differentiation potential and immunomodulating properties. Cell therapies require large cell numbers, which are not efficiently generated using conventional static expansion methods. Expansion of equine cord blood-derived MSCs (eCB-MSCs) in bioreactors, using microcarriers as an attachment surface, has the potential to generate large numbers of cells with increased reproducibility and homogeneity compared with static T-flask expansion. This study investigated the development of an expansion process using Vertical-Wheel (VW) bioreactors, a single-use bioreactor technology that incorporates a wheel instead of an impeller. Initially, microcarriers were screened at small scale to assess eCB-MSC attachment and growth and then in bioreactors to assess cell expansion and harvesting. The effect of different donors, serial passaging, and batch versus fed batch were all examined in 0.1 L VW bioreactors. The use of VW bioreactors with an appropriate microcarrier was shown to be able to produce cell densities of up to 1E6 cells/mL, while maintaining cell phenotype and functionality, thus demonstrating great potential for the use of these bioreactors to produce large cell numbers for cell therapies.

Reconstructing the Origins of the Somatostatin and Allatostatin-C Signaling Systems Using the Accelerated Evolution of Biodiverse Cone Snail Toxins.

Somatostatin and its related peptides (SSRPs) form an important family of hormones with diverse physiological roles. The ubiquitous presence of SSRPs in vertebrates and several invertebrate deuterostomes suggests an ancient origin of the SSRP signaling system. However, the existence of SSRP genes outside of deuterostomes has not been established, and the evolutionary history of this signaling system remains poorly understood. Our recent discovery of SSRP-like toxins (consomatins) in venomous marine cone snails (Conus) suggested the presence of a related signaling system in mollusks and potentially other protostomes. Here, we identify the molluscan SSRP-like signaling gene that gave rise to the consomatin family. Following recruitment into venom, consomatin genes experienced strong positive selection and repeated gene duplications resulting in the formation of a hyperdiverse family of venom peptides. Intriguingly, the largest number of consomatins was found in worm-hunting species (>400 sequences), indicating a homologous system in annelids, another large protostome phylum. Consistent with this, comprehensive sequence mining enabled the identification of SSRP-like sequences (and their corresponding orphan receptor) in annelids and several other protostome phyla. These results established the existence of SSRP-like peptides in many major branches of bilaterians and challenge the prevailing hypothesis that deuterostome SSRPs and protostome allatostatin-C are orthologous peptide families. Finally, having a large set of predator-prey SSRP sequences available, we show that although the cone snail's signaling SSRP-like genes are under purifying selection, the venom consomatin genes experience rapid directional selection to target receptors in a changing mix of prey.

Structure-function association between contrast sensitivity and retinal thickness (total, regional, and individual retinal layer) in patients with idiopathic epiretinal membrane.

PURPOSE: To investigate structure-function associations between retinal thickness, visual acuity (VA), and contrast sensitivity (CS), using the quantitative contrast sensitivity function (qCSF) method in patients with idiopathic epiretinal membrane (ERM). METHODS: Retrospective, cross-sectional observational study. Patients with a diagnosis of idiopathic ERM were included. Patients underwent complete ophthalmic examination, spectral-domain optical coherence tomography imaging (SD-OCT) (SPECTRALIS® Heidelberg), and CS testing using the qCSF method. Outcomes included area under the log CSF (AULCSF), contrast acuity (CA), and CS thresholds at 1, 1.5, 3, 6, 12, and 18 cycles per degree (cpd). RESULTS: A total of 102 eyes of 79 patients were included. Comparing standardized regression coefficients, retinal thickness in most ETDRS sectors was associated with larger reductions in AULCSF, CA, and CS thresholds at 3 and 6 cpd than those in logMAR VA. These differences in effect on VA and CS metrics were more pronounced in the central subfield and inner ETDRS sectors. Among the retinal layers, increased INL thickness had the most detrimental effect on visual function, being significantly associated with reductions in logMAR VA, AULCSF, CA, and CS thresholds at 3 and 6 cpd (all p < .01), as well as at 1.5 and 12 cpd (p < .05). CONCLUSION: Retinal thickness seems to be associated with larger reductions in contrast sensitivity than VA in patients with ERM. Measured with the qCSF method, contrast sensitivity may serve as a valuable adjunct visual function metric for patients with ERM.

A normative database of wide-field swept-source optical coherence tomography angiography quantitative metrics in a large cohort of healthy adults.

PURPOSE: Data from healthy eyes is needed to interpret optical coherence tomography angiography (OCTA) findings. However, very little normative data is available for wide-field swept-source OCTA (WF SS-OCTA), particularly 12 × 12-mm and disc-centered angiograms. Therefore, we aim to report quantitative metrics in a large sample of control eyes. METHODS: In this cross-sectional observational study, 482 eyes of 375 healthy adults were imaged on the 100 kHz Zeiss PLEX® Elite 9000 using protocols centered on the fovea (3 × 3, 6 × 6, and 12 × 12-mm) and optic disc (6 × 6 and 12 × 12-mm) between December 2018 and January 2022. The ARI Network (Zeiss Portal v5.4) was used to calculate vessel density (VD) and vessel skeletonized density (VSD) in the superficial capillary plexus, deep capillary plexus, and whole retina, as well as foveal avascular zone (FAZ) parameters. Mixed-effect multiple linear regression models were used for statistical analysis. RESULTS: The subjects' median age was 55 (38-63) years, and 201 (53.6%) were female. Greater age and worse best-corrected visual acuity (BCVA) were associated with significantly lower VD and VSD (p < 0.05). VD and VSD differed based on race and cataract status, but not sex, on some scan protocols (p < 0.05). FAZ circularity decreased with age, and FAZ dimensions differed based on race and ethnicity in certain scan protocols. CONCLUSIONS: We report a large database of parafoveal and peripapillary vascular metrics in several angiogram sizes. In referencing these values, researchers must consider characteristics such as age, race, and BCVA, but will have a valuable point of comparison for OCTA measurements in pathologic settings.

Overview of Equine Stem Cells: Sources, Practices, and Potential Safety Concerns.

Over the past 2 decades, equine veterinarians are turning increasingly to stem cell therapies to repair damaged tissues or to promote healing through modulation of the immune system. Research is ongoing into optimizing practices associated with stem cell product transport, dosage, and administration. Culture-expanded equine mesenchymal stem cell therapies seem safe, even when used allogeneically, but various safety concerns should be considered. Stem cells and cellular reprogramming tools hold great promise for future equine therapies.

The CO2 record at the Amazon Tall Tower Observatory: A new opportunity to study processes on seasonal and inter-annual scales.

High-quality atmospheric CO2  measurements are sparse in Amazonia, but can provide critical insights into the spatial and temporal variability of sources and sinks of CO2 . In this study, we present the first 6 years (2014-2019) of continuous, high-precision measurements of atmospheric CO2 at the Amazon Tall Tower Observatory (ATTO, 2.1°S, 58.9°W). After subtracting the simulated background concentrations from our observational record, we define a CO2 regional signal ( ΔCO2obs ) that has a marked seasonal cycle with an amplitude of about 4 ppm. At both seasonal and inter-annual scales, we find differences in phase between ΔCO2obs and the local eddy covariance net ecosystem exchange (EC-NEE), which is interpreted as an indicator of a decoupling between local and non-local drivers of ΔCO2obs . In addition, we present how the 2015-2016 El Niño-induced drought was captured by our atmospheric record as a positive 2σ anomaly in both the wet and dry season of 2016. Furthermore, we analyzed the observed seasonal cycle and inter-annual variability of ΔCO2obs together with net ecosystem exchange (NEE) using a suite of modeled flux products representing biospheric and aquatic CO2 exchange. We use both non-optimized and optimized (i.e., resulting from atmospheric inverse modeling) NEE fluxes as input in an atmospheric transport model (STILT). The observed shape and amplitude of the seasonal cycle was captured neither by the simulations using the optimized fluxes nor by those using the diagnostic Vegetation and Photosynthesis Respiration Model (VPRM). We show that including the contribution of CO2 from river evasion improves the simulated shape (not the magnitude) of the seasonal cycle when using a data-driven non-optimized NEE product (FLUXCOM). The simulated contribution from river evasion was found to be 25% of the seasonal cycle amplitude. Our study demonstrates the importance of the ATTO record to better understand the Amazon carbon cycle at various spatial and temporal scales.

An evolutionary genomics view on neuropeptide genes in Hydrozoa and Endocnidozoa (Myxozoa).

BACKGROUND: The animal phylum Cnidaria consists of six classes or subphyla: Hydrozoa, Scyphozoa, Cubozoa, Staurozoa, Anthozoa, and Endocnidozoa. Cnidarians have an early evolutionary origin, diverging before the emergence of the Bilateria. Extant members from this phylum, therefore, are important resources for understanding the evolution of the nervous system. Cnidarian nervous systems are strongly peptidergic. Using genomics, we have recently shown that three neuropeptide families (the X1PRX2amides, GRFamides, and GLWamides) are wide-spread in four (Scyphozoa, Cubozoa, Staurozoa, Anthozoa) out of six cnidarian classes or subphyla, suggesting that these three neuropeptide families emerged in the common cnidarian ancestor. In the current paper, we analyze the remaining cnidarian class, Hydrozoa, and the subphylum Endocnidozoa, to make firm conclusions about the evolution of neuropeptide genes in Cnidaria. RESULTS: We analyzed sixteen hydrozoan species with a sequenced genome or transcriptome, using a recently developed software program for discovering neuropeptide genes. These species belonged to various hydrozoan subclasses and orders, among them the laboratory models Hydra, Hydractinia, and Clytia. We found that each species contained three to five neuropeptide families. A common feature for all hydrozoans was that they contained genes coding for (i) X1PRX2amide peptides, (ii) GRFamide peptides, and (iii) GLWamide peptides. These results support our previous conclusions that these three neuropeptide families evolved early in evolution. In addition to these three neuropeptide families, hydrozoans expressed up to two other neuropeptide gene families, which, however, were only occurring in certain animal groups. Endocnidozoa (Myxozoa) are microscopically small endoparasites, which are strongly reduced. For long, it was unknown to which phylum these parasites belonged, but recently they have been associated with cnidarians. We analyzed nine endocnidozoan species and found that two of them (Polypodium hydriforme and Buddenbrockia plumatellae) expressed neuropeptide genes. These genes coded for neuropeptides belonging to the GRFamide and GLWamide families with structures closely resembling them from hydrozoans. CONCLUSIONS: We found X1PRX2amide, GRFamide, and GLWamide peptides in all species belonging to the Hydrozoa, confirming that these peptides originated in the common cnidarian ancestor. In addition, we discovered GRFamide and GLWamide peptide genes in some members of the Endocnidozoa, thereby linking these parasites to Hydrozoa.

A comparative genomics study of neuropeptide genes in the cnidarian subclasses Hexacorallia and Ceriantharia.

BACKGROUND: Nervous systems originated before the split of Proto- and Deuterostomia, more than 600 million years ago. Four animal phyla (Cnidaria, Placozoa, Ctenophora, Porifera) diverged before this split and studying these phyla could give us important information on the evolution of the nervous system. Here, we have annotated the neuropeptide preprohormone genes of twenty species belonging to the subclass Hexacorallia or Ceriantharia (Anthozoa: Cnidaria), using thirty-seven publicly accessible genome or transcriptome databases. Studying hexacorals is important, because they are versatile laboratory models for development (e.g., Nematostella vectensis) and symbiosis (e.g., Exaiptasia diaphana) and also are prominent reef-builders. RESULTS: We found that each hexacoral or ceriantharian species contains five to ten neuropeptide preprohormone genes. Many of these preprohormones contain multiple copies of immature neuropeptides, which can be up to 50 copies of identical or similar neuropeptide sequences. We also discovered preprohormones that only contained one neuropeptide sequence positioned directly after the signal sequence. Examples of them are neuropeptides that terminate with the sequence RWamide (the Antho-RWamides). Most neuropeptide sequences are N-terminally protected by pyroglutamyl (pQ) or one or more prolyl residues, while they are C-terminally protected by an amide group. Previously, we isolated and sequenced small neuropeptides from hexacorals that were N-terminally protected by an unusual L-3-phenyllactyl group. In our current analysis, we found that these N-phenyllactyl-peptides are derived from N-phenylalanyl-peptides located directly after the signal sequence of the preprohormone. The N-phenyllactyl- peptides appear to be confined to the hexacorallian order Actiniaria and do not occur in other cnidarians. On the other hand, (1) the neuropeptide Antho-RFamide (pQGRFamide); (2) peptides with the C-terminal sequence GLWamide; and (3) tetrapeptides with the X1PRX2amide consensus sequence (most frequently GPRGamide) are ubiquitous in Hexacorallia. CONCLUSIONS: We found GRFamide, GLWamide, and X1PRX2amide peptides in all tested Hexacorallia. Previously, we discovered these three neuropeptide classes also in Cubozoa, Scyphozoa, and Staurozoa, indicating that these neuropeptides originated in the common cnidarian ancestor and are evolutionarily ancient. In addition to these ubiquitous neuropeptides, other neuropeptides appear to be confined to specific cnidarian orders or subclasses.

Hard Block Degradable Polycarbonate Urethanes: Promising Biomaterials for Electrospun Vascular Prostheses.

We report biodegradable thermoplastic polyurethanes for soft tissue engineering applications, where frequently used carboxylic acid ester degradation motifs were substituted with carbonate moieties to achieve superior degradation properties. While the use of carbonates in soft blocks has been reported, their use in hard blocks of thermoplastic polyurethanes is unprecedented. Soft blocks consist of poly(hexamethylene carbonate), and hard blocks combine hexamethylene diisocyanate with the newly synthesized cleavable carbonate chain extender bis(3-hydroxypropylene)carbonate (BHPC), mimicking the motif of poly(trimethylene carbonate) with highly regarded degradation properties. Simultaneously, the mechanical benefits of segmented polyurethanes are exploited. A lower hard block concentration in BHPC-based polymers was more suitable for vascular grafts. Nonacidic degradation products and hard block dependent degradation rates were found. Implantation of BHPC-based electrospun degradable vascular prostheses in a small animal model revealed high patency rates and no signs of aneurysm formations. Specific vascular graft remodeling and only minimal signs of inflammatory reactions were observed.

The use of induced pluripotent stem cells in domestic animals: a narrative review.

Induced pluripotent stem cells (iPSCs) are undifferentiated stem cells characterized by the ability to differentiate into any cell type in the body. iPSCs are a relatively new and rapidly developing technology in many fields of biology, including developmental anatomy and physiology, pathology, and toxicology. These cells have great potential in research as they are self-renewing and pluripotent with minimal ethical concerns. Protocols for their production have been developed for many domestic animal species, which have since been used to further our knowledge in the progression and treatment of diseases. This research is valuable both for veterinary medicine as well as for the prospect of translation to human medicine. Safety, cost, and feasibility are potential barriers for this technology that must be considered before widespread clinical adoption. This review will analyze the literature pertaining to iPSCs derived from various domestic species with a focus on iPSC production and characterization, applications for tissue and disease research, and applications for disease treatment.

Why the hype - What are microRNAs and why do they provide unique investigative, diagnostic, and therapeutic opportunities in veterinary medicine?

MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression by inhibiting translation or inducing transcript degradation. MiRNAs act as fine-tuning factors that affect the expression of up to 60% of all mammalian protein coding genes. In contrast to proteins, there is widespread conservation of miRNA sequences across species. This conservation strongly suggests that miRNAs appeared early in evolution and have retained their functional importance. Cross-species conservation provides advantages when compiling candidate markers for health and disease compared to protein-based discoveries. This broad utility is accompanied by the emergence of inexpensive sequencing protocols for the identification of all RNAs in a sample (including miRNAs). With the use of miRNA mimics and antagonists, unique research questions can be answered in biological systems with 'cause and effect' methodology. MiRNAs are readily detectable in blood making them attractive candidates as biomarkers for disease. Here, we review their utility as biomarkers and their potential as therapeutic agents or targets to combat disease.

Pourquoi la frénésie ­ Que sont les microRNAs et pourquoi fournissent-ils des opportunités uniques pour investiguer, diagnostiquer et traiter en médecine vétérinaire? Les microRNAs (MiRNAs) sont de petits segments non-codants d'ARN qui régulent l'expression des gènes en inhibant la traduction ou en induisant la dégradation du transcript. Les MiRNAs agissent comme des facteurs d'ajustement fin qui affectent l'expression pouvant aller jusqu'à 60 % de tous les gènes mammaliens codant pour des protéines. Contrairement aux protéines, il y a un conservatisme étendu des séquences des miRNA à travers les espèces. Ce conservatisme suggère fortement que les miRNAs sont apparus tôt dans l'évolution et ont conservé leur importance fonctionnelle. La conservation inter-espèces fournie des avantages lors de la compilation de candidats marqueurs pour la santé et la maladie comparativement aux découvertes basées sur les protéines. Cette large utilité est accompagnée par l'émergence de protocoles de séquençage peu dispendieux pour l'identification de tous les ARNs dans un échantillon (incluant miRNAs). Avec l'utilisation d'imitations et d'antagonistes de miRNA, des questionnements rares en recherche peuvent être répondus dans des systèmes biologiques avec des méthodologies « cause et effet ¼. Les miRNAs sont facilement détectables dans le sang ce qui les rend des candidats attirants comme biomarqueurs de maladies. Ici, nous faisons une revue de leur utilité comme biomarqueurs et leur potentiel comme agents thérapeutiques ou cibles pour combattre des maladies.(Traduit par Dr Serge Messier).

De novo transcriptome assembly of the cubomedusa Tripedalia cystophora, including the analysis of a set of genes involved in peptidergic neurotransmission.

BACKGROUND: The phyla Cnidaria, Placozoa, Ctenophora, and Porifera emerged before the split of proto- and deuterostome animals, about 600 million years ago. These early metazoans are interesting, because they can give us important information on the evolution of various tissues and organs, such as eyes and the nervous system. Generally, cnidarians have simple nervous systems, which use neuropeptides for their neurotransmission, but some cnidarian medusae belonging to the class Cubozoa (box jellyfishes) have advanced image-forming eyes, probably associated with a complex innervation. Here, we describe a new transcriptome database from the cubomedusa Tripedalia cystophora. RESULTS: Based on the combined use of the Illumina and PacBio sequencing technologies, we produced a highly contiguous transcriptome database from T. cystophora. We then developed a software program to discover neuropeptide preprohormones in this database. This script enabled us to annotate seven novel T. cystophora neuropeptide preprohormone cDNAs: One coding for 19 copies of a peptide with the structure pQWLRGRFamide; one coding for six copies of a different RFamide peptide; one coding for six copies of pQPPGVWamide; one coding for eight different neuropeptide copies with the C-terminal LWamide sequence; one coding for thirteen copies of a peptide with the RPRAamide C-terminus; one coding for four copies of a peptide with the C-terminal GRYamide sequence; and one coding for seven copies of a cyclic peptide, of which the most frequent one has the sequence CTGQMCWFRamide. We could also identify orthologs of these seven preprohormones in the cubozoans Alatina alata, Carybdea xaymacana, Chironex fleckeri, and Chiropsalmus quadrumanus. Furthermore, using TBLASTN screening, we could annotate four bursicon-like glycoprotein hormone subunits, five opsins, and 52 other family-A G protein-coupled receptors (GPCRs), which also included two leucine-rich repeats containing G protein-coupled receptors (LGRs) in T. cystophora. The two LGRs are potential receptors for the glycoprotein hormones, while the other GPCRs are candidate receptors for the above-mentioned neuropeptides. CONCLUSIONS: By combining Illumina and PacBio sequencing technologies, we have produced a new high-quality de novo transcriptome assembly from T. cystophora that should be a valuable resource for identifying the neuronal components that are involved in vision and other behaviors in cubomedusae.

Cebranopadol: A Novel First-in-Class Potent Analgesic Acting via NOP and Opioid Receptors.

Cebranopadol is a novel first-in-class analgesic with highly potent agonistic activity at nociceptin/orphanin FQ peptide (NOP) and opioid receptors. It is highly potent and efficacious across a broad range of preclinical pain models. Its side effect profile is better compared to typical opioids. Mechanistic studies have shown that cebranopadol's activity at NOP receptors contributes to its anti-hyperalgesic effects while ameliorating some of its opioid-type side effects, including respiratory depression and abuse potential. Phase II of clinical development has been completed, demonstrating efficacy and good tolerability in acute and chronic pain conditions.This article focusses on reviewing data on the preclinical in vitro and in vivo pharmacology, safety, and tolerability, as well as clinical trials with cebranopadol.

[Auditory processing disorder: Our experience with questionnaires]. / Auditive Verarbeitung und Wahrnehmungsstörungen: Erfahrungen mit Fragebogeninstrumenten.

BACKGROUND: Impairments of sound discrimination, speech comprehension in background noise, memory, etc. can be assessed within the diagnosis of an auditory processing and perception disorder (AVWS) in a structured manner using the questionnaire (DGPP-AVWS-FB) provided by the German Society for Phoniatrics and Pedaudiology. The aim is to report on experiences with the use of this questionnaire in a pedaudiology practice. In particular, it was to be determined whether information on the auditory behaviour provided by parents is similar or different to information provided by kindergarten teachers (KGK) or teachers at school (LK). METHODS: During a nine-month period, all parents who presented their children to be examined for a possible AVWS were handed the DGPP-AVWS-FB to be completed by them and by KGK/LK. In order to compare the agreement of the judgements, two questionnaires on attention and concentration or on executive functions (DISYPS II, BRIEF or BRIEF-P) were also given. Data from children with peripheral hearing impairment or cognitive developmental disorder were not used. The correlation coefficient was then calculated for the respective items, scales and indices. RESULTS: Completed questionnaires were available at the end of the study period for a total of 20 primary school children and 7 kindergarten children. In kindergarten children, only KGK but not parents, in school children however, 1x only parents, 16x only LK and in the remaining 3 others both parents and LK suspected an impaired auditory processing. The evaluation of the DGPP-AVWS-FB ultimately reflected this different assessment of the symptoms: with the exception of children in whom both parents and LK suspected an AVWS, the information provided by the parents showed only little agreement with the information provided by the KGK/LK. In comparison, the responses to the other two questionnaires were also different, but the data on attention and hyperactivity in kindergarten children tended to be more similar. DISCUSSION: The data presented could be explained by a different behavior of the children at home or in kindergarten/school. It could also be that the same behavior is evaluated differently. Low correlations are already known for questionnaires on attention deficit/hyperactivity disorder and executive functions.For the clinical routine it is recommended to document the reported symptoms standardized with the DGPP-AVWS-FB and in particular to determine whether an abnormal auditory behavior is noticeable in only one or two or more environments.

[Adjuvant electrostimulation therapy for chronic rhinosinusitis]. / Adjuvante Elektrostimulationstherapie bei chronischer Rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is one of the most common chronic diseases in Germany and is often accompanied by years of chronic rhinosinusitis. According to the current German guideline "Rhinosinusitis", the nasal application of salt solutions, topical corticosteroids and in individual cases also systemic corticosteroids appear useful for a symptomatic therapy of CRS. The evidence for other therapeutic procedures such as acupuncture, homeopathy and phytotherapeutics is seen as insufficient. The aim of the present study was to investigate whether anti-inflammatory effects of electrostimulation therapy can also be demonstrated in CRS. METHODOLOGY: randomized, prospective single center study, primary setting; 16 patients with moderate chronic rhinosinusitis with polyps (cRScNP), corresponding to a Lund / Mackay score of 6-12; home based electrostimulation therapy (EST) with amplitude modulated current (base frequency of 4000 Hz, frequency band of 100-250 Hz) over 2 weeks adjuvant to a concurrent sinusitis therapy with topical corticosteroids; measurement of nasal nitric oxide concentration and self-assessment of complaints with the questionnaire instrument SNOT-20 GAV; survey points t0 before EST, t1 after EST, t2 6 weeks after t1. RESULTS: Home based EST was performed by 16 patients. The results indicate that the positive effects of electrostimulation therapy in inflammatory processes also exist in CRS. DISCUSSION: Adjuvant transsinuidal electrostimulation could thus enrich the conservative therapy of CRS. Further studies with larger collectives are desirable.

Vinyl Sulfonate Esters: Efficient Chain Transfer Agents for the 3D Printing of Tough Photopolymers without Retardation.

The formation of networks through light-initiated radical polymerization allows little freedom for tailored network design. The resulting inhomogeneous network architectures and brittle material behavior of such glassy-type networks limit the commercial application of photopolymers in 3D printing, biomedicine, and microelectronics. An ester-activated vinyl sulfonate ester (EVS) is presented for the rapid formation of tailored methacrylate-based networks. The chain transfer step induced by EVS reduces the kinetic chain length of the photopolymer, thus shifting the gel point to higher conversion, which results in reduced shrinkage stress and higher overall conversion. The resulting, more homogeneous network is responsible for the high toughness of the material. The unique property of EVS to promote nearly retardation-free polymerization can be attributed to the fact that after the transfer step no polymerizable double bond is formed, as is usually seen in classical chain transfer agents. Laser flash photolysis, theoretical calculations, and photoreactor studies were used to elucidate the fast chain transfer reaction and exceptional regulating ability of EVS. Final photopolymer networks exhibit improved mechanical performance making EVS an outstanding candidate for the 3D printing of tough photopolymers.

Aspiration, but not injection, decreases cultured equine mesenchymal stromal cell viability.

BACKGROUND: Recently, equine multipotent mesenchymal stromal cells (MSC) have received significant attention as therapy for various conditions due to their proposed regenerative and immune-modulating capacity. MSC are commonly administered to the patient through a hypodermic needle. Currently, little information is available on the effect of such injection has on equine MSC immediate and delayed viability. We hypothesize that viability of equine MSC is not correlated with needle diameter during aspiration and injection. RESULTS: Using a 3 mL syringe, manual injection of equine cord blood (CB) or bone marrow-derived (BM) MSC with no needle and needles ranging in size from 18 to 30 Ga did not affect immediate MSC viability. Similarly, 24 h post-injection, MSC delayed viability was not different between any of the tested needles as determined by a resazurin-based proliferation assay. Using a 3 mL syringe, aspiration of MSC through 20, 25, and 30 Ga needles resulted in significant decreases in immediate viability with no change in delayed viability when compared to aspiration without a needle. BM- and CB-MSC were observed to be of similar size with a diameter ± SD of 19.8 ± 2.7 and 20.4 ± 2.2 µm, respectively. In comparison, the smallest needles, (30 Ga) have an internal diameter of 160 µm. CONCLUSIONS: Following injection, needle diameter did not affect immediate or delayed viability of equine MSC. Following aspiration through needles sizes 20 Ga and smaller, immediate viability, but not delayed viability, decreased. As a result, an 18 Ga or larger needle should be utilized for aspiration of cell suspensions. In contrast, needle selection for MSC injection should be based on clinical preference and experience rather than concerns over decreasing MSC viability.