EP Rounds

Atopic dermatitis (AD) is a chronic remitting-relapsing inflammatory skin disorder. Due to the multifactorial pathogenesis, there are numerous therapeutic management approaches, mainly based on symptomatic treatments. In recent years Allergen Immunotherapy (AIT) has been progressively advanced as targeted disease-modifying treatment of allergic disease. The most recent guideline from the American Academy of Dermatology concludes that data available do not support its use in AD. The Joint Task Force and The European Academy of Dermatology suggest that clinicians can consider AIT treatment in selected patients characterized by aeroallergen sensitization, prevalently HDM, severe AD, clinical exacerbation after exposure to the causative allergen. Nevertheless, its role in AD is still under debate, especially in children.

Background: Antiretroviral therapy reduces systemic inflammation and immune activation, but not to levels like HIV-negative. Limited drug penetration within tissues has been argued as potential mechanism of persistent inflammation. Data on the role of inflammation on plasma/intracellular (IC) pharmacokinetics (PK) of ARV drugs through to downregulation/expression of cytochrome P450 3A/membrane transport proteins are limited. Aim of this study was to investigate the correlation between inflammation markers and plasma/IC PK of different ARVs regimen in HIV-positive patients. Methods: We included in the study ART-treated HIV+ pts switching to 3 different ARV regimens: 1) DTG-based dual-therapy plus boosted-PIs, 2) DTG-based triple-therapy without PIs, 3) DRV/c-based triple-therapy. Plasma and IC ARV drugs concentration means at the end of dosing interval (T0), IM on samples concomitantly with ARV PK determination: sCD14, CRP, IL-6 and LPS were analysed. Results: 60 samples from pts included in the switching study were used for measuring plasma and IC concentrations of HIV drugs. No significative differences between CRP, sCD14, IL-6 and LPS values in 3 arms of therapy were observed. Significant correlation was observed between tenofovir plasma concentrations and sCD14 (p<0.001), DRV plasma concentration and sCD14 (p=0,07) and DRV IC/plasma ratio and Log10 IL-6 concentrations (p=0.04). Furthermore, in 24 pts on DTG-TT, we observed a negative trend between DTG IC concentrations and sCD14 (p=0.09). Conclusions: Our preliminary data support the hypothesis of lower IC concentrations of DRV and DTG in pts with higher plasma IM, suggesting an interplay between HIV drug penetration and persistent inflammation in cART-treated HIV-positive patients.

Minimally invasive mitral valve surgery can be performed with or without robotic assistance. In this issue of the journal Zheng et al compare between these two approaches in a propensity matched study over a 5 year period and show that the two techniques have similar successful short and mid term outcomes. Although we are proponents of the robotic approach, we agree with their conclusions and discuss in this commentary some of the previously published studies that have shown similar findings.

Cell-to-cell variability in cell populations arises from a combination of intrinsic factors and extrinsic factors related to the milieu. However, the heterogeneity of high cell density suspension cultures for therapeutic protein production remains unknown. Here, we illustrate the increasing heterogeneity in the cellular transcriptome of serum-free adapted CHO K1 cells during high cell density suspension culture over time without concomitant changes in the genomic sequence. Cell cycle--dependent subpopulations and cell clusters, which typically appear in other single-cell transcriptome analyses of adherent CHO K1 cultures, were not found in these suspension cultures. Our results indicate that cell division changes the intracellular microenvironment and leads to cell cycle--dependent heterogeneity. Whole mitochondrial single-cell genome sequencing showed cell-to-cell mitochondrial genome variation and heteroplasmy within cells. Indeed, the mitochondrial genome sequencing method developed here enables the validation of cell clonality. The culture time-dependent increase in cellular heterogeneity observed in this study did not show any attenuation in this increasing heterogeneity. Future advances in bioengineering such as culture upscaling, prolonged culturing, and complex culture systems will be confronted with the need to assess and control cellular heterogeneity, and the method described here may prove useful for this purpose.

Wolves (Canis lupus) can exert top-down pressure and shape ecological communities through selective predation of ungulates and beavers (Castor Canadensis). Considering their ability to shape communities through predation, understanding wolf foraging decisions is critical to predicting their ecosystem level effects. Specifically, if wolves are optimal foragers, consumers that optimize tradeoffs between cost and benefits of prey acquisition, changes in these factors may lead to prey switching or negative-density dependent selection with potential consequences for community stability. For wolves, factors affecting cost and benefits include prey vulnerability, risk, reward, and availability which can vary temporally. We described wolf diet in by frequency of occurrence and percent biomass and characterized diet in relation to optimal foraging using prey remains found in wolf scats on Isle Royale National Park, Michigan, USA during May–October 2019–2020. We used logistic regression to estimate prey consumption over time. We predicted prey with temporal variation in cost (vulnerability and/or availability) such as adult and calf moose (Alces alces) and beaver to vary in wolves’ diet. We analyzed 206 scats and identified 62% of remains as beaver, 26% as and moose, and 12% as other (birds, smaller mammals, and wolves). Adult moose were more likely to occur in wolf scat in May, when moose are in poor condition following winter. Similarly, the occurrence of moose calves peaked June–mid July following parturition but before their vulnerability declined as they matured. In contrast, beaver occurrence in wolf scat did not change over time, possibly reflecting the importance of low handling cost prey items for recently introduced lone or paired wolves. Our results demonstrate that wolf diet is plastic and responsive to temporal changes in prey acquisition cost as predicted by optimal foraging theory. Temporal fluctuation in diet may influence wolves’ ecological role if prey respond to increased predation risk by altering their foraging or breeding behavior.

Cost-effective use of limited conservation resources requires understanding which data can most contribute to alleviating biodiversity declines. Interventions might reasonably prioritise life-cycle transitions with the greatest influence on population dynamics, yet some contributing vital rates are particularly challenging to document; such pragmatic decision-making risks suboptimal management if less is known about influential rates. We aimed to explore whether study effort aligns with demographic impact on population growth rate, λ. We parameterised a matrix population model using meta-analysis of vital rates for the common eider (Somateria mollissima), an increasingly threatened yet comparatively data-rich species of seaduck. Female common eiders exhibit intermittent breeding, with some established breeders skipping one or more years between breeding attempts. We accounted for this behaviour by building breeding propensity (= 0.72) into our model with a discrete and reversible ‘non-breeder’ stage (to which surviving adults transition with a probability of 0.28). The transitions between breeding and non-breeding states had twice the influence on λ than fertility (summed matrix-element elasticities of 24% and 11%, respectively), whereas almost 15 times as many studies document components of fertility than breeding propensity (n = 103 and n = 7, respectively). Through comparative re-analyses, we find similar results for two amphibian species, further supporting our finding that study effort does not always occur in proportion to relative influence on λ. Our workflow could form part of the toolkit informing future investment of finite resources, to avoid repeated disconnects between data needs and availability thwarting evidence-driven conservation.

Recent research in island biogeography has highlighted the important role of late Quaternary sea-level fluctuations in shaping biogeographical patterns in insular systems, but largely focused on volcanic oceanic systems. Through this study we aim to extend this work by investigating the role of late Quaternary sea-level fluctuations in shaping species richness patterns in continental shelf island systems. Focusing on the Aegean archipelago, we first reconstructed the area’s geography using published data, under three sea-level stands: 1) current; 2) median over the last nine Glacial-Interglacial cycles; 3) Late Glacial Maximum (LGM). We compiled taxon-island occupancy for angiosperms (70 islands) and centipedes (56 islands). We investigated the impact of present-day and past geographical settings on chorological groups by analysing Island Species-Area Relationships (ISARs) and using Generalized Linear Mixed Models selection based on multiple metrics of goodness-of-fit. Our results confirm that the Aegean’s geography has changed dramatically since the LGM, while the median sea-level scenario only modestly differs from the present configuration. Paleogeographical changes largely shaped Aegean plant diversity patterns, and to a lesser degree centipede species richness patterns. The LGM geographic configuration affected both native and endemic species diversity through establishing connections between land-bridge islands and the mainland. Particularly on land-bridge islands we detected supersaturation of native species and stronger underrepresentation of endemics on those same islands. Unlike oceanic islands, where the longer lasting median configuration has ample effect on the current species diversity, the shorter lasting LGM configurations promoted increased connectivity with the mainland counteracting processes promoting endemism. Our study shows that in terms of processes affecting species richness patterns, continental archipelagos differ fundamentally from oceanic systems, highlighting the importance of distinguishing between them while studying biota from the perspective of historical biogeography.

Inhibition of interleukin 6 (IL-6) signalling has been proposed as a potential cardioprotective strategy for patients with chronic kidney disease (CKD) but the direct renal effects of IL-6 inhibition are not established. A Mendelian randomization (MR) study was performed to investigate the association of genetically proxied inhibition of IL-6 signalling with estimated glomerular filtration rate (eGFR), CKD and blood urea nitrogen (BUN). Inverse variance weighted MR was used as the main analysis, with sensitivity analyses performed using simple median, weighted median and MR-Egger methods. There was no evidence for an association of genetically proxied inhibition of IL-6 signalling (scaled per unit decrease in natural log transformed C-reactive protein) with log eGFR (0.002, 95% confidence interval -0.004 – 0.008), BUN (0.088, 95% confidence interval -0.003 – 0.019) and CKD (odds ratio 1.018, 95% confidence interval 0.899 – 1.153). These findings suggest that inhibition of IL-6 signalling is unlikely to have a direct effect on renal function.

Objective: This systematic review aimed to systematize different designs of exercise-based pulmonary rehabilitation (PR) for children with asthma and explore which designs are optimal. Methods: PubMed, EMBASE, Cochrane Library, Web of Science Core Collection and MEDLINE were searched up until April 01, 2021, which was conducted for any relevant randomized controlled trials (RCTs) of exercise-based PR in childhood asthma. Language is limited to English. Network meta-analyses and standard meta-analyses were performed using STATA (version 16.0), quality analyses were performed using RevMan (version 5.3). Results: A total of 24 RCTs involving 1031 patients were included. 14 studies were endurance training, which was the most commonly used form of exercise, and 7 studies rehabilitation sites were conducted in hospitals. A network meta-analysis showed that compared with other forms of exercise, interval training significantly improved the PAQLQ (Pediatric Asthma Quality of Life Questionnaire), including activity scores [MD=3.02, 95% CI (1.74,4.30)], symptom scores [MD=2.68, 95% CI (2.04,3.32)], emotional scores [MD=2.47, 95% CI (0.91,4.03)], and total scores [MD=2.68, 95% CI (1.79,3.57)]. Interval training [MD=188.97, 95% CI (-59.27, 437.21)] also had a more significant effect on the 6MWT (6-minute walk test). No adverse events were found in this study. Exercise training had no significant effect on FEV 1(the forced expiratory volume at 1s to predicted value ratio) [WMD=0.59, 95% CI (-2.00, 3.19)], however, the combined of endurance training and respiratory training was found to significantly improve both FVC (the forced vital capacity to predicted value ratio) [MD=5.37, 95% CI (0.07,10.67)] and FEF25-75% (the forced expiratory flow between 25% and 75% of vital capacity ratio) [WMD=11.31, 95% CI (2.13, 20.48)]. Conclusions: Exercise-based PR is a safe and effective for childhood asthma. Interval training may be a core component of improving quality of life and exercise capacity in childhood asthma, the combination of respiratory training and endurance training has significant effects on lung function.This result should be viewed with caution, and high-quality RCTs are still needed to confirm its clinical efficacy,

Research in ecology and evolutionary biology (EEB) plays a key role in understanding and intervening in our current environmental and climate crisis. Although anthropogenic stressors and climate change continue to disproportionately affect Black, Indigenous, and people of colour (BIPOC) individuals, their valuable scientific voices are shockingly underrepresented within EEB. To underscore this problem, we present a case study on EEB PhD graduates in the US (1994-2018), which illustrates that BIPOC scholars are significantly underrepresented in their cohorts. We recommend key steps that the EEB Academy should take to increase representation of BIPOC scholars in EEB, including anti-racism education and practice, increased funding opportunities, integration of diverse cultural perspectives, and a community-minded shift in PhDs. Importantly, this advice is directed at those who wield power in the Academy (e.g., funding agencies, societies, institutions, departments, and faculty), rather than BIPOC scholars already struggling against inequitable frameworks in EEB.

Soil moisture signatures provide a promising solution to overcome the difficulty of evaluating soil moisture dynamics in hydrologic models. Soil moisture signatures are metrics that quantify the dynamic aspects of soil moisture timeseries and enable process-based model evaluations. To date, soil moisture signatures have been tested only under limited land-use types. In this study, we explore soil moisture signatures’ ability to discriminate different dynamics among contrasting land-uses. We applied a set of nine soil moisture signatures to datasets from six in-situ soil moisture networks worldwide. The dataset covered a range of land-use types, including forested and deforested areas, shallow groundwater areas, wetlands, urban areas, grazed areas, and cropland areas. Our set of signatures characterized soil moisture dynamics at three temporal scales: event, season, and a complete timeseries. Statistical assessment of extracted signatures showed that (1) event-based signatures can distinguish different dynamics for all the land-uses, (2) season-based signatures can distinguish different dynamics for some types of land-uses (deforested vs. forested, urban vs. greenspace, and cropped vs. grazed vs. grassland contrasts), (3) timeseries-based signatures can distinguish different dynamics for some types of land-uses (deforested vs. forested, urban vs. greenspace, shallow vs. deep groundwater, wetland vs. non-wetland, and cropped vs. grazed vs. grassland contrasts). Further, we compared signature-based process interpretations against literature knowledge; event-based and timeseries-based signatures generally matched well with previous process understandings from literature, but season-based signatures did not. This study will be a useful guideline for understanding how catchment-scale soil moisture dynamics in various land-uses can be described using a standardized set of hydrologically relevant metrics.

Healthcare interoperability unfolds the way for personalized healthcare services at a reduced cost. Furthermore, a decentralized system holds the promise to prevent compromises such as cyber-attacks due to data breaches. Hence, there is a need for a framework that seamlessly integrates and shares data across the system stakeholders. We propose SENSIBLE, a blockchain-powered, knowledge-driven data-sharing framework that gives patients complete control of their medical history and can extract rich information hidden in it using knowledge graphs (KGs). By incorporating both blockchain and KGs, we can provide a platform for secure data sharing amongst stakeholders by maintaining data privacy and integrity through data authentication and robust data integration. We present a Proof-of-Concept of the SENSIBLE network with Ethereum to share dynamic knowledge across stakeholders. Dynamic knowledge generation on the blockchain provides a two-fold advantage of cooperation and communication amongst the stakeholders in the healthcare ecosystem. This leads to operational ease through sharing relevant portions of complex information while also ensuring the isolation of sensitive medical data.

Key points·      Simultaneous translabyrinthine tumor resection and cochlear implantation is a promising treatment method with hearing rehabilitation for sporadic vestibular schwannomas.·      Size of vestibular schwannoma, distance to the modiolus, residual hearing and promontory stimulation electrical brainstem response audiometry are important preoperative predictive factors for chance of cochlear implantation. ·      Electrically evoked brain stem response audiometry with an intracochlear test electrode is an important additional tool during vestibular schwannoma resection to decide on cochlear implantation.    Sporadic vestibular schwannomas (VS) can be treated using radiation therapy, microsurgical resection, or a wait-and-scan approach. Most VS will require treatment after some period of observation. However, the currently available treatment options carry a high risk of loss of serviceable hearing. Some authors believe that the possibility of cochlear implantation in the setting of VS should completely change the treatment strategy for this disease(1). However, patient outcomes with CIs show a wide variation—with some patients having no auditory perception, while others exhibit open-set speech understanding(2). The intraoperative testing of cochlear nerve function using electrically evoked brainstem response audiometry (eABR) provides a means of objectively assessing cochlear nerve conduction, and has been increasingly applied in this setting(2, 3). In the present study, we aimed to assess outcomes of patients undergoing vestibular schwannoma resection and cochlear implantation, and to develop a new scoring system to preoperatively identify suitable patients for this treatment course. Appropriate preoperative classification of patients can have important impacts on patient counseling and expectations.DesignEach study participant gave their informed consent to participate. The trial was approved by the local ethics committee 1111/2017, and is registered at www.clinicaltrials.gov (NCT03745560). All 17 patients underwent translabyrinthine vestibular schwannoma resection, during which eABR were recorded with an intracochlear test electrode (ITE) before and after tumor resection. In cases with positive responses after complete tumor resection, a cochlear implant (CI) was placed. Overall, ten patients received a CI with a Flex 28 or Flex Standard electrode (MED-EL, Innsbruck, Austria) depending on cochlear duct length. Data availability statement The data that support the findings of this study are available from the corresponding author upon request.SettingThe study was conducted at a tertiary care center.Participants Seventeen patients with unilateral sporadic VS were screened between January 2017 and January 2020 (see Table 1). Inclusion criteria were as follows: sporadic vestibular schwannoma, no ipsilateral functional hearing, desire to undergo cochlear implantation, and general good health. Exclusion criteria were prior treatment for vestibular schwannoma, neurofibromatosis type 2, history of pathology requiring multiple head magnetic resonance imaging (MRI), or history of malignant disease of the head and neck. A lack of functional hearing was defined as ≤50% monosyllable recognition at 80 dB HL. Main outcome measuresThe patients’ preoperative findings and results were re-evaluated to develop a new scoring system for patient selection. All patients underwent MRI of the brain performed using a 3.0 Tesla magnetic resonance (MR) unit (Philips Achieva; Philips Medical Systems, Best, the Netherlands). To visualize the cerebellopontine angle, the MR protocol included a 3D balanced fast field echo sequence that was used for further assessment. Using a picture archiving and communication system (IMPAX; AGFA HealthCare, Bonn, Germany), all MR examinations were anonymized and randomly presented to a neuroradiologist who was not aware of any clinical data. Grading according to four-grade Koos classification system was carried out (4). Additionally, a four level grading system was used to evaluate intrameatal extension towards the modiolus (Table 2).Promontory stimulation eABR was performed with a gold coated rigid electrode with a rounded-bent (hockey stick) tip stimulation probe manufactured by MED-EL (Innsbruck, Austria)  and recorded with the Neuropack, Nihon Kohden, Tokyo. A positive response is defined as a clear wave V reproducible in latency and amplitude. In cases with a wave V that can only be seen at high stimulation intensities or that is not reproducible an unclear response is documented. No identifiable wave V is defined as a negative response.The pure-tone average (4-PTA) was calculated as the mean for each patient, using the results at frequencies of 0.5, 1, 2, and 4 kHz. Monosyllables were measured at 65 and 80 dB HL. Based on these results, patients were categorized in four groups as seen in Table 2. STARD guidelines were followed when reporting the data of this study. ResultsAfter six months of follow-up, ten patients were daily users of the CI. Their mean aided pure-tone average was 38 dB HL, and their mean WRS was 28% at 65 dB, and 52% at 80 dB. Outcomes for individual patients can be seen in Table 3. Nine of the ten patients had open-set speech understanding. The patient without open-set speech understanding has significant hearing loss on the contralateral side and a language barrier. Facial nerve outcomes according to House Brackman (HB) are shown in Table 3. In all cases, the six-month follow-up MRI showed no sign of residual or recurrent tumor. The scoring system Table 2 shows the scoring system that was developed. Besides Koos grading, results of promontory stimulation eABR were included. Our system also evaluated residual hearing, which is an important factor reflecting the state of the nerve and the cochlea before an intervention. Further, we identified relation to the modiolus as a predictive factor. Table 4 shows the scoring system applied to the presented patients. DiscussionVarious advancements over recent years have made CI a good option for restoring binaural hearing in patients with VS. Imaging sequences have been improved and CI magnets have been developed to reduce metal artifacts(5) and allow postoperative evaluation of the internal auditory canal and cerebellopontine angle for tumor follow-up(6). Another recent development is the possible use of intraoperative eABR with an ITE, enabling objective assessment of cochlear nerve functionality(2, 3). In the past, the outcome of CIs in the context of VS was considered unpredictable, and many patients did not benefit from this technique. However, the advent of testing systems, such as intraoperative eABR, permits more precise evaluation of possible outcomes. Although simultaneous VS resection and cochlear implantation is possible with only visual assessment of the cochlear nerve(7), eABR measurements are a useful tool for objectifying the surgeon’s assessment. Only two prior studies have described the use of eABR during translabyrinthine VS resection(2, 8). One study included eight patients(8). The other was a pilot study by our research group(2). In this previous manuscript, we demonstrate the intraoperative objective evaluation of the cochlear nerve with eABR, using an ITE, during translabyrinthine VS resection and cochlear implantation(2). Our preliminary results indicated that positive eABR results (clear wave V) seem to be reliable, and to correlate well with CI-aided auditory perception. This thesis was further supported by the results of our present study, in which all patients with positive eABR results and who received an implant showed auditory perception with their CI, and most (90%) even have open-set speech understanding. A remaining major challenge is to identify patients with a high chance of cochlear nerve preservation. Therefore, as a logical next step, the knowledge gained in this study was used to create a grading system with the aim of preoperatively determining candidacy, as was performed herein.Individuals with residual speech understanding were more likely to have positive eABR results, and to receive a CI. These results are in line with the findings of Sanna et al(7). In their study, individuals with good functional hearing underwent translabyrinthine VS resection and cochlear implantation. After tumor removal, surgeons evaluated the cochlear nerve and visually determined whether it was intact(7). Of the nineteen included patients, thirteen were able to receive a CI, of whom 84% use their CI daily or almost daily(7). Another identified predictive factor was the VS extension towards the cochlear modiolus. This anatomic structure also reportedly plays an important role when assessing CI candidacy in cases of malformation,(9) as well as the need of its preservation in intracochlear VSs(10). Obviously, tumor resection is increasingly challenging with greater VS size, reducing the possibility of nerve protection reflected by Koos grading. The last category of our scoring system was promontory stimulation. One issue with promontory stimulation is that it produces a substantial number of artefacts in awake patients. Another problem is that some patients do not tolerate stimulation well, leading to a wide variety of stimulations intensities between different individuals. Artefacts and said stimulation range diminish the interpretation possibilities and reliability of the results. One limitation of the present study was the relatively small sample size on which the scoring system was based. Nevertheless, this study represents the largest group of patients with vestibular schwannomas, in whom eABR was intraoperatively performed. As well as the first study assessing predictive factors for cochlear implantation which can be assessed preoperatively.Overall, our results indicated that patients with a Class I scoring had a very high chance of receiving a CI. Among patients categorized as Class II (6–8 points according to our system), the majority could be implanted, but they had a distinctly worse chance of receiving an implant, and thus careful counseling is essential in these cases. Patients categorized as Class III and IV were not able to be implanted with a CI. ConclusionSimultaneous translabyrinthine VS excision and cochlear implantation using intraoperative eABR measurements is a good option for hearing rehabilitation and provides binaural hearing. Preoperative accurate assessment of the size and extent of VS, audiometric testing, and promontory stimulation eABR improves preoperative patient selection, help manage patient expectations, and predict the possibility of cochlear implantation. References1.         Upadhyay U, Almefty RO, Dunn IF, Al-Mefty O. Letter to the Editor: Save the nerve. J Neurosurg. 2015;123(3):821-2.2.         Dahm V, Auinger AB, Honeder C, Riss D, Landegger LD, Moser G, et al. Simultaneous Vestibular Schwannoma Resection and Cochlear Implantation Using Electrically Evoked Auditory Brainstem Response Audiometry for Decision-making. Otol Neurotol. 2020;41(9):1266-73.3.         Patel NS, Saoji AA, Olund AP, Carlson ML. Monitoring Cochlear Nerve Integrity During Vestibular Schwannoma Microsurgery in Real-Time Using Cochlear Implant Evoked Auditory Brainstem Response and Streaming Neural Response Imaging. Otol Neurotol. 2020;41(2):e201-e7.4.         Koos WT, Day JD, Matula C, Levy DI. Neurotopographic considerations in the microsurgical treatment of small acoustic neurinomas. J Neurosurg. 1998;88(3):506-12.5.         Schwartz N, Rooth MA, Dillon MT, O'Connell BP, Dedmon MM, Huang BY, et al. MRI surveillance following concurrent cochlear implantation in cases of vestibular schwannoma resection. Am J Otolaryngol. 2020;41(4):102518.6.         Schwarz-Nemec U, Dahm V, Arnoldner C. Letter to the editor regarding worldwide 1st MED-EL Mi1200 SYNCHRONY cochlear implant magnet removal for MRI image artifact reduction by Wieser et al. Otolaryngology Case Reports. 2019;10(March):43-4.7.         Sanna M, Medina MD, Macak A, Rossi G, Sozzi V, Prasad SC. Vestibular Schwannoma Resection with Ipsilateral Simultaneous Cochlear Implantation in Patients with Normal Contralateral Hearing. Audiol Neurootol. 2016;21(5):286-95.8.         Roberts S, Levin B, Sanli H, Ferch R, Kong K, Eisenberg R. Simultaneous cochlear implantation and removal of acoustic neuroma: implications for hearing. J Laryngol Otol. 2020;134(6):519-25.9.         Grover M, Sharma S, Preetam C, Gupta G, Samdani S, Agarwal S, et al. New SMS classification of cochleovestibular malformation and its impact on decision-making. J Laryngol Otol. 2019;133(5):368-75.10.       Plontke SK. An Improved Technique of Subtotal Cochleoectomy for Removal of Intracochlear Schwannoma and Single-stage Cochlear Implantation. Otol Neurotol. 2020;41(7):e891.    Patient Demographics   ID Age (y) Sex Side 4-PTA   WRS @ 80 dB Contralateral 4-PTAC 1 47 f l 77 dB 20% SSD 6 dB      2 59 m r 68 dB 40% AHL 54 dB 3 55 f l 51 dB 5% SSD 20 dB 4 74 m r 85 dB 0% AHL 48 dB 5 42 f l 68 dB 0% SSD 8 dB 6 61 f l 64 dB 30% SSD 5 dB 7 69 f r ³ 100 dB 0% ³ 100 dB 65 dB 8 59 m r 60 dB 0% SSD 21 dB 9 44 m r 74 dB 0% SSD 6 dB 10 55 f r 49 dB 40% SSD 6 dB 11 56 f l ³ 100 dB 0% SSD 10 dB 12 60 f r 87 dB 0% SSD 16 dB 13 44 m l 75dB 0% AHL 55 dB 14 52 f l ³ 100 dB 0% SSD 25 dB 15 56 f l 40 dB 25% SSD 14 dB 16 62 f r 64 dB 0% SSD 20 dB 17 46 f l ³ 100 dB 0% ³ 100 dB 80 dB Total 55.4 (± 8.9 SD) m = 5 f = 12 l = 9 r = 8 74 dB (± 19 SD) 9% (± 15 SD) SSD = 12 AHL = 3 27 dB (± 23 SD)  Table 1: Age is given in years (y). Gender is described as f (female) or m (male). Puretone average (4-PTA) is calculated as average decibel (dB) hearing level (HL) at the frequencies 500 Hertz (Hz), 1000 Hz, 2000 Hz and 4000 Hz. Word recognition scores (WRS) are calculated using Freiburg monosyllables at (@) 80 dB HL. Hearing of the contralateral side resulted in the diagnoses of single sided deaf (SSD), asymmetric hearing loss (AHL) or bilateral complete hearing loss larger than 100 dB HL (³ 100 dB). Contralateral 4-PTA = 4-PTAC       Scoring System       Category Definition Points Koos Grading Koos 4 0 Koos 3 1 Koos 2 2 Koos 1 3   Extension Transmodiolar extension 0 Infiltration of modiolus 1 Contact with modiolus 2 No contact, no infiltration of modiolus 3   Hearing ³ 100 dB 4-PTA 0 80 < 100 dB 4-PTA 1 < 79 dB 4-PTA 2 > 0% monosyllables, any PTA 3   PS EABR No response 0 Unclear wave V 1 Stable wave V 2       Total Score Class IV 0 - 3 Class III 4 - 5 Class II 6 - 8 Class I 9 - 11   Table 2: Scoring system to identify patients with higher chances of nerve integrity in case of VS resection. A certain amount (0-3) of points are given in four categories. Points are added up and patients are categorized to a certain class which reflects the probability of cochlear implantation after translabyrinthine vestibular schwannoma excision. Promontory stimulation eABR (PS EABR)   Patient Outcomes   ID Koos CI 6-month Follow-up VII 1/2/3/4 yes/no 4-PTA WRS @ 65 dB WRS @ 80 dB HB – POD1 HB – 6 Mo FU 1 2 yes 35 dB 40% 65% 1 1 2 1 yes 30 dB 65% 65% 1 1 3 3 no n.a. n.a. n.a. 5 3 4 3 yes 36 dB 0% 30% 1 1 5 2 no n.a. n.a. n.a. 1 1 6 1 no n.a. n.a. n.a. 1 1 7 2 no n.a. n.a. n.a. 1 1 8 4 no n.a. n.a. n.a. 5 2 9 2 yes 35 dB 0% 20% 1 1 10 2 yes 34 dB 45% 85% 1 1 11 2 no n.a. n.a. n.a. 1 1 12 2 yes 35 dB 10% 45% 2 1 13 2 yes 51 dB n.p. n.p. 1 1 14 1 no n.a. n.a. n.a. 3 1 15 2 yes 33 dB 40% 60% 1 1 16 1 yes 43 dB 20% 40% 1 1 17 2 yes 35 dB 35% 55% 1 1    Table 3: Outcomes of seventeen included patients. The second column shows the size and extension of the vestibular schwannoma according to Koos grading one to four. The third column shows which patients were provided with a cochlear implant (CI) (yes) and which not (no). Column four - Puretone average (4-PTA) in CI aided condition calculated as average decibel (dB) hearing level (HL) at the frequencies 500 Hertz (Hz), 1000 Hz, 2000 Hz and 4000 Hz. Column five and six - word recognition scores (WRS) in CI aided condition are calculated using Freiburg monosyllables at (@) 65 and 80 dB HL. The last two columns show facial nerve function according to House Brackmann (HB) scale 1 to 6 on postoperative day one (POD 1) and at the 6 months follow-up appointment (6 Mo FU). n.p. - not performed due to a language barrier. n.a. – not applicable     Applied Point System   ID Koos Points Modiolus Audio PS eABR Points CIass CI 1 2 2 3 n.p. ³ 7 £ II yes 2 3 3 3 2 11 I yes 3 1 2 3 2 8 II no 4 1 3 1 2 7 II yes 5 2 2 2 2 8 II no 6 3 1 3 2 9 I no 7 2 0 0 1 3 IV no 8 0 1 2 2 5 III no 9 2 3 2 2 9 I yes 10 2 3 3 2 10 I yes 11 2 1 0 0 3 IV no 12 2 3 1 1 7 II yes 13 2 3 2 2 9 I yes 14 3 1 0 2 6 II no 15 2 3 3 2 10 I yes 16 3 2 2 2 9 I yes 17 2 2 0 2 6 II yes Results  0 - 3 0 - 3 0 - 3 0 - 2 0 - 11 I - IV yes/no  Table 4: Point system applied to the presented seventeen patients. Every column represents one of the categories and points given. Koos - Koos classification, Modiolus - extension (in connection to the Modiolus), Audio - audiometric results, summation of pure tone average and word recognition score) and PS eABR - promontory stimulation electrically evoked auditory brainstem response. In total, there are four categories. Points reflects the sum of all points. Class is the resulting group each patient is categorized into, according to amount of points. Patient 1 did not undergo PS eABR, which does not allow for a complete classification. CI – cochlear implant: yes if they were provided with a CI, no if no CI was placed. N.p. – not performed  

Background: Subxiphoid incisional hernias are one of the complications following a median sternotomy, a surgical procedure to provide access to the mediastinum. Incidence has been reported between 1-4%, although the true incidence is not well known due to its asymptomatic nature. Method: A comprehensive search was performed on multiple sites. Keywords included “incisional hernia OR Subxiphoid hernia” AND “Median sternotomy OR Cardiac Surgery OR Coronary artery bypass graft OR Transplant OR Valve replacement”. Articles up to 1st of August 2020 were included in this study. Results: 8 articles were included in the study, with a total number of 132 patient identified. The incidence ranged from 0.81% to 3.44%. There was a mixture of repair method and follow up period reported. Recurrence post-repair ranged from 10% to 43%. Conclusion: Subxiphoid incisional hernias remains challenging to manage. We have discussed the incidence, risk factors, preventions, and management of subxiphoid incisional hernias including both the open and laparoscopic technique.

Autoimmunity is the break of tolerance to self-antigens that leads to organ-specific or systemic diseases characterized by the presence of pathogenic autoreactive antibodies (AAb) produced by plasmablast and/or plasma cells. AAb are prevalent in the general population and not systematically associated with clinical symptoms. In contrast, in some individuals, these AAb are pathogenic and drive the development of signs and symptoms of antibody-mediated autoimmune diseases (AbAID). AAb production, isotype profiles, and glycosylations are promoted by pro-inflammatory triggers linked to genetic, environmental, and hormonal parameters. Recent evidence supports a role for pathogenic AAb of the IgE isotype in a number of AbAID. Autoreactive IgE can drive the activation of mast cells, basophils and other types of FcεRI-bearing cells and may play a role in promoting autoantibody production and other pro-inflammatory pathways. In this review, we discuss the current knowledge on the pathogenicity of autoreactive IgE in AbAID and their status as therapeutic targets. We also highlight unresolved issues including the need for assays that reproducibly quantify IgE AAbs, to validate their diagnostic and prognostic value, and to further study their pathophysiological contributions to AbAID.

Glycerol monooleate (GMO)-stabilized liquid water-in-vegetable oil (W/VO) emulsions are difficult to stabilize due to the desorption of GMO from the W-VO interface towards the oil phase. This work improved the stability of GMO-stabilized liquid 20 wt% water-in-canola oil (W/CO) emulsion by modifying the dispersed aqueous phase composition with hydrogen bond-forming agents. As a control, 20 wt% water-in-mineral oil (W/MO) emulsion was also utilized. Different concentrations of hydrogen bond-forming agents (citric acid (CA), ascorbic acid (AA), low methoxyl pectin (LMP)) with and without salts (sodium chloride (S) or calcium chloride (Ca)) was added to the aqueous phase before emulsification, which enhanced emulsifier binding to the water-oil interface. The emulsions were characterized by phase separation, stability against accelerated gravitation, microstructure and rheology. W/CO emulsion without any aqueous phase additive destabilized instantly, whereas W/MO emulsion stayed stable. The addition of hydrogen bond-forming agents and salts significantly improved emulsion stability. LMP, with many hydrogen bond-forming groups, was able to provide the highest emulsion stability after 7 days in both oils compared to AA, CA and their mixtures with S. Emulsions with both oils formed weak gels with viscous and elastic characteristics due to the formation of an extensive network of water droplet aggregates. Overall, the hydrogen bond-forming agents interacted with GMO at the interface, thereby improving their presence at the water droplet surface, allowing significantly improved stability of GMO-stabilized liquid W/CO emulsions. The knowledge developed in this research can be useful in applying GMO in stabilizing liquid water-in-oil emulsion without using any crystal network.

Expansins have the remarkable ability to loosen plant cell walls and cellulose material without showing catalytic activity and therefore have potential applications in biomass degradation. To support the study of sequence-structure-function relationships and the search for novel expansins, the Expansin Engineering Database (ExED, https://exed.biocatnet.de) collected sequence and structure data on expansins from Bacteria, Fungi, and Viridiplantae, and expansin-like homologues such as carbohydrate binding modules, glycoside hydrolases, loosenins, swollenins, cerato-platanins, and EXPNs. Based on global sequence alignment and protein sequence network analysis, the sequences are highly diverse. However, many similarities were found between the expansin domains. Newly created profile hidden Markov models of the two expansin domains enable standard numbering schemes, comprehensive conservation analyses, and genome annotation. Conserved key amino acids in the expansin domains were identified, a refined classification of expansins and carbohydrate binding modules was proposed, and new sequence motifs facilitate the search of novel candidate genes and the engineering of expansins.