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Objective: People with epilepsy (PwE) suffer from progressive brain atrophy, which is reflected as neuroaxonal loss on the retinal level. This study aims to provide initial insight into the longitudinal dynamics of the retinal neuroaxonal loss and possible driving factors., Methods: PwE and healthy controls (HC; 18-55 years of age) underwent spectral domain optical coherence tomography at baseline and 7.0 ± 1.5 and 6.7 ± 1.0 months later, respectively. The change in retinal thickness/volume and annualized percentage change (APC) were calculated for the peripapillary retinal nerve fiber layer (pRNFL), the macular RNFL (mRNFL), the ganglion cell inner plexiform layer (GCIP), the inner nuclear layer, and the total macular volume (TMV). Group comparisons and multiple linear models with stepwise backward selection were performed to evaluate associations with demographic and clinical parameters., Results: PwE (n = 44, 21 females, mean age = 35.6 ± 10.9 years) revealed a significant decrease in the pRNFL, mRNFL, GCIP, and TMV thickness or volume in the study interval. When compared to HC (n = 56, 37 females, mean age = 32.7 ± 8.3 years), the APC of the pRNFL (-.98 ± 3.13%/year) and the GCIP (-1.24 ± 2.56%/year) were significantly more pronounced in PwE (p = .01 and p = .046, respectively). Of note, atrophy of the mRNFL was significantly influenced by the number of antiseizure medications (ASMs; p = .047) and increasing age of PwE (p = .03). Contradictory results, however, were revealed for the impact of seizures., Significance: In epilepsy, progression of retinal neuroaxonal loss was already detectable at short-term follow-up. PwE who receive a high number of ASMs seem to be at risk for accelerated neuroaxonal loss, stressing the importance of well-considered and effective antiseizure therapy., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

It remains unresolved whether central nervous system involvement in treated classical galactosemia (CG) is a progressive neurodegenerative process. This study aimed to investigate retinal neuroaxonal degeneration in CG as a surrogate of brain pathology. Global peripapillary retinal nerve fibre layer (GpRNFL) and combined ganglion cell and inner plexiform layer (GCIPL) were analysed in 11 CG patients and 60 controls (HC) using spectral-domain optical coherence tomography. Visual acuity (VA) and low-contrast VA (LCVA) were acquired to test visual function. GpRNFL and GCIPL did not differ between CG and HC ( p > 0.05). However, in CG, there was an effect of intellectual outcome on GCIPL ( p = 0.036), and GpRNFL and GCIPL correlated with neurological rating scale scores ( p < 0.05). A single-case follow-up analysis showed GpRNFL (0.53-0.83%) and GCIPL (0.52-0.85%) annual decrease beyond the normal aging effect. VA and LCVA were reduced in CG with intellectual disability ( p = 0.009/0.006), likely due to impaired visual perception. These findings support that CG is not a neurodegenerative disease, but that brain damage is more likely to occur early in brain development. To clarify a minor neurodegenerative component in the brain pathology of CG, we propose multicenter cross-sectional and longitudinal studies using retinal imaging.

Arterial blood pressure is one of the vital signs monitored mandatory in anaesthetised patients. Even short episodes of intraoperative hypotension are associated with increased risk for postoperative organ dysfunction such as acute kidney injury and myocardial injury. Since there is little evidence whether higher alarm thresholds in patient monitors can help prevent intraoperative hypotension, we analysed the blood pressure data before (group 1) and after (group 2) the implementation of altered hypotension alarm settings. The study was conducted as a retrospective observational cohort study in a large surgical centre with 32 operating theatres. Alarm thresholds for hypotension alarm for mean arterial pressure (MAP) were altered from 60 (before) to 65 mmHg for invasive measurement and 70 mmHg for noninvasive measurement. Blood pressure data from electronic anaesthesia records of 4222 patients (1982 and 2240 in group 1 and 2, respectively) with 406,623 blood pressure values undergoing noncardiac surgery were included. We analysed (A) the proportion of blood pressure measurements below the threshold among all measurements by quasi-binomial regression and (B) whether at least one blood pressure measurement below the threshold occurred by logistic regression. Hypotension was defined as MAP < 65 mmHg. There was no significant difference in overall proportions of hypotensive episodes for mean arterial pressure before and after the adjustment of alarm settings (mean proportion of values below 65 mmHg were 6.05% in group 1 and 5.99% in group 2). The risk of ever experiencing a hypotensive episode during anaesthesia was significantly lower in group 2 with an odds ratio of 0.84 (p = 0.029). In conclusion, higher alarm thresholds do not generally lead to less hypotensive episodes perioperatively. There was a slight but significant reduction of the occurrence of intraoperative hypotension in the presence of higher thresholds for blood pressure alarms. However, this reduction only seems to be present in patients with very few hypotensive episodes., (© 2022. The Author(s).)

Many tropical mountain ecosystems (TME) are severely disturbed, requiring ecological restoration to recover biodiversity and ecosystem functions. However, the extent of restoration efforts across TMEs is not known due to the lack of syntheses on ecological restoration research. Here, based on a systematic review, we identify geographical and thematic research gaps, compare restoration interventions, and consolidate enabling factors and barriers of restoration success. We find that restoration research outside Latin-America, in non-forested ecosystems, and on socio-ecological questions is scarce. For most restoration interventions success is mixed and generally limited by dispersal and microhabitat conditions. Finally, we propose five directions for future research on tropical mountain restoration in the UN decade of restoration, ranging from scaling up restoration across mountain ranges, investigating restoration in mountain grasslands, to incorporating socio-economic and technological dimensions., (© 2021. The Author(s).)

In phenylalanine hydroxylase (PAH) deficiency, an easily feasible method to access the progression of neurodegeneration is warranted to contribute to current discussions on treatment indications and targets. The objective of the present study was to investigate whether optical coherence tomography (OCT) measures as markers of neurodegeneration differ between patients with PAH deficiency and healthy controls (HCs) according to phenotype and metabolic control. In this single-center cross-sectional study, 92 patients with different phenotypes of PAH deficiency [PAH deficiency not requiring treatment, early treated phenylketonuria (ETPKU), and late-diagnosed phenylketonuria (PKU)] compared with 76 HCs were examined using spectral-domain OCT. Indices of phenylalanine elevation and variability were correlated with OCT parameters. Late-diagnosed PKU patients showed reduced peripapillary retinal nerve fiber layer (pRNFL) thickness and combined ganglion cell and inner plexiform layer (GCIPL) volume. Adult ETPKU patients were found to have lower GCIPL volume ( p = 0.016), which correlated with the indices of phenylalanine control. In pediatric ETPKU patients with poor metabolic control, pRNFL was significantly reduced ( p = 0.004). Patients with PAH deficiency not requiring treatment did not exhibit retinal degeneration. Inner nuclear layer (INL) was significantly increased in the pediatric ETPKU patients, driven by those with current poor metabolic control ( p = 0.006). Our data provide evidence of retinal neuroaxonal degeneration and INL swelling, depending on the phenotype, current age, and metabolic control. These findings suggest that OCT is suitable to investigate neurodegeneration in PKU and we propose OCT as a sensitive, reliable, safe, low-burden, and low-cost examination for future multicenter studies., Competing Interests: The authors declare that this study received funding from Nutritia Metabolics. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. AL-H has received travel reimbursement from BioMarin and Sobi. KW has received travel reimbursement from Sobi and Amicus Therapeutics, and honoraria for lectures from Sobi and Nutritia Metabolic. KS has received travel reimbursement from Shire and BioMarin. KP has received research funding and/or honoraria for consultancy and/or speaker's bureau activity from BioMarin, Sobi, Dr. Schaer. JH reports a grant for OCT research from the Friedrich-Baur-Stiftung, personal fees, and non-financial support from Merck, Alexion, Novartis, Roche, Santhera, Biogen, Heidelberg Engineering, Sanofi Genzyme, and non-financial support of the Guthy-Jackson Charitable Foundation, all outside the submitted work. EM has received travel reimbursement from Sobi and Dr. Schär and was paid for advisory services from Sobi, APR, and Sanofi-Aventis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lotz-Havla, Weiß, Schiergens, Regenauer-Vandewiele, Parhofer, Christmann, Böhm, Havla and Maier.)

Aims: Amidst the Campos de Altitude (Highland Grasslands) in the Brazilian Atlantic Forest, woody communities grow either clustered in tree islands or interspersed within the herbaceous matrix. The functional ecology, diversity, and biotic processes shaping these plant communities are largely unstudied. We characterized the functional assembly and diversity of these tropical montane woody communities and investigated how they fit within Grime's CSR (C-competitor, S-stress-tolerant, R-ruderal) scheme, what functional trade-offs they exhibit, and how traits and functional diversity vary in response to bamboo presence/absence., Methods: To characterize the functional composition of the community, we sampled five leaf traits and wood density along transects covering the woody communities both inside tree islands and outside (i.e., isolated woody plants in the grasslands community). Then, we used Mann-Whitney test, t test, and variation partitioning to determine the effects of inside versus outside tree island and bamboo presence on community-weighted means, woody species diversity, and functional diversity., Results: We found a general SC/S strategy with drought-related functional trade-offs. Woody plants in tree islands had more acquisitive traits than those within the grasslands. Trait variation was mostly taxonomically than spatially driven, and species composition varied between inside and outside tree islands. Leaf thickness, wood density, and foliar water uptake were unrelated to CSR strategies, suggesting independent trait dimensions and multiple drought-coping strategies within the predominant S strategy. Islands with bamboo presence showed lower Simpson diversity, lower functional dispersion, lower foliar water uptake, and greater leaf thickness than in tree islands without bamboo., Conclusions: The observed functional assembly hints toward large-scale environmental abiotic filtering shaping a stress-tolerant community strategy, and small-scale biotic interactions driving small-scale trait variation. We recommend experimental studies with fire, facilitation treatments, ecophysiological and recruitment traits to elucidate on future tree island expansion and community response to climate change., Competing Interests: The authors have no conflicts of interest to declare., (© 2021 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

The epithelial sodium channel (ENaC) mediates the first step in Na+ reabsorption in epithelial cells such as kidney, colon, and airways and may consist of four homologous subunits (alpha, beta, gamma, delta). Predominantly, the alpha-subunit is expressed in these epithelia, and it usually forms functional channels with the beta- and gamma-subunits. The delta-subunit was first found in human brain and kidney, but the expression was also detected in human cell lines of lung, pancreatic, and colonic origin. When co-expressed with beta and gamma accessory subunits in heterologous systems, the two known isoforms of the delta-ENaC subunit (delta1 and delta2) can build amiloride-sensitive Na+ channels. In the present study we demonstrate the expression and function of the delta-subunit in human nasal epithelium (HNE). We cloned and sequenced the full-length cDNA of the delta-ENaC subunit and were able to show that in nasal tissue at least isoform 1 is expressed. Furthermore, we performed Western blot analyses and compared the cell surface expression of the delta-subunit with the classically expressed alpha-subunit by using immunofluorescence experiments. Thereby, we could show that the quantity of both subunits is almost similar. In addition, we show the functional expression of the delta-ENaC subunit with measurements in modified Ussing chambers, and demonstrate that in HNE a large portion of the Na+ transport is mediated by the delta-ENaC subunit. Therefore, we suppose that the delta-subunit may possess an important regulatory function and might interact with other ENaC subunits or members of the DEG/ENaC family in the human respiratory epithelium.