Background While open surgical repair continues to be the mainstay option for aortic arch reconstruction, the associated mortality, morbidity, and high turn-down rates have led to a need for the development of minimally invasive options for aortic arch repair. Though RELAY™ Branched (Terumo Aortic, Inchinnan, UK) represents a promising option for complex endovascular aortic arch repair, neurological complications remain a pertinent risk. Herein we seek to present multi-centre data from Europe documenting the neurological outcomes associated with RELAY™ Branched. Methods Prospective data collected between January 2019 and January 2022 associated with patients treated with RELAY™ single-, double-, and triple-branched endoprostheses from centres across Europe was retrospectively analysed with descriptive and distributive analysis. Follow up data from 30 days and 6-, 12-, and 24 months postoperatively was included. Patients follow up was evaluated for the onset of disabling stroke (DS) and non-disabling stroke (NDS). Results Technical success was achieved in 147 (99.3%) cases. Over 24 months period, in total, 6 (4.1%) patients suffered DS and 8 (5.4%) patients suffered NDS after undergoing aortic arch repair with RELAY™. All patients that developed postoperative DS had been treated with the double-branched RELAY™ endoprosthesis. Discussion The data presented herein demonstrates that RELAY™ Branched is associated with favourable neurological outcomes and excellent technical success rates. Key design features of the endoprosthesis and good perioperative management can contribute greatly to mitigating neurological complications following endovascular aortic arch repair.

Cholinesterase inhibitors have been shown to improve cognitive functioning in patients with Alzheimer’s Disease (AD), but are associated with side effects and only 20-40% of the patients clinically improve. In this study, we aimed to investigate the acute pharmacodynamic (PD) effects of a single dose of galantamine on CNS functioning in mild to moderate AD patients and its potential to predict long-term treatment response. This study consisted of a challenge phase, in which a single dose of 16 mg galantamine was administered to 50 mild to moderate AD patients in a double-blind, placebo-controlled cross-over fashion. Acute PD effects were monitored with use of a CNS test battery. In the subsequent treatment phase of the study, patients were treated with open-label galantamine according to regular care. After 6 months of galantamine treatment, patients were categorized as either responder or as non-responder based on their MMSE, NPI and DAD scores. An analysis of covariance was performed to study the difference in acute PD effects between responders and non-responders. Acute decreases of absolute frontal alpha (-20.4; 95%CI=-31.6,-7.47; p=.0046), beta (-15.7; 95% CI=-28.3,-0.93; p=.0390) and theta (-25.9; 95%CI=-38.4,-10.9; p=.0024) EEG parameters and of relative frontal theta power (-3.27%; 95%CI=-5.96,-0.58; p=.0187) on EEG after a single dose administration of galantamine significantly distinguished long-term treatment responders (n=11) from non-responders (n=32) after 6 months. This study demonstrates that patients who demonstrate a reduction in EEG power in the alpha and theta frequency after a single administration of galantamine 16 mg will most likely respond to treatment.

Om45 is a major protein of the yeast outer mitochondrial membrane under respiratory conditions. However, the cellular role of the protein has remained obscure. Previously, deletion mutant phenotypes have not been found, and clear amino acid sequence similarities that would allow inferring its functional role are not available. In this work, we describe synthetic petite mutants of UGO1 and GEM1 that depend on the presence of OM45 for respiratory growth, as well as the identification of several multicopy suppressors of the synthetic petite phenotypes. In the analysis of our mutants, we demonstrate that Om45 and Gem1 have a collaborative role in the maintenance of mitochondrial morphology, cristae structure, and mitochondrial DNA maintenance. A group of multicopy suppressors rescuing the synthetic lethal phenotypes of the mutants on non-fermentable carbon sources additionally supports this result. Our results imply that the synthetic petite phenotypes we observed are due to the disturbance of the inner mitochondrial membrane and point to this mitochondrial sub-compartment as the main target of action of Om45, Ugo1, and the yeast Miro GTPase Gem1.

BACKGROUND: This study aims to determine nicotine dependence levels in pre and during pandemic and its correlations with COVID-19 phobia among healthy men during controlled social life: a sample of primary care population. METHODS: This cross-sectional study was conducted with 472 healthy men in Çorum, Black Sea Region, Turkey between February 2019 and October 2020. An online questionnaire was used to collect data including demographic profile, smoking behavior, intention to quit, Fagerström Nicotine Dependence test (FTND) pre and during COVID-19 pandemic and COVID-19 phobia scale. RESULTS: In this study, a percentage change of +6.2, +0.8, +1.9, -2.7, -5.1 was found in very low, low, medium, high and very high dependence categories respectively between pre-pandemic and during controlled social life in pandemic. A percentage change of +2.8 was seen in terms of intention to quit smoking. The mean score for COVID-19 phobia was 65.9 ± 15.8 and almost two-thirds of the participants (62%) had medium and high COVID-19 phobia. Men with high/very high dependence had significantly more COVID-19 phobia than the other two groups. There was a significant correlation between FTND scores and COVID-19 phobia. CONCLUSIONS: There were considerable changes in dependence levels and COVID-19 phobia was more common in high/very high dependence group. Controlled social life should be considered a golden opportunity for predicting levels of nicotine dependence and will bring benefit for lower smoking prevalence. COVID-19, Nicotine dependence, Phobia, men, Primary health care.

Current workflows in academic ecology rarely allow an engagement of ecologists with philosophers, or with contemporary philosophical work. We argue that this is a missed opportunity for enriching ecological reasoning and practice, because many questions in ecology overlap with philosophical questions and with current topics in contemporary philosophy of science. One obstacle to a closer connection and collaboration between the fields is the limited awareness of scientists, including ecologists, of current philosophical questions, developments and ideas. In this article, we aim to overcome this obstacle and trigger more collaborations between ecologists and philosophers. First, we provide an overview of philosophical research relevant to ecologists. Second, we use examples to demonstrate that many ecological questions have a philosophical dimension and point to related philosophical work. We elaborate on one example -- the debate around the appropriate level of complexity of ecological models -- to show in more detail how philosophy can enrich ecology. Finally, we provide suggestions for how to initiate collaborative projects involving both ecologists and philosophers.

It is common practice in the development of bioprocesses to genetically modify a microorganism and study a large number of resulting mutants in order to select the ones that perform best for use at the industrial scale. At industrial scale, strict nutrient-controlled growth conditions are imposed to control the metabolic activity and growth rate of the microorganism, thereby enhancing the expression of the product of interest. Although it is known that microorganisms that perform best under these strictly controlled conditions are not the same as the ones that perform best under uncontrolled batch conditions, screening, and selection is predominantly performed under batch conditions. Tools that afford high throughput on the one hand and dynamic control over cultivation conditions on the other hand are not yet available. Microbioreactors offer the potential to address this problem, resolving the gap between bioprocess development and industrial scale use. In this review, we highlight the current state-of-the-art of microbioreactors that offer the potential to screen microorganisms under dynamically controlled conditions. We classify them into: (i) microtiter plate-based platforms, (ii) microfluidic chamber-based platforms, and (iii) microfluidic droplet-based platforms. We conclude this review by discussing the opportunities of nutrient-fed microbioreactors in the field of biotechnology.

Monarch butterflies are known for their spectacular annual migration in eastern North America, with millions of monarchs flying up to 4,500 kilometers to overwintering sites in central Mexico. Monarchs also live west of the Rocky Mountains, where they travel shorter distances to overwinter along the Pacific Coast. It is often assumed that eastern and western monarchs form distinct evolutionary units, but genomic studies to support this notion are lacking. We used a tethered flight mill to show that migratory eastern monarchs have greater flight performance than western monarchs, consistent with their greater migratory distances. However, analyzing more than 20 million SNPs in 43 monarch genomes, we found no evidence for genomic differentiation between eastern and western monarchs. Genomic analysis also showed identical and low levels of genetic diversity, and demographic analyses indicated similar effective population sizes and ongoing gene flow between eastern and western monarchs. Gene expression analysis of a subset of candidate genes during active flight revealed differential gene expression related to non-muscular motor activity. Our results demonstrate that eastern and western monarchs maintain migratory differences despite ongoing gene flow, and suggest that migratory differences between eastern and western monarchs are not driven by select major-effects alleles. Instead, variation in migratory distance and destination may be driven by environmentally induced differential gene expression, or by many alleles of small effect.

BackgroundAspirations are frequent in children with neurological impairment. They significantly increase the risk for acute and chronic respiratory insufficiencies leading to high morbidity and mortality. Laryngeal sensation deficits have been linked to aspirations in adults and are a suspected cause for dysphagia in children. In a similar neurological circuit as swallowing, laryngeal receptors trigger coughing as a protective airway reflex. The aim of this study was to examine the association between impaired laryngeal sensation (ILS), aspiration and coughing in neurologically impaired children.Design and MethodsIn a retrospective study, 110 children with suspected dysphagia who underwent a clinical evaluation of swallowing and a flexible endoscopic evaluation of swallowing (FEES) between 2013 and 2019 in the children’s university clinic Düsseldorf were analyzed. Laryngeal sensation was tested by the endoscopic touch method. Associations were computed using χ2-test.ResultsFifty-four patients (49.1%) had neurological impairment, 56 patients (50.9%) had no or other comorbidities and served as a control cohort. Children with neurological impairment suffered from ILS significantly more often than children with no or other comorbidities (χ²(1) = 4.63, p = .031). ILS was associated with all other FEES variables but did not correlate with coughing. The symptom coughing correlated with aspiration in the group of neurologically impaired children and in children ILS.Conclusion ILS is a potential cause of aspirations in children with neurological impairment.  Physicians need to pay special attention to the occurrence of coughing in children with neurological impairment and/or ILS since it signals aspirations that took place.

Predicting the fate of a microbial population (i.e., growth, gene expression…) remains a challenge, especially when this population is exposed to very dynamic environmental conditions, such as those encountered during continuous cultivation. Indeed, the dynamic nature of continuous cultivation process implies the potential deviation of the microbial population involving genotypic and phenotypic diversification. This work has been focused on the induction of the arabinose operon in Escherichia coli as a model system. As a preliminary step, the GFP level triggered by an arabinose-inducible ParaBAD promoter has been tracked by flow cytometry in chemostat with glucose-arabinose co-feeding. For a large range of glucose-arabinose co-feeding, the simultaneous occurrence of GFP positive and negative subpopulation was observed. In a second set of experiments, continuous cultivation was performed by adding either glucose or arabinose, based on the ability of individual cells for switching from low GFP to high GFP states, according to a technology called segregostat. In segregostat mode of cultivation, on-line flow cytometry analysis was used for adjusting the arabinose/glucose transitions based on the phenotypic switching capabilities of the microbial population. This strategy allowed finding an appropriate arabinose pulsing frequency, leading to a prolonged maintenance of the induction level with limited impact on phenotypic diversity for more than 60 generations. This result suggests that constraining individual cells into a given phenotypic trajectory is maybe not the best strategy for directing cell population. Instead, allowing individual cells switching around a predefined threshold seems to be a robust strategy leading to oscillating, but predictable, cell population behavior.

Cancer cachexia is one of the most common causes of death among cancer patients, no effective anti-cachectic treatment is currently available. In experimental cachectic animal models, aberrant activation of STAT3 in skeletal muscle has been found to contribute to muscle wasting. However, its clinical association, the factors regulating STAT3 activation, and the molecular mechanisms remain incompletely understood. Here, we show that an enhanced interaction between activated STAT3 and HSP90, which were observed in the skeletal muscle of cancer cachexia patients, is a crucial event for the development of cachectic muscle wasting. Administration of HSP90 inhibitors 17DMAG and PU-H71 alleviated the muscle wasting in C26 tumor-bearing cachectic mice or the myotube atrophy of C2C12 cells induced by C26 conditional medium. A mechanistic study indicated that in cachectic skeletal muscle, prolonged STAT3 activation transactivated FOXO1 by binding directly to its promoter and triggered the muscle wasting in a FOXO1-dependent manner; Our results demonstrate that the HSP90/STAT3/FOXO1 axis plays a critical role in the cachectic muscle wasting, which might serve as potential therapeutic target for the treatment of cancer cachexia.

Purpose Tear fluid N-Glycome from patients affected with vernal (VKC) and atopic keratoconjunctivitis (AKC) was investigated to identify specific changes in tears and to recognize possible glyco-biomarkers. Methods The analysis of N-glycans was performed using matrix-assisted laser desorption ionization mass spectrometry on single tear samples. Tears from control normal subjects (CTRL), VKC and AKC patients were processed and treated with peptide N-glycosidase F (PNGase F) to deglycosylate N-glycoproteins. Released N-glycans were purified, permethylated and analyzed by Matrix-Assisted Laser Desorption/Ionization-Time Of Flight Mass Spectrometry and tandem Mass Spectrometry (MALDI-TOF MS and MALDI-TOF MS/MS). Results More than 150 complex N-glycans, including highly fucosylated biantennary, triantennary, tetraantennary and bisecting species, were observed in our spectra. Three distinct patterns for CTRL, VKC and AKC patients were identified in terms of relative intensities for some N-glycans structures. Major variations involved bisecting and hyperfucosylated glycoforms. The most intense ions were associated to species at m/z 1907.0 (asialo, agalacto, bisected, biantennary structure – NGA2B) in CTRL MS profiles, at m/z 2605.3 and 2966.5 in VKC, and at m/z 2792.4 in AKC corresponding to a well-known biantennary, disialylated N-glycan. Several peaks were associated to structures bearing one or two Lewis X epitopes. Structures were confirmed by MS/MS analysis. Quantitative differences among the three groups were statistically significant. Conclusions Tear MS profiles are rich in specific glycoforms, particularly those with a high fucosylation degree, indicating both core and peripheral decoration. Tear N-glycome analysis provided important information for a better comprehension of VKC and AKC alterations at the molecular level

Large-scale patterns of biodiversity and the underlying mechanisms that regulate these patterns are central topics in biogeography and macroecology. The Qinghai-Tibetan Plateau (QTP) is a natural laboratory for studying these issues. However, most previous studies have focused on the entire QTP, and the independent physical geographical subunits in the region are not well understood. We studied the current plant diversity on the Kunlun Mountains, an independent physical geographical subunit located in northwest China, on the northern edge of the QTP. We integrated measures of species distribution, geological history, and phylogeography, and analyzed the taxonomic richness, origin time, and community phylogenetic structure of the plants present in the area. The distribution patterns of 1,911 seed plants highlighted that species were located mainly in the eastern regions of the Kunlun Mountains. Chinese endemic species of seed plants accounted for 29.8% of the total species on the Kunlun Mountains. The biodiversity patterns and mean divergence times (MDT) indicated that the eastern region of the Kunlun Mountains was the center for biodiversity conservation, particularly in the southeastern region, which has served as a museum for plant diversity on the Kunlun Mountains. According to the MDT, the origin time of the Kunlun Mountains’ flora (KMF) was early Miocene (19.40 Ma), and the KMF is ancient. The biogeographical roles of the Kunlun Mountains were corridor and sink, and the corresponding key processes were species immigration and extinction. The extant biodiversity on the Kunlun Mountains has occurred through species recolonization after climatic fluctuations and glaciations during the Quaternary. The Kunlun Mountains also formed a barrier, representing a boundary among multiple floras, and converted the QTP into a closed physical geographical unit. The nearest taxon index indicated that habitat filtering may have played an important role in biodiversity patterns.

The fire ant Solenopsis invicta exists in two alternate social forms: monogyne nests contain a single reproductive queen and polygyne nests contain multiple reproductive queens. This colony-level social polymorphism corresponds with individual differences in queen physiology, queen dispersal patterns, and worker discrimination behaviors, all evidently regulated by an inversion-based supergene that spans more than 13Mb of a “social chromosome,” contains over 400 protein-coding genes, and rarely undergoes recombination. The specific mechanisms by which this supergene influences expression of the many distinctive features that characterize the alternate forms remain almost wholly unknown. To advance our understanding of these mechanisms, we explore effects of social chromosome genotype and natal colony social form on gene expression in virgin queens sampled as they embarked on nuptial flights, using RNA-sequencing of two important tissues. We observe relatively minor effects of natal social form, that is, of the social/developmental environment, on gene expression profiles, but substantial effects of genotype, including i) supergene-associated gene upregulation, ii) allele-specific expression, and iii) pronounced extra-supergene trans-regulatory effects. These findings, along with observed spatial variation in differential and allele-specific expression within the supergene region, highlight the complex gene regulatory landscape that emerged following evolutionary divergence of the inversion-mediated Sb haplotype from its homolog that largely retained the ancestral gene order. The distinctive social chromosome-linked gene expression trajectories we document at the onset of a queen’s reproductive life expand the known record of relevant molecular correlates of a complex social polymorphism and point to putative genetic underpinnings of the alternate social syndromes.

Conventional piglets were inoculated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through different routes, including intranasal, endotracheal, intramuscular and intravenous ones. Although piglets were not susceptible to SARS-CoV-2 and lacked lesions or viral RNA in tissues/swabs, seroconversion was observed in pigs inoculated parenterally (intramuscularly or intravenously).

The muskrat (Ondatra zibethicus) is an iconic species in Canada, valued for both its fur and its integral role in wetland ecosystems, and widely regarded for its perseverance. However, the resilience of this semi-aquatic mammal seems to be in question now as increasing evidence points to widespread population declines. Recent analyses of harvest data across North America suggest a reduction in their numbers, but this has not been widely corroborated by population surveys. In this study we replicated historic muskrat house count surveys at two large Great Lakes coastal wetlands and present confirmation that declines in muskrat harvest correspond to actual declines in muskrat abundance. At the Point Pelee National Park marsh and the Matchedash Bay-Gray Marsh wetland we found that mean muskrat house counts declined by 93% and 91% respectively between historic surveys 40-50 years ago and contemporary surveys over the past five years. The factors responsible for these dramatic declines remain unclear but there may be a relationship with changes in the habitat quality of these wetlands that have occurred over the same time frame. Not only is the loss of muskrats an issue for the resulting loss of the wetland ecosystem services they provide, but it may be an indication of broader marsh ecosystem degradation. As such, a scarcity of muskrats should be considered a red flag for the state of biodiversity in our wetlands. Continued surveys and ongoing research are needed to shed more light on the current status of muskrat populations and their marsh habitats across their native range. Keywords: Fur harvest; Muskrat; Ondatra; Population decline; Typha; Wetlands

Acute epibulbar infections are one of the most frequently diagnosed ophthalmologic infections. They are usually self-limiting but can lead to a viral preseptal cellulitis mimicking a severe bacterial infection. Early diagnosis is important to shorten the course of recovery.

Typically, the Crack Tip Opening Displacement (CTOD) is used only to quantify the crack closure phenomenon. However, more information about crack tip phenomena can be extracted from the CTOD curves, which can be used for a better understanding of fatigue crack growth. The main objective here is the development of a numerical tool for the automatic analysis of CTOD plots, which can be obtained either numerically using the Finite Element Method (FEM) or experimentally using Digital Image Correlation (DIC). The parameters extracted are the elastic and plastic CTOD in loading and unloading regimes, the corresponding load ranges, the crack opening and closure levels and the dissipated energy. This tool is expected to promote a fast and efficient analysis of DIC and FEM results, facilitating the implementation of CTOD analysis in the fatigue community.

Scabies may present with unusual features like vesicles, pustules, and bullae. In the setting of an already burdened health sector, careful history taking is of utmost importance in order to avoid unnecessary and expensive investigations to reach a diagnosis.