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Summary: Intra‐operative cardiac arrests differ from most in‐hospital cardiac arrests because they reflect not only the patient's condition but also the quality of surgery and anaesthesia care provided. We assessed the relationship between intra‐operative cardiac arrest rates and country Human Development Index (HDI), and the changes occurring in these rates over time. We searched PubMed, EMBASE, Scopus, LILACS, Web of Science, CINAHL and SciELO from inception to 29 January 2020. For the global population, rates of intra‐operative cardiac arrest and baseline ASA physical status were extracted. Intra‐operative cardiac arrest rates were analysed by time, country HDI status and ASA physical status using meta‐regression analysis. Proportional meta‐analysis was performed to compare intra‐operative cardiac arrest rates and ASA physical status in low‐ vs. high‐HDI countries and in two time periods. Eighty‐two studies from 25 countries with more than 29 million anaesthetic procedures were included. Intra‐operative cardiac arrest rates were inversely correlated with country HDI (p = 0.0001); they decreased over time only in high‐HDI countries (p = 0.040) and increased with increasing ASA physical status (p < 0.0001). Baseline ASA physical status did not change in high‐HDI countries (p = 0.106), while it decreased over time in low‐HDI countries (p = 0.040). In high‐HDI countries, intra‐operative cardiac arrest rates (per 10,000 anaesthetic procedures) decreased from 9.59 (95%CI 6.59–13.16) pre‐1990 to 5.17 (95%CI 4.42–5.97) in 1990–2020 (p = 0.013). During the same time periods, no improvement was observed in the intra‐operative cardiac arrest rates in low‐HDI countries (p = 0.498). Odds ratios of intra‐operative cardiac arrest rates in ASA 3–5 patients were 8.48 (95%CI 1.67–42.99) times higher in low‐HDI countries than in high‐HDI countries (p = 0.0098). Intra‐operative cardiac arrest rates are related to country‐HDI and decreased over time only in high‐HDI countries. The widening gap in these rates between low‐ and high‐HDI countries needs to be addressed globally. [ABSTRACT FROM AUTHOR]

In vivo implantation of microelectrodes opens the door to studying neural circuits and restoring damaged neural pathways through direct electrical stimulation and recording. Although some neuroprostheses have achieved clinical success, electrode material properties, inflammatory response, and glial scar formation at the electrode-tissue interfaces affect performance and sustainability. Those challenges can be addressed by improving some of the materials' mechanical, physical, chemical, and electrical properties. This paper reviews materials and designs of current microelectrodes and discusses perspectives to advance neuroprosthetics performance., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Deciphering the immune organization of eukaryotes is important for human health and for understanding ecosystems. The recent discovery of antiphage systems revealed that various eukaryotic immune proteins originate from prokaryotic antiphage systems. However, whether bacterial antiphage proteins can illuminate immune organization in eukaryotes remains unexplored. Here, we use a phylogeny-driven approach to uncover eukaryotic immune proteins by searching for homologs of bacterial antiphage systems. We demonstrate that proteins displaying sequence similarity with recently discovered antiphage systems are widespread in eukaryotes and maintain a role in human immunity. Two eukaryotic proteins of the anti-transposon piRNA pathway are evolutionarily linked to the antiphage system Mokosh. Additionally, human GTPases of immunity-associated proteins (GIMAPs) as well as two genes encoded in microsynteny, FHAD1 and CTRC, are respectively related to the Eleos and Lamassu prokaryotic systems and exhibit antiviral activity. Our work illustrates how comparative genomics of immune mechanisms can uncover defense genes in eukaryotes., Competing Interests: Declaration of interests A patent application related to this work has been filled (EP22306832.1)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Evolutionary arms races between cells and viruses drive the rapid diversification of antiviral genes in diverse life forms. Recent discoveries have revealed the existence of immune genes that are shared between prokaryotes and eukaryotes and show molecular and mechanistic similarities in their response to viruses. However, the evolutionary dynamics underlying the conservation and adaptation of these antiviral genes remain mostly unexplored. Here, we show that viperins constitute a highly conserved family of immune genes across diverse prokaryotes and eukaryotes and identify mechanisms by which they diversified in eukaryotes. Our findings indicate that viperins are enriched in Asgard archaea and widely distributed in all major eukaryotic clades, suggesting their presence in the last eukaryotic common ancestor and their acquisition in eukaryotes from an archaeal lineage. We show that viperins maintain their immune function by producing antiviral nucleotide analogues and demonstrate that eukaryotic viperins diversified through serial innovations on the viperin gene, such as the emergence and selection of substrate specificity towards pyrimidine nucleotides, and through partnerships with genes maintained through genetic linkage, notably with nucleotide kinases. These findings unveil biochemical and genomic transitions underlying the adaptation of immune genes shared by prokaryotes and eukaryotes. Our study paves the way for further understanding of the conservation of immunity across domains of life., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The co-evolution of prokaryotes, phages, and mobile genetic elements (MGEs) over the past billions of years has driven the emergence and diversification of defense and anti-defense systems alike. Anti-defense proteins have diverse functional domains, sequences, and are typically small, creating a challenge to detect anti-defense homologs across the prokaryotic genomes. To date, no tools comprehensively annotate anti-defense proteins within a desired genome or MGE. Here, we developed "AntiDefenseFinder" - a free open-source tool and web service that detects 156 anti-defense systems (of one or more proteins) in any genomic sequence. Using this dataset, we identified 47,981 anti-defense systems distributed across prokaryotes, phage, and MGEs. We found that some genes co-localize in "anti-defense islands", including E. coli T4 and Lambda phages, although many are standalone. Out of the 112 systems detected in bacteria, 100 systems localize only or preferentially in prophages, plasmids, phage satellites, integrons, and integrative and conjugative elements. However, over 80% of anti-Pycsar protein 1 (Apyc1) resides in non-mobile regions of bacteria. Evolutionary and functional analyses revealed that Apyc1 likely originated in bacteria to regulate cNMP signaling, but was co-opted multiple times by phages to overcome cNMP-utilizing defenses. With the AntiDefenseFinder tool, we hope to facilitate the identification of the full repertoire of anti-defense systems in MGEs, the discovery of new protein functions, and a deeper understanding of host-pathogen arms race., Competing Interests: Conflict of interest statement: J.B.-D. is a scientific advisory board member of SNIPR Biome and Excision Biotherapeutics, a consultant to LeapFrog Bio and BiomX, and a scientific advisory board member and co-founder of Acrigen Biosciences and ePhective Therapeutics.

Immune defence mechanisms exist across the tree of life in such diversity that prokaryotic antiviral responses have historically been considered unrelated to eukaryotic immunity. Mechanisms of defence in divergent eukaryotes were similarly believed to be largely clade specific. However, recent data indicate that a subset of modules (domains and proteins) from prokaryote defence systems are conserved in eukaryotes and populate many stages of innate immune pathways. In this Essay, we propose the notion of ancestral immunity, which corresponds to the set of immune modules conserved between prokaryotes and eukaryotes. After offering a typology of ancestral immunity, we speculate on the selective pressures that could have led to the differential conservation of specific immune modules across domains of life. The exploration of ancestral immunity is in its infancy and appears full of promises to illuminate immune evolution, and also to identify and decipher immune mechanisms of economic, ecological, and therapeutic importance., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bernheim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Transposase genes are ubiquitous in all domains of life and provide a rich reservoir for the evolution of novel protein functions. Here we report deep evolutionary links between bacterial IS110 transposases, which catalyze RNA-guided DNA recombination using bridge RNAs, and archaeal/eukaryotic Nop5-family proteins, which promote RNA-guided RNA 2'-O-methylation using C/D-box snoRNAs. Based on conservation in the protein primary sequence, domain architecture, and three-dimensional structure, as well as common architectural features of the non-coding RNA components, we propose that programmable RNA modification emerged via exaptation of components derived from IS110-like transposons. Alongside recent studies highlighting the origins of CRISPR-Cas9 and Cas12 in IS605-family transposons, these findings underscore how recurrent domestication events of transposable elements gave rise to complex RNA-guided biological mechanisms., Competing Interests: COMPETING INTERESTS The authors declare no competing interests.

Integrons are genetic elements involved in bacterial adaptation which capture, shuffle and express genes encoding adaptive functions embedded in cassettes. These events are governed by the integron integrase through site-specific recombination between attC and attI integron sites. Using computational and molecular genetic approaches, here we demonstrate that the integrase also catalyses cassette integration into bacterial genomes outside of its known att sites. Once integrated, these cassettes can be expressed if located near bacterial promoters and can be excised at the integration point or outside, inducing chromosomal modifications in the latter case. Analysis of more than 5 × 10 5 independent integration events revealed a very large genomic integration landscape. We identified consensus recombination sequences, named attG sites, which differ greatly in sequence and structure from classical att sites. These results unveil an alternative route for dissemination of adaptive functions in bacteria and expand the role of integrons in bacterial evolution., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Simulation is a key tool in population genetics for both methods development and empirical research, but producing simulations that recapitulate the main features of genomic datasets remains a major obstacle. Today, more realistic simulations are possible thanks to large increases in the quantity and quality of available genetic data, and the sophistication of inference and simulation software. However, implementing these simulations still requires substantial time and specialized knowledge. These challenges are especially pronounced for simulating genomes for species that are not well-studied, since it is not always clear what information is required to produce simulations with a level of realism sufficient to confidently answer a given question. The community-developed framework stdpopsim seeks to lower this barrier by facilitating the simulation of complex population genetic models using up-to-date information. The initial version of stdpopsim focused on establishing this framework using six well-characterized model species (Adrion et al., 2020). Here, we report on major improvements made in the new release of stdpopsim (version 0.2), which includes a significant expansion of the species catalog and substantial additions to simulation capabilities. Features added to improve the realism of the simulated genomes include non-crossover recombination and provision of species-specific genomic annotations. Through community-driven efforts, we expanded the number of species in the catalog more than threefold and broadened coverage across the tree of life. During the process of expanding the catalog, we have identified common sticking points and developed the best practices for setting up genome-scale simulations. We describe the input data required for generating a realistic simulation, suggest good practices for obtaining the relevant information from the literature, and discuss common pitfalls and major considerations. These improvements to stdpopsim aim to further promote the use of realistic whole-genome population genetic simulations, especially in non-model organisms, making them available, transparent, and accessible to everyone., Competing Interests: ML, MC, GG, NP, GT, SB, VC, JC, IE, BH, AH, XH, LI, EN, JO, VP, AP, DP, MP, MR, CS, JS, AT, ST, PU, JV, RW, AW, YW, FB, RC, GG, RG, JK, AK, AR, PR, DS, IG No competing interests declared, AG is an employee of Embark Veterinary, Inc. The author declares that no other competing interests exist, JA is an employee of Ancestry DNA. The author declares that no other competing interests exist, AB is an employee of 54Gene, Inc. The author declares that no other competing interests exist, (© 2023, Lauterbur et al.)

Cultural transmission of reproductive success has been observed in many human populations as well as other animals. Cultural transmission of reproductive success consists of a positive correlation of nongenetic origin between the progeny size of parents and children. This correlation can result from various factors, such as the social influence of parents on their children, the increase of children's survival through allocare from uncles and aunts, or the transmission of resources. Here, we study the evolution of genomic diversity over time under cultural transmission of reproductive success. Cultural transmission of reproductive success has a threefold impact on population genetics: (1) the effective population size decreases when cultural transmission of reproductive success starts, mimicking a population contraction, and increases back to its original value when cultural transmission of reproductive success stops; (2) coalescent tree topologies are distorted under cultural transmission of reproductive success, with higher imbalance and a higher number of polytomies; and (3) branch lengths are reduced nonhomogenously, with a higher impact on older branches. Under long-lasting cultural transmission of reproductive success, the effective population size stabilizes but the distortion of tree topology and the nonhomogenous branch length reduction remain, yielding U-shaped site frequency spectra under a constant population size. We show that this yields a bias in site frequency spectra-based demographic inference. Considering that cultural transmission of reproductive success was detected in numerous human and animal populations worldwide, one should be cautious because inferring population past histories from genomic data can be biased by this cultural process., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Genetics Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Motivation: We present dnadna, a flexible python-based software for deep learning inference in population genetics. It is task-agnostic and aims at facilitating the development, reproducibility, dissemination and re-usability of neural networks designed for population genetic data., Results: dnadna defines multiple user-friendly workflows. First, users can implement new architectures and tasks, while benefiting from dnadna utility functions, training procedure and test environment, which saves time and decreases the likelihood of bugs. Second, the implemented networks can be re-optimized based on user-specified training sets and/or tasks. Newly implemented architectures and pre-trained networks are easily shareable with the community for further benchmarking or other applications. Finally, users can apply pre-trained networks in order to predict evolutionary history from alternative real or simulated genetic datasets, without requiring extensive knowledge in deep learning or coding in general. dnadna comes with a peer-reviewed, exchangeable neural network, allowing demographic inference from SNP data, that can be used directly or retrained to solve other tasks. Toy networks are also available to ease the exploration of the software, and we expect that the range of available architectures will keep expanding thanks to community contributions., Availability and Implementation: dnadna is a Python (≥3.7) package, its repository is available at gitlab.com/mlgenetics/dnadna and its associated documentation at mlgenetics.gitlab.io/dnadna/., (© The Author(s) 2022. Published by Oxford University Press.)

The measurement of birefringence variations related to nerve activity is a promising label-free technique for sensing compound neural action potentials (CNAPs). While widely applied in crustaceans, little is known about its efficiency on mammal peripheral nerves. In this work, birefringence recordings to detect CNAPs, and Stokes parameters measurements were performed in rat and lobster nerves. While single-trial detection of nerve activity in crustaceans was achieved successfully, no optical signal was detected in rats, even after extensive signal filtering and averaging. The Stokes parameters showed that a high degree of polarization of light is maintained in lobster sample, whereas an almost complete light depolarization occurs in rat nerve. Our results indicate that depolarization itself is not sufficient to explain the absence of birefringence signals in rats. We hypothesize that this absence comes from the myelin sheets, which constraint the birefringence changes to only take place at the nodes of Ranvier., (© 2022 Wiley-VCH GmbH.)

Background: Peyronie's disease (PD) is characterized by the formation of fibrous plaque in tunica albuginea, causing several problems in patients. The etiology of this disease is not fully understood, and there are few effective treatments. To better understand the molecular pathways of PD, we studied miR-29b, a microRNA that could be involved with this illness. MicroRNAs are endogenous molecules that act by inhibiting messenger RNA. MiR-29b regulates 11 of 20 collagen genes and the TGF-β1 gene, which are related to PD progression., Methods: We compared miR-29b expression in 11 patients with PD and 14 patients without PD (control group). For the patients with PD, we utilized samples from the fibrous plaque ( n = 9), from the tunica albuginea ( n = 11), and from the corpus cavernosum ( n = 8). For the control group, we utilized samples from the tunica albuginea ( n = 14) and from the corpus cavernosum ( n = 10). MiR-29b expression was determined by q-PCR., Results: We found a downregulation of miR-29b in the fibrous plaque, tunica albuginea and corpus cavernosum of patients with PD in comparison with the control group ( p = 0.0484, p = 0.0025, and p = 0.0016, respectively)., Conclusion: Although our study has a small sample, we showed for the first time an evidence that the downregulation of miR-29b is associated with PD.

Objective. The vagus nerve is considered to play a key role in the circadian rhythm. Chronic continuous analysis of the vagus nerve activity could contribute to a better understanding of the role of the vagus nerve in light-dark modulations. This paper presents a continuous analysis of spontaneous vagus nerve activity performed in four rats. Approach. We analyzed the vagus electroneurogram (VENG) and electroencephalogram (EEG) over a recording period of 28 d. Spike activity and heart rate estimation were derived from the VENG, and slow-wave activity was derived from the EEG. The presence of repetitive patterns was investigated with periodograms, cosinor fitting, autocorrelation, and statistical tests. The light-dark variations derived from the VENG spikes were compared with EEG slow waves, an established metric in circadian studies. Results. Our results demonstrate that light-dark variations can be detected in long-term vagus nerve activity monitoring. A recording period of about 7 d is required to characterize accurately the VENG light-dark variations. Significance. As a major outcome of this study, vagus nerve recordings hold the promise to help understand circadian regulation., (© 2022 IOP Publishing Ltd.)

Background: Gastric electrical stimulation (GES) has been studied for decades as a promising treatment for obesity. Stimulation pulses with fixed amplitude and pulse width are usually applied, but these have limitations with regard to overcoming habituation to GES and inter-subject variation. This study aims to analyze the efficacy of an adaptive GES protocol for reducing food intake and maintaining lean weight in dogs., Methods: Six beagle dogs were implanted with a remotely programmable gastric stimulator. An adaptive protocol was designed to increase the stimulation energy proportionally to the excess of food consumption, with respect to the dogs' maintenance energy requirements. After surgery and habituation to experimental conditions, the dogs went through both a control and a stimulation period of 4 weeks each, in a randomized order. The stimulation parameters were adapted daily. Body weight, food intake, food intake rate, and postprandial cutaneous electrogastrograms (EGG) were recorded to assess the effect of adaptive GES., Results: Adaptive GES decreased food intake and food intake rate (p < 0.05) resulting in weight maintenance. In the absence of GES, the dogs gained weight (p < 0.05). Postprandial EGG dominant frequency was accelerated by GES (p < 0.05). The strategy of adapting the stimulation energy was effective in causing significant mid-term changes., Conclusion: Adaptive GES is effective for reducing food intake and maintaining lean weight. The proposed adaptive strategy may offer benefits to counter habituation and adapt to inter-subject variation in clinical use of GES for obesity., (© 2021 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Bacteria have been shown to harbor a growing arsenal of various defense systems against phages. Maguin et al. have uncovered how two of the most frequent defense systems interact: the clustered regularly interspaced short palindromic repeats-Cas (CRISPR-Cas) system recycles by-products of the restriction-modification (RM) system to increase bacterial defense in the long run., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Bacteria and archaea have developed multiple antiviral mechanisms, and genomic evidence indicates that several of these antiviral systems co-occur in the same strain. Here, we introduce DefenseFinder, a tool that automatically detects known antiviral systems in prokaryotic genomes. We use DefenseFinder to analyse 21000 fully sequenced prokaryotic genomes, and find that antiviral strategies vary drastically between phyla, species and strains. Variations in composition of antiviral systems correlate with genome size, viral threat, and lifestyle traits. DefenseFinder will facilitate large-scale genomic analysis of antiviral defense systems and the study of host-virus interactions in prokaryotes., (© 2022. The Author(s).)

Integrons are flexible gene-exchanging platforms that contain multiple cassettes encoding accessory genes whose order is shuffled by a specific integrase. Integrons embedded within mobile genetic elements often contain multiple antibiotic resistance genes that they spread among nosocomial pathogens and contribute to the current antibiotic resistance crisis. However, most integrons are presumably sedentary and encode a much broader diversity of functions. IntegronFinder is a widely used software to identify novel integrons in bacterial genomes, but has aged and lacks some useful functionalities to handle very large datasets of draft genomes or metagenomes. Here, we present IntegronFinder version 2. We have updated the code, improved its efficiency and usability, adapted the output to incomplete genome data, and added a few novel functions. We describe these changes and illustrate the relevance of the program by analyzing the distribution of integrons across more than 20,000 fully sequenced genomes. We also take full advantage of its novel capabilities to analyze close to 4000 Klebsiella pneumoniae genomes for the presence of integrons and antibiotic resistance genes within them. Our data show that K. pneumoniae has a large diversity of integrons and the largest mobile integron in our database of plasmids. The pangenome of these integrons contains a total of 165 different gene families with most of the largest families being related with resistance to numerous types of antibiotics. IntegronFinder is a free and open-source software available on multiple public platforms.

Some evidence in vitro suggested that amoxicillin and fluoride could disturb the enamel mineralization., Objective: To assess the effect of amoxicillin and of the combination of amoxicillin and fluoride on enamel mineralization in rats., Methodology: In total, 40 rats were randomly assigned to four groups: control group (CG); amoxicillin group (AG - amoxicillin (500 mg/kg/day), fluoride group (FG - fluoridated water (100 ppm -221 mg F/L), and amoxicillin + fluoride group (AFG). After 60 days, the samples were collected from plasma and tibiae and analyzed for fluoride (F) concentration. The incisors were also collected to determine the severity of fluorosis using the Dental Fluorosis by Image Analysis (DFIA) software, concentration of F, measurements of enamel thickness, and hardness. The data were analyzed by ANOVA, Tukey's post-hoc test, or Games-Howell post-hoc test (α=0.05)., Results: Enamel thickness of the incisors did not differ statistically among the groups (p=0.228). Groups exposed to fluoride (AFG and FG) have higher F concentrations in plasma, bone and teeth than those not exposed to fluoride (CG and AG). The groups showed a similar behavior in the DFIA and hardness test, with the FG and AFG groups showing more severe fluorosis defects and significant lower hardness when compared with the AG and CG groups, with no difference from each other., Conclusion: The rats exposed to fluoride or fluoride + amoxicillin developed dental fluorosis, while exposure to amoxicillin alone did not lead to enamel defects.

For the past decades, simulation-based likelihood-free inference methods have enabled researchers to address numerous population genetics problems. As the richness and amount of simulated and real genetic data keep increasing, the field has a strong opportunity to tackle tasks that current methods hardly solve. However, high data dimensionality forces most methods to summarize large genomic data sets into a relatively small number of handcrafted features (summary statistics). Here, we propose an alternative to summary statistics, based on the automatic extraction of relevant information using deep learning techniques. Specifically, we design artificial neural networks (ANNs) that take as input single nucleotide polymorphic sites (SNPs) found in individuals sampled from a single population and infer the past effective population size history. First, we provide guidelines to construct artificial neural networks that comply with the intrinsic properties of SNP data such as invariance to permutation of haplotypes, long scale interactions between SNPs and variable genomic length. Thanks to a Bayesian hyperparameter optimization procedure, we evaluate the performance of multiple networks and compare them to well-established methods like Approximate Bayesian Computation (ABC). Even without the expert knowledge of summary statistics, our approach compares fairly well to an ABC approach based on handcrafted features. Furthermore, we show that combining deep learning and ABC can improve performance while taking advantage of both frameworks. Finally, we apply our approach to reconstruct the effective population size history of cattle breed populations., (© 2020 John Wiley & Sons Ltd.)

Introduction: The pandemic caused by the COVID-19 resulted in worldwide social isolation and leading to significant personal distress, particularly among health professionals on the front lines. Those factors' relevance and their impact on sexual function in this population have not yet been established., Aim: To evaluate the impact of the pandemic on sexual function in healthcare professionals and medical students at a reference center in the treatment of COVID-19 in Brazil., Methods: A cross-sectional analysis with online questionnaires about sexual function was sent to health professionals and medical students from the HC-FMUSP medical complex. The questionnaire evaluated Total Sexual and Masturbatory Frequency prior and during the pandemic, libido and sexual satisfaction changes with a detailed inquire about demographics and personal factors. An objective assessment of sexual function was also made using the validated sexual quotient questionnaires., Main Outcome Measures: Differences in intercourse frequency, libido, and overall sexual satisfaction, in a sample of healthcare professionals particularly vulnerable to the pandemic effects., Results: A total of 1,314 responses were available with a mean age of 37 years. Worsening of sexual satisfaction was reported by 44.5% of the participants, with the following associated factors: Lower libido, missing Nightlife, Higher Masturbatory Frequency, and isolation from the partner. Remaning sexualy actively and having higher sexual frequency appear to decrease the chance of worsening sexual function. Worsening of Libido was reported by 37% and had several associated factors, including missing of Nightlife, older age, isolation from the partner among others. Being male and sexually active was associated with a smaller chance of reporting lower libido., Conclusion: We were able to observe a sharp drop in Libido and General Sexual Satisfaction. Although an increase in pornography consumption and masturbatory frequency did occur, these factors were not associated with greater sexual satisfaction. The impact of COVID-19 on this population's sexual health is not to be underestimated and should be further studied in the follow-up of the pandemic. Neto RP, Nascimento BCG, Carvalho dos Anjos Silva G, et al. Impact of COVID-19 Pandemic on the Sexual Function of Health Professionals From an Epicenter in Brazil. Sex Med 2021;9:100408., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Intra-operative cardiac arrests differ from most in-hospital cardiac arrests because they reflect not only the patient's condition but also the quality of surgery and anaesthesia care provided. We assessed the relationship between intra-operative cardiac arrest rates and country Human Development Index (HDI), and the changes occurring in these rates over time. We searched PubMed, EMBASE, Scopus, LILACS, Web of Science, CINAHL and SciELO from inception to 29 January 2020. For the global population, rates of intra-operative cardiac arrest and baseline ASA physical status were extracted. Intra-operative cardiac arrest rates were analysed by time, country HDI status and ASA physical status using meta-regression analysis. Proportional meta-analysis was performed to compare intra-operative cardiac arrest rates and ASA physical status in low- vs. high-HDI countries and in two time periods. Eighty-two studies from 25 countries with more than 29 million anaesthetic procedures were included. Intra-operative cardiac arrest rates were inversely correlated with country HDI (p = 0.0001); they decreased over time only in high-HDI countries (p = 0.040) and increased with increasing ASA physical status (p < 0.0001). Baseline ASA physical status did not change in high-HDI countries (p = 0.106), while it decreased over time in low-HDI countries (p = 0.040). In high-HDI countries, intra-operative cardiac arrest rates (per 10,000 anaesthetic procedures) decreased from 9.59 (95%CI 6.59-13.16) pre-1990 to 5.17 (95%CI 4.42-5.97) in 1990-2020 (p = 0.013). During the same time periods, no improvement was observed in the intra-operative cardiac arrest rates in low-HDI countries (p = 0.498). Odds ratios of intra-operative cardiac arrest rates in ASA 3-5 patients were 8.48 (95%CI 1.67-42.99) times higher in low-HDI countries than in high-HDI countries (p = 0.0098). Intra-operative cardiac arrest rates are related to country-HDI and decreased over time only in high-HDI countries. The widening gap in these rates between low- and high-HDI countries needs to be addressed globally., (© 2021 Association of Anaesthetists.)

The anticaries potential of restorative ionomeric materials should be evaluated under a pH-cycling regime that simulates the caries process of demineralization and remineralization. Ten glass ionomer cement (GIC) materials and five resin-modified glass ionomer cement (RMGIC) materials were evaluated. A resin composite was used as a negative control. Six discs of each material were immersed for 6 and 18 hours each day in demineralizing (De-) and remineralizing (Re-) solutions, respectively. The solutions were changed daily over 12 days, during which the fluoride concentration was determined using an ion-specific electrode. The results were expressed as (1) the daily fluoride concentration in the Deand Re- solutions (μg F/ml), (2) the amount of fluoride released daily in the De- + Re- solution per area of specimens (μg F/cm2/day), and (3) the cumulative release over the 12-day period (μg F/cm2). During the first days, all materials showed a surge in fluoride release, followed by a gradual decline; however, three distinct patterns were observed, specifically: (1) greater fluoride release in the De- solution compared to the Resolution during the study period; (2) an initial higher release in De- solution; and (3) a similar release in both solutions over the whole period. The materials differed statistically (p<0.05) with respect to daily and cumulative fluoride release. One GIC (Maxxion R) and one RMGIC (Resiglass R) had the highest and lowest ability to release fluoride, respectively. In conclusion, the GICs and RMGICs evaluated exhibited distinct qualitative and quantitative patterns of fluoride release under conditions simulating the caries process, which might reflect their anticaries potential., (© Operative Dentistry, 2021.)

On-demand stimulation improves the efficacy of vagus nerve stimulation (VNS) in refractory epilepsy. The vagus nerve is the main peripheral parasympathetic connection and seizures are known to exhibit autonomic symptoms. Therefore, we hypothesized that seizure detection is possible through vagus nerve electroneurogram (VENG) recording. We developed a metric able to measure abrupt changes in amplitude and frequency of spontaneous vagus nerve action potentials. A classifier was trained using a "leave-one-out" method on a set of 6 seizures and 3 control recordings to utilize the VENG spike feature-based metric for seizure detection. We were able to detect pentylenetetrazol (PTZ) induced acute seizures in 6/6 animals during different stages of the seizure with no false detection. The classifier detected the seizure during an early stage in 3/6 animals and at the onset of tonic clonic stage of the seizure in 3/6 animals. EMG and motion artefacts often accompany epileptic activity. We showed the "epileptic" neural signal to be independent from EMG and motion artefacts. We confirmed the existence of seizure related signals in the VENG recording and proved their applicability for seizure detection. This detection might be a promising tool to improve efficacy of VNS treatment by developing new responsive stimulation systems.

Objective. To design and implement a setup for ex-vivo optical stimulation for exploring the effect of several key parameters (optical power and pulse duration), activation features (threshold, spatial selectivity) and recovery characteristics (repeated stimuli) in peripheral nerves. Approach. A nerve chamber allowing ex-vivo electrical and optical stimulation was designed and built. A 1470 nm light source was chosen to stimulate the nerve. A photodiode module was implemented for synchronization of the electrical and optical channels. Main results . Compound neural action potentials (CNAPs) were successfully generated with infrared light pulses of 200-2000 µ s duration and power in the range of 3-10 W. These parameters determine a radiant exposure for stimulation in the range 1.59-4.78 J cm -2 . Recruitment curves were obtained by increasing durations at a constant power level. Neural activation threshold is reached at a mean radiant exposure of 3.16 ± 0.68 J cm -2 and mean pulse energy of 3.79 ± 0.72 mJ. Repetition rates of 2-10 Hz have been explored. In eight out of ten sciatic nerves (SNs), repeated light stimuli induced a sensitization effect in that the CNAP amplitude progressively grows, representing an increasing number of recruited fibres. In two out of ten SNs, CNAPs were composed of a succession of peaks corresponding to different conduction velocities. Significance. The reported sensitization effect could shed light on the mechanism underlying infrared neurostimulation. Our results suggest that, in sharp contrast with electrical stimuli, optical pulses could recruit slow fibres early on. This more physiological order of recruitment opens the perspective for specific neuromodulation of fibre population who remained poorly accessible until now. Short high-power light pulses at wavelengths below 1.5 µ m offer interesting perspectives for neurostimulation., (© 2021 IOP Publishing Ltd.)

Objective. Finite element modelling has been widely used to understand the effect of stimulation on the nerve fibres. Yet the literature on analysis of spontaneous nerve activity is much scarcer. In this study, we introduce a method based on a finite element model, to analyse spontaneous nerve activity with a typical bipolar electrode recording setup, enabling the identification of spontaneously active fibres. We applied our method to the vagus nerve, which plays a key role in refractory epilepsy. Approach. We developed a 3D model including dynamic action potential (AP) propagation, based on the vagus nerve geometry. The impact of key recording parameters-inter-electrode distance and temperature-and uncontrolled parameters-fibre size and position in the nerve-on the ability to discriminate active fibres were quantified. A specific algorithm was implemented to detect and classify APs from recordings, and tested on six rat in-vivo vagus nerve recordings. Main results. Fibre diameters can be discriminated if they are below 3 μ m and 7 μ m, respectively for inter-electrode distances of 2 mm and 4 mm. The impact of the position of the fibre inside the nerve on fibre diameter discrimination is limited. The range of active fibres identified by modelling in the vagus nerve of rats is in agreement with ranges found at histology. Significance. The nerve fibre diameter, directly proportional to the AP propagation velocity, is related to a specific physiological function. Estimating the source fibre diameter is thus essential to interpret neural recordings. Among many possible applications, the present method was developed in the context of a project to improve vagus nerve stimulation therapy for epilepsy., (© 2021 IOP Publishing Ltd.)

Neurological visual impairments in children have multiple causes, some of them reversible while others are not. Hydrocephalus is one of the most important and common ones as it can result in permanent impairment. There are multiple causes of hydrocephalus, intraventricular hemorrhage being the main one. This generally occurs when the germinal matrix bleeds and is very common in preterm newborns. We present the clinical case of a patient with cerebral palsy, intraventricular hemorrhage, and hydrocephalus as a result of a preterm multiple pregnancy who developed optic atrophy during childhood secondary to ventricle-peritoneal shunt dysfunction. During the rehabilitation and treatment period, she received neurorehabilitation sessions, which improved her visual acuity and capacity. We found similarities and differences with other cases and we confirmed the importance of the treatment chosen for the recovery of visual capacity.

Background: Vagus nerve stimulation is a treatment for refractory epilepsy. The vagus nerve carries parasympathetic information and innervates multiple organs. As seizures are commonly associated with autonomic manifestations, we believe that biomarkers for diseases affecting autonomic functions such as epilepsy can be found in vagus nerve signals., New Method: We present a method to record vagus nerve electroneurogram (VENG) and detect in the VENG single unit activity in anesthetized rats during Pentylenetetrazol induced seizures using a true tripolar cuff electrode., Results: The VENG consisted of high amplitude bursts and lower amplitude bursts synchronous to respiration and heartbeat respectively. The average spikes exhibited a triphasic shape with duration below 1.5ms and root mean square amplitude varied between 5.5 +/- 0.2 μV and 11.4 +/- 3.1 μV depending on the type of recording. An increase of the contact distance resulted in a signal amplitude increase. Application of Lidocaine led to a total disappearance of the recorded spontaneous spiking of the nerve., Comparison With Existing Methods: True tripolar cuff electrodes exhibited a better performance in terms of artefact rejection, stability and reproducibility of the signal compared to commonly used hook electrodes which is of special interest in seizures where important motion and EMG artifacts are expected., Conclusion: We present a new method to record single unit activity of the vagus nerve during acute chemically induced seizures in rats and verified the neural origin of the recorded signals. This recording method might be a powerful tool to develop seizure biomarkers based on VENG., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Recombination systems are widely used as bioengineering tools, but their sites have to be highly similar to a consensus sequence or to each other. To develop a recombination system free of these constraints, we turned toward attC sites from the bacterial integron system: single-stranded DNA hairpins specifically recombined by the integrase. Here, we present an algorithm that generates synthetic attC sites with conserved structural features and minimal sequence-level constraints. We demonstrate that all generated sites are functional, their recombination efficiency can reach 60%, and they can be embedded into protein coding sequences. To improve recombination of less efficient sites, we applied large-scale mutagenesis and library enrichment coupled to next-generation sequencing and machine learning. Our results validated the efficiency of this approach and allowed us to refine synthetic attC design principles. They can be embedded into virtually any sequence and constitute a unique example of a structure-specific DNA recombination system., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Bacterial genomes, organized intracellularly as nucleoids, are composed of the main chromosome coexisting with different types of secondary replicons. Secondary replicons are major drivers of bacterial adaptation by gene exchange. They are highly diverse in type and size, ranging from less than 2 to more than 1000 kb, and must integrate with bacterial physiology, including to the nucleoid dynamics, to limit detrimental costs leading to their counter-selection. We show that large DNA circles, whether from a natural plasmid or excised from the chromosome tend to localize in a dynamic manner in a zone separating the nucleoid from the cytoplasm at the edge of the nucleoid. This localization is in good agreement with silico simulations of DNA circles in the nucleoid volume. Subcellular positioning systems counteract this tendency, allowing replicons to enter the nucleoid space. In enterobacteria, these systems are found in replicons above 25 kb, defining the limit with small randomly segregated plasmids. Larger replicons carry at least one of the three described family of systems, ParAB, ParRM, and StbA. Replicons above 180 kb all carry a ParAB system, suggesting this system is specifically required in the cases of large replicons. Simulations demonstrated that replicon size profoundly affects localization, compaction, and dynamics of DNA circles in the nucleoid volume. The present work suggests that presence of partition systems on the larger plasmids or chromids is not only due to selection for accurate segregation but also to counteract their unmixing with the chromosome and consequent exclusion from the nucleoid., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Although penile Doppler ultrasound (PDU) is a useful tool in evaluating erectile dysfunction (ED), an optimal erectile response might be limited because of an increased sympathetic discharge. Audiovisual sexual stimulation (AVSS) has been suggested to help improving PDU performance., Aim: To evaluate the use of AVSS as a tool to improve diagnostic accuracy of PDU studies., Methods: A total of 40 men (mean age: 61.8 ± 10.2 years) with ED were enrolled. PDU sessions were performed in a randomized fashion as follows: session A under intracavernous injection (ICI) alone and session B under ICI and AVSS with 7-day interval between sessions. Peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) were measured 5, 10, 15, and 20 minutes after ICI., Main Outcome Measure: Comparisons between PSV, EDV, and RI values were performed with and without AVSS. Univariable and multivariable analyses including clinical and demographic parameters were performed to evaluate predictors of an abnormal PDU., Results: 23 patients performed the first session without AVSS, and 17 performed the first session with AVSS. EDV and RI were better in AVSS session (p = 0.022 and 0.019). PSV was not influenced by AVSS (p = 0.768). The proportion of patients whose diagnosis was changed because of the AVSS was 4 of 40 (10.0%, 95% confidence interval [CI]: 2.8-23.7%). Of 12 patients with venous leak observed on the PDU without AVSS, 3 turned into normal after AVSS (25.0%, 95% CI: 5.5-57.2%). Of 4 men with arterial insufficiency observed on the PDU on ICI alone, 1 became normal after AVSS (25.0%, 95% CI: 0.6-80.6%). International Index of Erectile Function-5 scores were lower in patients with abnormal PDU (6.3 ± 3.3 vs 12.0 ± 5.8, p=0.003). On multivariable analysis, DM and International Index of Erectile Function-5 scores were the only independent predictors of abnormal PDU studies., Clinical Implications: False diagnoses of venous leak during PDU with ICI could be a result of an increased adrenergic discharge during the examination. Routine AVSS may be helpful to avoid error in diagnosis., Strength & Limitations: The study has randomized the use of AVSS in different session orders. Only one previously published study has used this strategy to control the accommodation effect in repeat studies, a common source of bias in the PDU literature. The main limitation is the absence of a rigidity assessment and a redosing protocol., Conclusion: Adding AVSS during PDU improves ICI response and may help clinicians evaluate penile hemodynamics more accurately. Carneiro F, Nascimento B, Miranda EP, et al. Audiovisual Sexual Stimulation Improves Diagnostic Accuracy of Penile Doppler Ultrasound in Patients With Erectile Dysfunction. J Sex Med 2020;17:249-256., (Copyright © 2019 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: There exist conflicting data regarding the accuracy of ICU nurses accurately assessing patient sleep using validated questionnaires. Using the Richards-Campbell Sleep Questionnaire (RSQ), we hypothesize that patient factors might influence nursing perception of their sleep., Methods: Patients in the ICU who met the inclusion criteria were asked to complete the sleep questionnaire, as were their nurses and intraclass correlation analysis was done., Results: 38 paired patient-nurse surveys were included for analysis. The mean difference in total average score of the RSQ was not significantly different between patients and nurses. There was fair intraclass correlation by patient age, black race, and admission for respiratory illnesses. A good intraclass correlation existed for non-blacks and admission for non-respiratory reasons. Most striking was the intraclass correlation by sex, with poor intraclass correlation for women compared to an excellent correlation for men., Conclusion: The results of our study confirm that patients in our ICU have poor sleep with a fair intraclass correlation. When examined by patient related factor, the greatest divergence between patient and nursing perception of sleep in the ICU using the RCSQ was patient female sex. More research is needed in this area to better understand the divergence and improve sleep in the ICU., Competing Interests: The authors have declared that no competing interests exist.

We present a computational method to identify conjugative systems in plasmids and chromosomes using the CONJscan module of MacSyFinder. The method relies on the identification of the protein components of the system using hidden Markov model profiles and then checking that the composition and genetic organization of the system is consistent with that expected from a conjugative system. The method can be assessed online using the Galaxy workflow or locally using a standalone software. The latter version allows to modify the models of the module (i.e., to change the expected components, their number, and their organization).CONJscan identifies conjugative systems, but when the mobile genetic element is integrative (ICE), one often also wants to delimit it from the chromosome. We present a method, with a script, to use the results of CONJscan and comparative genomics to delimit ICE in chromosomes. The method provides a visual representation of the ICE location. Together, these methods facilitate the identification of conjugative elements in bacterial genomes.