Risk factors for perianeurysmal vasogenic oedema (pavo) following embolization therapy: literature review.

Perianeurysmal vasogenic oedema (PAVO) is a rare complication associated post-embolisation of intracranial aneurysms. The prevalence, risk factors predisposing to susceptibility, and pathologic mechanisms underlying this process are not clearly understood. Since this complication may be associated with poor clinical outcomes, the authors designed this study to describe possible risk factors, underlying mechanisms, and management of PAVO through published case reports. Developing a priori protocol according to PRISMA guidelines, we searched MEDLINE/PubMed, Embase and Web of Science to identify case studies and reports of adult patients with intracranial aneurysms who developed perianeurysmal oedema following coil embolization therapy. Data extracted from these studies included patient demographics, aneurysm characteristics, coil type, PAVO characteristics, treatment, and outcomes. Quality was assessed using a standardized tool. 21 eligible studies of acceptable quality were identified, comprising 40 unique cases from 9 countries. The mean patient age was 56.4 years and 25 (62.5%) were female. Aneurysm size ranged from 6 to 30 mm, with a mean size of 15.2 mm; only 6 (15%) of cases were giant intracranial aneurysm (≥ 25 mm). The more frequent locations of intracranial aneurysms associated with PAVO were the ICA (50%) and posterior circulation (32.5%), with 7.5% and 10% of cases occurring in MCA and anterior circulation, respectively. 16 cases (40%) were treated with bare platinum coils, and 14 (35%) with a combination of BPCs and bioactive coils; in 10 cases (25%), the coil type was not mentioned. PAVO presented between 0 days and 8 years of coil embolization, with 23 (57.5% cases) presenting symptomatically in relation to brain region affected. Management strategies for PAVO included conservative, steroids, re-embolization, clipping, stenting, parent artery occlusion either as monotherapy or as combination therapy. Of reported studies, 26 treated cases (65%) resolved, with 8 (20%) remaining stable, and 4 (10%) deteriorating. PAVO can be associated with small or large intracranial aneurysms, bare and bioactive platinum coils, and all regions of the intracranial circulation. The understanding of the risk factors of this complication lies in the underlying mechanisms, which will ultimately guide appropriate patient follow-up and subsequent optimal management.

Lifetime Stressor Exposure and Psychophysiological Reactivity and Habituation to Repeated Acute Social Stressors.

This study addressed whether lifetime stressor exposure was associated with psychophysiological reactivity and habituation to a novel laboratory-based stressor. Eighty-six participants (Mage = 23.31 years, SD = 4.94) reported their exposure to lifetime non-sport and sport-specific stressors before completing two consecutive trials of the Trier Social Stress Test, while cardiovascular (i.e., heart rate) and endocrine (i.e., salivary cortisol) data were recorded. Exposure to a moderate number of lifetime non-sport and sport-specific stressors was associated with adaptive cardiovascular reactivity, whereas very low or very high stressor exposure was related to maladaptive reactivity. Moreover, experiencing a very low number of lifetime non-sport (but not sport-specific) stressors was associated with poorer habituation. In contrast, lifetime stressor severity was unrelated to cardiovascular reactivity. Finally, greater lifetime non-sport and sport-specific stressor counts were associated with blunted cortisol reactivity and poorer habituation. These results suggest that lifetime stressor exposure may influence sport performers' acute stress responses.

Skull Base Neurosurgery Eponyms: A Review of Notable Anatomical Landmarks.

Eponyms highlight the contributions made to medicine over the years, and celebrate individuals for their work involving diseases, pathologies, and anatomical landmarks. We have compiled an in-depth report of eponyms used in skull base neurosurgery, as well as the historical contexts of the personalities behind the names. A literature search identified 36 eponyms of the bones, foramina and ligaments of the skull base named after anatomists and physician-scientists. The 36 eponymous structures pinpointed include Arnold's canal, the foramen of Arnold, Bill's bar, Bertin's bones, Civinini's canal, Civinini's ligament, Civinini's process, sinodural angle of Citelli, Clivus of Blumenbach, Dorello's canal, the Eustachian tube, the eponymous cavernous sinus triangles of Parkinson, Kawase, Mullan, Dolenc, Glasscock and Hakuba, the Fallopian canal, the Glasserian fissure, Gruber's ligament, Haller cells, the spine of Henle, Highmore's antrum, the foramen of Huschke, Hyrtl's fissure, the Ingrassia process, Jacobson's canal, the MacEwen triangle, Meckel's cave, the Onodi air cell, the Pacchionian foramen, Fossa of Rosenmuller, the foramen of Vesalius, the Vidian canal, Trautman's triangle and the annular tendon of Zinn. Knowledge of the relevant eponyms enables succinct descriptions of important skull base structures, provides an understanding of associated clinical implications, and reminds us of the vast history of contributions to neurosurgery made by prominent figures in the field.

Cavernous sinus haemangioma: systematic review and pooled analysis relating to a rare skull base pathology.

Cavernous sinus haemangiomas (CSHs) are rare malformations of the microcirculation arising from the cavernous sinus. A systematic review and pooled data analysis of the associated clinical features, diagnostic modalities, management, and outcomes for CSHs was done. In total, 68 articles (338 cases) were eligible for analysis based on our selection criteria. The primary outcome measures were the occurrence of (i) and (ii) symptom resolution/improvement. Categorical outcome variables were assessed by binary logistic regression at 5% significance level. With headaches (39.9%) and diplopia (36.5%) as the most common presenting symptoms reported, dynamic contrast-enhanced MRI was the most commonly used diagnostic modality and was the most definitive pre-treatment imaging modality for diagnosing CSH with a sensitivity of 89.5%. The majority of CSHs were managed with radiosurgery (47.9% of cases), 37.9% by surgical resection alone, and 14.2% by a combination of both. Compared to patients that were treated with surgical resection only, those treated solely with radiosurgery had a 100% decrease in the odds of developing post-treatment complications (adjusted OR: 0.00, 95% CI: 0.00-0.002, p < 0.001), with a 5.03 times greater odds of symptom resolution/improvement (adjusted OR: 5.03, 95% CI: 1.89-13.4, p = 0.001). Patients that underwent combined therapy had a 79% reduction in risk of developing post-treatment complications (adjusted OR: 0.21, 95% CI: 0.06-0.68, p = 0.01), with no statistically significant difference in the odds of symptom resolution/improvement, compared to those that had surgery only. In conclusion, radiosurgery offered the best outcomes with regards to symptom resolution/improvement and post-treatment complications in patients with CSH.

Predictors of military veterans' engagement in bespoke recovery pathways and health and well-being outcomes.

PURPOSE/OBJECTIVE: The objective of this cross-sectional study was to assess how psychosocial variables predict U.K. military veterans' level of engagement in bespoke recovery pathways (Aim 1) and a sports-specific recovery pathway (Aim 2). A further purpose of this study was to test whether predictor variables indirectly predict outcome variables of physical health (Aim 3), mental health (Aim 4), and subjective vitality (Aim 5), when mediated through level of engagement with all recovery pathways and the sport recovery pathway. Research Method/Design: A cross-sectional battery of questionnaires were completed by 514 military veterans who had been enrolled in Help for Heroes recovery pathways (e.g., sports recovery pathway) from 3 months to 10 years. Data were analyzed by multinomial logistic and multiple linear regressions and mediation analyses using the PROCESS SPSS macro. RESULTS: Engagement in all recovery pathways (i.e., frequency and duration of attendance) was predicted by basic psychological needs frustration and perceived social support (Nagelkerke R² = .16). Sport-related social support (p < .05) and competence satisfaction (p < .001) were directly positively associated with mental health, and competence satisfaction with physical health (p < .001) and well-being (p < .001) on the sport recovery pathway. While perceived stress was directly negatively associated with mental health and well-being (p < .001). Mediation analyses revealed no significant, indirect effects of psychosocial variables on health and wellbeing through level of engagement. CONCLUSIONS/IMPLICATIONS: In sum, engagement in recovery pathways does not mediate the effects of psychosocial variables on veterans' health and well-being. Perceived social support, satisfaction of veterans' needs, and perceived stress were better predictors of health and well-being outcomes and should be an important focus of future research and recovery. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Dissecting OCT4 defines the role of nucleosome binding in pluripotency.

Pioneer transcription factors such as OCT4 can target silent genes embedded in nucleosome-dense regions. How nucleosome interaction enables transcription factors to target chromatin and determine cell identity remains elusive. Here, we systematically dissect OCT4 to show that nucleosome binding is encoded within the DNA-binding domain and yet can be uncoupled from free-DNA binding. Furthermore, accelerating the binding kinetics of OCT4 to DNA enhances nucleosome binding. In cells, uncoupling nucleosome binding diminishes the ability of OCT4 to individually access closed chromatin, while more dynamic nucleosome binding results in expansive genome scanning within closed chromatin. However, both uncoupling and enhancing nucleosome binding are detrimental to inducing pluripotency from differentiated cells. Remarkably, stable interactions between OCT4 and nucleosomes are continuously required for maintaining the accessibility of pluripotency enhancers in stem cells. Our findings reveal how the affinity and residence time of OCT4-nucleosome complexes modulate chromatin accessibility during cell fate changes and maintenance.

Military veteran athletes' experiences of competing at the 2016 Invictus Games: a qualitative study.

PURPOSE: Previous research has championed sport as a form of recovery for military veterans. Nevertheless, there is a lack of research on military veterans' experiences of international sporting competitions. The aim of this study was to explore military veterans' experiences of participation at the 2016 Invictus Games. METHODS: Fifteen military veterans (10 male, 5 female) who participated in the 2016 Invictus Games were recruited. Semi-structured interviews were conducted to explore experiences pre, during, and post-competition, and analyzed using applied thematic analysis. RESULTS: Three overarching themes were identified: Sources of motivation consisted of a range of veteran specific motives for getting involved with and continuing participation with the Games. Team and culture stressors encapsulated organizational demands related to the attitudes and behaviors of a sports team operating within the context of the Invictus Games. Impact of the games comprised veterans' perceptions of positive and negative consequences of being involved with the Games. CONCLUSIONS: The study provides insight into the multitude of motives military veterans have for engaging in sport, whilst also demonstrating the novel organizational demands that veteran athletes encounter. The findings also offer preliminary insight regarding the impact of the Games and the potential for psychoeducation program implementation to support athletes post-Games.Implications for RehabilitationThe Invictus Games were created for military veterans to use the power of sport to inspire recovery, support rehabilitation, and generate wider understanding and respect.Findings highlight that military veterans have unique motives to compete at the Invictus Games, including "reconnection with previously military life" and "being a role model".Whilst veterans encounter team and culture organizational stressors while competing, they share similar post-Games experiences to full-time athletes, including the concept of "post-games blues".Experiences shared by military veterans at the Invictus Games can aid in the promotion of sport as a viable form of recovery.Primary and secondary stress management strategies should be implemented with military veterans to reduce organizational stressors and their responses to them.Psychoeducation programmes should be introduced pre-Games to better prepare military veterans for their post-Games experience.

A Longitudinal Examination of Military Veterans' Invictus Games Stress Experiences.

This study explored patterns of change in stress variables (i.e., stressors, appraisals, emotions) encountered by wounded, injured, and sick military veterans in the build up to, during, and following an international sporting competition. The study also examined interactions between psychosocial variables and salivary biomarkers of stress and how these relate to veterans' health, well-being, illness, and performance. 40 Invictus Games (IG) athletes and a control group of 20 military veteran athletes completed questionnaires at seven time points over a 12-week period. Furthermore, participants provided morning and evening saliva samples at four time points to measure cortisol and secretory immunoglobulin A. Multilevel growth curve analyses revealed significant changes in growth trajectories of stress-related variables. For example, team and culture stressors and anger and dejection emotions significantly increased in the build up to competition, whilst challenge appraisals and excitement and happiness emotions significantly decreased over the same time-frame. A number of the stress related variables also predicted performance, well-being, and mental health. Specifically, organizational stressors and threat appraisals were found to negatively relate to performance, well-being, and mental health. Furthermore, whilst challenge appraisals and problem focused coping positively related to veterans' well-being, adopting emotion-focused and avoidance coping strategies negatively predicted well-being and mental health. Turning to emotions, experiencing anger, anxiety, and dejection negatively related to mental health, well-being and performance; whereas happiness and excitement displayed a positive relationship with these outcomes. The findings also highlighted that organizational stressor intensity was positively related to cortisol exposure at competition. To conclude, this study not only provides a novel, longitudinal, interdisciplinary insight into psychological and biological markers of the stress response as it relates to the performance, health, and well-being of military veterans, but also further contributes to theoretical understanding on the transactional nature of stress. Moreover, the findings significantly contribute to practice regarding how best to support this unique population in adaptively responding to and engaging with competitive sport.

A model for the evolution of prokaryotic DNA restriction-modification systems based upon the structural malleability of Type I restriction-modification enzymes.

Restriction Modification (RM) systems prevent the invasion of foreign genetic material into bacterial cells by restriction and protect the host's genetic material by methylation. They are therefore important in maintaining the integrity of the host genome. RM systems are currently classified into four types (I to IV) on the basis of differences in composition, target recognition, cofactors and the manner in which they cleave DNA. Comparing the structures of the different types, similarities can be observed suggesting an evolutionary link between these different types. This work describes the 'deconstruction' of a large Type I RM enzyme into forms structurally similar to smaller Type II RM enzymes in an effort to elucidate the pathway taken by Nature to form these different RM enzymes. Based upon the ability to engineer new enzymes from the Type I 'scaffold', an evolutionary pathway and the evolutionary pressures required to move along the pathway from Type I RM systems to Type II RM systems are proposed. Experiments to test the evolutionary model are discussed.

DNA target recognition domains in the Type I restriction and modification systems of Staphylococcus aureus.

Staphylococcus aureus displays a clonal population structure in which horizontal gene transfer between different lineages is extremely rare. This is due, in part, to the presence of a Type I DNA restriction-modification (RM) system given the generic name of Sau1, which maintains different patterns of methylation on specific target sequences on the genomes of different lineages. We have determined the target sequences recognized by the Sau1 Type I RM systems present in a wide range of the most prevalent S. aureus lineages and assigned the sequences recognized to particular target recognition domains within the RM enzymes. We used a range of biochemical assays on purified enzymes and single molecule real-time sequencing on genomic DNA to determine these target sequences and their patterns of methylation. Knowledge of the main target sequences for Sau1 will facilitate the synthesis of new vectors for transformation of the most prevalent lineages of this 'untransformable' bacterium.

The Type I Restriction Enzymes as Barriers to Horizontal Gene Transfer: Determination of the DNA Target Sequences Recognised by Livestock-Associated Methicillin-Resistant Staphylococcus aureus Clonal Complexes 133/ST771 and 398.

The Type I DNA restriction-modification (RM) systems of Staphylococcus aureus are known to act as a significant barrier to horizontal gene transfer between S. aureus strains belonging to different clonal complexes. The livestock-associated clonal complexes CC133/771 and CC398 contain Type I RM systems not found in human MRSA strains as yet but at some point transfer will occur. When this does take place, horizontal gene transfer of resistance will happen more easily between these strains. The reservoir of antibiotic resistance, virulence and host-adaptation genes present in livestock-associated MRSA will then potentially contribute to the development of newly evolving MRSA clones. The target sites recognised by the Type I RM systems of CC133/771 and CC398 were identified as CAG(N)5RTGA and ACC(N)5RTGA, respectively. Assuming that these enzymes recognise the methylation state of adenine, the underlined A and T bases indicate the unique positions of methylation. Target methylation points for enzymes from CC1 were also identified. The methylation points for CC1-1 are CCAY(N)5TTAA and those for CC1-2 are CCAY(N)6 TGT with the underline indicating the adenine methylation site thus clearing up the ambiguity noted previously (Roberts et al. 2013, Nucleic Acids Res 41:7472-7484) for the half sites containing two adenine bases.

The evolutionary pathway from a biologically inactive polypeptide sequence to a folded, active structural mimic of DNA.

The protein Ocr (overcome classical restriction) from bacteriophage T7 acts as a mimic of DNA and inhibits all Type I restriction/modification (RM) enzymes. Ocr is a homodimer of 116 amino acids and adopts an elongated structure that resembles the shape of a bent 24 bp DNA molecule. Each monomer includes 34 acidic residues and only six basic residues. We have delineated the mimicry of Ocr by focusing on the electrostatic contribution of its negatively charged amino acids using directed evolution of a synthetic form of Ocr, termed pocr, in which all of the 34 acidic residues were substituted for a neutral amino acid. In vivo analyses confirmed that pocr did not display any antirestriction activity. Here, we have subjected the gene encoding pocr to several rounds of directed evolution in which codons for the corresponding acidic residues found in Ocr were specifically re-introduced. An in vivo selection assay was used to detect antirestriction activity after each round of mutation. Our results demonstrate the variation in importance of the acidic residues in regions of Ocr corresponding to different parts of the DNA target which it is mimicking and for the avoidance of deleterious effects on the growth of the host.

ArdA proteins from different mobile genetic elements can bind to the EcoKI Type I DNA methyltransferase of E. coli K12.

Anti-restriction and anti-modification (anti-RM) is the ability to prevent cleavage by DNA restriction-modification (RM) systems of foreign DNA entering a new bacterial host. The evolutionary consequence of anti-RM is the enhanced dissemination of mobile genetic elements. Homologues of ArdA anti-RM proteins are encoded by genes present in many mobile genetic elements such as conjugative plasmids and transposons within bacterial genomes. The ArdA proteins cause anti-RM by mimicking the DNA structure bound by Type I RM enzymes. We have investigated ArdA proteins from the genomes of Enterococcus faecalis V583, Staphylococcus aureus Mu50 and Bacteroides fragilis NCTC 9343, and compared them to the ArdA protein expressed by the conjugative transposon Tn916. We find that despite having very different structural stability and secondary structure content, they can all bind to the EcoKI methyltransferase, a core component of the EcoKI Type I RM system. This finding indicates that the less structured ArdA proteins become fully folded upon binding. The ability of ArdA from diverse mobile elements to inhibit Type I RM systems from other bacteria suggests that they are an advantage for transfer not only between closely-related bacteria but also between more distantly related bacterial species.

DNA electrophoresis: historical and theoretical perspectives.

The technique of gel electrophoresis is now firmly established as a routine laboratory method for analyzing DNA. Here, we describe the development of the methodology as well as a brief explanation of how the technique works. There is a short introduction to pulsed-field agarose gel electrophoresis, which represents a critical advancement in the method that facilitates the analysis of very large fragments of DNA. Finally, theoretical considerations are included.

Mutations of the domain forming the dimeric interface of the ArdA protein affect dimerization and antimodification activity but not antirestriction activity.

ArdA antirestriction proteins are encoded by genes present in many conjugative plasmids and transposons within bacterial genomes. Antirestriction is the ability to prevent cleavage of foreign incoming DNA by restriction-modification (RM) systems. Antimodification, the ability to inhibit modification by the RM system, can also be observed with some antirestriction proteins. As these mobile genetic elements can transfer antibiotic resistance genes, the ArdA proteins assist their spread. The consequence of antirestriction is therefore the enhanced dissemination of mobile genetic elements. ArdA proteins cause antirestriction by mimicking the DNA structure bound by Type I RM enzymes. The crystal structure of ArdA showed it to be a dimeric protein with a highly elongated curved cylindrical shape [McMahon SA et al. (2009) Nucleic Acids Res 37, 4887-4897]. Each monomer has three domains covered with negatively charged side chains and a very small interface with the other monomer. We investigated the role of the domain forming the dimer interface for ArdA activity via site-directed mutagenesis. The antirestriction activity of ArdA was maintained when up to seven mutations per monomer were made or the interface was disrupted such that the protein could only exist as a monomer. The antimodification activity of ArdA was lost upon mutation of this domain. The ability of the monomeric form of ArdA to function in antirestriction suggests, first, that it can bind independently to the restriction subunit or the modification subunits of the RM enzyme, and second, that the many ArdA homologues with long amino acid extensions, present in sequence databases, may be active in antirestriction.

Impact of target site distribution for Type I restriction enzymes on the evolution of methicillin-resistant Staphylococcus aureus (MRSA) populations.

A limited number of Methicillin-resistant Staphylococcus aureus (MRSA) clones are responsible for MRSA infections worldwide, and those of different lineages carry unique Type I restriction-modification (RM) variants. We have identified the specific DNA sequence targets for the dominant MRSA lineages CC1, CC5, CC8 and ST239. We experimentally demonstrate that this RM system is sufficient to block horizontal gene transfer between clinically important MRSA, confirming the bioinformatic evidence that each lineage is evolving independently. Target sites are distributed randomly in S. aureus genomes, except in a set of large conjugative plasmids encoding resistance genes that show evidence of spreading between two successful MRSA lineages. This analysis of the identification and distribution of target sites explains evolutionary patterns in a pathogenic bacterium. We show that a lack of specific target sites enables plasmids to evade the Type I RM system thereby contributing to the evolution of increasingly resistant community and hospital MRSA.

Removal of a frameshift between the hsdM and hsdS genes of the EcoKI Type IA DNA restriction and modification system produces a new type of system and links the different families of Type I systems.

The EcoKI DNA methyltransferase is a trimeric protein comprised of two modification subunits (M) and one sequence specificity subunit (S). This enzyme forms the core of the EcoKI restriction/modification (RM) enzyme. The 3' end of the gene encoding the M subunit overlaps by 1 nt the start of the gene for the S subunit. Translation from the two different open reading frames is translationally coupled. Mutagenesis to remove the frameshift and fuse the two subunits together produces a functional RM enzyme in vivo with the same properties as the natural EcoKI system. The fusion protein can be purified and forms an active restriction enzyme upon addition of restriction subunits and of additional M subunit. The Type I RM systems are grouped into families, IA to IE, defined by complementation, hybridization and sequence similarity. The fusion protein forms an evolutionary intermediate form lying between the Type IA family of RM enzymes and the Type IB family of RM enzymes which have the frameshift located at a different part of the gene sequence.

Exploring the DNA mimicry of the Ocr protein of phage T7.

DNA mimic proteins have evolved to control DNA-binding proteins by competing with the target DNA for binding to the protein. The Ocr protein of bacteriophage T7 is the most studied DNA mimic and functions to block the DNA-binding groove of Type I DNA restriction/modification enzymes. This binding prevents the enzyme from cleaving invading phage DNA. Each 116 amino acid monomer of the Ocr dimer has an unusual amino acid composition with 34 negatively charged side chains but only 6 positively charged side chains. Extensive mutagenesis of the charges of Ocr revealed a regression of Ocr activity from wild-type activity to partial activity then to variants inactive in antirestriction but deleterious for cell viability and lastly to totally inactive variants with no deleterious effect on cell viability. Throughout the mutagenesis the Ocr mutant proteins retained their folding. Our results show that the extreme bias in charged amino acids is not necessary for antirestriction activity but that less charged variants can affect cell viability by leading to restriction proficient but modification deficient cell phenotypes.

Structure and operation of the DNA-translocating type I DNA restriction enzymes.

Type I DNA restriction/modification (RM) enzymes are molecular machines found in the majority of bacterial species. Their early discovery paved the way for the development of genetic engineering. They control (restrict) the influx of foreign DNA via horizontal gene transfer into the bacterium while maintaining sequence-specific methylation (modification) of host DNA. The endonuclease reaction of these enzymes on unmethylated DNA is preceded by bidirectional translocation of thousands of base pairs of DNA toward the enzyme. We present the structures of two type I RM enzymes, EcoKI and EcoR124I, derived using electron microscopy (EM), small-angle scattering (neutron and X-ray), and detailed molecular modeling. DNA binding triggers a large contraction of the open form of the enzyme to a compact form. The path followed by DNA through the complexes is revealed by using a DNA mimic anti-restriction protein. The structures reveal an evolutionary link between type I RM enzymes and type II RM enzymes.