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A one‑year snapshot of pediatric regional anesthesia at a French Tertiary University Hospital.

BACKGROUND: Regional anesthesia (RA) is a major component of multimodal perioperative analgesia in children. Despite proven benefits, pediatric RA practice shows marked inter-institutional and international variability, with global practice patterns remaining largely underreported. This study aimed to characterize current RA practices in a pediatric anesthesia department of a French tertiary university hospital. METHODS: This retrospective observational study of prospectively collected data over one year included all children aged 0-18 years receiving at least one RA procedure. The data analyzed comprised demographics, surgical characteristics, RA techniques, guidance methods, and pharmacologic agents. Each RA procedure was considered an independent event, and patients were stratified into five age groups. RESULTS: Over the study period, 907 patients (6.0 [1.0; 12.0] years) underwent 1073 RA procedures: 894 peripheral blocks (83%) and 179 neuraxial blocks (17%). Peripheral blocks predominated in children >6 months (90%), while 59% of neuraxial RA were in infants <6 months. RA was conducted under general anesthesia in 90% of cases; awake spinal anesthesia in small infants comprised most neuraxial procedures. Ultrasound guidance was used in 98% of peripheral blocks, and pre-puncture scanning preceded 22% of neuraxial procedures. Clonidine was used as an adjuvant in >60% of cases. CONCLUSIONS: This single-center cohort reports one year of pediatric RA practice, characterized by high RA implementation rates. While ultrasound guidance was standard for peripheral blocks, pre-puncture scanning remains infrequently used for neuraxial techniques, highlighting a potential margin for improvement based on current practice. Results highlight selective neuraxial strategies in vulnerable infants and routine adjuvant use to optimize postoperative analgesia. Findings confirm RA feasibility in daily pediatric anesthesia and support multicenter studies evaluating inter-institutional variability and outcomes impact.

Humans↗

[Aesthetic snapshot: study about cosmetic surgical procedures and complications].

A questionnaire was addressed to 600 members of the French Society of Plastic Reconstructive and Aesthetic Surgery. Out of 19,000 interventions, thanks to the analysis of 112 answers, we were able to get a good picture of the activity in aesthetic surgery, showing the number and type of complications experienced during each intervention. Cosmetic surgical procedure represents 35% of global surgical activity of the French plastic surgeon. The most frequent interventions are liposuction (19%), breast augmentation (16%), eye-lid surgery (14%), abdominoplasty (12%), mammaplasty (10%), facelift (10%) and rhinoplasty (8%). The techniques for which we register more than 10% of problems are: abdominoplasty and mammaplasty. The techniques for which we register between 5% and 10% of problems are: rhinoplasty, facelift and breast augmentation. The techniques for which we register less than 5% of problems are: liposuction and eye-lid surgery. On average, the most frequent cosmetic surgical procedures give rise to 7% of complications.

Adult↗

Burns inflicted by self or by others--an 11 year snapshot.

INTRODUCTION: In the United Kingdom, the incidence of assault by burning and of self inflicted burns increased significantly over the last decade. This has major implications both for service providers and society as a whole. Our aim was to investigate the differences in patients' characteristics, management and outcome following a burn sustained by either an assault or self immolation. METHODS: Acute admissions to a tertiary Burn Centre were retrospectively reviewed over an 11 year period (1994-2005). Demographic data and information regarding the circumstances surrounding the incident, burn severity, treatment and outcomes of the patients were collected. RESULTS: Over an 11 year period, 1745 patients were admitted to the tertiary Burn Centre. Of this total, 41 patients (mean age 29 years+/-16) sustained burns following an assault, a further 86 patients (mean age of 37 years+/-12) had self inflicted burn injuries; males were preponderant in both groups. In this series, a history of alcohol or substance abuse was present in 25% of both cohorts, 63% of the patients with self inflicted injuries having a previously diagnosed psychiatric disorder. Petrol, accelerants and other flammable liquids were the main agents chosen to inflict injury in both the assault and self inflicted groups. The burn depth and surface area distribution was greater in the self inflicted group compared to those assaulted (29% versus 21%). A difference was also noted in the pattern of distribution of burns between the two groups, as well as between genders although this difference was not significant. Two-thirds (67.4%) of the self immolated patients and 56% of the assaulted group required surgery. The length of hospital stay was similar for both groups, averaging 20 days. The crude mortality for the self inflicted group was 29%, whereas in the assaulted patients, the overall mortality was 4.9%. CONCLUSION: Although the incidence of burns caused either by assault or attempted suicide is low, the affected patients require a multidisciplinary approach. Their management requires significant medical, psychological occupational and social support. Increased awareness and education of those vulnerable individuals maybe of benefit to help prevent self inflicted injuries by burning.

Adolescent↗

Atomic snapshots of an RNA packaging motor reveal conformational changes linking ATP hydrolysis to RNA translocation.

Many viruses package their genome into preformed capsids using packaging motors powered by the hydrolysis of ATP. The hexameric ATPase P4 of dsRNA bacteriophage phi12, located at the vertices of the icosahedral capsid, is such a packaging motor. We have captured crystallographic structures of P4 for all the key points along the catalytic pathway, including apo, substrate analog bound, and product bound. Substrate and product binding have been observed as both binary complexes and ternary complexes with divalent cations. These structures reveal large movements of the putative RNA binding loop, which are coupled with nucleotide binding and hydrolysis, indicating how ATP hydrolysis drives RNA translocation through cooperative conformational changes. Two distinct conformations of bound nucleotide triphosphate suggest how hydrolysis is activated by RNA binding. This provides a model for chemomechanical coupling for a prototype of the large family of hexameric helicases and oligonucleotide translocating enzymes.

Adenosine Triphosphatases↗

Should activin betaC be more than a fading snapshot in the activin/TGFbeta family album?

The activin growth factors consist of dimeric proteins made up of activin beta subunits and have been shown to be essential regulators of diverse systems in physiology. Four subunits are known to be expressed in mammalian cells: betaA, betaB, betaC, and betaE. Surprisingly, deletion of activin betaC and betaE subunits in vivo does not affect embryonic development or adult physiology which has led to the activin betaC and betaE subunits being regarded as non-essential and unimportant. The steady accumulation of circumstantial evidence to the contrary has led this lab to reassess the role of the activin betaC subunit. Activin betaC protein is expressed more widely than indicated by mRNA localisation. Experiments overexpressing activin betaC subunit or adding exogenous Activin C in vitro are contradictory but suggest roles for activin betaC in regulating Activin A action in apoptosis and homeostasis. Sequestration of betaA subunits by dimerisation with betaC subunits to form Activin AC represents an intracellular regulator of Activin A bioactivity. Activins play a pivotal role in normal physiology and carcinogenesis, so any molecule, such as the activin betaC subunit, that can affect activin action is potentially significant. Advancing our understanding of the physiological role of the activin betaC subunit requires new tools and reagents. Direct detection of the Activin AC dimer will be essential and will necessitate the purification of heteromeric Activin AC protein. In addition, there is a need for the development of an in vivo model of activin betaC subunit overexpression. With development of these tools, research into activin action in development and physiology can expand to include the less well understood members of the activin family such as activin betaC.

Activins↗

A proteomic snapshot of the human heat shock protein 90 interactome.

Heat shock protein 90 (Hsp90) is a molecular chaperone which modulates several signalling pathways within a cell. By applying co-immunoprecipitation with endogeneous Hsp90, we were able to identify 39 novel protein interaction partners of this chaperone in human embryonic kidney cells (HEK293). Interestingly, levels of DNA-activated protein kinase catalytic subunit, an Hsp90 interaction partner found in this study, were found to be sensitive to Hsp90 inhibitor treatment only in HeLa cells but not in HEK293 cells referring to the tumorgenicity of this chaperone.

DNA-Activated Protein Kinase↗

Snapshots and snippets: general practitioners' reflections on professional space.

The paper presents the results of a mixed methods study of British general practitioners' (GPs) reflections on professional space in terms of practice and self-identity. Inter-textual content analysis of 12 biographic and photographic datasets revealed four themes: workspace, re-appropriated space, life space and sacred space. GPs are ambivalent about their working environments, spending time and energy creating 'best fit' spaces, until lack of function becomes an habituated part of daily routine. Whilst some appear helpless in the face of change, others are making their presence felt through embodied, personalized or authorial spaces.

Attitude of Health Personnel↗

User interpretations of future information system use: a snapshot with technological frames.

Integrated information systems for managing patient data transform the nature of hospital work to the extent that the work practices, the responsibilities, even the professional identities are likely to undergo major changes. Therefore, during the organizational implementation of the IS, attention should be paid to the future users and how they understand and see what is going on. Here the focus is on these interpretation processes, analyzed as technological frames. That is, people develop different assumptions, expectations and knowledge concerning new technology. During this sense-making process they build their idea of that technology, its technological frame. We analyzed the pre-implementation frames that could be discerned in 24 interviews of hospital personnel. Main influences on the frames in this case were the work role in the organization, knowledge about the new system, and attitudes toward the old systems. The social context appeared to have a significant influence in the users' interpretation processes and the frames seemed to be congruent within one group. So far, the incongruence between groups appeared to have caused no major problems for the implementation.

Attitude to Computers↗

Snapshots.

Explore the source record for details and available documents.

Cataract Extraction↗

The reaction mechanism of phospholipase D from Streptomyces sp. strain PMF. Snapshots along the reaction pathway reveal a pentacoordinate reaction intermediate and an unexpected final product.

Almost all enzyme-catalysed phosphohydrolytic or phosphoryl transfer reactions proceed through a five-coordinated phosphorus transition state. This is also true for the phospholipase D superfamily of enzymes, where the active site usually is made up of two identical sequence repeats of an HKD motif, positioned around an approximate 2-fold axis, where the histidine and lysine residues are essential for catalysis. An almost complete reaction pathway has been elucidated by a series of experiments where crystals of phospholipase D from Streptomyces sp. strain PMF (PLD(PMF)) were soaked for different times with (i) a soluble poor, short-chained phospholipid substrate and (ii) with a product. The various crystal structures were determined to a resolution of 1.35-1.75 A for the different time-steps. Both substrate and product-structures were determined in order to identify the different reaction states and to examine if the reaction actually terminated on formation of phosphatidic acid (the true product of phospholipase D action) or could proceed even further. The results presented support the theory that the phospholipase D superfamily shares a common reaction mechanism, although different family members have very different substrate preferences and perform different catalytic reactions. Results also show that the reaction proceeds via a phosphohistidine intermediate and provide unambiguous identification of a catalytic water molecule, ideally positioned for apical attack on the phosphorus and consistent with an associative in-line phosphoryl transfer reaction. In one of the experiments an apparent five-coordinate phosphorus transition state is observed.

Catalysis↗

A snapshot of viral evolution from genome analysis of the tectiviridae family.

The origin, evolution and relationships of viruses are all fascinating topics. Current thinking in these areas is strongly influenced by the tailed double-stranded (ds) DNA bacteriophages. These viruses have mosaic genomes produced by genetic exchange and so new natural isolates are quite dissimilar to each other, and to laboratory strains. Consequently, they are not amenable to study by current tools for phylogenetic analysis. Less attention has been paid to the Tectiviridae family, which embraces icosahedral dsDNA bacterial viruses with an internal lipid membrane. It includes viruses, such as PRD1, that infect Gram-negative bacteria, as well as viruses like Bam35 with Gram-positive hosts. Although PRD1 and Bam35 have closely related virion morphology and genome organization, they have no detectable sequence similarity. There is strong evidence that the Bam35 coat protein has the "double-barrel trimer" arrangement of PRD1 that was first observed in adenovirus and is predicted to occur in other viruses with large facets. It is very likely that a single ancestral virus gave rise to this very large group of viruses. The unprecedented degree of conservation recently observed for two Bam35-like tectiviruses made it important to investigate those infecting Gram-negative bacteria. The DNA sequences for six PRD1-like isolates (PRD1, PR3, PR4, PR5, L17, PR772) have now been determined. Remarkably, these bacteriophages, isolated at distinctly different dates and global locations, have almost identical genomes. The discovery of almost invariant genomes for the two main Tectiviridae groups contrasts sharply with the situation in the tailed dsDNA bacteriophages. Notably, it permits a sequence analysis of the isolates revealing that the tectiviral proteins can be dissected into a slowly evolving group descended from the ancestor, the viral self, and a more rapidly changing group reflecting interactions with the host.

Amino Acid Sequence↗

Structural snapshots of beta-1,4-galactosyltransferase-I along the kinetic pathway.

During the catalytic cycle of beta1,4-galactosyltransferase-1 (Gal-T1), upon the binding of Mn(2+) followed by UDP-Gal, two flexible loops, a long and a short loop, change their conformation from open to closed. We have determined the crystal structures of a human M340H-Gal-T1 mutant in the open conformation (apo-enzyme), its Mn(2+) and Mn(2+)-UDP-Gal-bound complexes, and of a pentenary complex of bovine Gal-T1-Mn(2+)-UDP-GalNAc-Glc-alpha-lactalbumin. These studies show that during the conformational changes in Gal-T1, the coordination of Mn(2+) undergoes significant changes. It loses a coordination bond with a water molecule bound in the open conformation of Gal-T1 while forming a new coordination bond with another water molecule in the closed conformation, creating an active ground-state structure that facilitates enzyme catalysis. In the crystal structure of the pentenary complex, the N-acetylglucosamine (GlcNAc) moiety is found cleaved from UDP-GalNAc and is placed 2.7A away from the O4 oxygen atom of the acceptor Glc molecule, yet to form the product. The anomeric C1 atom of the cleaved GalNAc moiety has only two covalent bonds with its non-hydrogen atoms (O5 and C2 atoms), similar to either an oxocarbenium ion or N-acetylgalactal form, which are crystallographically indistinguishable at the present resolution. The structure also shows that the newly formed, metal-coordinating water molecule forms a hydrogen bond with the beta-phosphate group of the cleaved UDP moiety. This hydrogen bond formation results in the rotation of the beta-phosphate group of UDP away from the cleaved GalNAc moiety, thereby preventing the re-formation of the UDP-sugar during catalysis. Therefore, this water molecule plays an important role during catalysis in ensuring that the catalytic reaction proceeds in a forward direction.

Acetylglucosamine↗

Crystal structure of archaeal recombinase RADA: a snapshot of its extended conformation.

Homologous recombination of DNA plays crucial roles in repairing severe DNA damage and in generating genetic diversity. The process is facilitated by a superfamily of recombinases: bacterial RecA, archaeal RadA and Rad51, and eukaryal Rad51 and DMC1. These recombinases share a common ATP-dependent filamentous quaternary structure for binding DNA and facilitating strand exchange. We have determined the crystal structure of Methanococcus voltae RadA in complex with the ATP analog AMP-PNP at 2.0 A resolution. The RadA filament is a 106.7 A pitch helix with six subunits per turn. The DNA binding loops L1 and L2 are located in close proximity to the filament axis. The ATP analog is buried between two RadA subunits, a feature similar to that of the active filament of Escherichia coli RecA revealed by electron microscopy. The disposition of the N-terminal domain suggests a role of the Helix-hairpin-Helix motif in binding double-stranded DNA.

Adenosine Triphosphatases↗

Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases.

Modulation of the acetylation state of histones plays a pivotal role in the regulation of gene expression. Histone deacetylases (HDACs) catalyze the removal of acetyl groups from lysines near the N termini of histones. This reaction promotes the condensation of chromatin, leading to repression of transcription. HDAC deregulation has been linked to several types of cancer, suggesting a potential use for HDAC inhibitors in oncology. Here we describe the first crystal structures of a human HDAC: the structures of human HDAC8 complexed with four structurally diverse hydroxamate inhibitors. This work sheds light on the catalytic mechanism of the HDACs, and on differences in substrate specificity across the HDAC family. The structure also suggests how phosphorylation of Ser39 affects HDAC8 activity.

Amino Acid Sequence↗

Crystallographic snapshots of Aspergillus fumigatus phytase, revealing its enzymatic dynamics.

Understanding of the atomic movements involved in an enzymatic reaction needs structural information on the active and inactive native enzyme molecules and on the enzyme-substrate, enzyme-intermediate, and enzyme-product(s) complexes. By using the X-ray crystallographic method, four crystal structures of Aspergillus fumigatus phytase were obtained at resolution higher than 1.7 A. The pH-dependent catalytic activity of A. fumigatus phytase was linked to three water molecules that may prevent the substrate from binding and thus block nucleophilic attack of the catalytic imidazole nitrogen. Comparison of various structures also identified the water molecule that attacks the phosphamide bond during the hydrolysis process, and established the hydrolysis pathway of the intermediate. Additionally, two reaction product phosphates were observed at the active site, suggesting a possible product release pathway after hydrolysis of the intermediate. These results can help explain the catalytic mechanism throughout the whole acid phosphatase family, as all key residues are conserved.

6-Phytase↗