A type VII secretion system of Streptococcus gallolyticus subsp. gallolyticus contributes to gut colonization and the development of colon tumors.

Streptococcus gallolyticus subspecies gallolyticus (Sgg) has a strong clinical association with colorectal cancer (CRC) and actively promotes the development of colon tumors. However, the molecular determinants involved in Sgg pathogenicity in the gut are unknown. Bacterial type VII secretion systems (T7SS) mediate pathogen interactions with their host and are important for virulence in pathogenic mycobacteria and Staphylococcus aureus. Through genome analysis, we identified a locus in Sgg strain TX20005 that encodes a putative type VII secretion system (designated as SggT7SST05). We showed that core genes within the SggT7SST05 locus are expressed in vitro and in the colon of mice. Western blot analysis showed that SggEsxA, a protein predicted to be a T7SS secretion substrate, is detected in the bacterial culture supernatant, indicating that this SggT7SST05 is functional. Deletion of SggT7SST05 (TX20005Δesx) resulted in impaired bacterial adherence to HT29 cells and abolished the ability of Sgg to stimulate HT29 cell proliferation. Analysis of bacterial culture supernatants suggest that SggT7SST05-secreted factors are responsible for the pro-proliferative activity of Sgg, whereas Sgg adherence to host cells requires both SggT7SST05-secreted and bacterial surface-associated factors. In a murine gut colonization model, TX20005Δesx showed significantly reduced colonization compared to the parent strain. Furthermore, in a mouse model of CRC, mice exposed to TX20005 had a significantly higher tumor burden compared to saline-treated mice, whereas those exposed to TX20005Δesx did not. Examination of the Sgg load in the colon in the CRC model suggests that SggT7SST05-mediated activities are directly involved in the promotion of colon tumors. Taken together, these results reveal SggT7SST05 as a previously unrecognized pathogenicity determinant for Sgg colonization of the colon and promotion of colon tumors.

Impact of Trauma Resuscitation Emergency Care Nurse Deployment in Trauma Activations in a Rural Trauma Center.

BACKGROUND: Although the role of a dedicated trauma nurse has been implemented in an urban setting, it has not been studied in the rural trauma setting. We instituted a trauma resuscitation emergency care (TREC) nurse role to respond to trauma activations at our rural trauma center. OBJECTIVE: This study aims to determine the impact of TREC nurse deployment on the timeliness of resuscitation interventions in trauma activations. METHODS: This pre- and postintervention study at a rural Level I trauma center compared the time to resuscitation interventions before (August 2018 to July 2019) and after (August 2019 to July 2020) deploying TREC nurses to trauma activations. RESULTS: A total of 2,593 participants were studied, of which 1,153 (44%) were in the pre-TREC group and 1,440 (56%) in the post-TREC group. After TREC deployment, the median (interquartile range [IQR]) emergency department times within the first hour decreased from 45 (31.23-53) to 35 (16-51) min ( p = .013). The median (IQR) time to the operating room within the first hour decreased from 46 (37-52) to 29 (12-46) min ( p = .001), and within the first 2 hr, decreased from 59 (43.8-86) to 48 (23-72) min ( p = .014). CONCLUSION: Our study found that TREC nurse deployment improved resuscitation intervention timeliness during the first 2 hr (early phase) of trauma activations.

Hemichordate genomes and deuterostome origins.

Acorn worms, also known as enteropneust (literally, 'gut-breathing') hemichordates, are marine invertebrates that share features with echinoderms and chordates. Together, these three phyla comprise the deuterostomes. Here we report the draft genome sequences of two acorn worms, Saccoglossus kowalevskii and Ptychodera flava. By comparing them with diverse bilaterian genomes, we identify shared traits that were probably inherited from the last common deuterostome ancestor, and then explore evolutionary trajectories leading from this ancestor to hemichordates, echinoderms and chordates. The hemichordate genomes exhibit extensive conserved synteny with amphioxus and other bilaterians, and deeply conserved non-coding sequences that are candidates for conserved gene-regulatory elements. Notably, hemichordates possess a deuterostome-specific genomic cluster of four ordered transcription factor genes, the expression of which is associated with the development of pharyngeal 'gill' slits, the foremost morphological innovation of early deuterostomes, and is probably central to their filter-feeding lifestyle. Comparative analysis reveals numerous deuterostome-specific gene novelties, including genes found in deuterostomes and marine microbes, but not other animals. The putative functions of these genes can be linked to physiological, metabolic and developmental specializations of the filter-feeding ancestor.

Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators.

The human X and Y chromosomes evolved from an ordinary pair of autosomes, but millions of years ago genetic decay ravaged the Y chromosome, and only three per cent of its ancestral genes survived. We reconstructed the evolution of the Y chromosome across eight mammals to identify biases in gene content and the selective pressures that preserved the surviving ancestral genes. Our findings indicate that survival was nonrandom, and in two cases, convergent across placental and marsupial mammals. We conclude that the gene content of the Y chromosome became specialized through selection to maintain the ancestral dosage of homologous X-Y gene pairs that function as broadly expressed regulators of transcription, translation and protein stability. We propose that beyond its roles in testis determination and spermatogenesis, the Y chromosome is essential for male viability, and has unappreciated roles in Turner's syndrome and in phenotypic differences between the sexes in health and disease.

Strict evolutionary conservation followed rapid gene loss on human and rhesus Y chromosomes.

The human X and Y chromosomes evolved from an ordinary pair of autosomes during the past 200-300 million years. The human MSY (male-specific region of Y chromosome) retains only three percent of the ancestral autosomes' genes owing to genetic decay. This evolutionary decay was driven by a series of five 'stratification' events. Each event suppressed X-Y crossing over within a chromosome segment or 'stratum', incorporated that segment into the MSY and subjected its genes to the erosive forces that attend the absence of crossing over. The last of these events occurred 30 million years ago, 5 million years before the human and Old World monkey lineages diverged. Although speculation abounds regarding ongoing decay and looming extinction of the human Y chromosome, remarkably little is known about how many MSY genes were lost in the human lineage in the 25 million years that have followed its separation from the Old World monkey lineage. To investigate this question, we sequenced the MSY of the rhesus macaque, an Old World monkey, and compared it to the human MSY. We discovered that during the last 25 million years MSY gene loss in the human lineage was limited to the youngest stratum (stratum 5), which comprises three percent of the human MSY. In the older strata, which collectively comprise the bulk of the human MSY, gene loss evidently ceased more than 25 million years ago. Likewise, the rhesus MSY has not lost any older genes (from strata 1-4) during the past 25 million years, despite its major structural differences to the human MSY. The rhesus MSY is simpler, with few amplified gene families or palindromes that might enable intrachromosomal recombination and repair. We present an empirical reconstruction of human MSY evolution in which each stratum transitioned from rapid, exponential loss of ancestral genes to strict conservation through purifying selection.

Sequence type 1 group B Streptococcus, an emerging cause of invasive disease in adults, evolves by small genetic changes.

The molecular mechanisms underlying pathogen emergence in humans is a critical but poorly understood area of microbiologic investigation. Serotype V group B Streptococcus (GBS) was first isolated from humans in 1975, and rates of invasive serotype V GBS disease significantly increased starting in the early 1990s. We found that 210 of 229 serotype V GBS strains (92%) isolated from the bloodstream of nonpregnant adults in the United States and Canada between 1992 and 2013 were multilocus sequence type (ST) 1. Elucidation of the complete genome of a 1992 ST-1 strain revealed that this strain had the highest homology with a GBS strain causing cow mastitis and that the 1992 ST-1 strain differed from serotype V strains isolated in the late 1970s by acquisition of cell surface proteins and antimicrobial resistance determinants. Whole-genome comparison of 202 invasive ST-1 strains detected significant recombination in only eight strains. The remaining 194 strains differed by an average of 97 SNPs. Phylogenetic analysis revealed a temporally dependent mode of genetic diversification consistent with the emergence in the 1990s of ST-1 GBS as major agents of human disease. Thirty-one loci were identified as being under positive selective pressure, and mutations at loci encoding polysaccharide capsule production proteins, regulators of pilus expression, and two-component gene regulatory systems were shown to affect the bacterial phenotype. These data reveal that phenotypic diversity among ST-1 GBS is mainly driven by small genetic changes rather than extensive recombination, thereby extending knowledge into how pathogens adapt to humans.

The first myriapod genome sequence reveals conservative arthropod gene content and genome organisation in the centipede Strigamia maritima.

Myriapods (e.g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific life history.

Similar outcomes between two-stage revisions for infection and aseptic hip revisions.

PURPOSE: Two-stage revision hip arthroplasty using an antibiotic-loaded spacer is the most widely performed procedure for infected hip arthroplasties. The clinical outcome of this type of surgery compared with aseptic joint revision with exchange of femoral and acetabular components is still controversial due to the relative lack of medium- to long-term follow-up. Therefore, we analysed clinical and radiological outcomes of septic two-stage revisions compared with aseptic hip revision surgeries. METHODS: In this retrospective study we assessed 82 consecutive patients who underwent two-stage revision for septic total hip (45 patients) or one-stage aseptic revision arthroplasty (37 patients). The average follow-up was 53 months for the aseptic group and 55 months for the septic group. For clinical evaluation, we used the Harris Hip Score (HHS) and the Merle d'Aubigné and Postel score. The postoperative pain level was determined with the visual analogue pain scale. RESULTS: The surgeries were performed 124 months (aseptic group) and 119 months (septic group) after primary total hip arthroplasty on average. The main indications for aseptic revision surgeries were aseptic loosening (96%), dislocation (2.2%), and periprosthetic fracture (2.2%). In the clinical outcome patients achieved 75.5 points in the aseptic group and 73.4 points in the septic group in the Harris Hip Score. The Merle d'Aubigné and Postel Score revealed 12.5 points for the aseptic group and 13.1 points for the septic group. Mean level of persisting pain was 0.8 (aseptic group) and 0.4 (septic group) on the visual analogue scale (VAS). Overall survival in the aseptic group was 85.6% at 9.8 years 82.7% at 10.1 years for the septic group, with a repeat revision rate of 8.1% and 6.7%, respectively. CONCLUSIONS: Performing aseptic acetabular and femoral revision hip arthroplasty showed equal clinical outcomes in relation to septic two-stage revision hip surgeries. Our results showed a tendency for better outcome in comparison with the information given in the literature for septic and nonseptic exchange arthroplasties, including a lower rate of re-revisions.

Outcome of isolated polyethylene tibial insert exchange after primary cemented total knee arthroplasty.

PURPOSE: Total knee arthroplasty using a modular design gives the possibility for an isolated exchange of the tibial polyethylene insert in patients with failed total knee arthroplasty. The success of this kind of surgery is still controversial. We analysed the clinical outcome after isolated tibial polyethylene insert exchange. METHODS: In this retrospective study we included 62 consecutive patients with an isolated tibial polyethylene insert exchange at our institution. The average follow-up was 35 months. For clinical evaluation we used the Oxford Knee score, the Knee Society score, the Turba score, and the Kujala score. The health-related quality of life was determined with the SF-36 score and the visual analogue pain scale. RESULTS: The operations were performed 73 months after primary total knee arthroplasty on average. The main reasons for isolated tibial polyethylene insert exchange were instability and wear. In the clinical outcome patients achieved 31.5 points in the Oxford Knee score, 120.5 points in the Knee Society score, 9.3 points in the Turba score, and 49.0 points in the Kujala score. Mean level of persisting pain was 2.2. In the SF-36 score patients achieved 36.3 points physical and 51.7 points mental. The overall survival for isolated tibial insert exchange revealed 72.2 % survival at 6.25 years follow-up with a repeat revision rate of 11 %. CONCLUSIONS: Isolated tibial polyethylene insert exchange revealed a good clinical outcome. There is a tendency for better results in comparison with the information given in literature for most of the parameters including a lower rate in repeat revision.

Outcome of a modular tapered uncemented titanium femoral stem in revision hip arthroplasty.

PURPOSE: Revision hip arthroplasty using a modular tapered design gives the possibility for customising the prostheses to the individual anatomy intra-operatively. The success of this kind of surgery is still controversial due to the relative lack of medium- to long-term follow-up. Therefore we analysed the clinical and radiological outcome of the modular MRP-TITAN stem with diaphyseal fixation in revision hip surgery. METHODS: In this retrospective study we included 136 consecutive patients with MRP-TITAN stem implanted during revision hip arthroplasty. The average follow-up was 55 months. For clinical evaluation we used the Harris Hip Score and the Merle d'Aubigné and Postel score. The health-related quality of life was determined with the visual analogue pain scale. RESULTS: The surgeries were performed 109 months after primary total hip arthroplasty on average. The main indications for the MRP-TITAN revision stem were aseptic loosening, infection, and periprosthetic fracture. In the clinical outcome, patients achieved 75.1 points in the Harris Hip Score and 14.4 points in the Merle d'Aubigné and Postel Score. Mean level of persisting pain was 0.7 (VAS). The overall survival of the MRP stem in revision hip arthroplasty revealed 85.6% survival at 9.75 years' follow-up with a repeat revision rate of 6.8%. CONCLUSIONS: Performing revision hip arthroplasty using the MRP-TITAN stem revealed a good clinical outcome. There is a tendency for better results in comparison with the information given in literature for cementless modular revision stems including a lower rate in re-revisions.

Finding the missing honey bee genes: lessons learned from a genome upgrade.

BACKGROUND: The first generation of genome sequence assemblies and annotations have had a significant impact upon our understanding of the biology of the sequenced species, the phylogenetic relationships among species, the study of populations within and across species, and have informed the biology of humans. As only a few Metazoan genomes are approaching finished quality (human, mouse, fly and worm), there is room for improvement of most genome assemblies. The honey bee (Apis mellifera) genome, published in 2006, was noted for its bimodal GC content distribution that affected the quality of the assembly in some regions and for fewer genes in the initial gene set (OGSv1.0) compared to what would be expected based on other sequenced insect genomes. RESULTS: Here, we report an improved honey bee genome assembly (Amel_4.5) with a new gene annotation set (OGSv3.2), and show that the honey bee genome contains a number of genes similar to that of other insect genomes, contrary to what was suggested in OGSv1.0. The new genome assembly is more contiguous and complete and the new gene set includes ~5000 more protein-coding genes, 50% more than previously reported. About 1/6 of the additional genes were due to improvements to the assembly, and the remaining were inferred based on new RNAseq and protein data. CONCLUSIONS: Lessons learned from this genome upgrade have important implications for future genome sequencing projects. Furthermore, the improvements significantly enhance genomic resources for the honey bee, a key model for social behavior and essential to global ecology through pollination.

The genome of the model beetle and pest Tribolium castaneum.

Tribolium castaneum is a member of the most species-rich eukaryotic order, a powerful model organism for the study of generalized insect development, and an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved the ability to interact with a diverse chemical environment, as shown by large expansions in odorant and gustatory receptors, as well as P450 and other detoxification enzymes. Development in Tribolium is more representative of other insects than is Drosophila, a fact reflected in gene content and function. For example, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, some being expressed in the growth zone crucial for axial elongation in short-germ development. Systemic RNA interference in T. castaneum functions differently from that in Caenorhabditis elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.

Can GPT-3.5 generate and code discharge summaries?

OBJECTIVES: The aim of this study was to investigate GPT-3.5 in generating and coding medical documents with International Classification of Diseases (ICD)-10 codes for data augmentation on low-resource labels. MATERIALS AND METHODS: Employing GPT-3.5 we generated and coded 9606 discharge summaries based on lists of ICD-10 code descriptions of patients with infrequent (or generation) codes within the MIMIC-IV dataset. Combined with the baseline training set, this formed an augmented training set. Neural coding models were trained on baseline and augmented data and evaluated on an MIMIC-IV test set. We report micro- and macro-F1 scores on the full codeset, generation codes, and their families. Weak Hierarchical Confusion Matrices determined within-family and outside-of-family coding errors in the latter codesets. The coding performance of GPT-3.5 was evaluated on prompt-guided self-generated data and real MIMIC-IV data. Clinicians evaluated the clinical acceptability of the generated documents. RESULTS: Data augmentation results in slightly lower overall model performance but improves performance for the generation candidate codes and their families, including 1 absent from the baseline training data. Augmented models display lower out-of-family error rates. GPT-3.5 identifies ICD-10 codes by their prompted descriptions but underperforms on real data. Evaluators highlight the correctness of generated concepts while suffering in variety, supporting information, and narrative. DISCUSSION AND CONCLUSION: While GPT-3.5 alone given our prompt setting is unsuitable for ICD-10 coding, it supports data augmentation for training neural models. Augmentation positively affects generation code families but mainly benefits codes with existing examples. Augmentation reduces out-of-family errors. Documents generated by GPT-3.5 state prompted concepts correctly but lack variety, and authenticity in narratives.

Functional Genomics of Gastrointestinal Escherichia coli Isolated from Patients with Cancer and Diarrhea.

We describe the epidemiology and clinical characteristics of 29 patients with cancer and diarrhea in whom Enteroaggregative Escherichia coli (EAEC) was initially identified by GI BioFire panel multiplex. E. coli strains were successfully isolated from fecal cultures in 14 of 29 patients. Six of the 14 strains were identified as EAEC and 8 belonged to other diverse E. coli groups of unknown pathogenesis. We investigated these strains by their adherence to human intestinal organoids, cytotoxic responses, antibiotic resistance profile, full sequencing of their genomes, and annotation of their functional virulome. Interestingly, we discovered novel and enhanced adherence and aggregative patterns for several diarrheagenic pathotypes that were not previously seen when co-cultured with immortalized cell lines. EAEC isolates displayed exceptional adherence and aggregation to human colonoids compared not only to diverse GI E. coli , but also compared to prototype strains of other diarrheagenic E. coli . Some of the diverse E. coli strains that could not be classified as a conventional pathotype also showed an enhanced aggregative and cytotoxic response. Notably, we found a high carriage rate of antibiotic resistance genes in both EAEC strains and diverse GI E. coli isolates and observed a positive correlation between adherence to colonoids and the number of metal acquisition genes carried in both EAEC and the diverse E. coli strains. This work indicates that E. coli from cancer patients constitute strains of remarkable pathotypic and genomic divergence, including strains of unknown disease etiology with unique virulomes. Future studies will allow for the opportunity to re-define E. coli pathotypes with greater diagnostic accuracy and into more clinically relevant groupings.

SMRT Sequencing of Paramecium Bursaria Chlorella Virus-1 Reveals Diverse Methylation Stability in Adenines Targeted by Restriction Modification Systems.

Chloroviruses (family Phycodnaviridae) infect eukaryotic, freshwater, unicellular green algae. A unique feature of these viruses is an abundance of DNA methyltransferases, with isolates dedicating up to 4.5% of their protein coding potential to these genes. This diversity highlights just one of the long-standing values of the chlorovirus model system; where group-wide epigenomic characterization might begin to elucidate the function(s) of DNA methylation in large dsDNA viruses. We characterized DNA modifications in the prototype chlorovirus, PBCV-1, using single-molecule real time (SMRT) sequencing (aka PacBio). Results were compared to total available sites predicted in silico based on DNA sequence alone. SMRT-software detected N6-methyl-adenine (m6A) at GATC and CATG recognition sites, motifs previously shown to be targeted by PBCV-1 DNA methyltransferases M.CviAI and M. CviAII, respectively. At the same time, PacBio analyses indicated that 10.9% of the PBCV-1 genome had large interpulse duration ratio (ipdRatio) values, the primary metric for DNA modification identification. These events represent 20.6x more sites than can be accounted for by all available adenines in GATC and CATG motifs, suggesting base or backbone modifications other than methylation might be present. To define methylation stability, we cross-compared methylation status of each GATC and CATG sequence in three biological replicates and found ∼81% of sites were stably methylated, while ∼2% consistently lack methylation. The remaining 17% of sites were stochastically methylated. When methylation status was analyzed for both strands of each target, we show that palindromes existed in completely non-methylated states, fully-methylated states, or hemi-methylated states, though GATC sites more often lack methylation than CATG sequences. Given that both sequences are targeted by not just methyltransferases, but by restriction endonucleases that are together encoded by PBCV-1 as virus-originating restriction modification (RM) systems, there is strong selective pressure to modify all target sites. The finding that most instances of non-methylation are associated with hemi-methylation is congruent with observations that hemi-methylated palindromes are resistant to cleavage by restriction endonucleases. However, sites where hemi-methylation is conserved might represent a unique regulatory function for PBCV-1. This study serves as a baseline for future investigation into the epigenomics of chloroviruses and their giant virus relatives.

Subtle genetic changes enhance virulence of methicillin resistant and sensitive Staphylococcus aureus.

BACKGROUND: Community acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) increasingly causes disease worldwide. USA300 has emerged as the predominant clone causing superficial and invasive infections in children and adults in the USA. Epidemiological studies suggest that USA300 is more virulent than other CA-MRSA. The genetic determinants that render virulence and dominance to USA300 remain unclear. RESULTS: We sequenced the genomes of two pediatric USA300 isolates: one CA-MRSA and one CA-methicillin susceptible (MSSA), isolated at Texas Children's Hospital in Houston. DNA sequencing was performed by Sanger dideoxy whole genome shotgun (WGS) and 454 Life Sciences pyrosequencing strategies. The sequence of the USA300 MRSA strain was rigorously annotated. In USA300-MRSA 2658 chromosomal open reading frames were predicted and 3.1 and 27 kilobase (kb) plasmids were identified. USA300-MSSA contained a 20 kb plasmid with some homology to the 27 kb plasmid found in USA300-MRSA. Two regions found in US300-MRSA were absent in USA300-MSSA. One of these carried the arginine deiminase operon that appears to have been acquired from S. epidermidis. The USA300 sequence was aligned with other sequenced S. aureus genomes and regions unique to USA300 MRSA were identified. CONCLUSION: USA300-MRSA is highly similar to other MRSA strains based on whole genome alignments and gene content, indicating that the differences in pathogenesis are due to subtle changes rather than to large-scale acquisition of virulence factor genes. The USA300 Houston isolate differs from another sequenced USA300 strain isolate, derived from a patient in San Francisco, in plasmid content and a number of sequence polymorphisms. Such differences will provide new insights into the evolution of pathogens.

Inflammation and Regeneration in the Dentin-pulp Complex: Net Gain or Net Loss?

The balance between the immune/inflammatory and regenerative responses in the diseased pulp is central to the clinical outcome, and this response is unique within the body because of its tissue site. Cariogenic bacteria invade the dentin and pulp tissues, triggering molecular and cellular events dependent on the disease stage. At the early onset, odontoblasts respond to bacterial components in an attempt to protect the tooth's hard and soft tissues and limit disease progression. However, as disease advances, the odontoblasts die, and cells central to the pulp core, including resident immune cells, pulpal fibroblasts, endothelial cells, and stem cells, respond to the bacterial challenge via their expression of a range of pattern recognition receptors that identify pathogen-associated molecular patterns. Subsequently, recruitment and activation occurs of a range of immune cell types, including neutrophils, macrophages, and T and B cells, which are attracted to the diseased site by cytokine/chemokine chemotactic gradients initially generated by resident pulpal cells. Although these cells aim to disinfect the tooth, their extravasation, migration, and antibacterial activity (eg, release of reactive oxygen species [ROS]) along with the bacterial toxins cause pulp damage and impede tissue regeneration processes. Recently, a novel bacterial killing mechanism termed neutrophil extracellular traps (NETs) has also been described that uses ROS signaling and results in cellular DNA extrusion. The NETs are decorated with antimicrobial peptides (AMPs), and their interaction with bacteria results in microbial entrapment and death. Recent data show that NETs can be stimulated by bacteria associated with endodontic infections, and they may be present in inflamed pulp tissue. Interestingly, some bacteria associated with pulpal infections express deoxyribonuclease enzymes, which may enable their evasion of NETs. Furthermore, although NETs aim to localize and kill invading bacteria using AMPs and histones, limiting the spread of the infection, data also indicate that NETs can exacerbate inflammation and their components are cytotoxic. This review considers the potential role of NETs within pulpal infections and how these structures may influence the pulp's vitality and regenerative responses.

Implementation of a Modified WHO Pediatric Procedural Sedation Safety Checklist and Its Impact on Risk Reduction.

BACKGROUND AND OBJECTIVES: Major adverse events (AEs) related to pediatric deep sedation occur at a low frequency but can be of high acuity. The high volume of deep sedations performed by 3 departments at our institution provided an opportunity to reduce variability and increase safety through implementation of a procedural sedation safety checklist. We hypothesized that implementation of a checklist would improve compliance of critical safety elements (CSEs) (primary outcome variable) and reduce the sedation-related AE rate (secondary outcome variable). METHODS: This process improvement project was divided into 5 phases: a retrospective analysis to assess variability in capture of CSE within 3 departments that perform deep sedation and the association between noncapture of CSE and AE occurrence (phase 1), design of the checklist and trial in simulation (phase 2), provider education (phase 3), implementation and interim analysis of checklist completion (phase 4), and final analysis of completion and impact on outcome (phase 5). RESULTS: We demonstrated interdepartmental variability in compliance with CSE completion prechecklist implementation, and we identified elements associated with AEs. Completion of provider education was 100% in all 3 departments. Final analysis showed a checklist completion rate of 75%, and its use significantly improved capture of several critical safety elements. Its use did not significantly reduce AEs (P = .105). CONCLUSIONS: This study demonstrates that the implementation of a sedation checklist improved process adherence and capture of critical safety elements; however, it failed to show a significant reduction in sedation-related AEs.

Complete Genome Sequence of Vibrio gazogenes ATCC 43942.

Vibrio gazogenes ATCC 43942 has the potential to synthesize a plethora of metabolites which are of clinical and agricultural significance in response to environmental triggers. The complete genomic sequence of Vibrio gazogenes ATCC 43942 is reported herein, contributing to the knowledge base of strains in the Vibrio genus.

Complete Genome Sequence of Streptococcus mitis Strain SVGS_061 Isolated from a Neutropenic Patient with Viridans Group Streptococcal Shock Syndrome.

Streptococcus mitisfrequently causes invasive infections in neutropenic cancer patients, with a subset of patients developing viridans group streptococcal (VGS) shock syndrome. We report here the first complete genome sequence ofS. mitisstrain SVGS_061, which caused VGS shock syndrome, to help elucidate the pathogenesis of severe VGS infection.