Gut microbes regroup to aid defence after infection.

Resident gut microbes can help to block infection, but the mechanisms involved are not fully understood. It has now been found that changes in the microbial community after infection boost the level of a molecule that combats harmful bacteria.

For the Love of the Game: Calculating the Premium Associated with Academic Surgical Practice.

OBJECTIVE: We sought to determine the premium associated with a career in academic surgery, as measured by compensation normalized to the work relative value unit (wRVU). BACKGROUND: An academic surgical career, embodying innovation and mentorship, offers intrinsic rewards, but is not well monetized. We know compensation for academic surgeons is less than their non-academic counterparts, but the value of clinical effort, as normalized to the wRVU, between academic and non-academic surgeons has not been well characterized. Thus, we analyzed the variations in the valuation of academic and non-academic surgical work from 2010 to 2022. METHODS: We utilized Medical Group Management Association Provider Compensation data from 2010, 2014, 2018, and 2022 to compare academic and non-academic surgeons. We analyzed raw total cash compensation (TCC), wRVU, TCC per wRVU (TCC/wRVU), and TCC to collections (TCCtColl). We calculated collections per wRVU (Coll/wRVU). We adjusted TCC and TCCtColl for inflation using the Consumer Price Index. Linear modeling for trend analysis was performed. RESULTS: Compared to non-academic, academic surgeons had lower TCC (2010: $500,415.0±23,666 vs. $631,515.5±23,948.2, -21%; 2022: $564,789.8±23,993.9 vs. $628,247.4±15,753.2, -10%), despite higher wRVUs (2022: 9,109.4±474.9 vs. 8,062.7±252.7) and higher Coll/wRVU (2022: 76.68±8.15 vs. 71.80±6.10). Trend analysis indicated TCC will converge in 2038 at an estimated $660,931. CONCLUSIONS: In 2022, academic surgeons had more clinical activity and superior organizational revenue capture, despite less total and normalized clinical compensation. Based on TCC/wRVUs, academia charges a premium of 16% over non-academic surgery. However, trend analysis suggests that TCC will converge within the next twenty years.

Survival Tree Provides Individualized Estimates of Survival After Lung Transplant.

INTRODUCTION: Identifying contributors to lung transplant survival is vital in mitigating mortality. To enhance individualized mortality estimation and determine variable interaction, we employed a survival tree algorithm utilizing recipient and donor data. METHODS: United Network Organ Sharing data (2000-2021) were queried for single and double lung transplants in adult patients. Graft survival time <7 d was excluded. Sixty preoperative and immediate postoperative factors were evaluated with stepwise logistic regression on mortality; final model variables were included in survival tree modeling. Data were split into training and testing sets and additionally validated with 10-fold cross validation. Survival tree pruning and model selection was based on Akaike information criteria and log-likelihood values. Estimated survival probabilities and log-rank pairwise comparisons between subgroups were calculated. RESULTS: A total of 27,296 lung transplant patients (8175 single; 19,121 double lung) were included. Stepwise logistic regression yielded 47 significant variables associated with mortality. Survival tree modeling returned six significant factors: recipient age, length of stay from transplant to discharge, recipient ventilator duration post-transplant, double lung transplant, recipient reintubation post-transplant, and donor cytomegalovirus status. Eight subgroups consisting of combinations of these factors were identified with distinct Kaplan-Meier survival curves. CONCLUSIONS: Survival trees provide the ability to understand the effects and interactions of covariates on survival after lung transplantation. Individualized survival probability with this technique found that preoperative and postoperative factors influence survival after lung transplantation. Thus, preoperative patient counseling should acknowledge a degree of uncertainty given the influence of postoperative factors.

Reclaiming Agency in Care Decisions and Barriers From the Perspectives of Individuals With Acquired Brain Injury and Their Family Members.

BACKGROUND: The ability to self-advocate or have a say in one's care is integral to personalised care after acquired brain injury (ABI). This study aimed to understand what constitutes self-advocacy and associated barriers and facilitators throughout hospital transitions and into the community. METHOD: Qualitative methodology was employed with semistructured interviews conducted with 12 people with ABI and 13 family members. Interviews were conducted at predischarge (in-person or via telephone) and 4 months postdischarge (via telephone) from the brain injury rehabilitation unit of a tertiary hospital. Data were thematically analysed using a hybrid deductive-inductive approach. RESULTS: Self-advocacy reflects the process of reclaiming agency or people's efforts to exert influence over care decisions after ABI. Agency varies along a continuum, often beginning with impaired processing of the self or environment (loss of agency) before individuals start to understand and question their care (emerging agency) and ultimately plan and direct their ongoing and future care (striving for agency). This process may vary across individuals and contexts. Barriers to self-advocacy for individuals with ABI include neurocognitive deficits that limit capacity and desire for control over decisions, unfamiliar and highly structured environments and lack of family support. Facilitators include neurocognitive recovery, growing desire to self-advocate and scaffolded support from family and clinicians. CONCLUSION: Self-advocacy after ABI entails a process of reclaiming agency whereby individuals seek to understand, question and direct their ongoing care. This is facilitated by neurocognitive recovery, growing capacity and desire and scaffolded supports. Research evaluating approaches for embedding self-advocacy skills early in brain injury rehabilitation is recommended. PATIENT OR PUBLIC CONTRIBUTION: Two caregivers with lived experience of supporting a family member with ABI were involved in the design and conduct of this study and contributed to and provided feedback on the manuscript.

A pathogen-specific sRNA influences enterohemorrhagic Escherichia coli fitness and virulence in part by direct interaction with the transcript encoding the ethanolamine utilization regulatory factor EutR.

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 relies on sRNAs to coordinate expression of metabolic and virulence factors to colonize the host. Here, we focus on the sRNA, named MavR (metabolism and virulence regulator), that is conserved among pathogenic Enterobacteriaceae. MavR is constitutively expressed under in vitro conditions that promote EHEC virulence gene expression. Using MS2-affinity purification coupled with RNA sequencing, the eutR transcript was identified as a putative target of MavR. EutR is a transcription factor that promotes expression of genes required for ethanolamine metabolism as well as virulence factors important for host colonization. MavR binds to the eutR coding sequence to protect the eutR transcript from RNase E-mediated degradation. Ultimately, MavR promotes EutR expression and in turn ethanolamine utilization and ethanolamine-dependent growth. RNAseq analyses revealed that MavR also affected expression of genes important for other metabolic pathways, motility, oxidative stress and attaching and effacing lesion formation, which contribute to EHEC colonization of the gastrointestinal tract. In support of the idea that MavR-dependent gene expression affects fitness during infection, deletion of mavR resulted in significant (∼10- to 100-fold) attenuation in colonization of the mammalian intestine. Altogether, these studies reveal an important, extensive, and robust phenotype for a bacterial sRNA in host-pathogen interactions.

Refining a capability development framework for building successful consumer and staff partnerships in healthcare quality improvement: A coproduced eDelphi study.

BACKGROUND: The capability of consumers and staff may be critical for authentic and effective partnerships in healthcare quality improvement (QI). Capability frameworks describe core knowledge, skills, values, attitudes, and behaviours and guide learning and development at individual and organizational levels. OBJECTIVE: To refine a capability framework for successful partnerships in healthcare QI which was coproduced from a scoping review. DESIGN: A two-round eDelphi design was used. The International Expert Panel rated the importance of framework items in supporting successful QI partnerships, and suggested improvements. They also rated implementation options and commented on the influence of context. PARTICIPANTS: Seven Research Advisory Group members were recruited to support the research team. The eDelphi panel included 53 people, with 44 (83%) and 42 (77. 8%) participating in rounds 1 and 2, respectively. They were from eight countries and had diverse backgrounds. RESULTS: The Research Advisory Group and panel endorsed the framework and summary diagram as valuable resources to support the growth of authentic and meaningful partnerships in QI across healthcare contexts, conditions, and countries. A consensus was established on content and structure. Substantial rewording included a stronger emphasis on growth, trust, respect, inclusivity, diversity, and challenging the status quo. The final capability development framework included three domains: Personal Attributes, Relationships and Communication, and Principles and Practices. The Equalizing Decision Making, Power, and Leadership capability was foundational and positioned across all domains. Ten capabilities with twenty-seven capability descriptions were also included. The Principles and Practices domain, Equalizing Decision Making, Power, and Leadership capability, and almost half (44.4%) of the capability descriptions were rated as more important for staff than consumers (p < .01). However, only the QI processes and practices capability description did not meet the inclusion threshold for consumers. Thus, the framework was applicable to staff and consumers. CONCLUSION: The refined capability development framework provides direction for planning and provision of learning and development regarding QI partnerships. PATIENT OR PUBLIC CONTRIBUTION: Two consumers were full members of the research team and are coauthors. A Research Advisory Group, inclusive of consumers, guided study execution and translation planning. More than half of the panel were consumers.

Longitudinal effects of time since injury and age at injury on outcomes of people with spinal cord injury in Queensland, Australia.

STUDY DESIGN: Longitudinal cohort study. OBJECTIVES: To investigate the longitudinal effects of time since injury and age at injury on outcomes of quality of life, physical function, secondary conditions and participation, in people with traumatic spinal cord injury (SCI). SETTING: Community resident people with spinal cord injury in Queensland, Australia. METHODS: A baseline sample of 270 people with SCI was recruited. Telephone surveys on measures of quality of life (WHOQOL-Bref), secondary conditions (Secondary Conditions Surveillance Instrument, subset), physical functioning (Functional Independence Measure motor subscale) and participation (Community Integration Measure) were conducted each year between 2004 and 2008, and again in 2018. Random-effect within-between models were used to determine the effect of time since injury and age at injury on each outcome variable. Inverse probability-of-censoring weights were used to correct for selection bias. RESULTS: There was an effect of time since injury on secondary conditions, with a one-year change associated with 9% higher odds of having worse Secondary Conditions Surveillance Instrument scores (odds ratio = 1.09, 95% confidence interval = 1.02, 1.17; p = 0.006). We did not find any evidence of a time since injury effect on quality of life, physical function, or participation. Similarly, we did not find any evidence of an age at injury effect on any outcome variable. CONCLUSIONS: Secondary conditions may increase with longer time since injury among people with SCI, suggesting appropriate formal and informal supports are required to minimise the impact of these emerging health problems as individuals age.

The sRNA DicF integrates oxygen sensing to enhance enterohemorrhagic Escherichia coli virulence via distinctive RNA control mechanisms.

To establish infection, enteric pathogens integrate environmental cues to navigate the gastrointestinal tract (GIT) and precisely control expression of virulence determinants. During passage through the GIT, pathogens encounter relatively high levels of oxygen in the small intestine before transit to the oxygen-limited environment of the colon. However, how bacterial pathogens sense oxygen availability and coordinate expression of virulence traits is not resolved. Here, we demonstrate that enterohemorrhagic Escherichia coli O157:H7 (EHEC) regulates virulence via the oxygen-responsive small RNA DicF. Under oxygen-limited conditions, DicF enhances global expression of the EHEC type three secretion system, which is a key virulence factor required for host colonization, through the transcriptional activator PchA. Mechanistically, the pchA coding sequence (CDS) base pairs with the 5' untranslated region of the mRNA to sequester the ribosome binding site (RBS) and inhibit translation. DicF disrupts pchA cis-interactions by binding to the pchA CDS, thereby unmasking the pchA RBS and promoting PchA expression. These findings uncover a feed-forward regulatory pathway that involves distinctive mechanisms of RNA-based regulation and that provides spatiotemporal control of EHEC virulence.

Feasibility and acceptability of a telehealth platform for delivering the Making Sense of Brain Tumour programme: A mixed-methods pilot study.

ABSTRACTGlioma is a common type of brain tumour that is associated with neurocognitive and psychosocial impairments. This study primarily aimed to investigate the feasibility and acceptability of a videoconferencing format of the Making Sense of Brain Tumour (Tele-MAST) programme. Recruited from a multidisciplinary brain tumour clinic, participants were randomly allocated to the 10-session Tele-MAST programme or standard care, with the latter group offered Tele-MAST after re-assessment. Semi-structured interviews explored participants' experiences of receiving psychological support via the videoconferencing platform. Measures of mental health and quality of life were administered at pre-intervention and post-intervention assessments. Of the 35 patients deemed eligible for the study, 14 (40% accrual) with high grade (71%) or low grade (29%) glioma participated. They were randomized to the Tele-MAST condition (n = 8) or standard care/waitlist (n = 6). Ten individuals commenced the Tele-MAST programme, of whom eight completed ≥8 sessions. The major themes that depicted their experience of the Tele-MAST programme were ease of access and benefits of remote delivery, tailored support and immediacy, and sense of connection versus disconnection. Most participants (63%) demonstrated clinically reliable improvement at post-intervention. These preliminary findings support the feasibility and acceptability of remote delivery of psychological support and highlight the need for a larger-scale evaluation of the Tele-MAST programme.

Different in so many ways: Exploring consumer, health service staff, and academic partnerships in a research advisory group through rapid ethnography.

INTRODUCTION: Consumer and community involvement (CCI) encompasses the range of consumer engagement activities across the research cycle. Research advisory groups (RAGs) are a common method of CCI that may empower the consumer voice in research. However, there is limited evaluation of RAGs to guide occupational therapists considering this as a CCI strategy in research. The aim of this study was to explore the processes and outcomes of a RAG partnership for an eDelphi study. METHODS: Rapid ethnography enabled a rich, thick description of the RAG through triangulation of field notes, a monthly research team log, focus groups, and an individual interview. Data were analysed using reflexive thematic analysis. Recruitment targeted consumers, health service staff, and academics with experience in CCI to enhance the diversity of perspectives guiding the eDelphi study. The RAG met four times over 4 months. FINDINGS: Seven diverse RAG members were recruited resulting in a RAG of 12 members, including the research team that included two consumers. Reflexive thematic analysis resulted in an overarching theme: Different in so many ways, which reinforced that authentic CCI in research continues to be rare even for stakeholders with experience in CCI. There were four subthemes: Set up for success, Authentic and capable facilitation, Structures and strategies for genuine partnerships, and A ripple effect of benefits. Findings added to the limited research regarding RAGs and highlighted that a short-term RAG with 12 diverse stakeholders was an effective strategy to foster mutually beneficial and meaningful collaboration. Partnering with two consumer co-researchers in RAG planning, implementation, and evaluation was central to success. CONCLUSION: Findings demonstrated that with careful co-planning and recruitment, capable facilitation with support of a committed research team (inclusive of consumers), and empowering meeting processes and structures, a short-term RAG resulted in many benefits to participants and enhanced research outcomes.

Consumer engagement in occupational therapy health-related research: A scoping review of the Australian Occupational Therapy Journal and a call to action.

INTRODUCTION: Consumer engagement in research is becoming an ethical, political, and moral imperative. The aim of this scoping review was to provide a snapshot of the current status of the emerging area of consumer engagement in occupational therapy health-related research, as published in the Australian Occupational Therapy Journal. METHODS: A scoping review was conducted of all health-related original research published in the Australian Occupational Therapy Journal for 5½ years, plus Early View, as at June 2019. Eligible papers were examined for consumer engagement content which included any active choice or control by consumers, beyond being a research participant. A recognised six stage methodology was used with quantitative and qualitative data analysed. Two consumers collaborated in interpreting the data including finalising themes, leading theme naming, developing key discussion points, and producing recommendations. RESULTS: Of the 123 eligible papers, 48 (39.02%) included consumer engagement. However, only two incorporated consumer engagement across all research phases-preparation, execution and translation. A total of 103 consumer engagement activities were charted and categorised across all papers. There were limited instances of consumer collaboration (14/103, 13.59%) or consumer-led research processes (15/103, 14.56%) reported. Four themes emerged: Parity in research partnerships; It's important to know the Who, What, When, How and So What of consumer involvement; Consumer engagement must be a two-way process-not a dead end street; and Meeting the challenge-being diverse and inclusive. CONCLUSION: Comprehensive consumer-researcher partnerships may not be common-place in health-related occupational therapy research in the Australian Occupational Therapy Journal. This paper is a call to action. Occupational therapists must embrace consumer research partnerships as a demonstration of the key philosophies of enabling and empowering consumers and communities. Collaboration with two consumers in finalising data analysis, results interpretation and reporting added a diverse and valuable perspective.

Effect of Lipidation on the Localization and Activity of a Lysozyme Inhibitor in Neisseria gonorrhoeae.

The Gram-negative pathogen Neisseria gonorrhoeae (gonococcus [Gc]) colonizes lysozyme-rich mucosal surfaces. Lysozyme hydrolyzes peptidoglycan, leading to bacterial lysis. Gc expresses two proteins, SliC and NgACP, that bind and inhibit the enzymatic activity of lysozyme. SliC is a surface-exposed lipoprotein, while NgACP is found in the periplasm and also released extracellularly. Purified SliC and NgACP similarly inhibit lysozyme. However, whereas mutation of ngACP increases Gc susceptibility to lysozyme, the sliC mutant is only susceptible to lysozyme when ngACP is inactivated. In this work, we examined how lipidation contributes to SliC expression, cellular localization, and resistance of Gc to killing by lysozyme. To do so, we mutated the conserved cysteine residue (C18) in the N-terminal lipobox motif of SliC, the site for lipid anchor attachment, to alanine. SliC(C18A) localized to soluble rather than membrane fractions in Gc and was not displayed on the bacterial surface. Less SliC(C18A) was detected in Gc lysates compared to the wild-type protein. This was due in part to some release of the C18A mutant, but not wild-type, protein into the extracellular space. Surprisingly, Gc expressing SliC(C18A) survived better than SliC (wild type)-expressing Gc after exposure to lysozyme. We conclude that lipidation is not required for the ability of SliC to inhibit lysozyme, even though the lipidated cysteine is 100% conserved in Gc SliC alleles. These findings shed light on how members of the growing family of lysozyme inhibitors with distinct subcellular localizations contribute to bacterial defense against lysozyme.IMPORTANCENeisseria gonorrhoeae is one of many bacterial species that express multiple lysozyme inhibitors. It is unclear how inhibitors that differ in their subcellular localization contribute to defense from lysozyme. We investigated how lipidation of SliC, an MliC (membrane-bound lysozyme inhibitor of c-type lysozyme)-type inhibitor, contributes to its localization and lysozyme inhibitory activity. We found that lipidation was required for surface exposure of SliC and yet was dispensable for protecting the gonococcus from killing by lysozyme. To our knowledge, this is the first time the role of lipid anchoring of a lysozyme inhibitor has been investigated. These results help us understand how different lysozyme inhibitors are localized in bacteria and how this impacts resistance to lysozyme.

The Ethanolamine-Sensing Transcription Factor EutR Promotes Virulence and Transmission during Citrobacter rodentium Intestinal Infection.

Enteric pathogens exploit chemical and nutrient signaling to gauge their location within a host and control expression of traits important for infection. Ethanolamine-containing molecules are essential in host physiology and play important roles in intestinal processes. The transcription factor EutR is conserved in the Enterobacteriaceae and is required for ethanolamine sensing and metabolism. In enterohemorrhagic Escherichia coli (EHEC) O157:H7, EutR responds to ethanolamine to activate expression of traits required for host colonization and disease; however, the importance of EutR to EHEC intestinal infection has not been examined. Because EHEC does not naturally colonize or cause disease in mice, we employed the natural murine pathogen Citrobacter rodentium as a model of EHEC virulence to investigate the importance of EutR in vivo EHEC and C. rodentium possess the locus of enterocyte effacement (LEE), which is the canonical virulence trait of attaching and effacing pathogens. Our findings demonstrate that ethanolamine sensing and EutR-dependent regulation of the LEE are conserved in C. rodentium Moreover, during infection, EutR is required for maximal LEE expression, colonization, and transmission efficiency. These findings reveal that EutR not only is important for persistence during the primary host infection cycle but also is required for maintenance in a host population.

Perceived Usability and Acceptability of Videoconferencing for Delivering Community-Based Rehabilitation to Individuals with Acquired Brain Injury: A Qualitative Investigation.

OBJECTIVES: There is limited research on the use of telerehabilitation platforms in service delivery for people with acquired brain injury (ABI), especially technologies that support delivery of services into the home. This qualitative study aimed to explore the perspectives of rehabilitation coordinators, individuals with ABI, and family caregivers on the usability and acceptability of videoconferencing (VC) in community-based rehabilitation. Participants' experiences and perceptions of telerehabilitation and their impressions of a particular VC system were investigated. METHODS: Guided by a theory on technology acceptance, semi-structured interviews were conducted with 30 participants from a community-based ABI service, including 13 multidisciplinary rehabilitation coordinators, 9 individuals with ABI, and 8 family caregivers. During the interview, they were shown a paper prototype of a telehealth portal for VC that was available for use. Interview transcripts were coded by two researchers and analysed thematically. RESULTS: The VC was used on average for 2% of client consultations. Four major themes depicted factors influencing the uptake of VC platforms; namely, the context or impetus for use, perceived benefits, potential problems and parameters around use, and balancing the service and user needs. Participants identified beneficial uses of VC in service delivery and strategies for promoting a positive user experience. CONCLUSIONS: Perceptions of the usability of VC to provide services in the home were largely positive; however, consideration of use on a case-by-case basis and a trial implementation was recommended to enhance successful uptake into service delivery.

The AraC Negative Regulator family modulates the activity of histone-like proteins in pathogenic bacteria.

The AraC Negative Regulators (ANR) comprise a large family of virulence regulators distributed among diverse clinically important Gram-negative pathogens, including Vibrio spp., Salmonella spp., Shigella spp., Yersinia spp., Citrobacter spp., and pathogenic E. coli strains. We have previously reported broad effects of the ANR members on regulators of the AraC/XylS family. Here, we interrogate possible broader effects of the ANR members on the bacterial transcriptome. Our studies focused on Aar (AggR-activated regulator), an ANR family archetype in enteroaggregative E. coli (EAEC) isolate 042. Transcriptome analysis of EAEC strain 042, 042aar and 042aar(pAar) identified more than 200 genes that were differentially expressed (+/- 1.5 fold, p<0.05). Most of those genes are located on the bacterial chromosome (195 genes, 92.85%), and are associated with regulation, transport, metabolism, and pathogenesis, based on the predicted annotation; a considerable number of Aar-regulated genes encoded for hypothetical proteins (46 genes, 21.9%) and regulatory proteins (25, 11.9%). Notably, the transcriptional expression of three histone-like regulators, H-NS (orf1292), H-NS homolog (orf2834) and StpA, was down-regulated in the absence of aar and may explain some of the effects of Aar on gene expression. By employing a bacterial two-hybrid system, LacZ reporter assays, pull-down and electrophoretic mobility shift assay (EMSA) analysis, we demonstrated that Aar binds directly to H-NS and modulates H-NS-induced gene silencing. Importantly, Aar was highly expressed in the mouse intestinal tract and was found to be necessary for maximal H-NS expression. In conclusion, this work further extends our knowledge of genes under the control of Aar and its biological relevance in vivo.

After the Fact(or): Posttranscriptional Gene Regulation in Enterohemorrhagic Escherichia coli O157:H7.

To adapt to ever-changing environments, pathogens quickly alter gene expression. This can occur through transcriptional, posttranscriptional, or posttranslational regulation. Historically, transcriptional regulation has been thoroughly studied to understand pathogen niche adaptation, whereas posttranscriptional and posttranslational gene regulation has only relatively recently been appreciated to play a central role in bacterial pathogenesis. Posttranscriptional regulation may involve chaperones, nucleases, and/or noncoding small RNAs (sRNAs) and typically controls gene expression by altering the stability and/or translation of the target mRNA. In this review, we highlight the global importance of posttranscriptional regulation to enterohemorrhagic Escherichia coli (EHEC) gene expression and discuss specific mechanisms of how EHEC regulates expression of virulence factors critical to host colonization and disease progression. The low infectious dose of this intestinal pathogen suggests that EHEC is particularly well adapted to respond to the host environment.

The Ethanolamine Permease EutH Promotes Vacuole Adaptation of Salmonella enterica and Listeria monocytogenes during Macrophage Infection.

Ethanolamine is a ubiquitous and essential molecule within a host. Significantly, bacterial pathogens exploit ethanolamine during infection to promote growth and regulate virulence. The ethanolamine permease EutH is dispensable for growth in vitro under standard conditions, whereas EutH is required for ethanolamine utilization at low pH. These findings suggested a model in which EutH facilitates diffusion of ethanolamine into the bacterial cell in acidic environments. To date, the ecological significance of this model has not been thoroughly investigated, and the importance of EutH to bacterial growth under physiologically relevant conditions is not known. During infection, immune cells internalize invading bacteria within an acidic, nutrient-depleted vacuole called the phagosome. Here, we investigated the hypothesis that EutH promotes bacterial survival following phagocytosis. Our findings indicate that EutH is important for survival and replication of the facultative intracellular pathogens Salmonella enterica serovar Typhimurium and Listeria monocytogenes during prolonged or transient exposure to the phagosome, respectively. Furthermore, in agreement with EutH being important in the acidic environment, neutralization of the vacuole abolished the requirement for EutH. Significantly, consistent with a role for EutH in promoting intramacrophage survival, EutH was not required during S Typhimurium local intestinal infection but specifically conferred an advantage upon dissemination to peripheral organs. These findings reveal a physiologically relevant and conserved role for EutH in spatiotemporal niche adaptation during infection.

A Novel Imaging Finding in Williams Syndrome: The Coral Sign.

A 16-year-old female, with a history of Williams syndrome, presented to our institution with a 2-week history of intermittent dizziness. Holter monitoring demonstrated occasional premature ventricular contractions with rare couplets and triplets as well as one short run of nonsustained ventricular tachycardia. Echocardiography revealed an abnormal and irregular left ventricular septum with multiple mobile, pedunculated muscular projections extending into the left ventricular cavity. Cardiac MR confirmed abnormally thickened trabeculations consisting of multiple parallel ridges of myocardium crossing the left ventricle. The appearance of these findings closely resembled bands of coral lining the ocean floor. As such, this finding can henceforth be known as the "coral sign." To our knowledge, no other reports of this finding in patients with Williams syndrome have been published.

A large family of anti-activators accompanying XylS/AraC family regulatory proteins.

AraC Negative Regulators (ANR) suppress virulence genes by directly down-regulating AraC/XylS members in Gram-negative bacteria. In this study, we sought to investigate the distribution and molecular mechanisms of regulatory function for ANRs among different bacterial pathogens. We identified more than 200 ANRs distributed in diverse clinically important gram negative pathogens, including Vibrio spp., Salmonella spp., Shigella spp., Yersinia spp., Citrobacter spp., enterotoxigenic (ETEC) and enteroaggregative E. coli (EAEC), and members of the Pasteurellaceae. By employing a bacterial two hybrid system, pull down assays and surface plasmon resonance (SPR) analysis, we demonstrate that Aar (AggR-activated regulator), a prototype member of the ANR family in EAEC, binds with high affinity to the central linker domain of AraC-like member AggR. ANR-AggR binding disrupted AggR dimerization and prevented AggR-DNA binding. ANR homologs of Vibrio cholerae, Citrobacter rodentium, Salmonella enterica and ETEC were capable of complementing Aar activity by repressing aggR expression in EAEC strain 042. ANR homologs of ETEC and Vibrio cholerae bound to AggR as well as to other members of the AraC family, including Rns and ToxT. The predicted proteins of all ANR members exhibit three highly conserved predicted α-helices. Site-directed mutagenesis studies suggest that at least predicted α-helices 2 and 3 are required for Aar activity. In sum, our data strongly suggest that members of the novel ANR family act by directly binding to their cognate AraC partners.

CT-guided Native Medical Renal Biopsy: Cortical Tangential versus Non-Tangential Approaches-A Comparison of Efficacy and Safety.

Purpose To review a single-center experience with the cortical tangential approach during computed tomography (CT)-guided native medical renal biopsy and to evaluate its efficacy and safety compared with those of a non-cortical tangential approach. Materials and Methods This retrospective study received institutional review board approval, with a waiver of the HIPAA requirement for informed consent. The number of cores, glomeruli, and complications were reviewed in 431 CT-guided medical renal biopsies performed between July 2007 and September 2015. A biopsy followed a cortical tangential approach if the needle path was parallel to the renal cortical surface, at a depth closer to the renal capsule than the renal pelvic fat. A sample was considered adequate if the biopsy yielded at least 10 glomeruli at light microscopy, one glomerulus at immunofluorescence microscopy, and one glomerulus at electron microscopy. The χ2 test, the t test, the Mann-Whitney test, and logistic regression modeling of sample adequacy were performed. Results One hundred fifty-six (36%) of 431 biopsies were performed with the cortical tangential approach. More cores were obtained for the cortical tangential group (2.6 vs 2.4, P = .001); biopsy needle gauge was not significantly different (P = .076). More adequate samples were obtained in the cortical tangential group (66.7% vs 49.8%, P = .001), with more glomeruli (23 vs 16, P = .014). Results were significant after controlling for needle gauge and number of cores (P = .008). The cortical tangential group had fewer complications (1.9% vs 7.3%, P = .018). Conclusion The cortical tangential approach, when applied to CT-guided native medical renal biopsies, results in higher rates of sample adequacy and lower rates of postprocedural complications. © RSNA, 2016.