Endotracheal Tube Dislodgment in a High Risk Pulmonary Hypertensive Patient due to Undiagnosed Tracheomegaly: A Case Report

Introduction Airway enlargement was first described histologically in 1872, but it was not clinically reported until 1932, when Dr. Mounier-Kuhn published his seminal radiographic studies.1 Since then, it is estimated that several hundred case reports have been published on congenital Mounier-Kuhn Syndrome (MKS), acquired tracheomegaly, and tracheobronchomegaly (TBM), yet only a few comprehensive literature reviews exist.2 Case This case report details an elective nasal procedure for a patient with a history of significant pulmonary hypertension ad COPD on 5L home O2 who had a symptomatic facial trauma. He was considered high risk secondary to his pulmonary disease, but he was considered medically optimized for surgery and had undergone a prior uncomplicated general anesthetic. An intraoperative endotracheal tube dislodgement necessitated emergency airway rescue with difficulty in re-establishing adequate ventilation resulting in the patient being brought to the ICU post-operatively. After a second endotracheal dislodgement shortly later, retrospective radiographic airway analysis revealed tracheal dimensions of 32 x 26mm, suggesting a previously undiagnosed tracheomegaly. Written consent and HIPAA authorization was obtained from the patient for the publication of this case report. Conclusion This case highlights the clinical importance for anesthesiologists to be aware of tracheobronchomegaly (TBM) despite limited provider experience with these patients and sparse reporting on the condition. It is underdiagnosed radiographically and may first present in the OR. TBM can manifest in many ways with potentially fatal complications thus it is vital for anesthesiologists to be able to recognize, troubleshoot, and potentially treat issues related to the disease

Independent evolution of neurotoxin and flagellar genetic loci in proteolytic Clostridium botulinum

<p>Abstract</p> <p>Background</p> <p>Proteolytic <it>Clostridium botulinum </it>is the causative agent of botulism, a severe neuroparalytic illness. Given the severity of botulism, surprisingly little is known of the population structure, biology, phylogeny or evolution of <it>C. botulinum</it>. The recent determination of the genome sequence of <it>C. botulinum </it>has allowed comparative genomic indexing using a DNA microarray.</p> <p>Results</p> <p>Whole genome microarray analysis revealed that 63% of the coding sequences (CDSs) present in reference strain ATCC 3502 were common to all 61 widely-representative strains of proteolytic <it>C. botulinum </it>and the closely related <it>C. sporogenes </it>tested. This indicates a relatively stable genome. There was, however, evidence for recombination and genetic exchange, in particular within the neurotoxin gene and cluster (including transfer of neurotoxin genes to <it>C. sporogenes</it>), and the flagellar glycosylation island (FGI). These two loci appear to have evolved independently from each other, and from the remainder of the genetic complement. A number of strains were atypical; for example, while 10 out of 14 strains that formed type A1 toxin gave almost identical profiles in whole genome, neurotoxin cluster and FGI analyses, the other four strains showed divergent properties. Furthermore, a new neurotoxin sub-type (A5) has been discovered in strains from heroin-associated wound botulism cases. For the first time, differences in glycosylation profiles of the flagella could be linked to differences in the gene content of the FGI.</p> <p>Conclusion</p> <p>Proteolytic <it>C. botulinum </it>has a stable genome backbone containing specific regions of genetic heterogeneity. These include the neurotoxin gene cluster and the FGI, each having evolved independently of each other and the remainder of the genetic complement. Analysis of these genetic components provides a high degree of discrimination of strains of proteolytic <it>C. botulinum</it>, and is suitable for clinical and forensic investigations of botulism outbreaks.</p

Understanding the individual to implement the ecosystem approach to fisheries management

Ecosystem-based approaches to fisheries management (EAFMs) have emerged as requisite for sustainable use of fisheries resources. At the same time, however, there is a growing recognition of the degree of variation among individuals within a population, as well as the ecological consequences of this variation. Managing resources at an ecosystem level calls on practitioners to consider evolutionary processes, and ample evidence from the realm of fisheries science indicates that anthropogenic disturbance can drive changes in predominant character traits (e.g. size at maturity). Eco-evolutionary theory suggests that human-induced trait change and the modification of selective regimens might contribute to ecosystem dynamics at a similar magnitude to species extirpation, extinction and ecological dysfunction. Given the dynamic interaction between fisheries and target species via harvest and subsequent ecosystem consequences, we argue that individual diversity in genetic, physiological and behavioural traits are important considerations under EAFMs. Here, we examine the role of individual variation in a number of contexts relevant to fisheries management, including the potential ecological effects of rapid trait change. Using select examples, we highlight the extent of phenotypic diversity of individuals, as well as the ecological constraints on such diversity. We conclude that individual phenotypic diversity is a complex phenomenon that needs to be considered in EAFMs, with the ultimate realization that maintaining or increasing individual trait diversity may afford not only species, but also entire ecosystems, with enhanced resilience to environmental perturbations. Put simply, individuals are the foundation from which population- and ecosystem-level traits emerge and are therefore of central importance for the ecosystem-based approaches to fisheries management

Casein Kinase II Phosphorylation of Spt6 Enforces Transcriptional Fidelity by Maintaining Spn1-Spt6 Interaction

Spt6 is a histone chaperone that associates with RNA polymerase II and deposits nucleosomes in the wake of transcription. Although Spt6 has an essential function in nucleosome deposition, it is not known whether this function is influenced by post-translational modification. Here, we report that casein kinase II (CKII) phosphorylation of Spt6 is required for nucleosome occupancy at the 5' ends of genes to prevent aberrant antisense transcription and enforce transcriptional directionality. Mechanistically, we show that CKII phosphorylation of Spt6 promotes the interaction of Spt6 with Spn1, a binding partner required for chromatin reassembly and full recruitment of Spt6 to genes. Our study defines a function for CKII phosphorylation in transcription and highlights the importance of post-translational modification in histone chaperone function

Adipocytes disrupt the translational programme of acute lymphoblastic leukaemia to favour tumour survival and persistence

The specific niche adaptations that facilitate primary disease and Acute Lymphoblastic Leukaemia (ALL) survival after induction chemotherapy remain unclear. Here, we show that Bone Marrow (BM) adipocytes dynamically evolve during ALL pathogenesis and therapy, transitioning from cellular depletion in the primary leukaemia niche to a fully reconstituted state upon remission induction. Functionally, adipocyte niches elicit a fate switch in ALL cells towards slow-proliferation and cellular quiescence, highlighting the critical contribution of the adipocyte dynamic to disease establishment and chemotherapy resistance. Mechanistically, adipocyte niche interaction targets posttranscriptional networks and suppresses protein biosynthesis in ALL cells. Treatment with general control nonderepressible 2 inhibitor (GCN2ib) alleviates adipocyte-mediated translational repression and rescues ALL cell quiescence thereby significantly reducing the cytoprotective effect of adipocytes against chemotherapy and other extrinsic stressors. These data establish how adipocyte driven restrictions of the ALL proteome benefit ALL tumours, preventing their elimination, and suggest ways to manipulate adipocyte-mediated ALL resistance

Interaction between non-executive and executive directors in English National Health Service trust boards: an observational study

Research funded by Burdett FoundationBackground National Health Service (NHS) trusts, which provide the majority of hospital and community health services to the English NHS, are increasingly adopting a ‘public firm’ model with a board consisting of executive directors who are trust employees and external non-executives chosen for their experience in a range of areas such as finance, health care and management. In this paper we compare the non-executive directors’ roles and interests in, and contributions to, NHS trust boards’ governance activities with those of executive directors; and examine non-executive directors’ approach to their role in board meetings. Methods Non-participant observations of three successive trust board meetings in eight NHS trusts (primary care trusts, foundation trusts and self-governing (non-foundation) trusts) in England in 2008–9. The observational data were analysed inductively to yield categories of behaviour reflecting the perlocutionary types of intervention which non-executive directors made in trust meetings. Results The observational data revealed six main perlocutionary types of questioning tactic used by non-executive directors to executive directors: supportive; lesson-seeking; diagnostic; options assessment; strategy seeking; and requesting further work. Non-executive board members’ behaviours in holding the executive team to account at board meetings were variable. Non-executive directors were likely to contribute to finance-related discussions which suggests that they did see financial challenge as a key component of their role. Conclusions The pattern of behaviours was more indicative of an active, strategic approach to governance than of passive monitoring or ‘rubber-stamping’. Nevertheless, additional means of maintaining public accountability of NHS trusts may also be required

Ancient DNA of the Extinct Lava Shearwater (Puffinus olsoni) from the Canary Islands Reveals Incipient Differentiation within the P. puffinus Complex

The loss of species during the Holocene was, dramatically more important on islands than on continents. Seabirds from islands are very vulnerable to human-induced alterations such as habitat destruction, hunting and exotic predators. For example, in the genus Puffinus (family Procellariidae) the extinction of at least five species has been recorded during the Holocene, two of them coming from the Canary Islands

Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature

Botulinum neurotoxins are diverse proteins. They are currently represented by at least seven serotypes and more than 40 subtypes. New clostridial strains that produce novel neurotoxin variants are being identified with increasing frequency, which presents challenges when organizing the nomenclature surrounding these neurotoxins. Worldwide, researchers are faced with the possibility that toxins having identical sequences may be given different designations or novel toxins having unique sequences may be given the same designations on publication. In order to minimize these problems, an ad hoc committee consisting of over 20 researchers in the field of botulinum neurotoxin research was convened to discuss the clarification of the issues involved in botulinum neurotoxin nomenclature. This publication presents a historical overview of the issues and provides guidelines for botulinum neurotoxin subtype nomenclature in the future.Peer reviewe

Model based dynamics analysis in live cell microtubule images

Background: The dynamic growing and shortening behaviors of microtubules are central to the fundamental roles played by microtubules in essentially all eukaryotic cells. Traditionally, microtubule behavior is quantified by manually tracking individual microtubules in time-lapse images under various experimental conditions. Manual analysis is laborious, approximate, and often offers limited analytical capability in extracting potentially valuable information from the data. Results: In this work, we present computer vision and machine-learning based methods for extracting novel dynamics information from time-lapse images. Using actual microtubule data, we estimate statistical models of microtubule behavior that are highly effective in identifying common and distinct characteristics of microtubule dynamic behavior. Conclusion: Computational methods provide powerful analytical capabilities in addition to traditional analysis methods for studying microtubule dynamic behavior. Novel capabilities, such as building and querying microtubule image databases, are introduced to quantify and analyze microtubule dynamic behavior

Understanding the individual to implement the ecosystem approach to fisheries management

Ecosystem-based approaches to fisheries management (EAFMs) have emerged as requisite for sustainable use of fisheries resources. At the same time, however, there is a growing recognition of the degree of variation among individuals within a population, as well as the ecological consequences of this variation. Managing resources at an ecosystem level calls on practitioners to consider evolutionary processes, and ample evidence from the realm of fisheries science indicates that anthropogenic disturbance can drive changes in predominant character traits (e.g. size at maturity). Eco-evolutionary theory suggests that human-induced trait change and the modification of selective regimens might contribute to ecosystem dynamics at a similar magnitude to species extirpation, extinction and ecological dysfunction. Given the dynamic interaction between fisheries and target species via harvest and subsequent ecosystem consequences, we argue that individual diversity in genetic, physiological and behavioural traits are important considerations under EAFMs. Here, we examine the role of individual variation in a number of contexts relevant to fisheries management, including the potential ecological effects of rapid trait change. Using select examples, we highlight the extent of phenotypic diversity of individuals, as well as the ecological constraints on such diversity. We conclude that individual phenotypic diversity is a complex phenomenon that needs to be considered in EAFMs, with the ultimate realization that maintaining or increasing individual trait diversity may afford not only species, but also entire ecosystems, with enhanced resilience to environmental perturbations. Put simply, individuals are the foundation from which population- and ecosystem-level traits emerge and are therefore of central importance for the ecosystem-based approaches to fisheries management