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In JoVE (1)

Other Publications (43)

Articles by Katherine Taylor in JoVE

 JoVE Immunology and Infection

In Vivo Imaging Systems (IVIS) Detection of a Neuro-Invasive Encephalitic Virus

1Experimental Pathology, University of Texas Medical Branch


JoVE 4429

Utilizing luciferase and in vivo imaging systems (IVIS) as a novel means to identify disease endpoints before clinical developments occur. IVIS has allowed us to visualize in real time the invasion of encephalitic viruses over multiple days, providing a more accurate disease model for future study. It has also allowed us to identify the potential protective features of antivirals and vaccines faster than currently utilized animal models. The capability to utilize individual animals over multiple time points ensures reduced animal requirements, costs, and overall morbidity to the animals utilized ensuring a more humane and more scientific means of disease study.

Other articles by Katherine Taylor on PubMed

Validation of Chest X-ray Comparisons for Unknown Decedent Identification

Comparing skeletal structures between antemortem and postmortem chest radiographs is widely used by forensic specialists from many disciplines to positively identify unknown decedents. However, validity assessments of this method have been fairly limited. This study had three objectives: 1) to quantify the reliability of ante- and postmortem chest radiograph comparison for decedent identification; 2) to identify useful radiologic features supporting decedent identification; and 3) to recognize sources of error in decedent identification related to use of comparative radiographs. A forensic pathologist, a forensic anthropologist, and two radiologists participated in the study. Our results showed that chest radiograph comparisons proved reliable, if basic decedent information was provided, and antemortem and postmortem radiographs were adequately positioned and exposed. A "morphological approach" using normal anatomical structures for comparison may provide the most efficient method for accurate identification.

Stretch-induced Ventricular Arrhythmias During Acute Ischemia and Reperfusion

Mechanical stretch has been demonstrated to have electrophysiological effects on cardiac muscle, including alteration of the probability of excitation, alteration of the action potential waveform, and stretch-induced arrhythmia (SIA). We demonstrate that regional ventricular ischemia due to coronary artery occlusion increases arrhythmogenic effects of transient diastolic stretch, whereas globally ischemic hearts showed no such increase. We tested our hypothesis that, during phase Ia ischemia, regionally ischemic hearts may be more susceptible to triggered arrhythmogenesis due to transient diastolic stretch. During the first 20 min of regional ischemia, the probability of eliciting a ventricular SIA (P(SIA)) by transient diastolic stretch increased significantly. However, after 30 min, P(SIA) decreased to a value comparable with baseline measurements, as expected during phase Ib, where most ventricular arrhythmias are of reentrant mechanisms. We also suggest that mechanoelectrical coupling may contribute to the nonreentrant mechanisms underlying reperfusion-induced arrhythmia. When coronary artery occlusion was relieved after 30 min of ischemia, we observed an increase in P(SIA) and the maintenance of this elevated level throughout 20 min of reperfusion. We conclude that mechanoelectrical coupling may underlie triggered arrhythmogenesis during phase 1a ischemia and reperfusion.

Promoting Health in Type 2 Diabetes: Nurse-physician Collaboration in Primary Care

The purpose of this study is to examine effects of a nurse-physician collaborative approach to care of patients with type 2 diabetes and to determine possible effect sizes for use in computing sample sizes for a larger study. Forty patients from a family practice clinic with type 2 diabetes were randomly assigned to control or experimental groups. The control group received standard care, whereas the experimental group received standard care plus home visits from a nurse, as well as consultation with an exercise specialist and/or nutritionist. Follow-up continued for 3 months. Clinical end points included standard measures of diabetes activity as well as quality-of-life indicators. Focus group interviews were used to explore patients' responses to the program. Although findings were not statistically significant, a trend toward small to moderate positive effect sizes was found in glycosylated hemoglobin and blood pressure. Quality of life measures also showed a trend toward small to moderate, but nonsignificant, improvements in physical functioning, bodily pain, vitality, social and global functioning, energy, impact of diabetes, and health distress. Focus group interviews indicated a very positive response from patients, who expressed feelings of empowerment. In this study, patients treated with nurse-physician collaboration demonstrated small, but nonsignificant, improvements in blood chemistry after only 3 months. Physical and social functioning, energy, and bodily pain also showed a small improvement. Changes in awareness of effects of diabetes on health and an expressed sense of self-efficacy suggest that effects could be sustainable over the longer term.

Methylene Blue Revisited: Management of Hypotension in a Pediatric Patient with Bacterial Endocarditis

Management of Congenital Tracheal Stenosis--using Spontaneous Ventilation to Facilitate Cardiopulmonary Bypass

We present an unusual case of an infant with life-threatening tracheal stenosis scheduled for repair utilizing cardiopulmonary bypass. After repeated attempts at intubation endtidal CO2 was absent. The child was eventually managed with spontaneous breathing sevoflurane via a facemask. The possible causes of absent endtidal CO2 after intubation are discussed.

Laparoscopic Surgery in the Pediatric Patient Post Fontan Procedure

We present two case reports describing laparoscopic surgery in patients who have undergone previous Fontan surgery and discuss the theoretical implications of laparoscopic surgery in these patients. A brief discussion of the late complications of Fontan surgery is included.

Pheromone Reception in Fruit Flies Expressing a Moth's Odorant Receptor

We have expressed a male-specific, pheromone-sensitive odorant receptor (OR), BmorOR1, from the silkworm moth Bombyx mori in an "empty neuron" housed in the ab3 sensilla of a Drosophila Deltahalo mutant. Single-sensillum recordings showed that the BmorOR1-expressing neurons in the transgenic flies responded to the B. mori pheromone bombykol, albeit with low sensitivity. These transgenic flies responded to lower doses of bombykol in an altered stimulation method with direct delivery of pheromone into the sensillum milieu. We also expressed a B. mori pheromone-binding protein, BmorPBP, in the BmorOR1-expressing ab3 sensilla. Despite the low levels of BmorPBP expression, flies carrying both BmorOR1 and BmorPBP showed significantly higher electrophysiological responses than BmorOR1 flies. Both types of BmorOR1-expressing flies responded to bombykol, and to a lesser extent to a second compound, bombykal, even without the addition of organic solvents to the recording electrode buffer. When the semiochemicals were delivered by the conventional puffing of stimulus on the antennae, the receptor responded to bombykol but not to bombykal. The onset of response was remarkably slow, and neural activity extended for an unusually long time (>1 min) after the end of stimulus delivery. We hypothesize that BmorOR1-expressing ab3 sensilla lack a pheromone-degrading enzyme to rapidly inactivate bombykol and terminate the signal. We also found an endogenous receptor in one of the sensillum types on Drosophila antenna that responds to bombykol and bombykal with sensitivity comparable to the pheromone-detecting sensilla on B. mori male antennae.

Host Immune Response and Differential Survival of the Sexes in Drosophila

Innate immunity is essential for the survival of organisms across the evolutionary spectrum. Drosophila is well studied as a model of innate immunity and has been instrumental in establishing principles of defense and gene signaling pathways that are shared with humans. Previous studies in Drosophila have not focused on differences between the sexes, and in this report we present evidence that it is essential to include differences between the sexes. Survival rates post-infection, after a fungal or bacterial infection, varied according to the combination of signaling pathway (Toll and Imd) and sex tested. We also found that antimicrobial protein gene mRNA levels for Drosomycin and Metchnikowin showed both similarities and differences between the sexes. These studies highlight the need to include both sexes in studies of immune function as well as the associated opportunities for advancing our understanding of immunity.

NIAID Resources for Developing New Therapies for Severe Viral Infections

Severe viral infections, including hemorrhagic fever and encephalitis, occur throughout the world, but are most prevalent in developing areas that are most vulnerable to infectious diseases. Some of these can also infect related species as illustrated by the threatened extinction of gorillas by Ebola infection in west and central Africa. There are no safe and effective treatments available for these serious infections. In addition to the logistical difficulties inherent in developing a drug for infections that are sporadic and occur mainly in the third world, there is the overwhelming barrier of no hope for return on investment to encourage the pharmaceutical industry to address these unmet medical needs. Therefore, the National Institute of Allergy and infectious Disease (NIAID) has developed and supported a variety of programs and resources to provide assistance and lower the barrier for those who undertake these difficult challenges. The primary programs relevant to the development of therapies for severe viral infections are described and three case studies illustrate how they have been used. In addition, contact information for accessing these resources is supplied.

Cognitive-behavioral Interventions to Reduce Suicide Behavior: a Systematic Review and Meta-analysis

Suicide behavior is a serious clinical problem worldwide, and understanding ways of reducing it is a priority. A systematic review and meta-analysis were carried out to investigate whether Cognitive-behavioral therapies (CBTs) would reduce suicide behavior. From 123 potential articles, 28 studies met the entry criteria. Overall, there was a highly significant effect for CBT in reducing suicide behavior. Subgroup analysis indicates a significant treatment effect for adult samples (but not adolescent), for individual treatments (but not group), and for CBT when compared to minimal treatment or treatment as usual (but not when compared to another active treatment). There was evidence for treatment effects, albeit reduced, over the medium term. Although these results appear optimistic in advocating the use of CBT in ameliorating suicidal thoughts, plans, and behaviors, evidence of a publication bias tempers such optimism.

Randomized, Controlled Trial of an Internet-facilitated Intervention for Reducing Binge Eating and Overweight in Adolescents

This study examined the efficacy of an Internet-facilitated intervention for weight maintenance and binge eating in adolescents.

Pulmonary Nodule Volume: Effects of Reconstruction Parameters on Automated Measurements--a Phantom Study

To prospectively evaluate in a phantom the effects of reconstruction kernel, field of view (FOV), and section thickness on automated measurements of pulmonary nodule volume.

Botryosphaeriaceae from Tuart (Eucalyptus Gomphocephala) Woodland, Including Descriptions of Four New Species

Eucalyptus gomphocephala (tuart) is a tree native to the southwest coast of Western Australia, where, in some areas, there is a significant decline in the health of tuart. Botryosphaeriaceous taxa have been isolated as endophytes and canker pathogens from numerous hosts in many parts of the world and have been implicated in the decline of E. gomphocephala. In the present study, endophytic fungi were isolated from a wide variety of native woody plant species (Acacia cochlearis, A. rostellifera, Allocasuarina fraseriana, Agonis flexuosa, Banksia grandis, E. gomphocephala, E. marginata and Santalum acuminatum), at two locations in native E. gomphocephala woodland; a site in decline at Yalgorup National Park and a healthy site at Woodman Point Regional Park. Of the 226 isolates obtained, 154 were botryosphaeriaceous taxa, 80% of which were found to be Neofusicoccum australe, isolated from all hosts at both collection sites. Four new species are described, Dothiorella moneti, Dothiorella santali, Neofusicoccum pennatisporum, and a species belonging to a genus only recently included in the Botryosphaeriaceae, Aplosporella yalgorensis. The other species isolated were Botryosphaeria dothidea on the new hosts A. rostellifera, A. cochlearis and E. marginata and Dichomera eucalypti, on the new host E. marginata. None of the new species formed lesions on excised stems of their host species, E. gomphocephala, or a common plantation species, E. globulus. However, Neofusicoccum australe formed lesions on excised stems of E. globulus and E. gomphocephala.

Imprecision in Automated Volume Measurements of Pulmonary Nodules and Its Effect on the Level of Uncertainty in Volume Doubling Time Estimation

Detection of small indeterminate pulmonary nodules (4 to 10 mm in diameter) in clinical practice is increasing, largely because of increased utilization and improved imaging technology. Although there currently exists software for CT scan machines that automate nodule volume estimation, the imprecision associated with volume estimates is particularly poor for nodules < or = 6 mm in diameter, with greater imprecision associated with increasing CT scan slice thickness. This study examined the effects of the volume estimation error associated with four CT scan slice thicknesses (0.625, 1.25, 2.50, and 5.00 mm) on estimates of volume doubling time (VDT) for solid nodules of various sizes.

Strategic Cognition in Paranoia: the Use of Thought Control Strategies in a Non-clinical Population

Recent work in the area of cognition and emotion has focused on the process as well as the content of thought. Metacognitive approaches have included studies of people's relationship with internal experience (cf. Teasdale and Barnard, 1993), and the overarching beliefs that guide allocation of internal resources to manage distress (cf. Wells, 2000). At the same time, cognitive models of psychosis have emphasized the clinical value of a multidimensional understanding of paranoia (Chadwick, 2006; Freeman and Garety, 2004b).

Chimeric Alphavirus Vaccine Candidates Protect Mice from Intranasal Challenge with Western Equine Encephalitis Virus

We developed two types of chimeric Sindbis virus (SINV)/western equine encephalitis virus (WEEV) alphaviruses to investigate their potential use as live virus vaccines against WEE. The first-generation vaccine candidate, SIN/CO92, was derived from structural protein genes of WEEV strain CO92-1356, and two second-generation candidates were derived from WEEV strain McMillan. For both first- and second-generation vaccine candidates, the nonstructural protein genes were derived from SINV strain AR339. Second-generation vaccine candidates SIN/SIN/McM and SIN/EEE/McM included the envelope glycoprotein genes from WEEV strain McMillan; however, the amino-terminal half of the capsid, which encodes the RNA-binding domain, was derived from either SINV or eastern equine encephalitis virus (EEEV) strain FL93-939. All chimeric viruses replicated efficiently in mammalian and mosquito cell cultures and were highly attenuated in 6-week-old mice. Vaccinated mice developed little or no detectable disease and showed little or no evidence of challenge virus replication; however, all developed high titers of neutralizing antibodies. Upon intranasal challenge with high doses of virulent WEEV strains, mice vaccinated with >or=10(5)PFU of SIN/CO92 or >or=10(4)PFU of SIN/SIN/McM or SIN/EEE/McM were completely protected from disease. These findings support the potential use of these live-attenuated vaccine candidates as safe and effective vaccines against WEE.

Emergency Interventional Lung Assist for Pulmonary Hypertension

We present a 15-yr-old-girl who underwent interventional lung assist via Novalung (Novalung GmbH, Lotzenaecker, Heckingen, Germany) insertion as a bridge to bilateral lung transplantation for pulmonary veno-occlusive disease. This is the first pediatric and smallest patient to receive the device. Central cannulation was chosen to optimize blood flow through the device by enabling larger-sized cannulae in a patient with high pulmonary artery pressure. Novalung provided circulatory support with oxygenation obviating the need for extracorporeal membrane oxygenation while waiting for lung transplantation.

Attributions for Hallucinations in Bipolar Affective Disorder

Attributions for hallucinations in the "schizophrenia" spectrum disorders have been subject to extensive investigation; however, in comparison very little is known about attributions for hallucinations in the bipolar disorders spectrum.

Understanding Factors Influencing Substance Use in People with Recent Onset Psychosis: A Qualitative Study

This qualitative study identifies factors influencing the use of substances in young people with recent onset psychosis. A purposive sample of 19 people aged between 16 and 35 years from an Early Intervention Service in the English National Health Service (NHS) was interviewed using a semi-structured guide. All had experienced a psychotic episode and were within 3 years of first contact with the service. All were either currently misusing substances or had been doing so in the 6 months prior to first contact with the service. All participants were/had been regular cannabis users and for 13(68%) cannabis was the primary drug of use. Thematic analysis identified four key themes in participants accounts of factors influencing their substance abuse: influence of perceived drug norms on behaviour; attributions for initial and ongoing drug-taking behaviour; changes in life goals affecting drug use; beliefs about the links between mental health and drug use. These findings have clear implications for interventions at a number of levels to support young people using substances in early psychosis including public health messages, education and psychological therapies.

Participation in Cervical Cancer Screening in Germany

My Lovely C-section

Katherine and Andrew Taylor chose to have a planned home birth. With the support of her husband, Andrew, and her midwife and doula, Katherine labored at home for 48 hours before transferring to the hospital. Baby Luke was born by cesarean about 20 hours later. Confident and supported, the Taylors were able to make informed decisions and have a positive birth experience, although it was not what they had planned.

Influence of Nodule Detection Software on Radiologists' Confidence in Identifying Pulmonary Nodules with Computed Tomography

With advances in technology, detection of small pulmonary nodules is increasing. Nodule detection software (NDS) has been developed to assist radiologists with pulmonary nodule diagnosis. Although it may increase sensitivity for small nodules, often there is an accompanying increase in false-positive findings. We designed a study to examine the extent to which computed tomography (CT) NDS influences the confidence of radiologists in identifying small pulmonary nodules.

A Comparative Genomic Map for Caulanthus Amplexicaulis and Related Species (Brassicaceae)

Adaptation to environment is the cornerstone of ecological genetics. The subject of this study is a wild relative of the sequenced and annotated model plant species, Arabidopsis thaliana. Caulanthus amplexicaulis var. barbarae lives on serpentine soils, known for high concentrations of heavy metals and low concentrations of essential plant macronutrients, and provides a compelling example of an organism's adaptation to environment. We constructed an F(2) linkage map, using a cross to the nonserpentine sister taxon, C. amplexicaulis var. amplexicaulis. C. amplexicaulis is a member of a highly diverse set of taxa (within the tribe Thelypodieae), described here as the 'Streptanthoid Complex' that are adapted to a broad range of environments, yet share a common n = 14 chromosome number and likely arose by a recent radiation. The linkage map consists of 97 polymorphic microsatellite markers, and 40 exon-primed intron-crossing markers based on A. thaliana exon sequences and Brassica ESTs. The map covers 14 linkage groups and has a total length of 1513 cM. Both the patterns of marker segregation and the comparative map indicate that C. amplexicaulis is a diploid organism with a compact genome. All exon-primed intron-crossing markers, and an unexpectedly large number of microsatellite markers (83%), had significant similarity to the A. thaliana genome, facilitating the development of a comparative genome map. As a proof of principle, we used the comparative map to identify candidate genes underlying differences in sepal colour between the two parent taxa. We demonstrate that the genomic tools developed here will be portable throughout the Streptanthoid Complex.

Permanent Genetic Resources Added to Molecular Ecology Resources Database 1 October 2010-30 November 2010

This article documents the addition of 277 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Ascochyta rabiei, Cambarellus chapalanus, Chionodraco hamatus, Coptis omeiensis, Cynoscion nebulosus, Daphnia magna, Gerbillus nigeriae, Isurus oxyrinchus, Lates calcarifer, Metacarcinus magister, Oplegnathus fasciatus, Pachycondyla verenae, Phaethon lepturus, Pimelodus grosskopfii, Rotylenchulus reniformis, Scomberomorus niphonius, Sepia esculenta, Terapon jarbua, Teratosphaeria cryptica and Thunnus obesus. These loci were cross-tested on the following species: Austropotamobius italicus, Cambarellus montezumae, Cambarellus puer, Cambarellus shufeldtii, Cambarellus texanus, Chionodraco myersi, Chionodraco rastrospinosus, Coptis chinensis, Coptis chinensis var. brevisepala, Coptis deltoidea, Coptis teeta, Orconectes virilis, Pacifastacus leniusculus, Pimelodus bochii, Procambarus clarkii, Pseudopimelodus bufonius, Rhamdia quelen, Sepia andreana, Sepiella maindroni, Thunnus alalunga, Thunnus albacares, Thunnus maccoyii, Thunnus orientalis, Thunnus thynnus and Thunnus tonggol.

Using Endobronchial Ultrasound Features to Predict Lymph Node Metastasis in Patients with Lung Cancer

Reliable staging of the mediastinum determines TNM classification and directs therapy for non-small cell lung cancer (NSCLC). Our aim was to evaluate predictors of mediastinal lymph node metastasis in patients undergoing endobronchial ultrasound (EBUS).

Parental Attitudes to Digital Recording: A Paediatric Hospital Survey

Digital recording is ubiquitous in the community. Its objectivity, permanence and utility in medical education have led to increasing use in health-care settings. As participants in this process, the perspectives of families are important to inform practice. We surveyed family members of hospitalized children to evaluate their opinions.

A Comparison of Cardiac Output by Thoracic Impedance and Direct Fick in Children with Congenital Heart Disease Undergoing Diagnostic Cardiac Catheterization

To evaluate the measurement of cardiac output (CO) using continuous electrical bioimpedance cardiography (Physioflow; Neumedx, Philadelphia, PA) (CO(PF)) with a simultaneous direct Fick measurement (CO(FICK)) in children with congenital heart disease.

Cardiac Arrest Upon Induction of Anesthesia in Children with Cardiomyopathy: an Analysis of Incidence and Risk Factors

It is thought that patients with cardiomyopathy have an increased risk of cardiac arrest on induction of anesthesia, but there is little available data. The purpose of this study was to identify the incidence and potential risk factors for cardiac arrest upon induction of anesthesia in children with cardiomyopathy in our institution.

Rapid, Non-invasive Imaging of Alphaviral Brain Infection: Reducing Animal Numbers and Morbidity to Identify Efficacy of Potential Vaccines and Antivirals

Rapid and accurate identification of disease progression are key factors in testing novel vaccines and antivirals against encephalitic alphaviruses. Typical efficacy studies utilize a large number of animals and severe morbidity or mortality as an endpoint. New technologies provide a means to reduce and refine the animal use as proposed in Hume's 3Rs (replacement, reduction, refinement) described by Russel and Burch. In vivo imaging systems (IVIS) and bioluminescent enzyme technologies accomplish the reduction of animal requirements while shortening the experimental time and improving the accuracy in localizing active virus replication. In the case of murine models of viral encephalitis in which central nervous system (CNS) viral invasion occurs rapidly but the disease development is relatively slow, we visualized the initial brain infection and enhance the data collection process required for efficacy studies on antivirals or vaccines that are aimed at preventing brain infection. Accordingly, we infected mice through intranasal inoculation with the genetically modified pathogen, Venezuelan equine encephalitis, which expresses a luciferase gene. In this study, we were able to identify the invasion of the CNS at least 3 days before any clinical signs of disease, allowing for reduction of animal morbidity providing a humane means of disease and vaccine research while obtaining scientific data accurately and more rapidly. Based on our data from the imaging model, we confirmed the usefulness of this technology in preclinical research by demonstrating the efficacy of Ampligen, a TLR-3 agonist, in preventing CNS invasion.

Measuring Nursing Essential Contributions to Quality Patient Care Outcomes

Workload Management System for Nursing (WMSN) is a core Army Medical Department business system that has provided near real-time, comprehensive nursing workload and manpower data for decision making at all levels for over 25 years. The Army Manpower Requirements and Documentation Agency populates data from WMSN into the Manpower Staffing Standards System (Inpatient module within Automated Staffing Assessment Model). The current system, Workload Management System for Nursing Internet (WMSNi), is an interim solution that requires additional functionalities for modernization and integration at the enterprise level. The expanding missions and approved requirements for WMSNi support strategic initiatives on the Army Medical Command balanced scorecard and require continued sustainment for multiple personnel and manpower business processes for both inpatient and outpatient nursing care. This system is currently being leveraged by the TRICARE Management Activity as an interim multiservice solution, and is being used at 24 Army medical treatment facilities. The evidenced-based information provided to Army decision makers through the methods used in the WMSNi will be essential across the Army Medical Command throughout the system's life cycle.

Protective Antigens Against Glanders Identified by Expression Library Immunization

Burkholderia are highly evolved Gram-negative bacteria that primarily infect solipeds but are transmitted to humans by ingestion and cutaneous or aerosol exposures. Heightened concern over human infections of Burkholderia mallei and the very closely related species B. pseudomallei is due to the pathogens' proven effectiveness as bioweapons, and to the increased potential for natural opportunistic infections in the growing diabetic and immuno-compromised populations. These Burkholderia species are nearly impervious to antibiotic treatments and no vaccine exists. In this study, the genome of the highly virulent B. mallei ATCC23344 strain was examined by expression library immunization for gene-encoded protective antigens. This protocol for genomic-scale functional screening was customized to accommodate the unusually large complexity of Burkholderia, and yielded 12 new putative vaccine candidates. Five of the candidates were individually tested as protein immunogens and three were found to confer significant partial protection against a lethal pulmonary infection in a murine model of disease. Determinations of peripheral blood cytokine and chemokine profiles following individual protein immunizations show that interleukin-2 (IL-2) and IL-4 are elicited by the three confirmed candidates, but unexpectedly interferon-γ and tumor necrosis factor-α are not. We suggest that these pathogen components, discovered using genetic immunization and confirmed in a conventional protein format, will be useful toward the development of a safe and effective glanders vaccine.

Prevalence and Indications for Video Recording in the Health Care Setting in North American and British Paediatric Hospitals

Health care video recording has demonstrated value in education, performance assessment, quality improvement and clinical care.

The Influence of Bisphosphonates on Viability, Migration, and Apoptosis of Human Oral Keratinocytes--in Vitro Study

Bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) is one of the most often seen side effects in patients treated with bisphosphonates, presenting clinically as a non-healing wound. One theory of BP-ONJ etiology describes a negative effect on soft tissues, especially on keratinocytes, which play an important role in oral wound healing and oral soft tissue regeneration. A high cell viability of keratinocytes, which can migrate to the affected location, is essential for wound healing. The aim of this in vitro study was to investigate the effect of differently potent bisphosphonates on human oral keratinocytes (HOK).Three nitrogen-containing bisphosphonates (ibandronate, pamidronate, and zoledronate) and one non-nitrogen-containing bisphosphonate (clodronate) were compared concerning their potency on cell viability (calcein assay and MTT assay), migration ability (Boyden chamber migration assay and scratch wound proliferation assay), and apoptosis (TUNEL assay) of HOK.The nitrogen-containing bisphosphonates, particularly highly potent pamidronate and zoledronate preparations, had a strong negative influence on cell viability, migration ability, and apoptosis of HOK. The non-nitrogen-containing clodronate even increased cell viability in higher concentrations.This study demonstrates that bisphosphonates have a strong influence on HOK on different cellular levels like cell viability, migration ability, and apoptosis rate. The results support the theory that BP-ONJ is a multifactorially caused disease.Furthermore, this in vitro study confirms the theory that perioperative interruption of bisphosphonate application during dental surgical procedures might be feasible to promote better tissue regeneration and wound healing.

Poor Accuracy of Noninvasive Cardiac Output Monitoring Using Bioimpedance Cardiography [PhysioFlow(R)] Compared to Magnetic Resonance Imaging in Pediatric Patients

Identification of low cardiac output (CO) states in anesthesia is important because preoperative hemodynamic optimization may improve outcome in surgery. Accurate real-time CO measurement would be useful in optimizing "goal-directed" therapy. We sought to evaluate the reliability and accuracy of CO measurement using bioimpedance cardiography (PhysioFlow®, NeuMeDx, Bristol, PA) in pediatric patients with and without cardiac disease undergoing anesthesia for magnetic resonance imaging (MRI).

CBT for Culture Change: Formulating Teams to Improve Patient Care

Increasingly, clinical psychologists and CBT trained clinicians work with and within teams. The cognitive model enables us to formulate the processes maintaining distress, and work with people to effect change. The model tends to be used to understand individuals' difficulties, but may be effective in making sense of problems within teams.

Prophylactic Application of CpG Oligonucleotides Augments the Early Host Response and Confers Protection in Acute Melioidosis

Prophylactic administration of CpG oligodeoxynucleotides (CpG ODNs) is known to confer protection against lethal sepsis caused by Burkholderia pseudomallei in the mouse model. The mechanisms whereby CpG regulates the innate immune response to provide protection against B. pseudomallei, however, are poorly characterized. In the present study, we demonstrate that intranasal treatment of mice with Class C CpG, results in recruitment of inflammatory monocytes and neutrophils to the lung at 48 h post-treatment. Mice infected with B. pseudomallei 48 h post-CpG treatment had reduced organ bacterial load and significantly altered cytokine and chemokine profiles concomitant with protection as compared to control animals. CpG administration reduced the robust production of chemokines and pro-inflammatory cytokines in blood, lung and spleen, observed following infection of non-treated animals. Death of control animals coincided with the time of peak cytokine production (day 1-3), while a moderate; sustained cytokine production in CpG-treated animals was associated with survival. In general, CpG treatment resulted in diminished expression of cytokines and chemokines post-infection, though IL-12p40 was released in larger quantities in CpG treated animals. In contrast to CpG-treated animals, the lungs of infected control animals were infiltrated with leukocytes, especially neutrophils, and large numbers of necrotic lesions were observed in lung sections. Therapeutic treatment of B. pseudomallei-infected animals with CpG at 24 h post-infection did not impact survival compared to control animals. In summary, protection of CpG-treated animals was associated with recruitment of inflammatory monocytes and neutrophils into the lungs prior to infection. These responses correspond with early control of bacterial growth, a dampened inflammatory cytokine/chemokine response, reduced lung pathology, and greatly increased survival. In contrast, a delay in recruitment of inflammatory cell populations, despite a robust production of pro-inflammatory cytokines, was associated with poorly controlled bacterial growth, severe lung pathology, and death of control animals.

Bipolar Disorder is a Two-edged Sword: A Qualitative Study to Understand the Positive Edge

Bipolar Disorder (BD) can have highly detrimental effects on the lives of people with the diagnosis and those who care about them. However, growing evidence suggests that aspects of bipolar experiences are also highly valued by some people.

Aortopulmonary Collateral Flow Volume Affects Early Postoperative Outcome After Fontan Completion: A Multimodality Study

Aortopulmonary collaterals are a frequent phenomenon in patients after bidirectional cavopulmonary connection. The aortopulmonary collateral flow volume can be quantified using cardiac magnetic resonance imaging. However, the significance of aortopulmonary collateral flow for the postoperative outcome after total cavopulmonary connection is unclear and was sought to be determined.

Natural Killer Cell Mediated Pathogenesis Determines Outcome of Central Nervous System Infection with Venezuelan Equine Encephalitis Virus in C3H/HeN Mice

TC83 is a human vaccine with investigational new drug status and is used as a prototype Venezuelan equine encephalitis virus for pathogenesis and antiviral research. Differing from other experimental models, the virus causes high titer infection in the brain and 90-100% mortality in the C3H/HeN murine model. To better characterize the susceptibility to disease development in C3H/HeN mice, we have analyzed the gene transcriptomes and cytokine production in the brains of infected mice. Our analysis indicated the potential importance of natural killer cells in the encephalitic disease development. This paper describes for the first time a pathogenic role for natural killer cells in VEEV encephalitis.

The Fear of Others: A Qualitative Analysis of Interpersonal Threat in Social Phobia and Paranoia

Background and Aims: The cognitive models indicate that people with social phobia and paranoia share a common fear of others. While we recognize clinical differences, it is likely that some of the same psychological processes contribute to the maintenance of both presentations, yet the nature and extent of these similarities and differences are not yet clearly understood. This study explored threat experiences in people with social phobia and persecutory delusions in order to elucidate these aspects of the respective cognitive models. Method: Accounts of interpersonal threat experiences were examined in nine people with social phobia and nine people with persecutory delusions. Verbatim transcripts were analyzed using thematic analysis. Results: Three major themes emerged from the data: participants' experience of threat, reactions while under threat, and subsequent reflections. Narrative coherence emerged as a superordinate theme. Typical fear responses were found in both groups, particularly in their reactions to threat. The key differences were in participants' perceptual experiences, ability to stand back from the threat following the event, and narrative coherence. Conclusions: The findings are discussed in relation to current cognitive models of social phobia and paranoia. Theoretical and clinical implications are drawn out, and highlight the need to examine attentional and metacognitive processes more closely if we are to understand the maintenance of perceived threat in these groups, and means of alleviating associated distress.

Rapid Depletion of Target Proteins Allows Identification of Coincident Physiological Responses

Targeted protein degradation is a powerful tool that can be used to create unique physiologies depleted of important factors. Current strategies involve modifying a gene of interest such that a degradation peptide is added to an expressed target protein and then conditionally activating proteolysis, either by expressing adapters, unmasking cryptic recognition determinants, or regulating protease affinities using small molecules. For each target, substantial optimization may be required to achieve a practical depletion, in that the target remains present at a normal level prior to induction and is then rapidly depleted to levels low enough to manifest a physiological response. Here, we describe a simplified targeted degradation system that rapidly depletes targets and that can be applied to a wide variety of proteins without optimizing target protease affinities. The depletion of the target is rapid enough that a primary physiological response manifests that is related to the function of the target. Using ribosomal protein S1 as an example, we show that the rapid depletion of this essential translation factor invokes concomitant changes to the levels of several mRNAs, even before appreciable cell division has occurred.

A Longitudinal Path Analysis of Peer Victimization, Threat Appraisals to the Self, and Aggression, Anxiety, and Depression Among Urban African American Adolescents

Threat appraisals-individuals' perceptions of how stressful situations may threaten their well-being-are an important but understudied mechanism that could explain links between peer victimization and adjustment. The goal of the present study was to examine relationships between physical and relational victimization by peers, threats to the self, and aggression, anxiety, and depression to better understand the cognitive evaluations that make youth vulnerable to negative adjustment. The sample comprised two cohorts of African American adolescents (N = 326; 54 % female; M = 12.1; SD = 1.6) and their maternal caregivers, who participated in three waves of a longitudinal study. Path models revealed significant direct effects from Time 1 relational victimization, but not physical victimization, to Time 2 threat appraisals (i.e., negative self-evaluations and negative evaluations by others), controlling for Time 1 threat appraisals. Significant direct effects were found from Time 2 threats of negative evaluations by others to Time 3 youth-reported aggression, controlling for Time 1 and Time 2 aggression. Significant direct effects also were found from Time 2 threats of negative self-evaluations to T3 youth-reported depression, controlling for Time 1 and Time 2 depression. Overall, findings highlight the need to consider the role of threats to the self in pathways from peer victimization to adjustment and the implications these appraisals have for youth prevention and intervention efforts.

Determinants and Clinical Significance of Flow Via the Fenestration in the Fontan Pathway: A Multimodality Study

BACKGROUND: The use of a fenestration in the Fontan pathway remains controversial, partly because its hemodynamic effects and clinical consequences are insufficiently understood. The objective of this study was to quantify the magnitude of fenestration flow and to characterize its hemodynamic consequences after an intermediate interval after surgery. METHODS: Twenty three patients with a fenestrated extracardiac conduit prospectively underwent investigation by cardiac magnetic resonance (CMR), echocardiography, and invasive manometry under the same general anesthetic 12±4months after Fontan surgery. Fenestration flow was determined using phase contrast CMR by subtracting flow in the Fontan pathway above the fenestration from Fontan flow below the fenestration. RESULTS: Fenestration flow constituted a mean of 31±12% (range 8-50%) of ventricular preload. It was associated with a lower Qp/Qs (r=-0.64, p=0.001) and oxygen saturation (r=-0.74, p<0.0001). Fenestration flow volume was correlated with pulmonary vascular resistance (r=0.45, p=0.04) and markers of ventricular diastolic function (early diastolic strain rate r=0.57, p=0.008 and ventricular untwist rate r=0.54, p=0.02). In 14 patients (61%) all of the net inferior vena cava flow and part of the superior vena cava flow were diverted into the systemic atrium and did not reach the lungs. CONCLUSIONS: Fenestration flow can be measured accurately with CMR. In two-thirds of the patients not only all of the inferior vena cava flow, but also some of the superior vena cava flow is diverted through the fenestration. Fenestration flow is driven by a balance between pulmonary vascular resistance and early diastolic ventricular function.

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