FEBio finite element model of a pediatric cervical spine.

OBJECTIVE: The underlying biomechanical differences between the pediatric and adult cervical spine are incompletely understood. Computational spine modeling can address that knowledge gap. Using a computational method known as finite element modeling, the authors describe the creation and evaluation of a complete pediatric cervical spine model. METHODS: Using a thin-slice CT scan of the cervical spine from a 5-year-old boy, a 3D model was created for finite element analysis. The material properties and boundary and loading conditions were created and model analysis performed using open-source software. Because the precise material properties of the pediatric cervical spine are not known, a published parametric approach of scaling adult properties by 50%, 25%, and 10% was used. Each scaled finite element model (FEM) underwent two types of simulations for pediatric cadaver testing (axial tension and cardinal ranges of motion [ROMs]) to assess axial stiffness, ROM, and facet joint force (FJF). The authors evaluated the axial stiffness and flexion-extension ROM predicted by the model using previously published experimental measurements obtained from pediatric cadaveric tissues. RESULTS: In the axial tension simulation, the model with 50% adult ligamentous and annulus material properties predicted an axial stiffness of 49 N/mm, which corresponded with previously published data from similarly aged cadavers (46.1 ± 9.6 N/mm). In the flexion-extension simulation, the same 50% model predicted an ROM that was within the range of the similarly aged cohort of cadavers. The subaxial FJFs predicted by the model in extension, lateral bending, and axial rotation were in the range of 1-4 N and, as expected, tended to increase as the ligament and disc material properties decreased. CONCLUSIONS: A pediatric cervical spine FEM was created that accurately predicts axial tension and flexion-extension ROM when ligamentous and annulus material properties are reduced to 50% of published adult properties. This model shows promise for use in surgical simulation procedures and as a normal comparison for disease-specific FEMs.

Finite element modeling to compare craniocervical motion in two age-matched pediatric patients without or with Down syndrome: implications for the role of bony geometry in craniocervical junction instability.

OBJECTIVE: Instability of the craniocervical junction (CCJ) is a well-known finding in patients with Down syndrome (DS); however, the relative contributions of bony morphology versus ligamentous laxity responsible for abnormal CCJ motion are unknown. Using finite element modeling, the authors of this study attempted to quantify those relative differences. METHODS: Two CCJ finite element models were created for age-matched pediatric patients, a patient with DS and a control without DS. Soft tissues and ligamentous structures were added based on bony landmarks from the CT scans. Ligament stiffness values were assigned using published adult ligament stiffness properties. Range of motion (ROM) testing determined that model behavior most closely matched pediatric cadaveric data when ligament stiffness values were scaled down to 25% of those found in adults. These values, along with those assigned to the other soft-tissue materials, were identical for each model to ensure that the only variable between the two was the bone morphology. The finite element models were then subjected to three types of simulations to assess ROM, anterior-posterior (AP) translation displacement, and axial tension. RESULTS: The DS model exhibited more laxity than the normal model at all levels for all of the cardinal ROMs and AP translation. For the CCJ, the flexion-extension, lateral bending, axial rotation, and AP translation values predicted by the DS model were 40.7%, 52.1%, 26.1%, and 39.8% higher, respectively, than those for the normal model. When simulating axial tension, the soft-tissue structural stiffness values predicted by the DS and normal models were nearly identical. CONCLUSIONS: The increased laxity exhibited by the DS model in the cardinal ROMs and AP translation, along with the nearly identical soft-tissue structural stiffness values exhibited in axial tension, calls into question the previously held notion that ligamentous laxity is the sole explanation for craniocervical instability in DS.

ECG quiz: Murphy's law strikes again!

ECG Quiz: An unusual ECG in a 77year old man with chest pain.

Innate immune cells and bacterial infection in zebrafish.

The physical attributes of the zebrafish, including optical transparency during embryogenesis, large clutch sizes, external development, and rapid organogenesis were features that initially attracted developmental biologists to use this vertebrate as an experimental model system. With the progressive development of an extensive genetic "tool kit" and an ever-growing number of transgenic reporter lines, the zebrafish model has evolved into an informative system in which to mimic and study aspects of human disease, including those associated with bacterial infections. This chapter provides detailed protocols for microinjection of bacterial strains into zebrafish larvae and subsequent experiments to investigate single-larva bacterial burdens, live imaging of specific neutrophil and macrophage bactericidal functions, and how these protocols may be applied to drug discovery approaches to uncover novel immunomodulatory drugs.

Lymphatic vessels arise from specialized angioblasts within a venous niche.

How cells acquire their fate is a fundamental question in developmental and regenerative biology. Multipotent progenitors undergo cell-fate restriction in response to cues from the microenvironment, the nature of which is poorly understood. In the case of the lymphatic system, venous cells from the cardinal vein are thought to generate lymphatic vessels through trans-differentiation. Here we show that in zebrafish, lymphatic progenitors arise from a previously uncharacterized niche of specialized angioblasts within the cardinal vein, which also generates arterial and venous fates. We further identify Wnt5b as a novel lymphatic inductive signal and show that it also promotes the 'angioblast-to-lymphatic' transition in human embryonic stem cells, suggesting that this process is evolutionarily conserved. Our results uncover a novel mechanism of lymphatic specification, and provide the first characterization of the lymphatic inductive niche. More broadly, our findings highlight the cardinal vein as a heterogeneous structure, analogous to the haematopoietic niche in the aortic floor.

Regulation of contact inhibition of locomotion by Eph-ephrin signalling.

Contact inhibition of locomotion (CIL) occurs when a cell stops migrating in a particular direction upon contact with another cell. Many cancer cells show Contact inhibition of locomotion when contacting one another but display contact-unimpeded migration following collision with noncancer cells. Here we review current understanding of Contact inhibition of locomotion, from Abercrombie's historical studies of cells in tissue culture to more recent analyses of Contact inhibition of locomotion in vivo. We discuss the cellular machinery required for CIL and the molecular signals that regulate it. We focus on our recent finding that in prostate cancer cells, Contact inhibition of locomotion is regulated by a balance between EphA and EphB receptor signalling. We show that, as recently described for chick heart fibroblasts, microtubule dynamics are required for Contact inhibition of locomotion in prostate cancer cells and we propose that stabilization of microtubules could account for defective Contact inhibition of locomotion between cancer cells and noncancer cells.

Survey of airway management strategies and experience of non-consultant doctors in intensive care units in the UK.

BACKGROUND: Airway problems continue to occur in intensive care setting. Management strategies, staffing, and availability of equipment can all have an influence. METHODS: We undertook a standardized telephone survey of airway management strategies, staffing, and airway equipment availability in general intensive care units (ICUs) in the UK, before the reporting of the Fourth National Audit Project of the Royal College of Anaesthetists and Difficult Airway Society. RESULTS: All 257 UK general ICUs were contacted and 77% replied. At the time of the survey, 6.3% of all ICU patients were judged by respondents to have an increased risk of airway complications. While 38% of respondents reported using individualized airway management plans for patients with higher risk airways, only 19% of the patients identified as 'at risk' had such a plan in place. Action plans for the management of unanticipated tracheal tube and tracheostomy displacement were available in 7% and 10% of ICUs, respectively, although 27% of respondents reported no training in recognition and management of these events. Few respondents could describe the equipment available for emergency transtracheal access on their ICU and 13% had no training in its use. More than half of the respondents (56%) routinely used continuous waveform capnography for patients with artificial airways. A fibrescope was available to all ICUs: immediately in 63% and after >5 min in 14%. In 33% of ICUs, the most junior doctor providing out-of-hours cover had not always obtained the Royal College of Anaesthetists initial assessment of competency in anaesthesia. One-third of ICU residents also had commitments outside the ICU. An additional anaesthetist for managing airway emergencies was available in all ICUs with 80% being on-site. CONCLUSIONS: There remains room for improvement in airway management strategies and resources in ICUs in the UK.

Effects of a mindfulness-based intervention during pregnancy on prenatal stress and mood: results of a pilot study.

Stress and negative mood during pregnancy increase risk for poor childbirth outcomes and postnatal mood problems and may interfere with mother-infant attachment and child development. However, relatively little research has focused on the efficacy of psychosocial interventions to reduce stress and negative mood during pregnancy. In this study, we developed and pilot tested an eight-week mindfulness-based intervention directed toward reducing stress and improving mood in pregnancy and early postpartum. We then conducted a small randomized trial (n=31) comparing women who received the intervention during the last half of their pregnancy to a wait-list control group. Measures of perceived stress, positive and negative affect, depressed and anxious mood, and affect regulation were collected prior to, immediately following, and three months after the intervention (postpartum). Mothers who received the intervention showed significantly reduced anxiety (effect size, 0.89; p<0.05) and negative affect (effect size, 0.83; p<0.05) during the third trimester in comparison to those who did not receive the intervention. The brief and nonpharmaceutical nature of this intervention makes it a promising candidate for use during pregnancy.

Molecular analysis of two cytochrome P450 monooxygenase genes required for paxilline biosynthesis in Penicillium paxilli, and effects of paxilline intermediates on mammalian maxi-K ion channels.

The gene cluster required for paxilline biosynthesis in Penicillium paxilli contains two cytochrome P450 monooxygenase genes, paxP and paxQ. The primary sequences of both proteins are very similar to those of proposed cytochrome P450 monooxygenases from other filamentous fungi, and contain several conserved motifs, including that for a haem-binding site. Alignment of these sequences with mammalian and bacterial P450 enzymes of known 3-D structure predicts that there is also considerable conservation at the level of secondary structure. Deletion of paxP and paxQ results in mutant strains that accumulate paspaline and 13-desoxypaxilline, respectively. These results confirm that paxP and paxQ are essential for paxilline biosynthesis and that paspaline and 13-desoxypaxilline are the most likely substrates for the corresponding enzymes. Chemical complementation of paxilline biosynthesis in paxG (geranygeranyl diphosphate synthase) and paxP, but not paxQ, mutants by the external addition of 13-desoxypaxilline confirms that PaxG and PaxP precede PaxQ, and are functionally part of the same biosynthetic pathway. A pathway for the biosynthesis of paxilline is proposed on the basis of these and earlier results. Electrophysiological experiments demonstrated that 13-desoxypaxilline is a weak inhibitor of mammalian maxi-K channels (Ki=730 nM) compared to paxilline (Ki=30 nM), indicating that the C-13 OH group of paxilline is crucial for the biological activity of this tremorgenic mycotoxin. Paspaline is essentially inactive as a channel blocker, causing only slight inhibition at concentrations up to 1 microM.

The effectiveness of spinal manipulation for the treatment of headache disorders: a systematic review of randomized clinical trials.

To carry out a systematic review of the literature examining the effectiveness of spinal manipulation for the treatment of headache disorders, computerized literature searches were carried out in Medline, Embase, Amed and CISCOM. Studies were included only if they were randomized trials of (any type of) spinal manipulation for (any type of) headache in human patients in which spinal manipulation was compared either to no treatment, usual medical care, a 'sham' intervention, or to some other active treatment. Two investigators independently extracted data on study design, sample size and characteristics, type of intervention, type of control/comparison, direction and nature of the outcome(s). Methodological quality of the trials was also assessed using the Jadad scale. Eight trials were identified that met our inclusion criteria. Three examined tension-type headaches, three migraine, one 'cervicogenic' headache, and one 'spondylogenic' chronic headache. In two studies, patients receiving spinal manipulation showed comparable improvements in migraine and tension headaches compared to drug treatment. In the 4 studies employing some 'sham' interventions (e.g. laser light therapy), results were less conclusive with 2 studies showing a benefit for manipulation and 2 studies failing to find such an effect. Considerable methodological limitations were observed in most trials, the principal one being inadequate control for nonspecific (placebo) effects. Despite claims that spinal manipulation is an effective treatment for headache, the data available to date do not support such definitive conclusions. It is unclear to what extent the observed treatment effects can be explained by manipulation or by nonspecific factors (e.g. of personal attention, patient expectation). Whether manipulation produces any long-term changes in these conditions is also uncertain. Future studies should address these two crucial questions and overcome the methodological limitations of previous trials.

Barriers to acceptance: an exploratory study of complementary/alternative medicine disuse.

BACKGROUND: Previous research indicates wide use of complementary and alternative medicine (CAM). While understanding this trend is certainly important, an equally meaningful although largely unexamined research question is: why do the majority of patients and individuals fail to avail themselves of such therapies? Understanding these factors may be particularly important given the increasing evidence suggesting that certain of these therapies may be efficacious. METHODS: A two-page survey that examined demographic characteristics, attitudes toward CAM, and rates of use of specific CAM therapies was mailed to a randomly selected sample of 1680 Stanford University alumni. A total of 601 responses were received (response rate, 35.8%). Multiple regression analyses were carried out to examine predictors of general CAM disuse and disuse of specific therapies. RESULTS: The following variables predicted disuse of CAM in general (p < 0.05): (1) being male (odds ratio [OR] 0.65; 95% confidence interval [CI] 0.44-0.98); (2) being healthy (OR 0.95; 95% CI 0.91-0.99); (3) lack of physician support for CAM use (OR 1.82; 95% CI 1.42-2.29); and (4) believing CAM treatments are ineffective or inferior (OR 0.27; 95% CI 0.19-0.38). Lack of knowledge about CAM approached significance (p = 0.068). With regards to specific therapies, the following patterns were seen: disuse of massage was associated with being male and younger; lack of physician support predicted disuse for all treatments except acupuncture and homeopathy; the belief that CAM treatments in general are ineffective predicted disuse of all therapies except chiropractic while the belief that chiropractic was ineffective predicted its disuse; the perception that CAM produced negative side-effects predicted disuse of chiropractic; lack of knowledge of CAM predicted disuse of herbs, chiropractic, and homeopathy; positive health status was associated with disuse of chiropractic; and finally, the perception that providers were not in accessible locations predicted disuse of all CAM therapies except homeopathy and meditation. CONCLUSIONS: Study findings indicate people are less likely to use CAM if they are male, are in good health, believe that the therapies are in general ineffective or inferior to conventional methods, perceive that conventional medical doctors are not supportive, and to a lesser extent feel they do not have adequate knowledge of CAM. Specifically, avoidance of chiropractic is associated with concerns for safety and side-effects. For treatments that are more provider-based as opposed to self-care based, lack of accessibility-to providers may explain disuse. As researchers continue to demonstrate the clinical efficacy of CAM therapies, these preliminary findings deserve attention because they highlight potential reasons why patients and physicians may be biased against or unable to avail themselves of such therapies.

The efficacy of "distant healing": a systematic review of randomized trials.

PURPOSE: To conduct a systematic review of the available data on the efficacy of any form of "distant healing" (prayer, mental healing, Therapeutic Touch, or spiritual healing) as treatment for any medical condition. DATA SOURCES: Studies were identified by an electronic search of the MEDLINE, PsychLIT, EMBASE, CISCOM, and Cochrane Library databases from their inception to the end of 1999 and by contact with researchers in the field. STUDY SELECTION: Studies with the following features were included: random assignment, placebo or other adequate control, publication in peer-reviewed journals, clinical (rather than experimental) investigations, and use of human participants. DATA EXTRACTION: Two investigators independently extracted data on study design, sample size, type of intervention, type of control, direction of effect (supporting or refuting the hypothesis), and nature of the outcomes. DATA SYNTHESIS: A total of 23 trials involving 2774 patients met the inclusion criteria and were analyzed. Heterogeneity of the studies precluded a formal meta-analysis. Of the trials, 5 examined prayer as the distant healing intervention, 11 assessed noncontact Therapeutic Touch, and 7 examined other forms of distant healing. Of the 23 studies, 13 (57%) yielded statistically significant treatment effects, 9 showed no effect over control interventions, and 1 showed a negative effect. CONCLUSIONS: The methodologic limitations of several studies make it difficult to draw definitive conclusions about the efficacy of distant healing. However, given that approximately 57% of trials showed a positive treatment effect, the evidence thus far merits further study.

Complementary and alternative medicine use among elderly persons: one-year analysis of a Blue Shield Medicare supplement.

BACKGROUND: Large scale surveys in the United States and abroad suggest that 35-60% of adults have used some form of complementary/alternative medicine (CAM). However, no studies to date have focused on predictors and patterns of CAM use among elderly persons. METHODS: The population surveyed were Californians enrolled in a Medicare risk product that offers coverage for acupuncture and chiropractic care. Surveys were mailed to 1597 members in 1997 and responses received by 728 (51% response rate). Health risk assessment data were also obtained at baseline and 12-15 months following enrollment in the plan. Multiple logistic regression analyses were carried out to examine predictors of CAM use. RESULTS: Forty-one percent of seniors reported use of CAM. Herbs (24%), chiropractic (20%), massage (15%), and acupuncture (14%) were the most frequently cited therapies. CAM users tended to be younger, more educated, report either arthritis and/or depression/anxiety, not be hypertensive, engage in exercise, practice meditation, and make more frequent physician visits. Use of CAM was not associated with any observed changes in health status. Respondents also expressed considerable interest in receiving third-party coverage for CAM. Although 80% reported that they had received substantial benefit from their use of CAM, the majority (58%) did not discuss the use of these therapies with their medical doctor. CONCLUSIONS: Findings suggest that there is significant interest in and use of complementary/alternative medicine among elderly persons. These results suggest the importance of further research into the use and potential efficacy of these therapies within the senior population.