Evaluating Lumbar Shape Deformation With Fabric Strain Sensors.

OBJECTIVE: To better study human motion inside the space suit and suit-related contact, a multifactor statistical model was developed to predict torso body shape changes and lumbar motion during suited movement by using fabric strain sensors that are placed on the body. BACKGROUND: Physical interactions within pressurized space suits can pose an injury risk for astronauts during extravehicular activity (EVA). In particular, poor suit fit can result in an injury due to reduced performance capabilities and excessive body contact within the suit during movement. A wearable solution is needed to measure body motion inside the space suit. METHODS: An array of flexible strain sensors was attached to the body of 12 male study participants. The participants performed specific static lumbar postures while 3D body scans and sensor measurements were collected. A model was created to predict the body shape as a function of sensor signal and the accuracy was evaluated using holdout cross-validation. RESULTS: Predictions from the torso shape model had an average root mean square error (RMSE) of 2.02 cm. Subtle soft tissue deformations such as skin folding and bulges were accurately replicated in the shape prediction. Differences in posture type did not affect the prediction error. CONCLUSION: This method provides a useful tool for suited testing and the information gained will drive the development of injury countermeasures and improve suit fit assessments. APPLICATION: In addition to space suit design applications, this technique can provide a lightweight and wearable system to perform ergonomic evaluations in field assessments.

Lumbar posture assessment with fabric strain sensors.

Astronauts are at risk for low back pain and injury during extravehicular activity because of the deconditioning of the lumbar region and biomechanical demands associated with wearing a spacesuit. To understand and mitigate injury risks, it is necessary to study the lumbar kinematics of astronauts inside their spacesuit. To expand on previous efforts, the purpose of this study was to develop and test a generalizable method to assess complex lumbar motion using 10 fabric strain sensors placed on the torso. Anatomical landmark positions and corresponding sensor measurements were collected from 12 male study participants performing 16 static lumbar postures. A multilayer principal component and regression-based model was constructed to estimate lumbar joint angles from the sensor measurements. Good lumbar joint angle estimation was observed (<9° mean error) from flexion and lateral bending joint angles, and lower accuracy (13.7° mean error) was observed from axial rotation joint angles. With continued development, this method can become a useful technique for measuring suited lumbar motion and could potentially be extrapolated to civilian work applications.

Two molecular transitions influence cardiac sodium channel gating.

Sodium channels from diverse excitable membranes are very similar in their structure, yet surprisingly heterogeneous in their behavior. The processes that govern the opening and closing of sodium channels have appeared difficult to describe in terms of a single, unifying molecular scheme. Now cardiac sodium channels have been analyzed by high-resolution single-channel recordings over a broad range of potentials. Channels exhibited both complex and simple gating patterns at different voltages. Such behavioral diversity can be explained by the balance between two molecular transitions whereby channels can exit the open state.

Molecular localization of an ion-binding site within the pore of mammalian sodium channels.

Sodium channels are the major proteins that underlie excitability in nerve, heart, and skeletal muscle. Chemical reaction rate theory was used to analyze the blockage of single wild-type and mutant sodium channels by cadmium ions. The affinity of cadmium for the native tetrodotoxin (TTX)-resistant cardiac channel was much higher than its affinity for the TTX-sensitive skeletal muscle isoform of the channel (microliters). Mutation of Tyr401 to Cys, the corresponding residue in the cardiac sequence, rendered microliters highly susceptible to cadmium blockage but resistant to TTX. The binding site was localized approximately 20% of the distance down the electrical field, thus defining the position of a critical residue within the sodium channel pore.

Adenovirus-mediated expression of a voltage-gated potassium channel in vitro (rat cardiac myocytes) and in vivo (rat liver). A novel strategy for modifying excitability.

Excitability is governed primarily by the complement of ion channels in the cell membrane that shape the contour of the action potential. To modify excitability by gene transfer, we created a recombinant adenovirus designed to overexpress a Drosophila Shaker potassium channel (AdShK). In vitro, a variety of mammalian cell types infected with AdShK demonstrated robust expression of the exogenous channel. Spontaneous action potentials recorded from cardiac myocytes in primary culture were abbreviated compared with noninfected myocytes. Intravascular infusion of AdShK in neonatal rats induced Shaker potassium channel mRNA expression in the liver, and large potassium currents could be recorded from explanted hepatocytes. Thus, recombinant adenovirus technology has been used for in vitro and in vivo gene transfer of ion channel genes designed to modify cellular action potentials. With appropriate targeting, such a strategy may be useful in gene therapy of arrhythmias, seizure disorders, and myotonic muscle diseases.

Local anesthetics as effectors of allosteric gating. Lidocaine effects on inactivation-deficient rat skeletal muscle Na channels.

Time- and voltage-dependent local anesthetic effects on sodium (Na) currents are generally interpreted using modulated receptor models that require formation of drug-associated nonconducting states with high affinity for the inactivated channel. The availability of inactivation-deficient Na channels has enabled us to test this traditional view of the drug-channel interaction. Rat skeletal muscle Na channels were mutated in the III-IV linker to disable fast inactivation (F1304Q: FQ). Lidocaine accelerated the decay of whole-cell FQ currents in Xenopus oocytes, reestablishing the wild-type phenotype; peak inward current at -20 mV was blocked with an IC50 of 513 microM, while plateau current was blocked with an IC50 of only 74 microM (P < 0.005 vs. peak). In single-channel experiments, mean open time was unaltered and unitary current was only reduced at higher drug concentrations, suggesting that open-channel block does not explain the effect of lidocaine on FQ plateau current. We considered a simple model in which lidocaine reduced the free energy for inactivation, causing altered coupling between activation and inactivation. This model readily simulated macroscopic Na current kinetics over a range of lidocaine concentrations. Traditional modulated receptor models which did not modify coupling between gating processes could not reproduce the effects of lidocaine with rate constants constrained by single-channel data. Our results support a reinterpretation of local anesthetic action whereby lidocaine functions as an allosteric effector to enhance Na channel inactivation.

Funding of pilot projects in Latin America: a tool for capacity building in occupational health research.

There is a global need for trained researchers who can address the increasing burden of illness and injury and prepare future generations of researchers. Developing countries have a special need for practical, action-oriented interventions to address workplace problems, based on identification of needs and priorities, development of locally available solutions, and consideration of the sociopolitical context of work and how best to translate research findings into policies. Effective translation and application of research products from industrialized nations to developing countries is essential, but differences in the contexts and local realities of other nations limit extrapolating such research. Funding pilot research projects in developing countries is an effective, practical, and useful tool for training new investigators in research techniques and developing collaborative relationships among countries.

Calcium binding to recoverin: implications for secondary structure and membrane association.

Recoverin is an EF-hand calcium-binding protein reportedly involved in the transduction of light by vertebrate photoreceptor cells. It also is an autoantigen in a cancer-associated degenerative disease of the retina. Measurements by circular dichroism presented here demonstrate that the binding of calcium to recoverin causes large structural changes. increasing the alpha-helical content of the protein and decreasing its beta-turn, beta-sheet and 'other' structures. The maximum helical content (67%) was observed at 100 microM free calcium and, unlike calmodulin, decreased as the calcium concentration was modulated in either direction from this value. Fluorescence measurements indicated that recoverin may aggregate or undergo structural changes independent of calcium binding as the calcium concentration is increased above 100 microM. EGTA also appeared to affect the structure of recoverin independent of its chelation of calcium. While calcium-induced conformational changes have been proposed to alter the membrane binding of recoverin through association of its myristoylated amino terminus, in the experiments presented here the partitioning of recoverin between the cytoplasmic and membrane compartments of the rod photoreceptor outer segment was unaffected by the concentration of calcium, therefore it appears unlikely that a calcium-myristoyl switch acts alone to anchor recoverin directly to the membrane. These experiments were conducted with native recoverin which is heterogeneously acylated, but mass spectrometry confirmed that simple chromatographic methods could be devised to isolate the different forms of recoverin for further studies.

A global survey of occupational health competencies and curriculum.

The World Health Organization has identified a worldwide shortage of occupational health professionals, but evidence suggests that the work and education of these professionals vary across countries. This survey examined the professional development of occupational physicians, occupational nurses, industrial hygienists, and ergonomists in terms of practice competencies and academic curriculum. Of 89 countries that received the survey, 48 (54%) responded. Important differences in competencies and curricula were identified for all groups. More competencies were identified more frequently in developed countries. Academic programs existed more often in developed countries, but curriculum contents varied. The study provides a concrete reference point for discussion and development of competencies and curriculum.

Effects of haemorrhage induced hypotension on coronary blood flow in an anaesthetised two vessel canine coronary stenosis-occlusion model.

STUDY OBJECTIVE: Previous experiments from our group have shown that left anterior descending coronary occlusion in the presence of hypotension caused by intravenous glyceryl trinitrate in an open chest canine model caused endocardial flow to fall in myocardium supplied by a stenosed circumflex coronary artery. The aim of the present study was to assess the effects of hypotension in a similar open chest model but without the vasodilating effect of glyceryl trinitrate on coronary vessels. DESIGN: Blood flow to and function of remote myocardium supplied by a stenosed circumflex coronary artery [gradient 27(SEM 3) mm Hg] was determined in anaesthetised dogs after haemorrhage induced hypotension [mean aortic pressure 70(3) mm Hg] and after left anterior descending coronary occlusion. Transmural blood flow was measured using microspheres and myocardial wall thickness with sonomicrometer crystals. SUBJECTS: 11 healthy mongrel dogs were used, weight 25 kg (range 19-33). MEASUREMENTS AND MAIN RESULTS: Haemorrhage induced hypotension in the setting of a circumflex stenosis reduced endocardial blood flow to the posterior myocardial bed from 0.84 (0.14) to 0.57(0.07) ml.min-1.g-1 but did not alter percent myocardial thickening. When the left anterior descending coronary artery was occluded in the presence of the circumflex stenosis and haemorrhage induced hypotension, there was no further decrease in endocardial blood flow to or thickening of the posterior myocardial bed, despite a reduction in mean coronary artery pressure from 54(3) to 43(3) mm Hg. CONCLUSIONS: These findings are in contrast to our previous findings where hypotension was induced by glyceryl trinitrate. Remote myocardial ischaemia appears to be attenuated in this two vessel stenosis-occlusion model in which hypotension is produced by haemorrhage.

Dispersion of ventricular activation and refractoriness in patients with idiopathic dilated cardiomyopathy.

We sought to evaluate the electrophysiologic substrate for ventricular arrhythmias and sudden cardiac death in patients with idiopathic dilated cardiomyopathy. When compared with controls, patients with cardiomyopathy had prolonged activation times, increased dispersion of activation and recovery, and prolonged duration of monophasic action potential recordings at 70%, but not at 90%, of repolarization.

Safety and effectiveness of placement of pacemaker and defibrillator leads in the axillary vein guided by contrast venography.

Despite evidence of an increased incidence of lead fracture, the infraclavicular subclavian approach remains the dominant approach for placement of pacemaker and implantable defibrillator leads. Although this complication can be prevented by lead placement in the cephalic vein or by recently described approaches for lead placement in the axillary vein, these approaches have not gained widespread acceptance. The purpose of this study was to evaluate the safety and efficacy of an alternative technique for lead placement that uses contrast-guided venipuncture of the axillary vein with a 5Fr micropuncture introducer set. A total of 50 patients underwent an attempt at placement of pacemaker or implantable defibrillator leads via the axillary vein using this new technique. Patients were randomized into 2 groups based on whether the initial attempt at axillary vein access was performed medial or lateral to the rib cage margin. Lead placement was successfully accomplished in 49 of the 50 patients using this technique. Initial success was achieved in each of 25 patients randomized to the medial approach compared with 18 of 24 patients randomized to the lateral approach to the axillary vein (75%). In each of the 6 patients in whom the initial technique failed, lead placement was subsequently achieved with the medial approach. In addition to a higher initial success rate, the medial approach was determined to be preferable as evidenced by a shorter lead placement time, a smaller number of contrast injections, and a reduced requirement for additional micropuncture guidewires. There were no major complications associated with either approach. Contrast-guided venipuncture of the axillary vein is a safe and effective approach to placement of endocardial leads.

Predictors of fluoroscopy time and estimated radiation exposure during radiofrequency catheter ablation procedures.

The objective of this study was to identify factors that predict fluoroscopy duration and radiation exposure during catheter ablation procedures. The patient population included 859 patients who participated in the Atakr Ablation System clinical trial at 1 of 9 centers (398 male and 461 female patients, aged 36 +/- 21 years). Each patient underwent catheter ablation of an accessory pathway, the atrioventricular junction, or atrioventricular nodal reentrant tachycardia using standard techniques. The duration of fluoroscopy was 53 +/- 50 minutes. Factors identified as independent predictors of fluoroscopy duration included patient age and sex, the success or failure of the ablation procedure, and the institution at which the ablation was performed. Catheter ablation in adults required longer fluoroscopy exposure than it did in children. Men required longer durations of fluoroscopy exposure than did women. The mean estimated "entrance" radiation dose was 1.3 +/- 1.3 Sv. The dose needed to cause radiation skin injury was exceeded during 22% of procedures. The overall mean effective absorbed dose from catheter ablation procedures was 0.025 Sv for female patients and 0.017 Sv for male patients. This degree of radiation exposure would result in an estimated 1,400 excess fatal malignancies in female patients and 2,600 excess fatal malignancies in male patients per 1 million patients.

Delayed sequelae of pituitary irradiation.

Since 1958, 781 patients at Lawrence Berkeley Laboratory have received helium-particle stereotactic radiosurgery to the adenohypophysis. Autopsy findings in 15 of these patients are reported. Ten patients received pituitary radiation (average dose, 116 Gy in six fractions) for progressive neovascularization retinopathy due to diabetes mellitus. Evidence of a time-dependent course of progressive fibrosis in their pituitary glands was found. Five patients were treated for eosinophilic adenomas. Although they had lower average doses of radiation (56 Gy in six fractions), their pituitary glands showed cystic cavitation of the adenomas. The adenomas thus appeared more radiosensitive than the normal pars anterior, which, in turn, was more radiosensitive than the adjacent neurohypophysis. No significant radiation changes were found in the surrounding brain or cranial nerves. The endocrine organs under pituitary control showed varying degrees of atrophy, and clinical tests revealed progressive hypofunction. It was concluded that charged-particle therapy produced a sharply delineated focal radiation lesion confined to the pituitary gland but did not cause injury to the critical structures of the surrounding central nervous system.

Comparison of adenosine effects on atrioventricular node reentry and atrioventricular reciprocating tachycardias.

BACKGROUND: Adenosine is an established first line therapy for the treatment of narrow complex tachycardias. The two most common etiologies of paroxysmal supraventricular tachycardia (SVT) are atrioventricular node reentry tachycardia (AVNRT) and atrioventricular reciprocating tachycardia (AVRT). HYPOTHESIS: We postulated that adenosine might have different effects on the termination of AVNRT vs. AVRT, and that these differences might assist in the noninvasive differentiation between these diagnoses. METHODS: Fifty-nine patients referred for the diagnosis and treatment of SVT were included in the study. All patients had SVT induced during electrophysiology testing, and each patient received adenosine during SVT. The adenosine dose, time to tachycardia termination, and site of tachycardia termination were recorded. Seventeen patients required isoproterenol administration to initiate SVT. This subset of patients was compared with those not requiring isoproterenol. RESULTS: There was no statistically significant difference in the adenosine dose or time to tachycardia termination when comparing patients with AVNRT with those with AVRT. All patients with AVNRT had termination of tachycardia in the antegrade direction with final activation in the atria. Patients requiring isoproterenol for tachycardia initiation experienced tachycardia termination significantly faster than those not requiring isoproterenol, although there was no difference in the dose of adenosine required for termination. CONCLUSION: These data demonstrate that patients with dual AV node physiology and AVNRT do not have altered sensitivity to adenosine compared with patients with AVRT and normal AV nodes. Further investigation will be required to determine the clinical utility of the significantly shorter time to tachycardia termination for patients receiving isoproterenol.

Prospects for genetic manipulation of cardiac excitability.

Despite impressive advances in the therapy of a number of types of heart disease in the last two decades, sudden cardiac death remains a public health problem of staggering dimensions. Current treatment options include antiarrhythmic drugs that have higher than desired failure rates and implantable defibrillators that incur significant costs to the patient and society. The development of therapies that better suppress the cardiac arrhythmias responsible for sudden cardiac death requires a broad and comprehensive understanding of the basic mechanisms underlying electrical instability in the heart. This study explores the scientific basis for a molecular genetic approach to modify cardiac excitability and thereby to create animal models of sudden cardiac death. The availability of such models will open up new avenues of research in arrhythmogenesis and facilitate the development of novel antiarrhythmic agents.

Histologic determination of the ischemic threshold of muscle in the canine compartment syndrome model.

Our objective was to define the critical tissue pressure at which irreversible muscle damage occurs and to compare our results to those thresholds advocated in the orthopaedic literature. A standard plasma infusion compartment syndrome model was created in a canine model. Four dogs were in each of four experimental groups with compartment pressure maintained as follows: (a) 30 mm Hg with support of diastolic blood pressure to a level > 50 mm Hg; (b) 20 mm Hg less than diastolic pressure; (c) 10 mm Hg less than diastolic blood pressure; (d) a level equal to the animal's diastolic blood pressure. All animals were sacrificed 14 days after the procedure. Histology revealed the following: (a) tissues pressurized to 30 mm Hg in a normotensive dog demonstrated no significant abnormalities; (b) tissues pressurized to 20 mm Hg less than diastolic revealed occasional cells undergoing regeneration but no evidence of infarction or fibrosis; (c) tissues pressurized to 10 mm Hg less than diastolic showed scattered small areas of infarction and fibrosis; and (d) tissues pressurized to diastolic blood pressure demonstrated more widespread infarction and scarring. The ischemic threshold of muscle, beyond which irreversible tissue damage occurs, is directly related to the difference in compartment and perfusion pressure. Our findings document this pressure to be 10 mm Hg less than diastolic blood pressure or within 30 mm Hg of mean arterial pressure. This data refutes the use of absolute tissue pressure values as a guide to the necessity of fasciotomy. To abort an impending compartment syndrome and avoid irreversible tissue injury and their sequelae, fasciotomy should be done if tissue pressure reaches within 10-20 mm Hg of diastolic pressure.

Chromosomal diversity in Lactococcus lactis and the origin of dairy starter cultures.

A large collection of Lactococcus lactis strains, including wild-type isolates and dairy starter cultures, were screened on the basis of their phenotype and the macrorestriction patterns produced from pulsed-field gel electrophoresis (PFGE) analysis of SmaI digests of genomic DNA. Three groups of dairy starter cultures, used for different purposes in the dairy industry, and a fourth group made up of strains isolated from the environment were selected for analysis of their chromosomal diversity using the endonuclease I-CeuI. Chromosome architecture was largely conserved with each strain having six copies of the rRNA genes, and the chromosome size of individual strains ranged between 2,240 and 2,688 kb. The origin of L. lactis strains showed the greatest correlation with chromosome size, and dairy strains, particularly those with the cremoris phenotype, had smaller chromosomes than wild-type strains. Overall, this study, coupled with analysis of the sequenced L. lactis genomes, provides evidence that defined strain dairy starter cultures have arisen from plant L. lactis strains. Adaptation of these strains to the dairy environment has involved loss of functions resulting in smaller chromosomes and acquisition of genes (usually plasmid associated) that facilitate growth in milk. We conclude that dairy starter cultures generally and the industrially used cremoris and diacetylactis phenotype strains in particular comprise a specialized group of L. lactis strains that have been selected to become an essential component of industrial processes and have evolved accordingly, so that they are no longer fit to survive outside the dairy environment.