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Postnatal enlargement of human tracheobronchial airways and implications for particle deposition.

In support of predictions for inhaled particle deposition, morphometric measurements were taken on 20 replica airway casts of people aged 11 days to 21 years. Measurements of right upper lobe airway lengths, diameters, and branching angles were made such that a growth model suitable as input to predictive equations for particle deposition efficiency was obtained. The tracheobronchial airways growth was describable by linear regressions on body length. The length-to-diameter ratio of growing airways did not change in any simple way as a function of airway generation. Airflow rates for a given state of physical activity for various ages were found from previously published data to be describable by linear regressions on body mass. Three states of physical exertion-low activity, light exertion, and heavy exertion-were used for modeling purposes. The computed particle deposition efficiencies indicate that under most circumstances smaller (younger) people will have greater tracheobronchial deposition efficiencies than larger (older) people. For example, tracheobronchial dose on a per kilogram body mass basis for 5-micron-diameter particles may be more than 6 times higher in the resting newborn than in the resting adult assuming equivalent deposition efficiencies above the larynx.

Adolescent↗

Skeletal structural adaptations to mechanical usage (SATMU): 1. Redefining Wolff's law: the bone modeling problem.

From the nature of a bone's endload and its local surface strains, the theory computes a modeling operator, Gamma (gamma), that predicts whether mechanical factors will cause lamellar bone modeling drifts, and where and of what kind. A given mechanical bone strain history then provides a separate modeling rate function, M, to specify the rate of such modeling drifts as fractions of the largest possible ones. Multiplying the two functions, e.g., gamma.M, then predicts mechanically controlled bone modeling responses for cortical and trabecular bone, both quantitatively and qualitatively. The theory correctly predicts each of the 6 known "principal adaptations" of lamellar bone, which provide a critical test of any such theory for this organ. The theory accounts for biologic, biomechanical, and clinical-pathologic knowledge not available in Wolff's time nor accounted for by most biomechanicians since. Existing proven methods can provide all numerical data needed to satisfy the theory's mathematical equations and already suggest provisional values for most of them. Its originator views the theory as the kernel of more and better theories to come rather than a finished work, a kernel that suggests a new and in some respects novel logical framework for analysing the problems, and a kernel that invites critique, refinement, and/or exploitation by others.

Adaptation, Physiological↗

Skeletal structural adaptations to mechanical usage (SATMU): 2. Redefining Wolff's law: the remodeling problem.

Basic multicellular unit (BMU)-based remodeling of lamellar bone causes bone turnover, net gains and losses of bone on some bone surfaces or "envelopes," and a remodeling space comprising bone temporarily absent due to evolving resorption spaces and incomplete refilling of them by new bone. Those features depend a) on how many new BMU arise annually, b) on how much bone each BMU has resorbed and c) formed upon its completion, and d) on how long the typical BMU takes to become completed. Because a, b, and c have limiting or maximal values in life that direct and/or indirect effects of mechanical usage of the skeleton can change, the theory presented here derives mechanical usage functions that express what fractions of those maxima a given mechanical usage history allows to happen. The theory predicts some changes in bone formation, resorption, balance, turnover, and remodeling space that depend on how remodeling responds to the vigor of a subject's mechanical usage. The theory can predict specific effects of specific mechanical challenges that experiments can test, and it fits abundant published evidence. As the kernel of a new approach to the problem it awaits critique and refinement by others. It plus the 3-way rule can redefine Wolff's law conceptually and also in mathematical and quantifiable form.

Adaptation, Physiological↗

Skeletal structural adaptations to mechanical usage (SATMU): 4. Mechanical influences on intact fibrous tissues.

This paper proposes that the growth in length of living fibrous tissue structures (tendon, ligament, fascia) responds primarily to circulating systemic rather than mechanical factors. However, growth of the thickness of those structures responds primarily to their mechanical tension loads in the special sense that, when the tissue's typical peak mechanical strains exceed a threshold value, its cells begin to add new collagen to increase its thickness, strength, and tension stiffness. When subsequent peak strains reduce to the threshold value, then further additions of collagen stop. That process defines mechanically controlled modeling of fibrous tissues. The collagen in these tissues can also develop mechanical microdamage (MDx) under repeated tension load-deload cycles. Special maintenance mechanisms normally repair that MDx to prevent accumulations that would threaten structural integrity. As a result, spontaneous complete ruptures of these structures can happen when MDx production exceeds its repair. These maintenance mechanisms also prevent gradual stretching under continuous tension loads, a process the author suggests calling creep compensation. When the creep compensation mechanism becomes incompetent, structures can stretch under continuous loads; when it becomes overactive, contractures can occur. The above meld of fact and inference provides the kernel of a general theory for the responses of the architecture and mechanical competence of intact fibrous tissues to mechanical usage.

Adaptation, Physiological↗

Biomechanics of the rostrum in crocodilians: a comparative analysis using finite-element modeling.

This article reports the use of simple beam and finite-element models to investigate the relationship between rostral shape and biomechanical performance in living crocodilians under a range of loading conditions. Load cases corresponded to simple biting, lateral head shaking, and twist feeding behaviors. The six specimens were chosen to reflect, as far as possible, the full range of rostral shape in living crocodilians: a juvenile Caiman crocodilus, subadult Alligator mississippiensis and Crocodylus johnstoni, and adult Caiman crocodilus, Melanosuchus niger, and Paleosuchus palpebrosus. The simple beam models were generated using morphometric landmarks from each specimen. Three of the finite-element models, the A. mississippiensis, juvenile Caiman crocodilus, and the Crocodylus johnstoni, were based on CT scan data from respective specimens, but these data were not available for the other models and so these--the adult Caiman crocodilus, M. niger, and P. palpebrosus--were generated by morphing the juvenile Caiman crocodilus mesh with reference to three-dimensional linear distance measured from specimens. Comparison of the mechanical performance of the six finite-element models essentially matched results of the simple beam models: relatively tall skulls performed best under vertical loading and tall and wide skulls performed best under torsional loading. The widely held assumption that the platyrostral (dorsoventrally flattened) crocodilian skull is optimized for torsional loading was not supported by either simple beam theory models or finite-element modeling. Rather than being purely optimized against loads encountered while subduing and processing food, the shape of the crocodilian rostrum may be significantly affected by the hydrodynamic constraints of catching agile aquatic prey. This observation has important implications for our understanding of biomechanics in crocodilians and other aquatic reptiles.

Alligators and Crocodiles↗

Improved training of house officers in a rheumatology consult service.

This study examined whether the clinical environment could be used to increase internal medicine house officers' adoption of care recommendations taught in a didactic conference. Subjects were 11 internal medicine house officers who served 6-week rheumatology elective rotations. At the start of each of four rotation periods, house officers attended a 1-hour conference in which periarticular rheumatic disorders associated with knee pain (anserine bursitis, pseudothrombophlebitis) and shoulder pain (bicipital tendinitis) were discussed. All house officers also practiced physical examination techniques on anatomic models simulating the disorders. During alternate rotation periods, reminder sheets were appended to the records of arthritis patients with histories of chronic knee or shoulder pain. The frequency with which house officers followed conference recommendations was documented by direct observation (6 house officers in 17 encounters with reminders, 5 house officers in 30 encounters without reminders). Specific questioning about a recent history of knee or shoulder pain and the performance of four of five recommended physical examination maneuvers were increased significantly by reminder sheets in patients' charts (P < 0.05 for all). Although rheumatology faculty often have limited options available to increase the number of house officer trainees or to intensify clinical activity, qualitative improvements within existing logistic parameters are feasible by assuring that the clinical environment (e.g., patient records) contains salient cues that will prompt desired actions.

Clinical Competence↗

The ADAM-integrin-tetraspanin complex in fetal and postnatal testicular cords.

New insights have emerged about the expression, during testicular cord formation, of the ADAM (a disintegrin and metalloprotease) domain family of proteins that combines both cell surface adhesion and proteolytic activity; this family includes integrins alpha3beta1 and alpha6beta1 and tetraspanins, a distinct family of proteins containing four transmembrane domains, a small and a large extracellular loop, and short cytoplasmic tails. ADAM3 (cyritestin), ADAM5, ADAM6, and ADAM15 are expressed in fetal rat testes. In contrast, the expression of the ADAM1/ADAM2 pair (fertilin alpha/fertilin beta, respectively) is not detected in fetal testis. Yet the expression of ADAM1 starts immediately after birth, and is followed within 24 hr by the expression of ADAM2. Therefore, the ADAM1/ADAM2 heterodimer is visualized far in advance of the meiotic and spermiogenic phase of spermatogenesis. A similar expression pattern was observed for integrin subunits alpha3, alpha6, and beta1, as well as for tetraspanins CD9, CD81, and CD98; the latter is a single-pass integrin subunit beta1-binding protein. ADAM2, integrin subunits alpha3, alpha6, and beta1, and tetraspanin CD9 and CD81 immunoreactive sites are observed in prespermatogonia (also known as primordial germ cells or gonocytes). A model is proposed in which the ADAM-integrin-tetraspanin complex, known to constitute a network of membrane microdomains called the tetraspanin web, may be involved in the migration of prespermatogonia from the center to the periphery of the testicular cords and in the reinitiation of mitotic activity during the initial wave of spermatogenesis. A complementary model consists in the rearrangement of the tetraspanin web in prespermatogonia/spermatogonia undergoing spontaneous or Fas-induced apoptosis upon coculturing with Sertoli cells. In this model, the cellular site involved in the formation of preapoptotic bodies is devoid of tetraspanin-integrin clusters, in contrast with nonapoptotic cells, which display a diffuse circumferential distribution. In apoptotic prespermatogonia, immunoreactive clusters are restricted to sites where the attachment of prespermatogonia/spermatogonia to Sertoli cell surfaces is still preserved.

Animals↗

Genomics spawns novel approaches to mosquito control.

In spite of advances in medicine and public health, malaria and other mosquito-borne diseases are on the rise worldwide. Although vaccines, genetically modified mosquitoes and safer insecticides are under development, herein we examine a promising new approach to malaria control through better repellents. Current repellents, usually based on DEET, inhibit host finding by impeding insect olfaction, but have significant drawbacks. We discuss how comparative genomics, using data from the Anopheles genome project, allows the rapid identification of members of three protein classes critical to insect olfaction: odorant-binding proteins, G-protein-coupled receptors, and odorant-degrading enzymes. A rational design approach similar to that used by the pharmaceutical industry for drug development can then be applied to the development of products that interfere with mosquito olfaction. Such products have the potential to provide more complete, safer and longer lasting protection than conventional repellents, preventing disease transmission by interrupting the parasite life cycle.

Animals↗

The evolutionary origins and significance of vertebrate left-right organisation.

In the last few years, an understanding has emerged of the developmental mechanism for the consistent internal left-right structure, termed situs, that characterises vertebrate anatomy. This involves largely vertebrate-conserved (i.e. 'phylotypic') gene expression cascades that encode 'leftness' and 'rightness' in appropriate tissues either side of the embryo's midline soon after gastrulation. Recent evidence indicates that the initial, directional symmetry breaking that initiates these cascades utilises mechanisms that are conserved or at least closely related in different vertebrate types. I describe a scenario whereby the capacity for directional modification of an otherwise bilateral body plan can be viewed as an adaptive innovation rather closely connected with vertebrate origins, enabling optimal 'design' for very active lifestyles. But an alternative scenario, while retaining the view that situs and indeed other vertebrate functional lateralisations are deeply adaptive, proposes that they originated in the co-optation of left-right developmental information inherited from a very early stage in metazoan diversification. It is proposed that a remote chordate ancestor lost its original or 'ur-bilaterian' symmetry to pass through an altogether non-symmetrical stage, and that the vertebrate dorsoventral midline plane is not descended from that original one. I review the considerable evidence in favour of this scenario, and discuss its wider implications for directional asymmetries across the Metazoa.

Anatomy↗

Hox and wings.

In many bilaterian phyla, appendages are morphological traits that characterise the identity of the various body parts. In pterygote insects, wings are dorsal appendages on the thorax. The famous "bithorax" fly created by Ed Lewis is the emblematic example of the role of Hox genes.1 Now, Tomoyasu et al.,2 using classical genetics, transgenesis and RNAi, have examined the function of thoracic Hox genes in the beetle Tribolium castaneum. Beetles have rigid elytra in place of the first pair of wings. Instead of the expected transformation of the elytron into a wing, loss of Hox genes' function leads to the homeotic transformation of the second pair of dorsal appendages, the wings, into elytra. This has important consequences for the way that we see the role of Hox genes in development and evolution.

Animals↗

The multidimensionality of cell behaviors underlying morphogenesis: a case study in ascidians.

Databases where different types of information from different sources can be integrated, cross-referenced and interactively accessed are necessary for building a quantitative understanding of the molecular and cell biology intrinsic to the morphogenesis of an embryo. Tassy and colleagues recently reported the development of software tailor-made to perform such a task, along with the generation and integration of three-dimensional anatomical models of embryos. They convincingly illustrated the utility of their approach by applying it to the early ascidian embryo.

Animals↗

Effects of an alternate dissection schedule on gross anatomy laboratory practical performance.

The current medical curricula reform that is taking place in many medical schools throughout the world has resulted in less time for gross anatomy laboratory instruction. In response, anatomists are using a variety of approaches (e.g., peer teaching, prosections, plastinated anatomical models, etc.) to adapt to these changes. To accommodate recent curricular reform at the University of Health Sciences College of Osteopathic Medicine, an alternating dissection schedule was implemented. The purpose of this study is to examine the effects of the alternating schedule on gross anatomy laboratory practical performance. Using a Mann-Whitney Rank Sum test, back and upper limb (back-upper limb), and lower extremity laboratory practical performance for students who dissected in every laboratory (EL group; n = 227) is compared to students who dissected in every other laboratory (EOL group; n = 254). For the back-upper limb part of the anatomy laboratory practical, the mean percentage scores for the EL and EOL groups were 74.5% and 68.1%, respectively (P < 0.001). The mean percentage scores for the EL and EOL groups on the lower limb portion of the anatomy lab practical were 75.9% and 75.6%, respectively (P = 0.994). These data suggest that the use of an alternating dissection schedule had an equivocal effect on the students' gross anatomy laboratory practical performance for these two sections. The reasons for these conflicting results may have been related to regional complexity or volume of information, and the sequence in which the regions were taught.

Anatomy↗

A graphic, three-dimensional teaching model to demonstrate the topography of the human heart.

A three-dimensional graphic model of the human heart and an accompanying description are presented as a teaching aid. Each of the four chambers is represented by a cube of equal size. Drawings of the model from various angles give views of each of the surfaces and show the interatrial, interventricular, and atrioventricular grooves, and superimposed coronary arteries and cardiac veins.

Coronary Vessels↗

Sources of error in quantitative coronary angiography.

Many studies have reported the accuracy of quantitative coronary angiography (QCA) based on experiments using moderated-size phantoms imaged under unrealistic radiographic conditions. However, these observations may not be generalizable to the setting of clinical angiography. To determine QCA accuracy in a realistic radiographic setting and evaluate the impact of the x-ray system line spread function, plexiglass phantoms were imaged inside and out of a human thorax. A realistic radiographic background was associated with a 38% increase in variability of results (p < 0.05). Low concentrations of contrast and large image intensifier input screens were associated with significantly larger errors and variability in results (p < 0.05). There was a systematic overestimation of diameter in the smallest phantom. A mathematical model of the x-ray line spread function was developed that explains the observed overestimation of the smallest phantom and provide a rational approach for correction of the line spread function for QCA. Many factors encountered in clinical coronary angiography such as nonuniform radiographic background, low concentrations of contrast, and small vessel diameters have a significant adverse impact on the accuracy and/or variability of gradient-based edge detection QCA systems.

Artifacts↗

On-line quantitative coronary analysis in clinical practice: one step closer to reality?

Quantitative coronary analysis is widely used in studies of progression/regression and restenosis of coronary lesions. On-line digital systems are used in diagnostic coronary angiography, and as a guide in coronary interventions. The aim of this investigation was to test the reliability of measures obtained with one commercially available on-line equipment. Well-visualized coronary lesions from patient studies were analyzed for variability in single-frame measurement. Procedural factors affecting the consistency of measurements were identified by repeated visualization of the same coronary lesion with hand- and power-injection of contrast in various positions in the field of the image intensifier, and by imaging of steel phantoms in the same positions. Steel phantoms closely resembling coronary lesions as encountered in practice were visualized in the most favourable radiologic setting compatible with clinical situations. Accuracy and precision of measurements were found to be worse than reported in validation studies. This may be due to a host of variables which may need to be tested in each laboratory performing on-line quantitative coronary angiography, when data so obtained are to be used in clinical decision making or in research studies.

Artifacts↗