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Noses and neurons: induction, morphogenesis, and neuronal differentiation in the peripheral olfactory pathway.

Non-axial mesenchymal/epithelial (M/E) induction guides peripheral olfactory pathway differentiation using cellular and molecular mechanisms similar to those in the developing limbs, aortic arches, and branchial arches. At each of these bilaterally symmetric sites off the midline axis, a thickened ectodermal epithelium is apposed to a specialized mesenchyme derived largely, but not exclusively, from the neural crest. The capacity of M/E interaction in the olfactory primordia (the combined olfactory placodal epithelium and adjacent mesenchyme) to induce a distinct class of sensory receptor neurons-olfactory receptor neurons-suggests that this mechanism has been modified to accommodate neurogenesis, neurite outgrowth, and axon guidance, in addition to musculoskeletal differentiation, chondrogenesis, and vasculogenesis. Accordingly, although the olfactory primordia share signaling molecules and transcriptional regulators with other bilaterally symmetric, non-axial sites such as limb buds, their activity may be adapted to mediate distinct aspects of cellular differentiation and process outgrowth during the initial assembly of a sensory pathway-the primary olfactory pathway-during early forebrain development.

Animals↗

Physical discomfort among visual display terminal users in a semiconductor manufacturing company: a study of prevalence and relation to psychosocial and physical/ergonomic factors.

The associations among several alleged psychosocial and physical/ergonomics risk factors and the visual and musculoskeletal discomforts were assessed in a cross-sectional study of 119 video display terminal (VDT) users in a semiconductor manufacturing company. Cases of discomfort were identified using self-reported discomfort symptoms through questionnaire surveys. Data on individual, physical/ergonomic, and psychosocial aspects were obtained. Multivariate logistic regression models were developed to predict physical discomforts of 11 body areas. The prevalence of upper extremity discomfort found in this semiconductor manufacturing company was 42%, which is similar to the prevalence among VDT users in telecommunication companies and the newspaper industry. Full-time VDT users (data-entry personnel, programming engineers, and CAD engineers) had significantly higher rates of physical discomfort (66%) than part-time VDT users (fabrication engineers) (41%). Physical/ergonomic variables were found more dominant than psychosocial factors for visual and upper extremity discomforts. However, psychosocial variables were the dominant for back and lower extremity discomfort, when compared with the subjectively characterized physical/ergonomic factors. Because both physical/ergonomics variables and psychosocial factors and some of their interactions were associated with visual and musculoskeletal discomfort, integrating psychosocial prevention with physical/ergonomic design improvements is an effective approach to reducing the prevalence of discomfort.

Adult↗

Human osteoprogenitor bone formation using encapsulated bone morphogenetic protein 2 in porous polymer scaffolds.

The ability to deliver, over time, biologically active osteogenic growth factors by means of designed scaffolds to sites of tissue regeneration offers tremendous therapeutic opportunities in a variety of musculoskeletal diseases. The aims of this study were to generate porous biodegradable scaffolds encapsulating an osteogenic protein, bone morphogenetic protein 2 (BMP-2), and to examine the ability of the scaffolds to promote human osteoprogenitor differentiation and bone formation in vitro and in vivo. BMP-2-encapsulated poly(DL-lactic acid) (PLA) scaffolds were generated by an innovative supercritical fluid process developed for solvent-sensitive and thermolabile growth factors. BMP-2 released from encapsulated constructs promoted adhesion, migration, expansion, and differentiation of human osteoprogenitor cells on three-dimensional scaffolds. Enhanced matrix synthesis and cell differentiation on growth factor-encapsulated scaffolds was observed after culture in an ex vivo model of bone formation developed on the basis of the chick chorioallantoic membrane model. BMP-2-encapsulated polymer scaffolds showed morphologic evidence of new bone matrix and cartilage formation after subcutaneous implantation and within diffusion chambers implanted into athymic mice as assessed by X-ray analysis and immunocytochemistry. The generation of three-dimensional biomimetic structures incorporating osteoinductive factors such as BMP-2 indicates their potential for de novo bone formation that exploits cell-matrix interactions and, significantly, realistic delivery protocols for growth factors in musculoskeletal tissue engineering.

Adolescent↗

A national qualitative survey of community-based musculoskeletal services in the UK.

OBJECTIVE: To determine the characteristics of community-based musculoskeletal services provided by primary care organizations within the UK. METHODS: Members of five professional groups within UK primary care organizations (n=461) were sent a questionnaire. RESULTS: The response rate by organization was 71% (328/461). Respondents described 350 community-based musculoskeletal services, 233/328 (71%) organizations had one or more musculoskeletal services within their community. Five main forms of service provision were: a scanning service, a rehabilitation service, physiotherapy services, joint or soft tissue injections and the implementation of integrated care pathways. In 162 services, patients were assessed, reviewed or triaged, by a 'non-consultant' health-care professional (physiotherapist or general practitioner), at an intermediate level between primary and secondary care. The purpose of the service was described in 292/350 services, only 39/350 had clear evaluation strategies and 53/350 had consideration of individual training needs. CONCLUSIONS: There are a wide range of musculoskeletal services flourishing within the community sector, whose quality may be variable. Whilst there is good evidence to suggest systematic planning of these services, we are concerned about the lack of data to support their effectiveness in terms of clinical outcomes, monitoring of service delivery standards and ongoing professional development of service providers. Commissioners of such services must ensure they have taken account of the evidence base and met any identified needs of local populations. Services should have a clear purpose with an appropriate evaluation strategy, and well-defined dissemination mechanisms. An integrated educational strategy for staff within the service must be sensitive to issues relating to accreditation, appraisal and revalidation.

Community Health Services↗

Relationship of running to musculoskeletal pain with age. A six-year longitudinal study.

OBJECTIVE: To determine, by longitudinal study, whether long-distance running, maintained for many years, is associated with increased musculoskeletal pain with age. METHODS: A 6-year prospective longitudinal study of 410 runners' club members and 289 community controls, age 53-75 years at study initiation, was conducted. Subjects were also categorized as ever-runners (n = 488) and never-runners (n = 211). The primary dependent variable was pain score as indicated on a horizontal double-anchored analog scale; data for this variable were available beginning in 1987. Statistical adjustment for age, education level, smoking, alcohol consumption, history of arthritis, and presence of other major medical conditions was done by analysis of covariance. Further analyses of previously reported associations of regular vigorous physical activity with decreased disability and mortality after 9 years were performed. RESULTS: The degree of musculoskeletal pain was slightly lower in the exercise group compared with controls, and the difference was statistically significant for women but not for men. Average adjusted pain scores for men were 18.3 (SEM 0.8) in runners' club members, 20.2 (1.2) in controls, 18.6 (0.8) in ever-runners, and 20.3 (1.6) in never-runners. For women, these scores were 17.5 (1.8) in runners' club members versus 22.8 (1.4) in controls (P < 0.05), and 17.2 in ever runners versus 23.7 (1.5) in never-runners (P < 0.002). Disability had continued to develop in runners' club members at a rate only one-third that in the controls after 9 years of observation. Mortality over 9 years consisted of 51 deaths, of which 41 were in the control group and only 10 were among runners' club members. CONCLUSION: Vigorous running activity over many years is not associated with an increase in musculoskeletal pain with age, and there may be a moderate decrease in pain, particularly in women. Vigorous physical activity is associated with greatly decreased levels of disability and with decreased mortality rates.

Age Factors↗

Effects of daily administration of prostaglandin E2 and its withdrawal on the lumbar vertebral bodies in male rats.

The effects of daily prostaglandin E2 (PGE2) treatment (on) and PGE2 treatment followed by withdrawal (on-off) on cancellous bone in lumbar vertebral bodies were studied in 7-month-old male Sprague-Dawley rats. The first groups of rats were given daily subcutaneous injections of 0, 1, 3, and 6 mg PGE2/kg/d for 60, 120, and 180 days, and the second group of rats were given PGE2 for 60 days followed by withdrawal for 60 and 120 days. Histomorphometric analyses were performed on double-fluorescent labeled undecalcified sections of fourth lumbar vertebral bodies. Systemic PGE2 treatment elevated cancellous bone mass of lumbar vertebral bodies 26-60% above control levels within 60 days and continued treatment maintained it for another 120 days, but the excess bone was lost after the treatment was withdrawn. PGE2 treatment for 60 days increased trabecular bone area, trabecular width, and bone formation parameters, and shortened remodeling periods in a dose-response manner. These changes were sustained at the levels achieved by 60-day treatment in the rats treated for 120 and 180 days. The eroded perimeter increased at day 60 and further at day 120 and then plateaued. In the on-off treated rats, the cancellous bone area, bone formation, and resorption parameters returned to near age-related controls by 60 days after withdrawal and were maintained there after 120 days of withdrawal. Therefore we conclude that the continuous treatment is needed in order to maintain the PGE2-induced bone gain. When these findings were compared to those previously reported for the proximal tibial metaphyses, we found that the proximal tibial spongiosa was much more responsive to PGE2 treatment than the fourth lumbar vertebral body.

Aging↗

Clinical MR in the year 2010.

This article tries to look into the future of magnetic resonance imaging. Deducing from six rules, it pinpoints the most likely developments of this imaging technique.

Brain Diseases↗

Complications and nonclosure rates of fasciotomy for trauma and related risk factors.

The objective of this study was to identify risk factors for the development of complications and unsatisfactory skin closure following fasciotomy for trauma. Risk factors included in the study are prolonged time from injury to fasciotomy, type of fasciotomy, site of injury, and kind of underlying injury. The study was a retrospective analysis of 100 consecutive fasciotomies done for trauma over a period of 38 months (December 1991 to January 1995) in a "level I" trauma center at a university-affiliated county teaching hospital. Ninety-four patients were eligible for analysis, 29 of whom (31%) developed complications at the fasciotomy site. The risk was increased for lower extremity versus upper extremity (34.3% versus 20.8%), prophylactic versus therapeutic (42.0% versus 24.6%), late (>8 hours) versus early (37% versus 25%), and vascular versus musculoskeletal (38.8% versus 22.2%) trauma cases. The same risk factors negatively influenced the ability to close the skin primarily. The four subgroups defined by vascular/nonvascular injury and upper/lower extremity site had significantly different nonclosure rates (p = 0.043). The rate was highest among the vascular/lower extremity group (60.5%) and lowest among the nonvascular/upper extremity group (15.4%). We concluded that fasciotomies in lower extremities, the presence of underlying vascular injuries, fasciotomies performed prophylactically, and a time between the injury and fasciotomy of more than 8 hours are associated with an increased risk for local complications. The same factors are associated with an increased need for skin grafting the wound.

Adult↗

Prostaglandin E2 prevents ovariectomy-induced cancellous bone loss in rats.

The object of this study was to determine whether prostaglandin E2 (PGE2) can prevent ovariectomy-induced cancellous bone loss. Thirty-five 3-month-old female Sprague-Dawley rats were divided into two groups. The rats in the first group were ovariectomized (OVX) while the others received sham operation (sham-OVX). The OVX group was further divided into three treatment groups. The daily doses for the three groups were 0, 1 and 6 mg PGE2/kg for 90 days. Bone histomorphometric analyses were performed on double-fluorescent-labeled undecalcified proximal tibial metaphysis (PTM). We confirmed that OVX induces massive cancellous bone loss (-80%) and a higher bone turnover (+143%). The new findings from the present study demonstrate that bone loss due to ovarian hormone deficiency can be prevented by a low-dose (1 mg) daily administration of PGE2. Furthermore, a higher-dose (6 mg) daily administration of PGE2 not only prevents bone loss but also adds extra bone to the proximal tibial metaphyses. PGE2 at the 1-mg dose level significantly increased trabecular bone area, trabecular width, trabecular node density, density of node to node, ratio of node to free end, and thus significantly decreased trabecular separation from OVX controls. At this dose level, these same parameters did not differ significantly from sham-OVX controls. However, at the 6-mg dose level PGE2, there were significant increases in trabecular bone area, trabecular width, trabecular node density, density of node to node, and ratio of node to free end, while there was significant decrease in trabecular separation from both OVX and sham-operated controls. The changes in indices of trabecular bone microanatomical structure indicated that PGE2 prevented bone loss as well as the disconnection of existing trabeculae. In summary, PGE2 administration to OVX rats decreased bone turnover and increased bone formation parameters resulting in a positive bone balance that prevented bone loss (in both lower and higher doses) and added extra bone to metaphyses of OVX rats (in higher dose). These findings support the strategy of the use of bone stimulation agents in the prevention of estrogen depletion bone loss (postmenopausal osteoporosis).

Aging↗

Experimental verification of a computational technique for determining ground reactions in human bipedal stance.

We have developed a three-dimensional (3D) biomechanical model of human standing that enables us to study the mechanisms of posture and balance simultaneously in various directions in space. Since the two feet are on the ground, the system defines a kinematically closed-chain which has redundancy problems that cannot be resolved using the laws of mechanics alone. We have developed a computational (optimization) technique that avoids the problems with the closed-chain formulation thus giving users of such models the ability to make predictions of joint moments, and potentially, muscle activations using more sophisticated musculoskeletal models. This paper describes the experimental verification of the computational technique that is used to estimate the ground reaction vector acting on an unconstrained foot while the other foot is attached to the ground, thus allowing human bipedal standing to be analyzed as an open-chain system. The computational approach was verified in terms of its ability to predict lower extremity joint moments derived from inverse dynamic simulations performed on data acquired from four able-bodied volunteers standing in various postures on force platforms. Sensitivity analyses performed with model simulations indicated which ground reaction force (GRF) and center of pressure (COP) components were most critical for providing better estimates of the joint moments. Overall, the joint moments predicted by the optimization approach are strongly correlated with the joint moments computed using the experimentally measured GRF and COP (0.78 < or = r(2) < or = 0.99,median,0.96) with a best-fit that was not statistically different from a straight line with unity slope (experimental=computational results) for postures of the four subjects examined. These results indicate that this model-based technique can be relied upon to predict reasonable and consistent estimates of the joint moments using the predicted GRF and COP for most standing postures.

Computer Simulation↗

Dynamic temporal and spatial regulation of the cdk inhibitor p57(kip2) during embryo morphogenesis.

The complete developmental expression pattern of the cyclin dependent kinase inhibitor (CDKI) p57(kip2) has not been reported, here we report a detailed study of the localization of p57(kip2) protein during mouse organogenesis. We show that p57(kip2) is coincident with key stages of differentiation of several organs, some but not all of which are affected in Beckwith-Weidermann syndrome, a human congenital syndrome characterized by foetal overgrowth and childhood tumours.

Animals↗

Antenatal sonographic diagnosis of clubfoot: a six-year experience.

In the period 1988 through 1993, 6351 pregnant women were referred to the Department of Obstetrics and Gynaecology, University "La Sapienza", Roma, for suspected fetal anomalies or maternofetal problems. All underwent serial transabdominal and/or transvaginal ultrasound scanning, which revealed a total of 235 fetuses with hydrocephalus, cardiac, or musculoskeletal malformations. Forty-one clubfeet were detected in 27 pregnancies in the early part of the second trimester of pregnancy. Of these, 14 feet in eight patients were isolated, and were classified as idiopathic. A clubfoot was associated with neural tube defects in six patients, with anomalies of the urinary and/or digestive system in a further six, with a cystic hygroma in two, and with other musculoskeletal abnormalities in the other six patients. Amniocentesis revealed an abnormal karyotype in six fetuses (22.2%). In only two cases was oligohydramnios present. In both these patients, a fetal urinary tract malformation was present Polyhydramnios was found in 18 cases, and a normal amount of amniotic fluid was found in the remaining seven cases. Polyhydramnios was present in six of the eight idiopathic clubfoot fetuses. Clubfoot is associated with musculoskeletal and visceral anomalies in a high proportion of cases. The association of clubfoot with polyhydramnios in a high proportion of cases does not support the hypothesis of intrauterine moulding as an etiological factor in its development. Ultrasonographical prenatal detection of a clubfoot should prompt amniocentesis, as the condition is associated with an abnormal karyotype in a significant proportion of cases.

Abnormalities, Multiple↗

The solid state environment orchestrates embryonic development and tissue remodeling.

Cell interactions with extracellular matrix and with other cells play critical roles in morphogenesis during development and in tissue homeostasis and remodeling throughout life. Extracellular matrix is information-rich, not only because it is comprised of multifunctional structural ligands for cell surface adhesion receptors, but also because it contains peptide signaling factors, and proteinases and their inhibitors. The functions of these groups of molecules are extensively interrelated. In this review, three primary cell culture models are described that focus on adhesion receptors and their roles in complex aspects of morphogenesis and remodeling: the regulation of proteinase expression by fibronectin and integrins in synovial fibroblasts; the regulation of osteoblast differentiation and survival by fibronectin, and the regulation of trophoblast differentiation and invasion by integrins, cadherins and immunoglobulin family adhesion receptors.

Animals↗

[MR-guided core biopsy of the shoulder: possibilities and experience with a vertically open 0.5T system].

PURPOSE: The availability of open whole body MRI magnets and MR-compatible instrumentarium were essential conditions for the progression of interventional MRI. The advantages of an MR-guided biopsy at the musculoskeletal system are the visualization of the puncture site of a representative area for tumor histology, the absence of exposure to radiation and the free selection of imaging planes. The purpose of the study was the development of a new technique of a secure MR-guided biopsy of intraosseus lesions in the humeral head. MATERIAL AND METHODS: MR-guided core biopsy of a intraosseus lesion of the humeral head was performed in five male patients on a vertical open, whole body MRI magnet (SIGNA SP/i 0.5T, GE Medical Systems). The technique using interactive MRI and the MR-compatible instrumentarium are described. RESULTS: A secure core biopsy could be obtained from a representative area for tumor histology in all cases. No complications occurred, especially no nerve or vessel lesion, no rotator cuff lesion and no intra-articular contamination of the shoulder joint were observed. CONCLUSION: A new technique is presented to obtain MR-guided core biopsies of intraosseous lesions of the humeral head. Furthermore, clinical indications of this technique are described.

Adult↗

[Guillain-Barré syndrome as differential diagnosis of intervertebral disk-induced nerve root compression].

INTRODUCTION: Diagnosis of Guillian-Barré Syndrome usually is not difficult, but diagnostic failure occurs for the variable initial presentation. Diagnosis is based on physical examination showing loss of motor strength in more than one limb and loss of deep tendon reflexes. Ventilatory assistance, pharmacologic maintenance of cardiovascular homeostasis, corticosteroids, IgG and plasma exchange are the dominant therapeutic measures. CASE: This article reports on a case of a 59-year old surgeon suffering from degenerative disc disease in the lumbar spine. The patient developed a severe course of the Guillian-Barré Syndrome with persisting motor weakness of the legs. CONCLUSION: If the primary problem at presentation is limb and back pain the pathology appears to be in the musculoskeletal rather than in neurological system. The awareness of this presentation of Guillian-Barré-Syndrome will eliminate delay in diagnosis.

Diagnosis, Differential↗

Predictive models of carpal tunnel syndrome causation among VDT operators.

Carpal tunnel syndrome (CTS), a cumulative trauma disorder of the hand and wrist, is one of the most common disabling injuries experienced by video-display terminal (VDT) operators. The purpose of this study was to develop a theoretically based operational quantitative predictive model of the risk of work-related CTS among VDT operators. A total of 100 female VDT operators, who performed a variety of office functions, were studied at a major midwestern university. Data were collected on job exposure, anthropometry and posture factors using questionnaires, direct observation and video-recording. Discriminant analysis and logistic regression were performed to develop the operational models. The results of the study indicated the following: (1) percentage of workday working with a VDT was the most significant factor and accounted for 60% of the variance explaining the causation of musculoskeletal discomforts associated with CTS; (2) discriminant function with six variables (i.e. work duration, trunk incline, wrist extension, wrist ulnar deviation, overall anthropometric measure, weighted anthropometric measure) correctly classified 73% of the CTS group and 72% of the non-CTS group; (3) using the logistic regression model, the probabilities associated with changes in the predictive variables as affecting CTS risk are presented such that increasing the daily work duration from 1 h to 4 h increases the probability of CTS risk from 0.45 to 0.92. The results of the study suggest that the main causation of CTS is job design, the secondary (and lesser cause) is posture associated with the workplace design and the least contributing factor to CTS causation is the individual's anthropometric make-up.

Analysis of Variance↗

Effects of spaceflight on rat humerus geometry, biomechanics, and biochemistry.

The effects of a 12.5-day spaceflight (Cosmos 1887 biosatellite) on the geometric, biomechanical, and biochemical characteristics of humeri of male specific pathogen-free rats were examined. Humeri of age-matched basal control, synchronous control, and vivarium control rats were contrasted with the flight bones to examine the influence of growth and space environment on bone development. Lack of humerus longitudinal growth occurred during the 12.5 days in spaceflight. In addition, the normal mid-diaphysial periosteal appositional growth was affected; compared with their controls, the spaceflight humeri had less cortical cross-sectional area, smaller periosteal circumferences, smaller anterior-posterior periosteal diameters, and smaller second moments of area with respect to the bending and nonbending axes. The flexural rigidity of the flight humeri was comparable to that of the younger basal control rats and significantly less than that of the synchronous and vivarium controls; the elastic moduli of all four groups, nonetheless, were not significantly different. Generally, the matrix biochemistry of the mid-diaphysial cross sections showed no differences among groups. Thus, the spaceflight differences in humeral mechanical strength and flexural rigidity were probably a result of the differences in humeral geometry rather than material properties.

Animals↗

Somatic symptoms of distress: an international primary care study.

The objective of this study was to examine cross-national differences in somatic symptoms associated with psychological distress. Data from the World Health Organization (WHO) collaborative study of psychological problems in general health care (5438 patients at 15 sites) were used to examine somatic symptoms associated with psychological distress. At each site, a stratified random sample of consecutive primary care patients completed the 28-item General Health Questionnaire (GHQ) and the Composite International Diagnostic Interview (CIDI). At all sites, the number of current CIDI somatic symptoms (whether medically explained or not) was strongly associated with current psychological distress (measured by selected GHQ-28 items). Pearson correlation of somatic symptom count with psychological distress score was .42 for all sites and ranged from .20 to .58 (p < .0001 at all sites). Across all sites, anxiety and depressive symptoms showed roughly the same association with somatic symptom counts, and specific somatic symptoms or symptom clusters did not show differential association with anxiety or depression. Although somatic symptoms did cluster into meaningful groups (gastrointestinal, neurological/conversion, autonomic, and musculoskeletal), these symptom groups did not show differential association with psychological distress. Examination of individual somatic symptoms and symptom clusters across sites did not reveal clear patterns of association according to geography or level of economic development. These data show a strong association between somatic symptoms and psychological distress, which did not vary across disparate cultures and levels of economic development. Cultural factors, however, may influence the meaning attached to symptoms or the likelihood of presentation for health care.

Adolescent↗