Left-right differences in the proximal femur's strength of post-menopausal women: a multicentric finite element study.

UNLABELLED: The strength of both femurs was estimated in 198 post-menopausal women through subject-specific finite element models. Important random differences between contralateral femurs were found in a significant number of subjects, pointing to the usefulness of further studies to understand if strength-based classification of patients at risk of fracture can be affected by laterality issues. INTRODUCTION: Significant, although small, differences exist in mineral density and anatomy of contralateral proximal femurs. These differences, and their combined effect, may result in a side difference in femurs' strength. However, this has never been tested on a large sample of a homogenous population. METHODS: The strength of both femurs was estimated in 198 post-menopausal women through CT-derived finite element models, built using a validated procedure, in sideways fall conditions. The impact of the resulting asymmetry on the classification of subjects at risk of fracture was analysed. RESULTS: The small difference observed between sides (the right femur on average 4 % stronger than the left) was statistically significant but mechanically negligible. In contrast, higher random differences (absolute difference between sides with respect to mean value) were found: on average close to 15 % (compared to 9.2 % for areal bone mineral density (aBMD) alone), with high scatter among the subjects. When using a threshold-based classification, the right and left femurs were discordant up to over 20 % of cases (K always lower than 0.60) but the left femur was concordant (mean K = 0.84) with the minimum strength between right and left. CONCLUSION: Considering both femurs may be important when trying to classify subjects at risk of failure with strength estimates. Future studies including fracture assessment would be necessary to quantify the real impact.

Locally measured microstructural parameters are better associated with vertebral strength than whole bone density.

UNLABELLED: Whole vertebrae areal and volumetric bone mineral density (BMD) measurements are not ideal predictors of vertebral fractures. We introduce a technique which enables quantification of bone microstructural parameters at precisely defined anatomical locations. Results show that local assessment of bone volume fraction at the optimal location can substantially improve the prediction of vertebral strength. INTRODUCTION: Whole vertebrae areal and volumetric BMD measurements are not ideal predictors of vertebral osteoporotic fractures. Recent studies have shown that sampling bone microstructural parameters in smaller regions may permit better predictions. In such studies, however, the sampling location is described only in general anatomical terms. Here, we introduce a technique that enables the quantification of bone volume fraction and microstructural parameters at precisely defined anatomical locations. Specific goals of this study were to investigate at what anatomical location within the vertebrae local bone volume fraction best predicts vertebral-body strength, whether this prediction can be improved by adding microstructural parameters and to explore if this approach could better predict vertebral-body strength than whole bone volume fraction and finite element (FE) analyses. METHODS: Eighteen T12 vertebrae were scanned in a micro-computed tomography (CT) system and FE meshes were made using a mesh-morphing tool. For each element, bone microstructural parameters were measured and correlated with vertebral compressive strength as measured experimentally. Whole bone volume fraction and FE-predicted vertebral strength were also compared to the experimental measurements. RESULTS: A significant association between local bone volume fraction measured at a specific central region and vertebral-body strength was found that could explain up to 90% of the variation. When including all microstructural parameters in the regression, the predictive value of local measurements could be increased to 98%. Whole bone volume fraction could explain only 64% and FE analyses 76% of the variation in bone strength. CONCLUSIONS: A local assessment of volume fraction at the optimal location can substantially improve the prediction of bone strength. Local assessment of other microstructural parameters may further improve this prediction but is not clinically feasible using current technology.

Genetic variability and phylogenetic aspects in species of the genus Macrobrachium.

The genus Macrobrachium includes prawns, which are widely distributed in lakes, floodplains, and rivers in tropical and subtropical regions of South America. This genus presents nearly 210 known species with great ecological and economic importance. However, few studies are related to the biology of these crustaceans. In this study, we analyzed the genetic variability and phylogenetic relationship between Macrobrachium amazonicum and Macrobrachium jelskii, which are closely related species. Additionally, they are syntopics and their taxonomy poses problems because it is difficult to differentiate between the species. We used the mitochondrial gene sequences COI and 16S rRNA to assess the genetic structure of these species in 3 populations that were collected from Tiete hydrographic basin (São Paulo State, Brazil). The interspecific comparison of samples that were collected at the same and different locations showed a low rate of genetic variability. This similarity was attributed to the recent introduction of these species in the regions that were sampled and the habitat conditions in which they inhabit. In addition, these results may be consistent with the hypothesis that they are a single species, interspecific hybrids, or metapopulation. The dendrogram analyses did not reveal the formation of clusters, confirming the disturbances in the genetic structure of the samples that were analyzed in this study. These data are pioneers to these crustaceans, and they confirm the ecological and evolutionary problems between these Macrobrachium species.

Extensive risk analysis of mechanical failure for an epiphyseal hip prothesis: a combined numerical-experimental approach.

There has been recent renewed interest in proximal femur epiphyseal replacement as an alternative to conventional total hip replacement. In many branches of engineering, risk analysis has proved to be an efficient tool for avoiding premature failures of innovative devices. An extensive risk analysis procedure has been developed for epiphyseal hip prostheses and the predictions of this method have been compared to the known clinical outcomes of a well-established contemporary design, namely hip resurfacing devices. Clinical scenarios leading to revision (i.e. loosening, neck fracture and failure of the prosthetic component) were associated with potential failure modes (i.e. overload, fatigue, wear, fibrotic tissue differentiation and bone remodelling). Driving parameters of the corresponding failure mode were identified together with their safe thresholds. For each failure mode, a failure criterion was identified and studied under the most relevant physiological loading conditions. All failure modes were investigated with the most suitable investigation tool, either numerical or experimental. Results showed a low risk for each failure scenario either in the immediate postoperative period or in the long term. These findings are in agreement with those reported by the majority of clinical studies for correctly implanted devices. Although further work is needed to confirm the predictions of this method, it was concluded that the proposed risk analysis procedure has the potential to increase the efficacy of preclinical validation protocols for new epiphyseal replacement devices.

Coherent detection of electron dephasing.

We show that an Aharonov-Bohm ring with asymmetric electron injection can act as a coherent detector of electron dephasing. The presence of a dephasing source in one of the two arms of a moderately-to-highly asymmetric ring changes the response of the system from total reflection to complete transmission while preserving the coherence of the electrons propagating from the ring, even for strong dephasing. We interpret this phenomenon as an implementation of an interaction-free measurement.

Genetic polymorphism, molecular characterization and relatedness of Macrobrachium species (Palaemonidae) based on RAPD-PCR.

The prawn genus Macrobrachium belongs to the family Palaemonidae. Its species are widely distributed in lakes, reservoirs, floodplains, and rivers in tropical and subtropical regions of South America. Globally, the genus Macrobrachium includes nearly 210 known species, many of which have economic and ecological importance. We analyzed three species of this genus (M. jelskii, M. amazonicum and M. brasiliense) using RAPD-PCR to assess their genetic variability, genetic structure and the phylogenetic relationship between them and to look for molecular markers that enable separation of M. jelskii and M. amazonicum, which are closely related syntopic species. Ten different random decamer primers were used for DNA amplification, yielding 182 fragments. Three of these fragments were monomorphic and exclusive to M. amazonicum or M. jelskii and can be used as specific molecular markers to identify and separate these two species. Similarity indices and a phylogenetic tree showed that M. amazonicum and M. jelskii are closest to each other, while M. brasiliense was the most differentiated species among them; this may be attributed to the different habitat conditions to which these species have been submitted. This information will be useful for further studies on these important crustacean species.

Comparison of patient-led, fibromyalgia-orientated physical activity and a non-specific, standardised 6-month physical activity program on quality of life in individuals with fibromyalgia: a protocol for a randomised controlled trial.

BACKGROUND: Exercise has been shown to significantly improve pain and function in individuals with fibromyalgia. Research into the effectiveness of exercise is often based on standardised exercise programmes that are chosen by the investigating clinical research team. However, such programmes may not necessarily be appealing to the participating patients. Furthermore, in addition to being taught exercises, patients with chronic conditions like fibromyalgia also need to learn to manage their condition themselves and so be actively involved in their treatment. The primary aim of this study is to compare the effects of two, 6-month physical activity programs on quality of life in patients with fibromyalgia. One group followed a patient-led, fibromyalgia-orientated programme (experimental) whilst the control group followed a standard, general exercise programme. METHODS: This protocol is an open-label, two-centre, randomised, controlled superiority trial. Two treatment arms will be compared: an experimental group (patient-led, fibromyalgia-orientated exercise) and a control group (general exercise program). The control group will participate in the exercise programme currently provided in our centre, which involves general, group exercise for patients with various pathologies. The experimental group will be taught the principles of exercise specifically for fibromyalgia during a one-to-one coaching session. They will then be guided in the choice of one or several types of exercise that they enjoy. They will be instructed to perform the exercise according to the recommendations for exercise in fibromyalgia with regard to intensity, duration and frequency. The protocol will last for 6 months; participants will then be followed-up for a further 6 months. They will also be encouraged to continue exercising after the end of the protocol. Outcomes will be evaluated at baseline, 6 and 12 months. The primary outcome will be quality of life (Fibromyalgia Impact Questionnaire) and the secondary outcomes will include measures of pain (including a visual analogue scale and the neuropathic characteristics of the pain), depression (Hospital Anxiety and Depression Scale), kinesiophobia (Tampa scale of kinesiophobia) and adherence (Polar OH1 heart rate monitor). DISCUSSION: The results of this study will show if patient-led, fibromyalgia-orientated exercise is more effective than a general exercise programme on fibromyalgia-related outcomes, including quality of life, and on adherence to continued exercise. TRIAL REGISTRATION: ClinicalTrials.gov NCT03895086 . Registration no. 2018-A02881-54. Registered on 29 March 2019.

Counteraction by MutT protein of transcriptional errors caused by oxidative damage.

Oxidized guanine (8-oxo-7,8-dihydroguanine; 8-oxo-G) is a potent mutagen because of its ambiguous pairing with cytosine and adenine. The Escherichia coli MutT protein specifically hydrolyzes both 8-oxo-deoxyguanosine triphosphate (8-oxo-dGTP) and 8-oxo-guanosine triphosphate (8-oxo-rGTP), which are otherwise incorporated in DNA and RNA opposite template A. In vivo, this cleaning of the nucleotide pools decreases both DNA replication and transcription errors. The effect of mutT mutation on transcription fidelity was shown to depend on oxidative metabolism. Such control of transcriptional fidelity by the ubiquitous MutT function has implications for evolution of RNA-based life, phenotypic expression, adaptive mutagenesis, and functional maintenance of nondividing cells.

Costs and benefits of high mutation rates: adaptive evolution of bacteria in the mouse gut.

We have shown that bacterial mutation rates change during the experimental colonization of the mouse gut. A high mutation rate was initially beneficial because it allowed faster adaptation, but this benefit disappeared once adaptation was achieved. Mutator bacteria accumulated mutations that, although neutral in the mouse gut, are often deleterious in secondary environments. Consistently, the competitiveness of mutator bacteria is reduced during transmission to and re-colonization of similar hosts. The short-term advantages and long-term disadvantages of mutator bacteria could account for their frequency in nature.

Can 3D ultrasound and doppler angiography of great arteries be included in second trimester ecocardiographic examination? A prospective study on low-risk pregnancy population.

The introduction of new applications such as the spatiotemporal image correlation (STIC) and the tomographic ultrasound imaging (TUI) has greatly enhanced the study of cardiac and vessels anatomy. The aim of our study was to assess the feasibility of including real-time volumetric 3D reconstruction of heart anatomy and Doppler angiography of great vessels during routine second trimester pregnancy scan, in a low-risk population. Visualization of the pulmonary veins, ductus venosus and inferior vena cava was significantly superior with 3D ultrasound. Therefore, STIC makes it possible to store heart beats for a mean time of 10 s, to replay acquired volumes in slow motion, to study the heart atrium along three axes and retrace volumetric image storage inversely from the apex to the base of the heart, making reconstruction of the four-chamber view and great artery outflow tract much easier and faster. Furthermore, the use of digital communication allow operators to store and send volume of images that can be postprocessed by external consultant specialists worldwide. Although 3D echocardiography is less time-consuming and independent of fetal positioning in utero when compared with 2D it may be premature to include 3D and 3D Doppler angiography among routine examination. However, the study of the outflow tracts by 2D echocardiography should be implemented in order to improve the diagnostic accuracy of CHDs. At present, only "targeted" cases in which a routine 2D scan has raised diagnostic doubts should undergo a second level sonography for a thorough 2D-3D examination of cardiac and vessels anatomy.

Severe brain damage from twin-twin transfusion syndrome treated with serial amnioreductions after 26 weeks: a case to reconsider the gestational age limits of laser therapy.

We report a case of monochorionic twin pregnancy complicated by twin-twin transfusion syndrome (TTTS) diagnosed in the late second trimester and treated with two amnioreductions. Three days after the first amniodrainage, the recipient twin developed intracranial ventriculomegaly and, similarly, after a few days, the donor showed signs of brain damage at MRI. We discuss the possible mechanism of brain damage of amnioreductions performed after 26 weeks of gestation in a monochorionic pregnancy with TTTS as a result of a placental 'steal' phenomenon.

Strain distribution in the proximal human femoral metaphysis.

There is significant interest in the stress-strain state in the proximal femoral metaphysis, because of its relevance for hip fractures and prosthetic replacements. The scope of this work was to provide a better understanding of the strain distribution, and of its correlation with the different directions of loading, and with bone quality. A total of 12 pairs of human femurs were instrumented with strain gauges. Six loading configurations were designed to cover the range of directions spanned by the hip joint force. Inter-specimen variability was reduced if paired specimens were considered. The principal strain magnitude varied greatly between loading configurations. This suggests that different loading configurations need to be simulated in vitro. The strain magnitude varied between locations but, on average, was compatible with the strain values measured in vivo. The strain magnitudes and the direction of principal tensile strain in the head and neck were compatible with the spontaneous fractures of the proximal femur reported in some subjects. The principal tensile strain was significantly larger where the cortical bone was thinner; the compressive strain was larger where the cortical bone was thicker. The direction of the principal strain varied significantly between measurement locations but varied little between loading configurations. This suggests that the anatomy and the distribution of anisotropic material properties enable the proximal femur to respond adequately to the changing direction of daily loading.

Stress shielding and stress concentration of contemporary epiphyseal hip prostheses.

After the first early failures, proximal femoral epiphyseal replacement is becoming popular again. Prosthesis-to-bone load transfer is critical for two reasons: stress shielding is suspected of being responsible for a number of failures of early epiphyseal prostheses; stress concentration is probably responsible of the relevant number of early femoral neck fractures in resurfaced patients. The scope of this work was to experimentally investigate the load transfer of a commercial epiphyseal prosthesis (Birmingham Hip Replacement (BHR)) and an innovative prototype proximal epiphyseal replacement. To investigate bone surface strain, ten cadaveric femurs were instrumented with 15 triaxial strain gauges. In addition the cement layer of the prototype was instrumented with embedded gauges to estimate the strain in the adjacent trabecular bone. Six different loading configurations were investigated, with and without muscles. For the BHR prosthesis, significant stress shielding was observed on the posterior side of the head-neck region (the strain was halved); a pronounced stress concentration was observed on the anterior surface (up to five times in some specimens); BHR was quite sensitive to the different loading configurations. For the prototype, the largest stress shielding was observed in the neck region (lower than the BHR; alteration less than 20 per cent); some stress concentration was observed at the head region, close to the rim of the prosthesis (alteration less than 20 per cent); the different loading configurations had similar effects. Such large alterations with respect to the pre-operative conditions were found only in regions where the strain level was low. Conversely, alterations were moderate where the strain was higher. Thus, prosthesis-to-bone load transfer of both devices has been elucidated; the prototype preserved a stress distribution closer to the physiological condition.

Reversal of compensatory flow in severe intrauterine growth restriction: middle cerebral artery and intracardiac volume flow modifications.

AIM: The aim of the study was to investigate cerebral and cardiac volume flow modifications in a group of preterm severely growth restricted (GR) fetuses with absent end diastolic flow (AEDF) in the umbilical artery. METHODS: Doppler indices of GR fetuses born at less than 32 weeks of gestation with AEDF in umbilical artery were longitudinally analyzed. Ductus venosus S/A, umbilical artery PI, middle cerebral artery (MCA) pulsatility index (PI), MCA volume flow and intracardiac flows were checked daily. The value of volume flow was determined by multiplying the vessel area obtained by means of a power angiography by the integral of the velocimetric curve. In Group 1 the time of delivery was decided when abnormal Doppler index in ductus venosus (S/A>3) was detected. In Group 2, decisions about delivery were based on maternal indications or on various cardiotocographic (CTG) abnormalities. The division in the two groups was made with a retrospective method. RESULTS: Fifteen GR fetuses were studied: seven cases entered Group 1 and eight cases Group 2. In Group 2 velocimetric (PI) and quantitative (volume flow) values remained stable until delivery. In all cases in Group 1 ductus venosus anomalies (S/A>3) were preceded by 24 hours by cerebral volume flow indices indicating the loss of MCA vasodilatation and by changes in intracardiac volume flow indices, while the PI increase in MCA was present only 24 hours after the changes detected by the volume flow study and were simultaneous to ductus venosus modifications. CONCLUSION: The decrease in volume flow through the middle cerebral artery occurs at least 24 hours before the increase of middle cerebral artery PI and before the ductus venosus anomalies. Flow through the four cardiac valves show modification in agreement to the changes of the middle cerebral artery flow.

Changes in femur stress after hip resurfacing arthroplasty: response to physiological loads.

BACKGROUND: Hip resurfacing arthroplasty is being increasingly considered as an alternative to total hip arthroplasty in young, active patients. Hip resurfacing arthroplasty is reported to preserve the normal joint mechanics. However, there is concern, in the short term, due to frequent occurrence of femoral neck fractures. METHODS: We evaluated changes in femoral mechanics after hip resurfacing arthroplasty. We used an experimentally validated, distributed material finite element model of a cadaveric femur before and after hip resurfacing arthroplasty. Bone stiffness and strength values representing normal, elderly and osteoporotic bone were used. For a physiological load case, bone strains were compared with literature values for total hip arthroplasty and a risk of fracture scalar calculated. FINDINGS: The changes in peak stresses after hip resurfacing arthroplasty were low in relation to the failure strength of bone and the fracture risk was low. The intact and implanted finite element models showed bone strains after hip resurfacing arthroplasty were closer to the intact condition than after total hip arthroplasty. INTERPRETATION: The bone stresses predicted after resurfacing in both the normal and aged femoral neck were not sufficient to be a potential cause of fracture.

Experimental validation of a finite element model of a composite tibia.

Composite bones are synthetic models made to simulate the mechanical behaviour of human bones. Finite element (FE) models of composite bone can be used to evaluate new and modified designs of joint prostheses and fixation devices. The aim of the current study was to create an FE model of a composite tibia and to validate it against results obtained from a comprehensive set of experiments. For this, 17 strain rosettes were attached to a composite tibia (model 3101, Pacific Research Laboratories, Vashon, Washington, USA). Surface strains and displacements were measured under 13 loading conditions. Two FE models were created on the basis of computed tomography scans. The models differed from each other in the mesh and material properties assigned. The experiments were simulated on them and the results compared with experimental results. The more accurate model was selected on the basis of regression analysis. In general, experimental strain measurements were highly repeatable and compared well with published results. The more accurate model, in which the inner elements representing the foam were assigned isotropic material properties and the elements representing the epoxy layer were assigned transversely isotropic material properties, was able to simulate the mechanical behaviour of the tibia with acceptable accuracy. The regression line for all axial loads combined had a slope of 0.999, an intercept of -6.24 microstrain, and an R2 value of 0.962. The root mean square error as a percentage was 5 per cent.

The rise and fall of mutator bacteria.

Bacteria with elevated mutation rates are frequently found among natural isolates. This is probably because of their ability to generate genetic variability, the substrate for natural selection. However, such high mutation rates can lead to the loss of vital functions. The evolution of bacterial populations may happen through alternating periods of high and low mutation rates. The cost and benefits of high mutation rates in the course of bacterial adaptive evolution are reviewed.

A new software tool for 3D motion analyses of the musculo-skeletal system.

BACKGROUND: Many clinical and biomechanical research studies, particularly in orthopaedics, nowadays involve forms of movement analysis. Gait analysis, video-fluoroscopy of joint replacement, pre-operative planning, surgical navigation, and standard radiostereometry would require tools for easy access to three-dimensional graphical representations of rigid segment motion. Relevant data from this variety of sources need to be organised in structured forms. Registration, integration, and synchronisation of segment position data are additional necessities. With this aim, the present work exploits the features of a software tool recently developed within a EU-funded project ('Multimod') in a series of different research studies. METHODS: Standard and advanced gait analysis on a normal subject, in vivo fluoroscopy-based three-dimensional motion of a replaced knee joint, patellar and ligament tracking on a knee specimen by a surgical navigation system, stem-to-femur migration pattern on a patient operated on total hip replacement, were analysed with standard techniques and all represented by this innovative software tool. Segment pose data were eventually obtained from these different techniques, and were successfully imported and organised in a hierarchical tree within the tool. FINDINGS: Skeletal bony segments, prosthesis component models and ligament links were registered successfully to corresponding marker position data for effective three-dimensional animations. These were shown in various combinations, in different views, from different perspectives, according to possible specific research interests. INTERPRETATION: Bioengineering and medical professionals would be much facilitated in the interpretation of the motion analysis measurements necessary in their research fields, and would benefit therefore from this software tool.

Tumor necrosis factor alpha induces apoptosis in mammary adenocarcinoma cells by an increase in intranuclear free Ca2+ concentration and DNA fragmentation.

The incubation of human mammary adenocarcinoma cells (BT-20) with tumor necrosis factor alpha in the absence or presence of cycloheximide resulted in progressive DNA fragmentation. This was preceded by a sustained increase in intracellular free Ca2+ concentration and was not detected in cells pretreated with intracellular Ca2+ chelators, calmodulin antagonists, or activators of protein kinase C. Image analysis of fura-2-loaded BT-20 cells treated with tumor necrosis factor alpha revealed that, in many cells, the initial increase in Ca2+ level occurred in a cellular region that corresponded to the localization of the nucleus. Our findings suggest that tumor necrosis factor alpha can promote an increase in intranuclear free Ca2+ which, in turn, may stimulate Ca(2+)-dependent endonuclease activity, resulting in DNA fragmentation and apoptosis.

Genetic barriers among bacteria.

Barriers to chromosomal gene transfer between bacterial species control their genetic isolation. These barriers, such as different microhabitats, the host ranges of genetic exchange vectors and restriction-modification systems, limit gene exchange, but the major limitation is genomic sequence divergence. The mismatch-repair system inhibits interspecies recombination, the inducible SOS system stimulates interspecies recombination, while natural selection determines the effective recombination frequencies.