Muscle fiber phenotype: a culprit of abnormal metabolism and function in skeletal muscle of humans with obesity.

The proportion of the different types of fibers in a given skeletal muscle contributes to its overall metabolic and functional characteristics. Greater proportion of type I muscle fibers is associated with favorable oxidative metabolism and function of the muscle. Humans with obesity have a lower proportion of type I muscle fibers. We discuss how lower proportion of type I fibers in skeletal muscle of humans with obesity may explain metabolic and functional abnormalities reported in these individuals. These include lower muscle glucose disposal rate, mitochondrial content, protein synthesis, and quality/contractile function, as well as increased risk for heart disease, lower levels of physical activity, and propensity for weight gain/resistance to weight loss. We delineate future research directions and the need to examine hybrid muscle fiber populations, which are indicative of a transitory state of fiber phenotype within skeletal muscle. We also describe methodologies for precisely characterizing muscle fibers and gene expression at the single muscle fiber level to enhance our understanding of the regulation of muscle fiber phenotype in obesity. By contextualizing research in the field of muscle fiber type in obesity, we lay a foundation for future advancements and pave the way for translation of this knowledge to address impaired metabolism and function in obesity.

Using exogenous organizational and regional hospital attributes to explain differences in case-mix adjusted hospital costs.

Diagnosis-related group (DRG) hospital reimbursement systems differentiate cases into cost-homogenous groups based on patient characteristics. However, exogenous organizational and regional factors can influence hospital costs beyond case-mix differences. Therefore, most countries using DRG systems incorporate adjustments for such factors into their reimbursement structure. This study investigates structural hospital attributes that explain differences in average case-mix adjusted hospital costs in Switzerland. Using rich patient and hospital-level data containing 4 million cases from 120 hospitals across 3 years, we show that a regression model using only five variables (number of discharges, ratio of emergency/ambulance admissions, rate of DRGs to patients, expected loss potential based on DRG mix, and location in large agglomeration) can explain more than half of the variance in average case-mix adjusted hospital costs, capture all cost variations across commonly differentiated hospital types (e.g., academic teaching hospitals, children's hospitals, birth centers, etc.), and is robust in cross-validations across several years (despite differing hospital samples). Based on our findings, we propose a simple practical approach to differentiate legitimate from inefficiency-related or unexplainable cost differences across hospitals and discuss the potential of such an approach as a transparent way to incorporate structural hospital differences into cost benchmarking and payment schemes.

Ten year experience with the concomitant Maze IV procedure for atrial fibrillation.

OBJECTIVE: The Maze IV (M-IV) procedure is regarded as the golden standard in treatment for surgical ablation of atrial fibrillation (AF); however, long-term follow-up results are scarce. We present our institutional 10-year experience. METHODS: We collected data of 117 consecutive patients who have undergone a concomitant M-IV procedure between April 2006 and April 2016. Primary endpoints are freedom of atrial arrhythmias and freedom of atrial arrhythmias off antiarrhythmic drugs (AAD). RESULTS: Forty-seven patients (40.2%) had paroxysmal AF. Two-thirds of the procedures included mitral valve surgery. The average follow-up time per patient was 3.8 years (SD 2.8). Freedom of AF at 1 year was 79%, at 5 years freedom of AF was 69% and freedom of AF off AAD was 56%. Predictors of AF recurrence in multivariate analysis were age, preoperative pacemakers, redo cardiac surgery and in-hospital AF. Preoperative PVI ablation was found to be a protective factor. CONCLUSIONS: The long-term outcomes of the M-IV procedure are good and remain stable over the years. Results could be improved if follow-up were to be intensified and recurrences dealt with aggressively. Key question: How many patients are free from AF in a 10-year period after concomitant M-IV surgical ablation? Key findings: In the long term around 70% of patients are free of AF with an increasing need for anti-arrhythmic drugs. Take home message: Early to midterm freedom from AF after concomitant M-IV procedure is high and remains stable after 3 years.

A student guide to proofreading and writing in science.

Scientific writing requires a distinct style and tone, whether the writing is intended for an undergraduate assignment or publication in a peer-reviewed journal. From the first to the final draft, scientific writing is an iterative process requiring practice, substantial feedback from peers and instructors, and comprehensive proofreading on the part of the writer. Teaching writing or proofreading is not common in university settings. Here, we present a collection of common undergraduate student writing mistakes and put forth suggestions for corrections as a first step toward proofreading and enhancing readability in subsequent draft versions. Additionally, we propose specific strategies pertaining to word choice, structure, and approach to make products more fluid and focused for an appropriate target audience.

Finite Element-Based Mechanical Assessment of Bone Quality on the Basis of In Vivo Images.

Beyond bone mineral density (BMD), bone quality designates the mechanical integrity of bone tissue. In vivo images based on X-ray attenuation, such as CT reconstructions, provide size, shape, and local BMD distribution and may be exploited as input for finite element analysis (FEA) to assess bone fragility. Further key input parameters of FEA are the material properties of bone tissue. This review discusses the main determinants of bone mechanical properties and emphasizes the added value, as well as the important assumptions underlying finite element analysis. Bone tissue is a sophisticated, multiscale composite material that undergoes remodeling but exhibits a rather narrow band of tissue mineralization. Mechanically, bone tissue behaves elastically under physiologic loads and yields by cracking beyond critical strain levels. Through adequate cell-orchestrated modeling, trabecular bone tunes its mechanical properties by volume fraction and fabric. With proper calibration, these mechanical properties may be incorporated in quantitative CT-based finite element analysis that has been validated extensively with ex vivo experiments and has been applied increasingly in clinical trials to assess treatment efficacy against osteoporosis.

Head-Neck Osteoplasty has Minor Effect on the Strength of an Ovine Cam-FAI Model: In Vitro and Finite Element Analyses.

BACKGROUND: Osteochondroplasty of the head-neck region is performed on patients with cam femoroacetabular impingement (FAI) without fully understanding its repercussion on the integrity of the femur. Cam-type FAI can be surgically and reproducibly induced in the ovine femur, which makes it suitable for studying corrective surgery in a consistent way. Finite element models built on quantitative CT (QCT) are computer tools that can be used to predict femoral strength and evaluate the mechanical effect of surgical correction. QUESTIONS/PURPOSES: We asked: (1) What is the effect of a resection of the superolateral aspect of the ovine femoral head-neck junction on failure load? (2) How does the failure load after osteochondroplasty compare with reported forces from activities of daily living in sheep? (3) How do failure loads and failure locations from the computer simulations compare with the experiments? METHODS: Osteochondroplasties (3, 6, 9 mm) were performed on one side of 18 ovine femoral pairs with the contralateral intact side as a control. The 36 femurs were scanned via QCT from which specimen-specific computer models were built. Destructive compression tests then were conducted experimentally using a servohydraulic testing system and numerically via the computer models. Safety factors were calculated as the ratio of the maximal force measured in vivo by telemeterized hip implants during the sheep's walking and running activities to the failure load. The simulated failure loads and failure locations from the computer models were compared with the experimental results. RESULTS: Failure loads were reduced by 5% (95% CI, 2%-8%) for the 3-mm group (p = 0.0089), 10% (95% CI, 6%-14%) for the 6-mm group (p = 0.0015), and 19% (95% CI, 13%-26%) for the 9-mm group (p = 0.0097) compared with the controls. Yet, the weakest specimen still supported more than 2.4 times the peak load during running. Strong correspondence was found between the simulated and experimental failure loads (R2 = 0.83; p < 0.001) and failure locations. CONCLUSIONS: The resistance of ovine femurs to fracture decreased with deeper resections. However, under in vitro testing conditions, the effect on femoral strength remains small even after 9 mm correction, suggesting that femoral head-neck osteochondroplasty could be done safely on the ovine femur. QCT-based finite element models were able to predict weakening of the femur resulting from the osteochondroplasty. CLINICAL RELEVANCE: The ovine femur provides a seemingly safe platform for scientific evaluation of FAI. It also appears that computer models based on preoperative CT scans may have the potential to provide patient-specific guidelines for preventing overcorrection of cam FAI.

Comparison of mixed and kinematic uniform boundary conditions in homogenized elasticity of femoral trabecular bone using microfinite element analyses.

Mechanical properties of human trabecular bone play an important role in age-related bone fragility and implant stability. Microfinite element (lFE) analysis allows computing the apparent elastic properties of trabecular bone for use in homogenized FE (hFE) analysis,but the results depend unfortunately on the type of applied boundary conditions(BCs). In this study, 167 human femoral trabecular cubic regions with a side length of 5.3mm were extracted from three proximal femora and analyzed using lFE analysis to compare systematically their stiffness with kinematic uniform BCs (KUBCs) and periodicity-compatible mixed uniform BCs (PMUBCs). The obtained elastic constants were then used in the volume fraction and fabric-based orthotropic Zysset­Curnier model to identify their respective model parameters. As expected, PMUBCs lead to more compliant apparent elastic properties than KUBCs, especially in shear. The differences in stiffness decreased with bone volume fraction and mean intercept length (MIL). Unlike KUBCs, PMUBCs were sensitive to heterogeneity of the biopsies. The Zysset­Curnier model fitted the apparent elastic constants successfully in both cases with adjusted coefficients of determination (r2adj) of 0.986 for KUBCs and 0.975 for PMUBCs. The proper use of these BCs for hFE analysis of whole bones will need to be investigated in future work.

Bonding-induced thermal conductance enhancement at inorganic heterointerfaces using nanomolecular monolayers.

Manipulating interfacial thermal transport is important for many technologies including nanoelectronics, solid-state lighting, energy generation and nanocomposites. Here, we demonstrate the use of a strongly bonding organic nanomolecular monolayer (NML) at model metal/dielectric interfaces to obtain up to a fourfold increase in the interfacial thermal conductance, to values as high as 430 MW m(-2) K(-1) in the copper-silica system. We also show that the approach of using an NML can be implemented to tune the interfacial thermal conductance in other materials systems. Molecular dynamics simulations indicate that the remarkable enhancement we observe is due to strong NML-dielectric and NML-metal bonds that facilitate efficient heat transfer through the NML. Our results underscore the importance of interfacial bond strength as a means to describe and control interfacial thermal transport in a variety of materials systems.

Experimental validation of finite element analysis of human vertebral collapse under large compressive strains.

Osteoporosis-related vertebral fractures represent a major health problem in elderly populations. Such fractures can often only be diagnosed after a substantial deformation history of the vertebral body. Therefore, it remains a challenge for clinicians to distinguish between stable and progressive potentially harmful fractures. Accordingly, novel criteria for selection of the appropriate conservative or surgical treatment are urgently needed. Computer tomography-based finite element analysis is an increasingly accepted method to predict the quasi-static vertebral strength and to follow up this small strain property longitudinally in time. A recent development in constitutive modeling allows us to simulate strain localization and densification in trabecular bone under large compressive strains without mesh dependence. The aim of this work was to validate this recently developed constitutive model of trabecular bone for the prediction of strain localization and densification in the human vertebral body subjected to large compressive deformation. A custom-made stepwise loading device mounted in a high resolution peripheral computer tomography system was used to describe the progressive collapse of 13 human vertebrae under axial compression. Continuum finite element analyses of the 13 compression tests were realized and the zones of high volumetric strain were compared with the experiments. A fair qualitative correspondence of the strain localization zone between the experiment and finite element analysis was achieved in 9 out of 13 tests and significant correlations of the volumetric strains were obtained throughout the range of applied axial compression. Interestingly, the stepwise propagating localization zones in trabecular bone converged to the buckling locations in the cortical shell. While the adopted continuum finite element approach still suffers from several limitations, these encouraging preliminary results towards the prediction of extended vertebral collapse may help in assessing fracture stability in future work.

Finite element based nonlinear normalization of human lumbar intervertebral disc stiffness to account for its morphology.

Disc degeneration, usually associated with low back pain and changes of intervertebral stiffness, represents a major health issue. As the intervertebral disc (IVD) morphology influences its stiffness, the link between mechanical properties and degenerative grade is partially lost without an efficient normalization of the stiffness with respect to the morphology. Moreover, although the behavior of soft tissues is highly nonlinear, only linear normalization protocols have been defined so far for the disc stiffness. Thus, the aim of this work is to propose a nonlinear normalization based on finite elements (FE) simulations and evaluate its impact on the stiffness of human anatomical specimens of lumbar IVD. First, a parameter study involving simulations of biomechanical tests (compression, flexion/extension, bilateral torsion and bending) on 20 FE models of IVDs with various dimensions was carried out to evaluate the effect of the disc's geometry on its compliance and establish stiffness/morphology relations necessary to the nonlinear normalization. The computed stiffness was then normalized by height (H), cross-sectional area (CSA), polar moment of inertia (J) or moments of inertia (Ixx, Iyy) to quantify the effect of both linear and nonlinear normalizations. In the second part of the study, T1-weighted MRI images were acquired to determine H, CSA, J, Ixx and Iyy of 14 human lumbar IVDs. Based on the measured morphology and pre-established relation with stiffness, linear and nonlinear normalization routines were then applied to the compliance of the specimens for each quasi-static biomechanical test. The variability of the stiffness prior to and after normalization was assessed via coefficient of variation (CV). The FE study confirmed that larger and thinner IVDs were stiffer while the normalization strongly attenuated the effect of the disc geometry on its stiffness. Yet, notwithstanding the results of the FE study, the experimental stiffness showed consistently higher CV after normalization. Assuming that geometry and material properties affect the mechanical response, they can also compensate for one another. Therefore, the larger CV after normalization can be interpreted as a strong variability of the material properties, previously hidden by the geometry's own influence. In conclusion, a new normalization protocol for the intervertebral disc stiffness in compression, flexion, extension, bilateral torsion and bending was proposed, with the possible use of MRI and FE to acquire the discs' anatomy and determine the nonlinear relations between stiffness and morphology. Such protocol may be useful to relate the disc's mechanical properties to its degree of degeneration.

Resveratrol Blunts Mitochondrial Loss in Slow and Mixed Skeletal Muscle Phenotypes of Non-Human Primates following a Long-Term High Fat/Sugar Diet.

Mitochondrial biogenesis and destruction in skeletal muscle are coordinated by distinct signaling pathways that are influenced by internal and exogenous variables including, but not limited to, muscle phenotype, physical activity, dietary composition, or drug administration. Previously we found that long-term resveratrol administration (up to 480 mg/day) ameliorates the slow-to-fast phenotypic shift in soleus muscles and promotes the expression in slow myosin heavy chain in the mixed plantaris muscle of non-human primates consuming a high fat/sugar (HFS) diet. Here, we expand on these earlier findings by examining whether mitochondrial content and the markers that dictate their biogenesis and mitophagy/autophagy are similarly affected by HFS and/or influenced by resveratrol while consuming this diet (HFSR). Compared to controls (n = 9), there was a ∼20-25% decrease in mitochondrial content in HFS (n = 8) muscles as reflected in the COX2- and CYTB-to-GAPDH ratios using PCR analysis, which was blunted by resveratrol in HFSR (n = 7) soleus and, to a lesser degree, in plantaris muscles. A ∼1.5 and 3-fold increase in Rev-erb-α protein was detected in HFSR soleus and plantaris muscles compared to controls, respectively. Unlike in HFSR animals, HFS soleus and plantaris muscles exhibited a ∼2-fold elevation in phosphor-AMPKα (Thr172). HFS soleus muscles had elevated phosphorylated-to-total TANK binding protein-1 (TBK1) ratio suggesting an enhancement in mito/autophagic events. Taken together, resveratrol appears to blunt mitochondrial losses with a high fat/sugar diet by tempering mito/autophagy rather than promoting mitochondrial biogenesis, suggesting that the quantity of daily resveratrol supplement ingested and/or its long-term consumption are important considerations.Supplemental data for this article is available online at http://dx.doi.org/ .

In situ synchrotron radiation µCT indentation of cortical bone: Anisotropic crack propagation, local deformation, and fracture.

The development of treatment strategies for skeletal diseases relies on the understanding of bone mechanical properties in relation to its structure at different length scales. At the microscale, indention techniques can be used to evaluate the elastic, plastic, and fracture behaviour of bone tissue. Here, we combined in situ high-resolution SRµCT indentation testing and digital volume correlation to elucidate the anisotropic crack propagation, deformation, and fracture of ovine cortical bone under Berkovich and spherical tips. Independently of the indenter type we observed significant dependence of the crack development due to the anisotropy ahead of the tip, with lower strains and smaller crack systems developing in samples indented in the transverse material direction, where the fibrillar bone ultrastructure is largely aligned perpendicular to the indentation direction. Such alignment allows to accommodate the strain energy, inhibiting crack propagation. Higher tensile hoop strains generally correlated with regions that display significant cracking radial to the indenter, indicating a predominant Mode I fracture. This was confirmed by the three-dimensional analysis of crack opening displacements and stress intensity factors along the crack front obtained for the first time from full displacement fields in bone tissue. The X-ray beam significantly influenced the relaxation behaviour independent of the tip. Raman analyses did not show significant changes in specimen composition after irradiation compared to non-irradiated tissue, suggesting an embrittlement process that may be linked to damage of the non-fibrillar organic matrix. This study highlights the importance of three-dimensional investigation of bone deformation and fracture behaviour to explore the mechanisms of bone failure in relation to structural changes due to ageing or disease. STATEMENT OF SIGNIFICANCE: Characterising the three-dimensional deformation and fracture behaviour of bone remains essential to decipher the interplay between structure, function, and composition with the aim to improve fracture prevention strategies. The experimental methodology presented here, combining high-resolution imaging, indentation testing and digital volume correlation, allows us to quantify the local deformation, crack propagation, and fracture modes of cortical bone tissue. Our results highlight the anisotropic behaviour of osteonal bone and the complex crack propagation patterns and fracture modes initiating by the intricate stress states beneath the indenter tip. This is of wide interest not only for the understanding of bone fracture but also to understand other architectured (bio)structures providing an effective way to quantify their toughening mechanisms in relation to their main mechanical function.

The elasto-plastic nano- and microscale compressive behaviour of rehydrated mineralised collagen fibres.

The hierarchical design of bio-based nanostructured materials such as bone enables them to combine unique structure-mechanical properties. As one of its main components, water plays an important role in bone's material multiscale mechanical interplay. However, its influence has not been quantified at the length-scale of a mineralised collagen fibre. Here, we couple in situ micropillar compression, and simultaneous synchrotron small angle X-ray scattering (SAXS) and X-ray diffraction (XRD) with a statistical constitutive model. Since the synchrotron data contain statistical information on the nanostructure, we establish a direct connection between experiment and model to identify the rehydrated elasto-plastic micro- and nanomechanical fibre behaviour. Rehydration led to a decrease of 65%-75% in fibre yield stress and compressive strength, and 70% in stiffness with a 3x higher effect on stresses than strains. While in agreement with bone extracellular matrix, the decrease is 1.5-3x higher compared to micro-indentation and macro-compression. Hydration influences mineral more than fibril strain with the highest difference to the macroscale when comparing mineral and tissue levels. The effect of hydration seems to be strongly mediated by ultrastructural interfaces while results provide insights towards mechanical consequences of reported water-mediated structuring of bone apatite. The missing reinforcing capacity of surrounding tissue for an excised fibril array is more pronounced in wet than dry conditions, mainly related to fibril swelling. Differences leading to higher compressive strength between mineralised tissues seem not to depend on rehydration while the lack of kink bands supports the role of water as an elastic embedding influencing energy-absorption mechanisms. STATEMENT OF SIGNIFICANCE: Characterising structure-property-function relationships in hierarchical biological materials helps us to elucidate mechanisms that enable their unique properties. Experimental and computational methods can advance our understanding of their complex behaviour with the potential to inform bio-inspired material development. In this study, we close a gap for bone's fundamental mechanical building block at micro- and nanometre length scales. We establish a direct connection between experiments and simulations by coupling in situ synchrotron tests with a statistical model and quantify the behaviour of rehydrated single mineralised collagen fibres. Results suggest a high influence of hydration on structural interfaces, and the role of water as an elastic embedding by outlining important differences between wet and dry elasto-plastic properties of mineral nanocrystals, fibrils and fibres.

Outcomes of WHO-conforming, longer, all-oral multidrug-resistant TB regimens and analysis implications.

BACKGROUND: Evidence of the effectiveness of the WHO-recommended design of longer individualized regimens for multidrug- or rifampicin-resistant TB (MDR/RR-TB) is limited.OBJECTIVES: To report end-of-treatment outcomes for MDR/RR-TB patients from a 2015-2018 multi-country cohort that received a regimen consistent with current 2022 WHO updated recommendations and describe the complexities of comparing regimens.METHODS: We analyzed a subset of participants from the endTB Observational Study who initiated a longer MDR/RR-TB regimen that was consistent with subsequent 2022 WHO guidance on regimen design for longer treatments. We excluded individuals who received an injectable agent or who received fewer than four likely effective drugs.RESULTS: Of the 759 participants analyzed, 607 (80.0%, 95% CI 77.0-82.7) experienced successful end-of-treatment outcomes. The frequency of success was high across groups, whether stratified on number of Group A drugs or fluoroquinolone resistance, and ranged from 72.1% to 90.0%. Regimens were highly variable regarding composition and the duration of individual drugs.CONCLUSIONS: Longer, all-oral, individualized regimens that were consistent with 2022 WHO guidance on regimen design had high frequencies of treatment success. Heterogeneous regimen compositions and drug durations precluded meaningful comparisons. Future research should examine which combinations of drugs maximize safety/tolerability and effectiveness.

Influence of mineralization and microporosity on tissue elasticity: experimental and numerical investigation on mineralized turkey leg tendons.

A combined experimental and numerical study correlating indentation stiffness with mineralization and microporosity was performed on mineralized turkey leg tendon. Two distinct tissue morphologies were distinguished by quantitative backscattered electron imaging and called "circumferential" and "interstitial" zones. These two zones showed different tissue organization, microporosity, and mineralization. Stiffness, measured by microindentation, was also different in the two zones. The mean field method of modeling of mineralized collagen fibers was employed to explain the differences.

A patient-specific computer tomography-based finite element methodology to calculate the six dimensional stiffness matrix of human vertebral bodies.

In most finite element (FE) studies of vertebral bodies, axial compression is the loading mode of choice to investigate structural properties, but this might not adequately reflect the various loads to which the spine is subjected during daily activities or the increased fracture risk associated with shearing or bending loads. This work aims at proposing a patient-specific computer tomography (CT)-based methodology, using the currently most advanced, clinically applicable finite element approach to perform a structural investigation of the vertebral body by calculation of its full six dimensional (6D) stiffness matrix. FE models were created from voxel images after smoothing of the peripheral voxels and extrusion of a cortical shell, with material laws describing heterogeneous, anisotropic elasticity for trabecular bone, isotropic elasticity for the cortex based on experimental data. Validated against experimental axial stiffness, these models were loaded in the six canonical modes and their 6D stiffness matrix calculated. Results show that, on average, the major vertebral rigidities correlated well or excellently with the axial rigidity but that weaker correlations were observed for the minor coupling rigidities and for the image-based density measurements. This suggests that axial rigidity is representative of the overall stiffness of the vertebral body and that finite element analysis brings more insight in vertebral fragility than densitometric approaches. Finally, this extended patient-specific FE methodology provides a more complete quantification of structural properties for clinical studies at the spine.

The effect of standard and low-modulus cement augmentation on the stiffness, strength, and endplate pressure distribution in vertebroplasty.

PURPOSE: Vertebroplasty restores stiffness and strength of fractured vertebral bodies, but alters their stress transfer. This unwanted effect may be reduced by using more compliant cements. However, systematic experimental comparison of structural properties between standard and low-modulus augmentation needs to be done. This study investigated how standard and low-modulus cement augmentation affects apparent stiffness, strength, and endplate pressure distribution of vertebral body sections. METHODS: Thirty-nine human thoracolumbar vertebral body sections were prepared by removing cortical endplates and posterior elements. The specimens were scanned with a HR-pQCT system and loaded in the elastic range. After augmentation with standard or low-modulus cement they were scanned again and tested in two steps. First, the contact pressure distribution between specimen and loading plates was measured with pressure-sensitive films. Then, they were loaded again in the elastic range and compressed until failure. Apparent stiffness was compared before and after augmentation, whereas apparent strength of augmented specimens was compared to a non-augmented reference group. RESULTS: Vertebral body sections with fillings connecting both endplates were on average 33% stiffer and 47% stronger with standard cement, and 27% stiffer and 30% stronger with low-modulus cement. In contrast, partial fillings showed no significant strengthening for both cements and only a slight stiffness increase (<16%). The averaged endplate pressure above/below the cement was on average 15% lower with low-modulus cement compared to standard cement. CONCLUSION: Augmentation connecting both endplates significantly strengthened and stiffened vertebral body sections also with low-modulus cement. A trend of reduced pressure concentrations above/below the cement was observed with low-modulus cement.

Assessment of a novel biomechanical fracture model for distal radius fractures.

BACKGROUND: Distal radius fractures (DRF) are one of the most common fractures and often need surgical treatment, which has been validated through biomechanical tests. Currently a number of different fracture models are used, none of which resemble the in vivo fracture location. The aim of the study was to develop a new standardized fracture model for DRF (AO-23.A3) and compare its biomechanical behavior to the current gold standard. METHODS: Variable angle locking volar plates (ADAPTIVE, Medartis) were mounted on 10 pairs of fresh-frozen radii. The osteotomy location was alternated within each pair (New: 10 mm wedge 8 mm / 12 mm proximal to the dorsal / volar apex of the articular surface; Gold standard: 10 mm wedge 20 mm proximal to the articular surface). Each specimen was tested in cyclic axial compression (increasing load by 100 N per cycle) until failure or -3 mm displacement. Parameters assessed were stiffness, displacement and dissipated work calculated for each cycle and ultimate load. Significance was tested using a linear mixed model and Wald test as well as t-tests. RESULTS: 7 female and 3 male pairs of radii aged 74 ± 9 years were tested. In most cases (7/10), the two groups showed similar mechanical behavior at low loads with increasing differences at increasing loads. Overall the novel fracture model showed a significant different biomechanical behavior than the gold standard model (p < 0,001). The average final loads resisted were significantly lower in the novel model (860 N ± 232 N vs. 1250 N ± 341 N; p = 0.001). CONCLUSION: The novel biomechanical fracture model for DRF more closely mimics the in vivo fracture site and shows a significantly different biomechanical behavior with increasing loads when compared to the current gold standard.

Paediatric HIV infection in Western Africa: the long way to the standard of care.

In sub-Saharan Africa, newborns and children continue to suffer from insufficient access to early diagnosis and antiretroviral (ARV) treatments. A survey had been conducted in Burkina Faso, Ghana and Ivory Coast, from January 2010 to February 2011 to identify the major challenges regarding HIV prophylaxis and treatment of children in western Africa. The results of this survey highlight that only a small proportion of HIV-exposed newborns receive ARV prophylaxis. However, this problem is often not perceived at the national level. The problem could be faced by improving the communication process between the peripheral health services and the national procurement system. Moreover, supporting the development of local pharmaceutical industries could facilitate the availability of child-sized drugs, contextualized to the socio-cultural needs of such area, adequate not only in terms of efficacy, safety and tolerability, but also in terms of palatability, storage, distribution and cost.

MOTS-c increases in skeletal muscle following long-term physical activity and improves acute exercise performance after a single dose.

Skeletal muscle adapts to aerobic exercise training, in part, through fast-to-slow phenotypic shifts and an expansion of mitochondrial networks. Recent research suggests that the local and systemic benefits of exercise training also may be modulated by the mitochondrial-derived peptide, MOTS-c. Using a combination of acute and chronic exercise challenges, the goal of the present study was to characterize the interrelationship between MOTS-c and exercise. Compared to sedentary controls, 4-8 weeks of voluntary running increased MOTS-c protein expression ~1.5-5-fold in rodent plantaris, medial gastrocnemius, and tibialis anterior muscles and is sustained for 4-6 weeks of detraining. This MOTS-c increase coincides with elevations in mtDNA reflecting an expansion of the mitochondrial genome to aerobic training. In a second experiment, a single dose (15 mg/kg) of MOTS-c administered to untrained mice improved total running time (12% increase) and distance (15% increase) during an acute exercise test. In a final experiment, MOTS-c protein translocated from the cytoplasm into the nucleus in two of six mouse soleus muscles 1 h following a 90-min downhill running challenge; no nuclear translocation was observed in the plantaris muscles from the same animals. These findings indicate that MOTS-c protein accumulates within trained skeletal muscle likely through a concomitant increase in mtDNA. Furthermore, these data suggest that the systemic benefits of exercise are, in part, mediated by an expansion of the skeletal muscle-derived MOTS-c protein pool. The benefits of training may persist into a period of inactivity (e.g., detraining) resulting from a sustained increase in intramuscular MOTS-c proteins levels.