PTER is a N-acetyltaurine hydrolase that regulates feeding and obesity.

Taurine is a conditionally essential micronutrient and one of the most abundant amino acids in humans1-3. In endogenous taurine metabolism, dedicated enzymes are involved in the biosynthesis of taurine from cysteine and in the downstream metabolism of secondary taurine metabolites4,5. One taurine metabolite is N-acetyltaurine6. Levels of N-acetyltaurine are dynamically regulated by stimuli that alter taurine or acetate flux, including endurance exercise7, dietary taurine supplementation8 and alcohol consumption6,9. So far, the identities of the enzymes involved in N-acetyltaurine metabolism, and the potential functions of N-acetyltaurine itself, have remained unknown. Here we show that the body mass index associated orphan enzyme phosphotriesterase-related (PTER)10 is a physiological N-acetyltaurine hydrolase. In vitro, PTER catalyses the hydrolysis of N-acetyltaurine to taurine and acetate. In mice, PTER is expressed in the kidney, liver and brainstem. Genetic ablation of Pter in mice results in complete loss of tissue N-acetyltaurine hydrolysis activity and a systemic increase in N-acetyltaurine levels. After stimuli that increase taurine levels, Pter knockout mice exhibit reduced food intake, resistance to diet-induced obesity and improved glucose homeostasis. Administration of N-acetyltaurine to obese wild-type mice also reduces food intake and body weight in a GFRAL-dependent manner. These data place PTER into a central enzymatic node of secondary taurine metabolism and uncover a role for PTER and N-acetyltaurine in body weight control and energy balance.

Deciphering molecular interactions by proximity labeling.

Many biological processes are executed and regulated through the molecular interactions of proteins and nucleic acids. Proximity labeling (PL) is a technology for tagging the endogenous interaction partners of specific protein 'baits', via genetic fusion to promiscuous enzymes that catalyze the generation of diffusible reactive species in living cells. Tagged molecules that interact with baits can then be enriched and identified by mass spectrometry or nucleic acid sequencing. Here we review the development of PL technologies and highlight studies that have applied PL to the discovery and analysis of molecular interactions. In particular, we focus on the use of PL for mapping protein-protein, protein-RNA and protein-DNA interactions in living cells and organisms.

Ultrasensitive Single-Molecule Enzyme Detection and Analysis Using a Polymer Microarray.

This report describes a novel method for isolating and detecting individual enzyme molecules using polymer arrays of picoliter microwells. A fluidic flow-cell device containing an array of microwells is fabricated in cyclic olefin polymer (COP). The use of COP microwell arrays simplifies experiments by eliminating extensive device preparation and surface functionalization that are common in other microwell array formats. Using a simple and robust loading method to introduce the reaction solution, individual enzyme molecules are trapped in picoliter microwells and subsequently isolated and sealed by fluorinated oil. The sealing is stable for hours in the COP device. The picoliter microwell device can measure enzyme concentrations in the low-femtomolar range by counting the number of active wells using a digital read-out. These picoliter microwell arrays can also easily be regenerated and reused.

Interferon-induced HERC5 is evolving under positive selection and inhibits HIV-1 particle production by a novel mechanism targeting Rev/RRE-dependent RNA nuclear export.

BACKGROUND: Type I interferon (IFN) inhibits virus replication by activating multiple antiviral mechanisms and pathways. It has long been recognized that type I IFNs can potently block HIV-1 replication in vitro; as such, HIV-1 has been used as a system to identify and characterize IFN-induced antiviral proteins responsible for this block. IFN-induced HERC5 contains an amino-terminal Regulator of Chromosome Condensation 1 (RCC1)-like domain and a carboxyl-terminal Homologous to the E6-AP Carboxyl Terminus (HECT) domain. HERC5 is the main cellular E3 ligase that conjugates the IFN-induced protein ISG15 to proteins. This E3 ligase activity was previously shown to inhibit the replication of evolutionarily diverse viruses, including HIV-1. The contribution of the RCC1-like domain to the antiviral activity of HERC5 was previously unknown. RESULTS: In this study, we showed that HERC5 inhibits HIV-1 particle production by a second distinct mechanism that targets the nuclear export of Rev/RRE-dependent RNA. Unexpectedly, the E3 ligase activity of HERC5 was not required for this inhibition. Instead, this activity required the amino-terminal RCC1-like domain of HERC5. Inhibition correlated with a reduction in intracellular RanGTP protein levels and/or the ability of RanGTP to interact with RanBP1. Inhibition also correlated with altered subcellular localization of HIV-1 Rev. In addition, we demonstrated that positive evolutionary selection is operating on HERC5. We identified a region in the RCC1-like domain that exhibits an exceptionally high probability of having evolved under positive selection and showed that this region is required for HERC5-mediated inhibition of nuclear export. CONCLUSIONS: We have identified a second distinct mechanism by which HERC5 inhibits HIV-1 replication and demonstrate that HERC5 is evolving under strong positive selection. Together, our findings contribute to a growing body of evidence suggesting that HERC5 is a novel host restriction factor.

Subject-specific material properties of the heel pad: An inverse finite element analysis.

Individuals with diabetes are at a higher risk of developing foot ulcers. To better understand internal soft tissue loading and potential treatment options, subject-specific finite element (FE) foot models have been used. However, existing models typically lack subject-specific soft tissue material properties and only utilize subject-specific anatomy. Therefore, this study determined subject-specific hindfoot soft tissue material properties from one non-diabetic and one diabetic subject using inverse FE analysis. Each subject underwent cyclic MRI experiments to simulate physiological gait and to obtain compressive force and three-dimensional soft tissue imaging data at 16 phases along the loading-unloading cycles. The FE models consisted of rigid bones and nearly-incompressible first-order Ogden hyperelastic skin, fat, and muscle (resulting in six independent material parameters). Then, calcaneus and loading platen kinematics were computed from imaging data and prescribed to the FE model. Two analyses were performed for each subject. First, the skin, fat, and muscle layers were lumped into a single generic soft tissue material and optimized to the platen force. Second, the skin, fat, and muscle material properties were individually determined by simultaneously optimizing for platen force, muscle vertical displacement, and skin mediolateral bulging. Our results indicated that compared to the individual without diabetes, the individual with diabetes had stiffer generic soft tissue behavior at high strain and that the only substantially stiffer multi-material layer was fat tissue. Thus, we suggest that this protocol serves as a guideline for exploring differences in non-diabetic and diabetic soft tissue material properties in a larger population.

A PTER-dependent pathway of taurine metabolism linked to energy balance.

Taurine is a conditionally essential micronutrient and one of the most abundant amino acids in humans1-3. In endogenous taurine metabolism, dedicated enzymes are involved in biosynthesis of taurine from cysteine as well as the downstream derivatization of taurine into secondary taurine metabolites4,5. One such taurine metabolite is N-acetyltaurine6. Levels of N-acetyltaurine are dynamically regulated by diverse physiologic perturbations that alter taurine and/or acetate flux, including endurance exercise7, nutritional taurine supplementation8, and alcohol consumption6,9. While taurine N-acetyltransferase activity has been previously detected in mammalian cells6,7, the molecular identity of this enzyme, and the physiologic relevance of N-acetyltaurine, have remained unknown. Here we show that the orphan body mass index-associated enzyme PTER (phosphotriesterase-related)10 is the principal mammalian taurine N-acetyltransferase/hydrolase. In vitro, recombinant PTER catalyzes bidirectional taurine N-acetylation with free acetate as well as the reverse N-acetyltaurine hydrolysis reaction. Genetic ablation of PTER in mice results in complete loss of tissue taurine N-acetyltransferase/hydrolysis activities and systemic elevation of N-acetyltaurine levels. Upon stimuli that increase taurine levels, PTER-KO mice exhibit lower body weight, reduced adiposity, and improved glucose homeostasis. These phenotypes are recapitulated by administration of N-acetyltaurine to wild-type mice. Lastly, the anorexigenic and anti-obesity effects of N-acetyltaurine require functional GFRAL receptors. Together, these data uncover enzymatic control of a previously enigmatic pathway of secondary taurine metabolism linked to energy balance.

Optimization of nonlinear hyperelastic coefficients for foot tissues using a magnetic resonance imaging deformation experiment.

Accurate prediction of plantar shear stress and internal stress in the soft tissue layers of the foot using finite element models would provide valuable insight into the mechanical etiology of neuropathic foot ulcers. Accurate prediction of the internal stress distribution using finite element models requires that realistic descriptions of the material properties of the soft tissues are incorporated into the model. Our investigation focused on the creation of a novel three-dimensional (3D) finite element model of the forefoot with multiple soft tissue layers (skin, fat pad, and muscle) and the development of an inverse finite element procedure that would allow for the optimization of the nonlinear elastic coefficients used to define the material properties of the skin muscle and fat pad tissue layers of the forefoot based on a Ogden hyperelastic constitutive model. Optimization was achieved by comparing deformations predicted by finite element models to those measured during an experiment in which magnetic resonance imaging (MRI) images were acquired while the plantar surface forefoot was compressed. The optimization procedure was performed for both a model incorporating all three soft tissue layers and one in which all soft tissue layers were modeled as a single layer. The results indicated that the inclusion of multiple tissue layers affected the deformation and stresses predicted by the model. Sensitivity analysis performed on the optimized coefficients indicated that small changes in the coefficient values (±10%) can have rather large impacts on the predicted nominal strain (differences up to 14%) in a given tissue layer.

A novel lunar bed rest analogue.

INTRODUCTION: Humans will eventually return to the Moon and thus there is a need for a ground-based analogue to enable the study of physiological adaptations to lunar gravity. An important unanswered question is whether or not living on the lunar surface will provide adequate loading of the musculoskeletal system to prevent or attenuate the bone loss that is seen in microgravity. Previous simulations have involved tilting subjects to an approximately 9.5 degrees angle to achieve a lunar gravity component parallel to the long-axis of the body. However, subjects in these earlier simulations were not weight-bearing, and thus these protocols did not provide an analogue for load on the musculoskeletal system. METHODS: We present a novel analogue which includes the capability to simulate standing and sitting in a lunar loading environment. A bed oriented at a 9.5 degrees angle was mounted on six linear bearings and was free to travel with one degree of freedom along rails. This allowed approximately 1/6 body weight loading of the feet during standing. "Lunar" sitting was also successfully simulated. RESULTS: A feasibility study demonstrated that the analogue was tolerated by subjects for 6 d of continuous bed rest and that the reaction forces at the feet during periods of standing were a reasonable simulation of lunar standing. During the 6 d, mean change in the volume of the quadriceps muscles was -1.6% +/- 1.7%. DISCUSSION: The proposed analogue would appear to be an acceptable simulation of lunar gravity and deserves further exploration in studies of longer duration.

Cost of treating diabetic foot ulcers in five different countries.

Most estimates in the literature for the economic cost of treating a diabetic foot ulcer (DFU) are from industrialized countries. There is also marked heterogeneity between the complexity of cases considered in the different studies. The goal of the present article was to estimate treatment costs and costs to patients in five different countries (Chile, China, India, Tanzania, and the United States) for two hypothetical, but well-defined, DFUs at the extreme ends of the complexity spectrum. A co-author, who is a treating physician in the relevant country, was asked to choose treatment plans that represented the typical application of local resources to the DFU. The outcomes were pre-defined as complete healing in case 1 and trans-tibial amputation in case 2, but the time course of treatment was determined by each investigator in a manner that would be typical for their clinic. The costs, in local currencies, for each course of treatment were estimated with the assistance of local hospital administrators. Typical reimbursement scenarios in each country were used to estimate the cost burden to the patient, which was then expressed as a percentage of the annual per capita purchasing power parity-adjusted gross domestic product. There were marked differences in the treatment plans between countries based on the availability of resources and the realities of local conditions. The costs of treatment for case 1 ranged from Int$102 to Int$3959 in Tanzania and in the United States, respectively. The cost for case 2 ranged from Int$3060 to Int$188,645 in Tanzania and in the United States, respectively. The cost burden to the patient varied from the equivalent of 6 days of average income in the United States for case 1 to 5.7 years of average annual income for case 2 in India. Although these findings do not take cost-effectiveness into account, they highlight the dramatic economic burden of a DFU for patients in some countries.

Miniaturized sensors to monitor simulated lunar locomotion.

INTRODUCTION: Human activity monitoring is a useful tool in medical monitoring, military applications, athletic coaching, and home healthcare. We propose the use of an accelerometer-based system to track crewmember activity during space missions in reduced gravity environments. It is unclear how the partial gravity environment of the Moorn or Mars will affect human locomotion. Here we test a novel analogue of lunar gravity in combination with a custom wireless activity tracking system. METHODS: A noninvasive wireless accelerometer-based sensor system, the activity tracking device (ATD), was developed. The system has two sensor units; one footwear-mounted and the other waist-mounted near the midlower back. Subjects (N=16) were recruited to test the system in the enhanced Zero Gravity Locomotion Simulator (eZLS) at NASA Glenn Research Center. Data were used to develop an artificial neural network for activity recognition. RESULTS: The eZLS demonstrated the ability to replicate reduced gravity environments. There was a 98% agreement between the ATD and force plate-derived stride times during running (9.7 km x h(-1)) at both 1 g and 1/6 g. A neural network was designed and successfully trained to identify lunar walking, running, hopping, and loping from ATD measurements with 100% accuracy. DISCUSSION: The eZLS is a suitable tool for examining locomotor activity at simulated lunar gravity. The accelerometer-based ATD system is capable of monitoring human activity and may be suitable for use during remote, long-duration space missions. A neural network has been developed to use data from the ATD to aid in remote activity monitoring.

Off-loading the diabetic foot for ulcer prevention and healing.

BACKGROUND: Retrospective and prospective studies have shown that elevated plantar pressure is a causative factor in the development of many plantar ulcers in diabetic patients and that ulceration is often a precursor of lower extremity amputation. In this article, we review the evidence that relieving areas of elevated plantar pressure (off-loading) can prevent and heal plantar ulceration. RESULTS: There is no consensus in the literature concerning the role of off-loading through footwear in primary or secondary prevention of ulcers. This is likely due to the wide diversity of intervention and control conditions tested, the lack of information about off-loading efficacy of the footwear used, and the absence of a target pressure threshold for off-loading. Uncomplicated plantar ulcers should heal in 6 to 8 weeks with adequate off-loading. The total contact cast and other nonremovable devices are most effective because they eliminate the problem of nonadherence to recommendations for using a removable device. Conventional or standard therapeutic footwear is not effective in ulcer healing. Recent United States and European surveys show a large discrepancy between guidelines and clinical practice in off-loading diabetic foot ulcers. Many clinics continue to use methods that are known to be ineffective or have not been proven effective, while ignoring methods that have been demonstrated to be efficacious. CONCLUSIONS: A number of strategies are proposed to address this situation, notably the adoption and implementation of recently established international guidelines, which are evidence-based and specific, by professional societies in the United States and Europe. Such an approach would change the often poor current expectations for healing diabetic plantar ulcers.

Muscle volume, strength, endurance, and exercise loads during 6-month missions in space.

INTRODUCTION: Decrements in muscular strength during long-duration missions in space could be mission-critical during construction and exploration activities. The purpose of this study was to quantify changes in muscle volume, strength, and endurance of crewmembers on the International Space Station (ISS) in the context of new measurements of loading during exercise countermeasures. METHODS: Strength and muscle volumes were measured from four male ISS crewmembers (49.5 +/- 4.7 yr, 179.3 +/- 7.1 cm, 85.2 +/- 10.4 kg) before and after long-duration spaceflight (181 +/- 15 d). Preflight and in-flight measurements of forces between foot and shoe allowed comparisons of loading from 1-g exercise and exercise countermeasures on ISS. RESULTS: Muscle volume change was greater in the calf (-10 to 16%) than the thigh (-4% to -7%), but there was no change in the upper arm (+0.4 to -0.8%). Isometric and isokinetic strength changes at the knee (range -10.4 to -24.1%), ankle (range -4 to -22.3%), and elbow (range -7.5 to -16.7%) were observed. Although there was an overall postflight decline in total work (-14%) during the endurance test, an increase in postflight resistance to fatigue was observed. The peak in-shoe forces during running and cycling on ISS were approximately 46% and 50% lower compared to 1-g values. DISCUSSION: Muscle volume and strength were decreased in the lower extremities of crewmembers during long-duration spaceflight on ISS despite the use of exercise countermeasures. in-flight countermeasures were insufficient to replicate the daily mechanical loading experienced by the crewmembers before flight. Future exercise protocols need careful assessment both in terms of intensity and duration to maximize the "dose" of exercise and to increase loads compared to the measured levels.

Enhanced daily load stimulus to bone in spaceflight and on earth.

INTRODUCTION: It has been hypothesized that bone loss arising from long-duration space travel is caused by a reduction in mechanical stimuli to the skeleton. The daily load stimulus (DLS) theory was first proposed to relate daily time histories of mechanical loading from ground reaction forces to bone homeostasis. In this methods paper, an enhanced daily load stimulus (EDLS) is proposed to account for recently developed theories on saturation and recovery of the osteogenic potential of bone with repeated cyclic loading and the potential benefits of standing. MODEL DEVELOPMENT: To determine periods of continuous activity (sitting, standing, walking, running, and other activity), an activity determination algorithm based on entire days of in-shoe forces was developed. The rainflow peak counting method was used to analyze the in-shoe force data from entire working days in preparation for the calculation of the EDLS. Parameters characterizing saturation and recovery with cyclical loading from running and walking as well as the effects of standing were estimated based on data in the literature. DISCUSSION: The activity algorithm proved to be accurate and robust when applied to in-shoe force data from entire waking days. The EDLS may be useful in prescribing "dose-based" exercise prescriptions to crewmembers during long-duration spaceflights and missions to the Moon and Mars. Validation of the proposed EDLS model will be possible with data from an ongoing human bed rest study examining changes in bone mineral density with controlled skeletal loading.

An ambulatory biomechanical data collection system for use in space: design and validation.

INTRODUCTION: Loss in bone mineral density and muscle strength in astronauts following long-duration spaceflight have been well documented, but the altered force and movement environments in microgravity which may contribute to these changes have not been well characterized. This paper describes the instrumentation, software, and data collection procedures developed for the "Foot" experiment that was conducted on the International Space Station (ISS) to provide insight into the biomechanics of daily activity in a microgravity environment. METHODS: The instrumentation used for data collection included the Ambulatory Data Acquisition System (ADAS), ADAS electromyography (EMG) modules, the Joint Excursion System, and the Total Force-Foot Ground interface system, which were all integrated into a specially designed Lower Extremity Monitoring Suit. There were 14 total channels of data that were collected at sampling rates between 8 Hz and 1024 Hz, including 7 channels of EMG, 4 channels of joint angle data, 2 channels of in-shoe ground reaction force, and a marker channel for event recording. Data were typically collected for between 6.5 and 11.8 h of activity during 4 d on Earth and 4-7 d in flight. RESULTS: Exemplar data sets collected preflight on astronauts in 1 g to validate the instrumentation are presented. DISCUSSION: We conclude that the system provides valid and useful biomechanical information on long-term activity. The analysis of data collected on-orbit using the system described here will be presented in a series of future papers characterizing the biomechanics of astronaut activity during complete working days on the Earth and on the ISS.

An MRI-compatible foot-loading device for assessment of internal tissue deformation.

It is well known that mechanical forces acting within the soft tissues of the foot can contribute to the formation of neuropathic ulcers in people with diabetes. Presently, only surface measurements of plantar pressure are used clinically to estimate risk status due to mechanical loading. It is currently not known how surface measurements relate to the three-dimensional (3-D) internal stress/strain state of the foot. This article describes the development of a foot-loading device that allows for the direct observation of the internal deformation of foot tissues under known forces. Ground reaction forces and plantar pressure distributions during normal walking were measured in ten healthy young adults. One instant in the gait cycle, when pressure under the metatarsal heads reached a peak, was extracted for simulation in an MR imager. T1-weighted 3-D gradient echo MRI sets were collected as the simulated walking ground reaction force was incrementally applied to the foot by the novel foot-loading device. The sub-metatarsal head soft-tissue thickness decreased rapidly at first and then reached a plateau. Peak plantar pressure measurements collected within the loading device (161+/-75kPa) were lower in magnitude and less focal than pressures measured during walking (492+/-91kPa). This finding implies that although the device successfully applied full peak walking ground reaction forces to the foot, they were not distributed in the same manner as during walking. Although not representative of gait, the data collected from this in vivo mechanical test are suitable for determination of foot tissue material properties or, when combined with finite element modeling, to examine the relationship between surface loading and internal stress.

Can the completeness of radiological cancer staging reports be improved using proforma reporting? A prospective multicentre non-blinded interventional study across 21 centres in the UK.

OBJECTIVES: Following a diagnosis of cancer, the detailed assessment of prognostic stage by radiology is a crucial determinant of initial therapeutic strategy offered to patients. Pretherapeutic stage by imaging is known to be inconsistently documented. We tested whether the completeness of cancer staging radiology reports could be improved through a nationally introduced pilot of proforma-based reporting for a selection of six common cancers. DESIGN: Prospective interventional study comparing the completeness of radiology cancer staging reports before and after the introduction of proforma reporting. SETTING: Twenty-one UK National Health Service hospitals. PARTICIPANTS: 1283 cancer staging radiology reports were submitted. MAIN OUTCOME MEASURES: Radiology staging reports across the six cancers types were evaluated before and after the implementation of proforma-based reporting. Report completeness was assessed using scoring forms listing the presence or absence of predetermined key staging data. Qualitative data regarding proforma implementation and usefulness were collected from questionnaires provided to radiologists and end-users. RESULTS: Electronic proforma-based reporting was successfully implemented in 15 of the 21 centres during the evaluation period. A total of 787 preproforma and 496 postproforma staging reports were evaluated. In the preproforma group, only 48.7% (5586/11 470) of key staging items were present compared with 87.3% (6043/6920) in the postproforma group. Thus, the introduction of proforma reporting produced a 78% improvement in staging completeness . This increase was seen across all cancer types and centres. The majority of participants found proforma reporting improved cancer reporting quality for their clinical practice . CONCLUSION: The implementation of proforma reporting results in a significant improvement in the completeness of cancer staging reports. Proforma-based assessment of cancer stage enables objective comparisons of patient outcomes across centres. It should therefore become an auditable quality standard for cancer care.

Reliability of surface EMG measurements over 12 hours.

Bone and muscle are both compromised during long-term space flight. Experiments are, therefore, in progress using surface electromyography (EMG) and joint angle measurements to compare muscle action on earth and in space over complete working days. To date, there is little information on the reliability of such long-term EMG measurements available in the literature. Therefore, the current study determined the reliability and feasibility of using surface EMG over a 12-h interval. Ten young subjects performed standardized isometric exercises at 30% of maximum voluntary effort every 2h throughout a normal working day, which included a period of self-chosen exercise. Surface electrodes remained in place over the biceps brachii (BB), vastus medialis (VM), and gastrocnemius (GN) throughout the day. The normalized integrated EMG for two of the three muscles showed no significant changes during the 12-h period, and only the first observation for VM showed a trend (p<0.1) of differences with three of the other measurement periods. The stability of surface EMG measurements over the 12-h period suggests that this methodology is feasible for use in future long-term EMG studies.

Reaching upward is more challenging to dynamic balance than reaching forward.

BACKGROUND: Older adults have less confidence in their ability to reach upward compared to reaching forward. The forward reach test may, therefore, not be ideally suited for detecting functional deficits that directly affect daily activities. METHODS: A new test of upward reach and forward reach (along a 50-degree track) were administered to young and older adults. Reach distance was adjusted for foot length and normalized to stature. The anterior safety margin was calculated by relating the center of pressure to the base of support. The extent to which age, sex, balance confidence, anthropometric, and center of pressure parameters contribute to forward and upward reach performance was assessed. FINDINGS: Reach and anterior safety margin scores were well-correlated between forward and upward reaching, but the upward reach test posed a greater challenge to dynamic balance - eliciting a smaller anterior safety margin from both older and younger subjects. Further, compared to young adults, older adults showed greater limitations in reach distance and balance parameters during upward reach compared with forward reach. An observational measure of reach strategy (whether or not the heels were raised from the platform during the test) differentiated between higher and lower reach performance for older adults. Anthropometric variables accounted for much of the variance in reach performance that would otherwise have been attributed to an age-related loss of functional capacity. Balance confidence scores also contributed to regression models predicting upward - but not forward - reach performance in older adults. INTERPRETATION: Though upward and forward reach performances were well related in this sample, a test of upward reach may be better suited to reveal early signs of functional decline in older adults than a test of forward reach.

Effect of pilot-hole size on the pullout strength of flexor digitorum longus transfer fixed with a bioabsorbable screw.

BACKGROUND: Fixation of tendon transfers with a bioabsorbable interference-fit screw has several advantages over other fixation methods: decreased dissection, operative time, and blood loss; preservation of tendon length; no interference with radiographic studies; no need for implant removal; and no barrier to revision surgery. Whether strength of fixation is affected by the size of the pilot hole has not been established. The purpose of this study was to determine the effect of pilot hole size on the pullout strength of a flexor digitorum longus (FDL) tendon secured into a bone analog using a 5.5-mm bioabsorbable screw. METHODS: Thirty FDL tendons were harvested from 15 cadaver specimens and secured into predrilled 4 x 4 x 4 cm bone cubes with a 5.5-mm Arthrex bioabsorbable screw (Arthrex, Naples, FL). The use of bone analog foam cubes ensured consistent porosity at the insertion site, eliminating the variations associated with varying bone densities of cadaver specimens. Pilot hole sizes studied were 5.0 mm, 5.5 mm, and 6.0 mm. Pullout tests were done with an servohydraulic testing frame (MTS, Eden Prairie, MN). RESULTS: There was no significant difference (p = 0.4) between the pullout forces and stresses among the three pilot hole sizes. All specimens failed at the interface between the FDL and the bioabsorbable screw. In the 6.0-mm pilot hole group, there was a trend for increased pullout strength with increased tendon size. CONCLUSIONS: With a bioabsorbable 5.5-mm screw used for FDL transfer, a pilot hole the same size or a half millimeter larger or smaller than the screw had no statistically significant effect on the strength of the construct, even with tendons of different sizes.

Space cycle: a human-powered centrifuge that can be used for hypergravity resistance training.

INTRODUCTION: This study represents the first step toward testing the hypothesis that hypergravity can be used as a unique resistance training modality for maintaining the health and function of skeletal muscle in microgravity. The primary objectives of this study were to use a human-powered short-arm centrifuge for the following: 1) to determine whether subjects could perform squats under hypergravity conditions without developing motion sickness or illusory motion; 2) to measure foot forces while performing squats under hypergravity conditions; and 3) to determine the mechanical power required to produce 1.5, 2.0, 2.5, and 3.0 Gz (head to foot) at the feet. METHODS: Subjects (22 males and 19 females) performed 10 squats each at 1.5, 2.0, 2.5, and 3.0 Gz on a human-powered short-arm centrifuge, the space cycle. Foot forces during each squat were monitored using insole force sensors, and normalized to foot forces measured at 1 Gz (relative foot forces). RESULTS: Illusory motion was minimized using a visual focal point, and did not affect the ability of subjects to perform squats. The mean standing relative foot forces at 3.0 Gz were 2.3 and 2.4 for the male and female subjects, respectively. The work rate required to power the space cycle was a linear function of Gz, and is well within the aerobic scope of untrained individuals. DISCUSSION: The findings of this study demonstrate that hypergravity can be used as an effective modality for loading skeletal muscle and that subjects can perform squat resistance exercise without developing motion sickness or illusory motion.