Xi’an Bell Tower (the Bell Tower) is a state-level ancient relic in China. The vibration caused by metro will exert adverse effect on the Bell Tower. This paper aims at presenting 3D-FEM models to predict the peak period velocity (PPV) of rammed earth base when the metro passing through the Bell Tower. The calculation results are compared with those of field test. Both results were found to be in good agreement. Furthermore, the results indicated that the effect of shock absorption measures is significant. The shock absorption tracks can obviously decrease the vibration of the Bell Tower, and the maximum decrease of PPV of the rammed earth base is 78.91 %. The proposed prediction has the potential to be developed as a decision and management tool for the evaluation of the risk associated with the influence of vibration caused by metro on buildings in urban areas. As one of four ancient capitals in the world, Xi’an was once the capital for 13 dynasties in Chinese history. The Bell Tower, as a city landmark, is a precious ancient building with a history of over 600 years, but its durability has been gradually weakened for the long history. Xian is now enjoying a boom in metro construction, which will unavoidably cause vibration for the Bell Tower. In the other word, even the tiniest vibrations may lead to fatigue failure for the Bell Tower since the continuous vibration.In 1970s to 1990s, some researches analyzed the deformation and failure rules of the ancient structures under the vibration according to field tests Mata . At the The influence of metro vibration on REB of the Bell Tower was studied in this paper which will provide valuable experience for protecting similar ancient cultural relics. In order to make an evaluation on the stability of the Bell tower, the field investigation was conducted in the paper firstly that can provide soil parameters for finite element model of the Bell Tower and get the soil layer structure and engineering characteristics. What is more, here we summarized a lot of vibration safety standards of buildings, and got the most suitable vibration safety standards for the Bell Tower. Thirdly, 3D-FEM models are made to simulate the working conditions including with or without shock absorption tracks and different train speeds. Finally, the calculation results are compared with field tests for verifying the correctness in the paper.As the symbol of Xi’an, the Bell tower was built in Ming dynasty, and was a classical brick-and-wood structure. The tower body was borne by 4 central cylinders and 12 surrounding cylinders, as shown in Fig. There are different vibration safety standards in different countries, including America, UK, Germany, Japan, Portugal, Swiss, and China, as shown in Table There are two metro lines under the Bell Tower, Metro Lines 2 and 6  Fig. . The conAccording to different sampling frequency, the time period and time increment size of the environmental vibration problem are studied in many Literatures  refers to nodal force vector changing along with time. The mass matrix, damping matrix and stiffness matrix as well as nodal force vector are calculated as follows:The motion equation of the structural system based on Hamilton principle Meng  is:1\docGenerally, it is assumed that the relationship between the damping matrix and mass matrix, stiffness matrix is in direct proportion, that is Rayleigh damping is adopted Chen , and theα and β and the damping ratio should satisfy the following relationship:ξk is the damping ratio; ωk is the inherent frequency; α and β are damping ratio coefficients.According to the orthogonal condition of the vibration mode, the undetermined constants ωi and ωj, and based on tests and similar structure data, the damping ratios of ξi and ξj can be obtained. From formula , including train type, number of wheels, wheel distance, train speed, running distance, etc. The train formation of Xi’an Metro is six trains Meng . So the A number of numerical simulations have been carried out to investigate the effects of metro vibration to the Bell Tower: (1) the distribution of PPV in REB; (2) the laws of P PV in different condition; (3) the effect of the shock absorption tracks.Vibration velocities of the REB in each condition were shown at Figs. As can be seen, (1) According to Figs. To evaluate the effect of the shock absorption tracks much directly, reduction of PPV was shown in Tables When there were no shock absorption measures, the PPV of the REB was 0.372–0.753 mm/s, beyond the standard value of 0.15–0.2 mm/s. In conditions 4–6 with shock absorption tracks, the PPV of the REB was 0.093–0.199 mm/s, which decreased to the allowable value range. When compared with the condition 1, the PPV of four points in condition 4 reduces by 71.75–73.57 %. Compared with condition 2, the PPV of four points in condition 5 reduces by 71.61–76.92 %. Compared with the condition 3, the PPV of four points in condition 6 reduces 71.51–78.91 %. Thus, the application of shock absorption tracks can largely weaken the influence of vibration on the Bell Tower.To validate the model, calculation results were compared with those of field tests (Ma et al. The PPV of four points under in condition 5 were consistent with field data, as shown in Table The vibration velocity of the REB does not increase monotonically with the increase of the train velocity; however, it is related to the train quantity, track category and running mode of train.When shock absorption tracks are not adopted, the PPV of the REB beyond the safety standard, which has the potential to induce severe damage to the Bell Tower. However, the PPV of the Bell Tower decreases greatly when vibration reduction track is adopted, and the PPV does not exceed the allowable maximum value, and the maximum decreases are 78.91 %. The whole predicted that the application of shock absorption tracks can weaken the influence of vibration on the Bell Tower to a great extent.After the verification on calculation result for the model in this article through on-site monitor, it is discovered that the model can quantitatively reflect the actual vibration response of the Bell Tower. Therefore, we will investigate the settlement of REB and the PPV of the wooden structure caused by vibration for the Bell Tower in the following study.In order to investigate influence of vibration on ancient architectures, this article summarized vibration standards and took PPV as the safe standard for the Bell Tower. Numerical analyses were done using the MIDAS/NX in six conditions and the following results were observed:


Prior research has focused primarily on sensorimotor collaboration and is generally limited to relatively constrained visuomotor tasks. Moreover, the mechanisms by which performance improvements are achieved during sensorimotor cooperation with haptic interaction remains unknown. We propose that the effects of role assignment, motor redundancy, and skill level in sensorimotor cooperation should be explicitly studied. Additionally, the importance of haptic interactions may be better revealed in tasks that do not require visual feedback. Finally, cooperative motor tasks that allow for motor improvement during solo performance to be examined may be particularly relevant for rehabilitation robotics. Identifying principles that guide human-human sensorimotor interactions may lead to the development of robots that can physically interact with humans in more intuitive and biologically inspired ways, thereby enhancing rehabilitation outcomes.Physical interactions between patients and therapists during rehabilitation have served as motivation for the design of rehabilitation robots, yet we lack a fundamental understanding of the principles governing such human-human interactions (HHI). Here we review the literature and pose important open questions regarding sensorimotor interaction during HHI that could facilitate the design of human-robot interactions (HRI) and haptic interfaces for rehabilitation. Based on the goals of physical rehabilitation, three subcategories of sensorimotor interaction are identified: The online version of this article (doi:10.1186/1743-0003-11-142) contains supplementary material, which is available to authorized users. Designing robots that can physically interact and move with humans to cooperatively perform motor tasks, physically assist in achieving motor goals, or aid in rehabilitation of movement is a grand challenge of robotics. Robots have the potential to improve rehabilitation by initiating treatment earlier than may otherwise be possible, increasing the intensity of training, creating enriched environments that simulate real-world conditions, and allowing patients to practice motor tasks that they may otherwise be unable to perform alone. However, for robotics to successfully serve such roles in rehabilitation, the interaction between robot and patient should be one that is intuitive and natural . Many prA complementary approach to augment the engineering approaches described above is to identify relevant sensorimotor principles of human-human interactions (HHI) that could guide the design and control of rehabilitation robots. It has been suggested that rehabilitation robots based upon principles of human-human sensorimotor interaction  would intwo brains, two hands) and bimanual interaction . Therefore, this review will focus on physical interactions between two humans with consideration to the perspective of what can be gained for understanding rehabilitation robotics. Readers are encouraged to seek out previous reviews of bimanual interaction [In this review we define HHI to be any sensorimotor interaction that occurs between two or more physically connected individuals. Participants do not necessarily need to be working towards a common motor goal, but in its application to physical rehabilitation this would generally be the case. Bimanual interactions performed by a single individual could be viewed as an additional form of motor interaction. In fact, bimanual interactions share similarities with HHI including the use of specialization strategies to coordinate the actions of each arm during motor performance . Howevereraction –40 to sueraction , 41.To address the gap in our understanding of fundamental principles governing HHI, here we outline areas of study in HHI that may be useful for guiding the design and use of rehabilitation robots. We begin by reviewing proposed taxonomies of HHI, and evaluating their application to physical rehabilitation. We then examine the existing HHI literature, analyzing the principles of HHI that have been elucidated to date, and the experimental paradigms and metrics used in their identification. Finally, we highlight important future directions and unanswered questions about the nature of physical interactions between human partners and how they may reveal general principles of HHI relevant to HRI in the context of rehabilitation.There is currently no widely accepted framework for understanding HHI in the context of its application to rehabilitation robotics. Here we will review the different ways in which HHI have been conceptualized, and elaborate on aspects of HHI classification with respect to the objectives of physical rehabilitation, the roles assigned to participants, and their relative skill level.social facilitation).The greater the number of participants performing simultaneously, the higher the performance level (learning and transfer).The transfer of performance from one team size to another varied (leadership) [The most important determinant of team performance was either the skill of the best solo performer (in quads) or the worst solo performer (in dyads) (dership) .As early as 1956, Wegner  proposedWhile all of these questions are germane to the questions facing rehabilitation roboticists, their approach did not examine how the interactions actually occur. This is critical for translating of findings to the design and use of robots that could participate in similar interactions.a prior i role assignment in the partnered visuomotor task. As a result, the roles described are adopted spontaneously and often changed over time. However, it is not clear that such emergent roles are immediately applicable to physical rehabilitation, where roles are typically assigned a priori and generally remain fixed.More recently, HHI has been classified according to the emergence of specific roles adopted by participants and the resulting interaction forces. Melendez-Calderon  used inta priori role assignment. Here, one member of a dyad is consistently directing the movement of another. They proposed that three factors could be used to classify the resulting motor interactions:the type of interaction force applied (i.e. assistive or resistive);how task forces, those generated from the dynamics of the task, are differentiated from externally applied guidance forces, andhow the weights of these two types of forces vary over time with respect to motor performance .Powell and O’Malley  adopted This approach provides important insights into the characterization of physical interactions within the context of physical rehabilitation and the differential role that each member of a dyad can adopt. One aspect of the interactions that is not considered is how they may differ depending on the goals associated with the motor interaction. For example, the forces may vary depending on whether the leader is providing assistance for a motor deficit, or aiming to train an individual to improve their motor ability beyond the partnered condition.competition, collaboration and cooperation. During competitive sensorimotor interactions both participants consider only their own effort and error. Such interactions typically emerge during the performance of antagonistic tasks, as exemplified by sports such as wrestling, where the gain of one agent results in loss of the other agent. In contrast, during collaborative and cooperative sensorimotor interactions, each participant considers there own effort and error as well as that of there partner, attempting to work together to identify a mutual beneficial resolution to a task. Therefore, unlike competitive interactions, collaborative and cooperative interactions occur in the performance of agonistic tasks, where gains and losses similarly affect both agents in a dyad, such as in rowing. Collaborative and cooperative interactions differ based on how roles are assigned to each participant and how that impacts their contribution to the interaction. In collaborative interactions there is no a priori role assignment. Roles are adopted in a spontaneous manner and subject to change. Emerging from this is an equal distribution of responsibilities or work between the participants. In contrast, during cooperative interactions roles are assigned a priori to each subject, and these roles are maintained throughout the performance of the interactive task. This creates asymmetric interests and an uneven distribution of sub-tasks between the participants such that while both individuals are working towards the same goal, they are doing so by performing different parts of the same task.Jarrasse  proposedAssistance and education are two forms of cooperation identified by Jarrasse [Jarrasse  that areJarrasse . From thOne important difference across these taxonomies is the ways in which the roles of the participants are defined. In the taxonomy proposed by Jarasse , roles ai.e. education and assistance). Here, leader-follower or teacher-student roles are predefined. However, the vast majority of the prior research involving HHI has focused on sensorimotor collaboration. Here, two individuals share a common goal, but have no pre-defined roles. Next we review prior studies in HHI, discussing the experimental paradigms, performance metrics, and the influence of haptic information during sensorimotor collaboration between two human partners  through which members of a dyad interact are sufficient to define the kinematics of the task , 55, 64.Various kinetic metrics have also been used to characterize HHI, often as a means to describe the contributions of each member in a dyad to the interactive visuomotor task. Ikeura  examinedMore complex constructs such as effort and efficiency , 70, 71 More recently, muscle activity has been recorded  as a wayDyads that are haptically linked can perform collaborative visuomotor tasks as well as  or fasteIn early HHI studies, social facilitation was suggested as a potential explanation for performance improvements in dyads versus solo performance . It is wa priori may confound our understanding of haptic interaction in cooperative HHI and HRI.In dyad performance during sensorimotor collaboration, the addition of haptic feedback improves visuomotor task performance compared to conditions where only visual feedback is available , 64, 71.Performance improvements by haptically linked dyads in visuomotor tasks are accompanied by alterations in the forces between participants. During visuomotor task performance, both members in a dyad apply higher forces than during either of their individual performances . This oce.g. pushing or pulling) between individuals in a haptically linked dyad were thought to stabilize HHI [Originally, the opposing forces . In a single study examining the forces that physical therapists apply during sensorimotor training, Galvez  found thIn future work it may be helpful to verify that elevated interaction forces facilitate the observed improvements in motor performance during dyad versus solo performance. To further probe the role of elevated interaction forces between human partners and how it may influence motor performance, one could imagine a simple experiment where several different conditions are tested. In each condition the initial interaction force (compressive and tensile) between the human partners is systematically varied. Motor performance from each condition could then be compared to examine the role of the elevated forces that have been observed during HHI.e.g. body-weight supported treadmill training). In such situations, haptic guidance via cooperative sensorimotor education may increase patient confidence and limit safety concerns, providing individuals the opportunity to identify not only the most effective, but also the most efficient movement strategies.In contrast to the work of Galvez , which fThus there remains a substantial gap in our understanding of how haptic feedback should be used during sensorimotor education to correct movement errors with the goal of promoting skilled individual performance. Currently we lack a framework and experimental data describing how humans physically interact, much less how therapists physically guide patients during rehabilitation. As a result there is not a solid scientific understanding of how this can best be achieved or what principles roboticists should attend to when designing robots for the purposes of rehabilitation.i.e. more cooperative and less collaborative interactions). Clearly defining the roles for each member of a dyad when studying cooperative HHI may allow for a more specific characterization of how the use of haptic information differs across the roles of leader and follower. It may also simplify data analysis, and provide specific insight regarding how a robot should emulate a leader versus a follower for the purposes of physical rehabilitation. Specifically, a more detailed analysis of the roles of dominance as examined through HHI may prove to be particularly relevant to identifying principles that could inform assist-as-needed control strategies implemented in rehabilitation robotics. As a patient’s performance improves, and the therapist’s role as leader decreases, with fewer or smaller errors requiring correction, what changes take place in regards to the interaction forces between them? Does the magnitude of the force decrease? Does the consistency with which forces are applied change? By examining how role assignments change over time with improvements in motor performance during HHI, we may develop a better understanding of how force interactions between humans and robots should be modeled in rehabilitation robotic control schemes. Interestingly, individuals in a haptically linked dyad prefer to interact with some dominance difference [Examining how the assignment of specialized roles influences HHI may be of particular relevance to rehabilitation robotics. During physical rehabilitation, therapists initially take on the role of leader by physically guiding the movements of the patient, who in turn takes on the role of follower. As motor recovery progresses, those roles may be altered, with the therapist assuming less and less of a leader role and the patient attempting movements independently or driving the learning. However, the difference in the role of leader versus that of follower in cooperative sensorimotor HHI among unimpaired adults is not well understood. Therefore, future research should be explicit about the roles of the participants in order to accurately represent motor interactions between therapist and patient . Similarly, therapist-patient interactions are often driven by haptic interactions. While it is likely that much of the information regarding motor goals can be communicated purely through haptic feedback and dynamic interactions [e.g. move or pass a small object a short distance, track a visual target), are rather limited and may not reflect the motor goals that are the focus of physical rehabilitation. By expanding the work on HHI to include motor goals common to rehabilitation , we may develop a better understanding of what force interactions are capable of encoding. In turn this may influence how roboticists design haptic interfaces for rehabilitation robotics. Ultimately, this relies on the selection of motor activities that can be performed with and without the use of vision and that allow for the assessment of motor complex motor goals in order to isolate the influence of haptic interactions.While a range of sensory information can be used to inform intentions and actions during cooperative motor tasks, many rehabilitation robots interact primarily with users through haptics (ractions , our undOur desire to develop robots that can physically interact with humans in intuitive and biologically inspired ways has revealed a vast field of human-human physical interaction that has only begun to be studied. It may be advantageous to design robots that can be optimized to the functioning of the human nervous system. However, much work is to be done in human-human sensorimotor interactions before any general principles of cooperative sensorimotor control can be firmly established. As a first step, we have identified some areas of potentially fruitful investigation to reveal principles of sensorimotor cooperation in HHI that are directly relevant to the design of physical interfaces and control schemes for rehabilitation robots. Specifically, we propose that new experimental paradigms should be developed that can address open questions of how motor redundancy, varying skill level, specific role assignment, and reliance on haptic feedback play a role in the haptic cues and physical interactions between individuals. In particular, more attention in the specific areas of sensorimotor assistance and sensorimotor education could provide some guidance in the design of haptic interfaces and controllers for rehabilitation robots. Possible motor tasks that could be used in such paradigms include but are not limited to: handshake, partner dance, sawing, carrying objects, leading an individual with visual impairment, and as a more direct clinical task, therapist-patient interactions during rehabilitation. While several of these tasks have served as motivation for a number of HHI studies, we still lack a basic understanding of the magnitude of forces used in these tasks. Additionally, how interaction forces contribute to task performance, or provide a channel for communicating information about motor performance, intent, and skill remains unknown. The identification of general principles of sensorimotor interaction between human partners may also be applicable to an alternative perspective of human-robot interaction in rehabilitation. While the application of HRI in rehabilitation has traditionally focused on the robot-patient interaction, future work may also wish to consider HRI in rehabilitation from the perspective of a robot interacting with a therapist. How might a robot that is focused on the therapist assist him or her in achieving their goals for the patient? While the nature and challenges presented by the interaction between robot and therapist are likely to be different from those of robot-patient interactions, principles derived from the study of HHI may serve to inform such interactions as well. Overall, the identification of guiding principles that drive human-human sensorimotor interactions have the potential to further the design, control and use of rehabilitation robots that can physically interact with humans in intuitive and biologically inspired ways, thereby enhancing rehabilitation outcomes.


The ab initio potential energy surface (PES) describing the interaction between the Ar atom and the rotating LiH molecule has been calculated very accurately and already discussed in our previous work [Computational and Theoretical Chemistry 993 (2012) 20–25]. This PES is employed to evaluate the de-excitation cross sections. The ab initio PES for the LiH(X1Σ+)-Ar(1S) Van der waals system is calculated at the coupled-cluster [CCSD(T)] approximation for a LiH length fixed to an experimental value of 3.0139 bohrs. The basis set superposition error (BSSE) is corrected and the bond functions are placed at mid-distance between the center of mass of LiH and the Ar atom. The cross sections are then derived in the close coupling (CC) approach and rate coefficients are inferred by averaging these cross sections over a Maxwell-Boltzmann distribution of kinetic energies. The 11 first rotational levels of rate coefficients are evaluated for temperatures ranging from 10 to 300 K. We notice that the de-excitation rate coefficients appear large in the order 10−10 cm−3 s−1 and show very low temperature dependence. The rate coefficients magnify significantly the propensity toward ∆ J = −1 transitions. These results confirm the same propensity already noted for the cross sections.A theoretical study of rotational collision of LiH(X Theoretically, the electronic structure methods, semi-empirical as well as ab initio, have been employed to calculate intermolecular potential energy surfaces to study the LiH in excited rotational levels by collision with the atoms H ] level of theory and with aug-cc-pVQZ Gaussian basis set for the H and Ar atoms and cc-pVQZ Gaussian basis set for the Li atom.In our previous work for the LiH-Ar system, we have reported the first quantum mechanical close coupling calculations of integral cross sections for transitions between the lower rotational levels of LiH induced by collision with Ar based on the 1Σ+)–Ar(1S) Van der Waals system using the rigid-rotor approximation and the Jacobi coordinate system in which re is the LiH internuclear distance, R the distance from the center of mass (c.m) of LiH to Ar atom, and θ the angle between the two distance vectors. The collinear LiH…Ar geometry corresponds to θ = 0° while the LiH bond length is frozen at the experimental equilibrium geometry of the ground state re = 3.0139 bohr  method  over a Maxwell-Boltzmann distribution of kinetic energies Ek following the procedure used in previous works  and Ek = E – Ej is the relative kinetic energy. The Table where J = − 1 transitions. This result confirms the same propensity observed with the cross sections and remains an important consequence of atmospherical chemistry.We notice that the downward rate coefficients depend on low temperature. This effect of temperature dependence has been seen by Taylor and Hinde  at littlJ for selected ∆J = −1, −2 and J → 1 transitions respectively. Except the ∆J = −1 transition at 10 K, the plots of rate coefficients exhibit the same trends and decrease with increasing J’ from J' = 2. For J → 1, the downward rate coefficients decrease with increasing J and the gap between the plots narrow considerably. In addition, the collision rate coefficients reflect the similar behavior with the general trends observed earlier for HCP-He –Ar(1S) van der Waals system computed in our previous work (Niane et al. In this work, using the −10, 2.7792 10−10 and 2.5272 10−10 cm3s−1. It is obvious that these results may be useful for the atmospherical chemistry as well as for experiments. Finally, encouraged by this result, we will be undertaking the study of the spectroscopy of complex and the vibrational dependence of potential energy surface which is crucial for the diatomic molecular.The downward rate coefficients at 300 K for the transitions 1 → 0, 2 → 1 and 3 → 2 are estimated respectively at 2.5664 10


Long-term exposure to fine particulate air pollution, such as particulate matter ≤ 2.5 μm in diameter (PM2.5), has been found associated with acute myocardial infarction (AMI) which is the most common cause of congestive HF. In this study, we have investigated the effect of combined metoprolol and terbutaline on cardiac function in a rat model of AMI exposed to PM2.5. Our results demonstrated that short-term exposure to PM2.5 contributes to aggravate cardiac function in rats with myocardial infarction. The combined use of β1-AR blocker and β2-AR agonist is superior to β1-AR blocker alone for the treatment of AMI rats exposed to PM2.5. The combination of β1-AR blocker and β2-AR agonist may decrease the mortality of patients with myocardial infarction who have been exposed to PM2.5.The pathophysiological mechanisms of heart failure (HF) stems were mainly from longstanding overactivation of the sympathetic nervous system and renin-angiotensin-aldosterone system. Recent studies highlighted the potential benefits of  Combined use of β1-AR blocker and β2-AR agonist has been proposed to treat chronic heart failure [olamines . β-AR hapes β1, β, and β3, process . In cont failure , and the failure , 8.μm (PM2.5) has been implicated as a risk factor on respiratory system and cardiovascular system [Recently, air pollution has been found to increase risks for a wide range of diseases. Studies indicate that in recent years exposure levels have increased significantly particularly in rapidly industrializing countries with large populations. Exposure to particulate matter with diameter less than or equal to 2.5 r system , 10. Parr system –13 or shr system , 15 PM er system , 17, echr system , 19, incr system , increasr system , 22, andr system , 24.β-AR subtypes on cardiac function in rats with myocardial infarction after administration of PM2.5. The aim of this study is to investigate the effect of metoprolol (a β1-AR blocker) and terbutaline (a β2-AR agonist) on cardiac function in a rat model of myocardial infarction rats after exposure to PM2.5.Until now, to the best of our knowledge, there were no studies on the effect of Adult male Sprague-Dawley rats weighing 200–250 g were obtained from the Laboratory Animal Center of Shanxi Medical University, China. All rats were housed in light-controlled animal quarters with temperature of 23 ± 2°C and were provided free access to food and libitum. This study was approved by the Bioethical Committee of Shanxi Medical University and all the procedures followed the National Guideline for the Care and Use of Laboratory Animals.2.5, rats were randomly assigned to two different study arms: one study arm without PM exposure and the second study arm with PM exposure.The rats were anesthetized with sodium pentobarbital  and underwent sterile surgery. Acute myocardial infarction (AMI) was induced by ligating the left anterior descending (LAD) coronary artery for the study group but without ligating the vessel for sham surgery group as previously described , 26. In n = 6 in each group): sham, AMI, metoprolol , terbutaline , and combined use of metoprolol (20 mg/kg body weight twice a day) and terbutaline (2 mg/kg body weight twice a day). Metoprolol and terbutaline were administered orally by gavage.In the first study, rats were divided into five groups . All the rats were anesthetized with sodium pentobarbital  and placed supine with extended neck on an angled board [2.5 at a final concentration of 40 mg/kg body weight was administrated through a cannula inserted into the trachea just above the bifurcation [n = 10 in each group): sham, AMI, metoprolol (20 mg/kg body weight twice a day), terbutaline (2 mg/kg body weight twice a day), and combined use of metoprolol (20 mg/kg body weight twice a day) and terbutaline (2 mg/kg body weight twice a day).For the second study, rats were exposed to PMurcation . This inmax and −dP/dtmax) were derived by computer algorithms.Rats were anesthetized with sodium pentobarbital , a polyethylene catheter connected with a pressure transducer was inserted into the left ventricular cavity via the right carotid artery . Left veTo evaluate the impact of metoprolol and terbutaline on cardiac performance, ECG was performed on all rats before and after MI, as well as after administration of each medication. ECG was performed under anesthetizing with sodium pentobarbital  to assess left ventricular function as previously described . Images μg. Proteins were transferred to a polyvinylidene membrane [Protein was extracted from frozen left ventricular tissue. Bovine serum albumin as a standard protein concentration was determined by the bicinchoninic acid protein assay . Equal proteins were loaded on 12% SDS-PAGE which were confirmed by Coomassie blue staining. The sample volume is 40 membrane , 32. Ratμm thickness were cut from each tissue block [2O2 and incubated with the reaction mixture containing TdT  and FITC-conjugated dUTP at 4°C overnight. One part of labeled DNA was visualized with fluorescent microscopy. Another part was incubated subsequently with alkaline phosphatase (AP) conjugated anti-FITC antibody for 1 h at 37°C and then visualized using AP-Red as the chromogen. Finally, the labeled DNA was detected with medical image analysis system. For negative control, TdT was omitted from the reaction mixture. Assays were performed in a blinded manner.To determine myocardial apoptosis, cardiac tissues from the MI group, sham group, MI + meto group, MI + terbu group, and MI + meto + terbu group were perfused first with 0.9% NaCl for 5 min and then with 4% paraformaldehyde in PBS (pH = 7.4) for 20 min. Ischemic regions were cut to 5 mm thickness at a level of left ventricular long axis and further fixed in 4% paraformaldehyde in PBS for 24 h at room temperature. Fixed tissues were embedded in a paraffin block and two slides at 5 ue block . The sliIncreased oxidative stress in the myocardium has been observed in heart failure animals; the GSH/GSSG ratio, a measure of overall cellular oxidative stress, was calculated to evaluate the degree of heart failure. Fresh left ventricular myocardial tissue was homogenized. The supernatant was collected for measuring total GSH using a GSH reductase-coupled enzymatic assay on a SPR-960B microplate reader . Total GSH was calculated from a standard curve of purified GSH, and glutathione disulfide (GSSG) was measured by masking the reduced GSH with 2-vinyl pyridine in the enzymatic assay. Total GSH = 2 × GSSG + GSH, GSH/GSSG was calculated .P < 0.05. Survival rates in each group were analyzed by the Kaplan-Meier method [SPSS 17.0 statistical software package was used for the statistical analysis. All quantitative data were presented as mean ± SD and analyzed by using the least-significant difference test of analysis of variance. Differences were considered statistically significant at r method .Representative M-mode recordings of diastolic and systolic left ventricular (LV) diameters were shown in The hemodynamic parameters of rats are presented in The proapoptotic protein (Bax) and antiapoptotic protein (Bcl-2) were determined by western blot . CompareMyocardial apoptosis in the MI group was significantly higher than that of the sham group. However, the degree of apoptosis after drug interventions was significantly lower in the MI + meto, MI + terbu, and MI + meto + terbu groups than in the MI group . The chaThe myocardial tissue GSH/GSSG was determined in sham and AMI animals . Compare2.5 was found with significant ventricular arrhythmia along with a further decrease of heart rate. Forty-eight hours after medication intervention, survival rates were 100%, 60%, 80%, 90%, and 100%, respectively. No significant differences were found between sham group and medication administrated groups (Rats exposure to PMd groups . There wIn the present study, significant increase of the ±dp/dt and LVSP and decrease of LVEDP were found in the single or combined use of metoprolol and terbutaline, compared with those in the untreated AMI group. In addition, combined use of metoprolol and terbutaline improved cardiac function significantly more than that of the treatment with metoprolol alone. In addition, cardiac remodeling was evidenced by the reduced FS and EF, as well as progressive dilation of the left ventricle in the AMI rats. This was associated with the increase of LVEDD and LVESD. Metoprolol or terbutaline alone or combined use of metoprolol and terbutaline can significantly ameliorate cardiac remodeling by reducing LVEDD and LVESD and increasing the FS and EF of left ventricle. The combined use of metoprolol and terbutaline had a better therapeutic response than that of metoprolol or terbutaline alone.β1-AR blocker could significantly improve cardiac function; therefore, they reduce the total mortality and morbidity in patients with heart failure [β-AR blocker could improve ventricular function and reduce cardiomyocyte apoptosis in myopathic turkeys [Numerous previous clinical studies have confirmed that long-term treatment with  failure –38. Our  turkeys . AMI or  turkeys . Our resβ1-AR blocker and β2-AR agonist may play an important role in the antioxidant effect as well as in AMI. This is consistent with the previous rat study, which demonstrated that carvedilol could attenuate myocardial inflammation and decrease the severity of myocarditis by the antioxidant action [Furthermore, we found that combined use of metoprolol and terbutaline suppressed oxidative stress-mediated myocyte apoptosis by increasing GSH/GSSG, which further confirmed that t action .β1-AR and β2-AR had significantly different signal transduction pathways [β2-AR signal transduction pathways conclude both Gs-AC-PKA pathway and Gi-PI3K-AKT pathway. Therefore, activation of β2-AR to a certain extent can inhibit apoptosis and improve cardiac function [Few studies found that pathways . β2-AR sfunction , 42.2.5 contributed to aggravate cardiac function in myocardial infarction rats. The mortality rate decreased after treatment of β1-AR blocker and β2-AR agonist. Many recent studies suggested that long-term exposure to low concentration of PM2.5 might alter vasomotor tone and induce vascular inflammation or atherosclerosis, increased risk of ischemic disease, and death due to pulmonary and systemic oxidative stress [Additionally, our studies demonstrated that short-term exposure to PMe stress , 14, 43.e stress .β1-AR blocker and β2-AR agonist. Our results suggested that reduction of myocardial oxidative stress by β1-AR blocker and β2-AR agonist plays an important role in AMI or heart failure. Combining β1-AR blocker with β2-AR agonist is better than the use of β1-AR blocker or β2-AR agonist alone. We conclude that β1-AR blocker and β2-AR agonist might be important clinical approach in the treatment of heart failure. Particularly, β1-AR blocker and β2-AR agonist may decrease the mortality after exposure to PM2.5.In our study, significant reversal of cardiac remodeling and improvement of hemodynamic function were found in the rat model of AMI after treatment of


Nanoconjugates showed significant enhancement in biological activity in comparison to free drug molecules. In this perspective, we report the synthesis of bioactive silver capped with 5-Amino-?-resorcylic acid hydrochloride dihydrate (AR). The The conjugation of AR to silver was confirmed through FTIR, UV¿vis and TEM techniques. The amount of AR conjugated with silver was characterized through UV¿vis spectroscopy and found to be 9% by weight. The stability of synthesized nanoconjugates against temperature, high salt concentration and pH was found to be good. Nanoconjugates, showed significant synergic enzyme inhibition effect against xanthine and urease enzymes in comparison to standard drugs, pure ligand and silver.Our synthesized nanoconjugate was found be to efficient selective xanthine and urease inhibitors in comparison to Ag and AR. On a per weight basis, our nanoconjugates required less amount of AR (about 11 times) for inhibition of these enzymes. In the new research areas of science, the research field of metal nanoparticles is an extensive and the most emerging field. The huge surface area of the metal nanoparticles is responsible for their diverse optical, chemical, magnetic, mechanical, and catalytic properties as compared to large bulk materials ,2]. Dif. Dif2]. in vivo applications, the stability of the suspensions was investigated against several parameters such as pH, temperature and salt concentration. Barron AgNPs (Ag) was prepared by reduction of AgNO3 with NaBH4. The in vitro antibacterial, antifungal, enzyme inhibition  and antioxidant activities of AgAR nanoconjugates were compared with pure AR, Ag and the commercially available antibiotics, enzyme inhibitors and antioxidants.Current research showed that conjugation of Ag to plant extracts boosted the enzyme inhibition and antimicrobial activities but these reports are not very systematic ,11]. In. In11]. 3, we observed a change in color from light brown to dark brown upon slow addition of NaBH4  in the spectrum of AR indicated the chelation of carboxylic group with silver. From FTIR characterization, a mechanism has been proposed for the synthesis of AgAR nanoconjugates and reported in Figure 4 has been involved in reduction of AgNO3 while carboxylic group of AR provide stability to AgNPs via electrostatic interactions . The IC50 of the compounds as calculated using EZ-Fit windows-based software . To compare the inhibitory activities of the compounds, allopurinol was used as standard. The reaction for each compound was performed in triplicate ..24].Measurement of superoxide radical scavenging activity was carried out by the modified method used by Ferda . The reaThe reaction mixture containing 5 ?L of (0.5 mg/mL) test samples (in DMSO) and 95 mL of DPPH (300 mmol) in ethanol, was taken in a 96-well microtitre plate and incubated in ELISA  at 37°C for 30 min. The absorbance was measured at 515 nm. RSA (%) was determined in triplicate by comparison with a DMSO containing controls. Ascorbic acid, butylated hydroxyanisole and N-acetyl cystine were used as the positive controls .AR: 5-Amino-?-resorcylic acid hydrochloride dihydrateAgAR: Silver nanoparticles capped with ARAgNPs: Silver nanoparticlesUV-Visible spectra: Ultra violet-visible spectraFTIR: Fourier transformed infraredTEM: Transmission electron microscopeThe authors state that they have no competing interests.SSN performed the synthesis of nanoparticles and wrote the manuscript. MRS supervised the whole work. AK and SSA helped in interpretation of biological data. NUI, SN and SQ helped with the analysis. All authors read and approved the final manuscript.3, NaBH4, AR and AgAR.Optical recognition of AgNOClick here for file4.Optimization of reaction conditions by changing the amount of Ag, AR and NaBHClick here for file


Most of the research in the area of psychosocial factors in rehabilitation after sports injuries has focused on risk behaviors, while relatively few studies have focused on behaviors that facilitate rehabilitation. The objective of our study was to understand the psychosocial features that characterize elite female football players who express a resilient behaviour during rehabilitation after a first-time anterior cruciate ligament (ACL) injury and reconstruction.A qualitative method was used based on individual in-person interviews and video communication of players who incurred a first-time ACL tear during the 2012 season of the Swedish Women’s Elite Football League. In total, 13 players had a first-time ACL and were interviewed post-season. The interviews were followed by a thematic content analysis. Based on this, eight players were identified as showing resilient behaviors during their rehabilitation and were included in the final analysis.Three core themes representing psychosocial factors that help players cope successfully with rehabilitation were identified: (I) constructive communication and rich interaction with significant others; (II) strong belief in the importance and efficacy of one’s own actions; and (III) the ability to set reasonable goals.The findings suggest three core themes of psychosocial factors that characterize first-time ACL-injured elite female football players showing resilience during rehabilitation after ACL reconstruction. Suggestions for medical teams about ways to support communication, self-efficacy, and goal-setting during the rehabilitation process, are provided. Anterior cruciate ligament (ACL) injury is a major problem in sport, especially in women’s team sports such as football . The rehResilience is a dynamic capability that helps people strive to realize their goals . We have exercised together with our physiotherapist…We have trained a lot together. I think it has helped us very much.” Still another player said “I have received a lot of support from the girls on the team. They have encouraged me a lot, it feels good … Supportive teammates are always important; they help me to think about other things.”Some examples of the support from coaches were: “Our coach has been really good; he has listened to me and often asked how I felt and so on” and “The coach pushed me to train harder on my own. It was great to feel that engagement from him.”II.Strong belief in the importance and efficacy of one’s own actionsOutside sport, players mentioned that everyday life was filled with positive interactions with others who encouraged and supported the rehabilitation processes. The experiences of communication with very close persons were especially noteworthy. As one player put it, “My Mom has been like a rock in a storm. She has always been there and been attentive to me, not necessarily giving loads of advice and that kind of thing; she has just been available.”Strong belief in the importance and efficacy of one’s own actions. Tolerance, persistence, acceptance, and life satisfaction were all features of this core theme.Different kinds of personality-related factors for helping injured players cope effectively during rehabilitation emerged in the analysis. Numerous players had positive, determined attitudes, yet at the same time maintained a mindful stance under the core theme “I don’t know. I was probably prepared for the operation and a long rehabilitation. I was organized already from the start. I told my physiotherapist to book a time with the doctor to arrange for the operation. Everything was progressing as it was supposed to. No problems at all.”III. Ability to set reasonable goalsSome players even expressed attitudes of endurance in preparation for the rehabilitation to come, sometimes based on a previous positive experience of recuperation from long-term injury. One player said, “I didn’t take it very hard. When I received the diagnosis, I was prepared. I had a positive attitude to the healing process and future opportunities to handle the injury.” Yet another player said, “It has been a process to understand, to permit myself to be sad. I have accepted this now.” For some players, there was acceptance and even satisfaction with their current life situations, coupled with an awareness of their inner potential. The strength of this acceptance (and self-efficacy) is evident in the following quote, “It’s really sad that it happened, but now I have new, bright perspectives and have received answers to many of my questions. This process has been important to me and now I am positive that I will play again.” Some players exhibited a high acceptance of their situations of being ACL-injured, which helped them endure the long rehabilitation period with confidence. One player reflected on the potential the injury generated, helping her understand her present life situation:“You should really take the time you need, use all your contacts and not be afraid to step on some toes. I have learned this from previous injury situations. We are professionals and because of that you should impose high demands on the resources in your environment and surroundings.”Under this core theme, a number of players appeared to be very focused and demonstrated strong goal-oriented behaviors during rehabilitation, with high self-generated motivation and clear plans for the future. Most of the players had already experienced successful rehabilitation from previous injuries. The following quote encapsulates how positive past rehabilitation experiences helped with their current situations:In much the same way, another player stated, “The ACL injury and the rehabilitation afterwards felt like a piece of cake. I remember I thought like that the last time I was severely injured”.One issue that repeatedly arose during the interviews was that players made plans and set clear goals for the future during rehabilitation. For instance, one player stated that, “My outlook and goal is to be back in 6 months after the operation … we play Champions League then. I will be physically and mentally ready at that time”.The main result of the present study, describing resilient athletes’ experiences of rehabilitation after ACL injuries, is that we identified three core themes representing psychosocial factors that appeared to help players cope with rehabilitation: constructive communication and rich interaction with significant others, a strong belief in the importance and efficacy of one’s own actions, and an ability to set reasonable goals.Analyzing the results of the narratives of the resilient players, it is striking how most of the players emphasized the adaptive and combined effects of supportive communications and interaction with significant persons both inside and outside their sport. Furthermore, it is also evident from the literature that a substantial part of previous research has focused on intra-individual resilience factors such as self-efficacy  and, to The resilient players were also characterized by having high beliefs in their own actions, including being success-oriented and having positive attitudes as they faced their rehabilitation periods. In many ways, they matched past profiles in previous studies on athletes who have experienced successful rehabilitation after severe sports injuries , 16. PerThe third core theme relates to the ability to organize oneself and plan for future activities using goals during the rehabilitation period. In part, this ability relates to the particularly relevant concept of dispositional optimism (as compared to optimistic behavior). Scheier et al.,  the origOne methodological issue to consider is that some players’ memory recall may have been inaccurate due to the fact that, on average, 6 months passed between the interviews and the injury dates, but the relatively high level of agreement between the findings and previous research speaks to the credibility of the results. One important sampling issue is that the resilient players played for/represented several different teams. It is therefore not possible to state definitively that the resilient players were predominantly located in supportive, constructive, and positively oriented teams, or had coaching staff sensitized to rehabilitation difficulties, or came from successful clubs. Another methodological consideration is whether adequate and quality data were collected to support the study (data saturation). It appears that the players’ narratives indicated behaviors that closely matched the dimensions of resilience, which include for instance self-efficacy, an ability to engage support and help, and learning from difficulties, characteristics often mentioned in the literature , 15. AnoAlso, another methodological issue important to reflect on is related to the selection of narrative constructivism as the theoretical foundation for the study. The reason for selecting this approach was that it emphasizes the importance of considering a person’s story as a reflection of his or her identity, emotions, and understanding of the past, present, and future . BecauseFinally, the focus of the study is not the rehabilitation speed or readiness for play but rather individual experiences of rehabilitation following the reconstruction of a first-time ACL injury and the factors that contribute to a resilient, successful rehabilitation. Because the approach is idiographic, no causal relationships could be claimed between the variables and the group of interest. Future studies, tentatively based on a biospsychosocial perspective, are therefore recommended to collect combinations of different type of data to provide further evidence to support the need to capture psychosocial data on injured athletes. Such evidence can guide the development of effective techniques that will facilitate rehabilitation.inclusive tactic that is also the task of teammates and coaches). Also, the medical team should aim to help the players increase their self-efficacy by acknowledging and reinforcing progress in the rehabilitation process, for example. A player’s self-efficacy is not solely held within the player and it can be increased or decreased depending on the social context and the contingencies of reinforcement and punishment in the sport and rehabilitation environments. It seems equally important for the medical team to encourage injured players to set daily goals for healing and improvement, as well as long-term goals for recovery. For the injured players, having experienced prior successful rehabilitations and thus having confidence and trust in their recovery, it is recommended that they take advantage of the time out as an opportunity to rest and reflect. Finally, for the injured players, it is suggested that they continuously take advantage of the social support systems that exist both inside and outside sport . This support appears to positively influence the sometimes long and arduous period that usually occurs during injury rehabilitation, or, as one player said of her physiotherapist and fellow injured athletes, “We have trained a lot together. I think it has helped us very much”.Building on the results of the present study, some practical suggestions based on adaptive behaviors of ACL-injured elite female football players during rehabilitation from ACL reconstructive surgery can be made. In the communication between the medical team and the injured player, it seems essential that both partners jointly draw up a plan for physical and mental recovery, in preparation for successful rehabilitation. Social support, in terms of communication and rich interaction, was a central theme in the present study, but curiously enough interaction with medical team was rarely mentioned. We can, however, on the strength of this theme put forward suggestions for medical team. This means that the medical team have an important mission to maintain constructive communication and rich interaction throughout the entire rehabilitation period. This implies not leaving the injured players isolated and outside the team (an It is concluded that the findings of the present study holds unique qualities resulting in resilient behavior during rehabilitation. Recommendations for medical teams are to focus foremost on supporting communication, self-efficacy, and goal-setting during the rehabilitation process of post ACL-reconstruction.ACL, anterior cruciate ligament


Injury rates in soccer are reported as one of the highest of all sports . Evidence also suggests that in amateur soccer, re-injury rates are as high as 30% often resulting in more severe subsequent injuries . It has been suggested that premature return to play is one of the main risk factors for re-injury . Coaches are intergral to the return to play decision in amateur soccer. However, little is known on what influences coaches decisions or how these decisions are supported by interactions with health professionals, including podiatrists.The purpose of this study was to understand coaches' experience of return to play decisions. A qualitative design using Interpretive Phenomenological Analysis (IPA) was implemented to elicit in-depth information from five amateur soccer coaches through semi-structured interviews. IPA focuses on the subjective lived experiences of the participants and the perceptions individuals have around this experience (Finlay 2009). IPA addresses the aims of the study by illuminating the coaches' experience of return to play and highlights the issues they perceive are of importance.coaches' subjectivity and limited collaboration with health professional's influences return to play decisions. In the absence of formal return to play guidelines and variable knowledge on injury management, coaches would make subjective decisions based on value of the player or importance of the game, even if the player was not fully rehabilitated. A lack of collaboration with health professionals about injured players resulted in reliance upon the player for communicating the rehabilitation plan and progress. This influenced the coaches' decisions as the player was not always seen as a reliable source.Several themes were illuminated from the data, with two of particular significance to podiatrists; Podiatrists may be able to impact on the high rates of re-injury in amateur soccer players if there was greater collaboration in injury rehabilitation between the health professional, player and coach. By enhancing the lines of communication this could also increase the understanding of injury rehabilitation, and reduce the subjectivity in amateur soccer coaches return to play decisions.


The objective of this study was to investigate the contribution of handgrip strength in predicting the functional outcome after hip fracture in women.We prospectively investigated white women (N = 193 of 207) who were consecutively admitted to a rehabilitation hospital after a hip fracture. We measured handgrip strength with a Jamar dynamometer , on admission to rehabilitation. Ability to function in activities of daily living was assessed by the Barthel index both on discharge from rehabilitation and at a 6-month follow-up.P < 0.001) and after 6 months . Significant associations between handgrip strength and Barthel index scores persisted after adjustment for age, comorbidities, pressure ulcers, medications in use, concomitant infections, body mass index, hip-fracture type, and Barthel index scores assessed both preinjury and on admission to rehabilitation (P = 0.001). Further adjustments for both Barthel index scores and Timed Up-and-Go test assessed at rehabilitation ending did not erase the significant association between handgrip strength and the Barthel index scores at the 6-month evaluation (P = 0.007). To define successful rehabilitation, we categorized the Barthel index scores as either high (85 or higher) or low (<85). The adjusted odds ratio for 1 SD increase in grip strength was 1.73  for having a high Barthel index score at the end of inpatient rehabilitation and 2.24 (95% CI 1.06–5.18) for having a high Barthel index score at the 6-month follow-up.We found significant correlations between handgrip strength measured before rehabilitation and Barthel index scores assessed both on discharge from rehabilitation (ρ = 0.52, Handgrip strength assessed before rehabilitation independently predicted the functional outcome both after inpatient rehabilitation and at a 6-month follow-up in hip-fracture women. Among them, a limited number of studies have pointed out low muscle strength as a negative prognostic factor.17 Indeed, isometric handgrip strength is strongly related with lower extremity muscle power, knee extension torque, and calf cross-sectional muscle area.18Muscle strength can be assessed by various techniques at different body sites. Although lower limbs are more relevant than upper limbs for gait and physical function, handgrip strength is measured very easily, and it has been widely used as a reliable and feasible surrogate for whole body strength.Our aim was to investigate the independent contribution of handgrip strength in predicting the functional outcome after hip fracture in women. We hypothesized that handgrip strength assessed at admission to inpatient rehabilitation could predict the ability to function in activities of daily living both at the end of inpatient rehabilitation and at a 6-month follow-up independently of several confounders.The study was performed in a city with about 1 million inhabitants. We evaluated 207 white women without cognitive impairment  and without prevalent motor impairment due to neurologic diseases, consecutively admitted to our physical medicine and rehabilitation division because of a hip fracture during a 12-month period (between January and December 2013). We focused on white patients because few nonwhite elderly subjects live in Italy. The women came from several orthopedic wards from various hospitals, and were referred for acute inpatient rehabilitation by the consultant physiatrists of the orthopedic wards. The criteria agreed upon for selecting hip-fracture women to undergo acute inpatient rehabilitation were health conditions allowing a total of 3 hours of physical therapy and/or occupational therapy daily, weight-bearing to tolerance on the fractured hip, and a potential high increase in the ability to function in activities of daily living due to an intensive rehabilitation regimen.Ten of the 207 women we evaluated were excluded from our study because their hip fractures resulted from either major trauma or cancer affecting bone. The remaining 197 women sustained fractures that either were spontaneous or resulted from minimal trauma . They all gave their informed consent to participate in the study. Four women could not complete inpatient rehabilitation because of acute concomitant diseases. The final study sample included 193 women whose data were included in the main analyses.Our rehabilitation protocol included 3 hours a day for 5 days a week of physical exercise to improve strength and balance, advice and training on the use of assistive devices, and training in mobility tasks and activities of daily living conducted by physical therapists and occupational therapists. At least 3 hours during the stay in the rehabilitation hospital were dedicated by a skilled occupational therapist to suggest targeted modifications of home environment and behavioral changes to prevent falls. The criterion for discharge from rehabilitation was the achievement of the highest possible Barthel index score (as judged by the responsible physiatrist) in the 3 following items: dressing, transfers, and walking. Institutional review board  approval was obtained for the study protocol.Handgrip strength was measured with a Jamar hand dynamometer within the third day since admission to the rehabilitation hospital. Testing was performed with the participant in sitting position and with her shoulder adducted and neutrally rotated, elbow flexed at 90° with the forearm in neutral position, and wrists between 0° and 30° of flexion and between 0° and 15° of ulnar deviation. The best recorded of 3 attempts of maximal voluntary contraction, performed at 1-minute intervals at nondominant arm, was considered for analyses.In each patient, we recorded age, number of medications in use, presence of pressure ulcers , number of concomitant diseases , infections , body mass index, and hip-fracture type .Functional evaluation, at both rehabilitation admission and discharge from the rehabilitation hospital, was assessed by skilled physiatrists by using the Barthel index . Also, the physiatrists assessed preinjury Barthel index scores by anamnesis. At a 6-month follow-up, the Barthel index scores were reevaluated by a skilled occupational therapist by telephone interviews in 148 of the 193 women. Data from 45 women were not available at the 6-month follow-up because they were not found (N = 25), had acute severe concomitant diseases (N = 6), died during the 6-month period (N = 4), or refused to participate in the telephonic interview (N = 10). The Barthel index assesses basic activities of daily living; its score ranges from 0  to 100 . The assessors were not aware of the results of handgrip strength measure at the time of Barthel index score evaluation.A Timed Up-and-Go (TUG) test was performed at the end of the rehabilitation course to determine the amount of time required for the subject to rise from a standard armchair, walk 3 meters away, turn, return, and sit down again. One practice and 1 test trial were performed for each participant. Before testing, a trained evaluator provided standardized verbal instructions regarding the test procedures. Time was recorded with a stopwatch started on the command “ready-set-go” and stopped as the participant sat down. Data were available for 167 of the 193 women. The remaining 26 women could not perform the TUG test because they were not able to walk without assistance.13 Linear multiple regression was also performed after substituting the Barthel index scores assessed at the 6-month follow-up  for the Barthel index score assessed at the end of inpatient rehabilitation. A further regression model with the Barthel index scores at the 6-month follow-up as the dependent variable included 2 additional covariates: Barthel index scores and TUG test both assessed on discharge from rehabilitation. Following area transformation of the dependent variables, the residuals were normally distributed in the regression models. Homoscedasticity was verified by plotting the residuals against the predicted values: the variance of the residuals looked homogeneous across levels of the predicted values. Collinearity diagnostics showed that the percent of variance in each predictor that could not be accounted for by the other predictors was always >75% (no redundant predictors were found). We had no missing data.We assessed the linear correlation between handgrip strength and Barthel index scores, by using a Spearman rank test, taking into account the nonnormal distribution of the outcome variables in our sample as shown by a Shapiro–Wilk test. Additionally, handgrip strength was included in a linear multiple regression model as an independent variable together with 9 potential confounders: Barthel index scores assessed both preinjury and on admission to rehabilitation, age, number of medications in use, presence of pressure ulcers, number of comorbidities, presence of concomitant infections, body mass index, and hip-fracture type. The dependent variable in the regression model was the Barthel index score on discharge. Because the Barthel index score was nonnormally distributed, area transformation was performed, using the formula (r-1/2)/w, where w is the number of observations and r is the rank.A further analysis was performed after categorization of the Barthel index scores into 2 groups both at the end of inpatient rehabilitation and at the 6-month follow-up: lower than 85 (“low score”) or 85 or higher (“high score”). The association between handgrip strength and high or low Barthel index score was adjusted for the 9 confounders listed above using a binary logistic regression because the dependent variable was dichotomous (having either a low or a high score). Handgrip strength expressed in SD units was included into the binary logistic regression model as an independent variable together with the 9 potential confounders.The statistical package used was SPSS, version 14 .Descriptives for the 193 women are shown in Table P < 0.001) and at the 6-month follow-up . The significant association between handgrip strength and the functional score persisted after adjustments for 9 potential confounders  for having a high Barthel index score at the end of inpatient rehabilitation (Table Handgrip strength assessed on admission to rehabilitation was significantly associated with the Barthel index scores categorized as either high (85 or higher) or low (<85). After adjustment for 9 potential confounders, the odds ratio for 1 SD increase in grip strength (5.7 kg) was 1.73  roughly doubled for each SD increase in grip strength. Although there is not a threshold for Barthel index scores universally agreed upon, several authors have indicated a cut point of 85 to define successful rehabilitation.22 Notably, the effect of handgrip strength was shown after multiple adjustments. Overall, the panel of prognostic factors we included in the regression model predicted 57% of the variance in Barthel index scores at the 6-month follow-up. Future prospective studies should aim at increasing the percentage of the variance in validated measures of functional outcome predicted by an early-stage examination. Likely, grip strength should be considered in any future predictive models.The clinical meaning of our study regards 2 aspects. First, we emphasize the relevancy of measuring handgrip strength to estimate the functional prognosis after hip fracture: handgrip strength is easily assessable and inexpensive,7 showed that grip-strength changes paralleled the changes of a self-reported 5-item mobility score during a 12-month period in 90 women following a hip fracture. Absolute values of handgrip strength were low in our sample,16 as expected in hip-fracture patients who are usually frail.23 Strengthening exercises performed either alone28 or as a part of multidimensional interventions30 actually had favorable effects on several outcome measures after hip fracture. This is in agreement with several reports in other frail subjects: strengthening exercises effectively counteracted age-related muscle loss improving both strength and performance, with modest requirements of time (sessions of 30 minutes twice per week) and equipment.32The second clinical meaning regards the rationale for interventions aimed at increasing muscle strength to optimize the functional recovery after hip fracture, given the link between muscle weakness and unfavorable outcome. In line with this observation, Visser et al11Among the covariates we included in our regression models, a significant prognostic role was found for Barthel index scores before fracture occurrence, at the beginning or at the end of inpatient rehabilitation, age, and 2 markers of comorbidity . These findings are in agreement with several previous reports.11 We assessed the functional recovery after hip fracture by using only 1 functional scale . However, the Barthel index is a validated scale in hip-fracture patients,33 and it has been widely used to evaluate functional outcome, the role played by several prognostic factors in affecting the functional outcome, and functional progress caused by either rehabilitation or other treatments after hip fracture.11 We did not assess any measures of participation or health-related quality of life.Our study has limitations. We evaluated white, cognitively intact women without neurologic impairment admitted to a single rehabilitation hospital in Italy, who were surgically operated on, and who were referred for inpatient rehabilitation. As a consequence, our data cannot be generalized to the overall population of patients who sustain hip fractures. We adjusted our results for several prognostic factors, but we did not collect data on other potential confounders, including nutritional state, prevalent vertebral fractures, depression, pain, social support, fear of falling, and balance confidence.11 and the independency of handgrip strength should be further examined. Together with other prognostic factors, grip strength may be helpful in selecting patients for proper rehabilitation protocols and settings. The unfavorable prognostic role of low muscle strength emphasizes the relevancy of resistance training to optimize recovery. Further research studies are needed to elucidate the characteristics of optimal strengthening exercise regimens.In conclusion, despite limitations of our study, data support the prognostic role of grip strength at admission to inpatient rehabilitation after a hip fracture. Models aimed at predicting the functional outcome in hip-fracture survivors should consider handgrip strength, although a number of factors have been shown to play a prognostic role,


Exercise therapy following total hip replacement (THR) is considered to be important during the initial postoperative care, but till date only a few evidence-based recommendations exist. The aim of this survey was to identify prescription standards among different rehabilitation professionals, for the exercise therapy management after THR in Germany.The study was a cross-sectional survey. Standardized questionnaires were sent to 38 eligible rehabilitation facilities in Germany. Participating surgeons, orthopaedic physicians, physiotherapists and exercise therapists rated the optimal early weight-bearing, resistance training, key components and dose of exercise therapy, and the hip loading during exercising. The returned questionnaires were then analyzed for level of agreement (≥80 %) among respondents.313 rehabilitation professionals from 28 clinics returned completed questionnaires and were considered eligible for analysis. Out of total respondents, 53.9 % (cemented THR) and 18.2 % (uncemented THR) recommended full weight-bearing within five days after surgery. Commencement of resistance training later than three weeks after surgery is recommended by 20.6 % (36 %) for cemented (uncemented) prosthesis. Feedback varied significantly amongst the professions. Regarding the overall objectives of rehabilitation after hip replacement, respondents agree in six out of eight requested items. Agreement concerning priorities of specific exercises was achieved in three out of twelve items. The recommended exercise therapy dose varied significantly with working experience (p = 0.02).Rehabilitation professionals mainly disagreed with the exercise therapy prescriptions following the total hip replacement during the initial postoperative care in Germany.The online version of this article (doi:10.1186/s12891-015-0646-7) contains supplementary material, which is available to authorized users. Total hip replacement (THR) is one of the most commonly practiced orthopaedic surgeries in developed countries . AccordiAn increasing number of authors complain that current rehabilitation practice seems to be more guided by personal and institutional (rehabilitation setting) factors rather than by scientific findings , 15, 16.The objective of this multicenter survey was to identify prescription standards and personal beliefs regarding the optimal exercise therapy treatment for inpatient rehabilitation, after total hip replacement in Germany. It is hypothesized that rehabilitation professionals and institutions differ regarding exercise therapy prescriptions, and in their viewpoint on effective exercise measures and the optimal load on the joint during initial postoperative period.The study was a cross-sectional survey of orthopaedic rehabilitation care professionals in Germany, conducted between November 2012 and November 2013.The orthopaedic rehabilitation centres participating in the study were recruited using a database of Germany-wide rehabilitation facilities . All facThe questionnaire was developed according to the current standards of exercise therapy in western countries  and GermDescriptive statistics were used to evaluate demographic data. Continuous variables were reported as mean (standard deviation) and categorical variables were presented as frequencies (n) and percentages (%). Agreement of the respondents concerning specific items of the questionnaire was the primary outcome. Questions on personal opinions on the importance of influencing factors on the postoperative rehabilitation treatment and on clinic-specific goals and measures of training therapy were assessed on five-point Likert scales. To define agreement for the item on the importance of influencing factors for the treatment, we condensed values 1 and 2 into “not important”, value 3 represents “medium important” and 4 and 5 combined to “important”. Regarding facility-specific goals and measures, we condensed values 1 and 2 into “high priority” and 4 and 5 into “low priority”. Value 3 represents “medium priority”. Analogously, the ten-point Likert scales assessing personal opinions on joint load of specific exercises were recoded into three categories. Values 1–3 represent “low stress”, 4–7 “intermediate stress” and 8–10 “high stress”, respectively. Agreement was defined, when more than 80 % of answers coincided in one of the three combined categories. This technique of measuring agreement has been previously reported –21. MarxThe questionnaire used for the survey was anonymous. No personal data were collected from respondents. A statement at the title page of the questionnaire included information regarding the study purpose and the anonymity of responses. The response to the survey was assumed to indicate their informed consent. As the study concerned a survey to be completed anonymously and once only, no review by the Medical Ethical Committee of the University was needed. This procedure was in agreement with previous studies using similar research designs in this research field . The stuAfter the initial database search, 379 potentially eligible rehabilitation facilities in Germany were contacted. From the 56 responding facilities 14.8 %), 38 agreed and were considered eligible, and received questionnaires. 28 clinics (73.7 %) located in 11 of the 16 states in Germany returned duly filled in 313 questionnaires of 168 (53.7 %) physiotherapists, 43 (13.7 %) rehabilitation physicians, 18 (5.8 %) orthopaedic surgeons and 84 (26.8 %) exercise therapists. A few clinics declined participation via telephone or email due to lack of time or lack of personals who agreed to complete the questionnaire. Other clinics did not respond to the initial or reminder e-mail. All 313 returned questionnaires were analyzed. A flowchart displaying the recruitment process is shown in Fig. 4.8 %, 38th day post-surgery. Disagreements were also observed for the best time to start resistance training. One fifth and one third of the respondents recommended to wait for more than three weeks following surgery for cemented and uncemented prostheses, respectively. The distribution of answers differed significantly between professions for cemented (p = 0.03) and uncemented (p < 0.001) prostheses, adjusted for professional experience, clinic type and number of THR patients per month. Surgeons recommended an early start of full resistance training as compared to therapists and rehabilitation physicians. Estimated means  for surgeons were 12.7 days  and 14.8 days  for cemented and uncemented prostheses, respectively. In contrast, estimated means for physiotherapists were 20.1 days  and 27.7 days , respectively.Participants agreed that the course and the quality of surgery as well as the constitution of the patients individually have a major impact on the postoperative rehabilitation treatment. Disagreement was assessed regarding the impact of the type of prosthesis for primary or secondary hip replacement Table . ResultsRegarding the overall objectives of rehabilitation after hip replacement predefined by the clinics respondents agreed that postoperative treatment should focus on improving mobility, gait, daily activities, hip strength to reduce pain and muscle imbalance (between 82.5 and 87.7 %). Disagreements were observed regarding the importance of balance control and core stability Table . When asParticipants were also asked for their personal opinions about what the perceived exertion in lower extremity resistance training should be 15 days and 3 months after THR. The Borg RPE scale after 15 days had a mean value of 12.6 (SD 1.9), indicating a “fairly light” to “somewhat hard” intensity. The rating was significantly influenced by the years of working experience (p = 0.02). One year working experience decreased the mean reported RPE by 0.03 . After 3 months, the optimal resistance training intensity was considered as mean RPE of 13.7 (SD 2.5). The profession had a significant impact on the reported RPE (p = 0.03). Rehabilitation physicians indicated the lowest estimated mean RPE  “fairly light” to “somewhat hard”), while physiotherapists and exercise therapists had the highest mean RPE value  “somewhat hard”).Therapists were asked to rate the hip joint load during specific exercises on a scale from one to ten. Mean values (standard deviations) for ergometer cycling, low speed, high resistance were 3.2 (1.7) and 6.5 (2.1), while for walking, standing on one leg and sitting, mean estimates were 6.0 (2.1), 7.9 (2.1) and 4.3 (2.1), respectively. Furthermore, standing up, bridging and abduction in lateral position yielded mean values (SD) of 6.5 (2.1), 5.9 (2.2) and 6.6 (2.2). Table This survey presents current prescription standards and personal beliefs regarding the optimal exercise therapy treatment for inpatient rehabilitation after hip replacement in Germany. While previous surveys , 14 in tThe main finding of this study was that all respondents agreed on the general objectives of rehabilitation, following THR but disagreed concerning the timing, dose and components of exercise therapy during the first few postoperative weeks.Considerable variations among respondents were found regarding the recommended beginning of full weight-bearing and resistance training after cemented and uncemented hip replacement. Till date no other surveys have collected the postoperative data on practice standards for these two milestones of postoperative treatment in THR patients. According to the current evidence –26, immeRegarding the beginning of full weight-bearing and resistance training, varying preferences were observed amongst different professions. Strengthening of lower extremity muscles is one of the major goals of rehabilitation following THR , 16. AltAgreement was found on the importance of gait training, stair climbing and individual physiotherapy. Comparable findings were reported in two recent surveys among rehabilitation professionals in the UK  and NethRespondents were also asked to express their beliefs regarding the optimal lower extremity resistance training intensity after hip replacement. Dose–response effects of postoperative exercise therapy have been rarely investigated , 12 and The survey also revealed uncertainty among rehabilitation professionals on the hip joint loading during walking, standing, cycling, stair climbing, chair rises, bridging and hip abduction. Only few studies with small sample sizes investigated the force acting on the hip during different activities –38. TheySeveral limitations should be considered for the final interpretation of results. From 379 contacted rehabilitation centers, 56 (14.8 %) expressed their interest to participate and were assessed for eligibility. Although no data is available for non-responding facilities, there could be several reasons that may have contributed to the low response rate. Firstly, an email address obtained from an online database was used to contact rehabilitation centers. No information was available, to confirm whether the request was actually forwarded to the head physician or to some other responsible personal. Further, it may have appeared that, due to lack of experience in the treating arthroplasty patients, some of the non-responding centers did not feel adequately qualified and confident to participate in the survey (e.g. orthopaedic diseases only as secondary diagnosis). Other potential reasons included the lack of interest as well as concerns regarding the dissemination of internal data. Finally, 28 rehabilitation centers returned 313 completed questionnaires, yielding a response rate of 7.4 %.It should also be noted that the results are limited to German rehabilitation settings. The postoperative management of total hip replacement is influenced by regional health care systems and therefore, can not be compared with various other states , 39. A tIn addition, the questionnaire was developed exclusively for the present survey and was pre-tested as well as adjusted by a few orthopedic physicians, physiotherapists and exercise therapists. Hence, the chosen categories of the questionnaire and response options provided are partly influenced by personal experience and do not fully exclude the possibility of being biased.Our survey suggests that decisions during rehabilitation practice following hip replacement in Germany are strongly influenced by personal experience and opinions and may vary largely among rehabilitation professionals. The observed lack of consensus regarding the most beneficial exercise therapy treatment observed may partly be due to substantial research deficit in this field , 8, 12. In conclusion, this survey reveals substantial disagreements among rehabilitation professionals regarding exercise therapy prescriptions during the first postoperative weeks after hip replacement in Germany. Surgeons and therapists differ in their recommendations on weight-bearing and resistance training. Physiotherapists and exercise therapists prefer a more conservative approach with a delayed start of weight-bearing and resistance training. This is in contrast to current evidence and might be explained with more extensive interactions between patient and therapist during individual treatment sessions. Furthermore, the beliefs and prescriptions of respondents regarding the estimated hip loading are only partly in agreement with reported true loadings in the literature. Further investigation should explore the influence of professional groups and facilities on THR rehabilitation. More evidence-based recommendations on beneficial exercise therapy dosages and components are needed in order to define reasonable guidelines and standards for postoperative treatment.


The principal components of plant productivity and nutritional value, from the standpoint of modern agriculture, are the acquisition and partitioning of organic carbon (C) and nitrogen (N) compounds among the various organs of the plant. The flow of essential organic nutrients among the plant organ systems is mediated by its complex vascular system, and is driven by a series of transport steps including export from sites of primary assimilation, transport into and out of the phloem and xylem, and transport into the various import-dependent organs. Manipulating C and N partitioning to enhance yield of harvested organs is evident in the earliest crop domestication events and continues to be a goal for modern plant biology. Research on the biochemistry, molecular and cellular biology, and physiology of C and N partitioning has now matured to an extent that strategic manipulation of these transport systems through biotechnology are being attempted to improve movement from source to sink tissues in general, but also to target partitioning to specific organs. These nascent efforts are demonstrating the potential of applied biomass targeting but are also identifying interactions between essential nutrients that require further basic research. In this review, we summarize the key transport steps involved in C and N partitioning, and discuss various transgenic approaches for directly manipulating key C and N transporters involved. In addition, we propose several experiments that could enhance biomass accumulation in targeted organs while simultaneously testing current partitioning models. The principal components of plant productivity and nutritional value, from the standpoint of modern agriculture, are the acquisition and partitioning of organic carbon (C) and nitrogen (N) compounds among the various organs of the plant. The initial step of C acquisition is the fixation of atmospheric C dioxide by photosynthesis followed by sugar partitioning to the non-photosynthetic tissues. N is primarily absorbed as inorganic salts from the soil solution and incorporated into amino acids in the root or shoot for subsequent transport to import-dependent tissues. These “sinks” are the primary consumers of newly assimilated sugars and amino acids, and include many essential organ systems such as expanding leaves, roots, seeds and fruits, storage tissue and organs, and secondary growth. As much as 80% of the C assimilated in mature leaves, and comparable amounts of amino acids, are exported in the phloem to satisfy the metabolic needs of the heterotrophic tissues . UnderstThe last several decades have produced substantial biochemical and molecular advances in our understanding of cell-to-cell and long-distance partitioning of sugars and amino acids in plants. These advances have created novel opportunities to manipulate partitioning pathways to enhance yield and/or nutritional quality. The basic premise of these approaches is that altering the expression of the transporters for a desired sugar or amino acid will result in the preferential accumulation of that compound (or a derivative thereof) in a target organ or tissue. The success of these efforts are predicated on accurate knowledge of the physiological and biochemical processes involved to predict the outcome. The goal of this review is to briefly summarize current understanding of the functional contributions of sugar and amino acid transport systems to plant growth and then focus on the limited number of studies where ectopic expression has been attempted. In many of these, the desired outcome has been at least partially achieved, and it is apparent that identifying the limitation—that is, why the full desired effect was not obtained—is necessary to achieve greater gains. Thus, the application of existing knowledge for biotechnology gains has in many cases identified new avenues of biological discovery in the complex interaction of nutrient use and growth. In addition, this review ventures experimental approaches for improving and targeting biomass partitioning to specific organs.+ symporters  that utilize the proton motive force for Suc/H+ symport are well characterized biochemically, genetically, and physiologically  is the primary form of reduced C transported long-distance in the vascular system of plants, and consequently has garnered the most attention. Suc is produced in the cytoplasm, either directly from the products of photosynthesis or from storage reserves. Once produced, it may remain in the cytoplasm to participate in other aspects of cellular metabolism or it may be compartmentalized, principally in the vacuole; it may pass through the symplasm—the collective cytoplasm of the plant—via plasmodesmata (PD); or it may undergo efflux to the apoplasm—the collective cell-wall space of the plant—and from there it may be taken up into the cytoplasm of an adjacent cell. As a relatively large polar solute, Suc requires protein transporters for efficient movement across membranes. Where the prevailing concentration gradients mandate energized transport, Suc/Hogically . Those Sogically . Suc/H+  process . Under c process .The primary fate of photoassimilated C is long-distance transport from photoautotrophic source leaves to heterotrophic organs. C partitioning via long-distance transport of sugars in the phloem has been extensively and recently reviewed  and is t+ transporters.Phloem unloading occurs all along the transport path to nourish lateral tissues and storage reserves, and occurs extensively in the sink organs. Unloading may be by efflux across plasma membranes to the apoplasm, or through the symplasm via PD, or both routes may be used in combination. Within the recipient tissues, symplasmic continuity with the CC/SE complex can be extensive for efficient post-phloem partitioning via PD, or isolated domains may force apoplasmic transport . GeneralArabidopsis has nine SUTs arranged in three sub-families, and monocots have an additional one or two families not represented in dicots (MST) gene family of Arabidopsis has 53 members, arranged in seven sub-families. The best characterized of these sub-families, and the one with members that localize to the plasma membrane and are thus most likely involved in intercellular transport, is the sugar transporter (STP) family, which contains 14 members . However, Suc uptake into intact cotyledons was only ∼23%, and when biomass accumulation was measured, a similar difference between excised and intact cotyledons was observed  using an endosperm-specific Hordein B1 promoter in wheat grains increased levels of storage protein, showing that enhanced Suc transport has positive impacts beyond carbohydrate alone  in a homozygous Atsuc2-4 background  rescued phloem loading in the Atsuc2-4 mutant; several other SUT genes implicated in high affinity Suc uptake were unable to restore efficient phloem transport . Simply expecting larger plants in general, or larger target organs, is naïve, even though this may be the desired outcome from an applied standpoint. Instead, these experiments will more likely help identify rate-limiting steps in the overall process of whole-plant partitioning, and thus lead to new prospects (targets) for manipulation, and uncover unrecognized interactions of C homeostasis and other aspects of physiology. A corollary to these experiments aiming to enhance productivity are those that disrupt partitioning to test prevailing and alternative models of C allocation.What future experiments could be done to enhance partitioning via apoplasmic loading? Molecular characterization of SWEET and SUT transporters provides, in principle, a complete framework to test hypotheses on the strategic release of Suc from one cell and loading into the adjacent cell. An obvious experiment is to overexpress  SWEET12 , for enhStSUT1 in storage parenchyma of pea cotyledons and HvSUT1 in wheat endosperm, described above. But here too, the complete pathway of Suc unloading, from the sieve elements to the final recipient cells need to be considered  organs. Targeted sink-specific manipulations may therefore be more fruitful for enhancing yield of specific organs, as evident from overexpression of nsidered . For exansidered . Tissue-Similarly, Suc unloading to the apoplasm in sink organs is associated with hydrolysis by cell wall invertase and uptake of the resulting hexose by hexose transporters. This is particularly prevalent in fruits undergoing rapid expansion and ripening . As the AtSTP13 in Arabidopsis seedlings led to increases in Glc uptake, and also led to increases in the sugars and biomass throughout the plants  was expressed in transgenic pea under the control of the Arabidopsis AAP1 promoter which directs expression throughout the phloem and in the seeds. S-methylmethionine (SMM) transport was targeted because it is identified as a major form of phloem mobile S in plants  to the sink tissue of the plant. Alternatively, one can increase the “pull” side of allocation by enhancing the uptake capacity of a desired sink, as PsAAP1 gene in transgenic pea using the Arabidopsis AtAAP1 promoter. In pea, the Arabidopsis promoter drove expression in the leaf companion cell/sieve element complex as well as the epidermal cells of the seed cotyledons, thereby generating enhanced amino acid transport capacity in both the source and sink tissues (Figure In a combined strategy, the Tegeder lab  has appls Figure . The traTransgenic manipulation of amino acid transport in plants has a real potential to increase the nutritional value of harvested tissue by increasing the overall N content and/or by targeted increases of specific amino acids, such as cysteine and methionine. However, it is clear from early transgenic experiments that altering amino acid distribution in the plant has a major impact on both N and C metabolism, which will require additional research to better understand the complex interactions between these macronutrients.HvSUT1 overexpression in endosperm increasing storage protein content (and consequently more N; VfAAP1 expression in seeds increasing seed biomass (and consequently more C; SUT overexpression in companion cells impacting P requirements (From the few published reports on efforts to manipulate C and N partitioning, it is evident that there is potential for agricultural improvements but also unexpected pleiotropic effects which limit the desired gains, and in some cases, have unpredicted effects on plant vigor. Of particular interest from both an applied and a basic science perspective are those reporting an influence on another nutrient, such as irements ; and MMPirements . These sStudying the phloem, phloem transport, and partitioning of nutrients directly is notoriously difficult , and thiAlthough advances in our understanding of C and N partitioning systems allow us to test hypotheses by manipulating transporter streams from the “push,” “pull” and combined sides, it is also clear that our current understanding is limited when looking at the bigger picture of source/sink relationships. Moreover, complex metabolic interactions between assimilation and utilization of essential nutrients confounds attempts to engineer C and N partitioning. A systems biology approach that compares whole plant nutrient partitioning in high yielding domesticated plants and less productive ancestral varieties may shed light on the labyrinth of interconnected networks that were modified during crop domestication and improvement. Nested association mapping populations, genome wide association studies, and whole-genome re-sequencing are some of the tools that could identify genetic changes in key genes and quantitative trait loci . In addiThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.