Virtual reality hand therapy: A new tool for nonopioid analgesia for acute procedural pain, hand rehabilitation, and VR embodiment therapy for phantom limb pain.

INTRODUCTION: Affordable virtual reality (VR) technology is now widely available. Billions of dollars are currently being invested into improving and mass producing VR and augmented reality products. PURPOSE OF THE STUDY: The purpose of the present study is to explore the potential of immersive VR to make physical therapy/occupational therapy less painful, more fun, and to help motivate patients to cooperate with their hand therapist. DISCUSSION: The following topics are covered: a) psychological influences on pain perception, b) the logic of how VR analgesia works, c) evidence for reduction of acute procedural pain during hand therapy, d) recent major advances in VR technology, and e) future directions-immersive VR embodiment therapy for phantom limb (chronic) pain. CONCLUSION: VR hand therapy has potential for a wide range of patient populations needing hand therapy, including acute pain and potentially chronic pain patients. Being in VR helps reduce the patients' pain, making it less painful for patients to move their hand/fingers during hand therapy, and gamified VR can help motivate the patient to perform therapeutic hand exercises, and make hand therapy more fun. In addition, VR camera-based hand tracking technology may be used to help therapists monitor how well patients are doing their hand therapy exercises, and to quantify whether adherence to treatment increases long-term functionality. Additional research and development into using VR as a tool for hand therapist is recommended for both acute pain and persistent pain patient populations.

Impact of static and dynamic A-form heterogeneity on the determination of RNA global structural dynamics using NMR residual dipolar couplings.

We examined how static and dynamic deviations from the idealized A-form helix propagate into errors in the principal order tensor parameters determined using residual dipolar couplings (rdcs). A 20-ns molecular dynamics (MD) simulation of the HIV-1 transactivation response element (TAR) RNA together with a survey of spin relaxation studies of RNA dynamics reveals that pico-to-nanosecond local motions in non-terminal Watson-Crick base-pairs will uniformly attenuate base and sugar one bond rdcs by approximately 7%. Gaussian distributions were generated for base and sugar torsion angles through statistical comparison of 40 RNA X-ray structures solved to <3.0 A resolution. For a typical number (>or=11) of one bond C-H base and sugar rdcs, these structural deviations together with rdc uncertainty (1.5 Hz) lead to average errors in the magnitude and orientation of the principal axis of order that are <9% and <4 degrees, respectively. The errors decrease to <5% and <4 degrees for >or=17 rdcs. A protocol that allows for estimation of error in A-form order tensors due to both angular deviations and rdc uncertainty (Aform-RDC) is validated using theoretical simulations and used to analyze rdcs measured previously in TAR in the free state and bound to four distinct ligands. Results confirm earlier findings that the two TAR helices undergo large changes in both their mean relative orientation and dynamics upon binding to different targets.

Argininamide binding arrests global motions in HIV-1 TAR RNA: comparison with Mg2+-induced conformational stabilization.

The structure and dynamics of the stem-loop transactivation response element (TAR) RNA from the human immunodeficiency virus type-1 (HIV-1) bound to the ligand argininamide (ARG) has been characterized using a combination of a large number of residual dipolar couplings (RDCs) and trans-hydrogen bond NMR methodology. Binding of ARG to TAR changes the average inter-helical angle between the two stems from approximately 47 degrees in the free state to approximately 11 degrees in the bound state, and leads to the arrest of large amplitude (+/-46 degrees ) inter-helical motions observed previously in the free state. While the global structural dynamics of TAR-ARG is similar to that previously reported for TAR bound to Mg2+, there are substantial differences in the hydrogen bond alignment of bulge and neighboring residues. Based on a novel H5(C5)NN experiment for probing hydrogen-mediated 2hJ(N,N) scalar couplings as well as measured RDCs, the TAR-ARG complex is stabilized by a U38-A27.U23 base-triple involving an A27.U23 reverse Hoogsteen hydrogen bond alignment as well as by a A22-U40 Watson-Crick base-pair at the junction of stem I. These hydrogen bond alignments are not observed in either the free or Mg2+ bound forms of TAR. The combined conformational analysis of TAR under three states reveals that ligands and divalent ions can stabilize similar RNA global conformations through distinct interactions involving different hydrogen bond alignments in the RNA.

Probing motions between equivalent RNA domains using magnetic field induced residual dipolar couplings: accounting for correlations between motions and alignment.

Approaches developed thus for extracting structural and dynamical information from RDCs have rested on the assumption that motions do not affect molecular alignment. However, it is well established that molecular alignment in ordered media is dependent on conformation, and slowly interconverting conformational substates may exhibit different alignment properties. Neglecting these correlation effects can lead to aberrations in the structural and dynamical analysis of RDCs and diminish the utility of RDCs in probing motions between domains having similar alignment propensities. Here, we introduce a new approach based on measurement of magnetic field induced residual dipolar couplings in nucleic acids which can explicitly take into account such correlations and demonstrate measurements of motions between two "magnetically equivalent" domains in the transactivation response element (TAR) RNA.

Mg2+-induced variations in the conformation and dynamics of HIV-1 TAR RNA probed using NMR residual dipolar couplings.

The effects of divalent Mg(2+) on the conformation and dynamics of the stem-loop transactivation response element (TAR) RNA from HIV-1 have been characterized using NMR residual dipolar couplings (RDCs). Order matrix analysis of one bond 13C-1H RDCs measured in TAR at [Mg(2+)]:[TAR] stoichiometric ratios of approximately 3:1 (TAR(3.0Mg)) and approximately 4.5:1 (TAR(4.5Mg)) revealed that Mg(2+) reduces the average inter-helical angle from 47(+/-5) degrees in TAR(free) to 5(+/-7) degrees in TAR(4.5Mg). In contrast to the TAR(free) state, the generalized degree of order for the two stems in TAR(4.5Mg) is found to be identical within experimental uncertainty, indicating that binding of Mg(2+) leads to an arrest of inter-helical motions in TAR(free). Results demonstrate that RDC-NMR methodology can provide new insight into the effects of Mg(2+) on both the conformation and dynamics of RNA.