Blood Flow Restriction Training for Chronic Quadriceps Weakness and Atrophy: A Case Report

Background and purpose The high load and intensity of traditional strength training may not always be appropriate or beneficial for certain patient populations such as the elderly or those with orthopedic injuries. In these cases blood flow restriction training with light resistance has been shown to be effective method of increasing strength and hypertrophy. However, what if traditional strength training is tolerated but not effective for an individual? The purpose of this case report is to describe the use of blood flow restriction training in a recreationally active male who was fully functional but continued with chronic unilateral quadriceps weakness and atrophy. Case Description A 37 year old male who participated in frequent physical activity and was functional for daily activities and hobbies presented with decreased quadriceps strength and atrophy 25 years post a well healed femur fracture. A 15% deficit was noted on initial evaluation during isokinetic testing along with a two centimeter difference in quadriceps girth. Light resistance, isotonic, single leg quadriceps strengthening was performed on the involved lower extremity with blood flow restriction. These exercises included straight leg raises, long arc knee extension and single leg press on the shuttle. A blood flow restriction device was used with the settings applied according to the instructions from the manufacturer. The cuff was placed as proximal as possible on the patient’s thigh. The unit continuously adjusted the pressure to maintain 80% occlusion throughout the exercise program. The exercises were performed two times a week for 6 weeks in addition to the patient’s normal exercise routine of high intensity interval training and weight lifting 2 times weekly. Outcomes Isokinetic testing was performed at initial evaluation, 3 weeks into the training program and upon completion at 6 weeks. Results indicated that at the end of the 6 week program the 15% deficit had improved to an 8% advantage over the uninvolved leg for a total percentage change of 27%. Girth measurement also increased by 1.5 centimeters. Discussion Blood flow restriction training has been used to improve quadriceps strength and muscle size. It has been used for increasing strength post injury or surgery, during immobilization and in the elderly. It has been used to augment traditional strength training in athletes. The patient in this case had been active with sports and normal exercise routines that included traditional strength training, college football and high intensity interval training since the time of injury. Despite remaining active and fully recovering range of motion and normal strength, as graded with a manual muscle test, atrophy remained 25 years later. Upon completion of 6 weeks of blood flow restricted training, hypertrophy and improved strength were noted; these changes were not able to be achieved in the past with traditional strength training at higher intensities and resistances

Formative Assessment and Academic Performance as Predictors of National Physical Therapy Examination Success

Physical therapy educational researchers have studied various factors that may or may not predict success on the National Physical Therapy Examination (NPTE). One factor that has not been studied extensively is the use of the Academic Practice Examination and Assessment Tool (APEAT) as a formative assessment. The purpose of this study was to determine the predictive power of the APEAT as a formative assessment along with Doctor of Physical Therapy (DPT) program grade point average (GPA) on success on the NPTE. Carless’s learning-oriented assessment theory was used as the theoretical foundation for this study and to guide the analysis of a formative assessment’s potential to predict success on a summative assessment. The research question was to determine how well APEAT scores and DPT program GPA can predict success on the NPTE. A quantitative, nonexperimental, correlational approach was used for this study to analyze retrospective data. A census from a DPT program in the southeastern United States was used for cohorts graduating from Summer 2019 to Summer 2020; the sample size was 209 student records. Data from the student records were analyzed with binomial logistic regression. APEAT scores and DPT program GPA were statistically significant predictors of success on the NPTE. APEAT was a weak predictor, while DPT program GPA was a strong predictor of success on the NPTE. The results from this study may be used at the local site to identify students who may need remediation before taking the NPTE and hence lead to positive social change for these students. Because NPTE success is tied to program accreditation, the results from this study can be used to improve programmatic outcomes and instill social change at the local site

Orientation-dependent backbone-only residue pair scoring functions for fixed backbone protein design

<p>Abstract</p> <p>Background</p> <p>Empirical scoring functions have proven useful in protein structure modeling. Most such scoring functions depend on protein side chain conformations. However, backbone-only scoring functions do not require computationally intensive structure optimization and so are well suited to protein design, which requires fast score evaluation. Furthermore, scoring functions that account for the distinctive relative position and orientation preferences of residue pairs are expected to be more accurate than those that depend only on the separation distance.</p> <p>Results</p> <p>Residue pair scoring functions for fixed backbone protein design were derived using only backbone geometry. Unlike previous studies that used spherical harmonics to fit 2D angular distributions, Gaussian Mixture Models were used to fit the full 3D (position only) and 6D (position and orientation) distributions of residue pairs. The performance of the 1D (residue separation only), 3D, and 6D scoring functions were compared by their ability to identify correct threading solutions for a non-redundant benchmark set of protein backbone structures. The threading accuracy was found to steadily increase with increasing dimension, with the 6D scoring function achieving the highest accuracy. Furthermore, the 3D and 6D scoring functions were shown to outperform side chain-dependent empirical potentials from three other studies. Next, two computational methods that take advantage of the speed and pairwise form of these new backbone-only scoring functions were investigated. The first is a procedure that exploits available sequence data by averaging scores over threading solutions for homologs. This was evaluated by applying it to the challenging problem of identifying interacting transmembrane alpha-helices and found to further improve prediction accuracy. The second is a protein design method for determining the optimal sequence for a backbone structure by applying Belief Propagation optimization using the 6D scoring functions. The sensitivity of this method to backbone structure perturbations was compared with that of fixed-backbone all-atom modeling by determining the similarities between optimal sequences for two different backbone structures within the same protein family. The results showed that the design method using 6D scoring functions was more robust to small variations in backbone structure than the all-atom design method.</p> <p>Conclusions</p> <p>Backbone-only residue pair scoring functions that account for all six relative degrees of freedom are the most accurate and including the scores of homologs further improves the accuracy in threading applications. The 6D scoring function outperformed several side chain-dependent potentials while avoiding time-consuming and error prone side chain structure prediction. These scoring functions are particularly useful as an initial filter in protein design problems before applying all-atom modeling.</p

Recruitment of rare 3-grams at functional sites: Is this a mechanism for increasing enzyme specificity?

<p>Abstract</p> <p>Background</p> <p>A wealth of unannotated and functionally unknown protein sequences has accumulated in recent years with rapid progresses in sequence genomics, giving rise to ever increasing demands for developing methods to efficiently assess functional sites. Sequence and structure conservations have traditionally been the major criteria adopted in various algorithms to identify functional sites. Here, we focus on the distributions of the 20³different types of <it>3</it>-grams (or triplets of sequentially contiguous amino acid) in the entire space of sequences accumulated to date in the UniProt database, and focus in particular on the rare <it>3</it>-grams distinguished by their high entropy-based information content.</p> <p>Results</p> <p>Comparison of the UniProt distributions with those observed near/at the active sites on a non-redundant dataset of 59 enzyme/ligand complexes shows that the active sites preferentially recruit <it>3</it>-grams distinguished by their low frequency in the UniProt. Three cases, Src kinase, hemoglobin, and tyrosyl-tRNA synthetase, are discussed in details to illustrate the biological significance of the results.</p> <p>Conclusion</p> <p>The results suggest that recruitment of rare <it>3</it>-grams may be an efficient mechanism for increasing specificity at functional sites. Rareness/scarcity emerges as a feature that may assist in identifying key sites for proteins function, providing information complementary to that derived from sequence alignments. In addition it provides us (for the first time) with a means of identifying potentially functional sites from sequence information alone, when sequence conservation properties are not available.</p

Synchronous Online Collaboration Using Google Doc to Promote Clinical Reasoning

It is important for faculty to be able to facilitate small group collaboration synchronously and promote higher-order thinking in an online setting. The purpose of this poster is to describe how the community of inquiry framework can guide the creative consideration of a commonly used tool, such as Google Doc, in a new way to facilitate higher-order thinking while promoting collaboration and clinical reasoning in entry-level physical therapy students. Google Doc is traditionally used to collaborate and share ideas asynchronously. However, with some inventive consideration, it can be used to facilitate collaboration during synchronous online meetings with students

Video with targeted feedback for psychomotor remediation in health sciences

Using timely and targeted feedback in video recordings for remediation in a health sciences psychomotor practical can improve student success. Tools such as GoReact and VoiceThread provide opportunities for instructors to provide targeted feedback. Feedback is time stamped and strategically placed at the correct location within the video clip. Using this type of video tool with feedback as part of a remediation plan has allowed students to repeatedly practice techniques and receive specific, targeted feedback from the instructor regarding skill performance. This has been used to successfully improve student outcomes in a clinical skills course in a health sciences program

Discrimination of native protein structures using atom–atom contact scoring

We introduce a method for discriminating correctly folded proteins from well designed decoy structures using atom–atom and atom–solvent contact surfaces. The measure used to quantify contact surfaces integrates the solvent accessible surface and interatomic contacts into one quantity, allowing solvent to be treated as an atom contact. A scoring function was derived from statistical contact preferences within known protein structures and validated by using established protein decoy sets, including the “Rosetta” decoys and data from the CASP4 structure predictions. The scoring function effectively distinguished native structures from all corresponding decoys in >90% of the cases, using isolated protein subunits as target structures. If contacts between subunits within quaternary structures are included, the accuracy increases to 97%. Interactions beyond atom–atom contact range were not required to distinguish native structures from the decoys using this method. The contact scoring performed as well or better than existing statistical and physicochemical potentials and may be applied as an independent means of evaluating putative structural models

Characterizing the unfolded states of proteins using single-molecule FRET spectroscopy and molecular simulations

To obtain quantitative information on the size and dynamics of unfolded proteins we combined single-molecule lifetime and intensity FRET measurements with molecular simulations. We compared the unfolded states of the 64-residue, α/β protein L and the 66-residue, all-β cold-shock protein CspTm. The average radius of gyration (R(g)) calculated from FRET data on freely diffusing molecules was identical for the two unfolded proteins at guanidinium chloride concentrations >3 M, and the FRET-derived R(g) of protein L agreed well with the R(g) previously measured by equilibrium small-angle x-ray scattering. As the denaturant concentration was lowered, the mean FRET efficiency of the unfolded subpopulation increased, signaling collapse of the polypeptide chain, with protein L being slightly more compact than CspTm. A decrease in R(g) with decreasing denaturant was also observed in all-atom molecular dynamics calculations in explicit water/urea solvent, and Langevin simulations of a simplified representation of the polypeptide suggest that collapse can result from either increased interresidue attraction or decreased excluded volume. In contrast to both the FRET and simulation results, previous time-resolved small-angle x-ray scattering experiments showed no collapse for protein L. Analysis of the donor fluorescence decay of the unfolded subpopulation of both proteins gives information about the end-to-end chain distribution and suggests that chain dynamics is slow compared with the donor life-time of ≈2 ns, whereas the bin-size independence of the small excess width above the shot noise for the FRET efficiency distributions may result from incomplete conformational averaging on even the 1-ms time scale

Effects of denaturants and osmolytes on proteins are accurately predicted by the molecular transfer model

Interactions between denaturants and proteins are commonly used to probe the structures of the denatured state ensemble and their stabilities. Osmolytes, a class of small intracellular organic molecules found in all taxa, also profoundly affect the equilibrium properties of proteins. We introduce the molecular transfer model, which combines simulations in the absence of denaturants or osmolytes, and Tanford's transfer model to predict the dependence of equilibrium properties of proteins at finite concentration of osmolytes. The calculated changes in the thermodynamic quantities (probability of being in the native basin of attraction, m values, FRET efficiency, and structures of the denatured state ensemble) with GdmCl concentration [C] for the protein L and cold shock protein CspTm compare well with experiments. The radii of gyration of the subpopulation of unfolded molecules for both proteins decrease (i.e., they undergo a collapse transition) as [C] decreases. Although global folding is cooperative, residual secondary structures persist at high denaturant concentrations. The temperature dependence of the specific heat shows that the folding temperature (TF) changes linearly as urea and trimethylamine N-oxide (TMAO) concentrations increase. The increase in TF in TMAO can be as large as 20°C, whereas urea decreases TF by as much as 35°C. The stabilities of protein L and CspTm also increase linearly with the concentration of osmolytes (proline, sorbitol, sucrose, TMAO, and sarcosine)