A novel biomechanical index for quality assessment of the upper-extremity movements in post-stroke patients.

BACKGROUND: While motor recovery is preferred to compensatory movements for stroke patients with mild to moderate motion impairment, current movement quality assessments rarely reflect the differences between a patient's pre- and post-stroke movement patterns. Such comparison can help therapists to identify the rate of the restoration of premorbid motion patterns and prescribe the most effective treatment. METHODS: This paper attempted to present a new biomechanical metric for the quality of upper-limb movements which uses the subject's optimal movements as a reference to evaluate his/her UL movement quality. To this end, an inverse optimal control algorithm was applied to find an estimation of the patient's premorbid motion patterns. The new biomechanical index was then calculated as a measure of similarity between the optimal and actual movement trajectories. In the next part, various simulation and clinimetric investigations were performed to evaluate the responses of the new index to variations of the movement quality as well as its test-retest reliability and concurrent validity. RESULTS: Simulation-based analyses demonstrated that the proposed index, in contrast to the previous popular biomechanical indices, can successfully detect a wide range of abnormalities in motion signals. In addition, it showed good test-retest reliability (ICC = 0.89) and moderate correlation with clinical indices, Fugl-Meyer Assessment (r = 0.66), Action Research Arm Test (r = 0.47), and ABILHAND (r = 0.27). CONCLUSIONS: Although the proposed index has the same degree of clinimetric properties as the previous metrics, the ability to identify the level of movement restoration and also various types and severities of motor disabilities may lead to better design and management of motor rehabilitation.

The association of folate deficiency with clinical and radiological severity of knee osteoarthritis.

CONTEXT: Folate deficiency is often observed in patients with inflammatory diseases, raising questions about its role in knee osteoarthritis (OA) progression. OBJECTIVES: This study aimed to assess the association of folate deficiency with the clinical and radiological severity of knee OA. METHODS: A prospective cross-sectional study was conducted from January 1, 2019 to January 1, 2020. Primary knee OA patients referred to orthopedic clinics in Zabol, Iran were included. Radiographic severity was gauged utilizing the Kellgren-Lawrence (KL) classification. For clinical severity, patients completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire. IBM SPSS v.27 facilitated the statistical analysis. RESULTS: Forty-nine knee OA patients, averaging 67.45±13.44 years in age, were analyzed. Spearman correlation analysis revealed a negative correlation between folate levels and both WOMAC and KL scores. The correlation was stronger between folate and KL score (Spearman correlation coefficient: -0.75) than between folate and WOMAC total score (Spearman correlation coefficient: -0.46). Additionally, a significantly higher KL score was observed in patients with folate deficiency (p=0.004). CONCLUSIONS: Our study highlights a significant correlation between folate deficiency and increased severity of OA, which is evident in radiological and clinical assessments. These findings suggest that folate plays a key role in OA pathogenesis and could be a modifiable factor in its management.

Assessment of effective mitigation and prediction of the spread of SARS-CoV-2 in Germany using demographic information and spatial resolution.

Non-pharmaceutical interventions (NPIs) are important to mitigate the spread of infectious diseases as long as no vaccination or outstanding medical treatments are available. We assess the effectiveness of the sets of non-pharmaceutical interventions that were in place during the course of the Coronavirus disease 2019 (Covid-19) pandemic in Germany. Our results are based on hybrid models, combining SIR-type models on local scales with spatial resolution. In order to account for the age-dependence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we include realistic prepandemic and recently recorded contact patterns between age groups. The implementation of non-pharmaceutical interventions will occur on changed contact patterns, improved isolation, or reduced infectiousness when, e.g., wearing masks. In order to account for spatial heterogeneity, we use a graph approach and we include high-quality information on commuting activities combined with traveling information from social networks. The remaining uncertainty will be accounted for by a large number of randomized simulation runs. Based on the derived factors for the effectiveness of different non-pharmaceutical interventions over the past months, we provide different forecast scenarios for the upcoming time.

Retaining the medial collateral ligament in high tibial medial open-wedge osteotomy mostly results in post-operative intra-articular gap reduction.

PURPOSE: The current study aimed to evaluate how open-wedge high tibial osteotomy (OWHTO) without the release of medial collateral ligament (MCL) changes in vivo intra-articular joint space after the surgery. METHODS: Patients with varus malalignment of the knee with an indication for OWHTO were included in this study. The intra-articular gap was measured before and 30 min after OWHTO without MCL release using a series of calibrated nerve hooks. The association of post-operative gap size with varus angle, medial proximal tibial angle (MPTA), lateral distal femoral angle (LDFA) and joint line convergence angle (JLCA) was also assessed. RESULTS: A total of 42 knees from 38 patients were evaluated. The mean size of the intra-articular gap of the medial compartment was 5.2 ± 1 mm before the osteotomy and 3.1 ± 2.2 mm at 30 min post-osteotomy. The size of the intra-articular gap decreased post-operatively in 30 knees (71.5%), increased in eight knees (19%) and remained the same in the remaining four knees (9.5%). Smaller MPTA and more correction were associated with a decrease in gap size after the osteotomy (p = 0.01 and p = 0.03, respectively). A significant negative correlation was observed between the correction size and the gap size after osteotomy (r = - 0.317, p = 0.04). CONCLUSION: Intra-articular pressure of the medial compartment increases in the majority of cases following OWHTO without MCL release. Until the factors affecting this increased pressure are thoroughly identified, MCL release seems to be a wiser option during OWHTO. LEVEL OF EVIDENCE: III.

Short to Mid-term Outcomes of Single-stage Reconstruction of Multiligament Knee Injury.

BACKGROUND: Multiligament knee injury (MLKI) is a complex orthopedic injury leading to the tear of at least two of the major knee ligaments. However, there is no consensus on the optimal management of this debilitating condition. Regarding this, the present study was performed to evaluate the outcomes of single-stage multiligament reconstruction surgery in patients with MLKI. METHODS: This retrospective study was conducted on 41 consecutive MLKI patients who underwent surgical reconstruction. Objective evaluation of the outcome included active extension and flexion. Furthermore, the subjective evaluation of the outcome was accomplished using the Lysholm scoring scale and International Knee Documentation Committee (IKDC) form in Persian. Postoperative complications were also recorded for all patients. RESULTS: The mean age of the participants was 31.95±7.82 years. In addition, the mean follow-up period and the mean time interval between the injury and surgery were recorded as 36.9±17.8 and 11.5±8.9 months, respectively. The mean Lysholm and IKDC scores were obtained as 86.9±11.5 and 70±18.7, respectively. The mean Lysholm and IKDC scores were not statistically different between the patients who underwent surgery less than 6 months after the injury and those subjected to reconstruction 6 months postinjury (P=0.07 and P=0.3, respectively). Seven patients showed postoperative restricted range of motion, which was resolved with physiotherapy. The only surgical complication was popliteal artery injury. CONCLUSION: As the findings indicated, the single-stage reconstruction of MLKI provided an acceptable outcome. However, several aspects of this reconstruction, such as the timing of the surgery, still remain to be resolved in future investigations.

A novel technology for multiplex gene expression analysis directly from whole blood samples stabilized at ambient temperature using an RNA-stabilizing buffer.

We describe a novel method, based on target-dependent chemical ligation of probes, which simplifies the multiplexed quantitation of gene expression from blood samples by eliminating the RNA purification step. Gene expression from seven genes was evaluated over a range of sample inputs (16.7 to 0.25 µL of whole blood in serial dilutions) from three healthy donors. Mean CVs were ≤11% for five technical replicates for whole blood inputs ≥2.1 µL. The method showed a limit of detection of 300 copies of RNA by using titration of in vitro transcripts for four genes. Gene expression measured on stabilized blood samples was highly correlated (Spearman rank correlation method, ρ = 0.80) to gene expression results obtained with RNA isolated from matched samples (three donors, five technical replicates). Gene expression changes determined with seven radiation-responsive genes on six healthy donor blood samples before and after ex vivo irradiation were highly correlated (ρ = 0.93) to those measured with a TaqMan quantitative real-time RT-PCR assay on RNA purified from matched samples. Thus, this method is reproducible, sensitive, and correlated to quantitative real-time RT-PCR and may be used to streamline the multiplex gene expression analysis of large numbers of stabilized blood samples without RNA purification.

A translatable predictor of human radiation exposure.

Terrorism using radiological dirty bombs or improvised nuclear devices is recognized as a major threat to both public health and national security. In the event of a radiological or nuclear disaster, rapid and accurate biodosimetry of thousands of potentially affected individuals will be essential for effective medical management to occur. Currently, health care providers lack an accurate, high-throughput biodosimetric assay which is suitable for the triage of large numbers of radiation injury victims. Here, we describe the development of a biodosimetric assay based on the analysis of irradiated mice, ex vivo-irradiated human peripheral blood (PB) and humans treated with total body irradiation (TBI). Interestingly, a gene expression profile developed via analysis of murine PB radiation response alone was inaccurate in predicting human radiation injury. In contrast, generation of a gene expression profile which incorporated data from ex vivo irradiated human PB and human TBI patients yielded an 18-gene radiation classifier which was highly accurate at predicting human radiation status and discriminating medically relevant radiation dose levels in human samples. Although the patient population was relatively small, the accuracy of this classifier in discriminating radiation dose levels in human TBI patients was not substantially confounded by gender, diagnosis or prior exposure to chemotherapy. We have further incorporated genes from this human radiation signature into a rapid and high-throughput chemical ligation-dependent probe amplification assay (CLPA) which was able to discriminate radiation dose levels in a pilot study of ex vivo irradiated human blood and samples from human TBI patients. Our results illustrate the potential for translation of a human genetic signature for the diagnosis of human radiation exposure and suggest the basis for further testing of CLPA as a candidate biodosimetric assay.

Functional analysis of expressed peptides that bind yeast STE proteins.

Peptides are potentially useful for target validation and other reverse genetic applications. For instance, if a specific protein is susceptible to peptide inhibition, it may have a higher probability of being vulnerable to small molecules. We used the yeast two-hybrid technique to identify and study peptide binders for three yeast proteins involved in pheromone response: Ste11p, Ste18p, and Ste50p. A subset of peptide binders was shown to inhibit pheromone response in cells using two different functional assays. In addition, we utilized a variant of the yeast two-hybrid method to examine relative binding affinities based on competitive interactions in yeast. Our results suggest that binding affinity and inhibitory potency of peptides do not correlate perfectly and that peptide-protein interactions can be complex and unpredictable. Taken together these results suggest that while peptides are useful as in vivo inhibitors of protein function, caution must be exercised when choosing peptides for further studies and when inferring affinities from expression phenotypes.

Genetic selection for modulators of a retinoic-acid-responsive reporter in human cells.

We used a genetic screening methodology, a human cell line bearing a retinoic-acid-responsive enhanced GFP reporter, and a flow sorter to recover dominant modulators of reporter expression. Four inducers and three suppressors that were fused to the C terminus of a protein scaffold for stability were isolated and their mechanisms of action studied. Mutagenesis experiments indicated that six of these dominant agents exerted their effects at the protein level. The single cDNA coding fragment that was isolated comprised the central 64-amino-acid section of human cyclophilin B, which contained its peptidyl-prolyl isomerase domain; this cyclophilin fragment repressed expression of the retinoic-acid-responsive reporter. The remaining clones encoded peptides shorter than 30 amino acids unrelated to known gene open reading frames. Genetic epistasis studies between the strongest inducer, R3, and a dominant-negative mutant of RARalpha suggest that the two factors function in the same pathway. Transcript microarray analyses suggest that R3 induced a subset of the retinoid-responsive genes in melanoma cells. Finally, yeast two-hybrid assays and co-immunoprecipitation studies of human cell extracts identified PAT1 as a protein that interacts with R3.