Monitoring Wound Healing with Topically Applied Optical NanoFlare mRNA Nanosensors.

An effective wound management strategy needs accurate assessment of wound status throughout the whole healing process. This can be achieved by examining molecular biomarkers including proteins, DNAs, and RNAs. However, existing methods for quantifying these biomarkers such as immunohistochemistry and quantitative polymerase chain reaction are usually laborious, resource-intensive, and disruptive. This article reports the development and utilization of mRNA nanosensors (i.e., NanoFlare) that are topically applied on cutaneous wounds to reveal the healing status through targeted and semi-quantitative examination of the mRNA biomarkers in skin cells. In 2D and 3D in vitro models, the efficacy and efficiency of these nanosensors are demonstrated in revealing the dynamic changes of mRNA biomarkers for different stages of wound development. In mouse models, this platform permits the tracking and identification of wound healing stages and a normal and diabetic wound healing process by wound healing index in real time.

Can Shoulder Muscle Activity Be Evaluated With Ultrasound Shear Wave Elastography?

BACKGROUND: Quantitative assessment of rotator cuff muscle activity is important in the treatment of shoulder disorders. However, the known methods for assessing rotator cuff muscle activity thus far have been inaccurate, invasive, and inconvenient. QUESTIONS/PURPOSES: (1) Does the activity of the deltoid, supraspinatus, and infraspinatus muscles measured using ultrasound shear wave elastography have a linear correlation with muscle activity assessed using generally used methods, including isokinetic dynamometry and electromyography? (2) Does the activity of the deltoid, supraspinatus, and infraspinatus muscles measured using shear wave elastography show good intraobserver and interobserver reliability? METHODS: Twelve volunteers participated in intrasession reliability experiments. They were asked to perform isometric abduction, external rotation, and scaption contractions (defined as elevation of the arm within the plane of the scapula with neutral arm rotation) gradually increased from 0% to 75% of maximal voluntary contraction. The joint torque, electromyographic activity, and shear elastic modulus were synchronously measured in the middeltoid, supraspinatus, and infraspinatus muscles. The validity of the elastic modulus value was assessed using regression analysis between normalized torque and electromyographic root mean square values. For intraobserver and interobserver reliability measurements, repeated experiments were performed with the same protocol. RESULTS: The shear elastic modulus and normalized joint torque with isokinetic dynamometry showed a linear relationship in all muscles (deltoid, supraspinatus, and infraspinatus) and each of the ultrasonography planes (longitudinal and transverse) (mean R > 0.8 and p < 0.001 for all measurements). For the supraspinatus muscle, the mean slope of the relationship between shear elastic modulus in the longitudinal plane and the normalized joint torque during scaption contraction was 1.28 ± 0.39 kPa/%MVC (mean R = 0.93 ± 0.21, p < 0.001). Furthermore, similar results were obtained in relation to electromyography root mean square values (mean R > 0.8 and p < 0.001 in all measurements). For the supraspinatus muscle, the mean slope of the relationship between shear elastic modulus in the longitudinal plane and electromyographic (EMG) root mean square was 0.96 ± 0.27 kPa/%EMG (mean R = 0.91 ± 0.08, p < 0.001). The intraobserver and interobserver reliabilities were excellent in all positions (abduction, external rotation, and scaption) and in both the longitudinal and transverse ultrasonography planes (all intraclass correlation coefficients are > 0.85). CONCLUSIONS: Shoulder muscle activity can be noninvasively evaluated with ultrasound shear wave elastography. Clinician and scientists should consider the application of this technique in cases in which evaluation of shoulder muscle activity is required. The next step after this study will be to check the shear elastic modulus of rotator cuff muscle in patients with rotator cuff tear. We plan to evaluate the correlation between shear elastic modulus and joint torque according to tear size and fatty infiltration status of rotator cuff muscle. CLINICAL RELEVANCE: Shear wave electrography can be used to measure various tissue elasticities in both static and dynamic modes. It may be a useful tool to evaluate pre- and postoperative rotator cuff muscle activity in a relatively simple manner. Shoulder function after reverse total shoulder arthroplasty associated with deltoid muscle activity also may be evaluated. Changes in tissue tightness in shoulder disorders caused by increase soft tissue stiffness (ie, adhesive capsulitis and glenohumeral internal rotation deficit) can be evaluated.

Comparative postural stability in patients with lateral meniscus versus medial meniscus tears.

BACKGROUND: Types of mechanoreceptors may differ between the medial and lateral menisci, suggesting that postural stability may differ between patients with medial and lateral meniscus tears. However, to date, postural stability has not been compared in patients with medial and lateral meniscus tears. This study used stabilometry to compare postural stability in patients with medial and lateral meniscus tears. METHODS: Postural stability and thigh muscle strength were assessed in 24 patients with medial and 18 patients with lateral meniscus tears. Postural stability was determined by measuring the anteroposterior (APSI), mediolateral (MLSI), and overall (OSI) stability indices using stabilometry. Maximal torque (60°/s) of the quadriceps and hamstring was evaluated using an isokinetic testing device. RESULTS: The three stability indices, OSI, APSI, and MLSI, in both involved and uninvolved knees were all significantly greater in patients with lateral than with medial meniscus tears. (P<0.001 for all OSI, APSI, and MLSI in both involved and uninvolved knees, except for P=0.005 for MLSI of involved knees). In patients with medial meniscus tears, both OSI (1.4±0.4 vs. 1.1±0.4, P=0.037) and MLSI (0.9±0.3 vs. 0.8±0.3, P=0.041) were significantly higher on the injured than the uninjured side. In patients with lateral meniscus tears, none of the stability indices differed significantly between injured and uninjured knee joints. CONCLUSION: Postural stability of both the injured and uninjured knee joints was poorer in patients with lateral than with medial meniscus tears.

The Characteristics of Shoulder Muscles in Archery Athletes.

BACKGROUND: This study evaluated the shoulder girdle muscle characteristics of elite archery athletes and provides suggestions for archery training programs. METHODS: This study enrolled 15 cases of high level archery athletes (7 males, 8 females) and 30 cases of (15 males, 15 females) sex, age-matched, healthy, non-athletic individuals. We measured peak torques of flexion (FL), extension (EX), abduction (ABD), adduction (ADD), external rotation (ER) and internal rotation (IR) of both shoulders at an angular velocity of 30°/sec, 60°/sec, and 180°/sec. The peak torques and peak torque ratios of FL/EX, ABD/ADD, and ER/IR of the two groups were compared. RESULTS: The archer group had a greater peak torque of IR and ADD, but only in the left shoulder (p<0.05). In the same group, both shoulders had greater peak torque of EX and lower peak torque of FL. The peak torque ratios of FL/EX of both shoulders were significantly lower in the archer group at all three angular velocities (p<0.05). The peak torque ratios of ABD/ADD were significantly greater in only the left shoulder of the archer group (p<0.05). CONCLUSIONS: The prominent characteristics of the shoulder girdle muscles of an elite archer are stronger adductor muscles of the bow shoulder and stronger extensors of both shoulders, as compared to healthy, non-athletic individuals. These muscle groups of the shoulder probably contribute a major role in maintaining the accuracy and stability during archery shooting. Hence, a training program that selectively enhances the adductor and extensor muscles could prove helpful in enhancing the archery skills of the athlete.

Proprioception in Patients With Anterior Cruciate Ligament Tears: A Meta-analysis Comparing Injured and Uninjured Limbs.

BACKGROUND: Because of a reduction in the number of mechanoreceptors or alterations of their characteristics, anterior cruciate ligament (ACL) tears lead not only to mechanical instability but also to impaired proprioception. Purpose/Hypothesis: This study analyzed whether ACL tears cause a greater decrease in proprioception in injured than in uninjured knees. The hypothesis was that knee proprioception after ACL tears would decrease more in injured than in contralateral uninjured knees, regardless of the method used to measure knee proprioception. STUDY DESIGN: Meta-analysis. METHODS: We identified studies comparing proprioception in ACL-injured and contralateral intact knees using threshold for detection of passive motion (TTDPM) or joint position sense (JPS) tests. JPS was assessed by measuring the reproduction of passive positioning (RPP) or active repositioning (RAP) of the knee. RESULTS: Sixteen studies were included in this meta-analysis. The pooled results of subgroup analyses of TTDPM for both 20° and 40° of knee flexion showed that mean angle of error was 0.23° (95% CI, 0.08°-0.37°) greater in ACL-injured than in contralateral intact knees ( P = .002). Pooled data RAP and RPP subgroup analyses also showed that the mean angle of error was 0.94° higher in ACL-injured than in contralateral intact knees. The mean difference in angle of error between ACL-injured and contralateral intact knees was 0.71° greater (95% CI, 0.68°-0.74°; P < .001) by JPS than by TTDPM. CONCLUSION: Proprioception of ACL-injured knees was decreased compared with contralateral intact knees, as determined by both joint movement (kinesthesia) and joint position. The magnitude of loss of proprioception was greater in joint position than in joint movement.

Tension Pneumopericardium after Pericardiocentesis.

Pneumopericardium is defined as the presence of air inside the pericardial space. Usually, it is reported as a complication of blunt or penetrating chest trauma, but rare iatrogenic and spontaneous cases have been reported. Pneumopericardium is relatively stable if it does not generate a tension effect on the heart. However, it may progress to tension pneumopericardium, which requires immediate pericardial aspiration. We report a case of iatrogenic pneumopericardium occurred in a 70-year-old man who presented dyspnea at emergency department. The patient underwent pericardiocentesis for cardiac tamponade due to large pericardial effusion, and iatrogenic tension pneumopericardium occurred due to misuse of the drainage device. After evacuating the pericardial air through the previously implanted catheter, the patient became stable. We report this case to increase the awareness of this fatal condition and to help increase the use of precautions against the development of this condition during emergency procedures.

Influence of Anterior Cruciate Ligament Tear on Thigh Muscle Strength and Hamstring-to-Quadriceps Ratio: A Meta-Analysis.

Theoretical compensation after anterior cruciate ligament (ACL) tear could cause quadriceps weakness and hamstring activation, preventing anterior tibial subluxation and affecting the expected hamstring-to-quadriceps ratio. Although quadriceps weakness often occurs after ACL tears, it remains unclear whether hamstring strength and hamstring-to-quadriceps ratio increase in ACL deficient knees. This meta-analysis compared the isokinetic muscle strength of quadriceps and hamstring muscles, and the hamstring-to-quadriceps ratio, of the injured and injured limbs of patients with ACL tears. This meta-analysis included all studies comparing isokinetic thigh muscle strengths and hamstring-to-quadriceps ratio in the injured and uninjured legs of patients with ACL tear, without or before surgery. Thirteen studies were included in the meta-analysis. Quadriceps and hamstring strengths were 22.3 N∙m (95% CI: 15.2 to 29.3 N∙m; P<0.001) and 7.4 N∙m (95% CI: 4.3 to 10.5 N∙m; P<0.001) lower, respectively, on the injured than on the uninjured side. The mean hamstring-to-quadriceps ratio was 4% greater in ACL deficient than in uninjured limbs (95% CI: 1.7% to 6.3%; P<0.001). Conclusively, Decreases were observed in both the quadriceps and hamstring muscles of patients with ACL tear, with the decrease in quadriceps strength being 3-fold greater. These uneven reductions slightly increase the hamstring-to-quadriceps ratio in ACL deficient knees.

Correlation between Quadriceps Endurance and Adduction Moment in Medial Knee Osteoarthritis.

It is not clear whether the strength or endurance of thigh muscles (quadriceps and hamstring) is positively or negatively correlated with the adduction moment of osteoarthritic knees. This study therefore assessed the relationships between the strength and endurance of the quadriceps and hamstring muscles and adduction moment in osteoarthritic knees and evaluated predictors of the adduction moment. The study cohort comprised 35 patients with unilateral medial osteoarthritis and varus deformity who were candidates for open wedge osteotomy. The maximal torque (60°/sec) and total work (180°/sec) of the quadriceps and hamstring muscles and knee adduction moment were evaluated using an isokinetic testing device and gait analysis system. The total work of the quadriceps (r = 0.429, P = 0.037) and hamstring (r = 0.426, P = 0.045) muscles at 180°/sec each correlated with knee adduction moment. Preoperative varus deformity was positively correlated with adduction moment (r = 0.421, P = 0.041). Multiple linear regression analysis showed that quadriceps endurance at 180°/sec was the only factor independently associated with adduction moment (ß = 0.790, P = 0.032). The adduction moment of osteoarthritic knees correlated with the endurance, but not the strength, of the quadriceps muscle. However, knee adduction moment did not correlate with the strength or endurance of the hamstring muscle.

Effect of Time after Anterior Cruciate Ligament Tears on Proprioception and Postural Stability.

This study was designed to compare proprioception and postural stability in patients with acute (time from injury ≤ 3 months) and chronic (time from injury > 3 months) ACL tears, and to evaluate the correlation between time interval after ACL injury and proprioception. Thigh muscle strength, postural stability, and joint position sense were compared in 48 patients with acute ACL tears and in 28 with chronic ACL tears. Maximal torque (60°/sec) of the quadriceps and hamstring was evaluated using an isokinetic testing device. Postural stability was determined from the anterior-posterior (APSI), medial-lateral (MLSI), and overall (OSI) stability indices using stabilometry. Joint position sense was also tested by reproduction of passive positioning (RPP). Muscle strengths and stability indices on both the involved and uninvolved sides were similar in the acute and chronic ACL tear groups. RPP on the involved side was significantly greater in the chronic than in the acute ACL tear group (7.8° vs. 5.6°, P = 0.041). Two of three stability indices (APSI, OSI) and RPP were significantly greater on the involved than the uninvolved side in the chronic ACL tear group.

Lack of Correlation between Dynamic Balance and Hamstring-to-Quadriceps Ratio in Patients with Chronic Anterior Cruciate Ligament Tears.

PURPOSE: The purpose of this study was to evaluate the quadriceps and hamstring muscle strength and hamstring-to-quadriceps (HQ) ratio, as well as the relationships of these parameters with dynamic balance, in patients with anterior cruciate ligament (ACL) rupture. MATERIALS AND METHODS: We compared 25 patients diagnosed with chronic unilateral ACL tears and 25 age-matched healthy volunteers. The maximal torque of the quadriceps and hamstring and dynamic balance were measured. RESULTS: Although the isokinetic maximal peak torques were about 50% lower in the quadriceps (57%, p<0.001) and hamstring (56%, p=0.001) muscles in the chronic ACL tear group than in the control group, their HQ ratios were similar (56%±17% vs. 58%±6%, p=0.591). HQ ratio was significantly correlated with anterior-posterior stability index (r=-0.511, p=0.021) and overall stability index (r=-0.476, p=0.034) in control group, but these correlations were not observed in chronic ACL tear group. CONCLUSIONS: Thigh muscle strength was about 50% lower in the chronic ACL tear group than in the control group, but the HQ ratio was similar. The dynamic balance of the knee was not influenced by thigh muscle strength but was influenced by HQ ratio in healthy young individuals. However, HQ ratio was not correlated with dynamic knee balance in chronic ACL tear patients.

Quadriceps Strength and Endurance After Posterior Cruciate Ligament Tears Versus Matched Group With Anterior Cruciate Ligament Tears.

PURPOSE: This study was designed to compare the preoperative strengths and endurances of the quadriceps and hamstring muscles in patients with anterior cruciate ligament (ACL) versus posterior cruciate ligament (PCL) tears. METHODS: Quadriceps and hamstring muscle strength and endurance were compared between 20 prospectively enrolled patients with isolated PCL tears and a retrospective, matched control group of 20 patients with isolated ACL tears. The maximal torque (60°/s) and total work (180°/s) of the quadriceps and hamstring were evaluated with an isokinetic testing device. RESULTS: Total work (1,094.4 ± 505.8 J v 797.5 ± 332.7 J, P = .035) and peak torque (129.9 ± 56.2 N ∙ m v 98.2 ± 37.4 N ∙ m, P = .046) of the quadriceps muscle on the involved side were higher in the PCL tear group than in the ACL tear group. However, there were no significant differences between the PCL tear group and ACL tear group in hamstring muscle strength (45.8 ± 42.3 N ∙ m and 46.0 ± 24.4 N ∙ m, respectively; P = .940) and endurance (429.3 ± 238.9 J and 382.4 ± 256.1 J, respectively; P = .574) on the involved side. CONCLUSIONS: The strength and endurance of the quadriceps muscle of the injured limb were greater after PCL tears than after ACL tears. However, there were no significant between-group differences in hamstring muscle strength and endurance on the involved side. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Serial changes in knee muscle strength after anterior cruciate ligament reconstruction using hamstring tendon autografts.

PURPOSE: The purpose of this study was to evaluate serial changes in quadriceps and hamstring muscle strength over the first postoperative year in patients who underwent anterior cruciate ligament (ACL) reconstruction with an autologous hamstring tendon graft and to reveal which of these 2 muscles lost more strength and recovered more slowly after autologous hamstring ACL reconstruction. METHODS: Isokinetic muscle strength was measured preoperatively and at 6 months and 1 year postoperatively in 20 patients who underwent ACL reconstruction. The maximal torque (60°/s) and total work (180°/s) of the quadriceps and hamstring were evaluated using an isokinetic testing device. The isokinetic muscle strength and endurance of the injured legs were expressed as percentages of those of the uninjured legs at the same time point. RESULTS: Both quadriceps and hamstring muscle strength at 60°/s and endurance at 180°/s of the injured relative to the uninjured leg was 50% preoperatively. Quadriceps muscle strength and endurance of the injured leg increased to 70% at 6 months and 80% at 1 year postoperatively, whereas hamstring muscle strength and endurance increased to 80% at 6 months and 80% at 1 year. CONCLUSIONS: Knee muscle strength recovered progressively after ACL reconstruction using autologous hamstring tendons but did not fully recover, being about 80% that of the uninjured leg even 1 year after surgery. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Postural stability in patients with anterior cruciate ligament tears with and without medial meniscus tears.

PURPOSE: To compare postural stability in patients with isolated anterior cruciate ligament (ACL) tears and ACL tears with associated meniscal tears. METHODS: Quadriceps and hamstring muscle strength and their ratio, as well as the relationships of these parameters with postural stability, were compared in 23 patients with isolated ACL tears and 27 with combined ACL and medial meniscus tears. Postural stability was determined from the anterior-posterior, medial-lateral, and overall stability indices using the Biodex Stability System. RESULTS: On both the involved and uninvolved sides, there were no differences in mean stability indices, including anterior-posterior, medial-lateral, and overall stability indices, in patients with isolated and combined ACL tears. In patients with isolated ACL tears, both overall (2.3 ± 1.2 vs. 1.8 ± 1.4, p = 0.033) and medial-lateral (1.2 ± 0.6 vs. 1.0 ± 0.5, p = 0.031) stability indices were significantly higher on the involved compared to the uninvolved side. These differences, however, were not observed in the combined ACL tear group. CONCLUSION: No significant differences in postural instability on the affected and unaffected sides were observed in patients with isolated ACL tears and those with combined ACL and medial meniscus tears. These findings indicate that there is no need to reduce the goal of restoring proprioception in patients with combined compared with isolated ACL tears. LEVEL OF EVIDENCE: III.

Artemisinic acid is a regulator of adipocyte differentiation and C/EBP δ expression.

Adipocyte dysfunction is associated with the development of obesity. In this study, artemisinic acid, which was isolated from Artemisia annua L., inhibited adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells (hAMSCs) and its mechanism of action was determined. The mRNA levels of peroxidase proliferation-activated receptor (PPAR) γ and CCAAT/enhancer binding protein (C/EBP) α, late adipogenic factors, were reduced by artemisinic acid. Moreover, the mRNA levels of the PPAR γ target genes lipoprotein lipase, CD36, adipocyte protein, and liver X receptor were down-regulated by artemisinic acid. Artemisinic acid reduced expression of the C/EBP δ gene without impacting C/EBP ß. In addition, attempts to elucidate a possible mechanism underlying the artemisinic acid-mediated effects revealed that reduced expression of the C/EBP δ gene was mediated by inhibiting Jun N-terminal kinase (JNK). Additionally, artemisinic acid also reduced the expression of the adipogenesis-associated genes glucose transporter-4 and vascular endothelial growth factor. In addition to the interference of artemisinic acid with adipogenesis, artemisinic acid significantly attenuated tumor necrosis factor-α-induced secretion of interleukin-6 by undifferentiated hAMSCs, thus influencing insulin resistance and the inflammatory state characterizing obesity. Taken together, these findings indicate that inhibiting adipogenic differentiation of hAMSCs by artemisinic acid occurs primarily through reduced expression of C/EBP δ, which is mediated by the inhibition of JNK and suggest that aremisinic acid may be used as a complementary treatment option for obesity associated with metabolic syndrome.