Fluorescence-Shadowing Nanoparticle Clusters for Real-Time Monitoring of Tumor Progression.

Monitoring tumor progression is important for elucidating appropriate therapeutic strategies in response to anticancer therapeutics. To fluorescently monitor the in vivo levels of tumor-specific enzymes, we prepared matrix metalloprotease (MMP)-responsive gold nanoparticle (AuNP) clusters to sense tumor microenvironments. Specifically, AuNPs and quantum dots (QDs) were surface-engineered with two poly(ethylene glycol) [PEG] shells and cyclooctyne moieties, respectively, for the copper-free click reaction. Upon "peeling off" of the secondary shell from the double-PEGylated AuNPs under MMP-rich conditions, shielded azide moieties of the AuNPs were displayed toward the QD, and those two particles were clicked into nanoparticle clusters. This consequently resulted in a dramatic size increase and fluorescence quenching of QDs via fluorescence energy transfer (FRET) due to the molecular proximity of the particles. We observed that FRET efficiency was modulated via changes in MMP levels and exposure time. Cancer cell numbers exhibited a strong correlation with FRET efficiency, and in vivo studies that employed solid tumor models accordingly showed that FRET efficiency was dependent on the tumor size. Thus, we envision that this platform can be tailored and optimized for tumor monitoring based on MMP levels in solid tumors.

Associations of isokinetic and isotonic knee strength with knee function and activity level after anterior cruciate ligament reconstruction: a prospective cohort study.

BACKGROUND: Although isokinetic dynamometry often serves as a reference to assess the concurrent validity of weight-machine isotonic strength testing, it is unknown whether isokinetic knee strength is associated with knee function and activity level more strongly than isotonic knee strength in patients with an anterior cruciate ligament reconstruction (ACLR). This study aimed to compare the associations of isokinetic and isotonic knee strength with knee function and work-and-sports activity levels in patients with ACLR. METHODS: One-hundred and six patients with a unilateral ACLR participated. At three months post-ACLR, isokinetic quadriceps and hamstrings strength was measured using an isokinetic dynamometer whilst isotonic strength was measured using weight machines. At six months post-ACLR, patients performed the single-leg hop-for-distance test. Self reported knee function and work-and-sports activity levels were assessed by the Lysholm Knee Score and Tegner Activity Score, respectively. RESULTS: In multivariable analyses, isotonic and isokinetic quadriceps strength limb symmetry indices (LSIs) were significantly associated with all outcomes (P≤0.03) and had comparable predictive performance. Isotonic and isokinetic hamstrings strength LSIs were significantly associated with Lysholm scores (P≤0.03) and isotonic hamstrings strength was additionally significantly associated with hop-for-distance LSI (P=0.01). CONCLUSIONS: Weight machine-derived isotonic quadriceps strength was independently and consistently associated with knee function and work-and-sport activity level post-ACLR. Isokinetic knee strength was not more strongly associated than isotonic knee strength with the various outcomes. These findings have logistic and economic implications because the isokinetic dynamometer system is relatively expensive and its operation requires more logistic effort and technical skills.

A modified straight leg raise test to differentiate between sural nerve pathology and Achilles tendinopathy. A cross-sectional cadaver study.

BACKGROUND: A modified straight leg raise test for the sural nerve (SLRSURAL) has been proposed to assist in the differential diagnosis of sural nerve pathology in people with posterior calf or ankle pain, or lateral foot pain. The biomechanical rationale is that strain in the dorsolateral ankle and foot structures following dorsiflexion-inversion can be selectively increased in the sural nerve with hip flexion. There are however no studies which have investigated whether hip flexion can increase strain in the sural nerve at the ankle. OBJECTIVES: To measure strain and longitudinal excursion of the sural nerve and Achilles tendon during a modified SLR. DESIGN: Cross-sectional cadaver study, with a repeated-measures design. METHOD: Strain and excursion were measured unilaterally in seven embalmed cadavers using differential transducers and a digital calliper. Data were analysed with repeated-measures ANOVAs (p < 0.05). RESULTS: With hip flexion (mean (SD): 54.6 (10.6) degrees), strain increased in the sural nerve (0.9 (0.5)%; p = 0.008), but not in the Achilles tendon (0.3 (0.3)%; p = 0.16). The sural nerve moved 1.0 (0.5) mm proximally with hip flexion (p = 0.02). CONCLUSIONS: The load placed on the sciatic nerve following hip flexion is transmitted distally to the sural nerve. These findings provide biomechanical support for the SLRSURAL. The relatively small changes in strain and excursion were most likely due to limited available ankle mobility in the tested cadavers. Further research is required to establish the diagnostic accuracy of SLRSURAL in a clinical setting.