Swimming Microrobot Optical Nanoscopy.

Optical imaging plays a fundamental role in science and technology but is limited by the ability of lenses to resolve small features below the fundamental diffraction limit. A variety of nanophotonic devices, such as metamaterial superlenses and hyperlenses, as well as microsphere lenses, have been proposed recently for subdiffraction imaging. The implementation of these micro/nanostructured lenses as practical and efficient imaging approaches requires locomotive capabilities to probe specific sites and scan large areas. However, directed motion of nanoscale objects in liquids must overcome low Reynolds number viscous flow and Brownian fluctuations, which impede stable and controllable scanning. Here we introduce a new imaging method, named swimming microrobot optical nanoscopy, based on untethered chemically powered microrobots as autonomous probes for subdiffraction optical scanning and imaging. The microrobots are made of high-refractive-index microsphere lenses and powered by local catalytic reactions to swim and scan over the sample surface. Autonomous motion and magnetic guidance of microrobots enable large-area, parallel and nondestructive scanning with subdiffraction resolution, as illustrated using soft biological samples such as neuron axons, protein microtubulin, and DNA nanotubes. Incorporating such imaging capacities in emerging nanorobotics technology represents a major step toward ubiquitous nanoscopy and smart nanorobots for spectroscopy and imaging.

Multimodal Management of Coexisting Atlantoaxial Subluxation and Spinal Stenosis in an Older Adult: A Case Report and Literature Review.

This case report investigates the diagnostic and therapeutic challenges caused by the coexistence of atlantoaxial subluxation and spinal stenosis in a 70-year-old male patient with chronic progressive numbness in both hands. A detailed assessment showed that the patient's symptoms were primarily caused by spinal stenosis, not atlantoaxial subluxation. Considering the patient's age and preference for nonsurgical treatment, a conservative chiropractic care plan was implemented, significantly improving his symptoms and quality of life. This case highlights the potential benefit of conservative chiropractic care in managing such complex cases, emphasizes the need for meticulous diagnosis, and requires further research to validate these findings and develop comprehensive management guidelines.

Conservative Management of Low Back Pain and Scoliosis in a Patient With Rheumatoid Arthritis: Eight Years Follow-Up.

Scoliosis in patients with rheumatoid arthritis (RA) can cause significant pain and disability. RA has been extensively studied in relation to the cervical spine, yet the pathology of the thoracic and lumbar spine in RA patients has been largely overlooked. A 66-year-old woman, with longstanding RA and severe scoliosis, presented to the chiropractic clinic with a five-month history of exacerbated low back pain radiating to the right lower limb. The patient was treated with a combination of full-spine mechanical spinal distraction, spinal manipulative therapy, mechanical distraction of the cervical spine, and soft tissue treatment (scraping therapy). Thereafter, the patient recovered from the pain and radiculopathy and showed improvements in the radiological parameters, walking gait, and postural balance. Radiography was performed at the 12-month, four-year, and eight-year follow-up appointments and revealed improvements in symptoms, posture, and scoliosis. Although the treatment for RA-related scoliosis is similar to that for other types of scoliosis, due to the nature of RA, treatment should be tailored to individual patients. This case report highlights the importance of considering chiropractic therapy for the management of lumbar scoliosis in patients with RA, as a comprehensive treatment plan resulted in improved spinal balance, mobility, gait, posture, and quality of life.

Parotid Oncocytoma on 99mTc-Sestamibi Scintigraphy and SPECT/CT.

ABSTRACT: Oncocytomas in the parotid gland are a rare benign neoplasm composed of mitochondrial-rich oncocytes. Here we present the case of an 85-year-old man with a history of biopsy-proven right parotid gland oncocytoma who underwent 99mTc-sestamibi scintigraphy and SPECT/CT in the context of primary hyperparathyroidism. Focal intense uptake of radiotracer is detected within the right parotid gland on sestamibi scintigraphy. SPECT/CT confirms the localization of sestamibi uptake to the hyperattenuating parotid gland oncocytoma.

Bilateral ovarian metastasis of clear-cell renal cell carcinoma: A case report.

Renal cell carcinoma (RCC) accounts for 2-3% of all adult malignancies. Clear-cell type RCC is the most common type, accounting for approximately 75% of all renal cancer cases. The most common sites of metastasis include the lung, bone, and liver. Ovarian metastasis of RCC is an exceptionally rare occurrence with only 41 cases reported in the literature with only 11 of these cases involving the bilateral ovaries. Here we present a case of clear-cell RCC arising from the left kidney with metastatic involvement of bilateral ovaries in a 48-year-old woman.

Axis-dependent anisotropy in protein unfolding from integrated nonequilibrium single-molecule experiments, analysis, and simulation.

We present a comprehensive study that integrates experimental and theoretical nonequilibrium techniques to map energy landscapes along well defined pull-axis specific coordinates to elucidate mechanisms of protein unfolding. Single-molecule force-extension experiments along two different axes of photoactive yellow protein combined with nonequilibrium statistical mechanical analysis and atomistic simulation reveal energetic and mechanistic anisotropy. Steered molecular dynamics simulations and free-energy curves constructed from the experimental results reveal that unfolding along one axis exhibits a transition-state-like feature where six hydrogen bonds break simultaneously with weak interactions observed during further unfolding. The other axis exhibits a constant (unpeaked) force profile indicative of a noncooperative transition, with enthalpic (e.g., H-bond) interactions being broken throughout the unfolding process. Striking qualitative agreement was found between the force-extension curves derived from steered molecular dynamics calculations and the equilibrium free-energy curves obtained by Jarzynski-Hummer-Szabo analysis of the nonequilibrium work data. The anisotropy persists beyond pulling distances of more than twice the initial dimensions of the folded protein, indicating a rich energy landscape to the mechanically fully unfolded state. Our findings challenge the notion that cooperative unfolding is a universal feature in protein stability.

A Rare Case of Vulvar Hibernoma Treated With Resection.

Hibernoma is a rare benign neoplasm of brown adipose tissue most frequently involving the thigh, shoulder, back, and neck. Differentiating this benign entity from other lipomatous tumors such as well-differentiated liposarcoma is essential, given the different surgical approaches and prognosis associated with each diagnosis. It is helpful for the radiologist to recognize the uncommon locations of hibernoma, as well as characteristic imaging features, in order to properly include it in the differential considerations. Here we present a rare case of symptomatic vulvar hibernoma in a 25-year-old woman treated with surgical excision.

Magnetization transfer enhanced vascular-space-occupancy (MT-VASO) functional MRI.

Vascular-space-occupancy (VASO) MRI is a novel technique that uses blood signal nulling to detect blood volume alterations through changes in tissue signal. VASO has relatively low signal to noise ratio (SNR) because only 10-20% of tissue signal remain at the time of blood nulling. Here, it is shown that by adding a magnetization transfer (MT) prepulse it is possible to increase SNR either by attenuating the initial tissue magnetization when the MT pulse is placed before inversion, or, accelerating the recovery process when the pulse is applied after the inversion. To test whether the MT pulse would affect the blood nulling time in VASO, MT effects in blood were measured both ex vivo in a bovine blood phantom and in vivo in human brain. Such effects were found to be sufficiently small (<2.5%) under a saturation power or=40 ppm to allow use of the same nulling time. Subsequently, functional MRI experiments using MT-VASO were performed in human visual cortex at 3 Tesla. The relative signal changes in MT-VASO were of the same magnitude as in VASO, while the contrast to noise ratio (CNR) was enhanced by 44+/-12% and 36+/-11% respectively. Therefore, MT-VASO should provide a means for increasing inherently low CNR in VASO experiments while preserving the CBV sensitivity.

Split-Dose 18F-FDG PET/CT-Guided Microwave Ablation for Liver Metastasis Recurrence with Immediate Treatment Assessment.

A 48-y-old man with a history of colon cancer presented with recurrent hepatic metastasis along a prior microwave ablation bed. Split-bolus, intraprocedural 18F-FDG PET was performed to guide repeat microwave ablation and immediately confirm complete treatment. PET-guided ablation is highly accurate for targeting and treating malignant hepatic lesions and feasible for nonspecialized tertiary care hospitals without an onsite cyclotron.

Size-induced enhancement of chemical exchange saturation transfer (CEST) contrast in liposomes.

Liposome-based chemical exchange saturation transfer (lipoCEST) agents have shown great sensitivity and potential for molecular magnetic resonance imaging (MRI). Here we demonstrate that the size of liposomes can be exploited to enhance the lipoCEST contrast. A concise analytical model is developed to describe the contrast dependence on size for an ensemble of liposomes. The model attributes the increased lipoCEST contrast in smaller liposomes to their larger surface-to-volume ratio, causing an increased membrane water exchange rate. Experimentally measured rates correlate with size, in agreement with the model. The water permeability of liposomal membrane is found to be 1.11 +/- 0.14 microm/s for the specific lipid composition at 22 degrees C. Availability of the model allows rational design of the size of liposomes and quantification of their properties. These new theoretical and experimental tools are expected to benefit applications of liposomes to sensing the cellular environment, targeting and imaging biological processes, and optimizing drug delivery properties.

Perfusion Imaging in Acute Traumatic Brain Injury.

Traumatic brain injury (TBI) is a significant problem worldwide and neuroimaging plays a critical role in diagnosis and management. Recently, perfusion neuroimaging techniques have been explored in TBI to determine and characterize potential perfusion neuroimaging biomarkers to aid in diagnosis, treatment, and prognosis. In this article, computed tomography (CT) bolus perfusion, MR imaging bolus perfusion, MR imaging arterial spin labeling perfusion, and xenon CT are reviewed with a focus on their applications in acute TBI. Future research directions are also discussed.

Differential inducibility of rat pulmonary CYP1A1 by cigarette smoke and wood smoke.

Mainstream cigarette smoke (CS) and wood smoke (WS) were compared in terms of their pulmonary CYP1A1 inducibility. The inducibility was assessed in pulmonary microsomes from rats exposed to freshly generated CS or WS and in rat lung explants treated with extracts of CS or WS total particulate matter (TPM). Mutagenicity in Salmonella typhimurium TA98 and TA100, an effect established for CS and WS in previous studies, was also examined as a test of the biological activity of the smoke samples in the present study. Pulmonary microsomal CYP1A1 activity (as measured by ethoxyresorufin O-deethylase), was induced 4.4-fold and 8.3-fold following exposure of rats to smoke from a single cigarette and three cigarettes, respectively, relative to the activity in control rats. The induction was paralleled by elevated CYP1A1 mRNA level (by northern blot analysis). WS, in contrast to CS, induced neither pulmonary CYP1A1 activity nor mRNA in exposed rats. CYP1A1 protein (by western blot analysis) was induced in cultured rat lung explants by extracts of CS TPM or by a high concentration (496 nM) of benzo[a]pyrene (B[a]P) but not by extracts of WS TPM or a low concentration (0.110 nM) of B[a]P. The induction by high B[a]P concentration was inhibited by extracts of CS or WS TPM, with the inhibition by extracts of WS TPM (75%) being greater than that by extracts of CS TPM (31%). Extracts of CS TPM were as mutagenic as extracts of WS TPM to Salmonella typhimurium TA98 but were more mutagenic than extracts of WS TPM to Salmonella typhimurium TA100. The results show that CS and WS are mutagenic but that WS differs from CS in its inability to induce pulmonary CYP1A1.

Texture-based Quantification of Centrilobular Emphysema and Centrilobular Nodularity in Longitudinal CT Scans of Current and Former Smokers.

RATIONALE AND OBJECTIVES: The effect of smoking cessation on centrilobular emphysema (CLE) and centrilobular nodularity (CN), two manifestations of smoking-related lung injury on computed tomography (CT) images, has not been clarified. The objective of this study is to leverage texture analysis to investigate differences in extent of CLE and CN between current and former smokers. MATERIALS AND METHODS: Chest CT scans from 350 current smokers, 401 former smokers, and 25 control subjects were obtained from the multicenter COPDGene Study, a Health Insurance Portability and Accountability Act-compliant study approved by the institutional review board of each participating clinical study center. Additionally, for 215 of these subjects, a follow-up CT scan was obtained approximately 5 years later. For each CT scan, 5000 circular regions of interest (ROIs) of 35-pixel diameter were randomly selected throughout the lungs. The patterns present in each ROI were summarized by 50 computer-extracted texture features. A logistic regression classifier was leveraged to classify each ROI as normal lung, CLE, or CN, and differences in the percentages of normal lung, CLE, and CN by study group were assessed. RESULTS: Former smokers had significantly more CLE (P <0.01) but less CN (P <0.001) than did current smokers, even after adjustment for important covariates such as patient age, GOLD stage, smoking history, forced expiratory volume in 1 second, gas trapping, and scanner model. Among patients with longitudinal CT scans, continued smoking led to a slight increase in CLE (P = 0.13), whereas sustained abstinence from smoking led to further reduction in CN (P <0.05). CONCLUSIONS: The proposed texture-based approach quantifies the extent of CN and CLE with high precision. Differences in smoking-related lung disease between longitudinal scans of current smokers and longitudinal scans of former smokers suggest that CN may be reversible on smoking cessation.

EGFR protein expression in non-small cell lung cancer predicts response to an EGFR tyrosine kinase inhibitor--a novel antibody for immunohistochemistry or AQUA technology.

INTRODUCTION: Epidermal growth factor receptor (EGFR) protein expression in non-small cell lung cancer (NSCLC) is not recommended for predicting response to EGFR tyrosine kinase inhibitors (TKI) due to conflicting results, all using antibodies detecting EGFR external domain (ED). We tested the predictive value of EGFR protein expression for response to an EGFR TKI with an antibody that detects the intracellular domain (ID) and compared fluorescence-based Automated QUantitative Analysis (AQUA) technology to immunohistochemistry (IHC). METHODS: Specimens from 98 gefitinib-treated NSCLC Japanese patients were evaluated by IHC (n = 98 of 98) and AQUA technology (n = 70 of 98). EGFR ID (5B7)- and ED-specific antibodies (3C6 and 31G7) were compared. RESULTS: EGFR expression evaluated with 5B7 was significantly higher in responders versus nonresponders to gefitinib both with IHC and with AQUA. ED-specific antibodies did not significantly predict response. Using AQUA and ID-specific antibody resulted in the best prediction performance with a positive and negative predictive value (PPV/NPV) for responders of 50% and 87%, respectively. EGFR expression with ID-specific antibody and AQUA also predicted responders in EGFR-mutated patients. Increased EGFR expression with the ID antibody is associated with increased median progression free survival (PFS; 11.7 months vs. 5.0, log rank, P = 0.034) and overall survival (OS; 38.6 vs. 14.9, P = 0.040) from gefitinib therapy. CONCLUSIONS: EGFR protein expression using an ID-specific antibody specifically predicts response to gefitinib in NSCLC patients, including in EGFR-mutated patients, and increased PFS/OS from gefitinib. These data suggest that the choice of diagnostic antibody and methodology matters to predict response and outcome to specific therapies. The potential clinical application needs further validation. Clin Cancer Res; 17(24); 7796-807. ©2011 AACR.

Oxygenation and hematocrit dependence of transverse relaxation rates of blood at 3T.

Knowledge of the transverse relaxation rates R2 and R2* of blood is relevant for quantitative assessment of functional MRI (fMRI) results, including calibration of blood oxygenation and measurement of tissue oxygen extraction fractions (OEFs). In a temperature controlled circulation system, these rates were measured for blood in vitro at 3T under conditions akin to the physiological state. Single spin echo (SE) and gradient echo (GRE) sequences were used to determine R2 and R2*, respectively. Both rates varied quadratically with deoxygenation, and changes in R2* were found to be due predominantly to changes in R2. These data were used to estimate intravascular blood oxygenation level dependent (BOLD) contributions during visual activation. Due to the large R2* in venous blood, intravascular SE BOLD signal changes were larger than GRE effects at echo times above 30 ms. When including extravascular effects to estimate the total BOLD effect, GRE BOLD dominated due to the large tissue volume fraction.

Single-molecule detection of structural changes during Per-Arnt-Sim (PAS) domain activation.

The Per-Arnt-Sim (PAS) domain is a ubiquitous protein module with a common three-dimensional fold involved in a wide range of regulatory and sensory functions in all domains of life. The activation of these functions is thought to involve partial unfolding of N- or C-terminal helices attached to the PAS domain. Here we use atomic force microscopy to probe receptor activation in single molecules of photoactive yellow protein (PYP), a prototype of the PAS domain family. Mechanical unfolding of Cys-linked PYP multimers in the presence and absence of illumination reveals that, in contrast to previous studies, the PAS domain itself is extended by approximately 3 nm (at the 10-pN detection limit of the measurement) and destabilized by approximately 30% in the light-activated state of PYP. Comparative measurements and steered molecular dynamics simulations of two double-Cys PYP mutants that probe different regions of the PAS domain quantify the anisotropy in stability and changes in local structure, thereby demonstrating the partial unfolding of their PAS domain upon activation. These results establish a generally applicable single-molecule approach for mapping functional conformational changes to selected regions of a protein. In addition, the results have profound implications for the molecular mechanism of PAS domain activation and indicate that stimulus-induced partial protein unfolding can be used as a signaling mechanism.