Water and lipid content of breast tissue measured by six-wavelength time-domain diffuse optical spectroscopy.

Significance: The water and lipid content of normal breast tissue showed mammary gland characteristics with less influence from the chest wall using six-wavelength time-domain diffuse optical spectroscopy (TD-DOS) in a reflectance geometry. Aim: To determine the depth sensitivity of a six-wavelength TD-DOS system and evaluate whether the optical parameters in normal breast tissue can distinguish dense breasts from non-dense breasts. Approach: Measurements were performed in normal breast tissue of 37 breast cancer patients. We employed a six-wavelength TD-DOS system to measure the water and lipid content in addition to the hemoglobin concentration. The breast density in mammography and optical parameters were then compared. Results: The depth sensitivity of the system for water and lipid content was estimated to be ∼15 mm. Our findings suggest that the influence of the chest wall on the water content is weaker than that on the total hemoglobin concentration. In data with evaluation conditions, the water content was significantly higher (p < 0.001) and the lipid content was significantly lower (p < 0.001) in dense breast tissue. The water and lipid content exhibited a high sensitivity and specificity to distinguish dense from non-dense breasts in receiver-operating-characteristic curve analysis. Conclusions: With less influence from the chest wall, the water and lipid content of normal breast tissue measured by a reflectance six-wavelength TD-DOS system, together with ultrasonography, can be applied to distinguish dense from non-dense breasts.

Viscoelastic phase separation model for ternary polymer solutions.

When a polymer solution undergoes viscoelastic phase separation, the polymer-rich phase forms a network-like structure even if it is a minor phase. This unique feature is induced by polymer dynamics, which are constrained by the temporal entanglement of polymer chains. The fundamental mechanisms of viscoelastic phase separation have already been elucidated by theory and experiments over the past few decades; however, it is not yet well understood how viscoelastic phase separation occurs in multicomponent polymer solutions. Here, we construct a new viscoelastic phase separation model for ternary polymer solutions that consist of a polymer, solvent, and nonsolvent. Our simulation results reveal that a network-like structure is formed in the ternary bulk system through a phase separation mechanism similar to that observed in binary polymer solutions. A difference in dynamics is also found in that the solvent, whose affinity to the polymer is similar to that of the nonsolvent, moves freely between the polymer-rich and water-rich phases during phase separation. These findings are considered important for understanding the phase separation mechanism of ternary mixtures often used in the manufacture of polymeric separation membranes.

Highly Ordered Nanocellular Polymeric Foams Generated by UV-Induced Chemical Foaming.

Nanocellular polymer foams have shown significant potential for industrial applications because of their superior thermal, mechanical, and optical properties. Some of these properties may be further improved by enhancing the ordering of cell structures. However, it is challenging for conventional foaming methods to control both the cell size and ordering at the nanoscale. Here, we show an innovative method to produce highly ordered nanocellular polymer foams by incorporating the self-assembly of an asymmetric diblock copolymer with the UV-induced chemical foaming technique. The minor domains are designed to generate a gaseous compound from the partial cleavage of the functional group. It is demonstrated that the gas-producing reaction can be accelerated at a temperature low enough to prevent melting of the whole self-assembled template, by mixing a small amount of photoacid generator into the copolymer, followed by UV irradiation. The result is the production of polymer foams with the nanoscale cells highly aligned to the self-assembled domains.

Effect of Source-Detector Distance on the Measurement of Hemoglobin Using Near-Infrared Spectroscopy in Breast Cancer.

We measured total hemoglobin concentrations in breast tumors by near-infrared time-resolved spectroscopy. Muscles interfere with measurement when the probe is close to the chest wall. Since the target area of measurement depends on the distance between the light source and probe detector, we inferred that this issue could be solved by reducing the source-detector distance. The purpose of this study was to examine the effects of the source-detector distance on the measurement of total hemoglobin concentration in the breast. We examined 26 patients with breast tumors. Total hemoglobin concentration was measured in tumors and the contralateral normal breasts at source-detector distances of 20 and 30 mm. The difference in total hemoglobin concentration between each tumor and the contralateral breast was calculated. The normal breast total hemoglobin concentration was significantly smaller for the source-detector distance of 20 mm than for the source-detector distance of 30 mm. Differences in source-detector distance did not significantly affect tumor total hemoglobin. The difference in total hemoglobin concentration between the tumor and the contralateral breast obtained at the source-detector distance of 20 mm was significantly higher than that obtained at the source-detector distance of 30 mm. From these results, we considered that measurement with a source-detector distance of 20 mm is less affected by the chest wall than with a source-detector distance of 30 mm and that the difference in total hemoglobin concentration between the tumor and the contralateral breast at a source-detector distance of 20 mm can better reflect the net total hemoglobin concentrations of the breast tumors. In conclusion, using a probe with a source-detector distance of 20 mm can more accurately evaluate the total hemoglobin concentration in breast tumors.

Stable tissue-simulating phantoms with various water and lipid contents for diffuse optical spectroscopy.

We introduced a method for producing solid phantoms with various water-to-lipid ratios that can simulate the absorption, and to some extent the scattering characteristics of human breast tissue. We also achieved phantom stability for a minimum of one month by solidifying the emulsion phantoms. The characteristics of the phantoms were evaluated using the six-wavelength time-domain diffuse optical spectroscopy (TD-DOS) system we developed to measure water and lipid contents and hemoglobin concentration. The TD-DOS measurements were validated with a magnetic resonance imaging system.

Factors affecting measurement of optic parameters by time-resolved near-infrared spectroscopy in breast cancer.

The purpose of this study was to evaluate the effects of the thickness and depth of tumors on hemoglobin measurements in breast cancer by optical spectroscopy and to demonstrate tissue oxygen saturation (SO2) and reduced scattering coefficient (µs') in breast tissue and breast cancer in relation to the skin-to-chest wall distance. We examined 53 tumors from 44 patients. Total hemoglobin concentration (tHb), SO2, and µs' were measured by time-resolved spectroscopy (TRS). The skin-to-chest wall distance and the size and depth of tumors were measured by ultrasonography. There was a positive correlation between tHb and tumor thickness, and a negative correlation between tHb and tumor depth. SO2 in breast tissue decreased when the skin-to-chest wall distance decreased, and SO2 in tumors tended to be lower than in breast tissue. In breast tissue, there was a negative correlation between µs' and the skin-to-chest wall distance, and µs' in tumors was higher than in breast tissue. Measurement of tHb in breast cancer by TRS was influenced by tumor thickness and depth. Although SO2 seemed lower and µs' was higher in breast cancer than in breast tissue, the skin-to-chest wall distance may have affected the measurements.

Hemodynamic Measurements of the Human Adult Head in Transmittance Mode by Near-Infrared Time-Resolved Spectroscopy.

Using a near-infrared time-resolved spectroscopy (TRS) system, we measured the human head in transmittance mode to obtain the optical properties and the hemodynamic changes of deep brain tissues in seven healthy adult volunteers during hyperventilation. For six out of seven volunteers, we obtained the optical signals with sufficient intensity within 10 sec. of sampling. We confirmed that it is possible to non-invasively measure the hemodynamic changes of the human head during hyperventilation, even in the transmittance measurements by the developed TRS system. These results showed that the level of deoxygenated hemoglobin was significantly increased, and the level of oxygenated and total hemoglobin and tissue oxygen saturation were also significantly decreased during hyperventilation. We expect that this TRS technique will be applied to clinical applications for measuring deep brain tissues and deep biological organs.

Effect of the chest wall on the measurement of hemoglobin concentrations by near-infrared time-resolved spectroscopy in normal breast and cancer.

BACKGROUND: Optical imaging and spectroscopy using near-infrared light have great potential in the assessment of tumor vasculature. We previously measured hemoglobin concentrations in breast cancer using a near-infrared time-resolved spectroscopy system. The purpose of the present study was to evaluate the effect of the chest wall on the measurement of hemoglobin concentrations in normal breast tissue and cancer. METHODS: We measured total hemoglobin (tHb) concentration in both cancer and contralateral normal breast using a near-infrared time-resolved spectroscopy system in 24 female patients with breast cancer. Patients were divided into two groups based on menopausal state. The skin-to-chest wall distance was determined using ultrasound images obtained with an ultrasound probe attached to the spectroscopy probe. RESULTS: The apparent tHb concentration of normal breast increased when the skin-to-chest wall distance was less than 20 mm. The tHb concentration in pre-menopausal patients was higher than that in post-menopausal patients. Although the concentration of tHb in cancer tissue was statistically higher than that in normal breast, the contralateral normal breast showed higher tHb concentration than cancer in 9 of 46 datasets. When the curves of tHb concentrations as a function of the skin-to-chest wall distance in normal breast were applied for pre- and post-menopausal patients separately, all the cancer lesions plotted above the curves. CONCLUSIONS: The skin-to-chest wall distance affected the measurement of tHb concentration of breast tissue by near-infrared time-resolved spectroscopy. The tHb concentration of breast cancer tissue was more precisely evaluated by considering the skin-to-chest wall distance.

Limb fitting for quadruple amputees: report of two cases of symmetrical peripheral gangrene caused by pneumococcal purpura fulminans.

BACKGROUND: We report our experiences of prosthetic fitting in quadruple amputees. Two patients underwent quadruple amputation after suffering from disseminated intravascular coagulation in conjunction with pneumococcemia with purpura fulminans. CASE DESCRIPTION AND METHODS: The first patient, a 52-year-old man, underwent bilateral transradial, left transtibial, and right transfemoral amputation, and the second patient, a 62-year-old man, underwent bilateral transradial and bilateral transfemoral amputation, both for symmetrical peripheral gangrene subsequent to septic shock. FINDINGS AND OUTCOMES: The amputations were accompanied by skin damage due to ischemic tissue changes both on the stumps and on the nose and/or lips. The combination of the intensive prosthetic rehabilitation program and supportive medical care led to completely independent functioning, including driving a car, with the use of four prosthetic limbs and a wheelchair in both cases. CONCLUSION: Early initiation of a multidisciplinary approach can properly address impairments and minimize future disability.

Hexameric helicase deconstructed: interplay of conformational changes and substrate coupling.

Hexameric helicases are molecular motor proteins that utilize energy obtained from ATP hydrolysis to translocate along and/or unwind nucleic acids. In this study, we investigate the dynamic behavior of the Simian Virus 40 hexameric helicase bound to DNA by performing molecular dynamics simulations employing a coarse-grained model. Our results elucidate the two most important molecular features of the helicase motion. First, the attractive interactions between the DNA-binding domain of the helicase and the DNA backbone are essential for the helicase to exhibit a unidirectional motion along the DNA strand. Second, the sequence of ATP binding at multiple binding pockets affects the helicase motion. Specifically, concerted ATP binding does not generate a unidirectional motion of the helicase. It is only when the binding of ATP occurs sequentially from one pocket to the next that the helicase moves unidirectionally along the DNA. Interestingly, in the reverse order of sequential ATP binding, the helicase also moves unidirectionally but in the opposite direction. These observations suggest that in nature ATP molecules must distinguish between different available ATP binding pockets of the hexameric helicase in order to function efficiently. To this end, simulations reveal that the binding of ATP in one pocket induces an opening of the next ATP-binding pocket and such an asymmetric deformation may coordinate the sequential ATP binding in a unidirectional manner. Overall, these findings may provide clues toward understanding the mechanism of substrate translocation in other motor proteins.

Response of biochemical markers of bone metabolism to exercise intensity in thoroughbred horses.

We studied the response of biochemical markers of bone metabolism to exercise intensity in horses. Four horses were walked on a mechanical walker for one week (pre-exercise). Then they performed low-speed exercise on a high-speed treadmill in the first week and medium-speed exercise in the second week and high-speed exercise in the third week of training. We measured two indices of bone resorption, serum hydroxyproline concentration and the urinary deoxypyridinoline/creatinine ratio, and serum osteocalcin (OC) concentration as an index of bone formation. Both indices of bone resorption gradually decreased during the experiment. Serum OC concentration did not change in the first week but was significantly lower in the second and the third weeks compared to in the pre-exercise period and in the first week. These results suggest that the low-speed exercise decreased bone resorption but did not affect bone formation, which possibly results in increasing bone mineral content and strengthening of bones. The high-speed exercise decreased bone formation and bone resorption, i.e., bone turnover was suppressed. The low-speed exercise may be preferable for increasing bone mineral content.

Influence of confinement on the fragility of antiplasticized and pure polymer films.

We investigate by molecular dynamics simulation how thin film confinement modifies the fragility of a model glass-forming liquid characterized previously in the bulk. Film confinement is found to reduce the relative fragility of the polymer fluid, leading to effects similar to simulations of the addition of an antiplasticizer additive. A reduction of fragility is not observed for the antiplasticized polymer film. These effects are interpreted in terms of variation in the string (cooperatively moving segments) concentration with film confinement and the addition of antiplasticizing additives.

Local mechanical properties of polymeric nanocomposites.

The inclusion of a nanoparticle into a polymer matrix is studied by efficient Monte Carlo simulations. The resulting structural changes in the melt and glass exhibit a strong dependence on the strength of the polymer attraction to the surface of the filler. The mechanical properties of the nanocomposite are analyzed in detail through a formalism that permits calculation of local elastic constants. The average shear and Young's modulus of the nanocomposite are higher than those of the pure polymer for neutral or attractive nanoparticles. For repulsive particles, these moduli are lower. Simulation of local properties reveals that a glassy layer is formed in the vicinity of the attractive filler, contributing to the increased strength of the composite material. In contrast, a region of negative moduli emerges around repulsive fillers, which provides a mechanism for frustration relief and a lowering of the glass transition temperature.

Isothermal stress and elasticity tensors for ions and point dipoles using Ewald summations.

The isothermal stress tensor and isothermal elasticity tensor for systems of point charges and of nonpolarizable point dipoles are derived from the strain derivatives of the free energy. For the case of point dipoles, it is shown that the angular dependence of the interaction potential gives rise to additional contributions to the stress and elasticity tensors not recognized previously.

Local dynamic mechanical properties in model free-standing polymer thin films.

High-frequency sinusoidal oscillations of a coarse-grained polymer model are used to calculate the local dynamic mechanical properties (DMPs) of free-standing polymer thin films. The storage modulus G(') and loss modulus G(") are examined as a function of position normal to the free surfaces. It is found that mechanically soft layers arise near the free surfaces of glassy thin films, and that their thickness becomes comparable to the entire film thickness as the temperature approaches the glass transition T(g). As a result, the overall stiffness of glassy thin films decreases with film thickness. It is also shown that two regions coexist in thin films just at the bulk T(g); a melt-like region (G(')G(")) in the middle of the film. Our findings on the existence of a heterogeneous distribution of DMPs in free-standing polymer thin films provide insights into recent experimental measurements of the mechanical properties of glassy polymer thin films.

Mechanical heterogeneities in model polymer glasses at small length scales.

Molecular simulations of a model, deeply quenched polymeric glass show that the elastic moduli become strongly inhomogeneous at length scales comprising several tens of monomers; these calculations reveal a broad distribution of local moduli, with regions of negative moduli coexisting within a matrix of positive moduli. It is shown that local moduli have the same physical meaning as that traditionally ascribed to moduli obtained from direct measurements of local constitutive behaviors of macroscopic samples.