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Manipulation and precise delivery of optical energies in the regions of interest within specimens require different strategies. Hence, proper control of input beam parameters is a prerequisite. One of the prominent methods is metasurface optics, capable of crafting properties of light at nanoscales. Here, the generation of an abrupt autofocusing (AAF) beam by a nanophotonic metasurface for biomedical applications is demonstrated. Fluorescence guided laser microprofiling of mouse cardiac samples is experimentally investigated, using the AAF beam to deliver optical energy selectively to specific locations. In addition, photocoagulation of ex vivo swine skin tissue is performed and observed through optical coherence tomography. The results show great potentials for integrating metasurface optics to realize miniature laser surgery instruments for wide applications in biomedicine.

Author(s): Chen, Jeon-Hor; Bahri, Shadfar; Mehta, Rita S; Carpenter, Philip M; McLaren, Christine E; Chen, Wen-Pin; Fwu, Peter T; Hsiang, David JB; Lane, Karen T; Butler, John A; Su, Min-Ying | Abstract: Background and objectivesTo investigate accuracy of magnetic resonance imaging (MRI) for measuring residual tumor size in breast cancer patients receiving neoadjuvant chemotherapy (NAC).MethodsNinety-eight patients were studied. Several MRI were performed during NAC for response monitoring, and the residual tumor size was measured on last MRI after completing NAC. Covariates, including age, tumor characteristics, biomarkers, NAC regimens, MRI scanners, and time from last MRI to operation, were analyzed. Univariate and Multivariate linear regression models were used to determine the predictive value of these covariates for MRI-pathology size discrepancy as the outcome measure.ResultsThe mean (±SD) of the absolute difference between MRI and pathological residual tumor size was 1.0 ± 2.0 cm (range, 0-14 cm). Univariate regression analysis showed tumor type, morphology, HR status, HER2 status, and MRI scanner (1.5 T or 3.0 T) were significantly associated with MRI-pathology size discrepancy (all P l 0.05). Multivariate regression analyses demonstrated that only tumor type, tumor morphology, and biomarker status considering both HR and HER-2 were independent predictors (P = 0.0014, 0.0032, and 0.0286, respectively).ConclusionThe accuracy of MRI in evaluating residual tumor size depends on tumor type, morphology, and biomarker status. The information may be considered in surgical planning for NAC patients.

The aim of this study was to evaluate the change of breast density in the normal breast of patients receiving neoadjuvant chemotherapy (NAC). Forty-four breast cancer patients were studied. MRI acquisition was performed before treatment (baseline), and 4 and 12 weeks after treatment. A computer-algorithm-based program was used to segment breast tissue and calculate breast volume (BV), fibroglandular tissue volume (FV), and percent density (PD) (the ratio of FV over BV × 100%). The reduction of FV and PD after treatment was compared with baseline using paired t-tests with a Bonferroni-Holm correction. The association of density reduction with age was analyzed. FV and PD after NAC showed significant decreases compared with the baseline. FV was 110.0 ml (67.2, 189.8) (geometric mean (interquartile range)) at baseline, 104.3 ml (66.6, 164.4) after 4 weeks (p < 0.0001), and 94.7 ml (60.2, 144.4) after 12 weeks (comparison with baseline, p < 0.0001; comparison with 4 weeks, p = 0.016). PD was 11.2% (6.4, 22.4) at baseline, 10.6% (6.6, 20.3) after 4 weeks (p < 0.0001), and 9.7% (6.2, 17.9) after 12 weeks (comparison with baseline, p = 0.0001; comparison with 4 weeks, p = 0.018). Younger patients tended to show a higher density reduction, but overall correlation with age was only moderate (r = 0.28 for FV, p = 0.07, and r = 0.52 for PD, p = 0.0003). Our study showed that breast density measured from MR images acquired at 3T MR can be accurately quantified using a robust computer-aided algorithm based on non-parametric non-uniformity normalization (N3) and an adaptive fuzzy C-means algorithm. Similar to doxorubicin and cyclophosphamide regimens, the taxane-based NAC regimen also caused density atrophy in the normal breast and showed reduction in FV and PD. The effect of breast density reduction was age related and duration related.

While recent data have supported the capacity for a neonatal heart to undergo cardiomyogenesis, it is unclear whether these new cardiomyocytes arise from an immature cardiomyoblast population or from the division of mature cardiomyocytes. By following the expression of enhanced Green Fluorescent Protein (eGFP) in an Nkx2.5 enhancer-eGFP transgenic mice, we have identified a population of immature cells that can undergo cardiomyogenic as well as smooth muscle cell differentiation in the neonatal heart. Here, we examined growth factors and small molecule regulators that potentially regulate the proliferation and cardiomyogenic versus smooth muscle cell differentiation of neonatal Nkx2.5-GFP (+) cells in vitro. We found that A83-01 (A83), an inhibitor of TGF-βRI, was able to induce an expansion of neonatal Nkx2.5-eGFP (+) cells. In addition, the ability of A83 to expand eGFP (+) cells in culture was dependent on signalling from the mitogen-activated protein kinase kinase (MEK) as treatment with a MEK inhibitor, PD0325901, abolished this effect. On the other hand, activation of neonatal Nkx2.5-eGFP (+) cells with TGF-β1, but not activin A nor BMP2, led to smooth muscle cell differentiation, an effect that can be reversed by treatment with A83. In summary, small molecule inhibition of TGF-β signalling may be a promising strategy to induce the expansion of a rare population of postnatal cardiomyoblasts.

Background and purpose: Piceatannol is more potent than resveratrol in free radical scavenging in association with antiarrhythmic and cardioprotective activities in ischaemic-reperfused rat hearts. The present study aimed to investigate the antiarrhythmic efficacy and the underlying ionic mechanisms of piceatannol in rat hearts. Experimental approach: Action potentials and membrane currents were recorded by the whole-cell patch clamp techniques. Fluo-3 fluorimetry was used to measure cellular Ca2+ transients. Antiarrhythmic activity was examined from isolated Langendorff-perfused rat hearts. Key results: In rat ventricular cells, piceatannol (3–30 µmol·L−1) prolonged the action potential durations (APDs) and decreased the maximal rate of upstroke (Vmax) without altering Ca2+ transients. Piceatannol decreased peak INa and slowed INa inactivation, rather than induced a persistent non-inactivating current, which could be reverted by lidocaine. Resveratrol (100 µmol·L−1) decreased peak INa without slowing INa inactivation. The inhibition of peak INa or Vmax was associated with a negative shift of the voltage-dependent steady-state INa inactivation curve without altering the activation threshold. At the concentrations more than 30 µmol·L−1, piceatannol could inhibit ICa,L, Ito, IKr, Ca2+ transients and Na+-Ca2+ exchange except IK1. Piceatannol (1–10 µmol·L−1) exerted antiarrhythmic activity in isolated rat hearts subjected to ischaemia-reperfusion injury. Conclusions and implications: The additional hydroxyl group on resveratrol makes piceatannol possessing more potent in INa inhibition and uniquely slowing INa inactivation, which may contribute to its antiarrhythmic actions at low concentrations less than 10 µmol·L−1.

Objective To evaluate the American College of Rheumatology (ACR) starter set of quality measures for rheumatoid arthritis (RA) in an actual patient cohort that preceded publication of the quality measures. Methods We retrospectively applied the 2006 ACR quality criteria to a prospectively studied cohort of 568 patients with RA treated by 1,932 unique physicians including 255 different rheumatologists between the years 1999 and 2003. Data on performance were obtained from self-report surveys and medical record review within 12 months. Results At least 1 joint examination was performed in 98% of patients. Patient and physician global assessments were reported for 79% and 74% of patients, respectively. A total of 85% of patients received disease-modifying antirheumatic drugs (DMARDs). DMARD adjustments were made for 50% of patients in whom increasing disease activity was noted at least once and for 64% of patients in whom increasing disease activity was noted during 2 (of 4) 3-month periods within the year. Compared with self-report surveys, medical records substantially underreported performance on quality measures. Conclusion The ACR-endorsed quality measures for RA can be assessed using available data sources. When both self-report and medical record data are used, adherence rates, designed to serve as minimum standards of care, were moderate or high for most measures. Prior to using indicators to compare quality across groups, specific strategies for operationalizing measures and for using accurate data sources to assess adherence to the measures should be defined.

The type VI adenylyl cyclase (AC6), one of the nine different isotypes of membrane-bound adenylyl cyclases (ACs), is known to produce beneficial effects on failing hearts. AC6 is a major AC isoform...

Objective. To construct quality measures with measurement validity and meaning for clinicians. Methods. We conducted a prospective cohort study of rates of change in disease-modifying antirheumatic drug (DMARD) and/or systemic corticosteroid drug or dose for 568 patients with rheumatoid arthritis (RA) across 6,159 clinical encounters within 12 months to examine how changes in clinical specifications change adherence. Results. Rates of DMARD change were sensitive to specifications regarding the intensity of disease activity (severe or moderate), duration of specified disease activity, and length of the observation period. Over 12 months, the proportions of 377 patients with severe disease activity observed for 1-month, 2-month, and 3-month time blocks who had a change in DMARD drug or dose were 36%, 57%, and 74%, respectively. Over 12 months, a change in DMARD drug or dose was observed for 44%, 50%, and 68% of 377 patients with severe disease within 3 months, 6 months, and 12 months, respectively, of the patient meeting criteria for severe disease activity. A change in DMARD drug or dose was observed for 21%, 23%, and 34% of 149 patients with moderate disease activity within 3, 6, and 12 months, respectively, of the patient meeting criteria for moderate disease activity. Conclusion. Rates of pharmacologic interventions for patients with moderate and severe RA disease activity vary substantially by intensity and duration of disease activity and by duration of period for observing change. Lack of precision in explicit process criteria could substantially mislead comparisons of quality of care across comparison groups.

The SF-12 health survey encompasses all eight SF-36 scales (physical function, role-physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) and can be administered in 2–3 minutes (Ware et al. 1993; Ware, Kosinski, and Keller 1995). Four of the eight health concepts are measured using two items each and the other four concepts are measured using one item each. Previous studies have found that the SF-12 can reproduce more than 90 percent of the variance in both the physical component summary (PCS) and mental component summary (MCS) scores of the SF-36 (Ware, Kosinski, and Keller 1995; Ware et al. 2002). Item missing data is not uncommon in self-report surveys. The standard SF-12 scoring algorithm, however, is a weighted sum of the SF-12 items and requires answers to all 12 individual items in order to calculate PCS and MCS summary scores. However, missing items are likely to occur in any study that collects data by self-administration. Studies have shown that among patients with missing SF-12 items, approximately 50 percent have missing data on only one of the 12 items (Ware et al. 2002). Yet, by using the standard SF-12 scoring algorithm, even one missing item will yield missing data on the SF-12 PCS and MCS. The loss of observations because of missing SF-12 items can reduce analytical power, increase variation in parameter estimates, and potentially lead to bias, particularly when the SF-12 is the primary outcome of interest in a study. Therefore, an algorithm that can efficiently and accurately estimate PCS and MCS scores with partially missing SF-12 data would be valuable to researchers. Since the SF-12 PCS and MCS scores are directly weighted functions of SF-12 items, the amount of missing data will have a significant impact on the imputed value. Hence, the imputation algorithm may need to apply different models according to the degree of “missingness.” As the number of missing SF-12 items increases, the available information and predicting power from SF-12 items diminishes. When the number of missing SF-12 items reaches a certain level, the available SF-12 items may no longer carry sufficient information to produce accurate parameter estimates of SF-12 PCS and MCS scores. In these situations, additional patient information may help in estimation. We applied a multi-pattern regression-based algorithm for imputing SF-12 PCS and MCS scores. This algorithm fits different imputation models according to the amount of SF-12 information missing. These imputation models are either a function of the available SF-12 items alone, or are a function of the available SF-12 items plus additional patient characteristics. Through simulation analyses using baseline and follow-up data 2 years later, we have evaluated and validated the imputation algorithm.

Author(s): Kahn, Katherine L; Liu, Honghu; Adams, John L; Chen, Wen-Pin; Tisnado, Diana M; Carlisle, David M; Hays, Ron D; Mangione, Carol M; Damberg, Cheryl L | Abstract: ObjectiveTo illustrate, using empirical data, methodological challenges associated with patient responses to longitudinal surveys regarding the quality of process of care and health status, including overall response rate, differential response rate, and stability of responses with time.Data sources/study settingPrimary patient self-report data were collected from 30,308 patients in 1996 and 13,438 patients in 1998 as part of a two-year longitudinal study of quality of care and health status of patients receiving care delivered by 63 physician organizations (physician groups) across three West Coast states.Study designWe analyzed longitudinal, observational data collected by Pacific Business Group on Health (PBGH) from patients aged 18-70 using a four-page survey in 1996 and a similar survey in 1998 to assess health status, satisfaction, use of services, and self-reported process of care. A subset of patients with self-reported chronic disease in the 1996 study received an enriched survey in 1998 to more fully detail processes of care for patients with chronic disease.Data collection/extraction methodsWe measured response rate overall and separately for patients with chronic disease. Logistic regression was used to assess the impact of 1996 predictors on response to the follow-up 1998 survey. We compared process of care scores without and with nonresponse weights. Additionally, we measured stability of patient responses over time using percent agreement and kappa statistics, and examined rates of gender inconsistencies reported across the 1996 and 1998 surveys.Principal findingsIn 1998, response rates were 54 percent overall and 63 percent for patients with chronic disease. Patient demographics, health status, use of services, and satisfaction with care in 1996 were all significant predictors of response in 1998, highlighting the importance of analytic strategies (i.e., application of nonresponse weights) to minimize bias in estimates of care and outcomes associated with longitudinal quality of care and health outcome analyses. Process of care scores weighted for nonresponse differed from unweighted scores (pl.001). Stability of responses across time was moderate, but varied by survey item from fair to excellent.ConclusionsLongitudinal analyses involving the collection of data from the same patients at two points in time provide opportunities for analysis of relationships between process and outcomes of care that cannot occur with cross-sectional data. We present empirical results documenting the scope of the problems and discuss options for responding to these challenges. With increasing emphasis in the United States on quality reporting and use of financial incentives for quality in the health care market, it is important to identify and address methodological challenges that potentially threaten the validity of quality-of-care assessments.

The cadherin/catenin complex plays a key role in the initiation of cell-cell recognition, and adhesion, and the elaboration of structural and functional organization in multicellular tissues and organs. It is associated with tumor metastasis and also acts as an "invasion suppressor" of cancer cells. Nasopharyngeal carcinoma (NPC) is notorious for its highly metastatic nature. The expression of the E-cadherin/catenin complex is down-regulated in NPC tumor specimens. To obtain better insight into the intercellular adhesive property of NPC cells, we used immunofluorescence microscopy, immunoprecipitation, and immunoblot analysis to examine the expression of the classical cadherins and beta-catenin in a NPC cell line, TW-039. The results demonstrate a change in the distribution of E-cadherin from cytosolic flakes to cell-cell contacts with increasing time in culture. Between days 1 and 5 after plating, the detergent-insoluble fraction of E-cadherin increased from 20% to 37% of total E-cadherin, and that for P-cadherin increased from 33% to 40%. By contrast, the values for beta-catenin remained unchanged (26% and 25%). Both immunofluorescence and immunoblot studies suggested that P-cadherin may be involved in pioneer contact adhesion of TW-039 cells. Interestingly, E-, P-, and N-cadherin are co-expressed in this cell line. Immunoprecipitation studies also showed that other members of the cadherin family may be involved in the contact adhesion of TW-039 cells.

The antiarrhythmic potential of acrophyllidine, a natural furoquinoline alkaloid isolated from the plant, Acronychia halophylla, has been documented. In the present study, the electrophysiological effects of acrophyllidine in Langendorff-perfused rat hearts and isolated cardiomyocytes were examined. In isolated rat heart (constant pressure), acrophyllidine suppressed ischemia/reperfusion-induced polymorphic ventricular tachyarrhythmias with an EC 50 value of 4.4 μM. In the perfused whole-heart model (constant flow), acrophyllidine increased the atrioventricular and His-Purkinje system conduction intervals, ventricular repolarization time (VRT), and basic cycle length and also prolonged the refractory periods of the AV node, His-Purkinje system and ventricle. In isolated rat ventricular myocytes, acrophyllidine prolonged the action potential duration (APD) and decreased both the maximal upstroke velocity of depolarization (V max ) and action potential amplitude in a concentration-dependent manner. Whole-cell voltage clamp studies show that acrophyllidine blocked the Na + channel (IC 50 = 3.6 μM) with a negative-shift of its voltage-dependent steady-state inactivation curve and slowing of its recovery from inactivation. Similarly, Ca 2+ inward current (I Ca ) was inhibited but to a lesser extent. Acrophyllidine also suppressed the transient outward (I to ) (IC 50 equals; 4.5 μM) and the steady-state outward K + current (I SS ) (IC 50 = 3.4 μM). The inhibition of I to was associated with an acceleration of its rate of inactivation. Additionally, acrophyllidine suppressed I to in a time-dependent manner and caused a negative-shift of the steady-state inactivation curve and a slowed rate of recovery from inactivation. It is concluded that acrophyllidine blocks Na +, I to and I SS channels and in similar concentrations partly blocks Ca 2+ channel. These changes alter the electrophysiological properties of the conduction system and may be responsible for the termination of the ischaemia/ reperfusion induced ventricular arrhythmias.

Taxol affects microtubule dynamics by promoting microtubule assembly. To obtain a better insight into possible cross-talk between the microtubule- and actin-based cytoskeletons, we studied the short-term effects of Taxol treatment on the expression of actin and the E-cadherin/catenin complex in the nasopharyngeal carcinoma cell line TW-039 using immunofluorescence, immunoprecipitation, and immunoblotting methods. Morphologic changes in actin filaments, including ventral actin clumps and perijunctional actin blebs, were seen at Taxol concentrations > or =1 microM. Levels of detergent-soluble E-cadherin fell to 53% or 58% compared to controls in cells treated, respectively, with 1 or 5 microM Taxol, while levels of detergent-soluble beta-catenin fell to 76% or 74%. Levels of the detergent-soluble pool of alpha- and gamma-catenin and the detergent-insoluble pool of the E-cadherin/catenin complex were unchanged by Taxol treatment and no significant difference was seen in the levels of adenomatous polyposis coli or glycogen synthase-3beta or tyrosine phosphorylation patterns. These results suggest that modulation of microtubule dynamics by Taxol may have effects on the expression of actin and the cytosolic E-cadherin and beta-catenin in nasopharyngeal carcinoma cells through pathways not involving the phosphorylation of beta-catenin.

The morphology of segmented polyurethane (PU) elastomers was studied by means of ESR at various temperatures ranging from 100K-450K. The PU's were based on 4,4'-diphenylmethane diisocyanate (MDI), poly (oxytetramethylene) glycols (PTMO) and hydroxyl-terminated random compolymers of tetrahydrofuran and 3-methyl-tetrahydrofuran (THF/Me-THF). Purified 1,4-butanediol (BD) was used as a chain extender. The nitroxide probe, 4-hydroxy-2-2',6-6'-tetramethylpiperidine-1-oxyl (TEMPOL), was used to label the polyurethanes by reaction with an NCO group of MDI. Analysis of the electron spin resonance (ESR) spectra suggested that the label situates at heterogeneous sites, which means that a two-phase domain is present. The morphologies at 300K and 400K were compared. It was found from ESR spectra that polyurethanes made from soft segments having higher MW exhibited greater phase separation at 300K than their corresponding elastomers made from lower MW soft segments. However, at 400K the more isotropic ESR spectra for the PUs containing higher MW soft segments suggested that the PUs were more mobile than their analogs having lower MW soft segments. The introduction of 3-methyl side groups decreased the phase mixing at 400K due to steric hindrance.

The objective of this study was to develop a process for the production of both high-fructose rice syrup and high-protein rice flour from broken rice. The rice flour was obtained from broken rice by using either a dry or wet milling method. The glucose produced from the slurry of various raw materials by treating with α-amylase and glucoamylase was compared. Results indicated that cassava and corn starch were better raw materials than rice flour. However, the filtered residue of liquefied rice slurry could be recovered as high-protein rice flour. The particle size of rice flour had a small effect on the glucose yield. The orthogonal-array table (L27) method of experimental design was employed to determine optimum conditions for liquefaction. The glucose yield based on starch was 90.8±3.6% under the following optimum conditions α-amylase, 0.12%; rice flour, 20%; temperature, 96°C; time, 90 min. The filtrate from liquefied rice slurry was saccharified at 60°C with three different concentrations of glucoamylase. The higher the enzyme concentration, the shorter the time required to reach the maximum yield. After saccharification, the glucose solution was decolourised, desalted and concentrated to 40% d.s. and then isomerised to fructose at 60°C under continuous operation by using immobilised glucose isomerase packed in a column. The isomerised syrup was then purified and concentrated to 71% d.s. The final high-fructose rice syrup contained 50% glucose, 42% fructose and 3% maltose. After liquefaction, the rice slurry was centrifuged and the precipitate was dried by either spray or drum drying. The composition of these two high-protein rice flours was almost the same and the protein content was about three times as high as the raw material. There were significant differences in surface structure of rice flour and high-protein rice flours, as observed by the scanning electron microscope.

Addition of acetaldehyde to strawberry juice caused an increase in colour density and decrease in anthocyanin content on storage. When both acetaldehyde and catechin were added, these changes were intensified. However, addition of catechin alone did not affect colour density. The results indicated that an increase in colour density required the simultaneous presence of anthocyanins, acetaldehyde and catechin. Big differences in colour measured by Hunter colorimeter were also obtained between strawberry juices with and without acetaldehyde.