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Inflammation is a complex biological response of the human body to external or internal stimuli, such as invading pathogens, defective cells, or irritating substances. One important indicator of inflammatory conditions or the progress of various diseases, such as cancer, cardiovascular diseases, neurological diseases, connective tissue diseases, sepsis, or Alzheimer's disease, is the concentration level of inflammatory biomarkers, including immunoglobulins, cytokines, and C-reactive protein (CRP). Since inflammatory biomarkers are highly correlated with each other, it is important to measure them simultaneously. To enable continuous and dynamic inflammatory biomarker detection, we utilized localized surface plasmon resonance (LSPR) to perform label-free molecule sensing. Since the LSPR sensing mechanism requires only a small sensing area with simplified optical setup, it can be easily integrated with a microfluidic device. To simplify reagent operation complexity, we developed an automated microfluidic control system to control reagent guiding and switching in the immunoassay with less manual processes and potential operation errors. Our results successfully demonstrated multiplex IgG, TNF-α, and CRP measurement with only 60 μL assay volume and 3.5 h assay time. In each test, 20 sensing spot measurements under four different reagent conditions can be performed. Overall, we envision that the LSPR sensor integrated automated microfluidic control system could perform rapid, multiplex, and multiparallel continuous inflammatory biomarker detection, which would be beneficial for various applications, such as immune status monitoring, diagnosis and prognosis of inflammatory diseases.

Glyoxal and methylglyoxal are oxoaldehydes derived from the degradation of glucose-protein conjugates and from lipid peroxidation, and they are also present in the environment. This study investigated the site-specific reaction of glyoxal and methylglyoxal with the amino acid residues on human hemoglobin using a shot-gun proteomic approach with nanoflow liquid chromatography/nanospray ionization tandem mass spectrometry (nanoLC-NSI/MS/MS). In human hemoglobin incubated with glyoxal, modification on 8 different sites, including lysine residues at α-Lys-11, α-Lys-16, α-Lys-56, β-Lys-17, β-Lys-66, β-Lys-144, and arginine residues at α-Arg-92 and β-Arg-30, was observed using a data-dependent scan. In methylglyoxal-treated hemoglobin, there were specific residues, namely, α-Arg-92, β-Lys-66, β-Arg-30, and β-Lys-144, forming carboxyethylation as well as the dehydrated product hydroimidazolone at α-Arg-92 and β-Arg-30. These lysine and arginine modifications were confirmed by accurate mass measurement and the MS(2) and MS(3) spectra. The most intensive signal of each modified peptide was used as the precursor ion to perform the product ion scan. The relative extent of modifications was semiquantified simultaneously relative to the native reference peptide by nanoLC-NSI/MS/MS under the selected reaction monitoring (SRM) mode. The extent of these modifications increased dose-dependently with increasing concentrations of glyoxal or methylglyoxal. Six out of the eight modifications induced by glyoxal and three out of the six modifications induced by methylglyoxal were detected in hemoglobin freshly isolated from human blood samples. The relative extent of modification of these post-translational modifications was quantified in poorly controlled type 2 diabetes mellitus patients (n = 20) and in nondiabetic control subjects (n = 21). The results show that the carboxymethylated peptides at α-Lys-16, α-Arg-92, β-Lys-17, β-Lys-66, and the peptide at α-Arg-92 with methylglyoxal-derived hydroimidazolone are significantly higher in diabetic patients than in normal individuals (p value

Health education is compulsory for patients with chronic and life-threatening disease, especially for those with diabetes mellitus (DM). This study aimed to examine the long-term effectiveness of the Diabetes Conversation Map Program (DCMP) among DM patients in Taiwan. A quasi-experimental research design using convenience sampling and nonrandom group assignment was applied to recruit 95 type 2 diabetic subjects from a hospital in Taiwan. In addition to routine care, the experiment group (n = 49) received 7 sessions of DCMP that delivered over 2 months, while the control group (n = 46) received only routine care during the same period. We conducted structured questionnaire survey and reviewed medical record at 3 time points (before DCMP, 3 days after DCMP, and 3 months after DCMP completion) to collect the effectiveness data. The effectiveness was determined using the generalized estimating equation model. We found that improvements in the body mass index, blood glucose, glycated hemoglobin, self-monitoring of blood glucose, and diabetic health literacy in the DCMP group compared with controls (all P values

Objective: Recent case reports suggest that zolpidem usage may be associated with infection events. The aim of this study was to determine the risk of infection events in patients with sleep disturbance taking zolpidem in a full 3-year follow-up study. Methods: A total of 17474 subjects with a diagnosis of sleep disturbance in 2002 and 2003 were identified, of whom 5882 had used zolpidem after recruitment. A Cox proportional hazard model was used to estimate the 3-year infection event-free rates for the patients using zolpidem and those not using zolpidem after adjusting for confounding factors. To maximize case ascertainment, only patients hospitalized for infection events were included. Results: A total of 646 patients had had infection events, 331 (5.63%) of whom had been taking zolpidem and 315 (2.71%) had not. Zolpidem usage increased the risk of infection events. After adjustments for gender, age, co-morbidities, and other medications, patients using zolpidem with cDDD 1-28, 29-84, and >84 had hazard ratios of 1.67 (95% CI, 1.32e2.11), 1.91 (95% CI, 1.47e2.49) and 1.62 (95% CI, 1.32e1.98) respectively, compared with patients who did not use zolpidem. Conclusions: Zolpidem increased the risk of infection events in sleep disturbance patients. This increased risk of infection should be explained to sleep disturbance patients, and prescriptions of zolpidem to chronic insomnia patients should be restricted.

Objective The aim of this study was to evaluate the results of thyroid fine needle aspiration cytology (FNAC) and identify reasons for discrepancies between the cytological and histological diagnoses in our institution. Materials and Methods We evaluated the results of 1064 FNACs obtained from 737 patients, of which 98 underwent subsequent thyroid surgery. Results Histological analyses revealed that benign diagnoses based on FNAC were correct in 76 of the 80 benign cases (95%), with four cases being underdiagnosed (false negatives). Two of the four cases were due to incidental findings of papillary microcarcinomas. The third case was due to a cytologic sampling error and the fourth was due to cytologic underdiagnosis. Furthermore, malignant diagnoses based on FNAC were correct in 17 of the 18 malignant cases (94%), with one case being over-diagnosed (false positive) due to over-interpretation of Hurthle cells as carcinomatous cells. The accuracy, positive predictive value, and negative predictive value were 94.9%, 94.4%, and 95.0%, respectively. Conclusion Overall, FNAC is a sensitive and specific method for the pre-operative screening of thyroid nodules. However, due to limitations under some specific circumstances, such as papillary microcarcinoma, bizarre Hurthle cells, follicular neoplasm and technical difficulty during the aspiration, the management of thyroid nodules must not only depend on the results of FNAC but should also be correlated with clinical findings before surgical intervention.

Parameters of glucose dynamics recorded by the continuous glucose monitoring system (CGMS) could help in the control of glycemic fluctuations, which is important in diabetes management. Multiscale entropy (MSE) analysis has recently been developed to measure the complexity of physical and physiological time sequences. A reduced MSE complexity index indicates the increased repetition patterns of the time sequence, and, thus, a decreased complexity in this system. No study has investigated the MSE analysis of glucose dynamics in diabetes. This study was designed to compare the complexity of glucose dynamics between the diabetic patients ( n = 17) and the control subjects ( n = 13), who were matched for sex, age, and body mass index via MSE analysis using the CGMS data. Compared with the control subjects, the diabetic patients revealed a significant increase ( P < 0.001) in the mean (diabetic patients 166.0 ± 10.4 vs. control subjects 93.3 ± 1.5 mg/dl), the standard deviation (51.7 ± 4.3 vs. 11.1 ± 0.5 mg/dl), and the mean amplitude of glycemic excursions (127.0 ± 9.2 vs. 27.7 ± 1.3 mg/dl) of the glucose levels; and a significant decrease ( P < 0.001) in the MSE complexity index (5.09 ± 0.23 vs. 7.38 ± 0.28). In conclusion, the complexity of glucose dynamics is decreased in diabetes. This finding implies the reactivity of glucoregulation is impaired in the diabetic patients. Such impairment presenting as an increased regularity of glycemic fluctuating pattern could be detected by MSE analysis. Thus, the MSE complexity index could potentially be used as a biomarker in the monitoring of diabetes.

This paper reviews the prospects of thin-film silicon-on-sapphire (TFSOS) CMOS technology in microwave applications in the 1-5 GHz regime and beyond and presents the first demonstration of microwave integrated circuits based on this technology, MOSFET's optimized for microwave use, with 0.5-/spl mu/m optically defined gate lengths and a T-gate structure, have f/sub t/ values of 25 GHz (14 GHz) and f/sub max/ values of 66 GHz (41 GHz) for n-channel (p-channel) devices and have noise figure values below 1 db at 2 GHz, some of the best reported performance characteristics of any silicon-based MOSFET's to date. On-chip spiral inductors exhibit quality factors above ten. Circuit performance compares favorably with that of other CMOS-based technologies and approach performance levels similar to those obtained by silicon bipolar technologies. The results demonstrate the significant potential of this technology for microwave applications.

BACKGROUND: Statins reduce cardiovascular risks but increase the risk of new-onset diabetes (NOD). The aim of this study is to determine what effect, if any, statins have on the risk of NOD events in a population-based case-control study. An evaluation of the relationship between age and statin-exposure on NOD risks was further examined in a female Asian population. METHOD: In a nationwide case-controlled study, the authors assessed 1065 female NOD patients and 10650 controls with matching ages, genders and physician visit dates. The impact of statin-exposure on NOD was examined through multiple logistic regression models. Subgroup analysis for exploring the risk of NOD and statin-exposure in different age groups was performed. RESULTS: Statin-exposure was statistically significantly associated with increased new-onset diabetes risks using multivariate analysis. Interaction effect between age and statin-exposure on NOD risk was noted. For atorvastatin, the risk of cDDDs>60 was highest among the 55-64 year-olds (adjusted odds ratio [OR], 8.0; 95% confidence interval [CI], 2.57-24.90). For rosuvastatin, the risk of cDDDs>60 was highest among the 40-54 year-olds (adjusted OR, 14.8; 95% CI, 2.27-96.15). For simvastatin, the risk of cDDDs>60 was highest among the 55-64 year-olds (adjusted OR, 15.8; 95% CI, 5.77-43.26). For pravastatin, the risk of cDDDs>60 was highest among the 55-64 year-olds (adjusted OR, 14.0; 95% CI, 1.56-125.18). CONCLUSIONS: This population-based study found that statin use is associated with an increased risk of NOD in women. The risk of statin-related NOD was more evident for women aged 40-64 years compared to women aged 65 or more, and was cumulative-dose dependent. The use of statins should always be determined by weighing the clinical benefits and potential risks for NOD, and the patients should be continuously monitored for adverse effects.

Measured and modelled characteristics are reported for a new geometry for contacting AlGaAs-GaAs heterojunction bipolar transistors (HBTs), which provides lower thermal resistance and lower emitter inductance than does the conventional approach. Common-emitter connected HBTs are mounted emitter side down on a metal heatsink, which also serves as electrical ground. Connections to the base and collector are made with substrate vias that extend through the GaAs substrate from the backside of the wafer. This configuration was measured to have values of thermal resistance as small as 0.23 K/mW for a 132 /spl mu/m/sup 2/ emitter area HBT, in agreement with simulations. An output power per unit emitter area of 2.9 mW//spl mu/m/sup 2/ (total power of 370 mW) at 9 GHz was observed.