Rapid quasi-periodic oscillations in the relativistic jet of BL Lacertae.

Blazars are active galactic nuclei (AGN) with relativistic jets whose non-thermal radiation is extremely variable on various timescales1-3. This variability seems mostly random, although some quasi-periodic oscillations (QPOs), implying systematic processes, have been reported in blazars and other AGN. QPOs with timescales of days or hours are especially rare4 in AGN and their nature is highly debated, explained by emitting plasma moving helically inside the jet5, plasma instabilities6,7 or orbital motion in an accretion disc7,8. Here we report results of intense optical and γ-ray flux monitoring of BL Lacertae (BL Lac) during a dramatic outburst in 2020 (ref. 9). BL Lac, the prototype of a subclass of blazars10, is powered by a 1.7 × 108 MSun (ref. 11) black hole in an elliptical galaxy (distance = 313 megaparsecs (ref. 12)). Our observations show QPOs of optical flux and linear polarization, and γ-ray flux, with cycles as short as approximately 13 h during the highest state of the outburst. The QPO properties match the expectations of current-driven kink instabilities6 near a recollimation shock about 5 parsecs (pc) from the black hole in the wake of an apparent superluminal feature moving down the jet. Such a kink is apparent in a microwave Very Long Baseline Array (VLBA) image.

Gemcitabine combined with cisplatin vs. taxane, cisplatin, and fluorouracil in the treatment of locally advanced nasopharyngeal carcinoma: a retrospective case-control study.

OBJECTIVE: Reports of the efficacy of induction chemotherapy (IC) combined with concurrent chemoradiotherapy (CCRT) on locoregionally advanced nasopharyngeal carcinoma (NPC) are scarce. This study aimed to compare the clinical outcomes of the GP (gemcitabine plus cisplatin) regimen and the TPF (taxane, cisplatin and 5-FU) regimen combined with CCRT in patients with NPC. PATIENTS AND METHODS: This study retrospectively analyzed 827 patients with advanced NPC who received IC combined with CCRT in People's Hospital of Rizhao, China from January 2006 to June 2012. The propensity score method was used to reduce the effects of the observed confounding between the GP and TPF groups. Study end points were disease-free survival (DFS) and overall survival (OS). In total, 694 patients received GP or TPF as the IC treatment program. Propensity score matching identified 166 patients in each cohort. RESULTS: The 5-year OS and DFS rates of the entire cohort were 83.5% and 80.9%, respectively. GP was associated with a significantly improved 5 year OS (87.4% vs. 79.2%, p< 0.001), and DFS (86.2% vs. 78.5%, p< 0.001) rates compared with the TPF group. In the PSM (propensity score-matching) cohort, the GP group showed a significantly better OS (HR, 1.842, 95% CI:1.627-2.588; p= 0.011), and DFS (HR, 1.904, 95% CI: 1.742-2.737; p= 0.004) compared with the TPF group in multivariable analyses. The prevalence of acute adverse events of neutropenia and leukopenia were higher in severe (grade 3-4) adverse blood events in the TPF group (p<0.05). Thrombocytopenia had more adverse reactions in the GP group (p<0.05). The main non-hemotoxicities were nausea and vomiting, while the TPF group was slightly higher (p=0.031). CONCLUSIONS: The clinical efficacy of the GP regimen combined with CCRT for the treatment of locoregionally advanced NPC may be better than that of the TPF regimen.

Blazar spectral variability as explained by a twisted inhomogeneous jet.

Blazars are active galactic nuclei, which are powerful sources of radiation whose central engine is located in the core of the host galaxy. Blazar emission is dominated by non-thermal radiation from a jet that moves relativistically towards us, and therefore undergoes Doppler beaming. This beaming causes flux enhancement and contraction of the variability timescales, so that most blazars appear as luminous sources characterized by noticeable and fast changes in brightness at all frequencies. The mechanism that produces this unpredictable variability is under debate, but proposed mechanisms include injection, acceleration and cooling of particles, with possible intervention of shock waves or turbulence. Changes in the viewing angle of the observed emitting knots or jet regions have also been suggested as an explanation of flaring events and can also explain specific properties of blazar emission, such as intra-day variability, quasi-periodicity and the delay of radio flux variations relative to optical changes. Such a geometric interpretation, however, is not universally accepted because alternative explanations based on changes in physical conditions-such as the size and speed of the emitting zone, the magnetic field, the number of emitting particles and their energy distribution-can explain snapshots of the spectral behaviour of blazars in many cases. Here we report the results of optical-to-radio-wavelength monitoring of the blazar CTA 102 and show that the observed long-term trends of the flux and spectral variability are best explained by an inhomogeneous, curved jet that undergoes changes in orientation over time. We propose that magnetohydrodynamic instabilities or rotation of the twisted jet cause different jet regions to change their orientation and hence their relative Doppler factors. In particular, the extreme optical outburst of 2016-2017 (brightness increase of six magnitudes) occurred when the corresponding emitting region had a small viewing angle. The agreement between observations and theoretical predictions can be seen as further validation of the relativistic beaming theory.

Fiber inline Mach-Zehnder interferometer based on femtosecond laser inscribed waveguides.

A new type of Mach-Zehnder interferometer device based on in-fiber optical waveguides, fabricated by direct femtosecond laser pulse inscription in a single-mode fiber has been demonstrated and successfully employed for temperature and strain measurement. The in-fiber waveguide can couple the light out from the fiber core and guide it along the cladding region before directing it back into the fiber core. Such an inner structured interferometer device is compact and robust, can be constructed in a flexible and precisely controlled manner, and hence is expected to have many potential applications.

Multimode fiber tip Fabry-Perot cavity for highly sensitive pressure measurement.

We demonstrate an optical Fabry-Perot interferometer fiber tip sensor based on an etched end of multimode fiber filled with ultraviolet adhesive. The fiber device is miniature (with diameter of less than 60 µm), robust and low cost, in a convenient reflection mode of operation, and has a very high gas pressure sensitivity of -40.94 nm/MPa, a large temperature sensitivity of 213 pm/°C within the range from 55 to 85 °C, and a relatively low temperature cross-sensitivity of 5.2 kPa/°C. This device has a high potential in monitoring environment of high pressure.

PROFEAT Update: A Protein Features Web Server with Added Facility to Compute Network Descriptors for Studying Omics-Derived Networks.

The studies of biological, disease, and pharmacological networks are facilitated by the systems-level investigations using computational tools. In particular, the network descriptors developed in other disciplines have found increasing applications in the study of the protein, gene regulatory, metabolic, disease, and drug-targeted networks. Facilities are provided by the public web servers for computing network descriptors, but many descriptors are not covered, including those used or useful for biological studies. We upgraded the PROFEAT web server http://bidd2.nus.edu.sg/cgi-bin/profeat2016/main.cgi for computing up to 329 network descriptors and protein-protein interaction descriptors. PROFEAT network descriptors comprehensively describe the topological and connectivity characteristics of unweighted (uniform binding constants and molecular levels), edge-weighted (varying binding constants), node-weighted (varying molecular levels), edge-node-weighted (varying binding constants and molecular levels), and directed (oriented processes) networks. The usefulness of the network descriptors is illustrated by the literature-reported studies of the biological networks derived from the genome, interactome, transcriptome, metabolome, and diseasome profiles.

Crescent shaped Fabry-Perot fiber cavity for ultra-sensitive strain measurement.

Optical Fabry-Perot interferometer sensors based on inner air-cavity is featured with compact size, good robustness and high strain sensitivity, especially when an ultra-thin air-cavity is adopted. The typical shape of Fabry-Perot inner air-cavity with reflection mode of operation is elliptic, with minor axis along with and major axis perpendicular to the fiber length. The first reflection surface is diverging whereas the second one is converging. To increase the visibility of the output interference pattern, the length of major axis should be large for a given cavity length. However, the largest value of the major axis is limited by the optical fiber diameter. If the major axis length reaches the fiber diameter, the robustness of the Fabry-Perot cavity device would be decreased. Here we demonstrate an ultra-thin crescent shaped Fabry-Perot cavity for strain sensing with ultra-high sensitivity and low temperature cross-sensitivity. The crescent-shape cavity consists of two converging reflection surfaces, which provide the advantages of enhanced strain sensitivity when compared with elliptic or D-shaped FP cavity. The device is fabricated by fusion splicing an etched multimode fiber with a single mode fiber, and hence is simple in structure and economic in cost.

A new insight into high-strength Ti62Nb12.2Fe13.6Co6.4Al5.8 alloys with bimodal microstructure fabricated by semi-solid sintering.

It is well known that semi-solid forming could only obtain coarse-grained microstructure in a few alloy systems with a low melting point, such as aluminum and magnesium alloys. This work presents that semi-solid forming could also produce novel bimodal microstructure composed of nanostructured matrix and micro-sized (CoFe)Ti2 twins in a titanium alloy, Ti62Nb12.2Fe13.6Co6.4Al5.8. The semi-solid sintering induced by eutectic transformation to form a bimodal microstructure in Ti62Nb12.2Fe13.6Co6.4Al5.8 alloy is a fundamentally different approach from other known methods. The fabricated alloy exhibits high yield strength of 1790 MPa and plastic strain of 15.5%. The novel idea provides a new insight into obtaining nano-grain or bimodal microstructure in alloy systems with high melting point by semi-solid forming and into fabricating high-performance metallic alloys in structural applications.

Functional and association studies of the cholesteryl ester transfer protein (CETP) gene in a Wannan Black pig model.

Some polymorphisms of the human CETP gene are causally and significantly associated with serum lipids levels; however, the information regarding this gene in pigs is sparse. To evaluate the effects of CETP on blood lipid traits and fat deposition in pig, porcine CETP tissue expression patterns were observed by quantitative real-time polymerase chain reaction (qPCR) first. High expression was detected in liver, spleen, gluteus medius (GM) muscle and backfat. A de novo polymorphism (AF333037:g.795C>T) in the intron 1 region of porcine CETP was identified. This polymorphism was further genotyped by direct sequencing of the PCR products of 390 Wannan Black pigs, a Chinese native breed population. Association analyses at 45 and 300 days of age revealed highly significant associations between CETP genotypes and serum lipid traits. Furthermore, this polymorphism was proved to be associated with differences in liver CETP mRNA levels: pigs at 300 days of age with the TT genotype had higher levels than did those with other genotypes (P = 0.021). Additionally, analysis at 300 days of age showed that GM CETP mRNA expression correlated positively with serum lipids levels as well as with carcass backfat thickness and intramuscular fat content in GM. These results indicate that CETP is involved in serum, adipose and muscle lipid metabolism in pigs. The mechanisms underlying such relationships and their functional implications are worthy of further research.

Correlation of endogenous hormonal levels, fibroglandular tissue volume and percent density measured using 3D MRI during one menstrual cycle.

BACKGROUND: We measured breast density (BD) on MRI and correlated with endogenous hormonal levels. PATIENTS AND METHODS: Twenty-four premenopausal women received four weekly breast MRI. A blood sample was collected on the same day of MRI. BD was measured using a computer-based algorithm. The generalized estimation equation method was applied to model mean fibroglandular tissue volume (FV) and mean percent density (PD) from predictor variables including estradiol, progesterone, and week during a cycle. RESULTS: In week 3, a borderline significant correlation between estradiol and PD (r = 0.43, P = 0.04), estradiol and FV (r = 0.40, P = 0.05) and between progesterone and FV (r = 0.42, P = 0.04) was noted. The FV and PD measured in weeks 4 and 1 were higher than in weeks 2 and 3, adjusted for variation in endogenous estradiol and progesterone, indicating that the hormone change could not account for the changes in density. No lag effect of endogenous hormone on the change of FV or PD was noted (all P-values > 0.05). CONCLUSIONS: Our results showed that BD is not strongly associated with the endogenous hormone. Their association with breast cancer risk was likely coming from different mechanisms, and they should be considered as independent risk factors.

Thaliporphine preserves cardiac function of endotoxemic rabbits by both directly and indirectly attenuating NFκB signaling pathway.

Cardiac depression in sepsis is associated with the increased morbidity and mortality. Although myofilaments damage, autonomic dysfunction, and apoptosis play roles in sepsis-induced myocardial dysfunction, the underlying mechanism is not clear. All of these possible factors are related to NFκB signaling, which plays the main role in sepsis signaling. Thaliporphine was determined to possess anti-inflammatory and cardioprotective activity by suppressing NFκB signaling in rodents. The purpose of this study is to further prove this protective effect in larger septic animals, and try to find the underlying mechanisms. The systolic and diastolic functions were evaluated in vivo by pressure-volume analysis at different preloads. Both preload-dependent and -independent hemodynamic parameters were performed. Inflammatory factors of whole blood and serum samples were analyzed. Several sepsis-related signaling pathways were also determined at protein level. Changes detected by conductance catheter showed Thaliporphine could recover impaired left ventricular systolic function after 4 hours LPS injection. It could also reverse the LPS induced steeper EDPVR and gentler ESPVR, thus improve Ees, Ea, and PRSW. Thaliporphine may exert this protective effect by decreasing TNFα and caspase3 dependent cell apoptosis, which was consistent with the decreased serum cTnI and LDH concentration. Thaliporphine could protect sepsis-associated myocardial dysfunction in both preload-dependent and -independent ways. It may exert these protective effects by both increase of "good"-PI3K/Akt/mTOR and decrease of "bad"-p38/NFκB pathways, which followed by diminishing TNFα and caspase3 dependent cell apoptosis.

MicroRNA in osteoarthritis.

Osteoarthritis (OA) is the most prevalent degenerative joint disease and is accompanied by pain and joint dysfunction. Its clinical treatment tends to be unsatisfactory. Novel targets in OA include genes that are involved in OA pathophysiology and have been discovered using gene network, epigenetic and microRNA (miRNA) approaches. miRNA has been implicated in important cellular processes such as lipid metabolism, apoptosis, differentiation and organ development. The importance of miRNA regulation in cellular function is becoming increasingly clear as new miRNA targets are revealed. The present review summarizes the current evidence of the important role played by miRNA in determining the complex gene expression patterns of OA chondrocytes and their role in the regulation of transcription, and possible demethylation mechanisms that might be applicable in OA. In summary, miRNA may have important diagnostic and therapeutic potential, and might provide a novel means of treating OA.

Intracellular zinc release-activated ERK-dependent GSK-3ß-p53 and Noxa-Mcl-1 signaling are both involved in cardiac ischemic-reperfusion injury.

Oxidative stress and nitrosative stress are both suggested to be involved in cardiac ischemia-reperfusion (I/R) injury. Using time-lapse confocal microscopy of cardiomyocytes and high-affinity O(2)(-•) and Zn(2+) probes, this study is the first to show that I/R, reactive oxygen species (ROS), and reactive nitrogen species (RNS) all cause a marked increase in the [O(2)(-•)](i), resulting in cytosolic and mitochondrial Zn(2+) release. Exposure to a cell-penetrating, high-affinity Zn(2+)(i) chelator, TPEN, largely abolished the Zn(2+)(i) release and markedly protected myocytes from I/R-, ROS-, RNS-, or Zn(2+)/K(+) (Zn(2+)(i) supplementation)-induced myocyte apoptosis for at least 24 h after TPEN removal. Flavonoids and U0126 (a MEK1/2 inhibitor) largely inhibited the myocyte apoptosis and the TPEN-sensitive I/R- or Zn(2+)(i) supplement-induced persistent extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation, dephosphorylation of p-Ser9 on glycogen synthase kinase 3ß (GSK-3ß), and the translocation into and accumulation of p-Tyr216 GSK-3ß and p53 in, the nucleus. Silencing of GSK-3ß or p53 expression was cardioprotective, indicating that activation of the ERK-GSK-3ß-p53 signaling pathway is involved in Zn(2+)-sensitive myocyte death. Moreover, the ERK-dependent Noxa-myeloid cell leukemia-1 (Mcl-1) pathway is also involved, as silencing of Noxa expression was cardioprotective and U0126 abolished both the increase in Noxa expression and in Mcl-1 degradation. Thus, acute upstream Zn(2+)(i) chelation at the start of reperfusion and the use of natural products, that is, flavonoids, may be beneficial in the treatment of cardiac I/R injury.

Serine-385 phosphorylation of inwardly rectifying K+ channel subunit (Kir6.2) by AMP-dependent protein kinase plays a key role in rosiglitazone-induced closure of the K(ATP) channel and insulin secretion in rats.

AIMS/HYPOTHESIS: Rosiglitazone, an insulin sensitiser, not only improves insulin sensitivity but also enhances insulin secretory capacity by ameliorating gluco- and lipotoxicity in beta cells. Rosiglitazone can stimulate insulin secretion at basal and high glucose levels via a phosphatidylinositol 3-kinase (PI3K)-dependent pathway. We hypothesised that regulation of phosphorylation of the ATP-sensitive potassium (K(ATP)) channel might serve as a key step in the regulation of insulin secretion. METHODS: Insulin secretory responses were studied in an isolated pancreas perfusion system, cultured rat islets and MIN6 and RINm5F beta cells. Signal transduction pathways downstream of PI3K were explored to link rosiglitazone to K(ATP) channel conductance with patch clamp techniques and insulin secretion measured by ELISA. RESULTS: Rosiglitazone stimulated AMP-activated protein kinase (AMPK) activity and induced inhibition of the K(ATP) channel conductance in islet beta cells; both effects were blocked by the PI3K inhibitor LY294002. Following stimulation of AMPK by 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a pharmacological activator, both AICAR-stimulated insulin secretion and inhibition of K(ATP) channel conductance were unaffected by LY294002, indicating that AMPK activation occurs at a site downstream of PI3K activity. The serine residue at amino acid position 385 of Kir6.2 was found to be the substrate phosphorylation site of AMPK when activated by rosiglitazone or AICAR. CONCLUSIONS/INTERPRETATION: Our data indicate that PI3K-dependent activation of AMPK is required for rosiglitazone-stimulated insulin secretion in pancreatic beta cells. Phosphorylation of the Ser(385) residue of the Kir6.2 subunit of the K(ATP) channel by AMPK may play a role in insulin secretion.

Visfatin: a potential therapeutic target for rheumatoid arthritis.

Rheumatoid arthritis (RA) is usually a chronic, systemic inflammatory disorder primarily targeting the synovium and articular cartilage. It is incurable, costly and responds poorly to treatment. Methotrexate alone or in combination with conventional and/or biological disease-modifying antirheumatic drugs (DMARDs) is often used to induce remission of active disease. The effectiveness of treatment is, however, limited and most patients develop chronic disability and require total knee arthroplasty or total hip replacement. Emerging therapies targeting specific cytokines and growth factors in the RA inflammatory cascade offer potent new means of modifying disease activity. Recently, increased concentrations of adipokines, including visfatin, mainly produced by adipocytes in serum and joint synovial fluid, were found in RA patients. Visfatin has important pro-inflammatory and catabolic roles in RA pathogenesis and is now being studied as a potential therapeutic target for RA. Here we discuss the relationship between visfatin and RA and its potential as a therapeutic target for RA.

Red mold rice prevents the development of obesity, dyslipidemia and hyperinsulinemia induced by high-fat diet.

OBJECTIVE: To investigate the influences of red mold rice (RMR) on obesity and related metabolic abnormalities. METHODS AND RESULTS: The 3T3-L1 cell line was used to examine the effects of RMR extracts on preadipocytes and on mature adipocytes. Both water and ethanol extracts of RMR had inhibitory effects on 3T3-L1 preadipocyte proliferation and differentiation. Water extracts of RMR enhanced the lipolysis activity in mature adipocytes, which negatively correlated with the triglyceride content within cells. RMR treatment did not affect heparin-releasable lipoprotein lipase activity in mature adipocytes. Furthermore, animal studies were carried out to explore the antiobesity effects of RMR. The control group of male Wistar rats were fed regular laboratory feed, whereas the other groups were fed the high-fat (HF) diet supplemented with lovastatin, rice or RMR (0.4 and 2%, w w(-1)). The relative caloric intakes of the control and HF groups were 3.34 and 4.85 kcal g(-1), respectively. After 6 weeks, rats treated with RMR at the 0.4 and 2% doses had lower weight gain and less fat pads mass accompanied with smaller fat cells than did the HF-diet rats. These effects probably resulted from an increase in the lipolysis activity of adipose tissue and a reduction in food/energy consumption. On the other hand, the RMR supplement significantly reduced serum total cholesterol, serum low-density lipoprotein (LDL) cholesterol, the ratio of LDL to high-density lipoprotein (HDL) cholesterol and serum insulin in the HF group. Moreover, the 2% RMR treatment significantly increased serum HDL cholesterol. CONCLUSION: This study reveals for the first time that RMR can prevent body fat accumulation and improve dyslipidemia. The antiobesity effects of RMR mainly derive from the lipolytic activity and mild antiappetite potency of RMR. In addition, extracts of RMR suppressed the proliferation and differentiation in 3T3-L1 preadipocytes, which might have contributed to the inhibition of new adipocyte formation or hyperplasia in adipose tissue.

Electromechanical characterization of cinnamophilin, a natural thromboxane A2 receptor antagonist with anti-arrhythmic activity, in guinea-pig heart.

BACKGROUND AND PURPOSE: Cinnamophilin, a thromboxane A(2) receptor antagonist, has been identified as a prominent anti-arrhythmic agent in rat heart. This study aimed to determine its electromechanical and anti-arrhythmic effects in guinea-pig hearts. EXPERIMENTAL APPROACH: Microelectrodes were used to study action potentials in ventricular papillary muscles. Fluo-3 fluorimetric ratio and whole-cell voltage-clamp techniques were used to record calcium transients and membrane currents in single ventricular myocytes, respectively. Intracardiac electrocardiograms were obtained and the anti-arrhythmic efficacy was determined from isolated perfused hearts. KEY RESULTS: In papillary muscles, cinnamophilin decreased the maximal rate of upstroke (V(max)) and duration of action potential, and reduced the contractile force. In single ventricular myocytes, cinnamophilin reduced Ca(2+) transient amplitude. Cinnamophilin decreased the L-type Ca(2+) current (I(Ca,L))(IC(50)=7.5 microM) with use-dependency, induced a negative shift of the voltage-dependent inactivation and retarded recovery from inactivation. Cinnamophilin also decreased the Na(+) current (I(Na)) (IC(50)=2.7 microM) and to a lesser extent, the delayed outward (I(K)), inward rectifier (I(K1)), and ATP-sensitive (I(K,ATP)) K(+) currents. In isolated perfused hearts, cinnamophilin prolonged the AV nodal conduction interval and Wenckebach cycle length and the refractory periods of the AV node, His-Purkinje system and ventricle, while shortening the ventricular repolarization time. Additionally, cinnamophilin reduced the occurrence of reperfusion-induced ventricular fibrillation. CONCLUSIONS AND IMPLICATIONS: These results suggest that the promising anti-arrhythmic effect and the changes in the electromechanical function induced by cinnamophilin in guinea-pig heart can be chiefly accounted for by inhibition of I(Ca,L) and I(Na).

Assessment of American College of Rheumatology quality criteria for rheumatoid arthritis in a pre-quality criteria patient cohort.

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.

Application of explicit process of care measurement to rheumatoid arthritis: Moving from evidence to practice.

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.

Effects of alginate coated on PLGA microspheres for delivery tetracycline hydrochloride to periodontal pockets.

The effects of alginate coated on tetracycline (Tc) loaded poly (D, L-lactic-co-glycolic acid) (PLGA) microspheres fabricated by double emulsion solvent evaporation technique for local delivery to periodontal pocket were investigated. Alginate coated PLGA microspheres showed smoother surface but enlarged their particle sizes compared with those of uncoated ones. In addition, alginate coated microspheres enhanced Tc encapsulation efficiency (E.E.) from 11.5 +/- 0.5% of uncoated ones to 17.9 +/- 0.5%. Moreover, all of the coated PLGA microspheres even fabricated at different conditions could prolong Tc release from 9-12 days with 50% or higher in cumulative release of Tc compared with those of uncoated ones. The swelling ratios of PLGA microspheres for alginate coated or uncoated ones, one of the possible mechanisms for enhancing Tc release for the coated ones, were measured. The results showed that 20% or higher in swelling ratio for the coated microspheres at the earlier stage of hydration (e.g. < or = 24 h) could be an important factor to result in high Tc release compared to the uncoated ones. In conclusion, alginate coated Tc loaded PLGA microspheres could enhance Tc delivery to periodontal pocket by enhancing drug encapsulated efficiency, released quantities and sustained release period compared with uncoated ones.