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Objectives This study documents trends in risk-adjusted quality and cost for a variety of inpatient surgical procedures among Medicare beneficiaries from 2002 through 2015, which can provide valuable insight on future strategies to improve public health and health care. Methods We focused on 11 classes of inpatient surgery, defined by the Agency for Health Research and Quality’s (AHRQ’s) Clinical Classification System. The surgical classes studied included a wide range of surgeries, including tracheostomy, heart valve procedures, colorectal resection, and wound debridement, among others. For each surgical class, we assessed trends in treatment costs and quality outcomes, as defined by 30-day survival without unplanned readmissions, among Medicare beneficiaries receiving these procedures during hospital stays. Quality and costs were adjusted for patient severity based on demographics, comorbidities, and community context. We also explored surgical innovations of these 11 classes of inpatient surgery from 2002–2015. Results We found significant improvements in quality for 7 surgical classes, ranging from 0.08% (percutaneous transluminal coronary angioplasty) to 0.74% (heart valve procedures) per year. Changes in cost varied by surgery, the significant decrease in cost ranged from -2.59% (tracheostomy) to -0.34% (colorectal resection) per year. Treatment innovation occurred with respect to surgical procedures utilized for heart valve procedures and colorectal resection, which may be associated with the decrease in surgical cost. Conclusions Our results suggest that there was significant quality improvement for 7 surgery categories over the 14-year study period. Costs decreased significantly for 6 surgery categories, and increased significantly for 3 other categories.

The aim of the present study was to investigate the speech preparation processes of adults who stutter (AWS). Fifteen AWS and fifteen adults with fluent speech (AFS) participated in the experiment. The event-related potentials (ERPs) were recorded in a foreperiod paradigm. The warning signal (S1) was a color square, and the following imperative stimulus (S2) was either a white square (the Go signal that required participants to name the color of S1) or a white dot (the NoGo signal that prevents participants from speaking). Three differences were found between AWS and AFS. First, the mean amplitude of the ERP component parietal positivity elicited by S1 (S1-P3) was smaller in AWS than in AFS, which implies that AWS may have deficits in investing working memory on phonological programming. Second, the topographic shift from the early phase to the late phase of contingent negative variation occurred earlier for AWS than for AFS, thus suggesting that the motor preparation process is promoted in AWS. Third, the NoGo effect in the ERP component parietal positivity elicited by S2 (S2-P3) was larger for AFS than for AWS, indicating that AWS have difficulties in inhibiting a planned speech response. These results provide a full picture of the speech preparation and response inhibition processes of AWS. The relationship among these three findings is discussed. However, as stuttering was not manipulated in this study, it is still unclear whether the effects are the causes or the results of stuttering. Further studies are suggested to explore the relationship between stuttering and the effects found in the present study.

The tumor-to-brain communication has been emphasized by recent converging evidences. This study aimed to compare the difference of brain glucose metabolism between patients with non-small cell lung cancer (NSCLC) and control subjects.NSCLC patients prior to oncotherapy and control subjects without malignancy confirmed by 6 months follow-up were collected and underwent the resting state 18F-fluoro-D-glucose (FDG) PET/CT. Normalized FDG metabolism was calculated by a signal intensity ratio of each brain region to whole brain. Brain glucose metabolism was compared between NSCLC patients and control group using two samples t-test and multivariate test by statistical parametric maps (SPM) software.Compared with the control subjects (n = 76), both brain glucose hyper- and hypometabolism regions with significant statistical differences (P

The aim of this study was to evaluate the survival outcomes and toxicity of postoperative chemoradiotherapy with capecitabine and concurrent intensity-modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT) in patients with stage II and III rectal cancer.We recruited 184 patients with pathologically proven, stage II or III rectal cancer. Following total mesorectal excision (TME), the patients were treated with capecitabine and concurrent IMRT/3D-CRT. The treatment regimen consisted of two cycles of oral capecitabine (1600 mg/m2/day), administered twice daily from day 1-14 of radiotherapy, followed by a 7-day rest. The median pelvic dose was 50 Gy in 25 fractions. Oxaliplatin-based adjuvant chemotherapy was administered after the chemoradiotherapy.The 5-year overall survival, disease-free survival and locoregional control (LRC) rates were 85.1%, 80% and 95.4%, respectively. Grade 3 and 4 toxicities were observed in 28.3% of patients during treatment. Grade 3 or 4 late toxicity, including neurotoxicity or gastrointestinal toxicity, was only observed in nine patients (4.9%).This study demonstrated that capecitabine chemotherapy with concurrent IMRT/3D-CRT following TME is safe, is well tolerated and achieves superior LRC and favorable survival rates, with acceptable toxicity.

Krüppel-like factor (KLF) 5, which initiates vascular smooth muscle cell (VSMC) proliferation, also participates in Angiotensin (Ang) II-induced vascular remodeling. The protective effect of rosiglitazone on vascular remodeling may be due to their impact on VSMC proliferation. However, the underlying mechanisms involved remain unclear. This study was designed to investigate whether the antiproliferation effects of rosiglitazone are mediated by regulating Ang II/KLF5 response. We found that, in aortas of Ang II-infused rats, vascular remodeling and KLF5 expression were markedly increased, and its target gene cyclin D1 was overexpressed. Co-treatment with rosiglitazone diminished these changes. In growth-arrested VSMCs, PPAR-γ agonists (rosiglitazone and 15d-PGJ2) dose-dependently inhibited Ang II-induced cell proliferation and expression of KLF5 and cyclin D1. Moreover, these effects were attenuated by the PPAR-γ antagonists GW9662, bisphenol A diglycidyl ether and PPAR-γ specific siRNA. Furthermore, rosiglitazone inhibited Ang II-induced phosphorylation of protein kinase C (PKC) ζ and extracellular signal-regulated kinase (ERK) 1/2 and activation of early growth response protein (Egr). In conclusion, in Ang II-stimulated VSMCs, rosiglitazone might have an antiproliferative effect through mechanisms that include reducing KLF5 expression, and a crosstalk between PPAR-γ and PKCζ/ERK1/2/Egr may be involved in. These findings not only provide a previously unrecognized mechanism by which PPAR-γ agonists inhibit VSMC proliferation, but also document a novel evidence for the beneficial vascular effect of PPAR-γ activation.

OBJECTIVE: To determine whether the New Cooperative Medical Insurance Scheme (NCMS) is associated with decreased levels of catastrophic health expenditure and reduced impoverishment due to medical expenses in rural households of China. METHODS: An analysis of a national representative sample of 38,945 rural households (129,635 people) from the 2008 National Health Service Survey was performed. Logistic regression models used binary indicator of catastrophic health expenditure as dependent variable, with household consumption, demographic characteristics, health insurance schemes, and chronic illness as independent variables. RESULTS: Higher percentage of households experiencing catastrophic health expenditure and medical impoverishment correlates to increased health care need. While the higher socio-economic status households had similar levels of catastrophic health expenditure as compared with the lowest. Households covered by the NCMS had similar levels of catastrophic health expenditure and medical impoverishment as those without health insurance. CONCLUSION: Despite over 95% of coverage, the NCMS has failed to prevent catastrophic health expenditure and medical impoverishment. An upgrade of benefit packages is needed, and effective cost control mechanisms on the provider side needs to be considered.

BACKGROUND AND PURPOSE: Iron deposition and white matter (WM) maturation are very important for brain development in infants. It has been reported that the R2* and phase values originating from the gradient-echo sequence could both reflect the iron and myelination. The aim of this study was to investigate age-related changes of R2* and phase value, and compare their performances for monitoring iron deposition and WM maturation in infant brains. METHODS: 56 infants were examined by enhanced T2 star weighted angiography (ESWAN) and diffusion tensor imaging in the 1.5T MRI system. The R2* and phase values were measured from the deep gray nuclei and WM. Fractional anisotropy (FA) values were measured only in the WM regions. Correlation analyses were performed to explore the relation among the two parameters (R2* and phase values) and postmenstrual age (PMA), previously published iron concentrations as well as FA values. RESULTS: We found significantly positive correlations between the R2* values and PMA in both of the gray nuclei and WM. Moreover, R2* values had a positive correlation with the iron reference concentrations in the deep gray nuclei and the FA in the WM. However, phase values only had the positive correlation with PMA and FA in the internal capsule, and no significant correlation with PMA and iron content in the deep gray nuclei. CONCLUSIONS: Compared with the phase values, R2* may be a preferable method to estimate the iron deposition and WM maturation in infant brains.

BACKGROUND:People with chronic non-communicable diseases (NCD) are particularly vulnerable to socioeconomic inequality due to their long-term expensive health needs. This study aimed to assess socioeconomic-related inequality in health service utilization among NCD patients in China and to analyze factors associated with this disparity. METHODS:Data were taken from the 2008 Chinese National Health Survey, in which a multiple stage stratified random sampling method was employed to survey 56,456 households. We analyzed the distribution of actual use, need-expected use, and need-standardized usage of outpatient services (over a two-week period) and inpatient services (over one-year) across different income groups in 27,233 adult respondents who reported as having a NCD. We used a concentration index to measure inequality in the distribution of health services, which was expressed as HI (Horizontal Inequity Index) for need-standardized use of services. A non-linear probit regression model was employed to detect inequality across socio-economic groups. RESULTS:Pro-rich inequity in health services among NCD patients was more substantial than the average population. A higher degree of pro-rich inequity (HI = 0.253) was found in inpatient services compared to outpatient services (HI = 0.089). Despite a greater need for health services amongst those of lower socio-economic status, their actual use is much less than their more affluent counterparts. Health service underuse by the poor and overuse by the affluent are evident. Household income disparity was the greatest inequality factor in NCD service use for both outpatients (71.3%) and inpatients (108%), more so than health insurance policies. Some medical insurance schemes, such as the MIUE, actually made a pro-rich contribution to health service inequality (16.1% for outpatient and 12.1% for inpatient). CONCLUSIONS:Inequality in health services amongst NCD patients in China remains largely determined by patient financial capability. The current insurance schemes are insufficient to address this inequity. A comprehensive social policy that encompasses a more progressive taxation package and redistribution of social capital as well as pro-poor welfare is needed.

BACKGROUND: This study aimed to elucidate clinical significance of anaplastic lymphoma kinase (ALK) rearrangement in selected advanced non-small cell lung cancer (NSCLC), to compare the application of different ALK detection methods, and especially evaluate a possible association between ALK expression and clinical outcomes in crizotinib-treated patients. METHODS: ALK status was assessed by fluorescent in situ hybridization (FISH), immunohistochemistry (IHC) and quantitative RT-PCR (qRT-PCR) in 173 selected advanced NSCLC patients. Clinicopathologic data, genotype status and survival outcomes were analyzed. Moreover, the association of ALK expression with clinical outcomes was evaluated in ALK FISH-positive crizotinib-treated patients including two patients with concurrent epidermal growth factor receptor (EGFR) mutation. RESULTS: The positivity detection rate of ALK rearrangement by FISH, IHC and qRT-PCR was 35.5% (59/166), 35.7% (61/171), and 27.9% (34/122), respectively. ALK rearrangement was observed predominantly in young patients, never or light smokers, and adenocarcinomas, especially with signet ring cell features and poor differentiation. Median progression-free survival (PFS) of crizotinib-treated patients was 7.6 months. The overall survival (OS) of these patients was longer compared with that of crizotinib-naive or wild-type cohorts, but there was no significant difference in OS compared with patients with EGFR mutation. ALK expression did not associate with PFS; but, when ALK expression was analyzed as a dichotomous variable, moderate and strong ALK expression had a decreased risk of death (P = 0.026). The two patients with concomitant EGFR and ALK alterations showed difference in ALK expression, response to EGFR and ALK inhibitors, and overall survival. CONCLUSIONS: Selective enrichment according to clinicopathologic features in NSCLC patients could highly improve the positivity detection rate of ALK rearrangement for ALK-targeted therapy. IHC could provide more clues for clinical trial design and therapeutic strategies for ALK-positive NSCLC patients including patients with double genetic aberration of ALK and EGFR.

BACKGROUND: The consumption of dairy products may influence the risk of type 2 diabetes mellitus (T2DM), but inconsistent findings have been reported. Moreover, large variation in the types of dairy intake has not yet been fully explored. METHODS AND RESULTS: We conducted a systematic review and meta-analysis to clarify the dose-response association of dairy products intake and T2DM risk. We searched PubMed, EMBASE and Scopus for studies of dairy products intake and T2DM risk published up to the end of October 2012. Random-effects models were used to estimate summary relative risk (RR) statistics. Dose-response relations were evaluated using data from different dairy products in each study. We included 14 articles of cohort studies that reported RR estimates and 95% confidence intervals (95% CIs) of T2DM with dairy products intake. We found an inverse linear association of consumption of total dairy products (13 studies), low-fat dairy products (8 studies), cheese (7 studies) and yogurt (7 studies) and risk of T2DM. The pooled RRs were 0.94 (95% CI 0.91-0.97) and 0.88 (0.84-0.93) for 200 g/day total and low-fat dairy consumption, respectively. The pooled RRs were 0.80 (0.69-0.93) and 0.91 (0.82-1.00) for 30 g/d cheese and 50 g/d yogurt consumption, respectively. We also found a nonlinear association of total and low-fat dairy intake and T2DM risk, and the inverse association appeared to be strongest within 200 g/d intake. CONCLUSION: A modest increase in daily intake of dairy products such as low fat dairy, cheese and yogurt may contribute to the prevention of T2DM, which needs confirmation in randomized controlled trials.

Accurate and timely glucose monitoring is essential in intensive care units. Real-time continuous glucose monitoring system (CGMS) has been advocated for many years to improve glycemic management in critically ill patients. In order to determine the effect of calibration time on the accuracy of CGMS, real-time subcutaneous CGMS was used in 18 critically ill patients. CGMS sensor was calibrated with blood glucose measurements by blood gas/glucose analyzer every 12 hours. Venous blood was sampled every 2 to 4 hours, and glucose concentration was measured by standard central laboratory device (CLD) and by blood gas/glucose analyzer. With CLD measurement as reference, relative absolute difference (mean±SD) in CGMS and blood gas/glucose analyzer were 14.4%±12.2% and 6.5%±6.2%, respectively. The percentage of matched points in Clarke error grid zone A was 74.8% in CGMS, and 98.4% in blood gas/glucose analyzer. The relative absolute difference of CGMS obtained within 6 hours after sensor calibration (8.8%±7.2%) was significantly less than that between 6 to 12 hours after calibration (20.1%±13.5%, p

Peripheral CD8(+) T cells are defective in both IL-15 and IL-15Rα knock-out (KO) mice; however, whether IL-15/IL-15Rα deficiency has a similar effect on CD8 single-positive (SP) thymocytes remains unclear. In this study, we investigated whether the absence of IL-15 transpresentation in IL-15Rα KO mice results in a defect in thymic CD8 single positive (SP) TCR(hi) thymocytes. Comparison of CD8SP TCR(hi) thymocytes from IL-15Rα KO mice with their wild type (WT) counterparts by flow cytometry showed a significant reduction in the percentage of CD69(-) CD8SP TCR(hi) thymocytes, which represent thymic premigrants. In addition, analysis of in vivo 5-bromo-2-deoxyuridine (BrdU) incorporation demonstrated that premigrant expansion of CD8SP TCR(hi) thymocytes was reduced in IL-15Rα KO mice. The presence of IL-15 transpresentation-dependent expansion in CD8SP TCR(hi) thymocytes was assessed by culturing total thymocytes in IL-15Rα-Fc fusion protein-pre-bound plates that were pre-incubated with IL-15 to mimic IL-15 transpresentation in vitro. The results demonstrated that CD8SP thymocytes selectively outgrew other thymic subsets. The contribution of the newly divided CD8SP thymocytes to the peripheral CD8(+) T cell pool was examined using double labeling with intrathymically injected FITC and intravenously injected BrdU. A marked decrease in FITC(+) BrdU(+) CD8(+) T cells was observed in the IL-15Rα KO lymph nodes. Through these experiments, we identified an IL-15 transpresentation-dependent proliferation process selective for the mature CD8SP premigrant subpopulation. Importantly, this process may contribute to the maintenance of the normal peripheral CD8(+) T cell pool.

Nitrogen is an essential element for plant growth and yield. Improving Nitrogen Use Efficiency (NUE) of crops could potentially reduce the application of chemical fertilizer and alleviate environmental damage. To identify new NUE genes is therefore an important task in molecular breeding. Macroautophagy (autophagy) is an intracellular process in which damaged or obsolete cytoplasmic components are encapsulated in double membraned vesicles termed autophagosomes, then delivered to the vacuole for degradation and nutrient recycling. One of the core components of autophagosome formation, ATG8, has been shown to directly mediate autophagosome expansion, and the transcript of which is highly inducible upon starvation. Therefore, we postulated that certain homologs of Saccharomyces cerevisiae ATG8 (ScATG8) from crop species could have potential for NUE crop breeding. A soybean (Glycine max, cv. Zhonghuang-13) ATG8, GmATG8c, was selected from the 11 family members based on transcript analysis upon nitrogen deprivation. GmATG8c could partially complement the yeast atg8 mutant. Constitutive expression of GmATG8c in soybean callus cells not only enhanced nitrogen starvation tolerance of the cells but accelerated the growth of the calli. Transgenic Arabidopsis over-expressing GmATG8c performed better under extended nitrogen and carbon starvation conditions. Meanwhile, under optimum growth conditions, the transgenic plants grew faster, bolted earlier, produced larger primary and axillary inflorescences, eventually produced more seeds than the wild-type. In average, the yield was improved by 12.9%. We conclude that GmATG8c may serve as an excellent candidate for breeding crops with enhanced NUE and better yield.

The transcription factor Lmx1b is essential for the differentiation and survival of central serotonergic (5-HTergic) neurons during embryonic development. However, the role of Lmx1b in adult 5-HTergic neurons is unknown. We used an inducible Cre-LoxP system to selectively inactivate Lmx1b expression in the raphe nuclei of adult mice. Pet1-CreER(T2) mice were generated and crossed with Lmx1b(flox/flox) mice to obtain Pet1-CreER(T2); Lmx1b(flox/flox) mice (which termed as Lmx1b iCKO). After administration of tamoxifen, the level of 5-HT in the brain of Lmx1b iCKO mice was reduced to 60% of that in control mice, and the expression of tryptophan hydroxylase 2 (Tph2), serotonin transporter (Sert) and vesicular monoamine transporter 2 (Vmat2) was greatly down-regulated. On the other hand, the expression of dopamine and norepinephrine as well as aromatic L-amino acid decarboxylase (Aadc) and Pet1 was unchanged. Our results reveal that Lmx1b is required for the biosynthesis of 5-HT in adult mouse brain, and it may be involved in maintaining normal functions of central 5-HTergic neurons by regulating the expression of Tph2, Sert and Vmat2.

BACKGROUND: IL-17-secreting CD8+ T cells (Tc17 subset) have recently been defined as a subpopulation of effector T cells implicated in the pathogenesis of autoimmune diseases. The role of Tc17 and correlation with Th17 cells in the pathophysiology of immune thrombocytopenia (ITP) remain unsettled. DESIGN AND METHODS: We studied 47 ITP patients (20 newly-diagnosed and 27 with complete response) and 34 healthy controls. IL-17-producing CD3+CD8+ cells (Tc17) and IL-17-producing CD3+CD8- cells (Th17) were evaluated by flow cytometry and expressed as a percentage of the total number of CD3+ cells. Specific anti-platelet glycoprotein (GP) GPIIb/IIIa and/or GPIb/IX autoantibodies were measured by modified monoclonal antibody specific immobilization of platelet antigens. Peripheral blood mononuclear cells of ITP patients were isolated, incubated in the presence of 0, 0.25, 0.5, or 1 µmol/L of dexamethasone for 72 h, and collected to detect Tc17 and Th17 cells by flow cytometric analysis. RESULTS: IL-17 was expressed on CD3+CD8- and CD3+CD8+ T cells. The percentages of Tc17 and Th17 cells in newly-diagnosed patients were significantly elevated compared to controls, and Tc17 was decreased after clinical treatment. The Th17∶Tc17 ratio was significantly lower in newly-diagnosed patients compared with controls, and was increased in patients who had complete response. There was a significantly positive correlation between Tc17 and Th17 cells in the control group, but not in the ITP patients. A positive correlation existed between Tc17 and the CD8∶CD4 ratio, as well as CD8+ cells in patients with ITP. The frequencies of Tc17 were marginally higher in autoantibody-negative patients than autoantibody-positive patients. Moreover, both Tc17 and Th17 cell percentages decreased as the concentration of dexamethasone in the culture media increased in ITP patients. CONCLUSIONS: Tc17 and the Th17 subset are involved in the immunopathology of ITP. Blocking the abnormally increased number of Tc17 may be a reasonable therapeutic strategy for ITP.

Background: This study aimed to elucidate clinical significance of anaplastic lymphoma kinase (ALK) rearrangement in selected advanced non-small cell lung cancer (NSCLC), to compare the application of different ALK detection methods, and especially evaluate a possible association between ALK expression and clinical outcomes in crizotinib-treated patients. Methods: ALK status was assessed by fluorescent in situ hybridization (FISH), immunohistochemistry (IHC) and quantitative RT-PCR (qRT-PCR) in 173 selected advanced NSCLC patients. Clinicopathologic data, genotype status and survival outcomes were analyzed. Moreover, the association of ALK expression with clinical outcomes was evaluated in ALK FISH-positive crizotinib-treated patients including two patients with concurrent epidermal growth factor receptor (EGFR) mutation. Results: The positivity detection rate of ALK rearrangement by FISH, IHC and qRT-PCR was 35.5% (59/166), 35.7% (61/171), and 27.9% (34/122), respectively. ALK rearrangement was observed predominantly in young patients, never or light smokers, and adenocarcinomas, especially with signet ring cell features and poor differentiation. Median progression-free survival (PFS) of crizotinib-treated patients was 7.6 months. The overall survival (OS) of these patients was longer compared with that of crizotinib-naive or wild-type cohorts, but there was no significant difference in OS compared with patients with EGFR mutation. ALK expression did not associate with PFS; but, when ALK expression was analyzed as a dichotomous variable, moderate and strong ALK expression had a decreased risk of death (P = 0.026). The two patients with concomitant EGFR and ALK alterations showed difference in ALK expression, response to EGFR and ALK inhibitors, and overall survival. Conclusions: Selective enrichment according to clinicopathologic features in NSCLC patients could highly improve the positivity detection rate of ALK rearrangement for ALK-targeted therapy. IHC could provide more clues for clinical trial design and therapeutic strategies for ALK-positive NSCLC patients including patients with double genetic aberration of ALK and EGFR. [ABSTRACT FROM AUTHOR]