Tumor-suppressive miR-145 co-repressed by TCF4-ß-catenin and PRC2 complexes forms double-negative regulation loops with its negative regulators in colorectal cancer.

The frequently dysregulated Wnt/ß-catenin signaling in different malignancies, by activation of its own or orchestration with other co-factors, regulates various oncogenic or tumor-suppressive genes. Among these genes, miRNAs, which are negative posttranscriptional regulators, are also embedded in the Wnt signaling network. Different from the Wnt-induced oncogenic miRNAs, the specific mechanism underlying the Wnt-repressed tumor-suppressive miRNAs is much less understood. In our study, firstly by analyzing a ChIP-seq dataset against TCF4, the core transcription factor for initiation of Wnt signaling in colorectal cancer (CRC) cells, we screened out several tumor-suppressive miRNAs potentially regulated by Wnt signaling. Then through siRNA-mediated knock-down tests and protein and chromatin immunoprecipitations, we found the TCF4-ß-catenin complex can recruit the histone trimethylation complex PRC2 as a co-repressor while binding to the TCF4-binding element (TBE) in the promoter regions of miR-145, miR-132 and miR-212. Thus, upon Wnt signaling activation, the PRC2-mediated trimethylation of histone H3 at lysine 27 increases at these promoter regions, leading to decreased miRNA levels. Furthermore, we found that by targeting TCF4 and SUZ12, the key components of the negative regulation complexes, the tumor-suppressive miR-145 co-repressed by Wnt signaling and histone trimethylation, forms double-negative regulation loops with its negative regulators in CRC cells. And the inverse associations between miR-145 and its targets/negative regulators have also been demonstrated in nude mice and clinical samples. Collectively, we elucidated the detailed molecular mechanism of how dysregulated Wnt/ß-catenin signaling and tumor-suppressive miRNAs reciprocally regulate each other in CRC cells.

[Development of a Laser On-Line Cement Raw Material Analysis Equipment].

In engineering construction, cement quality directly affects the safety of construction projects. So it is necessary that we use qualified cement in the engineering structure. It is of great signification that a method detects cement raw material rapidly to adjust the mixture ratio of raw ores to ensure the cement quality. Traditional detection method needs sampling, sample preparation and test, etc. With many procedures, the test results are seriously lagged behind the production process. This paper introduces a set of online analysis equipment to determinate elemental composition of cement powder timely based on laser induced breakdown spectroscopy. This equipment is composed of a LIBS detection system and a pneumatic system. The equipment can achieve the real-time measurement for it needn't sample preparation. Thus, it can guide cement raw material proportioning in time. In this paper, we have quantitatively analyzed the main components of Al2O3, CaO, Fe2O3, MgO and SiO2 in the cement raw materials using the full spectrum normalization method as well as the support vector machine. The corresponding maximum absolute errors were 0.34%, 0.35%, 0.07%, 0.14%, and 0.55%, respectively. Results showed that the measurement results of the newly developed LIBS equipment are in accord with those of the conventional chemical method. Furthermore, the measurement precision is in line with X-Ray fluorescence spectrometry. It is confirmed that the LIBS technique could be a prospect method for determination of elemental composition in the cement production industries.

Predicting potentially avoidable hospitalizations.

BACKGROUND: Hospitalizations due to ambulatory care sensitive conditions (ACSCs) are widely accepted as an indicator of primary care access and effectiveness. However, broad early intervention to all patients in a health care system may be deemed infeasible due to limited resources. OBJECTIVE: To develop a predictive model to identify high-risk patients for early intervention to reduce ACSC hospitalizations, and to explore the predictive power of different variables. METHODS: The study population included all patients treated for ACSCs in the VA system in fiscal years (FY) 2011 and 2012 (n=2,987,052). With all predictors from FY2011, we developed a statistical model using hierarchical logistic regression with a random intercept to predict the risk of ACSC hospitalizations in the first 90 days and the full year of FY2012. In addition, we configured separate models to assess the predictive power of different variables. We used a random split-sample method to prevent overfitting. RESULTS: For hospitalizations within the first 90 days of FY2012, the full model reached c-statistics of 0.856 (95% CI, 0.853-0.860) and 0.856 (95% CI, 0.852-0.860) for the development and validation samples, respectively. For predictive power of the variables, the model with only a random intercept yielded c-statistics of 0.587 (95% CI, 0.582-0.593) and 0.578 (95% CI, 0.573-0.583), respectively; with patient demographic and socioeconomic variables added, the c-statistics improved to 0.725 (95% CI, 0.720-0.729) and 0.721 (95% CI, 0.717-0.726), respectively; adding prior year utilization and cost raised the c-statistics to 0.826 (95% CI, 0.822-0.830) and 0.826 (95% CI,0.822-0.830), respectively; the full model was reached with HCCs added. For the 1-year hospitalizations, only the full model was fitted, which yielded c-statistics of 0.835 (95% CI, 0.831-0.837) and 0.833 (95% CI, 0.830-0.837), respectively, for development and validation samples. CONCLUSIONS: Our analyses demonstrate that administrative data can be effective in predicting ACSC hospitalizations. With high predictive ability, the model can assist primary care providers to identify high-risk patients for early intervention to reduce ACSC hospitalizations.

Impact of patient-level risk adjustment on the findings about nurse staffing and 30-day mortality in veterans affairs acute care hospitals.

BACKGROUND: Studies about nurse staffing and patient outcomes often lack adequate risk adjustment because of limited access to patient information. OBJECTIVE: The aim of this study was to examine the impact of patient-level risk adjustment on the associations of unit-level nurse staffing and 30-day inpatient mortality. METHODS: This retrospective cross-sectional study included 284,097 patients discharged during 2007-2008 from 446 acute care nursing units at 128 Veterans Affairs medical centers. The association of nurse staffing with 30-day mortality was assessed using hierarchical logistic models under three levels of risk-adjustment conditions: using no patient information (low), using patient demographics and diagnoses (moderate), or using patient demographics and diagnoses plus physiological measures (high). RESULTS: Discriminability of the models improved as the level of risk adjustment increased. The c-statistics for models of low, moderate, and high risk adjustment were 0.64, 0.74, and 0.88 for non-ICU patients and 0.66, 0.76, and 0.88 for ICU patients. For non-ICU patients, higher RN skill mix was associated with lower 30-day mortality across all three levels of risk adjustment. For ICU patients, higher total nursing hours per patient day was strongly associated with higher mortality with moderate risk adjustment (p = .0002), but this counterintuitive association was not significant with low or high risk adjustment. DISCUSSION: Inadequate risk adjustment may lead to biased estimates about nurse staffing and patient outcomes. Combining physiological measures with commonly used administrative data is a promising risk-adjustment approach to reduce potential biases.

Association between serum platelet-derived growth factor BB and degree of liver damage, fibrosis and hepatitis B e antigen (HBeAg) status in CHB patients.

BACKGROUND/AIMS: The objective of this study was to determine the association of PDGF-BB with degree of liver damage, fibrosis and HBeAg status in CHB patients. METHODOLOGY: A total of 740 patients with previously untreated chronic hepatitis B were included in the study. We conducted the correlations analysis of se-rum PDGF-BB with the age, gender, medical history, se-rum HBV-DNA, liver function parameters and serum fibrosis markers (HA, PCIII, CIV, LN), analyzed the cor-relations of degree of liver damage with liver fibrosis markers and the serum levels of PDGF-BB and compared serum liver fibrosis markers and levels of PDGF- BB between HbeAg-negative and HbeAg-positive CHB patients. RESULTS: Liver function parameters and se-rum liver fibrosis markers were significantly correlated with serum PDGF-BB (p<0.01). Liver fibrosis markers and serum levels of PDGF-BB in CHB were positive correlated with degree of liver damage. Serum levels of PDGF-BB in HBeAg-negative CHB was significantly higher than that in the HBeAg-positive CHB (p<0.05). CONCLUSIONS: Serum levels of PDGF-BB can reflect degree of liver damage and degree of liver fibrosis in CHB.Serum levels of PDGF-BB in HBeAg-negative CHB were higher than the HBeAg-positive CHB.

Nurse staffing and patient care costs in acute inpatient nursing units.

OBJECTIVE: Studies suggest that a business case for improving nurse staffing can be made to increase registered nurse (RN) skill mix without changing total licensed nursing hours. It is unclear whether a business case for increasing RN skill mix can be justified equally among patients of varying health needs. This study evaluated whether nursing hours per patient day (HPPD) and skill mix are associated with higher inpatient care costs within acute medical/surgical inpatient units using data from the Veterans Health Administration. METHODS: Retrospective cross-sectional study, including 139,360 inpatient admissions to 292 acute medical/surgical units at 125 Veterans Health Administration medical centers between February and June 2003, was conducted. Dependent variables were inpatient costs per admission and costs per patient day. RESULTS: The average costs per surgical and medical admission were $18,624 and $6,636, respectively. Costs per admission were positively associated with total nursing HPPD among medical admissions ($164.49 per additional HPPD, P<0.001), but not among surgical admissions. Total nursing HPPD and RN skill mix were associated with higher costs per hospital day for both medical admissions ($79.02 per additional HPPD and $5.64 per 1% point increase in nursing skill mix, both P<0.001) and surgical admissions ($112.47 per additional HPPD and $13.31 per 1% point increase in nursing skill mix, both P<0.001). Patients experiencing complications or transferring to an intensive care unit had higher inpatient costs than other patients. CONCLUSIONS: The association of nurse staffing level with costs per admission differed for medical versus surgical admissions.

Organizational factors associated with decreased mortality among Veterans Affairs patients with an ICU stay.

In-hospital mortality rates associated with an ICU stay are high and vary widely among units. This variation may be related to organizational factors such as staffing patterns, ICU structure, and care processes. We aimed to identify organizational factors associated with variation in in-hospital mortality for patients with an ICU stay. This was a retrospective observational cross-sectional study using administrative data from 34 093 patients from 171 ICUs in 119 Veterans Health Administration hospitals. Staffing and patient data came from Veterans Health Administration national databases. ICU characteristics came from a survey in 2004 of ICUs within the Veterans Health Administration. We conducted multilevel multivariable estimation with patient-, unit-, and hospital-level data. The primary outcome was in-hospital mortality. Of 34 093 patients, 2141 (6.3%)died in the hospital. At the patient level, risk of complications and having a medical diagnosis were significantly associated with a higher risk of mortality. At the unit level, having an interface with the electronic medical record was significantly associated with a lower risk of mortality. The finding that electronic medical records integrated with ICU information systems are associated with lower in-hospital mortality adds support to existing evidence on organizational characteristics associated with in-hospital mortality among ICU patients.

[The association between chronic periodontitis and hypertension in rural adult Uygur residents].

OBJECTIVE: To explore the association between chronic periodontitis and hypertension in rural adult Uygur residents. METHODS: A total of 1415 Uygur residents aged 18 and over were selected by random multistage and probability proportional to size from 364 villages in Moyu county of Xinjiang Uygur autonomous region, all subjects received questionnaire, physical examination and biochemical analysis and oral examination. The subjects were categorized as periodontitis group and no periodontitis group, the periodontitis group was further categorized as mild, moderate and severe periodontitis subgroup. The relationship between chronic periodontitis with hypertension was analyzed by Spearman correlation. Binary logistic regression was used to calculate the influential factors for hypertension. RESULTS: The prevalence rates of chronic periodontitis and hypertension were 66.0% (934/1415) and 33.8% (478/1415), respectively. The prevalence rates of hypertension were 18.7% (90/481), 35.1% (131/373), 32.3% (62/192), 52.8% (195/369) in no periodontitis, mild, moderate and severe periodontitis groups, respectively. Spearman correlation showed an association of chronic periodontitis with hypertension (r(s) = 0.273, P < 0.01). After adjustment for age, gender, body mass index, waist circumference, glycometabolism disorder, hyperlipidemia, chronic kidney disease, multiple logistic regression analysis showed that periodontitis was significantly associated with hypertension (OR = 1.75, 95%CI: 1.30 - 2.36, P < 0.01). Compared with no periodontitis, mild (OR = 1.76, 95%CI: 1.26 - 2.48, P < 0.01) and severe (OR = 2.26, 95%CI: 1.57 - 3.26, P < 0.01) periodontitis were significantly associated with hypertension while moderate periodontitis was not significantly associated with hypertension (OR = 1.21, 95%CI: 0.80 - 1.84, P > 0.05). CONCLUSION: This study showed an independent association of periodontitis with hypertension in this study cohort.

[Difference in properties of spontaneous electric activities of visceral nociceptive neurons in bilateral anterior cingulate gyrus of cats].

The aim of the present study is to explore the role of anterior cingulate gyrus (ACG) in bilateral cerebral cortex in visceral nociceptive sensation. Electrical stimulation of greater splanchnic nerve (GSN) was used as visceral nociceptive stimulus, and intracellular recording techniques in vivo was used to record and analyze the responses to stimuli and spontaneous electric activities of the neurons in the bilateral ACG. According to the responses to electrical stimulation of GSN, the neurons in the bilateral ACG were divided into GSN-stimulus-relative neurons (GSRNs) and GSN-stimulus-irrelative ones. According to the characteristics of the evoked responses to electrical stimulation of the GSN, GSRNs could be further classified into visceral nociceptive neurons (VNNs) and non-visceral nociceptive neurons (NVNNs). VNNs included specific visceral nociceptive neurons (SVNNs) and non-specific visceral nociceptive neurons (NSVNNs). The results showed that the percentage of GSRNs in the contralateral ACG (38.18%) was significantly higher than that in the ipsilateral ACG (29.49%, P<0.01), suggesting although GSN afferent fibers project to bilateral ACG, they mainly project to the contralateral ACG. Compared with ipsilateral ACG, contralateral ACG possessed lower proportion of SVNNs and higher proportion of NSVNNs (P<0.01). The absolute values of resting potentials (RP) of GSRNs, VNNs, NVNNs and SVNNs in ipsilateral ACG were less than those of corresponding neurons in contralateral ACG. However, there were no significant differences in the absolute values of RP of NSVNNs between ipsilateral and contralateral ACG. There were no significant differences in modes, frequencies and amplitudes of spontaneous electric activities of VNNs and NVNNs between ipsilateral and contralateral ACG. Additionally, the percentage of neurons having spontaneous electric activities from VNNs was significantly higher than that from NVNNs, which indicated that the excitability of VNNs was higher than that of the NVNNs in bilateral ACG. These results suggest that the patterns and degrees of the responses to nociceptive GSN-stimulation of the ipsilateral and contralateral ACG are different, thus providing new experimental data for the asymmetry of functions of the bilateral brain.

Nurse staffing and healthcare-associated infections in a national healthcare system that implemented a nurse staffing directive: Multi-level interrupted time series analyses.

BACKGROUND: In 2010, the Veterans Health Administration Office of Nursing Services (VHA ONS) issued a Staffing Methodology (SM) Directive, standardizing the method of determining appropriate nurse staffing for VHA facilities. OBJECTIVES: To assess associations between the Directive, nurse staffing trends, and healthcare-associated infections. RESEARCH DESIGN: We conducted multi-level interrupted time series analyses of nurse staffing trends and the rates of two healthcare-associated infections before and after implementation of the Directive, October 1, 2008 - June 30, 2014. SUBJECTS: Acute care, critical care, mental health acute care, and longterm care nursing units (called Community Living Centers, CLC in VHA) among 285 VHA facilities were included in nurse staffing trends analyses, while acute and critical care units in 123 facilities were used in the analysis of infection rates. MEASURES: Monthly rates were calculated at the facility unit level and included nursing hours per patient day (NHPPD) for all nursing personnel and number of catheter-associated urinary tract infections (CAUTI) and central line-associated bloodstream infections (CLABSI) per 1000 device days. RESULTS: Nursing hours per patient day increased in both time periods. However, the differential change in rate of nursing hours per patient day following implementation of the Directive was not statistically significant. On average, we found a statistically significant decrease of 0.05 unit in the post-Directive central line-associated bloodstream infection rates associated with a unit increase in nursing hours per patient day. CONCLUSIONS: System-wide implementation of Staffing Methodology may be one contributing factor impacting patient outcomes.

Equivalence of two healthcare costing methods: bottom-up and top-down.

This paper compares two quite different approaches to estimating costs: a 'bottom-up' approach, represented by the US Department of Veterans Affairs' (VA) Decision Support System that uses local costs of specific inputs; and a 'top-down' approach, represented by the costing system created by the VA Health Economics Resource Center, which assigns the VA national healthcare budget to specific products using various weighting systems. Total annual costs per patient plus the cost for specific services (e.g. clinic visit, radiograph, laboratory, inpatient admission) were compared using scatterplots, correlations, mean difference, and standard deviation of individual differences. Analysis are based upon 2001 costs for 14 915 patients at 72 facilities. Correlations ranged from 0.24 for the cost of outpatient encounters to 0.77 for the cost of inpatient admissions, and 0.85 for total annual cost. The mean difference between costing methods was $707 ($4168 versus $3461) for total annual cost. The standard deviation of the individual differences was $5934. Overall, the agreement between the two costing systems varied by the specific cost being measured and increased with aggregation. Administrators and researchers conducting cost analyses need to carefully consider the purpose, methods, characteristics, strengths, and weaknesses when selecting a method for assessing cost.

Molecular design of 1,2,4,5-tetrazine-based high-energy density materials.

The heats of formation (HOFs) for a series of 1,2,4,5-tetrazine derivatives were calculated by using density functional theory (DFT), Hartree Fork (HF), and Møller-Plesset (MP2) as well as semiempirical methods. The effects of different basis bets on HOFs were also considered. Our results show that the -CN or -N3 group plays a very important role in increasing the HOF values of the 1,2,4,5-tetrazine derivatives. An analysis of the bond dissociation energies for the weakest bonds indicates that substitutions of the -N3, -NH2, -CN, -OH, or -Cl group are favorable for enhancing the thermal stability of 1,2,4,5-tetrazine, but the -NHNH2, -NHNO2, -NO2, -NF2, or -COOH group produces opposite effects. The calculated detonation velocities and pressures indicate that the -NF2 or -NO2 group is very helpful for enhancing the detonation performance for the derivatives, but the case is quite the contrary for the -CN, -NH2, or -OH group. Considered the detonation performance and thermal stability, three derivatives may be regarded as potential candidates of high-energy density materials (HEDMs).

Line authority for nurse staffing and costs for acute inpatient care.

There is little empirical evidence evaluating the effects of recent, widespread changes in nurse executive roles and nursing management structures on the costs of patient care. This retrospective cross-sectional study examined the relationship between line authority for nurse staffing and patient care costs (total, nursing, and non-nursing cost) using data from 124 Department of Veterans Affairs (VA) medical centers. After controlling for patient, facility, and market characteristics, nursing line authority was significantly associated with lower nursing cost per admission. Our results provide some evidence that a reduction in nursing line authority may adversely impact nursing costs.

Multiple "Omics" data-based biomarker screening for hepatocellular carcinoma diagnosis.

The huge prognostic difference between early and late stage hepatocellular carcinoma (HCC) is a challenging diagnostic problem. Alpha-fetoprotein is the mostly widely used biomarker for HCC used in the clinic, however it's sensitivity and specificity of is not optimal. The development and application of multiple biotechnologies, including next generation sequencing, multiple "omics" data, that include genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics has been used for HCC diagnostic biomarker screening. Effective biomarkers/panels/models have been identified and validated at different clinical levels. A large proportion of these have a good diagnostic performance for HCC, especially for early HCC. In this article, we reviewed the various HCC biomarkers derived from "omics" data and discussed the advantages and disadvantages for diagnosis HCC.

DNA methylation-regulated and tumor-suppressive roles of miR-487b in colorectal cancer via targeting MYC, SUZ12, and KRAS.

Human colorectal cancer (CRC), characterized by its high morbidity and lethality, seriously threatens human health and lives. MicroRNA-487b (miR-487b) is currently reported to be aberrantly expressed in several tumors, but the detailed functions and underlying mechanisms of miR-487b in CRC remain unclear. Here, we found that miR-487b is downregulated in CRC cell lines and is markedly decreased in tumor specimens derived from CRC patients. MiR-487b inhibits cell proliferation, migration and invasion and promotes the apoptosis of CRC cells in vitro. Statistical analysis of clinical samples indicates that miR-487b may serve as a biomarker for early CRC diagnosis. Inverse correlations between the expression levels of MYC, SUZ12, and KRAS and that of miR-487b exist in vitro and in CRC patient tissue specimens. Further experiments demonstrated the regulatory effects of miR-487b on MYC, SUZ12, and KRAS, and the disruption of these genes partially restores the miR-487b inhibitor-induced phenotype. Additionally, miR-487b promoter region is in a DNA hypermethylated condition and the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-Aza) increases the levels of miR-487b but suppresses the expression of MYC, SUZ12, and KRAS in a time- and concentration-dependent manner in CRC cells. Collectively, miR-487b is regulated by DNA methylation and it functions as a tumor suppressor in CRC mainly through targeting MYC, SUZ12, and KRAS. Our study provides insight into the regulatory network in CRC cells, offering a new target for treating CRC patients.

The association between nursing factors and patient mortality in the Veterans Health Administration: the view from the nursing unit level.

CONTEXT: Nurse staffing is not the same across an entire hospital. Nursing care is delivered in geographically-based units, with wide variation in staffing levels. In particular, staffing in intensive care is much richer than in nonintensive care acute units. OBJECTIVE: To evaluate the association of in-hospital patient mortality with registered nurse staffing and skill mix comparing hospital and unit level analysis using data from the Veterans Health Administration (VHA). DESIGN, SETTINGS, AND PATIENTS: A retrospective observational study using administrative data from 129,579 patients from 453 nursing units (171 ICU and 282 non-ICU) in 123 VHA hospitals. METHODS: We used hierarchical multilevel regression models to adjust for patient, unit, and hospital characteristics, stratifying by whether or not patients had an ICU stay during admission. MAIN OUTCOME MEASURE: In-hospital mortality. RESULTS: : Of the 129,579 patients, mortality was 2.9% overall: 6.7% for patients with an ICU stay compared with 1.6% for those without. Whether the analysis was done at the hospital or unit level affected findings. RN staffing was not significantly associated with in-hospital mortality for patients with an ICU stay (OR, 1.02; 95% CI, 0.99-1.03). For non-ICU patients, increased RN staffing was significantly associated with decreased mortality risk (OR, 0.91; 95% CI, 0.86-0.96). RN education was not significantly associated with mortality. CONCLUSIONS: Our findings suggest that the association between RN staffing and skill mix and in-hospital patient mortality depends on whether the analysis is conducted at the hospital or unit level. Variable staffing on non-ICU units may significantly contribute to in-hospital mortality risk.

Nurses' intention to resign and avoidance of emergency department violence: A moderated mediation model.

BACKGROUND: Studies that examined the negative impact of violence in emergency departments on nurses' leave and avoidance behavior are well-documented. However, few studies provided an integrated model of how and when violence influences their leave and avoidance behavior. PURPOSE: The study adopted Affective Events Theory to propose and examine a model of violent events, negative emotions, and (leave and avoidance) behaviors on nurses in emergency departments and further analyzed whether the model is salient to nurses' occupational burnout, nursing experience, and nursing rank. METHOD: The sample included 123 emergency department nurses at a teaching hospital in northern, Taiwan. RESULTS: All participants had experienced violent incidents within the preceding 6 months. Moderated mediation analysis suggested that nurses experienced one of two emotional processes following violent incidents: "violence-negative feelings toward work-intention to resign" or "violence-negative emotion and physical symptoms-avoidance tendencies." Moreover, nurses with high burnout levels expressed weaker intention to resign after violent incidents, while nurses with more experience and higher rank were less likely to avoid violence after violent incidents. CONCLUSION: Emergency nurses do not simply elect to escape but may engage in avoidance behavior. This study revealed that how violent incidents affect nurses' resignation or avoidance behaviors depends on how they feel. Occupational burnout and nurses' attributes affected their behavior.

Utilization and expenditures of veterans obtaining primary care in community clinics and VA medical centers: an observational cohort study.

BACKGROUND: To compare VA inpatient and outpatient utilization and expenditures of veterans seeking primary care in community-based outpatient clinics (CBOCs) and VA medical centers (VAMCs) in fiscal years 2000 (FY00) and 2001. METHODS: The sample included 25,092 patients who obtained primary care exclusively from 108 CBOCs in FY00, 26,936 patients who obtained primary care exclusively from 72 affiliated VAMCs in FY00, and 11,450 "crossover" patients who obtained primary care in CBOCs and VAMCs in FY00. VA utilization and expenditure data were drawn from the VA's system-wide cost accounting system. Veteran demographic characteristics and a 1999 Diagnostic Cost Group risk score were obtained from VA administrative files. Outpatient utilization (primary care, specialty care, mental health, pharmacy, radiology and laboratory) and inpatient utilization were estimated using count data models and expenditures were estimated using one-part or two-part models. The second part of two-part models was estimated using generalized linear regressions. RESULTS: CBOC patients had a slightly more primary care visits per year than VAMC patients (p < 0.0001), but lower primary care costs (-$71, p < 0.0001). CBOC patients had lower odds of one or more specialty, mental health, ancillary visits and hospital stays per year, and fewer numbers of visits and stays if they had any and lower specialty, mental health, ancillary and inpatient expenditures (all, p < 0.0001). As a result, CBOC patients had lower total outpatient and overall expenditures than VAMC patients (p < 0.0001). CONCLUSION: CBOCs provided veterans improved access to primary care and other services, but expenditures were contained because CBOC patients who sought health care had fewer visits and hospital stays than comparable VAMC patients. These results suggest a more complex pattern of health care utilization and expenditures by CBOC patients than has been found in prior studies. This study also illustrates that CBOCs continue to be a critical primary care and mental health access point for veterans.

Epigenetically regulated miR-145 suppresses colon cancer invasion and metastasis by targeting LASP1.

MiR-145 is a tumor-suppressive microRNA that participates in the malignant progression of colorectal cancer (CRC). Although miR-145 has been reported to inhibit proliferation and to induce apoptosis of CRC cells, the reports about its role in invasion and metastasis are controversial. The regulation of miR-145 its own expression also requires further elucidation. In this study, we firstly found that miR-145 is markedly downregulated in the metastatic tumors of CRC patients. Then through gain- and loss-of function studies, we demonstrated that miR-145 suppresses the invasion and metastasis of CRC cells. We also provided experimental evidences which include direct binding assays and verifications on tissue specimens to confirm that LIM and SH3 protein 1 (LASP1) is a direct target of miR-145. Furthermore, we identified the core promoter regions of miR-145 and observed the cooperation between histone methylation and transcription factors through binding to these core promoter regions to regulate the expression of miR-145 in CRC cells. Our study provides an insight into the regulatory network in CRC cells, thus offering new targets for treating CRC patients.