Publications by authors named "Yumei Cao"

66 Publications

Decreased miR-214-3p activates NF-κB pathway and aggravates osteoarthritis progression.

EBioMedicine 2021 Mar 11;65:103283. Epub 2021 Mar 11.

Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia. Electronic address:

Background: Osteoarthritis (OA), a disease with whole-joint damage and dysfunction, is the leading cause of disability worldwide. The progressive loss of hyaline cartilage extracellular matrix (ECM) is considered as its hallmark, but its exact pathogenesis needs to be further clarified. MicroRNA(miRNA) contributes to OA pathology and may help to identify novel biomarkers and therapies against OA. Here we identified miR-214-3p as an important regulator of OA.

Methods: qRT-PCR and in situ hybridization were used to detect the expression level of miR-214-3p. The function of miR-214-3p in OA, as well as the interaction between miR-214-3p and its downstream mRNA target (IKBKB), was evaluated by western blotting, immunofluorescence, qRT-PCR and luciferase assay. Mice models were introduced to examine the function and mechanism of miR-214-3p in OA in vivo.

Findings: In our study, we found that miR-214-3p, while being down-regulated in inflamed chondrocytes and OA cartilage, regulated ECM metabolism and cell apoptosis in the cartilage. Mechanically, the protective effect of miR-214-3p downregulated the IKK-β expression and led to the dysfunction of NF-κB signaling pathway. Furthermore, intra-articular injection of miR-214-3p antagomir in mice joints triggered spontaneous cartilage loss while miRNA-214-3p agomir alleviated OA in the experimental mouse models.

Interpretation: Decreased miR-214-3p activates the NF-κB signaling pathway and aggravates OA development through targeting IKKβ, suggesting miR-214-3p may be a novel therapeutic target for OA.

Funding: This study was financially supported by grants from the National Natural Science Foundation of China (81,773,532, 81,974,342).
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http://dx.doi.org/10.1016/j.ebiom.2021.103283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957119PMC
March 2021

Development, Validation, and Evaluation of a Simple Machine Learning Model to Predict Cirrhosis Mortality.

JAMA Netw Open 2020 11 2;3(11):e2023780. Epub 2020 Nov 2.

Veterans Affairs (VA) Health Services Research and Development Service Center for Innovations in Quality, Effectiveness, and Safety, Houston, Texas.

Importance: Machine-learning algorithms offer better predictive accuracy than traditional prognostic models but are too complex and opaque for clinical use.

Objective: To compare different machine learning methods in predicting overall mortality in cirrhosis and to use machine learning to select easily scored clinical variables for a novel cirrhosis prognostic model.

Design, Setting, And Participants: This prognostic study used a retrospective cohort of adult patients with cirrhosis or its complications seen in 130 hospitals and affiliated ambulatory clinics in the integrated, national Veterans Affairs health care system from October 1, 2011, to September 30, 2015. Patients were followed up through December 31, 2018. Data were analyzed from October 1, 2017, to May 31, 2020.

Exposures: Potential predictors included demographic characteristics; liver disease etiology, severity, and complications; use of health care resources; comorbid conditions; and comprehensive laboratory and medication data. Patients were randomly selected for model development (66.7%) and validation (33.3%). Three different statistical and machine learning methods were evaluated: gradient descent boosting, logistic regression with least absolute shrinkage and selection operator (LASSO) regularization, and logistic regression with LASSO constrained to select no more than 10 predictors (partial pathway model). Predictor inclusion and model performance were evaluated in a 5-fold cross-validation. Last, the predictors identified in the most parsimonious (the partial path) model were refit using maximum-likelihood estimation (Cirrhosis Mortality Model [CiMM]), and its predictive performance was compared with that of the widely used Model for End Stage Liver Disease with sodium (MELD-Na) score.

Main Outcomes And Measures: All-cause mortality.

Results: Of the 107 939 patients with cirrhosis (mean [SD] age, 62.7 [9.6] years; 96.6% male; 66.3% white, 18.4% African American), the annual mortality rate ranged from 8.8% to 15.3%. In total, 32.7% of patients died within 3 years, and 46.2% died within 5 years after the index date. Models predicting 1-year mortality had good discrimination for the gradient descent boosting (area under the receiver operating characteristics curve [AUC], 0.81; 95% CI, 0.80-0.82), logistic regression with LASSO regularization (AUC, 0.78; 95% CI, 0.77-0.79), and the partial path logistic model (AUC, 0.78; 95% CI, 0.76-0.78). All models showed good calibration. The final CiMM model with machine learning-derived clinical variables offered significantly better discrimination than the MELD-Na score, with AUCs of 0.78 (95% CI, 0.77-0.79) vs 0.67 (95% CI, 0.66-0.68) for 1-year mortality, respectively (DeLong z = 17.00; P < .001).

Conclusions And Relevance: In this study, simple machine learning techniques performed as well as the more advanced ensemble gradient boosting. Using the clinical variables identified from simple machine learning in a cirrhosis mortality model produced a new score more transparent than machine learning and more predictive than the MELD-Na score.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.23780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610191PMC
November 2020

Molecular characterization of a novel cytorhabdovirus associated with paper mulberry mosaic disease.

Arch Virol 2020 Nov 26;165(11):2703-2707. Epub 2020 Aug 26.

National Citrus Engineering and Technology Research Center, Citrus Research Institute, Southwest University, Chongqing, China.

A novel cytorhabdovirus, tentatively named "paper mulberry mosaic-associated virus" (PMuMaV), was discovered and identified by transcriptome sequencing (RNA-seq), small RNA sequencing (sRNA-seq), and RT-PCR amplification. The whole-genome sequence of PMuMaV is 13,736 nucleotides (nt) in length and contains six open reading frames (ORFs) encoding a nucleocapsid protein (N), a phosphoprotein (P), a putative movement protein (P3), a matrix protein (M), a glycoprotein (G), and an RNA-dependent RNA polymerase (L). The coding sequences are flanked by a 194-nt leader and a 370-nt trailer sequence at the 3' terminus and 5' terminus, respectively. Pairwise sequence comparisons showed that PMuMaV is related to northern cereal mosaic virus (NCMV, 38.97%), barley yellow striate mosaic virus (BYSMV, 38.86%), and maize yellow striate virus (MYSV, 38.76%), and phylogenetic analysis also placed these viruses together into the same branch, thus suggesting that PMuMaV is a member of a new species in the genus Cytorhabdovirus.
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http://dx.doi.org/10.1007/s00705-020-04786-1DOI Listing
November 2020

Effectiveness of Elbasvir/Grazoprevir in US Veterans with Chronic Hepatitis C Virus Genotype 1b Infection.

Infect Dis Ther 2020 Jun 15;9(2):355-365. Epub 2020 Apr 15.

Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey VA Medical Center, Houston, TX, USA.

Introduction: Real-world treatment of hepatitis C virus (HCV) infection is complicated by many factors that are controlled for in the rigorous clinical trial setting. The aim of the present study was to assess the efficacy of elbasvir/grazoprevir in a Veterans Affairs population with chronic HCV genotype 1b infection.

Methods: This was a retrospective analysis of a cohort of patients aged ≥ 18 years with chronic HCV genotype 1b infection and ≥ 1 prescription of elbasvir/grazoprevir between February 1, 2016, and August 31, 2017. The primary analysis was conducted in the per-protocol population, which included all patients who had at least 11 weeks of treatment and had an available assessment for sustained virologic response (SVR) based on virologic data post-follow-up week 4.

Results: The per-protocol population included 3371 patients. Overall, 97.3% of patients were male, 60.3% were black, and 85.5% were HCV treatment-experienced. Comorbidities in this population included hypertension (74.4%), history of alcohol use (55.7%), and depression (54.8%). In total, 97.5% of patients (3288/3371) achieved SVR. Among patient sub-groups, SVR was achieved by 96.0% (290/302) of those with chronic kidney disease stage 4/5, 97.8% (1527/1561) of those with a history of drug use, and 96.6% (831/860) of those with cirrhosis. No statistically significant differences were observed in the proportions of patients achieving SVR, regardless of age, race, HCV treatment history, viral load level, treatment regimen/duration, history of drug or alcohol use, HIV co-infection, or chronic kidney disease.

Conclusion: Elbasvir/grazoprevir was highly effective in individuals with HCV genotype 1b infection in a large national Veterans Affairs clinical setting.
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http://dx.doi.org/10.1007/s40121-020-00293-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237563PMC
June 2020

[Daxx overexpression inhibits AngⅡ-induced proliferation and migration in vascular smooth muscle cells].

Nan Fang Yi Ke Da Xue Xue Bao 2019 Oct;39(10):1173-1179

School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China.

Objective: To construct a recombinant lentiviral expression vector pCDH-Daxx-EGFP to investigate the effect of Daxx on the proliferation of vascular smooth muscle cells (VSMCs).

Methods: The recombinant lentiviral expression vector pCDHDaxx-EGFP was constructed using PCR-based accurate synthesis method. After identification by sequencing and enzyme digestion, the recombinant lentiviral vector was contransfected into 293T cells with lentivirus packaging vector. The recombinant lentivirus particles were collected and purified to infect VSMCs, whose expression of Daxx was detected with Western boltting. The cells infected with the empty vector pCDH-EGFP or pCDH-Daxx-EGFP were incubated in serum-free medium or in the presence of angiotensin Ⅱ (AngⅡ). The cell viability was determined with MTT assay, and the cell cycle changes were analyzed with flow cytometry. The cell migration ability was assessed using a scratch wound healing assay. The expression of p-Akt protein in the cells was detected using Western blotting.

Results: Double enzyme digestion and sequencing confirmed successful construction of the recombinant plasmid. Compared with the cells infected with the empty vector, the cells infected with pCDH-Daxx-EGFP exhibited significantly increased expressions of Daxx protein ( < 0.05). AngⅡ treatment of the cells infected with the pCDH-Daxx-EGFP, as compared with the cells infected with the empty vector, significantly lowered the cell viability, S phase cell ratio and cell migration ability ( < 0.05), and significantly decreased the expression level of p-Akt protein ( < 0.05).

Conclusions: We successfully constructed the recombinant lentiviral vector pCDH-Daxx-EGFP and overexpressed Daxx in primary cultured VSMCs using this vector. Daxx overexpression can inhibit AngⅡ-induced proliferation and migration in VSMCs probably by regulating p-Akt protein.
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http://dx.doi.org/10.12122/j.issn.1673-4254.2019.10.07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6867952PMC
October 2019

Long-Term Risk of Hepatocellular Carcinoma in HCV Patients Treated With Direct Acting Antiviral Agents.

Hepatology 2020 01 19;71(1):44-55. Epub 2019 Aug 19.

Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX.

Sustained virologic response (SVR) after direct acting antiviral agents (DAAs) holds promise for reducing hepatocellular cancer (HCC). DAAs have recently been available long enough to estimate the long-term risk. We conducted a retrospective cohort study of hepatitis C virus (HCV) patients who achieved SVR with DAAs from 129 Veterans Health Administration hospitals between January 1, 2015, and December 31, 2015, with follow-up through September 30, 2018. We calculated the overall and quarterly HCC incidence rates. We examined the effect of demographic, clinical, and behavioral factors and the decline or increase of FIB-4 and aspartate aminotransferase to platelet ratio index (APRI) on HCC risk. Among the 18,076 patients with SVR, 544 incident cases of HCC were diagnosed during the mean 2.9 years of follow-up. The cumulative 1, 2, and 3-year risks of HCC were 1.1%, 1.9% and 2.8%, respectively. Cirrhosis was strongly associated with HCC risk (adjusted hazard ratio = 4.13, 95% confidence interval = 3.34-5.11). The quarterly incidence rate of HCC remained stable between 1.00 and 1.23/100 person-years (PY) and 1.5 to 2.3/100 PY in patients with cirrhosis. The risk of HCC was the highest in patients who had persistently high FIB-4/APRI and both with and without cirrhosis. HCC risk fell in patients with cirrhosis who experienced a decrease of FIB-4/APRI scores yet remained higher than the accepted threshold for HCC surveillance. HCC risk was also higher in patients with alcohol use, older age, and infection with HCV genotype 3. Most patients treated at an early stage of liver fibrosis had a stable low risk. Conclusion: Patients successfully treated with DAAs and at risk of HCC did not regress after 3.6 years of follow-up. HCC risk remained above the accepted thresholds for surveillance in patients with cirrhosis. These data have important implications for HCC surveillance in cured HCV patients.
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http://dx.doi.org/10.1002/hep.30823DOI Listing
January 2020

Risk of Hepatocellular Cancer Recurrence in Hepatitis C Virus+ Patients Treated with Direct-Acting Antiviral Agents.

Dig Dis Sci 2019 11 30;64(11):3328-3336. Epub 2019 Apr 30.

Sections of Gastroenterology and Hepatology and Health Services Research, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, 2002 Holcombe Blvd. (MS152), Houston, TX, 77030, USA.

Background: With advent of direct-acting antiviral agents (DAA), hepatitis C virus (HCV) treatment is dramatically increasing. Although few studies reported rates of hepatocellular carcinoma (HCC) recurrence following DAA treatment, there have been no studies that followed sufficient number of DAA-treated patients after successful HCC treatment to examine HCC recurrence.

Methods: We conducted a cohort study of HCV+ patients who had successfully treated HCC before initiating DAAs. We conducted medical record reviews to confirm HCC diagnosis, treatment, and remission prior to DAA initiation, and subsequent HCC recurrence. We calculated HCC recurrence rate and examined the recurrent tumor characteristics. We used Cox proportional hazard model to identify factors associated with HCC recurrence.

Results: We identified 264 HCV+ patients who received DAAs after an average of 30.9 (20.6) months following HCC treatment. HCC recurred in 26.1% patients during 23.3 (9.8) months follow-up, at a rate of 0.38 [0.30, 0.48] per 1000 person-month. Most (82.3%) recurrent HCC were early stage. Receiving non-curative treatment for HCC was associated with a higher risk of recurrence than curative treatment (HR = 2.06, [1.24, 3.40]). The risk of HCC recurrence decreased with longer duration between HCC treatment completion and DAA initiation (HR = 0.97, [0.95, 0.99] per additional month). Compared with patients who achieved sustained virological response (SVR), those without SVR had significantly increased risk of HCC recurrence (HR = 4.17, [1.48, 11.75]).

Conclusions: We conclude that most HCV+ patients with HCC benefit from DAA treatment; however, timing of DAA initiation after HCC treatment should be carefully considered.
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http://dx.doi.org/10.1007/s10620-019-05641-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819241PMC
November 2019

The Role of Tumor Oxygenation Tested by Magnetic Resonance Imaging (MRI) in Prostate Cancer Grading.

Med Sci Monit 2019 Apr 5;25:2505-2510. Epub 2019 Apr 5.

Department of Urology, Provincial Hospital Affiliated to Shandong University, Ji'nan, Shandong, China (mainland).

BACKGROUND Prostate cancer is a common malignant tumor in males. Prostate cancer grading is an important basis for evaluation of invasion. The purpose of this article was to use dynamic enhanced scan magnetic resonance imaging (MRI) to quantitatively investigate the relationship between tumor oxygenation value and prostate cancer pathological Gleason score. MATERIAL AND METHODS A total of 312 prostate cancer patients diagnosed by needle biopsy who received MRI dynamic enhanced scan were enrolled in this study. Multiparameter oxygen concentration image based on MRI was applied to test pO2 in tumors. Multiple spin resonance image relaxation time edit sequence and weak field diffusion model were used to estimate oxygen saturation level and pO2. hematoxylin and eosin staining and Gleason score were used to determine biological behavior and prognosis. RESULTS According to the Gleason score system, there were 28 cases with a score of 10, 112 cases with a score of 9, 56 cases with a score of 8, and 116 cases with a score lower than 7. The enrolled patients were divided into groups: 116 cases into the middle-to-well differentiation group (Gleason score ≤7) and 196 cases into the poorly differentiation group (Gleason score at 8 to 10). Prostate cancer tumor oxygenation value was positively correlated with Gleason score (r=0.349, P<0.05) or PSA (r=0.432, P<0.05). Tumor oxygenation value in Gleason ≤7 group was obviously different from that in the group with Gleason score between 9 and 10 (P<0.05). CONCLUSIONS Tumor oxygenation value in prostate cancer was positively correlated with Gleason score. Tumor oxygenation value might be useful in clinics to evaluate prostate cancer grading and prognosis.
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http://dx.doi.org/10.12659/MSM.913110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463617PMC
April 2019

Implementation of a Population-Based Cirrhosis Identification and Management System.

Clin Gastroenterol Hepatol 2018 08 24;16(8):1182-1186.e2. Epub 2018 May 24.

Center for Innovation to Implementation, Palo Alto Veterans Affairs Medical Center, Palo Alto, California; Division of Primary Care and Population Health, Stanford University, Palo Alto, California.

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http://dx.doi.org/10.1016/j.cgh.2018.01.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185902PMC
August 2018

Apatinib promotes apoptosis of the SMMC-7721 hepatocellular carcinoma cell line via the PI3K/Akt pathway.

Oncol Lett 2018 Apr 12;15(4):5739-5743. Epub 2018 Feb 12.

Department of Pediatrics, Heze Medical College, Heze, Shandong 274000, P.R. China.

The present study investigated the inhibitory effects of apatinib on the proliferation of the SMMC-7721 hepatocellular carcinoma cell line to explore the possible mechanism. The MTT assay was used to detect the inhibitory effects of the different concentrations of apatinib on the proliferation of SMMC-7721 cells. Annexin V/PI double staining was performed to investigate the effects of apatinib on the apoptosis of SMMC-7721 cells. Expression of the apoptosis-related genes and after apatinib treatment was detected by reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis. Expression of the PI3K, p-PI3K, Akt and p-Akt proteins after apatinib treatment was detected using western blot analysis. The MTT results showed that apatinib inhibited the proliferation of SMMC-7721 cells. Annexin V/PI double staining showed that apatinib induced the apoptosis of SMMC-7721 cells in a concentration-dependent manner. Results of RT-qPCR and western blot analysis showed that apatinib was able to induce the expression of pro-apoptotic genes and and inhibited the expression of anti-apoptotic gene . In addition, the western blot analysis revealed that p-PI3K and p-Akt was significantly decreased following apatinib treatment, while no significant differences were found in the total protein levels of PI3K and Akt. The results of the present show that apatinib is capable of promoting the apoptosis of SMMC-7721 cells by inhibiting the PI3K/Akt signal transduction pathway, upregulating the expression of pro-apoptotic genes and , and downregulating the expression level of the anti-apoptotic gene .
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http://dx.doi.org/10.3892/ol.2018.8031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840725PMC
April 2018

Risk of Hepatocellular Cancer in HCV Patients Treated With Direct-Acting Antiviral Agents.

Gastroenterology 2017 10 19;153(4):996-1005.e1. Epub 2017 Jun 19.

Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Section of Gastroenterology and Hepatology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, Texas.

Background And Aims: The risk of hepatocellular cancer (HCC) after sustained virological response (SVR) with direct-acting antivirals (DAA) is unclear. Our aim was to examine the risk and determinants of HCC in patients cured with DAA.

Methods: We conducted a retrospective cohort study of hepatitis C virus patients who were treated with DAA in any of the 129 Veterans Health Administration hospitals between January 1, 2015 and December 31, 2015. We calculated the annual incidence rates of HCC by SVR. We used Cox regression models to compare the risk of HCC in patients with vs those without SVR and to identify factors associated with incident HCC among patients with SVR. We reviewed a sample of HCC patients for tumor size and stage at diagnosis.

Results: Among 22,500 patients treated with DAA (19,518 with SVR; 2982 without SVR), the mean (standard deviation) age was 61.6 (6.1) years, and 39.0% had cirrhosis. There were 271 new cases of HCC, including 183 in patients with SVR. Compared with patients without SVR, those with SVR had a significantly reduced risk of HCC (0.90 vs 3.45 HCC/100 person-years; adjusted hazard ratio, 0.28, 95% CI=0.22-0.36). Patients with cirrhosis had the highest annual incidence of HCC after SVR (1.82 vs 0.34/100 person-years in patients without cirrhosis; adjusted hazard ratio, 4.73. 95% CI, 3.34-6.68). Most (>44.8%) HCC were classified as stage I. Maximum size of the largest lesion was ≤5 cm in over 75% of cases.

Conclusions: Among patients treated with DAA, SVR was associated with a considerable reduction in the risk of HCC. We did not find any evidence to suggest that DAAs promote HCC. However, in patients with SVR, the absolute risk of HCC remained high in patients with established cirrhosis. These patients should be considered for ongoing HCC surveillance.
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http://dx.doi.org/10.1053/j.gastro.2017.06.012DOI Listing
October 2017

Paneth cell defects in Crohn's disease patients promote dysbiosis.

JCI Insight 2016 06 2;1(8):e86907. Epub 2016 Jun 2.

Department of Pediatrics, Division of Gastroenterology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Background: Paneth cell dysfunction has been implicated in a subset of Crohn's disease (CD) patients. We previously stratified clinical outcomes of CD patients by using Paneth cell phenotypes, which we defined by the intracellular distribution of antimicrobial proteins. Animal studies suggest that Paneth cells shape the intestinal microbiome. However, it is unclear whether Paneth cell phenotypes alter the microbiome complexity in CD subjects. Therefore, we analyzed the correlation of Paneth cell phenotypes with mucosal microbiome composition and ileal RNA expression in pediatric CD and noninflammatory bowel disease (non-IBD) patients.

Methods: Pediatric CD ( = 44) and non-IBD ( = 62) patients aged 4 to 18 were recruited prior to routine endoscopic biopsy. Ileal mucosal samples were analyzed for Paneth cell phenotypes, mucosal microbiome composition, and RNA transcriptome.

Results: The prevalence of abnormal Paneth cells was higher in pediatric versus adult CD cohorts. For pediatric CD patients, those with abnormal Paneth cells showed significant changes in their ileal mucosal microbiome, highlighted by reduced protective microbes and enriched proinflammatory microbes. Ileal transcriptome profiles showed reduced transcripts for genes that control oxidative phosphorylation in CD patients with abnormal Paneth cells. These transcriptional changes in turn were correlated with specific microbiome alterations. In non-IBD patients, a subset contained abnormal Paneth cells. However, this subset was not associated with alterations in the microbiome or host transcriptome.

Conclusion: Paneth cell abnormalities in human subjects are associated with mucosal dysbiosis in the context of CD, and these changes are associated with alterations in oxidative phosphorylation, potentially in a feedback loop.

Funding: The research was funded by Helmsley Charitable Trust (to T.S. Stappenbeck, R.J. Xavier, and D.P.B. McGovern), Crohn's and Colitis Foundation of America (to N.H. Salzman, T.S. Stappenbeck, R.J. Xavier, and C. Huttenhower), and Doris Duke Charitable Foundation grant 2014103 (to T.C. Liu).
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033844PMC
http://dx.doi.org/10.1172/jci.insight.86907DOI Listing
June 2016

Risk and Predictors of Variceal Bleeding in Cirrhosis Patients Receiving Primary Prophylaxis With Non-Selective Beta-Blockers.

Am J Gastroenterol 2016 12 27;111(12):1778-1787. Epub 2016 Sep 27.

Section of Gastroenterology and Hepatology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.

Objectives: Prior studies have demonstrated the efficacy of non-selective beta-blockers (NSBB) in preventing first variceal bleeding in patients with cirrhosis. However, little is known about the overall effectiveness of NSBB in routine clinical care.

Methods: We conducted a retrospective cohort study of cirrhotic patients without prior bleeding who initiated a NSBB (propranolol, nadolol) at any Veterans Administration facility between 2008 and 2013. The primary outcome was variceal bleeding within 12 months. We conducted Cox-proportional hazards analyses to identify demographic, clinical, and NSBB-related (type of NSBB, mean dose, dose change, and heart rate response) factors associated with variceal bleeding.

Results: Of 5,775 patients, 678 (11.7%) developed variceal bleeding. Mean daily dose of NSBB was <40 mg in 58.8%, 18.1% had either upward or downward titration in NSBB dose, and 9.8% had hemodynamic response. Patients who were younger, with ascites, greater medical comorbidity, and higher MELD (Model for end-stage liver disease) scores had a higher risk of variceal bleeding. Patients on a higher daily dose (>60 vs. <40 mg, adjusted hazard ratio (HR) 0.64; 95% confidence interval (CI): 0.51-0.81), who had either upward or downward dose titration (adjusted HR 0.69; 95% CI: 0.52-0.90 and 0.64; 95% CI 0.45-0.90, respectively), and those who achieved hemodynamic response (adjusted HR 0.75; 95% CI=0.57-1.0) had lower risk.

Conclusions: Approximately 12% of patients bled while being on NSBB for primary prophylaxis. A higher NSBB dose and dose titration were protective; yet most patients did not have the NSBB dose titrated to the recommended levels. Our data highlight the need for careful monitoring of cirrhotic patients on NSBB.
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http://dx.doi.org/10.1038/ajg.2016.440DOI Listing
December 2016

Evaluation of an oral health education session for Early Head Start home visitors.

J Public Health Dent 2016 06 27;76(3):167-70. Epub 2016 Jan 27.

Department of Pediatrics, Center for the Advancement of Underserved Children, Medical College of Wisconsin, Milwaukee, WI, USA.

Objectives: Home visiting programs promote the education and health of Early Head Start (EHS) children and pregnant women. However, EHS's oral health component is unevenly implemented. We conducted an educational intervention to improve oral health knowledge and motivational interviewing techniques among Wisconsin EHS home visitors.

Methods: A questionnaire assessing oral health-related knowledge and confidence was administered to home visitors before and after an educational session. Changes between pre/post-responses were analyzed with McNemar's test and Wilcoxon Signed Rank test.

Results: After the intervention there were increases in both knowledge and confidence related to oral health communication. Knowledge increases were observed in such topics as fluoridation, dental caries, and caregivers' role in assisting and supervising children's tooth brushing.

Conclusions: A brief educational intervention was associated with increased home visitor knowledge and confidence in communicating oral health messages to EHS caregivers and pregnant women.
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http://dx.doi.org/10.1111/jphd.12140DOI Listing
June 2016

Influence of gestational age and birth weight in neonatal cholesterol response to total parenteral nutrition.

J Clin Lipidol 2016 Jul-Aug;10(4):891-897.e1. Epub 2016 Apr 28.

Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA; Zablocki Veterans Affairs Medical Center, Milwaukee, WI, USA.

Background: Premature and critically ill infants receiving total parenteral nutrition (TPN) are at risk for dyslipidemia, and altered cholesterol levels in early life may contribute to later cardiovascular risk. Data regarding plasma cholesterol response to TPN in young infants are lacking.

Objective: To determine the changes in plasma cholesterol levels during the first week of life in infants receiving TPN and a comparison group of infants who did not receive TPN during routine care.

Methods: In a prospective, pilot cohort study, 38 neonates (30 TPN vs. 8 No-TPN) underwent serial blood sampling during the first week of life. Gas chromatography-mass spectrometry was used to measure cholesterol in plasma and TPN administered to study participants.

Results: Baseline cholesterol level was similar between groups. In contrast to infants who did not receive TPN, cholesterol levels during the first week of life were significantly higher than baseline in infants receiving TPN (maximum cholesterol response 34% vs. 103% change from baseline, No-TPN vs. TPN, respectively, P = .036). After adjusting for cumulative cholesterol received by infants receiving TPN, maximum cholesterol response remained inversely related to gestational age and birth weight (P < .05).

Conclusion: Plasma cholesterol significantly increases during the first week of life in neonates receiving TPN. A higher cholesterol response was induced by TPN in infants of lower gestational age and birth weight.
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http://dx.doi.org/10.1016/j.jacl.2016.03.005DOI Listing
October 2017

Efficacy of mindfulness-based addiction treatment (MBAT) for smoking cessation and lapse recovery: A randomized clinical trial.

J Consult Clin Psychol 2016 Sep;84(9):824-838

Department of Psychology, Rice University.

Objective: To compare the efficacy of Mindfulness-Based Addiction Treatment (MBAT) to a Cognitive Behavioral Treatment (CBT) that matched MBAT on treatment contact time, and a Usual Care (UC) condition that comprised brief individual counseling.

Method: Participants (N = 412) were 48.2% African American, 41.5% non-Latino White, 5.4% Latino, and 4.9% other, and 57.6% reported a total annual household income < $30,000. The majority of participants were female (54.9%). Mean cigarettes per day was 19.9 (SD = 10.1). Following the baseline visit, participants were randomized to UC (n = 103), CBT (n = 155), or MBAT (n = 154). All participants were given self-help materials and nicotine patch therapy. CBT and MBAT groups received 8 2-hr in-person group counseling sessions. UC participants received 4 brief individual counseling sessions. Biochemically verified smoking abstinence was assessed 4 and 26 weeks after the quit date.

Results: Logistic random effects model analyses over time indicated no overall significant treatment effects (completers only: F(2, 236) = 0.29, p = .749; intent-to-treat: F(2, 401) = 0.9, p = .407). Among participants classified as smoking at the last treatment session, analyses examining the recovery of abstinence revealed a significant overall treatment effect, F(2, 103) = 4.41, p = .015 (MBAT vs. CBT: OR = 4.94, 95% CI: 1.47 to 16.59, p = .010, Effect Size = .88; MBAT vs. UC: OR = 4.18, 95% CI: 1.04 to 16.75, p = .043, Effect Size = .79).

Conclusion: Although there were no overall significant effects of treatment on abstinence, MBAT may be more effective than CBT or UC in promoting recovery from lapses. (PsycINFO Database Record
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061584PMC
http://dx.doi.org/10.1037/ccp0000117DOI Listing
September 2016

Race and Gender Differences in the Use of Direct Acting Antiviral Agents for Hepatitis C Virus.

Clin Infect Dis 2016 08 30;63(3):291-9. Epub 2016 Apr 30.

Center for Innovation to Implementation (Ci2i): Fostering High Value Care, VA Palo Alto Healthcare System, and Stanford, California.

Background: Direct acting antiviral agents (DAA) are highly effective yet expensive. Disparities by race and/or gender often exist in the use of costly medical advances as they become available.

Methods: We examined a cohort of hepatitis C virus (HCV) patients who received care at the Veterans Administration facilities nationwide. We evaluated the effect of race and gender on DAA receipt after adjusting for socioeconomic status, liver disease severity, comorbidity, and propensity for healthcare use. To determine if disparities had changed over time, we conducted a similar analysis of HCV patients who were seen in the previous standard of care treatment era.

Results: Of the 145 596 patients seen in the current DAA era, 17 791 (10.2%) received treatment during the first 16 months of DAA approval. Black patients had 21% lower odds of receiving DAA than whites (odds ratio [OR] = 0.79; 95% confidence interval [CI], .75, .84). Overall, women were as likely to receive treatment as men (OR = 0.99; 95% CI, .90-1.09). However, the odds of receiving DAAs were 29% lower for younger women compared with younger men (OR = 0.71, 95% CI, .54-.93). Similar to the DAA cohort, black patients had significantly lower odds of receiving treatment than whites (OR = 0.74, 95% CI, .69-.79) in the previous treatment era. The racial difference between the 2 eras did not reach statistical significance.

Conclusions: There were unexplained differences among HCV population subgroups in the receipt of new DAA treatment. Targeted interventions are needed for black patients and younger women.
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http://dx.doi.org/10.1093/cid/ciw249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276931PMC
August 2016

Early outpatient follow-up and 30-day outcomes in patients hospitalized with cirrhosis.

Hepatology 2016 08 28;64(2):569-81. Epub 2016 Apr 28.

Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX.

Unlabelled: Preventing readmission has been the focus of numerous quality improvement efforts across many conditions. Early outpatient follow-up has been proposed as the best mechanism for reducing readmissions. The extent to which early outpatient follow-up averts readmission or improves outcomes in cirrhosis is not known. We evaluated the relationship between early outpatient follow-up and short-term readmission and mortality in patients with cirrhosis. We conducted a retrospective cohort study of patients with cirrhosis who were hospitalized with a liver-related diagnosis and discharged to home from 122 Veterans Administration hospitals between 2010 and 2013. We defined early follow-up as an outpatient visit with a clinician within 7 days after discharge. We propensity matched patients who received early visit with those who did not have any visit and examined the associations between early follow-up and all-cause readmission and mortality within 8-30 days after discharge. Of 25,217 patients hospitalized with cirrhosis, 8,123 (32.2%) had an early follow-up visit within 7 days of discharge. A total of 3,492 (13.8%) patients were readmitted and 1,185 (4.6%) died between 8 and 30 days after discharge. In the propensity-matched sample (N = 16,238), patients with early outpatient follow-up visit had a slightly higher risk of readmission (15.3% vs. 13.8%; hazard ratio [HR] =1.10; 95% confidence interval [CI] = 1.02-1.19), but significantly lower risk of mortality (3.2% vs. 5.2%; HR = 0.60; 95% CI = 0.51-0.70) than those without early visit. The findings persisted in several subgroup and sensitivity analyses.

Conclusions: Early outpatient follow-up after discharge was associated with a small increase in readmissions but lower overall mortality in patients with cirrhosis. Transitional care may be effective in improving short-term outcomes in patients with cirrhosis, but readmission performance measures would miss this effect. (Hepatology 2016;64:569-581).
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http://dx.doi.org/10.1002/hep.28558DOI Listing
August 2016

Bacteriocin production augments niche competition by enterococci in the mammalian gastrointestinal tract.

Nature 2015 Oct 19;526(7575):719-22. Epub 2015 Oct 19.

Division of Gastroenterology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.

Enterococcus faecalis is both a common commensal of the human gastrointestinal tract and a leading cause of hospital-acquired infections. Systemic infections with multidrug-resistant enterococci occur subsequent to gastrointestinal colonization. Preventing colonization by multidrug-resistant E. faecalis could therefore be a valuable approach towards limiting infection. However, little is known about the mechanisms E. faecalis uses to colonize and compete for stable gastrointestinal niches. Pheromone-responsive conjugative plasmids encoding bacteriocins are common among enterococcal strains and could modulate niche competition among enterococci or between enterococci and the intestinal microbiota. We developed a model of colonization of the mouse gut with E. faecalis, without disrupting the microbiota, to evaluate the role of the conjugative plasmid pPD1 expressing bacteriocin 21 (ref. 4) in enterococcal colonization. Here we show that E. faecalis harbouring pPD1 replaces indigenous enterococci and outcompetes E. faecalis lacking pPD1. Furthermore, in the intestine, pPD1 is transferred to other E. faecalis strains by conjugation, enhancing their survival. Colonization with an E. faecalis strain carrying a conjugation-defective pPD1 mutant subsequently resulted in clearance of vancomycin-resistant enterococci, without plasmid transfer. Therefore, bacteriocin expression by commensal bacteria can influence niche competition in the gastrointestinal tract, and bacteriocins, delivered by commensals that occupy a precise intestinal bacterial niche, may be an effective therapeutic approach to specifically eliminate intestinal colonization by multidrug-resistant bacteria, without profound disruption of the indigenous microbiota.
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http://dx.doi.org/10.1038/nature15524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4978352PMC
October 2015

Factors Associated With Increased Reading Frequency in Children Exposed to Reach Out and Read.

Acad Pediatr 2015 Nov-Dec;15(6):651-7. Epub 2015 Sep 26.

Medical College of Wisconsin, Milwaukee, Wisc. Electronic address:

Objective: A 2014 American Academy of Pediatrics Policy Statement on Literacy Promotion recommends providers endorse daily caregiver-child reading during health supervision visits. Reach Out and Read (ROR) is a widely used model of office-based early literacy promotion. We hypothesized that exposure to ROR and other variables such as reading as part of a bedtime routine positively correlate with caregiver-child reading frequency.

Methods: This is a cross-sectional study based on a convenience sample of caregivers at 8 ROR-Milwaukee sites, which serve predominantly low-income populations in Milwaukee. On the basis of results of previously validated questionnaires, odds ratios were calculated to determine which variables are significantly associated with caregivers' reading to children 0 to 2 (rarely), 3 to 6 (often), and 7 (daily) days per week. Random forest analysis was performed to examine relative importance of variables in predicting caregivers' reading frequency.

Results: A total of 256 caregivers were eligible for analysis; those who reported receiving ≥4 books from pediatricians read to children more days per week compared to those receiving fewer books (5.07 vs 3.61, P < .001) and were more likely to read daily (odds ratio 3.07, 95% confidence interval 1.80-5.23). Caregivers' interest in reading, number of children's books in the home, reading as part of a bedtime routine, and number of books received from pediatricians were among the most important variables in distinguishing rarely, often, and daily reading caregivers.

Conclusions: Exposure to ROR-Milwaukee's intervention is associated with increased reading frequency. Identified variables such as reading as a bedtime routine and number of children's books in the home should be targets for future literacy-promoting interventions.
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http://dx.doi.org/10.1016/j.acap.2015.08.008DOI Listing
December 2016

Risk Factors for Abnormal Developmental Trajectories in Young Children With Congenital Heart Disease.

Circulation 2015 Aug;132(8):755-61

From Herma Heart Center, Children's Hospital of Wisconsin, Milwaukee (K.A.M., J.T.); and Departments of Pediatrics (R.H., L.B., Y.C., C.B.), Anesthesiology (G.H.), and Surgery (J.S.T.), Medical College of Wisconsin, Milwaukee.

Background: Children with congenital heart disease are at risk for developmental delay. This study sought to identify early risk factors for abnormal developmental trajectories in children with congenital heart disease.

Methods And Results: Children with congenital heart disease at high risk for developmental delay, without known genetic abnormality, and with ≥3 assessments by the use of the Bayley Scales of Infant and Toddler Development, Third Edition, were studied. Logistic regression was used to assess the impact of patient and clinical factors on cognitive, language, and motor score trajectories; classified as: average or improved if all scores were ≥85 (<1 standard deviation below the mean) or increased to ≥85 and never decreased; or abnormal if all scores were <85, fell to <85 and never improved, or fluctuated above and below 85. Data on 131 children with 527 Bayley Scales of Infant and Toddler Development, Third Edition assessments were analyzed. Subject age was 5.5 to 37.4 months. Overall, 56% had cognitive, language, and motor development in the average range. Delays occurred in single domains in 23%. Multiple domains were delayed in 21%. More cardiac surgeries, longer hospital stay, poorer linear growth, and tube feeding were associated with worse outcomes in all domains (P<0.05). In the multivariable model, the need for tube feeding was a risk factor for having an abnormal developmental trajectory (odds ratio, 5.1-7.9). Minority race and lack of private insurance had significant relationships with individual domains.

Conclusions: Longitudinal developmental surveillance identified early factors that can help quantify the risk of developmental delay over time. Strategies to improve modifiable factors and early therapeutic intervention can be targeted to children at highest risk.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.114.014521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4551137PMC
August 2015

Is Aortic Valve Leaflet Morphology Predictive of Outcome in Pediatric Aortic Valve Stenosis?

Congenit Heart Dis 2015 Nov-Dec;10(6):552-60. Epub 2015 Jul 29.

Division of Pediatric Cardiology, Children's Hospital of Wisconsin, Milwaukee, Wis, USA.

Background: Initial palliative treatment of congenital aortic valve stenosis consists of either surgical commissurotomy or transcatheter balloon valvuloplasty. The basis for selection of primary approach usually is ill defined. It was hypothesized that aortic valve characteristics may be helpful in directing choice of intervention. This study assesses the impact of valve morphology on time to reintervention after catheter- or surgical-based therapy.

Methods: A retrospective review of preprocedural echocardiographic aortic outflow characteristics was compared with outcomes of primary surgical or balloon valve interventions. Characteristics studied included (1) annular dimension; (2) leaflet number; (3) leaflet excursion; and (4) degree of leaflet coaptation. Patients included those <20 years with a primary diagnosis of aortic stenosis (AS) and no other hemodynamically significant lesions at our institutions from 2000 to 2011. A total of 102 patients were included, 31 classified as having critical and 71 as having noncritical aortic stenosis. Of the patients, 79 were male, and 50 underwent primary catheter intervention. Echo parameters were compared with procedural outcome as defined by death or need for reintervention. Receiver operator curves were utilized to determine the point within each morphologic feature where the greatest difference occurred. This was utilized as the distinguishing point within each the morphologic group. Analysis was conducted separately for critical and noncritical aortic stenosis.

Results: Kaplan-Meier analysis demonstrated no significant difference in time to reintervention or death whether initial palliation consisted of surgical commissurotomy or balloon valvuloplasty with respect to any of the morphologic characteristics studied.

Conclusion: Patients with AS do equally well with surgical commissurotomy or balloon valvuloplasty as initial palliation. This holds true for those with either critical or noncritical aortic stenosis. Valve morphology did not help in selection of initial palliative strategy. Current technologies should enable an improved selection of initial palliative approach through thoughtful, randomized trials.
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http://dx.doi.org/10.1111/chd.12278DOI Listing
October 2016

Coping Mediates the Association of Mindfulness with Psychological Stress, Affect, and Depression Among Smokers Preparing to Quit.

Mindfulness (N Y) 2015 Jun 18;6(3):433-443. Epub 2014 Jan 18.

Department of Health Disparities Research - Unit 1440, The University of Texas MD Anderson Cancer Center, PO Box 301402, Houston, TX, 77230-1402.

It is not surprising that smoking abstinence rates are low given that smoking cessation is associated with increases in negative affect and stress that can persist for months. Mindfulness is one factor that has been broadly linked with enhanced emotional regulation. This study examined baseline associations of self-reported trait mindfulness with psychological stress, negative affect, positive affect, and depression among 158 smokers enrolled in a smoking cessation treatment trial. Several coping dimensions were evaluated as potential mediators of these associations. Results indicated that mindfulness was negatively associated with psychological stress, negative affect and depression, and positively associated with positive affect. Furthermore, the use of relaxation as a coping strategy independently mediated the association of mindfulness with psychological stress, positive affect, and depression. The robust and consistent pattern that emerged suggests that greater mindfulness may facilitate cessation and attenuate vulnerability to relapse among smokers preparing for cessation. Furthermore, relaxation appears to be a key mechanism underlying these associations. The ClinicalTrials.gov identifier is NCT00297479.
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http://dx.doi.org/10.1007/s12671-014-0276-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5296771PMC
June 2015

Kinetics of phytosterol metabolism in neonates receiving parenteral nutrition.

Pediatr Res 2015 Aug 21;78(2):181-9. Epub 2015 Apr 21.

1] Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin [2] Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin.

Background: Phytosterols in soybean oil (SO) lipids likely contribute to parenteral nutrition-associated liver disease (PNALD) in infants. No characterization of phytosterol metabolism has been done in infants receiving SO lipids.

Methods: In a prospective cohort study, 45 neonates (36 SO lipid vs. 9 control) underwent serial blood sample measurements of sitosterol, campesterol, and stigmasterol. Mathematical modeling was used to determine pharmacokinetic parameters of phytosterol metabolism and phytosterol exposure.

Results: Compared to controls, SO lipid-exposed infants had significantly higher levels of sitosterol and campesterol (P < 0.01). During SO lipid infusion, sitosterol and campesterol reached half of steady-state plasma levels within 1.5 and 0.8 d, respectively. Steady-state level was highest for sitosterol (1.68 mg/dl), followed by campesterol (0.98 mg/dl), and lowest for stigmasterol (0.01 mg/dl). Infants born < 28 wk gestational age had higher sitosterol steady-state levels (P = 0.03) and higher area under the curve for sitosterol (P = 0.03) during the first 5 d of SO lipid (AUC5) than infants born ≥ 28 wk gestational age.

Conclusion: Phytosterols in SO lipid accumulate rapidly in neonates. Very preterm infants receiving SO lipid have higher sitosterol exposure, and may have poorly developed mechanisms of eliminating phytosterols that may contribute to their vulnerability to PNALD.
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http://dx.doi.org/10.1038/pr.2015.78DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546827PMC
August 2015

Comparison of WHO and CDC growth charts in predicting pulmonary outcomes in cystic fibrosis.

J Pediatr Gastroenterol Nutr 2015 Mar;60(3):378-83

*Division of Pediatric Pulmonology, Medical College of Wisconsin †Quantitative Health Sciences ‡Cystic Fibrosis Program, Children's Hospital of Wisconsin ||Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Medical College of Wisconsin, Milwaukee, WI.

Objectives: The relation of weight-for-length (WFL) and weight-for-age (WFA) measurements with pulmonary function in patients with cystic fibrosis (CF) using the World Health Organization (WHO) growth standards has not been evaluated. The objective of the present study was to show that the relation of WFL and WFA measurements at 2 years with forced expiratory volume in 1 second (FEV1) at 6 to 8 years differs when using the WHO versus the Centers for Disease Control and Prevention (CDC) growth charts.

Methods: We assessed 1155 patients in the CF Foundation Patient Registry born between 2001 and 2004. Comparisons were made between the CDC and WHO growth charts.

Results: The WFL percentiles are significantly higher for the WHO growth standards compared with those for the CDC growth charts (median and interquartile range [IQR] WHO--64.8 [41.7-84.9], CDC--48.1 [23.7-75.7], P < 0.0001). WFL and WFA percentiles at 2 years on both charts are strongly associated with FEV1 at 6 to 8 years of age. The FEV1 at 6 to 8 years was statistically significantly lower for children who were classified as reaching a WFL ≥ 50 th percentile at 2 years by WHO standards alone versus those who qualified by both growth charts (median and IQR 103 [94-115] vs 107 [96-117], P < 0.05). Continued weight gain between 2 and 6 years was associated with a higher lung function at age 6 to 8 years.

Conclusions: Although children attaining the 50th WFL percentile on the WHO growth chart by age 2 years have a lower FEV1 at 6 years than children attaining the same percentile on the CDC chart, both groups of children attain clinically normal FEV1. Further studies are needed to determine whether this difference is clinically meaningful.
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http://dx.doi.org/10.1097/MPG.0000000000000610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469983PMC
March 2015

Rescue of homeostatic regulation of striatal excitability and locomotor activity in a mouse model of Huntington's disease.

Proc Natl Acad Sci U S A 2015 Feb 2;112(7):2239-44. Epub 2015 Feb 2.

Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461

We describe a fast activity-dependent homeostatic regulation of intrinsic excitability of identified neurons in mouse dorsal striatum, the striatal output neurons. It can be induced by brief bursts of activity, is expressed on a time scale of seconds, limits repetitive firing, and can convert regular firing patterns to irregular ones. We show it is due to progressive recruitment of the KCNQ2/3 channels that generate the M current. This homeostatic mechanism is significantly reduced in striatal output neurons of the R6/2 transgenic mouse model of Huntington's disease, at an age when the neurons are hyperactive in vivo and the mice begin to exhibit locomotor impairment. Furthermore, it can be rescued by bath perfusion with retigabine, a KCNQ channel activator, and chronic treatment improves locomotor performance. Thus, M-current dysfunction may contribute to the hyperactivity and network dysregulation characteristic of this neurodegenerative disease, and KCNQ2/3 channel regulation may be a target for therapeutic intervention.
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http://dx.doi.org/10.1073/pnas.1405748112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4343133PMC
February 2015

Pediatric solid organ transplant recipients: transition to home and chronic illness care.

Pediatr Transplant 2015 Feb 26;19(1):118-29. Epub 2014 Nov 26.

Department of Pediatric Gastroenterology, Hepatology and Nutrition, Medical College of Wisconsin, Milwaukee, WI, USA; Children's Hospital of Wisconsin, Milwaukee, WI, USA.

Pediatric SOT recipients are medically fragile and present with complex care issues requiring high-level management at home. Parents of hospitalized children have reported inadequate preparation for discharge, resulting in problems transitioning from hospital to home and independently self-managing their child's complex care needs. The aim of this study was to investigate factors associated with the transition from hospital to home and chronic illness care for parents of heart, kidney, liver, lung, or multivisceral recipients. Fifty-one parents from five pediatric transplant centers completed questionnaires on the day of hospital discharge and telephone interviews at three wk, three months, and six months following discharge from the hospital. Care coordination (p = 0.02) and quality of discharge teaching (p < 0.01) was significantly associated with parent readiness for discharge. Readiness for hospital discharge was subsequently significantly associated with post-discharge coping difficulty (p = 0.02) at three wk, adherence with medication administration (p = 0.03) at three months, and post-discharge coping difficulty (p = 0.04) and family management (p = 0.02) at six months post-discharge. The results underscore the important aspect of education and care coordination in preparing patients and families to successfully self-manage after hospital discharge. Assessing parental readiness for hospital discharge is another critical component for identifying risk of difficulties in managing post-discharge care.
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http://dx.doi.org/10.1111/petr.12397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4280334PMC
February 2015

Predicting Multiple Facets of School Functioning in Pediatric Chronic Pain: Examining the Direct Impact of Anxiety.

Clin J Pain 2015 Oct;31(10):867-75

*Department of Anesthesiology, Medical College of Wisconsin, Children's Hospital of Wisconsin §Department of Pediatrics and Quantitative Health Sciences ∥Department of Quantitative Health Sciences, Medical College of Wisconsin, Milwaukee, WI †Cincinnati Children's Hospital Medical Center, Division of Behavioral Medicine and Clinical Psychology ‡Department of Psychology, University of Cincinnati, Cincinnati, OH.

Objectives: The relationships among chronic pain, anxiety, and school functioning are complex, and school functioning is often negatively impacted in youth with chronic pain. The objective of this study was to empirically test a model of associations between constructs predicting school functioning in youth with chronic pain to examine the direct effect of anxiety on school attendance and other indicators of school-related disability.

Materials And Methods: Participants included 349 youth and their parents (311 mothers and 162 fathers) who attended a multidisciplinary pain clinic. Youth, mothers, fathers, and clinicians completed assessments of clinical outcomes important to family and clinician perceptions of school functioning; youth, mothers, and fathers completed an assessment of youth anxiety. Structural equation modeling was used to examine interrelations among predictors.

Results: Measurement and structural models for predicting youth school functioning provided a very good fit of the data to the conceptual model. Anxiety was directly related to problems with school attendance and avoidance, concentration, and keeping up with schoolwork.

Discussion: Anxiety was a robust predictor of school functioning across a range of domains. Evaluating anxiety symptoms in pediatric chronic pain will likely facilitate case conceptualization and treatment planning. This study supports a shift in focus from pain to anxiety as the driving force of school impairment in youth with chronic pain.
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http://dx.doi.org/10.1097/AJP.0000000000000181DOI Listing
October 2015

Social support mediates the association of health literacy and depression among racially/ethnically diverse smokers with low socioeconomic status.

J Behav Med 2014 Dec 8;37(6):1169-79. Epub 2014 Apr 8.

Department of Health Disparities Research, Unit 1440, The University of Texas MD Anderson Cancer Center, P.O. Box 301402, Houston, TX, 77230-1402, USA,

Nearly half of U.S. adults have health literacy (HL) difficulties, and lack the ability to effectively obtain, process, and understand health information. Poor HL is associated with depression, yet mechanisms of this relation are unclear. This study examined whether social support mediated the relation between HL and depressive symptoms in 200 low-socioeconomic status (SES), racially/ethnically diverse smokers enrolled in cessation treatment. Mediation analyses were conducted using bootstrapping and controlling for SES and nicotine dependence. In simple mediation models, social support [Interpersonal Support Evaluation List (ISEL) total, subscales (Appraisal, Belonging, Tangible)] mediated the effect of HL on depression, such that lower HL was associated with lower perceived support, which predicted higher depressive symptoms (ps < .05). A multiple mediation model, with ISEL subscales entered simultaneously as mediators, was significant (p < .05) but only the Belonging subscale demonstrating independent significance (p < .05). Thus, social support may be a critical factor underlying the HL-depression relationship in low-SES, racially/ethnically diverse smokers.
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http://dx.doi.org/10.1007/s10865-014-9566-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231826PMC
December 2014

Subjective social status predicts quit-day abstinence among homeless smokers.

Am J Health Promot 2014 Sep-Oct;29(1):43-5

Purpose: Smoking prevalence is alarmingly high among the homeless. Few studies have focused on predictors of smoking abstinence in this population. Subjective social status, a person's ranking of their own social standing relative to others in the United States or in their own self-defined communities, has predicted smoking cessation among domiciled smokers in analyses adjusted for objective socioeconomic status and other demographic variables. This study examined if subjective social status predicted quit-day abstinence among homeless smokers making a quit attempt.

Design: Longitudinal study using self-reported survey data.

Setting: Transitional homeless shelter in Dallas, Texas.

Subjects: A total of 57 homeless smokers enrolled in a cessation program.

Measures: Predictors were the Subjective Social Status-U.S (SSS-U.S.) and the Subjective Social Status-Community (SSS-Community) ladders measured 1 week pre quit. Covariates were sociodemographics and tobacco dependence measured 1 week pre quit. The outcome was self-reported and biochemically verified smoking abstinence on the quit day. Analysis . Covariate-adjusted logistic regression models.

Results: Higher rankings on the SSS-U.S. ladder, but not the SSS-Community ladder, predicted abstinence on the quit day (p = .005).

Conclusion: Lower rankings on the SSS-U.S. ladder predicted increased risk of relapse on the quit day or the inability to quit at all. The SSS-U.S. ladder might be useful in identifying homeless smokers needing additional preparation and intervention before initiating a quit attempt.
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http://dx.doi.org/10.4278/ajhp.130228-ARB-88DOI Listing
August 2016