bluuebunny/crossref_metadata_2025 huggingface dataset:
Downregulation of the microtubule associated protein Tau impairs process outgrowth and myelin basic protein mRNA transport in oligodendrocytes
Authors: Seiberlich Veronika , Bauer Nina G. , Schwarz Lisa , Ffrench‐Constant Charles , Goldbaum Olaf , Richter‐Landsberg Christiane
Published: April 2015

Oligodendrocytes, the myelin forming cells of the CNS, are characterized by their numerous membranous extensions, which enwrap neuronal axons and form myelin sheaths. During differentiation oligodendrocytes pass different morphological stages, downregulate the expression of the proteoglycan NG2, and acquire major myelin specific proteins, such as myelin basic proteins (MBP) and proteolipid protein. MBP mRNA is transported in RNA granules along the microtubules (MTs) to the periphery and translated locally. MTs participate in the elaboration and stabilization of the myelin forming extensions and are essential for cellular sorting processes. Their dynamic properties are regulated by microtubule associated proteins (MAPs). The MAP tau is present in oligodendrocytes and involved in the regulation and stabilization of the MT network. To further elucidate the functional significance of tau in oligodendrocytes, we have downregulated tau by siRNA technology and studied the effects on cell differentiation and neuron‐glia contact formation. The data show that tau knockdown impairs process outgrowth and leads to a decrease in MBP expression. Furthermore, MBP mRNA transport to distant cellular extensions is impaired and cells remain in the NG2 stage. In myelinating cocultures with dorsal root ganglion neurons, oligodendrocyte precursor cells after tau miR RNA lentiviral knockdown develop into NG2 positive cells with very long and thin processes, contacting axons loosely, but fail to form internodes. This demonstrates that tau is important for MBP mRNA transport and involved in process formation. The disturbance of the balance of tau leads to abnormalities in oligodendrocyte differentiation, neuron‐glia contact formation and the early myelination process. GLIA 2015;63:1621–1635
Different danger signals differently impact on microglial proliferation through alterations of ATP release and extracellular metabolism
Authors: George Jimmy , Gonçalves Francisco Q. , Cristóvão Gonçalo , Rodrigues Lisa , Meyer Fernandes José Roberto , Gonçalves Teresa , Cunha Rodrigo A. , Gomes Catarina A.
Published: April 2015

Microglia rely on their ability to proliferate in the brain parenchyma to sustain brain innate immunity and participate in the reaction to brain damage. We now studied the influence of different danger signals activating microglia, both internal (typified by glutamate, associated with brain damage) and external (using a bacterial lipopolysaccharide, LPS), on the proliferation of microglia cells. We found that LPS (100 ng/mL) increased, whereas glutamate (0.5 mM) decreased proliferation. Notably, LPS decreased whereas glutamate increased the extracellular levels of ATP. In contrast, LPS increased whereas glutamate decreased the extracellular catabolism of ATP into adenosine through ecto‐nucleotidases and ecto‐5’‐nucleotidase. Finally, apyrase (degrades extracellular ATP) abrogated glutamate‐induced inhibition of microglia proliferation; conversely, inhibitors of ecto‐nucleotidases (ARL67156 or α,β‐methylene ADP) and adenosine deaminase (degrades extracellular adenosine) abrogated the LPS‐induced increase of microglia proliferation, which was blocked by a selective A2A receptor antagonist, SCH58261 (50 nM). Overall, these results highlight the importance of the extracellular purinergic metabolism to format microglia proliferation and influence the spatio‐temporal profile of neuroinflammation in different conditions of brain damage. GLIA 2015;63:1636–1645
Ledipasvir and sofosbuvir in patients with genotype 1 hepatitis C virus infection and compensated cirrhosis: An integrated safety and efficacy analysis
Authors: Reddy K. Rajender , Bourlière Marc , Sulkowski Mark , Omata Masao , Zeuzem Stefan , Feld Jordan J. , Lawitz Eric , Marcellin Patrick , Welzel Tania M. , Hyland Robert , Ding Xiao , Yang Jenny , Knox Steven , Pang Phillip , Dvory‐Sobol Hadas , Subramanian G. Mani , Symonds William , McHutchison John G. , Mangia Alessandra , Gane Edward , Mizokami Masashi , Pol Stanislas , Afdhal Nezam
Published: April 2015

Patients with hepatitis C virus (HCV) infection and cirrhosis are underrepresented in clinical trials of interferon‐free regimens of direct‐acting antiviral agents, making it difficult to optimize therapy. We performed a post‐hoc analysis of data from seven clinical trials to evaluate the efficacy and safety of the fixed‐dose combination of ledipasvir (LDV) and sofosbuvir (SOF), with and without ribavirin (RBV), in 513 treatment‐naïve and previously treated patients with genotype 1 HCV and compensated cirrhosis. All patients received LDV‐SOF for 12 or 24 weeks with or without RBV. We determined the rates of sustained virological response (SVR) 12 weeks after treatment (SVR12) overall and for subgroups. Of the 513 patients analyzed, 69% were previously treated and 47% had failed previous treatment with a protease‐inhibitor regimen. Overall, 493 patients (96%; 95% confidence interval [CI]: 94%‐98%) achieved SVR12, 98% of treatment‐naïve and 95% of previously treated patients. SVR12 rates did not vary greatly by treatment duration (95% of patients receiving 12 weeks and 98% of patients receiving 24 weeks of treatment), nor by addition of RBV (95% of patients receiving LDV‐SOF alone and 97% of those who received LDV‐SOF plus RBV), although previously treated patients receiving 12 weeks of LDV‐SOF without RBV had an SVR12 rate of 90%. One patient discontinued LDV‐SOF because of an adverse event (AE). The most common AEs were headache (23%), fatigue (16%‐19%), and asthenia (14%‐16%). One patient (<1%) of those receiving LDV‐SOF alone, and 4 (2%) of those receiving LDV‐SOF plus RBV had treatment‐related serious AEs. Conclusions: This analysis suggests that 12 weeks of LDV‐SOF is safe and effective for treatment‐naïve patients with HCV genotype 1 and compensated cirrhosis. The relatively lower SVR in treatment‐experienced patients treated with 12 weeks of LDV‐SOF raises the question of whether these patients would benefit from adding RBV or extending treatment duration to 24 weeks. (Hepatology 2015;62:79‐86)
Standard assessments of frailty are validated predictors of mortality in hospitalized patients with cirrhosis
Authors: Tapper Elliot B. , Finkelstein Daniel , Mittleman Murray A. , Piatkowski Gail , Lai Michelle
Published: April 2015

The risk of morbidity and mortality for hospitalized patients with cirrhosis is high and incompletely captured by conventional indices. We sought to evaluate the predictive role of frailty in an observational cohort study of inpatients with decompensated cirrhosis between 2010 and 2013. The primary outcome was 90‐day mortality. Secondary outcomes included discharge to a rehabilitation hospital, 30‐day readmission, and length of stay. Frailty was assessed with three metrics: activities of daily living (ADL), the Braden Scale, and the Morse fall risk score. A predictive model was validated by randomly dividing the population into training and validation cohorts: 734 patients were admitted 1358 times in the study period. The overall 90‐day mortality was 18.3%. The 30‐day readmission rate was 26.6%, and the rate of discharge to a rehabilitation facility was 14.3%. Adjusting for sex, age, Model for End‐Stage Liver Disease, sodium, and Charlson index, the odds ratio for the effect of an ADL score of less than 12 of 15 on mortality is 1.83 (95% confidence interval [CI] 1.05‐3.20). A predictive model for 90‐day mortality including ADL and Braden Scale yielded C statistics of 0.83 (95% CI 0.80‐0.86) and 0.77 (95% CI 0.71‐0.83) in the derivation and validation cohorts, respectively. Discharge to a rehabilitation hospital is predicted by both the ADL (<12) and Braden Scale (<16), with respective adjusted odds ratios of 3.78 (95% CI 1.97‐7.29) and 6.23 (95% CI 2.53‐15.4). Length of stay was associated with the Braden Scale (<16) (hazard ratio = 0.63, 95% CI 0.44‐0.91). No frailty measure was associated with 30‐day readmission. Conclusions: Readily available, standardized measures of frailty predict 90‐day mortality, length of stay, and rehabilitation needs for hospitalized patients with cirrhosis. (Hepatology 2015;62:584–590
The camKK2/camKIV relay is an essential regulator of hepatic cancer
Authors: Lin Fumin , Marcelo Kathrina L. , Rajapakshe Kimal , Coarfa Cristian , Dean Adam , Wilganowski Nathaniel , Robinson Holly , Sevick Eva , Bissig Karl‐Dimiter , Goldie Lauren C. , Means Anthony R. , York Brian
Published: April 2015

Hepatic cancer is one of the most lethal cancers worldwide. Here, we report that the expression of Ca2+/calmodulin‐dependent protein kinase kinase 2 (CaMKK2) is significantly up‐regulated in hepatocellular carcinoma (HCC) and negatively correlated with HCC patient survival. The CaMKK2 protein is highly expressed in all eight hepatic cancer cell lines evaluated and is markedly up‐regulated relative to normal primary hepatocytes. Loss of CaMKK2 function is sufficient to inhibit liver cancer cell growth, and the growth defect resulting from loss of CaMKK2 can be rescued by ectopic expression of wild‐type CaMKK2 but not by kinase‐inactive mutants. Cellular ablation of CaMKK2 using RNA interference yields a gene signature that correlates with improvement in HCC patient survival, and ablation or pharmacological inhibition of CaMKK2 with STO‐609 impairs tumorigenicity of liver cancer cells in vivo. Moreover, CaMKK2 expression is up‐regulated in a time‐dependent manner in a carcinogen‐induced HCC mouse model, and STO‐609 treatment regresses hepatic tumor burden in this model. Mechanistically, CaMKK2 signals through Ca2+/calmodulin‐dependent protein kinase 4 (CaMKIV) to control liver cancer cell growth. Further analysis revealed that CaMKK2 serves as a scaffold to assemble CaMKIV with key components of the mammalian target of rapamycin/ribosomal protein S6 kinase, 70 kDa, pathway and thereby stimulate protein synthesis through protein phosphorylation. Conclusion: The CaMKK2/CaMKIV relay is an upstream regulator of the oncogenic mammalian target of rapamycin/ribosomal protein S6 kinase, 70 kDa, pathway, and the importance of this CaMKK2/CaMKIV axis in HCC growth is confirmed by the potent growth inhibitory effects of genetically or pharmacologically decreasing CaMKK2 activity; collectively, these findings suggest that CaMKK2 and CaMKIV may represent potential targets for hepatic cancer. (Hepatology 2015;62:505–520
Retargeting of bile salt export pump and favorable outcome in children with progressive familial intrahepatic cholestasis type 2
Authors: Varma Sharat , Revencu Nicole , Stephenne Xavier , Scheers Isabelle , Smets Françoise , Beleza‐Meireles Ana , Reding Raymond , Roskams Tania , Sokal Etienne M.
Published: April 2015

We investigated predictors of clinical evolution in progressive familial intrahepatic cholestasis type 2 patients and how they relate to bile salt export pump (BSEP) expression and its (re)targeting. Our retrospective study included 22 children with progressive familial intrahepatic cholestasis type 2. Clinical, biochemical, and histological characteristics were reviewed on admittance and following treatment with either ursodeoxycholic acid alone (10 mg/kg thrice daily, n = 19) or partial biliary diversion (n = 3). Immunostaining of BSEP was performed in 20 patients. Response to treatment was defined as normalization of pruritus, disappearance of jaundice, and alanine aminotransferase (ALT) levels <1.5 times the upper limit of normal. Ten of 22 patients were responders, and paired biopsies were available in six. De novo or retargeted canalicular expression of BSEP occurred in four of these six, two of whom exhibited baseline intracellular expression. Twelve of 22 were nonresponders and exhibited earlier onset of jaundice (<9 months), neonatal cholestasis, and higher ALT levels. An ALT >165 IU/L produced 72% sensitivity and 55% specificity in predicting nonresponse. Seven patients were still responding at last follow‐up (median = 20 months, range 5‐67 months). Three responders relapsed after 56, 72, and 82 months, respectively. Of nine surviving responders, median relapse‐free survival time was 72 months (95% confidence interval 48‐96 months) and 5‐year relapse‐free survival was 75% (95% confidence interval 33‐100%). Intracellular BSEP at baseline was seen in six, of whom five were responders. Genetic analysis was performed in 17 of 22, confirming diagnosis in 13 (76%) and in four (24%) in whom only heterozygous mutation was identified. Conclusion: De novo or retargeted canalicular expression of BSEP occurs in treatment responders; children with late‐onset presentation, lower ALT, and intracellular BSEP expression are likely to respond, at least transiently, to nontransplant treatment. (Hepatology 2015;62:198‐206)
The use of ketamine as an antidepressant: a systematic review and meta‐analysis
Authors: Coyle Caoimhe M. , Laws Keith R.
Published: April 2015

Objective

The current meta‐analysis examines the effects of ketamine infusion on depressive symptoms over time in major depressive disorder (MDD) and bipolar disorder (BD).

Methods

Following a systematic review of the literature, data were extracted from 21 studies (n = 437 receiving ketamine) and analysed at four post‐infusion time points (4 h, 24 h, 7 days and 12–14 days). The moderating effects of several factors were assessed including: repeat/single infusion, diagnosis, open‐label/participant‐blind infusion, pre–post/placebo‐controlled design and the sex of patients.

Results

Effect sizes were significantly larger for repeat than single infusion at 4 h, 24 h and 7 days. For single infusion studies, effect sizes were large and significant at 4 h, 24 h and 7 days. The percentage of males was a predictor of antidepressant response at 7 days. Effect sizes for open‐label and participant‐blind infusions were not significantly different at any time point.

Conclusions

Single ketamine infusions elicit a significant antidepressant effect from 4 h to 7 days; the small number of studies at 12–14 days post infusion failed to reach significance. Results suggest a discrepancy in peak response time depending upon primary diagnosis — 24 h for MDD and 7 days for BD. The majority of published studies have used pre–post comparison; further placebo‐controlled studies would help to clarify the effect of ketamine over time. Copyright © 2015 John Wiley & Sons, Ltd.
Effects of urbanization and stormwater control measures on streamflows in the vicinity of Clarksburg, Maryland, USA
Authors: Rhea Lee , Jarnagin Taylor , Hogan Dianna , Loperfido J. V. , Shuster William
Published: April 2015

Understanding the efficacy of revised watershed management methods is important to mitigating the impacts of urbanization on streamflow. We evaluated the influence of land use change, primarily as urbanization, and stormwater control measures on the relationship between precipitation and stream discharge over an 8‐year period for five catchments near Clarksburg, Montgomery County, Maryland, USA. A unit‐hydrograph model based on a temporal transfer function was employed to account for and standardize temporal variation in rainfall pattern, and properly apportion rainfall to streamflow at different time lags. From these lagged relationships, we quantified a correction to the precipitation time series to achieve a hydrograph that showed good agreement between precipitation and discharge records. Positive corrections appeared to include precipitation events that were of limited areal extent and therefore not captured by our rain gages. Negative corrections were analysed for potential causal relationships. We used mixed‐model statistical techniques to isolate different sources of variance as drivers that mediate the rainfall–runoff dynamic before and after management. Seasonal periodicity mediated rainfall–runoff relationships, and land uses (i.e. agriculture, natural lands, wetlands and stormwater control measures) were statistically significant predictors of precipitation apportionment to stream discharge. Our approach is one way to evaluate actual effectiveness of management efforts in the face of complicating circumstances and could be paired with cost data to understand economic efficiency or life cycle aspects of watershed management. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
Investigating the uncertainty of satellite altimetry products for hydrodynamic modelling
Authors: Domeneghetti Alessio , Castellarin Attilio , Tarpanelli Angelica , Moramarco Tommaso
Published: April 2015

Satellite altimetry products are increasingly used in many hydraulic applications, and recent studies demonstrate their suitability for the calibration of hydraulic models. The study investigates the effect of satellite‐data uncertainty on the calibration of a quasi‐two‐dimensional (quasi‐2D) model of the middle‐lower portion of the Po river (~140 km). We refer to extended (~16 years of observations) ERS and ENVISAT altimetry products (i.e. River and Lake Hydrology data, RLH) to investigate the effect of (i) record length (i.e. number of satellite measurements at a given satellite track) and (ii) data uncertainty (i.e. altimetry measurements errors) on the calibration of the quasi‐2D model. We first present an assessment of ERS and ENVISAT altimetry errors and then perform the investigations in a Monte Carlo framework by generating datasets of synthetic altimetry products. The results of our analysis further emphasize the suitability of satellite data for the calibration of hydraulic models, providing also a quantitative assessment of the effect of the uncertainty of altimetry products. The analysis highlights the higher accuracy of ENVISAT data, which ensures a stable calibration with ~1.5 years of data (Mean Absolute Error, MAE, lower than 0.4 m, ~0.2 m of which results directly from the uncertainty of ENVISAT data). ERS‐based calibrations become stable with longer series (~3.5–5 years of data), and the negative effect of uncertainty in ERS data is higher (i.e. MAE of 0.6–0.9 m, of which 0.4–0.6 m results from the uncertainty of ERS measurements). Copyright © 2015 John Wiley & Sons, Ltd.
Chemical exposures in the workplace and breast cancer risk: A prospective cohort study
Authors: Ekenga Christine C. , Parks Christine G. , Sandler Dale P.
Published: April 2015

We investigated the relationship between workplace chemical exposures and breast cancer risk among women enrolled in the Sister Study, a prospective cohort study of US and Puerto Rican women. A total of 47,640 participants reported work outside of the home. Workplace exposure to eleven agents (acids, dyes or inks, gasoline or other petroleum products, glues or adhesives, lubricating oils, metals, paints, pesticides, soldering materials, solvents and stains or varnishes) was characterized based on self‐reports of frequency and duration of use. Approximately 14% of the study population reported exposure to only one agent and 11% reported working with two or more of the 11 agents in their lifetime. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for each agent, adjusting for established breast cancer risk factors. During follow‐up, 1,966 cases of breast cancer were reported. Although there were no significant associations between ever use of the eleven agents evaluated and breast cancer risk, women with cumulative exposure to gasoline or petroleum products at or above the highest quartile cutoff had an elevated risk of total (HR: 2.3, 95%CI: 1.1–4.9) and invasive (HR: 2.5, 95%CI: 1.1–5.9) breast cancer compared with women in the lowest quartile group (ptrend = 0.03). Workplace exposure to soldering materials was associated with an increased risk of premenopausal breast cancer (HR = 1.8, 95% CI = 1.1–3.0). Findings support the need for further studies to elucidate the role of occupational chemicals in breast cancer etiology.
Alpha fetoprotein mediates HBx induced carcinogenesis in the hepatocyte cytoplasm
Authors: Zhang Chao , Chen Xiangmei , Liu Hui , Li Hui , Jiang Wei , Hou Wenting , McNutt Michael A. , Lu Fengmin , Li Gang
Published: April 2015

Although tumor‐associated fetal protein AFP has demonstrated utility as a clinical tumor marker, the significance of intracellular AFP is still unclear. The aim of this study was to explore the role of cytoplasmic AFP during HBx induced carcinogenesis, which had not previously been recognized; 614 HCC patients were analyzed for correlation of HBV infection with AFP level, and much higher AFP levels were found in HBsAg positive patients. Tumor tissue specimens from 20 HCC patients were used for analysis of AFP and GADD45α. Analysis of HCC specimens showed that upregulation of cytoplasmic AFP is associated with down‐regulation of GADD45α in neoplastic tissue. Transfected HBx promotes transcription of AFP by acting on the elements in the AFP gene regulatory region. HBx itself did not directly impact transcription of GADD45α. However, the obstruction of RAR signaling by HBx induced elevation of AFP, which led to down‐regulation of GADD45α. Cytoplasmic AFP was able to interact with RAR, disrupting its entrance into the nucleus and binding to the elements in the regulatory region of the GADD45α gene. Knockdown of AFP in siRNA‐transfected AFP positive cell lines was synchronously associated with an incremental increase of RAR binding to DNA, as well as upregulation of GADD45α and it was contrary in AFP gene‐transfected AFP negative cell lines. These results indicate cytoplasmic AFP is not only a histochemical tumor biomarker for human hepatoma but is also an intracellular signal molecule and potential participant in HBx induced hepatocarcinogenesis.
Postmenopausal hormone therapy–also use of estradiol plus levonorgestrel‐intrauterine system is associated with an increased risk of primary fallopian tube carcinoma
Authors: Koskela‐Niska Virpi , Pukkala Eero , Lyytinen Heli , Ylikorkala Olavi , Dyba Tadeusz
Published: April 2015

Data on the possible impact of postmenopausal hormone therapy (HT) on the incidence of rare primary fallopian tube carcinoma (PFTC) are scarce. Therefore, we conducted a nationwide case‐control study analyzing the association between the use of different HTs and PFTC. All women aged 50 years or older with an incident PFTC (n = 360) during 1995–2007 were identified from the Finnish Cancer Registry. For each case of PFTC, ten age‐ and place of residence‐matched controls were selected from the Finnish National Population Register, which also provided information on parity. Data on HT purchases were received from the Prescription Register, and data on hysterectomies and sterilizations from the National Care Register. Controls with a salpingectomy before the PFTC diagnosis of the respective case were excluded. The PFTC risk in relation to different HTs was estimated with a conditional logistic regression model, adjusted for parity, age at last delivery, hysterectomy and sterilization. The use for five years or more of estradiol combined with levonorgestrel‐releasing‐intrauterine system (odds ratio 2.84, 95% confidence interval 1.10–7.38) and sequential estradiol‐progestin therapy (EPT; 3.37; 2.23–5.08) were both linked with increases in the risk of PFTC, while the risk with use of estradiol‐only therapy or continuous EPT was not statistically significantly increased. The OR for the use of tibolone for one year or more was 1.56 (0.55–4.41). The use of HT is related to an increased risk of PFTC, particularly when a progestin component is intrauterine or systemic progestin is given in sequential manner.
A type of novel fluorescent magnetic carbon quantum dots for cells imaging and detection
Authors: Su Xi , Xu Yi , Che Yulan , Liao Xin , Jiang Yan
Published: April 2015

A new type of multifunctional fluorescent magnetic carbon quantum dots SPIO@CQDs(n) ([superparamagnetic iron oxide nanoparticles (SPIO), carbon quantum dots, (CQDs)]) with magnetic and fluorescence properties was designed and prepared through layer‐by‐layer self‐assembly method. The as‐synthesized SPIO@CQDs(n) exhibited different emission colors including blue, green, and red when they were excited at different excitation wavelengths, and its fluorescent intensity increased as the increase of CQD layer (n). SPIO@CQDs(n) with quite low toxicity could mark cytoplasm with fluorescence by means of nonimmune markers. The mixture sample of liver cells L02 and hepatoma carcinoma cells HepG2 was taken as an example, and HepG2 cells were successfully separated and detected effectively by SPIO@CQDs(n), with a separation rate of 90.31%. Importantly, the designed and prepared SPIO@CQDs(n) are certified to be wonderful biological imaging and magnetic separation regents. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3956–3964, 2015.
Synthesis of 5,5′‐(ethane‐1,2‐diyl)bis(3‐((5‐bromo‐6‐methyl‐2‐tertiaryaminopyrimidin‐4‐yl)thio)‐4H‐1,2,4‐triazol‐4‐amines) and Their Novel bis‐cyclized Products, 1,2‐bis(pyrimido[5,4e][1,2,4] triazolo[3,4‐b][1,3,4]thiadiazin‐3‐yl)ethane, as Potential Inhibitors of 15‐Lipoxygenase
Authors: Asghari Tayebe , Bakavoli Mehdi , Eshghi Hossein , Saberi Sattar , Ebrahimpour Zahra
Published: April 2015

Several new derivatives of 5,5′‐(ethane‐1,2‐diyl)bis(3‐((5‐bromo‐6‐methyl‐2‐tertiaryamino pyrimidin‐4‐yl)thio)‐4H‐1,2,4‐triazol‐4‐amine) (4a, 4b, 4c, 4d, 4e, 4f) and their novel cyclized products, 1,2‐bis(pyrimido[5,4‐e][1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐3‐yl)ethane (5a, 5b, 5c, 5d, 5e, 5f) were synthesized and evaluated as potential inhibitors of 15‐lipoxygenase (15‐LO). The compounds 4c (1‐methylpiperazine) and 4d (1‐ethylpiperazine) showed the best IC50 of 15‐LO inhibition (IC50 = 4.15 and 2.9 μM, respectively).
Frequency and clinical relevance of inconsistent code status documentation
Authors: Weinerman Adina S. , Dhalla Irfan A. , Kiss Alex , Etchells Edward E. , Wu Robert C. , Wong Brian M.
Published: April 2015

BACKGROUND

Accurate and complete documentation of hospitalized patients' code status is important to ensure that healthcare providers take appropriate action in the event of a cardiac arrest.

OBJECTIVE

Determine the frequency and clinical relevance of incomplete and inconsistent code status documentation.

DESIGN

Point‐prevalence study.

SETTING

Academic medical centers.

PATIENTS

Patients admitted to general internal medicine wards.

MEASUREMENTS

Frequency and clinical relevance of inconsistent code status documentation across 5 documentation sources.

RESULTS

Thirty‐eight (20%; 95% confidence interval [CI], 14%‐26%) of 187 patients had complete and consistent code status documentation. Another 27 (14%; 95% CI, 9%‐19%) patients had no code status documentation. The remaining 122 (65%; 95% CI, 58%‐72%) patients had at least 1 code status documentation inconsistency. Of these, 38 (20%; 95% CI, 14%‐26%) patients had a clinically relevant code status documentation inconsistency. Multivariate logistic regression analysis demonstrated that increased age (odds ratio [OR] = 1.07 [95% CI, 1.05‐1.10] for every 1‐year increase in age, P < 0.001) and patients receiving comfort measures (OR = 9.39 [95% CI, 1.35–65.19], P = 0.02) were independently associated with a clinically relevant code status documentation inconsistency.

CONCLUSIONS

Incomplete and inconsistent documentation of code status occurred frequently in hospitalized patients, especially elderly patients and patients receiving comfort measures. Having multiple, poorly integrated code status documentation sources leads to a significant number of concerning inconsistencies that create opportunities for healthcare providers to inappropriately deliver or withhold resuscitative measures that conflict with patients' expressed wishes. Institutions need to be aware of this potential documentation hazard and take steps to minimize code status documentation inconsistencies. Journal of Hospital Medicine 2015;10:491–496. © 2015 Society of Hospital Medicine
Fine structure of the male genital system of the predatory mite Rhagidia halophila (Rhagidiidae, Prostigmata, Actinotrichida)
Authors: Alberti Gerd , Ehrnsberger Rainer
Published: April 2015

The male genital system of the actinotrichid mite Rhagidia halophila is described and compared with other mites and arachnids. The large testes are composed of germinal and glandular parts and produce numerous small sperm cells. The glandular parts are connected via a testicular bridge. Spermiogenesis occurs in cysts containing spermatids in equal stages of development. Cysts of spermatids are embedded in huge somatic cells. The nuclei of the spermatids loose their envelope. Mature sperm cells are simple exhibiting a ring‐shaped chromatin body and lacking an acrosomal complex. They are most similar to the sperm cells of the related mite Linopodes motatorius. The spermatopositor contains the ejaculatory duct divided into a dorsal channel and a ventral channel that are connected via a narrow passage. At its distal end, the spermatopositor is divided into three eugenital lips. The function of the spermatopositor during deposition of the peculiar thread‐like spermatophores is discussed. Details of the sensilla of the spermatopositor and the progenital lips are reported. The genital papillae located on the inner side of the progenital lips exhibit characteristics of cells performing transport of ions and/or water. The results confirm the overall similarity of actinotrichid genital systems, which is profoundly different from that of anactinotrichid mites. With reference to other Arachnida it is corroborated that testes and sperm structure of Actinotrichida are most similar to that of Solifugae. However, synapomorphies between sperm cells of Rhagidia and Solifugae that could suggest a closer relationship between these two taxa as was suggested in earlier studies were not recognizable. On the contrary, the sperm cells of Rh. halophila being devoid of an acrosomal complex appeared to be more apomorphic than those of many other actinotrichid mites as well as Solifugae. J. Morphol. 276:832–859, 2015. © 2015 Wiley Periodicals, Inc.
Breast cancer subtype intertumor heterogeneity: MRI‐based features predict results of a genomic assay
Authors: Sutton Elizabeth J. , Oh Jung Hun , Dashevsky Brittany Z. , Veeraraghavan Harini , Apte Aditya P. , Thakur Sunitha B. , Deasy Joseph O. , Morris Elizabeth A.
Published: April 2015

Purpose

To investigate the association between a validated, gene‐expression‐based, aggressiveness assay, Oncotype Dx RS, and morphological and texture‐based image features extracted from magnetic resonance imaging (MRI).

Materials and Methods

This retrospective study received Internal Review Board approval and need for informed consent was waived. Between 2006–2012, we identified breast cancer patients with: 1) ER+, PR+, and HER2– invasive ductal carcinoma (IDC); 2) preoperative breast MRI; and 3) Oncotype Dx RS test results. Extracted features included morphological, histogram, and gray‐scale correlation matrix (GLCM)‐based texture features computed from tumors contoured on pre‐ and three postcontrast MR images. Linear regression analysis was performed to investigate the association between Oncotype Dx RS and different clinical, pathologic, and imaging features. P < 0.05 was considered statistically significant.

Results

Ninety‐five patients with IDC were included with a median Oncotype Dx RS of 16 (range: 0–45). Using stepwise multiple linear regression modeling, two MR‐derived image features, kurtosis in the first and third postcontrast images and histologic nuclear grade, were found to be significantly correlated with the Oncotype Dx RS with P = 0.0056, 0.0005, and 0.0105, respectively. The overall model resulted in statistically significant correlation with Oncotype Dx RS with an R‐squared value of 0.23 (adjusted R‐squared = 0.20; P = 0.0002) and a Spearman's rank correlation coefficient of 0.49 (P < 0.0001).

Conclusion

A model for IDC using imaging and pathology information correlates with Oncotype Dx RS scores, suggesting that image‐based features could also predict the likelihood of recurrence and magnitude of chemotherapy benefit. J. Magn. Reson. Imaging 2015;42:1398–1406.
High‐temporal velocity‐encoded MRI for the assessment of left ventricular inflow propagation velocity: Comparison with color M‐mode echocardiography
Authors: Calkoen Emmeline E. , Marsan Nina Ajmone , Bax Jeroen J. , van den Boogaard Pieter J. , Roest Arno A.W. , de Roos Albert , Westenberg Jos J.M.
Published: April 2015

Purpose

To develop an alternative method for Vp‐assessment using high‐temporal velocity‐encoded magnetic resonance imaging (VE‐MRI). Left ventricular (LV) inflow propagation velocity (Vp) is considered a useful parameter in the complex assessment of LV diastolic function and is measured by Color M‐mode echocardiography.

Materials and Methods

A total of 43 patients diagnosed with ischemic heart failure (61 ± 11 years) and 22 healthy volunteers (29 ± 13 years) underwent Color M‐mode echocardiography and VE‐MRI to assess the inflow velocity through the mitral valve (mean interexamination time 14 days). Temporal resolution of VE‐MRI was 10.8–11.8 msec. Local LV inflow velocity was sampled along a 4‐cm line starting from the tip of the mitral leaflets and for consecutive sample points the point‐in‐time was assessed when local velocity exceeded 30 cm/s. From the position–time relation, Vp was calculated by both the difference quotient (Vp‐MRI‐DQ) as well as from linear regression (Vp‐MRI‐LR).

Results

Good correlation was found between Vp‐echo and both Vp‐MRI‐DQ (r = 0.83, P < 0.001) and Vp‐MRI‐LR (r = 0.84, P < 0.001). Vp‐MRI showed a significant but small underestimation as compared to Vp measured by echocardiography (Vp‐MRI‐DQ: 5.5 ± 16.2 cm/s, P = 0.008; Vp‐MRI‐LR: 9.9 ± 15.2 cm/s, P < 0.001). Applying age‐related cutoff values for Vp to identify LV impaired relaxation, kappa‐agreement with echocardiography was 0.72 (P < 0.001) for Vp‐MRI‐DQ and 0.69 (P < 0.001) for Vp‐MRI‐LR.

Conclusion

High temporal VE‐MRI represents a novel approach to assess Vp, showing good correlation with Color M‐mode echocardiography. In healthy subjects and patients with ischemic heart failure, this new method demonstrated good agreement with echocardiography to identify LV impaired relaxation. J. Magn. Reson. Imaging 2015;42:1297–1304.
Cetacean diversity of the continental shelf and slope off southern australia
Authors: Gill Peter C. , Pirzl Rebecca , Morrice Margie G. , Lawton Kieran
Published: April 2015

We recorded a diverse cetacean assemblage from systematic aerial surveys in productive upwelling waters off southern Australia in 2002–2013. Surveys recorded 133 sightings of 15 identified cetacean species consisting of 7 mysticete (baleen) whale species, 8 odontocete (toothed) species, and 384 sightings of unidentified dolphins. This is the first assessment of cetacean diversity for the region and we found diversity to be comparable with other productive regions elsewhere. Differential spatial and temporal distributions of mysticete and odontocete species were apparent, and were associated with habitat variables and seasonal migration cycles. The study contributes new information to assist the environmental planning and management of activities in the region, including oil, and gas exploration and production, fishing, shipping, and renewable energy development. © 2015 The Wildlife Society.
Soil Amendment Improves Tree Growth and Soil Carbon and Nitrogen Pools in Mongolian Pine Plantations on Post‐Mining Land in Northeast China
Authors: Hu Ya‐Lin , Niu Zhi‐Xin , Zeng De‐Hui , Wang Cheng‐Yi
Published: April 2015

Mining activities leave large areas of post‐mining lands to be reclaimed. Increases in soil C and N pools and N availability are important to successfully reestablish trees on post‐mining land. In this study, we determined C and N concentrations and natural stable isotope of 13C and 15N in soil and plant in Mongolian pine (Pinus sylvestris L. var. mongolica Litv.) plantations 8 years after establishment on non‐mined land (NM), post‐mining land without soil amendment (NAM), and post‐mining land with soil amendment (AM) in a placer gold mining region of Northeast China. We found that the growth of Mongolian pine was significantly slower on NAM as compared with NM (decreasing by 73% in tree height and 63% in basal diameter), but tree growth improved on AM. Soil C and N concentrations, plant N concentration, and soil δ15N value decreased in the order of NM > AM > NAM, implying that soil N availability decreased in post‐mining land, but soil amendment could increase soil N availability. However, the values of δ15N in plant tissues of Mongolian pine were higher on NAM than on NM and AM, suggesting that soil inorganic N form absorbed by trees might be changed when trees were directly planted on post‐mining land with lower soil N availability. In addition, the values of δ13C in 1‐ and 2‐year‐old leaves of Mongolian pine were lowest when planted on NAM, indicating a decrease in intrinsic water‐use efficiency of Mongolian pine. Our results suggest that soil amendment helps us establish forests successfully on post‐mining lands. Copyright © 2015 John Wiley & Sons, Ltd.
Relative Contribution of Rill/Interrill and Gully/Channel Erosion to Small Reservoir Siltation in Mediterranean Environments
Authors: Ben Slimane Abir , Raclot Damien , Evrard Olivier , Sanaa Mustapha , Lefevre Irène , Le Bissonnais Yves
Published: April 2015

Reservoir siltation because of water erosion is an important environmental issue in Mediterranean countries where storage of clear surface water is crucial for their economic and agricultural development. The high density of gully systems observed in Mediterranean regions raises the question of their contribution to reservoir siltation. In this context, this study quantified the absolute and relative contributions of rill/interrill and gully/channel erosion in sediment accumulation at the outlet of small Tunisian catchments (0·1–10 km2) during the last 15 years (1995–2010). To this end, a fingerprinting method based on measurements of caesium‐137 and total organic carbon combined with long‐term field monitoring of catchment sediment yield was applied to five catchments in order to cover the diversity of environmental conditions found along the Tunisian Ridge and in the Cape Bon region. Results showed the very large variability of erosion processes among the selected catchments, with rill/interrill erosion contributions to sediment accumulated in outlet reservoirs ranging from 20 to 80%. Overall, rill/interrill erosion was the dominant process controlling reservoir siltation in three catchments whereas gully/channel erosion dominated in the other two catchments. We identified the presence of marly gypsum substrates and the proportion of catchment surface covered by soil management/conservation measures as the main drivers of erosion process variability at the catchment scale. These results provided a sound basis to propose guidelines for erosion mitigation in these Mediterranean environments and suggested to apply models simulating both rill/interrill and gully/channel erosion in catchments of the region. Copyright © 2015 John Wiley & Sons, Ltd.
High risk of delisting or death in liver transplant candidates following infections: Results from the North American consortium for the study of end‐stage liver disease
Authors: Reddy K. Rajender , O'Leary Jacqueline G. , Kamath Patrick S. , Fallon Michael B. , Biggins Scott W. , Wong Florence , Patton Heather M. , Garcia‐Tsao Guadalupe , Subramanian Ram M. , Thacker Leroy R. , Bajaj Jasmohan S. ,   for the North American Consortium for the Study of End‐Stage Liver Disease
Published: April 2015

Because Model for End‐Stage Liver Disease (MELD) scores at the time of liver transplantation (LT) increase nationwide, patients are at an increased risk for delisting by becoming too sick or dying while awaiting transplantation. We quantified the risk and defined the predictors of delisting or death in patients with cirrhosis hospitalized with an infection. North American Consortium for the Study of End‐Stage Liver Disease (NACSELD) is a 15‐center consortium of tertiary‐care hepatology centers that prospectively enroll and collect data on infected patients with cirrhosis. Of the 413 patients evaluated, 136 were listed for LT. The listed patients' median age was 55.18 years, 58% were male, and 47% were hepatitis C virus infected, with a mean MELD score of 2303. At 6‐month follow‐up, 42% (57/136) of patients were delisted/died, 35% (47/136) underwent transplantation, and 24% (32/136) remained listed for transplant. The frequency and types of infection were similar among all 3 groups. MELD scores were highest in those who were delisted/died and were lowest in those remaining listed (25.07, 24.26, 17.59, respectively; P < 0.001). Those who were delisted or died, rather than those who underwent transplantation or were awaiting transplantation, had the highest proportion of 3 or 4 organ failures at hospitalization versus those transplanted or those continuing to await LT (38%, 11%, and 3%, respectively; P = 0.004). For those who were delisted or died, underwent transplantation, or were awaiting transplantation, organ failures were dominated by respiratory (41%, 17%, and 3%, respectively; P < 0.001) and circulatory failures (42%, 16%, and 3%, respectively; P < 0.001). LT‐listed patients with end‐stage liver disease and infection have a 42% risk of delisting/death within a 6‐month period following an admission. The number of organ failures was highly predictive of the risk for delisting/death. Strategies focusing on prevention of infections and extrahepatic organ failure in listed patients with cirrhosis are required. Liver Transpl 21:881‐888, 2015. © 2015 AASLD.
Diet rich in high glucoraphanin broccoli reduces plasma LDL cholesterol: Evidence from randomised controlled trials
Authors: Armah Charlotte N. , Derdemezis Christos , Traka Maria H. , Dainty Jack R. , Doleman Joanne F. , Saha Shikha , Leung Wing , Potter John F. , Lovegrove Julie A. , Mithen Richard F.
Published: April 2015

Scope

Cruciferous‐rich diets have been associated with reduction in plasma LDL‐cholesterol (LDL‐C), which may be due to the action of isothiocyanates derived from glucosinolates that accumulate in these vegetables. This study tests the hypothesis that a diet rich in high glucoraphanin (HG) broccoli will reduce plasma LDL‐C.

Methods and results

One hundred and thirty volunteers were recruited to two independent double‐blind, randomly allocated parallel dietary intervention studies, and were assigned to consume either 400 g standard broccoli or 400 g HG broccoli per week for 12 weeks. Plasma lipids were quantified before and after the intervention. In study 1 (37 volunteers), the HG broccoli diet reduced plasma LDL‐C by 7.1% (95% CI: –1.8%, –12.3%, p = 0.011), whereas standard broccoli reduced LDL‐C by 1.8% (95% CI +3.9%, –7.5%, ns). In study 2 (93 volunteers), the HG broccoli diet resulted in a reduction of 5.1% (95% CI: –2.1%, –8.1%, p = 0.001), whereas standard broccoli reduced LDL‐C by 2.5% (95% CI: +0.8%, –5.7%, ns). When data from the two studies were combined the reduction in LDL‐C by the HG broccoli was significantly greater than standard broccoli (p = 0.031).

Conclusion

Evidence from two independent human studies indicates that consumption of high glucoraphanin broccoli significantly reduces plasma LDL‐C.
Multisite evaluations of a T2‐relaxation‐under‐spin‐tagging (TRUST) MRI technique to measure brain oxygenation
Authors: Liu Peiying , Dimitrov Ivan , Andrews Trevor , Crane David E. , Dariotis Jacinda K. , Desmond John , Dumas Julie , Gilbert Guillaume , Kumar Anand , Maclntosh Bradley J. , Tucholka Alan , Yang Shaolin , Xiao Guanghua , Lu Hanzhang
Published: April 2015

Purpose

Venous oxygenation (Yv) is an important index of brain physiology and may be indicative of brain diseases. A T2‐relaxation‐under‐spin‐tagging (TRUST) MRI technique was recently developed to measure Yv. A multisite evaluation of this technique would be an important step toward broader availability and potential clinical utilizations of Yv measures.

Methods

TRUST MRI was performed on a total of 250 healthy subjects, 125 from the developer's site and 25 each from five other sites. All sites were equipped with a 3 Tesla (T) MRI of the same vendor. The estimated Yv and the standard error (SE) of the estimation εYv were compared across sites.

Results

The averaged Yv and εYv across six sites were 61.1% ± 1.4% and 1.3% ± 0.2%, respectively. Multivariate regression analysis showed that the estimated Yv was dependent on age (P = 0.009) but not on performance site. In contrast, the SE of the Yv estimation was site‐dependent (P = 0.024) but was less than 1.5%. Further analysis revealed that εYv was positively associated with the amount of subject motion (P < 0.001) but negatively associated with blood signal intensity (P < 0.001).

Conclusion

This work suggests that TRUST MRI can yield equivalent results of Yv estimation across different sites. Magn Reson Med 75:680–687, 2016. © 2015 Wiley Periodicals, Inc.
Sensitive imaging of magnetic nanoparticles for cancer detection by active feedback MR
Authors: Li Zhao , Hsu Chao‐Hsiung , Dimitrov Nikolay , Hwang Dennis W. , Chang Hsin‐Wei , Hwang Lian‐Pin , Lin Yung‐Ya
Published: April 2015

Purpose

Sensitive imaging of superparamagnetic nanoparticles or aggregates is of great importance in MR molecular imaging and medical diagnosis. For this purpose, a conceptually new approach, termedactive feedback magnetic resonance, was developed.

Methods

In the presence of the Zeeman field, a dipolar field is induced by the superparamagnetic nanoparticles or aggregates. Such dipolar field creates spatial and temporal (due to water diffusion) variations to the precession frequency of the nearby water1H magnetization. Sensitive imaging of magnetic nanoparticles or aggregates can be achieved by manipulating the intrinsic spin dynamics by selective self‐excitation and fixed‐point dynamics under active feedback fields.

Results

Phantom experiments of superparamagnetic nanoparticles; in vitro experiments of brain tissue with blood clots; and in vivo mouse images of colon cancers, with and without labeling by magnetic nanoparticles, suggest that this new approach provides enhanced, robust, and positive contrast in imaging magnetic nanoparticles or aggregates for cancer detection.

Conclusion

The spin dynamics originated from selective self‐excitation and fixed‐point dynamics under active feedback fields have been shown to be sensitive to dipolar fields generated by magnetic nanoparticles. Magn Reson Med 74:33–41, 2015. © 2014 Wiley Periodicals, Inc.
Sensitivity of chemical shift‐encoded fat quantification to calibration of fat MR spectrum
Authors: Wang Xiaoke , Hernando Diego , Reeder Scott B.
Published: April 2015

Purpose

To evaluate the impact of different fat spectral models on proton density fat fraction quantification using chemical shift‐encoded MRI (CSE‐MRI).

Methods

In a simulation study, spectral models of fat were compared pairwise. Comparison of magnitude fitting and mixed fitting was performed over a range of echo times and fat fractions. In vivo acquisitions from 41 patients were reconstructed using seven published spectral models of fat. T2‐corrected stimulated echo acquisition mode MR spectroscopy was used as a reference.

Results

The simulations demonstrated that imperfectly calibrated spectral models of fat result in biases that depend on echo times and fat fraction. Mixed fitting was more robust against this bias than magnitude fitting. Multipeak spectral models showed much smaller differences among themselves than from the single‐peak spectral model. In vivo studies showed that all multipeak models agreed better (for mixed fitting, the slope ranged from 0.967 to 1.045 using linear regression) with the reference standard than the single‐peak model (for mixed fitting, slope = 0.76).

Conclusion

It is essential to use a multipeak fat model for accurate quantification of fat with CSE‐MRI. Furthermore, fat quantification techniques using multipeak fat models are comparable, and no specific choice of spectral model has been shown to be superior to the rest. Magn Reson Med 75:845–851, 2016. © 2015 Wiley Periodicals, Inc.