bluuebunny/crossref_metadata_2025 huggingface dataset:
Circadian Clock Control of Hepatic Lipid Metabolism: Role of Small Heterodimer Partner (Shp)
Authors: Wang Li , Liangpunsakul Suthat
Published: July 2016

Hepatic steatosis, the accumulation of triglyceride droplets in the hepatocytes, is a common hepatic pathology seen in subjects with obesity/metabolic syndrome and those with excessive alcohol use. The pathogenesis underlying hepatic steatosis is complex. Recent studies have shown the specific role played by the molecular clock mechanism in the control of lipid metabolism and that the disruption of these tissue clocks may lead to the disturbances in lipid homeostasis. This review reports a novel role of small heterodimer partner in maintaining triglyceride and lipoprotein homeostasis through neuronal PAS domain protein 2.
Verapamil eluting stents as a possible treatment for vasospasm after subarachnoid hemorrhage
Authors: Bhambri Pallavi , Sarvi Ali , Wong John H , Sundararaj Uttandaraman , Mitha Alim P
Published: July 2016

Objective

The only pharmacologic prophylaxis for cerebral vasospasm after subarachnoid hemorrhage is oral nimodipine. A novel way to mitigate this risk may be to design a drug eluting stent that elutes verapamil over the time period typically associated with vasospasm. In this study, we explore different methods of coating nitinol stents with a bioabsorbable polymer and determine the release profile of various verapamil coated stents for the potential treatment of vasospasm.

Methods

Nitinol stents were coated with different concentrations of poly(lactic acid-co-glycolic acid) (PLGA) in chloroform solution and using three coating techniques: dip coating, spin coating, and electrospinning. Morphology of the coatings were studied with scanning electron microscopy. 12 verapamil eluting stents were then prepared using different verapamil concentrations and coatings with different numbers of layers. Drug release behaviors were studied using UV spectroscopy for 21 days.

Results

Electrospinning at 20% w/v resulted in a smooth uniform coating without significant surface irregularities, and may be the most effective technique to coat stents. Stents with a single layer of PLGA/verapamil coating showed a two phase release profile (initial burst release followed by a slow rate of release) whereas stents with a bilayer coating showed a lower level of initial release followed by a slower sustained release phase.

Conclusions

Development of verapamil eluting stents that elute drug over the time course typical of cerebral vasospasm, and for either immediate or prophylactic treatment, is technically feasible. Further in vitro and in vivo studies are required to determine whether this can improve the outcome of patients after subarachnoid hemorrhage.
The long-term effect of bundle care for catheter-related blood stream infection: 5-year follow-up
Authors: Hsin Ho-Tsung , Hsu Meng-Shiuan , Shieh Jiann-Shing
Published: July 2016

Objective

To address the importance of bundle care for catheter-related infection (CRBSI) on the basis of long-term observation in a catheter-abundant cardiovascular intensive care unit (CVICU).

Design

Prospective longitudinal cohort study.

Setting

CVICU of a tertiary referring medical centre in northern Taiwan.

Participants

Around 1400 critically ill patients annually for 5 years in the CVICU (from January 2010 to June 2015). CRBSI bundle care has been applied ever since by a multidisciplinary team.

Main outcome measures

CRBSI per 1000 catheter days, bloodstream infection (BSI) per 1000 inpatient days, and catheter utilisation rates.

Results

From January 2010 to June 2015 (22 quarters), there were in total 45 140 inpatient days and 24 163 catheter days, with an overall central venous catheter utilisation rate of 53.5%. The duration of the indwelled catheter was 6.3±1.2 days. The beginning CRBSI rate was 7.0 per 1000 catheter days and was significantly decreased to 0.7 per 1000 catheter days (p<0.001). Regarding the time series, cubic polynomial function depicted the CRBSI decrement most vividly (R2=0.501, p=0.005). In addition, the improvement in overall BSIs (2010 Q1, 4.4 per 1000 inpatient days to 2015 Q2, 0.5 per 1000 inpatient days, p<0.001) significantly correlated with the decrease in CRBSI (r=0.86, p<0.001).

Conclusions

Through the bundle care, we successfully reduced CRBSIs. After 5 years of follow-up, we observed that the effect of bundle care was stepwise and persistent, as long as we kept working on this integrated project.
A simulation study on the hydrogen storage properties of fullerene family molecules Cx(x = 56,60,70) and their hydrides
Authors: Dai Wei , Xiao Ming , Chen Mu-Qing , Xu Jia-Jing , Tang Yong-Jian
Published: August 2016

Hydrogen storage is a key factor for the application of hydrogen energy. From first principle calculation, we have acquired the energy barrier for hydrogen molecules to pass through the hexagonal rings and pentagonal rings of the fullerene. Then the absorption energy and energy barrier are used to analyze the hydrogen adsorption capacity of the fullerene family and their hydrides. We have also studied the hydrogen storage properties of the fullerene family and their hydrides by grand canonical Monte Carlo method. It is found that the weight density of hydrogen storage at ambient temperature and pressure can reach 7.71 wt.%. The results show that it is difficult for hydrogen to get into the carbon cage of the fullerene because of the high energy barrier, while it is beneficial to destroy the fullerene structure for the processes of absorption and desorption. Meanwhile, fullerene hydrogenation is an effective method to improve the hydrogen storage properties. Our study facilitates the design and synthesis of hydrogen storage materials, and provides theoretical support to improve the hydrogen storage capability for materials.
Heat capacity and monogamy relations in the mixed-three-spin XXX Heisenberg model at low temperatures
Authors: Zad Hamid Arian , Movahhedian Hossein
Published: August 2016

Heat capacity of a mixed-three-spin (1/2,1,1/2) antiferromagnetic XXX Heisenberg chain is precisely investigated by use of the partition function of the system for which, spins (1,1/2) have coupling constant [Formula: see text] and spins (1/2,1/2) have coupling constant [Formula: see text]. We verify tripartite entanglement for the model by means of the convex roof extended negativity (CREN) and concurrence as functions of temperature T, homogeneous magnetic field B and the coupling constants [Formula: see text] and [Formula: see text]. As shown in our previous work, [H. A. Zad, Chin. Phys. B 25 (2016) 030303.] the temperature, the magnetic field and the coupling constants dependences of the heat capacity for such spin system have different behaviors for the entangled and separable states, hence, we did some useful comparisons between this quantity and negativities of its organized bipartite (sub)systems at entangled and separable states. Here, we compare the heat capacity of the mixed-three-spin (1/2,1,1/2) system with the CREN and the tripartite concurrence (as measures of the tripartite entanglement) at low temperature. Ground state phase transitions, and also, transition from ground state to some excited states are explained in detail for this system at zero temperature. Finally, we investigate the heat capacity behavior around those critical points in which these quantum phase transitions occur.
Unfree Labor
Authors: Calvão Filipe
Published: August 2016

This review examines the ambiguous condition of unfree labor in modern, Fordist, or postindustrial systems of exploitation. Unfree labor is reviewed across two multidisciplinary strands of research. The first pertains to forms of coercion and exploitation of labor in situations of human mobility or bondage—so-called modern-day slavery and human trafficking. The second attends to the effects of precariousness and dependency conceived at the interstice of recent theorizations of affect and belonging. Whereas the first case is framed as an exception, morally and legally condemned, the second is presented as a new ordinary form of inequality. A theoretical and empirical engagement that straddles both literatures under the prism of unfree labor consolidates this renewed anthropological focus on work. This review suggests that the objectification and dehumanization of labor should be placed back at the heart of anthropological reflection to pave the way for a refined scrutiny of exploitation, inequality, and dispossession.
Neurovascular cross talk in diabetic retinopathy: Pathophysiological roles and therapeutic implications
Authors: Moran Elizabeth P. , Wang Zhongxiao , Chen Jing , Sapieha Przemyslaw , Smith Lois E. H. , Ma Jian-xing
Published: July 2016

Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population in developed countries, and its prevalence will increase as the global incidence of diabetes grows exponentially. DR begins with an early nonproliferative stage in which retinal blood vessels and neurons degenerate as a consequence of chronic hyperglycemia, resulting in vasoregression and persistent retinal ischemia, metabolic disequilibrium, and inflammation. This is conducive to overcompensatory pathological neovascularization associated with advanced proliferative DR. Although DR is considered a microvascular complication, the retinal microvasculature is intimately associated with and governed by neurons and glia; neurodegeneration, neuroinflammation, and dysregulation of neurovascular cross talk are responsible in part for vascular abnormalities in both early nonproliferative DR and advanced proliferative DR. Neuronal activity directly regulates microvascular dilation and blood flow in the process of neurovascular coupling. Retinal neurons also secrete guidance cues in response to injury, ischemia, or metabolic stress that may either promote or suppress vascular outgrowth, either alleviating or exacerbating DR, contingent on the stage of disease and retinal microenvironment. Neurodegeneration, impaired neurovascular coupling, and dysregulation of neuronal guidance cues are key events in the pathogenesis of DR, and correcting these events may prevent or delay development of advanced DR. The review discusses the mechanisms of neurovascular cross talk and its dysregulation in DR, and their potential therapeutic implications.
Fine-Tuning Cancer Immunotherapy: Optimizing the Gut Microbiome
Authors: Pitt Jonathan M. , Vétizou Marie , Waldschmitt Nadine , Kroemer Guido , Chamaillard Mathias , Boneca Ivo Gomperts , Zitvogel Laurence
Published: July 2016

The equilibrium linking the intestinal microbiota, the intestinal epithelium, and the host immune system establishes host health and homeostasis, with perturbations of this balance resulting in chronic inflammatory and autoimmune immunopathologies. The mutualistic symbiosis between gut microbiota and host immunity raises the possibility that dysbiosis of the intestinal content also influences the outcome of cancer immunotherapy. Here, we present our recent findings that specific gut-resident bacteria determine the immunotherapeutic responses associated with CTLA-4 checkpoint blockade. This new evidence hints that interindividual differences in the microbiome may account for the significant heterogeneity in therapeutic and immunopathologic responses to immune checkpoint therapies. We discuss how this new understanding could improve the therapeutic coverage of immune checkpoint inhibitors, and potentially limit their immune-mediated toxicity, through the use of adjunctive “oncomicrobiotics” that indirectly promote beneficial immune responses through optimizing the gut microbiome. Cancer Res; 76(16); 4602–7. ©2016 AACR.
Mechanism-Based Drug Combinations with the DNA Strand–Breaking Nucleoside Analog CNDAC
Authors: Liu Xiaojun , Jiang Yingjun , Nowak Billie , Hargis Sarah , Plunkett William
Published: July 2016

CNDAC (2′-C-cyano-2′-deoxy-1-β-d-arabino-pentofuranosyl-cytosine, DFP10917) and its orally bioavailable prodrug, sapacitabine, are undergoing clinical trials for hematologic malignancies and solid tumors. The unique action mechanism of inducing DNA strand breaks distinguishes CNDAC from other deoxycytidine analogs. To optimize the clinical potentials of CNDAC, we explored multiple strategies combining CNDAC with chemotherapeutic agents targeting distinct DNA damage repair pathways that are currently in clinical use. The ability of each agent to decrease proliferative potential, determined by clonogenic assays, was determined in paired cell lines proficient and deficient in certain DNA repair proteins. Subsequently, each agent was used in combination with CNDAC at fixed concentration ratios. The clonogenicity was quantitated by median effect analysis, and a combination index was calculated. The c-Abl kinase inhibitor imatinib had synergy with CNDAC in HCT116 cells, regardless of p53 status. Inhibitors of PARP1 that interfere with homologous recombination (HR) repair or base excision repair (BER) and agents such as temozolomide that cause DNA damage repaired by the BER pathway were also synergistic with CNDAC. The toxicity of the nitrogen mustards bendamustine and cytoxan, or of platinum compounds, which generate DNA adducts repaired by nucleotide excision repair and HR, was additive with CNDAC. An additive cell killing was also achieved by the combination of CNDAC with taxane mitotic inhibitors (paclitaxel and docetaxel). At concentrations that allow survival of the majority of wild-type cells, the synergistic or additive combination effects were selective in HR-deficient cells. This study provides mechanistic rationales for combining CNDAC with other active drugs. Mol Cancer Ther; 15(10); 2302–13. ©2016 AACR.
ERBB2 Overexpression Establishes ERBB3-Dependent Hypersensitivity of Breast Cancer Cells to Withaferin A
Authors: Liu Wenjun , Barnette Annalise R. , Andreansky Samita , Landgraf Ralf
Published: July 2016

The catalytically deficient ERBB3 strongly synergizes with the receptor tyrosine kinase ERBB2, and elevated levels represent an overall risk factor for unfavorable disease outcomes in breast cancer. Although itself not a target of pan-ERBB kinase inhibitors, it contributes to resistance in ERBB2-targeted treatment regiments. The steroidal lactone Withaferin A (WA) has established broad anticancer properties through several modes of action and was shown to be effective against triple-negative breast cancers at elevated concentrations. We found that ERBB2 overexpression does render cells hypersensitive to WA. Although ERBB2 downregulation is one aspect of WA treatment at high concentrations, it is not causal for the elevated sensitivity at lower dosages. Instead, WA targets the ability of ERBB3 to amplify ERBB2 signaling. ERBB3 receptor levels, constitutive phosphorylation of both ERBB3 and ERBB2, as well as signaling through AKT are eliminated by WA treatment. By targeting ERBB2/ERBB3 as a functional unit, it is also effective in cases in which ERBB2-directed inhibitors, such as lapatinib, alone show reduced potency. Hence, WA or derivatives thereof may present a low toxicity addition to ERBB2-targeting therapeutics, especially in cases in which ERBB3 involvement is driving resistance or reduced overall sensitivity. Mol Cancer Ther; 15(11); 2750–7. ©2016 AACR.
The Tyrosine Kinase Inhibitor Imatinib Augments Extracellular Fluid Exchange and Reduces Average Collagen Fibril Diameter in Experimental Carcinoma
Authors: Olsson P. Olof , Gustafsson Renata , in 't Zandt René , Friman Tomas , Maccarana Marco , Tykesson Emil , Oldberg Åke , Rubin Kristofer , Kalamajski Sebastian
Published: July 2016

A typical obstacle to cancer therapy is the limited distribution of low molecular weight anticancer drugs within the carcinoma tissue. In experimental carcinoma, imatinib (STI571) increases efficacy of synchronized chemotherapy, reduces tumor interstitial fluid pressure, and increases interstitial fluid volume. STI571 also increases the water-perfusable fraction in metastases from human colorectal adenocarcinomas. Because the mechanism(s) behind these effects have not been fully elucidated, we investigated the hypothesis that STI571 alters specific properties of the stromal extracellular matrix. We analyzed STI571-treated human colorectal KAT-4/HT-29 experimental carcinomas, known to have a well-developed stromal compartment, for solute exchange and glycosaminoglycan content, as well as collagen content, structure, and synthesis. MRI of STI571-treated KAT-4/HT-29 experimental carcinomas showed a significantly increased efficacy in dynamic exchanges of solutes between tumor interstitium and blood. This effect was paralleled by a distinct change of the stromal collagen network architecture, manifested by a decreased average collagen fibril diameter, and increased collagen turnover. The glycosaminoglycan content was unchanged. Furthermore, the apparent effects on the stromal cellular composition were limited to a reduction in an NG2-positive stromal cell population. The current data support the hypothesis that the collagen network architecture influences the dynamic exchanges of solutes between blood and carcinoma tissue. It is conceivable that STI571 reprograms distinct nonvascular stromal cells to produce a looser extracellular matrix, ultimately improving transport characteristics for traditional chemotherapeutic agents. Mol Cancer Ther; 15(10); 2455–64. ©2016 AACR.
In Vivo Antitumor Activity of a Recombinant IL7/IL15 Hybrid Cytokine in Mice
Authors: Song Yinhong , Liu Yalan , Hu Rong , Su Min , Rood Debra , Lai Laijun
Published: July 2016

Both IL7 and IL15 have become important candidate immunomodulators for cancer treatment. However, IL7 or IL15 used alone suffers from shortcomings, such as short serum half-life and limited antitumor effect. We have cloned and expressed a recombinant (r) IL7/IL15 fusion protein in which IL7 and IL15 are linked by a flexible linker. We then compared the antitumor effect of rIL7/IL15 with the individual factors rIL7 and/or rIL15. We show here that rIL7/IL15 has a higher antitumor activity than the combination of the individual factors in both murine B16F10 melanoma and CT-26 colon cancer models. This was associated with a significant increase in tumor infiltration of T cells, DCs, and NK cells and a decrease in regulatory T cells (Tregs). In addition, rIL7/IL15-treated DCs had higher expression of costimulatory molecules CD80 and CD86. The higher antitumor activity of rIL7/IL15 is likely due to its longer in vivo half-life and different effects on immune cells. Our results suggest that rIL7/IL15 may offer a new tool to enhance antitumor immunity and treat cancer. Mol Cancer Ther; 15(10); 2413–21. ©2016 AACR.
Targeting Homologous Recombination by Pharmacological Inhibitors Enhances the Killing Response of Glioblastoma Cells Treated with Alkylating Drugs
Authors: Berte Nancy , Piée-Staffa Andrea , Piecha Nadine , Wang Mengwan , Borgmann Kerstin , Kaina Bernd , Nikolova Teodora
Published: July 2016

Malignant gliomas exhibit a high level of intrinsic and acquired drug resistance and have a dismal prognosis. First- and second-line therapeutics for glioblastomas are alkylating agents, including the chloroethylating nitrosoureas (CNU) lomustine, nimustine, fotemustine, and carmustine. These agents target the tumor DNA, forming O6-chloroethylguanine adducts and secondary DNA interstrand cross-links (ICL). These cross-links are supposed to be converted into DNA double-strand breaks, which trigger cell death pathways. Here, we show that lomustine (CCNU) with moderately toxic doses induces ICLs in glioblastoma cells, inhibits DNA replication fork movement, and provokes the formation of DSBs and chromosomal aberrations. Since homologous recombination (HR) is involved in the repair of DSBs formed in response to CNUs, we elucidated whether pharmacologic inhibitors of HR might have impact on these endpoints and enhance the killing effect. We show that the Rad51 inhibitors RI-1 and B02 greatly ameliorate DSBs, chromosomal changes, and the level of apoptosis and necrosis. We also show that an inhibitor of MRE11, mirin, which blocks the formation of the MRN complex and thus the recognition of DSBs, has a sensitizing effect on these endpoints as well. In a glioma xenograft model, the Rad51 inhibitor RI-1 clearly enhanced the effect of CCNU on tumor growth. The data suggest that pharmacologic inhibition of HR, for example by RI-1, is a reasonable strategy for enhancing the anticancer effect of CNUs. Mol Cancer Ther; 15(11); 2665–78. ©2016 AACR.
FLIP: A Targetable Mediator of Resistance to Radiation in Non–Small Cell Lung Cancer
Authors: McLaughlin Kylie A. , Nemeth Zsuzsanna , Bradley Conor A. , Humphreys Luke , Stasik Izabela , Fenning Catherine , Majkut Joanna , Higgins Catherine , Crawford Nyree , Holohan Caitriona , Johnston Patrick G. , Harrison Timothy , Hanna Gerard G. , Butterworth Karl T. , Prise Kevin M. , Longley Daniel B.
Published: July 2016

Resistance to radiotherapy due to insufficient cancer cell death is a significant cause of treatment failure in non–small cell lung cancer (NSCLC). The endogenous caspase-8 inhibitor FLIP is a critical regulator of cell death that is frequently overexpressed in NSCLC and is an established inhibitor of apoptotic cell death induced via the extrinsic death receptor pathway. Apoptosis induced by ionizing radiation (IR) has been considered to be mediated predominantly via the intrinsic apoptotic pathway; however, we found that IR-induced apoptosis was significantly attenuated in NSCLC cells when caspase-8 was depleted using RNA interference (RNAi), suggesting involvement of the extrinsic apoptosis pathway. Moreover, overexpression of wild-type FLIP, but not a mutant form that cannot bind the critical death receptor adaptor protein FADD, also attenuated IR-induced apoptosis, confirming the importance of the extrinsic apoptotic pathway as a determinant of response to IR in NSCLC. Importantly, when FLIP protein levels were downregulated by RNAi, IR-induced cell death was significantly enhanced. The clinically relevant histone deacetylase (HDAC) inhibitors vorinostat and entinostat were subsequently found to sensitize a subset of NSCLC cell lines to IR in a manner that was dependent on their ability to suppress FLIP expression and promote activation of caspase-8. Entinostat also enhanced the antitumor activity of IR in vivo. Therefore, FLIP downregulation induced by HDAC inhibitors is a potential clinical strategy to radiosensitize NSCLC and thereby improve response to radiotherapy. Overall, this study provides the first evidence that pharmacological inhibition of FLIP may improve response of NCSLC to IR. Mol Cancer Ther; 15(10); 2432–41. ©2016 AACR.
Imaging Intraplaque Inflammation in Carotid Atherosclerosis With
18
F-Fluorocholine Positron Emission Tomography–Computed Tomography
Authors: Vöö Stefan , Kwee Robert M. , Sluimer Judith C. , Schreuder Floris H. B. M. , Wierts Roel , Bauwens Matthias , Heeneman Sylvia , Cleutjens Jack P. M. , van Oostenbrugge Robert J. , Daemen Jan-Willem H. , Daemen Mat J. A. P. , Mottaghy Felix M. , Kooi M. Eline
Published: July 2016

Background—

18
F-fluorocholine (
18
F-FCH) uptake is associated with cell proliferation and activity in tumor patients. We hypothesized that
18
F-FCH could similarly be a valuable imaging tool to identify vulnerable plaques and associated intraplaque inflammation and atheroma cell proliferation.

Methods and Results—

Ten consecutive stroke patients (90% men, median age 66.5 years, range, 59.4–69.7) with ipsilateral >70% carotid artery stenosis and who underwent carotid endarterectomy were included in the study. Before carotid endarterectomy, all patients underwent positron emission tomography to assess maximum
18
F-FCH uptake in ipsilateral symptomatic carotid plaques and contralateral asymptomatic carotid arteries, which was corrected for background activity, resulting in a maximum target-to-background ratio (TBRmax). Macrophage content was assessed in all carotid endarterectomy specimens as a percentage of CD68
+
-staining per whole plaque area (plaqueCD68
+
) and as a maximum CD68
+
percentage (maxCD68
+
) in the most inflamed section/plaque. Dynamic positron emission tomography imaging demonstrated that an interval of 10 minutes between
18
F-FCH injection and positron emission tomography acquisition is appropriate for carotid plaque imaging. TBRmax in ipsilateral symptomatic carotid plaques correlated significantly with plaqueCD68
+
(Spearman’s ρ=0.648,
P
=0.043) and maxCD68
+
(ρ=0.721,
P
=0.019) in the 10 corresponding carotid endarterectomy specimens. TBRmax was significantly higher (
P
=0.047) in ipsilateral symptomatic carotid plaques (median: 2.0; interquartile range [Q1–Q3], 1.5–2.5) compared with the contralateral asymptomatic carotid arteries (median: 1.4; Q1–Q3, 1.3–1.6). TBRmax was not significantly correlated to carotid artery stenosis (ρ=0.506,
P
=0.135).

Conclusions—

In vivo uptake of
18
F-FCH in human carotid atherosclerotic plaques correlated strongly with degree of macrophage infiltration and recent symptoms, thus
18
F-FCH positron emission tomography is a promising tool for the evaluation of vulnerable plaques.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01899014.
Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure
Authors: Hunter Wynn G. , Kelly Jacob P. , McGarrah Robert W. , Khouri Michel G. , Craig Damian , Haynes Carol , Ilkayeva Olga , Stevens Robert D. , Bain James R. , Muehlbauer Michael J. , Newgard Christopher B. , Felker G. Michael , Hernandez Adrian F. , Velazquez Eric J. , Kraus William E. , Shah Svati H.
Published: July 2016

Background

Metabolic impairment is an important contributor to heart failure (
HF
) pathogenesis and progression. Dysregulated metabolic pathways remain poorly characterized in patients with
HF
and preserved ejection fraction (
HF
p
EF
). We sought to determine metabolic abnormalities in
HF
p
EF
and identify pathways differentially altered in
HF
p
EF
versus
HF
with reduced ejection fraction (
HF
r
EF
).

Methods and Results

We identified
HF
p
EF
cases,
HF
r
EF
controls, and no‐
HF
controls from the
CATHGEN
study of sequential patients undergoing cardiac catheterization.
HF
p
EF
cases (N=282) were defined by left ventricular ejection fraction (
LVEF
) ≥45%, diastolic dysfunction grade ≥1, and history of
HF
;
HF
r
EF
controls (N=279) were defined similarly, except for having
LVEF
<45%. No‐
HF
controls (N=191) had
LVEF
≥45%, normal diastolic function, and no
HF
diagnosis. Targeted mass spectrometry and enzymatic assays were used to quantify 63 metabolites in fasting plasma. Principal components analysis reduced the 63 metabolites to uncorrelated factors, which were compared across groups using
ANCOVA
. In basic and fully adjusted models, long‐chain acylcarnitine factor levels differed significantly across groups (
P<
0.0001) and were greater in
HF
r
EF
than
HF
p
EF
(
P
=0.0004), both of which were greater than no‐
HF
controls. We confirmed these findings in sensitivity analyses using stricter inclusion criteria, alternative
LVEF
thresholds, and adjustment for insulin resistance.

Conclusions

We identified novel circulating metabolites reflecting impaired or dysregulated fatty acid oxidation that are independently associated with
HF
and differentially elevated in
HF
p
EF
and
HF
r
EF
. These results elucidate a specific metabolic pathway in
HF
and suggest a shared metabolic mechanism in
HF
along the
LVEF
spectrum.
Impact of Increased Early Statin Administration on Ischemic Stroke Outcomes: A Multicenter Electronic Medical Record Intervention
Authors: Flint Alexander C. , Conell Carol , Klingman Jeff G. , Rao Vivek A. , Chan Sheila L. , Kamel Hooman , Cullen Sean P. , Faigeles Bonnie S. , Sidney Steve , Johnston S. Claiborne
Published: July 2016

Background

Statin administration early in ischemic stroke may influence outcomes. Our aim was to determine the clinical impact of increasing statin administration early in ischemic stroke hospitalization.

Methods and Results

This is a retrospective analysis of a multicenter electronic medical record (
EMR
) intervention to increase early statin administration in ischemic stroke across all 20 hospitals of an integrated healthcare delivery system. A stroke
EMR
order set was modified from an “opt‐in” to “opt‐out” mode of statin ordering. Outcomes were mortality by 90 days, discharge disposition, and increase in stroke severity. We examined the relationship between intervention and outcome using autoregressive integrated moving average (ARIMA) time‐series modeling. The
EMR
intervention increased both overall in‐hospital statin administration (from 87.2% to 90.7%,
P
<0.001) and early statin administration (from 16.9% to 26.3%,
P
<0.001). ARIMA models showed a small increase in the rate of survival (difference in probability [
P
diff
]=0.02,
P
=0.016) and discharge to home or rehabilitation facility (
P
diff
=0.04,
P
=0.034) associated with the intervention. The increase in statin administration <8 hours was associated with much larger increases in survival (
P
diff
=0.17,
P
=0.033) and rate of discharge to home or rehabilitation (
P
diff
=0.29,
P
=0.011), as well as a decreased rate of neurological deterioration in‐hospital (
P
diff
=−0.14,
P
=0.026).

Conclusions

A simple
EMR
change increased early statin administration in ischemic stroke and was associated with improved clinical outcomes. This is, to our knowledge, the first
EMR
intervention study to show that a modification of an electronic order set resulted in improved clinical outcomes.
Nitrite Therapy Ameliorates Myocardial Dysfunction via H
2
S and Nuclear Factor‐Erythroid 2‐Related Factor 2 (Nrf2)‐Dependent Signaling in Chronic Heart Failure
Authors: Donnarumma Erminia , Bhushan Shashi , Bradley Jessica M. , Otsuka Hiroyuki , Donnelly Erinn L. , Lefer David J. , Islam Kazi N.
Published: July 2016

Background

Bioavailability of nitric oxide (
NO
) and hydrogen sulfide (H
2
S) is reduced in heart failure (
HF
). Recent studies suggest cross‐talk between
NO
and H
2
S signaling. We previously reported that sodium nitrite (Na
NO
2
) ameliorates myocardial ischemia‐reperfusion injury and HF. Nuclear factor‐erythroid‐2‐related factor 2 (Nrf2) regulates the antioxidant proteins expression and is upregulated by H
2
S. We examined the Na
NO
2
effects on endogenous H
2
S bioavailability and Nrf2 activation in mice subjected to ischemia‐induced chronic heart failure (CHF).

Methods and Results

Mice underwent 60 minutes of left coronary artery occlusion and 4 weeks of reperfusion. Na
NO
2
(165 μg/kgic) or vehicle was administered at reperfusion and then in drinking water (100 mg/L) for 4 weeks. Left ventricular (LV), ejection fraction (EF),
LV
end diastolic (
LVEDD
) and systolic dimensions (
LVESD
) were determined at baseline and at 4 weeks of reperfusion. Myocardial tissue was analyzed for oxidative stress and respective gene/protein‐related assays. We found that Na
NO
2
therapy preserved LVEF, LVEDD and LVSD at 4 weeks during ischemia‐induced HF. Myocardial malondialdehyde and protein carbonyl content were significantly reduced in Na
NO
2
‐treated mice as compared to vehicle, suggesting a reduction in oxidative stress. Na
NO
2
therapy markedly increased expression of Cu,Zn‐superoxide dismutase, catalase, and glutathione peroxidase during 4 weeks of reperfusion. Furthermore, Na
NO
2
upregulated the activity of Nrf2, as well as H
2
S‐producing enzymes, and ultimately increased H
2
S bioavailability in ischemia‐induced CHF in mice as compared with vehicle.

Conclusions

Our results demonstrate that Na
NO
2
therapy significantly improves LV function via increasing H
2
S bioavailability, Nrf2 activation, and antioxidant defenses.
New laws, new needs: the role of wood science in global policy efforts to reduce illegal logging and associated trade
Authors: Johnson Andrea , Laestadius Lars
Published: July 2016

This article describes new laws and policies that are being put in place to reduce illegal logging and associated trade in illegally sourced wood products. We place special emphasis on the demands posed by the Lacey Act in the United States, and highlight the subsequent needs for new knowledge and capacity in the field of basic and applied wood science. These needs include clear links among botanical and trade names; efficient and user-friendly methods for identifying the species and provenance of timber and derived fiber products, and for tracking these products from their origin to point of sale; and enhanced technologies and training for law enforcement activities.
Inside Wood – A Web resource for hardwood anatomy
Authors: Wheeler Elisabeth A.
Published: July 2016

Inside Wood is an Internet-accessible wood anatomy reference, research, and teaching tool. The InsideWood database has coded wood anatomical descriptions based on the IAWA List of Microscopic Features for Hardwood Identification and is accompanied by a collection of photomicrographs. As of November 2010 there were over 5,800 descriptions and 36,000 images of modern woods, and over 1,600 descriptions and 2,000 images of fossil woods. CITES-listed timber species and other endangered woody plants are included in this digital collection hosted by North Carolina State University’s library. This web site has value in helping with wood identification because it has a multiple entry key that allows searching by presence or absence of IAWA features and it serves as a virtual reference collection whereby descriptions and images can be retrieved by searching by scientific or common name or other keywords.
A brief review of machine vision in the context of automated wood identification systems
Authors: Hermanson John C. , Wiedenhoeft Alex C.
Published: July 2016

The need for accurate and rapid field identification of wood to combat illegal logging around the world is outpacing the ability to train personnel to perform this task. Despite increased interest in non-anatomical (DNA, spectroscopic, chemical) methods for wood identification, anatomical characteristics are the least labile data that can be extracted from solidwood products, independent of wood processing (sawing, drying, microbial attack). Wood identification using anatomical characteristics is thus still a viable approach to the wood identification problem, and automating the process of identification is an attractive and plausible solution. The undisputed increase of computer power and image acquisition capabilities, along with the decrease of associated costs, suggests that it is time to move toward non-human based automated wood identification systems and methods. This article briefly reviews the foundations of image acquisition and processing in machine vision systems and overviews how machine vision can be applied to wood identification.
The Applicat ion of DNA methods to Timber Tracking and Origin Verificat ion
Authors: Lowe Andrew J. , Cross Hugh B.
Published: July 2016

Molecular marker methods can be used at a variety of levels to identify wood, from species identification, through regional and concession source verification, down to tracking individual logs. This short review describes the most appropriate molecular marker methods currently being applied or developed for: species identification (DNA barcoding), verification of source, either at the regional scale (through phylogeographic methods) or concession (population genetic assignment), and for tracking individual logs or wood products (DNA fingerprinting). This review finds that for almost all applications, molecular marker methods offer tremendous promise for use in timber tracking at all levels and can be easily automated offering quick, cheap and high-volume processing and with an expressed statistical certainty of results. However, despite the promise of molecular marker methods, some problems remain, most notably in identifying variation at gene loci that distinguish between the scale of biological organization of interest (from species to individuals), and appropriate DNA extraction methods for dried wood and old tissue sources, and recent advances in these areas are reviewed.
Molecular Identification of Fitzroya Cupressoides, Sequoia Sempervirens, and Thuja Plicata Wood Using Taxon-Specific RDNA-ITS Primers
Authors: Hanssen Felix , Wischnewski Niko , Moreth Ute , Magel Elisabeth A.
Published: July 2016

The nuclear ribosomal DNA internal transcribed spacer (rDNA-ITS) region was PCR amplified and sequenced from the wood of three specimens of Fitzroya cupressoides, nine specimens of Sequoia sempervirens, and ten specimens of Thuja plicata. The full lengths of the ITS regions are 1110 bp for F. cupressoides, 1096 bp for S. sempervirens, and 1138 bp for T. plicata, and thus in the range of 975 bp to 1125 bp which is reported for members of the Cupressaceae. Length variation of ITS regions is due to differences in the length of the spacer region ITS1. Intraspecific variations of the sequences of rDNA-ITS regions were one bp in F. cupressoides, and 18 bp in S. sempervirens and T. plicata. Based on the interspecific sequence divergence of the ITS region, taxon-specific primers were designedfor the detection of F. cupressoides, S. sempervirens and T. plicata. The primer sequences were selected from the highly divergent ITS1 spacer. The specificity of the primers was checked by lengths and sequence of the amplicons, and the primers detected the target organism, solely, across 40 conifer species. Our data establish the molecular basis for DNA-based wood identification in these species.
The use of near Infrared Spectroscopy to Identify solid wood Specimens of Swietenia Macrophylla0 (Cites Appendix II)
Authors: Braga Jez Willian Batista , Pastore Tereza Cristina Monteiro , Coradin Vera Teresinha Rauber , Camargos José Arlete Alves , da Silva Allan Ribeiro
Published: July 2016

Near infrared spectroscopy (NIRS) has been shown effective as a tool for identifying Swietenia when tested as laboratory-processed powder, but testing such powdered wood is not readily adaptable to the fieldidentification of wood. This study explored the efficacy of a fiber optic NIRS scan of solid wood surfaces to separate Swietenia macrophylla King, Carapa guianensis Aubl., Cedrela odorata L., and Micropholis melinoniana Pierre. Transverse, radial, and tangential surfaces were scanned to determine if the surface from which data were collected influenced the spectra recorded. Surfaces were scanned before and after removing the oxidized surface layer of the blocks to test effects of exposure on the spectra. Partial least squares for discriminant analysis models were developed for each taxon separately, based on a calibration set composed of at least 67 samples and a test set with at least 45 samples. The anatomical surface scanned, but not the presence of an oxidized layer, influenced the spectra for each species, necessitating the comparison of the same planes of section. The discriminant models showed small errors for each species, indicating that reliable identifications can be made with NIRS of solid wood surfaces in these species.
It’s about Time! CEOs’ Temporal Dispositions, Temporal Leadership, and Corporate Entrepreneurship
Authors: Chen Jianhong , Nadkarni Sucheta
Published: July 2016

How CEOs think and feel about time may have a big influence on their firms’ strategies. We examine how two distinct CEO temporal dispositions—time urgency (the feeling of being chronically hurried) and pacing style (one’s pattern of effort over time in working toward deadlines)—each influence corporate entrepreneurship, a key strategic behavior. We propose that CEOs’ temporal leadership—how they manage the temporal aspects of top management teams’ activities—mediates the relationships between their temporal dispositions and corporate entrepreneurship—firms’ innovation, corporate venturing, and strategic renewal activities. Using a sample of 129 small and medium-sized Chinese firms, we find that CEOs’ time urgency is positively related to their temporal leadership, which in turn is positively related to corporate entrepreneurship. We also examine the effects of three distinct pacing styles: early-action, meaning the CEO exerts the most effort early in the task process and relaxes as the deadline nears; steady-action, meaning the CEO spreads out effort evenly across the time allotted; and deadline-action, meaning the CEO is most active as the deadline nears. We find that the deadline-action style inhibits CEOs’ temporal leadership, but the steady-action and early-action styles have similar effects on their temporal leadership. This study explicates the dispositional basis of executives’ subjective views of time, demonstrating how CEOs’ temporal dispositions shape firms’ behaviors.
Can Babies Remember Trauma? Symbolic Forms of Representation in Traumatized Infants
Authors: Coates Susan W.
Published: July 2016

Three important areas of current inquiry concerning early trauma—the respective roles of reality and fantasy, age-related capacity for the symbolic representation of trauma, and attachment status—are approached through clinical case reports of three children seen initially at very early ages. The findings are relevant to the issue of whether preverbal infants can experience traumatic events that later are available to interpretation. The focus is for the most part on event traumas—single harrowing, life-threatening experiences—occurring at quite early ages. Three main points are emphasized. First, toddlers and infants (including neonates) can experience intense pain and show symptoms of traumatization. They are capable of experiencing an event as harrowing and life-threatening. Second, these events are capable of being memorialized or symbolically represented, that is, stored in memory in a way that can affect later behavior and learning. Third, how that traumatization resolves itself, or fails to, can be decisively affected by the functioning of the attachment system.
The Relevance of Bionian Thinking to the Treatment of PTSD Patients
Authors: Potik David
Published: July 2016

Analysts who conduct trauma-focused treatments have much to learn from Wilfred Bion’s contributions to the understanding and treatment of PTSD. Concepts such as catastrophe and catastrophic change can illuminate the subjective experience of PTSD patients, the beta screen concept sheds light on dissociative phenomena, and, as shown in a clinical vignette, the analyst can use his alpha function to transform the patient’s fragmented raw material into alpha elements. A second clinical vignette shows how during a cognitive intervention the analyst can impart this alpha function to the patient and use his reverie to help the patient assimilate previously intolerable fragments into a coherent narrative. Finally, the idea of knowing mental pain (Bion’s K) is discussed in relation to the processing of traumatic memories.
Serum Bilirubin Levels and the Presence and Progression of Abdominal Aortic Aneurysms
Authors: Vuruşkan Ertan , Saraçoğlu Erhan , Düzen İrfan Veysel
Published: July 2016

The relationship between bilirubin levels and peripheral artery disease has been documented. Our aim was to demonstrate the possible relationship between serum bilirubin levels and abdominal aortic aneurysms (AAAs). The study included 219 patients, 110 had a previous diagnosis of AAA and 109 patients were normal controls. Only patients with AAAs which had a size of 40 to 54 mm were included in the study. Baseline laboratory values and 2 computerized tomographic measurements 12 months apart were recorded. Patients with AAA had significantly higher white blood cell (WBC) counts and neutrophil–lymphocyte ratio (NLR) but lower total and direct bilirubin levels compared with the control patients ( P < .05). Multivariate logistic regression analysis showed that WBC, NLR, and total and direct bilirubin levels were independent predictors of the presence of an AAA ( P = .03, P = .001, P = .001, and P = .001, respectively). White blood cells and total bilirubin level were independent predictors of a rapidly enlarging AAA (>10 mm/y, P = .002 and P < .001, respectively). This study demonstrated that increased WBC and decreased total bilirubin levels were independent predictors of an AAA, especially the subgroup in which the AAA was rapidly expanding.
Platelet-to-Lymphocyte Ratio Predicts Contrast-Induced Acute Kidney Injury in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
Authors: Velibey Yalcin , Oz Ahmet , Tanik Ozan , Guvenc Tolga Sinan , Kalenderoglu Koray , Gumusdag Ayca , Akdeniz Evliya , Bozbay Mehmet , Tekkesin Ahmet Ilker , Guzelburc Ozge , Hayiroglu Mert Ilker , Alper Ahmet Taha , Ugur Murat , Eren Mehmet
Published: July 2016

We aimed to investigate the relationship between platelet-to-lymphocyte ratio (PLR) and contrast-induced acute kidney injury (CI-AKI) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). A total of 2563 patients diagnosed with STEMI and underwent primary pPCI were retrospectively included in the study. Levels of PLR and creatinine were measured before and at 72 hours after pPCI. Patients were divided into 2 groups: non-CI-AKI group and CI-AKI group. Contrast-induced acute kidney injury occurred in 6.4% of the overall study population. Patients in the CI-AKI group had significantly higher PLR than those in the non-CI-AKI group (169.18 ± 81.01 vs 149.49 ± 74.54, P < .001). In logistic regression analysis, PLR was an independent predictor of CI-AKI (odds ratio [OR]: 1.774, 95% CI: 1.243-2.532, P = .002), along with age, use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prior to the procedure, preprocedural creatinine level, amount of contrast material used during the procedure, and hypertension. Increased PLR levels are independently associated with a greater risk of CI-AKI in patients undergoing primary PCI for STEMI.
Family Business and the 1%
Authors: Carney Michael , Nason Robert S.
Published: July 2016

Growing concern about economic inequality has generated a polarized narrative regarding the causes and consequences of extreme wealth. We contend that divided ideological positions obscure a more mundane reality about the typical wealthiest 1% households. Using data from the triennial survey of consumer finance, we demonstrate that there is substantial heterogeneity within the 1%. Contrary to public discourse, the typical 1% household does not have wealth reflective of popular rich lists, but derives a significant share of its wealth from ownership and active management of small- to medium-sized private enterprise. We use these findings to shed new insights on business families’ relationship to economic inequality and open promising new areas of inquiry regarding the role of the family business in society.
Classroom Management Affects Literacy Development of Students With Emotional and Behavioral Disorders
Authors: Garwood Justin D. , Vernon-Feagans Lynne ,   Family Life Project Key Investigators
Published: July 2016

Many children with behavior problems perform poorly academically and can disrupt regular classroom instruction. Although good classroom management strategies can benefit children with behavior problems, it is not clear whether these students need consistently good classroom management across the early elementary school years to improve their academic performance. The current study examined the quality of classroom management from kindergarten through third grade experienced by children who were rated as exhibiting symptoms of emotional and behavioral disorders (EBD) in the classroom to understand the cumulative effects in relationship to third-grade reading performance. Results indicated that higher-quality classroom management in the first 4 years of school was significantly related to higher scores on standardized measures of reading achievement in third grade for boys exhibiting EBD, but girls exhibiting EBD appeared unaffected by the quality of teachers’ classroom management during this same time. Practitioner implications and future research needs are discussed.