bluuebunny/crossref_metadata_2025 huggingface dataset:
An Investigation into the Effects of Force Applied During Deposition on Latent Fingermarks and Inked Fingerprints Using a Variable Force Fingerprint Sampler
Authors: Fieldhouse Sarah J.
Published: November 2014

Physical factors, including the magnitude of the force applied during fingermark deposition, may affect friction ridge surface area and clarity, and the quantity of residue transferred. Consistency between fingermarks may be required; for example, in research projects, yet differences between marks are likely to exist when physical factors are not controlled. Inked fingerprints and latent fingermarks were deposited at 1–10 N at 1 N increments using a variable force fingerprint sampler to control the force, angle of friction ridge and surface contact, and the duration of friction ridge and surface contact. Statistically significant differences existed between the length and width measurements of the inked prints (p ≤ 0.05), particularly at lower forces. Scanning electron microscopy and surface plot analysis demonstrated how differences in force applied during deposition affected ridge surface area, displacement of latent residue, and differences in the quantity of residue transferred. Consistency between inked prints was demonstrated at equivalent forces.
Ethanol Attenuation of Long‐Term Depression in the Nucleus Accumbens Can Be Overcome by Activation of TRPV1 Receptors
Authors: Renteria Rafael , Jeanes Zachary M. , Morrisett Richard A.
Published: November 2014

Background

Altered expression of synaptic plasticity within the nucleus accumbens (NAc) constitutes a critical neuroadaptive response to ethanol (EtOH) and other drugs of abuse. We have previously reported that N‐methyl‐D‐aspartate receptor (NMDAR)‐dependent long‐term depression (LTD) is markedly affected by chronic intermittent ethanol exposure in vivo; however, endocannabinoid (eCB)‐dependent synaptic depression, despite being very well‐documented in the dorsal striatum, is much less well understood in the NAc.

Methods

Whole cell patch clamp electrophysiology was used to investigate interactions between these different plasticity‐induction systems. Excitatory postsynaptic currents (EPSCs) were measured in the NAc shell and NMDAR‐LTD was induced by a pairing protocol (500 stimuli at 1 Hz stimulation [low‐frequency stimulation (LFS)] paired with postsynaptic depolarization to −50 mV). AM251, a CB1 receptor antagonist, was used to determine whether this form of LTD is modulated by eCBs. To determine the effect of EtOH on a purely eCB‐dependent response in the NAc, depolarization‐induced suppression of excitation (DSE) was used in the presence of 40 mM EtOH. Finally, we determined whether the enhancement of eCB signaling with URB597, a fatty acid amide hydrolase inhibitor, and AM404, an anandamide re‐uptake inhibitor would also modulate LFS LTD in the presence of NMDAR blockade or EtOH.

Results

In the presence of AM251, the LFS pairing protocol resulted in NMDAR‐dependent long‐term potentiation that was blocked with either EtOH or DL‐APV. We also found that DSE in the NAc shell was blocked by AM251 and suppressed by EtOH. Enhanced eCB signaling rescued NAc‐LTD expression in the presence of EtOH through a distinct mechanism requiring activation of TRPV1 receptors.

Conclusions

EtOH modulation of synaptic plasticity in the NAc is dependent upon a complex interplay between NMDARs, eCBs, and TRPV1 receptors. These findings demonstrate a novel form of TRPV1‐dependent LTD in the NAc shell that may be critical for EtOH dependence.
Methods to Analyze Treatment Effects in the Presence of Missing Data for a Continuous Heavy Drinking Outcome Measure When Participants Drop Out from Treatment in Alcohol Clinical Trials
Authors: Witkiewitz Katie , Falk Daniel E. , Kranzler Henry R. , Litten Raye Z. , Hallgren Kevin A. , O'Malley Stephanie S. , Anton Raymond F. ,   In conjunction with the Alcohol Clinical Trials Initiative (ACTIVE) Workgroup
Published: November 2014

Background

Attrition is common in alcohol clinical trials and the resultant loss of data represents an important methodological problem. In the absence of a simulation study, the drinking outcomes among those who are lost to follow‐up are not known. Individuals who drop out of treatment and continue to provide drinking data, however, may be a reasonable proxy group for making inferences about the drinking outcomes of those lost to follow‐up.

Methods

We used data from the COMBINE study, a multisite, randomized clinical trial, to examine drinking during the 4 months of treatment among individuals who dropped out of treatment but continued to provide drinking data (i.e., “treatment dropouts;” n = 185). First, we estimated the observed treatment effect size for naltrexone versus placebo in a sample that included both treatment completers (n = 961) and treatment dropouts (n = 185; total N = 1,146), as well as the observed treatment effect size among just those who dropped out of treatment (n = 185). In both the total sample (N = 1,146) and the dropout sample (n = 185), we then deleted the drinking data after treatment dropout from those 185 individuals to simulate missing data. Using the deleted data sets, we then estimated the effect of naltrexone on the continuous outcome percent heavy drinking days using 6 methods to handle missing data (last observation carried forward, baseline observation carried forward, placebo mean imputation, missing = heavy drinking days, multiple imputation (MI), and full information maximum likelihood [FIML]).

Results

MI and FIML produced effect size estimates that were most similar to the true effects observed in the full data set in all analyses, while missing = heavy drinking days performed the worst.

Conclusions

Although missing drinking data should be avoided whenever possible, MI and FIML yield the best estimates of the treatment effect for a continuous outcome measure of heavy drinking when there is dropout in an alcohol clinical trial.
Chronic Binge Alcohol Administration Accentuates Expression of Pro‐Fibrotic and Inflammatory Genes in the Skeletal Muscle of Simian Immunodeficiency Virus–Infected Macaques
Authors: Dodd Tracy , Simon Liz , LeCapitaine Nicole J. , Zabaleta Jovanny , Mussell Jason , Berner Paul , Ford Stephen , Dufour Jason , Bagby Gregory J. , Nelson Steve , Molina Patricia E.
Published: November 2014

Background

Chronic binge alcohol (CBA) administration exacerbates skeletal muscle (SKM) wasting at the terminal stage of simian immunodeficiency virus (SIV) infection in rhesus macaques. This is associated with a pro‐inflammatory and oxidative milieu which we have previously shown to be associated with a disrupted balance between anabolic and catabolic mechanisms. In this study, we attempted to characterize the SKM gene expression signature in CBA‐administered SIV‐infected macaques, using the same animals from the previous study.

Methods

Administration of intragastric alcohol or sucrose to male rhesus macaques began 3 months prior to SIV infection and continued throughout the duration of study. Gene transcriptomes of SKM excised at necropsy (~10 months post‐SIV) from healthy na\xEFve control (Control), sucrose‐administered, SIV‐infected (SUC‐SIV), and CBA‐administered, SIV‐infected (CBA‐SIV) macaques were evaluated in microarray data sets. The Protein Analysis Through Evolutionary Relationships classification tool was used to filter differentially regulated genes based on their predicted function into select biological processes relevant to SKM wasting which were inflammation, extracellular matrix (ECM) remodeling, and metabolism.

Results

In total, 1,124 genes were differentially regulated between SUC‐SIV and Controls, 2,022 genes were differentially expressed between the CBA‐SIV and Controls, and 836 genes were differentially expressed between CBA‐SIV and SUC‐SIV animals. The relevance of altered gene expression was reflected in the up‐regulation of pro‐inflammatory CCL‐2, CCL‐8, CX3CL1, SELE, HP, and TNFRS10A mRNA expression. In addition, ECM remodeling was reflected in the up‐regulation of TIMP‐1, MMP 2, and MMP 9 mRNA expression and transforming growth factor‐beta 1 protein expression. In addition, hydroxyproline content and picrosirius staining reflected increased collagen deposition in the CBA‐SIV muscle tissue.

Conclusions

The results of the study demonstrate SKM inflammation as an important underlying mechanism for muscle wasting. In addition, the study provides evidence of SKM fibrotic transformation as a factor in CBA‐induced accentuation of SIV‐associated muscle wasting.
Stress‐Related Alcohol Consumption in Heavy Drinkers Correlates with Expression of miR‐10a, miR‐21, and Components of the TAR‐RNA‐Binding Protein‐Associated Complex
Authors: Beech Robert D. , Leffert Janine J. , Lin Aiping , Hong Kwangik A. , Hansen Julie , Umlauf Sheila , Mane Shrikant , Zhao Hongyu , Sinha Rajita
Published: November 2014

Background

Alterations in stress‐related gene expression may play a role in stress‐related drinking and the risk of alcohol dependence.

Methods

Microarrays were used to measure changes in gene expression in peripheral blood in nonsmoking, social drinking subjects exposed to 3 types of personalized imagery: neutral, stressful (but not alcohol related), and alcohol‐related cues. Gene expression was measured at baseline, immediately after, and 1 hour after stimulus presentation. Subjects were allowed to drink up to 750 cc of beer in a “taste test” following stimulus presentation in each imagery condition, and the amount of beer consumed was recorded. Gene‐expression levels were compared in 2 groups of nonsmoking subjects (n = 11/group): heavy drinkers (HD; defined as regular alcohol use over the past year of at least 8 standard drinks per week for women and at least 15 standard drinks per week for men), and moderate drinkers (MD; defined as up to 7 standard drinks per week for women and 14 standard drinks per week for men). Expression of microRNA‐10a (miR‐10a) and microRNA‐21 (miR‐21) was assessed by quantitative real‐time polymerase chain reaction.

Results

After correction for multiple testing (false discovery rate < 0.05), 79 genes were identified that changed by >1.3‐fold in the HD group, but not the MD group, following exposure to stress. No changes were observed for any of these genes in either group following exposure to neutral or alcohol‐related imagery. Pathway analysis suggested that many of these genes, form part of the transactivation responsive (TAR)‐RNA‐binding protein (TRBP)‐associated complex and are positively regulated by miR‐10a and miR‐21. Expression of both miR‐10a and miR‐21 was up‐regulated following psychological stress in HD, but not MD subjects; however, the differences between groups were not statistically significant. Expression levels of both microRNAs was correlated (miR‐10a, R2 = 0.59, miR‐21 R2 = 0.57) with amount drunk in HD, but not MD subjects.

Conclusions

Expression of miR‐10a, miR‐21, and several of their target genes is regulated by acute psychological stress and is correlated with stress‐induced drinking in a laboratory setting. Alterations in miRNA expression may be one mechanism linking psychological stress with changes in gene expression and increased alcohol intake in binge/HD.
Heavy Alcohol Use in Lung Donors Increases the Risk for Primary Graft Dysfunction
Authors: Lowery Erin M. , Kuhlmann Erica A. , Mahoney Erin L. , Dilling Daniel F. , Kliethermes Stephanie A. , Kovacs Elizabeth J.
Published: November 2014

Background

Heavy alcohol use is known to increase the risk of acute lung injury and the acute respiratory distress syndrome. This is in part due to increased production of reactive oxygen species. We hypothesized that recipients of lungs from heavy drinkers would be more susceptible to lung injury following transplantation.

Methods

In this retrospective cohort study, donor histories and transplant outcomes were reviewed in 192 consecutive lung transplant recipients. Donors were classified as No Alcohol Use, Moderate Alcohol Use, or Heavy Alcohol Use based on documented donor histories.

Results

Freedom from mechanical ventilation took longer in the lung transplant recipients whose donors had Heavy Alcohol Use, compared with those whose donors had No Alcohol Use or Moderate Alcohol Use (p = 0.01). At admission to the intensive care unit, the Heavy Alcohol Use group had median PaO2/FiO2 ratio 219 (interquartile range [IQR]: 162 to 382), compared with 305 (IQR: 232 to 400) in the Moderate Alcohol Use group and 314 (IQR: 249 to 418) in the No Alcohol Use group (p = 0.005). The odds of developing severe primary graft dysfunction (PGD) in the Heavy Alcohol Use group versus the No Alcohol Use group were 8.7 times greater (95% confidence interval 1.427 to 53.404, p = 0.019) after controlling for factors known to be associated with PGD.

Conclusions

Recipients of donors with a heavy alcohol use history had an over 8 times greater risk of developing severe PGD following lung transplant. The increase in PGD resulted in poorer gas exchange in the recipients of donor lungs from heavy alcohol users, and these recipients subsequently required mechanical ventilation for a longer time following transplant. Further investigation into lung donors with heavy alcohol use histories is necessary to determine those at highest risk for PGD following transplant.
Social Isolation Rearing Increases Nucleus Accumbens Dopamine and Norepinephrine Responses to Acute Ethanol in Adulthood
Authors: Karkhanis Anushree N. , Locke Jason L. , McCool Brian A. , Weiner Jeffrey L. , Jones Sara R.
Published: November 2014

Background

Early‐life stress is associated with increased vulnerability to alcohol addiction. However, the neural substrates linking chronic childhood/adolescent stress and increased risk of alcohol addiction are not well understood. In the nucleus accumbens (NAc), dopamine (DA) and norepinephrine (NE) signaling can be profoundly influenced by stress, anxiety, and drugs of abuse, including ethanol (EtOH). Here, we employed a rodent model of early‐life stress that results in enduring increases in behavioral risk factors of alcoholism to gain a better understanding of how chronic adolescent stress may impact the EtOH sensitivity of DA and NE release in the NAc.

Methods

Male Long–Evans rats were either group housed (GH; 4 rats/cage) or socially isolated (SI; 1 rat/cage) for 6 weeks beginning on postnatal day 28. SI and GH rats were tested in adulthood for anxiety‐like behaviors (elevated plus maze), and the effects of EtOH (1 and 2 g/kg; intraperitoneally.) on NAc DA and NE were assessed by microdialysis.

Results

SI animals showed increased anxiety‐like behavior compared to GH animals. Although SI had no effect on baseline levels of DA or NE, baseline DA levels were positively correlated with anxiety measures. In addition, while no significant differences were observed with 1 g/kg EtOH, the 2 g/kg dose induced significantly greater DA release in SI animals. Moreover, EtOH (2 g/kg) only elevated NAc NE levels in SI rats.

Conclusions

These results suggest that chronic early‐life stress sensitizes accumbal DA and NE release in response to an acute EtOH challenge. A greater EtOH sensitivity of DA and NE release dynamics in the NAc may contribute to increases in behavioral risk factors of alcoholism, like greater EtOH self‐administration, that are observed in SI rats.
Prenatal Alcohol Exposure Alters Response of Kisspeptin‐ir Neurons to Estradiol and Progesterone in Adult Female Rats
Authors: Sliwowska Joanna H. , Bodnar Tamara S. , Weinberg Joanne
Published: November 2014

Background

Prenatal alcohol exposure (PAE) has adverse effects on reproductive function and hypothalamic–pituitary–gonadal (HPG) activity. Kisspeptin neurons play a role in mediating feedback effects of estradiol (E2) and progesterone (P4) on the HPG axis. We hypothesized that PAE will have long‐term effects on the response of kisspeptin neurons to E2 and P4.

Methods

Adult female rats (53 to 58 days) from prenatal ad libitum‐fed control (C), pair‐fed (PF), and alcohol‐exposed (PAE) groups were subjected to Sham ovariectomy (OVX) or OVX without or with replacement with low or high physiological levels of E2 and P4, and terminated under basal conditions. E2 and P4 levels, and the response of kisspeptin‐ir neurons in the arcuate (ARC) and anteroventral periventricular (AVPV) nuclei to these hormones, were measured. As the E2 signal is conveyed to kisspeptin neurons via estrogen receptor‐α (ER‐α), we investigated PAE effects on the number of kisspeptin‐ir/ER‐α‐ir neurons. To determine whether PAE alters interactions between kisspeptin and gonadotropin‐releasing hormone (GnRH) neurons, close contacts between kisspeptin‐ir fibers and GnRH‐ir cell bodies were examined.

Results

Our data present the novel finding that kisspeptin‐ir neurons in the ARC of PAE females show differential responses to E2 and to the combined treatment with E2 and P4 compared with controls: (i) OVX increased the number of kisspeptin‐ir neurons in C and PF, but not PAE females compared with their Sham counterparts; (ii) E2 replacement restored kisspeptin‐ir cell numbers to Sham levels in C and PF females but caused a robust down‐regulation of kisspeptin‐ir neurons below Sham levels in PAE females; (iii) OVX and replacement with high physiological concentrations of E2 resulted in fewer kisspeptin‐ir cells in PAE than C females; (iv) OVX and replacement with high levels of both E2 and P4 markedly decreased the number of kisspeptin‐ir neurons, below levels observed following E2 alone, in PF and C females, but had no significant effect in PAE females.

Conclusions

These data suggest that a possible mechanism underlying adverse effects of PAE on HPG function involves actions of alcohol on the kisspeptin system.
Adolescent Alcohol Exposure Alters GABAA Receptor Subunit Expression in Adult Hippocampus
Authors: Centanni Samuel W. , Teppen Tara , Risher Mary‐Louise , Fleming Rebekah L. , Moss Julia L. , Acheson Shawn K. , Mulholland Patrick J. , Pandey Subhash C. , Chandler L. Judson , Swartzwelder H. S.
Published: November 2014

Background

The long‐term consequences of adolescent alcohol abuse that persist into adulthood are poorly understood and have not been widely investigated. We have shown that intermittent exposure to alcohol during adolescence decreased the amplitude of GABAA receptor (GABAAR)‐mediated tonic currents in hippocampal dentate granule cells in adulthood. The aim of this study was to investigate the enduring effects of chronic intermittent alcohol exposure during adolescence or adulthood on the expression of hippocampal GABAARs.

Methods

We used a previously characterized tissue fractionation method to isolate detergent resistant membranes and soluble fractions, followed by Western blots to measure GABAAR protein expression. We also measured mRNA levels of GABAAR subunits using quantitative real‐time polymerase chain reaction.

Results

Although the protein levels of α1‐, α4‐, and δ‐GABAAR subunits remained stable between postnatal day (PD) 30 (early adolescence) and PD71 (adulthood), the α5‐GABAAR subunit was reduced across that period. In rats that were subjected to adolescent intermittent ethanol (AIE) exposure between PD30 and PD46, there was a significant reduction in the protein levels of the δ‐GABAAR, in the absence of any changes in mRNA levels, at 48 hours and 26 days after the last ethanol (EtOH) exposure. Protein levels of the α4‐GABAAR subunit were significantly reduced, but mRNA levels were increased, 26 days (but not 48 hours) after the last AIE exposure. Protein levels of α5‐GABAAR were not changed by AIE, but mRNA levels were reduced at 48 hours but normalized 26 days after AIE. In contrast to the effects of AIE, chronic intermittent ethanol (CIE) exposure during adulthood had no effect on expression of any of the GABAAR subunits examined.

Conclusions

AIE produced both short‐ and long‐term alterations of GABAAR subunits mRNA and protein expression in the hippocampus, whereas CIE produced no long‐lasting effects on those measures. The observed reduction of protein levels of the δ‐GABAAR, specifically, is consistent with previously reported altered hippocampal GABAAR‐mediated electrophysiological responses after AIE. The absence of effects of CIE underscores the emerging view of adolescence as a time of distinctive vulnerability to the enduring effects of repeated EtOH exposure.
The P Wave Time‐Frequency Variability Reflects Atrial Conduction Defects before Paroxysmal Atrial Fibrillation
Authors: Alcaraz Raúl , Martínez Arturo , Rieta José J.
Published: November 2014

Background

The study of atrial conduction defects associated with the onset of paroxysmal atrial fibrillation (PAF) can be addressed by analyzing the P wave from the surface electrocardiogram (ECG). Traditionally, signal‐averaged ECGs have been mostly used for this purpose. However, this alternative hinders the possibility to quantify every single P wave, its variability over time, as well as to obtain complimentary and evolving information about the arrhythmia. This work analyzes the time progression of several time and frequency P wave features as potential indicators of atrial conduction variability several hours preceding the onset of PAF.

Methods

The longest sinus rhythm interval from 24‐hour Holter recordings of 46 PAF patients was selected. Next, the 2 hours before the onset of PAF were extracted and divided into two 1‐hour periods. Every single P wave was automatically delineated and characterized by 16 time and frequency metrics, such as its duration, absolute energy in several frequency bands and high‐to‐low‐frequency energy ratios. Finally, the P wave variability over each 1‐hour period was estimated from the 16 features making use of a least‐squares linear fitting. As a reference, the same parameters were also estimated from a set of 1‐hour ECG segments randomly chosen from a control group of 53 healthy subjects age‐, gender‐, and heart rate‐matched.

Results

All the analyzed metrics provided an increasing P wave variability trend as the onset of PAF approximated, being P wave duration and P wave high‐frequency energy the most significant individual metrics. The linear fitting slope α associated with P wave duration was (2.48 ± 1.98)×10‐2 for healthy subjects, (23.8 ± 14.1)×10‐2for ECG segments far from PAF and for (81.8 ± 48.7)×10‐2ECG segments close to PAF p = 6.96×10‐22. Similarly, the P wave high‐frequency energy linear fitting slope was (2.42 ± 4.97)×10‐9, (54.2 ± 107.1)×10‐9 and (274.2 ± 566.1)×10‐9, respectively (p = 2.85×10‐20). A univariate discriminant analysis provided that both P wave duration and P wave high‐frequency energy could discern among the three ECG sets with diagnostic ability around 80%, which was improved up to 88% by combining these metrics in a multivariate discriminant analysis.

Conclusion

Alterations in atrial conduction can be successfully quantified several hours before the onset of PAF by estimating variability over time of several time and frequency P wave features.
Synthesis of Novel Hybrids Inspired from Bromopyrrole Alkaloids Inhibiting MMP‐2 and ‐12 as Antineoplastic Agents
Authors: Rane Rajesh A. , Naphade Shital S. , Bangalore Pavan Kumar , Palkar Mahesh B. , Patel Harun M. , Shaikh Mahamadhanif S. , Alwan Wesam S. , Karpoormath Rajshekhar
Published: November 2014

Synthesis of novel set of forty semicarbazide/thiosemicarbazide hybrids inspired from marine bromopyrrole alkaloids is reported. Biological screening of these hybrids against a panel of five human cancer cell lines identified a number of hits endowed with interesting cytotoxicity profile. Compounds 5c and 5e (IC50 = 0.03 μm), 5t (IC50 = 0.03 μm), 4s (IC50 = 0.07 μm), and 5n (IC50 = 0.01 μm) displayed maximum cytotoxicity toward hormone‐dependent breast cancer cells MCF7, hepatic cancer cells WRL68, colon cancer cells CaCO2 and mouth and oral cancer cells KB403, respectively. The most active hits were further investigated for their potential to inhibit MMP‐2 and MMP‐12. Compound 5e showed maximum activity (IC50 = 1.8 μm) toward MMP‐2. Further, we preformed anti‐invasive assay on the most active compounds, where CaCO2 tumor cell migration was significantly decreased (77.9%) by hybrid 5e. The non‐toxicity toward human VERO cells (IC50 = 83.1 to 231.8 μm) indicated the selectivity of most active hits (5c, 5e, 5t and 5n) toward cancer cells.
Comparative analysis of portal hepatic infiltrating leucocytes in acute drug-induced liver injury, idiopathic autoimmune and viral hepatitis
Authors: Foureau D M , Walling T L , Maddukuri V , Anderson W , Culbreath K , Kleiner D E , Ahrens W A , Jacobs C , Watkins P B , Fontana R J , Chalasani N , Talwalkar J , Lee W M , Stolz A , Serrano J , Bonkovsky H L
Published: November 2014

Drug-induced liver injury (DILI) is often caused by innate and adaptive host immune responses. Characterization of inflammatory infiltrates in the liver may improve understanding of the underlying pathogenesis of DILI. This study aimed to enumerate and characterize leucocytes infiltrating liver tissue from subjects with acute DILI (n = 32) versus non-DILI causes of acute liver injury (n = 25). Immunostains for CD11b/CD4 (Kupffer and T helper cells), CD3/CD20 (T and B cells) and CD8/CD56 [T cytotoxic and natural killer (NK) cells] were evaluated in biopsies from subjects with acute DILI, either immunoallergic (IAD) or autoimmune (AID) and idiopathic autoimmune (AIH) and viral hepatitis (VH) and correlated with clinical and pathological features. All biopsies showed numerous CD8+ T cells and macrophages. DILI cases had significantly fewer B lymphocytes than AIH and VH and significantly fewer NK cells than VH. Prominent plasma cells were unusual in IAD (three of 10 cases), but were associated strongly with AIH (eight of nine) and also observed in most with AID (six of nine). They were also found in five of 10 cases with VH. Liver biopsies from subjects with DILI were characterized by low counts of mature B cells and NK cells in portal triads in contrast to VH. NK cells were found only in cases of VH, whereas AIH and VH both showed higher counts of B cells than DILI. Plasma cells were associated most strongly with AIH and less so with AID, but were uncommon in IAD.
Ketamine‐An Update on Its Clinical Uses and Abuses
Authors: Xu Jian , Lei Hong
Published: November 2014

This review highlights the recent clinical research that supports the therapeutic utility of ketamine as a multifaceted drug. After long‐term use as a dissociative anesthetic, it has re‐emerged as a useful agent for ameliorating pain, asthmaticus, and depression. In addition, it is also a substance of abuse. Chronic ketamine abuse over prolonged periods (weeks, months, and years) can produce toxicity to the gastrointestinal and urinary tract. In this review, we described the recent progress on its clinical uses and abuses.
Cyclic mechanical stress modulates neurotrophic and myelinating gene expression of Schwann cells
Authors: Zhang L. , Yang X. , Yue Y. , Ye J. , Yao Y. , Fu Y. , Li G. , Yao Q. , Lin Y. , Gong P.
Published: November 2014

Objectives

This study aimed to investigate the response of Schwann cells to cyclic compressive and tensile stresses of different durations of stimulation.

Materials and methods

RSC96 cells were subjected to cyclic tensile stress or compressive stress; for either, cells in five groups were treated for 0, 1, 2, 24 and 48 h respectively. Enzyme‐linked immunosorbent assay was conducted to detect secretion of nerve growth factor (NGF), brain‐derived neurotrophic factor (BDNF), neurotrophin‐3 and neurotrophin‐4 in the culture medium. Real‐time PCR was conducted to quantify mRNA expression of neurotrophins including NGF, BDNF, neurotrophin‐3 and neurotrophin‐4, and myelin‐related genes including Sox10, Krox20, neuregulin 1, NCAM, N‐cadherin, P0, MAG and MBP. Immunofluorescent staining was performed to visualize Krox20 and F‐actin in the tensile groups.

Results

Within 24 h, cells treated with cyclic tensile stress expressed and secreted significantly more BDNF, while cyclic compression down‐regulated BDNF expression. Cells treated with both tensile and compressive stress down‐regulated expression of NRG1, NCAM, Krox20 and Sox10 at all time points. Expression of N‐cadherin was not affected by either stretch or compression. F‐actin was down‐regulated by tensile stress.

Conclusions

Both tensile and compressive loading down‐regulated expression of several important myelin‐related Schwann cells genes and thus facilitated demyelination. Tensile stress meanwhile promoted secretion of BDNF by Schwann cells within 24 h, which may contribute to maintenance and repair of damaged axons. These effects of mechanical stress might have been mediated by the actin cytoskeleton.
Value of Two‐Dimensional Strain Imaging in Prediction of Myocardial Function Recovery after Percutaneous Revascularization of Infarct‐Related Artery
Authors: Shehata Mohamed
Published: November 2014

Background

Speckle tracking is integrated into echocardiographic systems for evaluation of left ventricular (LV) function by means of automated function imaging (AFI). This study aimed at evaluating role of AFI‐based strain in predicting postpercutaneous coronary intervention (PCI) LV function recovery.

Methods

Fifty patients with anterior wall myocardial infarction and impaired LV ejection fraction (LVEF) were prospectively enrolled. All patients showed positive viability results concerning left anterior descending (LAD) artery territory using low‐dose dobutamine stress echocardiography (LDSE). All patients underwent strain imaging using AFI (before and after PCI).

Result

Mean age of the study population was 56.2 ± 5.4 years, 34 (68%) being males. 24 (48%) patients showed post‐PCI LV function recovery after 4 months. They showed higher pre‐PCI LVEF and AFI‐based strain values. Logistic regression analysis presented baseline LVEF as an independent predictor of LV function recovery (Odds ratio = 0.7026, 95% CI: 0.54–0.93). A pre‐PCI AFI strain value of −4.5% (sensitivity: 84% and specificity: 75%) for LAD territory and −9.5% (sensitivity and specificity of 50%) for global LV predicted LV function recovery.

Conclusion

Assessment of global and territorial LV strains using AFI; is of added value upon viability assessment using LDSE. Higher baseline LVEF and strain values are associated with post‐PCI LV function recovery.
Inhibition in the lateral septum increases sucrose intake and decreases anorectic effects of stress
Authors: Mitra Arojit , Lenglos Christophe , Timofeeva Elena
Published: November 2014

Sucrose‐overeating rats with decreased anorectic response to stress showed lower stress‐induced activation of c‐fos expression in the lateral septum (LS). The present study tested a hypothesis that neuronal inhibition in the LS is important for the development and maintenance of the sucrose‐overeating phenotype. Sucrose overeating was developed with weekly episodes of food restriction (21 h per day, 4 days per week) followed by 1‐h access to sucrose. The anorectic effects of stress on 1‐h sucrose intake were estimated using weekly foot shock stress sessions. The development of the sucrose‐overeating phenotype was accompanied by a decrease in the anorectic effects of stress and by an increase in LS mRNA expression of a γ‐aminobutyric acid (GABA) synthesising enzyme, glutamic acid decarboxylase 67 in stressed rats. Direct recordings of neuronal firing in the LS in rats submitted to repeated weekly cycles of food restriction, sucrose refeeding and stress showed that the development of sucrose overeating increased the percentage of LS neurons inhibited during anticipation and at the start of clusters (CS) of sucrose licking. In addition, the CS‐excited LS neurons showed a decrease in responsiveness to sucrose during the development of sucrose overeating. Direct injection of baclofen, an agonist of the GABAB receptor, into the LS decreased the anorectic effects of stress and increased sucrose intake. These results suggest that an increase in inhibitory effects in the LS is important for the development of sucrose overeating and the decreased anorectic effects of stress.
Estimation of soil properties at the field scale from satellite data: a comparison between spatial and non‐spatial techniques
Authors: Castaldi F. , Casa R. , Castrignanò A. , Pascucci S. , Palombo A. , Pignatti S.
Published: November 2014

A study was carried out to investigate the usefulness of multispectral and hyperspectral satellite information for the estimation of soil properties of agronomic importance such as soil texture and organic matter (SOM) in cultivated fields by comparing different estimation procedures. Images acquired from the Advanced Land Imager (ALI) and Hyperion sensors on board the EO‐1 satellite were used, in combination with ground‐sampling data from an agricultural field in central Italy, to evaluate the advantage of taking into account the spatial correlation between pixels. For this purpose, partial least squares regression (PLSR), ordinary least square (OLS) regression, regression with correlated errors (restricted maximum likelihood; REML) and ordinary kriging (OK) were compared through leave‐one‐out cross‐validation. In order to predict soil variables by different models, the predictors of OLS and REML regressions were obtained from principal component analysis (PCA), PLSR and the minimum noise fraction (MNF) transformations of spectral data on bare soil or vegetation images. The PLSR did not provide satisfactory results in terms of root mean square error (RMSE) and ratio of performance to interquartile range (RPIQ) statistics, even with hyperspectral data, mainly because of the poor signal to noise ratio (SNR) of the Hyperion sensor. The estimation accuracy increased by using the MNF method in combination with a linear mixed effect model. A multivariate approach was sometimes better than univariate ordinary kriging (OK), demonstrating the value of including Hyperion bare soil or vegetation data in the estimation procedure. Hyperspectral data provided better results than multispectral data for clay, sand and especially for SOM estimation, highlighting the value of high‐resolution spectral data for soil‐related applications.
The risk‐return trade‐off between solitary and eusocial reproduction
Authors: Fu Feng , Kocher Sarah D. , Nowak Martin A.
Published: November 2014

Social insect colonies can be seen as a distinct form of biological organisation because they function as superorganisms. Understanding how natural selection acts on the emergence and maintenance of these colonies remains a major question in evolutionary biology and ecology. Here, we explore this by using multi‐type branching processes to calculate the basic reproductive ratios and the extinction probabilities for solitary vs. eusocial reproductive strategies. We find that eusociality, albeit being hugely successful once established, is generally less stable than solitary reproduction unless large demographic advantages of eusociality arise for small colony sizes. We also demonstrate how such demographic constraints can be overcome by the presence of ecological niches that strongly favour eusociality. Our results characterise the risk‐return trade‐offs between solitary and eusocial reproduction, and help to explain why eusociality is taxonomically rare: eusociality is a high‐risk, high‐reward strategy, whereas solitary reproduction is more conservative.
Are you Paying Attention? Female Wolf Spiders Increase Dragline Silk Advertisements When Males do not Court
Authors: Havrilak Jamie A. , Shimmel Kristen M. , Rypstra Ann L. , Persons Matthew H.
Published: November 2014

Females of many spider species invest in chemical advertisements to attract males, yet variation in investment relative to the presence or quality of males remains poorly understood. Males of the wolf spider Pardosa milvina court females longer and more intensively when in contact with female silk and also court more intensively when encountering silk from virgin rather than mated females; therefore, females may use silk as a medium to advertise their receptivity to mate. We estimated female investment in advertisements by measuring variation in the quantity and type of silk deposited by females in the presence or absence of males and among males that varied in their courtship intensity. We measured dragline silk, cord silk, and attachment disk deposition from females on gridded sheets of paper in response to four stimuli over a 30‐min period (n = 39/treatment): (1) an intensively (high) courting male with access to female silk, (2) a weakly courting or non‐courting male (low) without access to female silk, (3) no male present, but female silk present (silk control), and (4) no stimulus present (control). Females produced significantly more dragline silk and significantly less cord silk in the presence of low‐courting males compared to any other treatment, but we found no difference in attachment disk deposition across treatments. Our results suggest that females invest more heavily in dragline deposition when encountering low‐courting males. Additional studies are necessary to determine the relative role of different silk types in male–female sexual communication.
Increased serum nonesterified fatty acid and low ionised calcium concentrations are associated withpost partumcolic in mares
Authors: Holcombe S. J. , Embertson R. M. , Kurtz K. A. , Roessner H. A. , Wismer S. E. , Geor R. J. , Kaneene J. B.
Published: November 2014

Reasons for performing study

Increased serum nonesterified fatty acids (NEFA) and decreased serum electrolytes are linked to abdomasal displacements inpost partumdairy cattle.Post partumcolic in mares may be associated with metabolic changes specific to pregnancy and the periparturient period.

Objectives

To determine if fluctuations in serumNEFA, ionised calcium (iCa) and magnesium (iMg) occurred in periparturient mares and if these alterations were associated withpost partumcolic.

Study design

Longitudinal observational study.

Methods

Mares from 3 farms in centralKentucky were enrolled. Blood samples were collected 14 days prior to the estimated foaling date, within 4 days post parturition, and 14 and 28 days after foaling for batch analysis of serumNEFA,iCaandiMg. Health information was provided by farm managers and veterinarians. Data were analysed usingKruskal–Wallis χ2statistic for nonparametric data and a matched case/control approach. Repeated measures logistic regression models were developed.

Results

SerumNEFAswere higher at 14–1 day before foaling (mean ± s.d., mmol/l), 0.28 ± 0.12,P= 0.04 and from foaling to 4 days after foaling, 0.29 ± 0.20 (P= 0.05) in mares that developed colic compared with those that did not colic, 0.19 ± 0.05 and 0.21 ± 0.14, respectively. Ionised calcium was lower at 15–28 days post foaling in mares that showed colic, 1.50 ± 0.17 compared to mares that did not colic, 1.60 ± 0.12,P= 0.02. Risk of colic inpost partummares increased 38% for each 0.1 mmol/l increase in serumNEFA(odds ratio = 1.38, 95% confidence interval 1.06–1.81,P= 0.02).

Conclusions

Mares withpost partumcolic had significantly higher serumNEFAand lower iCa prior to the colic episode compared with mares that did not develop colic. Monitoring these metabolic alterations may lead to predictive and preventive colic strategies forpost partummares.
A possible contribution of endothelial CCN1 downregulation due to Fli1 deficiency to the development of digital ulcers in systemic sclerosis
Authors: Saigusa Ryosuke , Asano Yoshihide , Taniguchi Takashi , Yamashita Takashi , Takahashi Takehiro , Ichimura Yohei , Toyama Tetsuo , Tamaki Zenshiro , Tada Yayoi , Sugaya Makoto , Kadono Takafumi , Sato Shinichi
Published: November 2014

CCN1 is a pleiotropic molecule involved in angiogenesis and postnatal vasculogenesis, both of which are impaired in systemic sclerosis (SSc). To elucidate the potential role of CCN1 in the development of SSc, we investigated CCN1 expression in the lesional skin of SSc patients and SSc animal models and the clinical correlation of serum CCN1 levels. CCN1 expression was markedly decreased in dermal small blood vessels of SSc patients compared with those of healthy controls, while comparable between normal and SSc dermal fibroblasts. Transcription factor Fli1, whose deficiency due to epigenetic suppression is implicated in the pathogenesis of SSc, occupied the CCN1 promoter and gene silencing of Fli1 resulted in the reduction of CCN1 expression in human dermal microvascular endothelial cells. Consistently, CCN1 expression was suppressed uniformly and remarkably in dermal blood vessels of Fli1+/− mice and partially in those of endothelial cell‐specific Fli1 knockout mice. Furthermore, serum CCN1 levels were significantly decreased in SSc patients with previous and current history of digital ulcers as compared to those without. Collectively, these results suggest that endothelial CCN1 downregulation at least partially due to Fli1 deficiency may contribute to the development of digital ulcers in SSc patients. This study further supports the idea that epigenetic downregulation of Fli1 is a potential predisposing factor in the pathogenesis of SSc.
Management strategy evaluation: best practices
Authors: Punt André E , Butterworth Doug S , de Moor Carryn L , De Oliveira José A A , Haddon Malcolm
Published: November 2014

Management strategy evaluation (MSE) involves using simulation to compare the relative effectiveness for achieving management objectives of different combinations of data collection schemes, methods of analysis and subsequent processes leading to management actions. MSE can be used to identify a ‘best’ management strategy among a set of candidate strategies, or to determine how well an existing strategy performs. The ability of MSE to facilitate fisheries management achieving its aims depends on how well uncertainty is represented, and how effectively the results of simulations are summarized and presented to the decision‐makers. Key challenges for effective use of MSE therefore include characterizing objectives and uncertainty, assigning plausibility ranks to the trials considered, and working with decision‐makers to interpret and implement the results of the MSE. This paper explores how MSEs are conducted and characterizes current ‘best practice’ guidelines, while also indicating whether and how these best practices were applied to two case‐studies: the Bering–Chukchi–Beaufort Seas bowhead whales (Balaena mysticetus; Balaenidae) and the northern subpopulation of Pacific sardine (Sardinops sagax caerulea; Clupeidae).
The effect of row spacing on alfalfa seed and forage production under irrigated Mediterranean agricultural conditions
Authors: Chocarro C. , Lloveras J.
Published: November 2014

We evaluated the effect of row spacing on seed and forage yields in alfalfa (Medicago sativa L.) using combined seed and forage production plots, in an irrigated Mediterranean agricultural environment. We compared three row distances (20, 40 and 60 cm) in two cultivars at a seed rate of 25 kg ha−1 over a period of 4 years. We measured the seed yield and yield components as well as forage production. The 4‐year average revealed an overall clean seed yield of 367 kg ha−1 declining over time, without significant differences in row distances. The number of shoots per square metre differed significantly as a function of row spacing, with averages of 357, 226 and 172 shoots m−2 for row widths of 20, 40 and 60 cm respectively. The row spacing did not affect the number of racemes per shoot (23·1), the number of pods per raceme (7·2), the number of seeds per pod (6·5) or the thousand seed weight (1·667 g). The average forage production was 20·1, 18·5 and 17·9 Mg DM ha−1 for row distances of 20, 40 and 60 cm, respectively, with higher yields associated with smaller row distances. Our data demonstrate that row spacing >20 cm does not confer any advantage to the production of alfalfa seed under irrigated Mediterranean agricultural conditions and that close spacing can significantly increase forage yields in the same environment.
Indirect Rule and Varieties of Governance
Authors: Naseemullah Adnan , Staniland Paul
Published: November 2014

This article reexamines the venerable concept of indirect rule. We argue, drawing on evidence from colonial and postcolonial South Asia, that indirect rule actually represented a diverse set of governance forms that need to be clearly distinguished. Using a new typology of varieties of governance, we show that colonial governments establishedsuzerain,hybrid, andde juregovernance, in addition to direct rule across territories, based on the incentives and constraints of the state. The repertoire of governance forms narrowed and changed but did not disappear during decolonization, showing that the postcolonial state had powerful reasons to maintain forms of heterodox governance. Dramatic shifts, alongside enduring continuity, challenge a simple narrative of path dependence and the adherence to tradition, instead showing that governments have made conscious choices about how to govern. We conclude by discussing the implications of these arguments for broader understandings of state power.
Octavia Butler and the Aesthetics of the Novel
Authors: Pickens Therí A.
Published: November 2014

Octavia Butler depicts a character with physical or mental disability in each of her works. Yet scholars hesitate to discuss her work in terms that emphasize the intersection with disability. Two salient questions arise: How might it change Butler scholarship if we situated intersectional embodied experience as a central locus for understanding her work? Once we privilege such intersectionality, how might this transform our understanding of the aesthetics of the novel? In this paper, I reorient the criticism of Butler's work such that disability becomes one of the social categories under consideration. I read two prominent analyses of Butler's work because their interpretations—black feminist in orientation—centralize black female identity as a category of analysis. I contend these analyses grapple with ideas that can only be fully understood with disability as an integral portion of the discussion. Since categories of analysis like race, disability, and gender require and create cultural tropes and challenge accepted forms, I outline three components of Butler's aesthetic: open‐ended conclusions that frustrate the narrative cohesion associated with the novel form, intricate depictions of power that potentially alienate the able‐bodied reader, and contained literary chaos that upends the idea of ontological fixity.
One‐dimensional cutting stock with a limited number of open stacks: bounds and solutions from a new integer linear programming model
Authors: Arbib Claudio , Marinelli Fabrizio , Ventura Paolo
Published: November 2014

We address a one‐dimensional cutting stock problem where, in addition to trim‐loss minimization, cutting patterns must be sequenced so that no more than s different part types are in production at any time. We propose a new integer linear programming formulation whose constraints grow quadratically with the number of distinct part types and whose linear relaxation can be solved by a standard column generation procedure. The formulation allowed us to solve problems with 20 part types for which an optimal solution was unknown.
SO, WHAT'S NEW?
Authors: Eswar Sapnoti
Published: November 2014

New research by Sapnoti Eswar examines whether using derivatives to mitigate risk prevents firms from innovating
UNRULY BEHAVIOUR
Authors: Crainer Stuart
Published: November 2014

Ever spent time idly watching clever ads featuring animals on YouTube? Sarah Wood, co‐founder and COO of social video company Unruly, tells Stuart Crainer how she has helped build a business on knowing why
FROM BANKER TO BAKER VIA CANDLESTICK MAKER
Authors: Zilberkweit Ian
Published: November 2014

Ian Zilberkweit went from being a director in HSBC's Corporate Finance Group to growing one of Russia's largest bakery café chains. He reflects on the shift from City power lunches to making dough in Moscow
THE DISRUPTIVE ENTREPRENEUR
Authors: Coomber Steve
Published: November 2014

Atte Miettinen talks peaks, profits and bytes with Steve Coomber
MY DAY
Authors: Ettinger Pablo
Published: November 2014

Pablo Ettinger is the co‐founder of Caffè Nero, chairman of Streetlife.com and much more. He opens the diary of his portfolio life