bluuebunny/crossref_metadata_2025 huggingface dataset:
Who Needs Laboratories and Who Needs Statins?
Authors: Pandya Ankur , Weinstein Milton C. , Salomon Joshua A. , Cutler David , Gaziano Thomas A.
Published: January 2014

Background—

Early detection and treatment of cardiovascular disease (CVD) risk factors produces significant clinical benefits, but no consensus exists on optimal screening algorithms. This study aimed to evaluate the comparative and cost-effectiveness of staged laboratory-based and non–laboratory-based total CVD risk assessment.

Methods and Results—

We used receiver operating characteristic curve and cost-effectiveness modeling methods to compare strategies with and without laboratory components and used single-stage and multistage algorithms, including approaches based on Framingham risk scores (laboratory-based assessments for all individuals). Analyses were conducted using data from 5998 adults in the Third National Health and Nutrition Examination Survey without history of CVD using 10-year CVD death as the main outcome. A microsimulation model projected lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios for 60 Framingham-based, non–laboratory-based, and staged screening approaches. Across strategies, the area under the receiver operating characteristic curve was 0.774 to 0.780 in men and 0.812 to 0.834 in women. There were no statistically significant differences in area under the receiver operating characteristic curve between multistage and Framingham-based approaches. In cost-effectiveness analyses, multistage strategies had incremental cost-effectiveness ratios of $52 000/QALY and $83 000/QALY for men and women, respectively. Single-stage/Framingham-based strategies were dominated (higher cost and lower QALYs) or had unattractive incremental cost-effectiveness ratios (>$300 000/QALY) compared with single-stage/non–laboratory-based and multistage approaches.

Conclusions—

Non–laboratory-based CVD risk assessment can be useful in primary CVD prevention as a substitute for laboratory-based assessments or as the initial component of a multistage approach. Cost-effective multistage screening strategies could avoid 25% to 75% of laboratory testing used in CVD risk screening with predictive power comparable with Framingham risks.
Archetypal Arg169Cys Mutation in NOTCH3 Does Not Drive the Pathogenesis in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leucoencephalopathy via a Loss-of-Function Mechanism
Authors: Cognat Emmanuel , Baron-Menguy Céline , Domenga-Denier Valérie , Cleophax Sabine , Fouillade Charles , Monet-Leprêtre Marie , Dewerchin Mieke , Joutel Anne
Published: January 2014

Background and Purpose—

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy, the most common heritable small vessel disease of the brain, is caused by dominant mutations in the NOTCH3 receptor that stereotypically lead to age-dependent Notch3
ECD
deposition in the vessels. NOTCH3 loss of function has been demonstrated for few mutations. However, whether this finding applies to all mutations and whether a loss-of-function mechanism drives the manifestations of the disease remain yet unknown. This study investigated the in vivo functionality of the Arg169Cys archetypal mutation.

Methods—

We used mice with constitutive or conditional reduction of NOTCH3 activity, mice harboring the Arg169Cys mutation at the endogenous
Notch3
locus (
Notch3

Arg170Cys

), and mice overexpressing the Arg169Cys NOTCH3 mutant (
TgPAC-Notch3

R169C

) on either a
Notch3
wild-type or a null background. NOTCH3 activity was monitored in the brain arteries by measuring the expression of NOTCH3 target genes using real-time polymerase chain reaction. Notch3
ECD
deposits were assessed by immunohistochemistry. Brain parenchyma was analyzed for vacuolation and myelin debris in the white matter and infarcts.

Results—

We identified a subset of genes appropriate to detect NOTCH3 haploinsufficiency in the adult. Expression of these genes was unaltered in
Notch3

Arg170Cys

mice, despite marked Notch3
ECD
deposits. Elimination of wild-type NOTCH3 did not influence the onset and burden of white matter lesions in 20-month-old TgPAC-Notch3
R169C
mice, and 20-month-old Notch3-null mice exhibited neither infarct nor white matter changes.

Conclusions—

These data provide strong evidence that cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy can develop without impairment of NOTCH3 signaling and argue against a loss of NOTCH3 function as a general driving mechanism for white matter lesions in cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy.
Are Arterial Calcifications a Marker of Remodeling in Vertebrobasilar Territory?
Authors: Pikija Slaven , Magdič Jožef , Knific Alenka
Published: January 2014

Background and Purpose—

Intracranial atherosclerosis is responsible for a substantial proportion of stroke, and vessel calcifications as seen on native computed tomographic scans could be an estimate of its burden. The presence of vertebrobasilar artery calcifications is associated with risk factors.

Methods—

This study is a retrospective clinical study on 449 consecutive patients with stroke. Native computed tomographic scans were assessed for the presence of calcification in the intracranial segment of vertebrobasilar artery, and the area of each vessel was calculated from 2 perpendicular diameters. A comprehensive assessment of standard risk factors was recorded.

Results—

A total of 245 (54.6%) patients had visible calcifications in vertebrobasilar artery. Calcifications were positively associated with advanced age (odds ratio, 1.04; 95% confidence interval, 1.02–1.06;
P
<0.001), larger total vessel area (odds ratio, 1.01; 95% confidence interval, 1.00–1.01;
P
<0.001), and history of previous transient ischemic attack/stroke (odds ratio, 1.82; 95% confidence interval, 1.08–3.07;
P
=0.024).

Conclusions—

Higher prevalence of calcifications in vertebrobasilar artery territory of patients with stroke is associated with advanced age, larger arterial area, and history of previous transient ischemic attack/stroke.
A revision of the genus Notothylas (Notothyladaceae, Anthocerotophyta) in China
Authors: PENG TAO , ZHU RUI-LIANG
Published: January 2014

The genus Notothylas in China contains four species. One new species, Notothylas yunnanensis, is described and illustrated. The new species is characterized by each proximal spore surface with a small central hollow, irregularly arranged, rectangular to quadrate epidermal cells of the capsule, and absence of a special dehiscence line in the capsule. A key to the species of Notothylas in China is provided.
Large carpenter bees in Argentina: systematics and notes on the biology of Xylocopa subgenus Neoxylocopa (Hymenoptera: Apidae)
Authors: LUCIA MARIANO , ABRAHAMOVICH ALBERTO H.
Published: January 2014

A systematic revision of the species of the genus Xylocopa subgenus Neoxylocopa in Argentina is provided. Seven species are included: X. atamisquensis Lucia & Abrahamovich, X. augusti Lepeletier, X. eximia Pérez, X. frontalis (Olivier), X. mendozana Enderlein, X. nigrocincta Smith and X. tacanensis Moure. The males of X. eximia and X. nigrocincta are described for the first time. Xylocopa jujuyensis Brèthes is a new junior synonym of X. nigrocincta. Photographs, occurrence maps, and identification keys for the species are presented. Information on the nest architecture and substratum preference are also given.
Stimulant side effects: prefrontal/basal ganglia circuit control at dopamine D1/D2 receptors
Authors: Levy Florence , Dadds Mark R
Published: January 2014

Background:

While side effects of stimulant medication used to treat children for attention deficit hyperactivity disorder have been clinically described as mild but variable, there is little or no research or understanding of biological mechanisms involved.

Method:

The present short review extends the ‘tonic-phasic’ dopamine hypothesis in terms of prefrontal and subcortical dopamine receptor (D1/D2) imbalance.

Results:

The minor allele of the dopamine D1 receptor predicts the ‘zombie-like’ motor side effect clinically described in some children treated with stimulant medications.

Conclusion:

Stimulant side effects may be best understood as reflecting imbalance in parallel cortico-thalamic-striatal circuits, and motor side effects as a result of prefrontal D1/D2 imbalance allowing greater motor inhibitory effects at subcortical D2 receptors. This is a variation of the ‘tonic-phasic’ hypothesis, which takes D1 allelic variation into account.
Methodological Positionings and Perspectives
Authors: Diaz-Bone Rainer
Published: January 2014

The article compares the French economics of convention (EC) with institutional logics approach (IL). Both approaches share a perspective on a pluralism of deeper structures for coordination in organizations and fields. The differences in theoretical embedding, theoretical concepts, and underlying methodological positions are worked out. While IL is closely linked to a “culturalist methodological holism,” EC is linked to a methodological position of a “complex pragmatic situationalism.” Still, the reception of EC in the current strand of IL is weak. Reception (in both directions) and comparison should avoid reducing these approaches to single concepts as “convention” or “institutional logics” and respect their embeddedness in different theoretical traditions and methodological cultures. Analytical dimensions for comparison of institutional approaches are proposed.
Participant experiences of a community-based maintenance program post-pulmonary rehabilitation
Authors: Desveaux Laura , Beauchamp Marla , Rolfe Debbie , Goldstein Roger , Brooks Dina
Published: January 2014

The aim of the present study was to describe the perspectives of individuals with chronic obstructive pulmonary disease (COPD) who participated in a minimally supervised maintenance exercise intervention and identify the barriers and facilitators associated with participation. The intervention was delivered in a community center and was designed to maintain exercise capacity and quality of life following discharge from pulmonary rehabilitation. This study utilized qualitative focus groups (FGs) involving individuals with COPD ( n = 12) who had been attending the maintenance community program for at least 6 months. All individuals who met the inclusion criteria for the FGs consented to participate. Four themes were identified: (1) issues around attendance; (2) perceived benefits of the program; (3) perceived burdens of the program; and (4) recommendations for program improvement. Participants expressed more benefits than barriers, stating that their experience of improved function and quality of life facilitated their attendance. Barriers included exacerbations, fatigue, access to transportation, and weather. Participants endorsed the benefits of a community-based maintenance exercise program after pulmonary rehabilitation. Minimally supervised community-based programs with access to a case manager may provide a useful approach to enhancing adherence to exercise.
The impact of chronic obstructive pulmonary disease-related fears on disease-specific disability
Authors: Keil Daniel C , Stenzel Nikola M , Kühl Kerstin , Vaske Isabelle , Mewes Ricarda , Rief Winfried , Kenn Klaus
Published: January 2014

Anxiety is frequently observed in persons with chronic obstructive pulmonary disease (COPD). Although anxiety in persons with COPD is multifaceted, it is mostly assessed as a general psychopathological condition. Consequently, the objectives of this study were to revise an existing questionnaire assessing relevant anxieties for use in clinical practice and research, to examine the association between COPD-related fears and disability, and finally to develop norms for COPD-related fears. Disease severity (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage, use of long-term oxygen), sociodemographic characteristics, COPD-specific disability (COPD assessment test), and psychopathology (depression, general anxiety, somatoform symptoms, and disease-related fears) were obtained from a sample of 1025 individuals with COPD via the Internet. We used the COPD Anxiety Questionnaire (German: CAF) for the assessment of different fears that have been found to be relevant in COPD: fear of dyspnea, fear of physical activity, fear of progression, fear of social exclusion, and sleep-related worries. Mean COPD-specific disability was high (22.87). After explanatory and confirmatory factor analyses, a revised version of the CAF was constructed. The economical and user-friendly CAF-R showed adequate reliability and expected correlations with convergent and discriminant constructs. Gender-specific norms are provided for use in clinical practice and research. Even after controlling for GOLD stage, sociodemographic variables, and psychopathology, COPD-related fears contributed incrementally to disease-specific disability. The CAF-R is an economical and reliable tool to assess different specific fears in COPD. Results indicate that disease-specific fears have an impact on disability, supporting the assumption that detailed assessment of anxiety in COPD should be included in clinical practice.
Show Some Emotion?
Authors: Sanders Jackie , Munford Robyn , Liebenberg Linda , Henaghan Mark
Published: January 2014

There is debate about the proper role of emotions in research; however, in the pursuit of certain research questions, an emotional impact on researchers is unavoidable and has the potential to engulf researchers and research processes. This article explores the emotional challenges involved in completing a large, mixed-methods research project focused on high-risk youth. We outline four dilemmas researchers confronted as they managed the emotional impact of the fieldwork: tentative disclosures, catharsis, hopelessness, and motivation. Understanding these dilemmas enhanced the analysis and the conceptual work of the research.
An Intersensory Interaction Account of Priming Effects—and Their Absence
Authors: Klatzky Roberta L. , Creswell J. David
Published: January 2014

Psychological researchers have found that exposures to stimuli (primes) can subsequently influence people’s behavior by pathways that would seem to be quite remote. For example, people exposed to words associated with older adults may walk more slowly. Recently priming studies, particularly those showing dramatic effects on social behavior, have been under scrutiny because of the unreliability of empirical results. In this article, we shed light on the issue by describing a general model of intersensory interaction, in which two or more sources of information provide an estimate or “bid” on a property of the world, with the perceptual outcome being a weighted combination of the bids. When it is extended by adding bids that stem from memory or inference, the model identifies systematic factors that might undermine priming, including random variation in estimates, contextual influences on memory retrieval and inference, competition among information sources, and cognitive control. These factors are not only explanatory but are predictive of when priming effects can be expected. Our hope is that by promoting the understanding of underlying processes that may explain how primes can influence behavior, the bidding model and the general approach that it represents offer novel insights into the hotly debated area of priming research.
Priming, Replication, and the Hardest Science
Authors: Cesario Joseph
Published: January 2014

Concerns have been raised recently about the replicability of behavioral priming effects, and calls have been issued to identify priming methodologies with effects that can be obtained in any context and with any population. I argue that such expectations are misguided and inconsistent with evolutionary understandings of the brain as a computational organ. Rather, we should expect priming effects to be highly sensitive to variations in experimental features and subject populations. Such variation does not make priming effects frivolous or capricious but instead can be predicted a priori. However, absent theories specifying the precise contingencies that lead to such variation, failures to replicate another researcher’s findings will necessarily be ambiguous with respect to the inferences that can be made. Priming research is not yet at the stage where such theories exist, and therefore failures are uninformative at the current time. Ultimately, priming researchers themselves must provide direct replications of their own effects; researchers have been deficient in meeting this responsibility and have contributed to the current state of confusion. The recommendations issued in this article reflect concerns both with the practice of priming researchers and with the inappropriate expectations of researchers who have failed to replicate others’ priming effects.
Organizational Commitment and Turnover Intention in Union and Non-Union Firms
Authors: Park Hong Y. , Christie Raymond L. , Sype Gail E.
Published: January 2014

There are differences in organizational architecture between union and non-union construction firms in early 1990s. The construction industry has traditionally been dominated by strong union firms. However, non-union construction firms began to emerge in the 1990s and this change caused to bring conflicts between union and non-union construction firms. This presents a unique opportunity to study employees’ attitude toward organization. This article investigates workers’ attitudes toward union and non-union construction firms in terms of organizational commitment (OC) and turnover intention. Control variables in OC and turnover intention include personal characteristics, job characteristics, group−leader relations and organizational characteristics. The study found that employees in union firms are more committed to the organization than non-union organization, but they have higher intention to job turnover although the regression coefficients of union variable in commitment and turnover intention are not statistically significant at the conventional level of significance.
Elavl1a regulates zebrafish erythropoiesis via posttranscriptional control of gata1
Authors: Li Xi , Lu Yi-Chien , Dai Kezhi , Torregroza Ingrid , Hla Timothy , Evans Todd
Published: January 2014

Key Points

Elavl1 is a protein that binds to the 3′-UTR of RNA encoding Gata1. Elavl1 controls embryonic erythropoiesis by enhancing expression of Gata1.
A genome-wide scan for signatures of selection in Chinese indigenous and commercial pig breeds
Authors: Yang Songbai , Li Xiuling , Li Kui , Fan Bin , Tang Zhonglin
Published: January 2014

Background

Modern breeding and artificial selection play critical roles in pig domestication and shape the genetic variation of different breeds. China has many indigenous pig breeds with various characteristics in morphology and production performance that differ from those of foreign commercial pig breeds. However, the signatures of selection on genes implying for economic traits between Chinese indigenous and commercial pigs have been poorly understood.

Results

We identified footprints of positive selection at the whole genome level, comprising 44,652 SNPs genotyped in six Chinese indigenous pig breeds, one developed breed and two commercial breeds. An empirical genome-wide distribution of Fst (F-statistics) was constructed based on estimations of Fst for each SNP across these nine breeds. We detected selection at the genome level using the High-Fst outlier method and found that 81 candidate genes show high evidence of positive selection. Furthermore, the results of network analyses showed that the genes that displayed evidence of positive selection were mainly involved in the development of tissues and organs, and the immune response. In addition, we calculated the pairwise Fst between Chinese indigenous and commercial breeds (CHN VS EURO) and between Northern and Southern Chinese indigenous breeds (Northern VS Southern). The IGF1R and ESR1 genes showed evidence of positive selection in the CHN VS EURO and Northern VS Southern groups, respectively.

Conclusions

In this study, we first identified the genomic regions that showed evidences of selection between Chinese indigenous and commercial pig breeds using the High-Fst outlier method. These regions were found to be involved in the development of tissues and organs, the immune response, growth and litter size. The results of this study provide new insights into understanding the genetic variation and domestication in pigs.
Atorvastatin treatment attenuates renal injury in an experimental model of ischemia–reperfusion in rats
Authors: Wu Kefei , Lei Wenjing , Tian Jianwei , Li Hongyan
Published: January 2014

Background

Recent studies in animal models have shown that statins can protect against renal failure independent of their lipid-lowering actions, and there is also an association between statin use and improved renal function after suprarenal aortic clamping. We investigated the hypothesis that post-ischemic acute renal failure could be ameliorated with atorvastatin (ATO) treatment and the possible molecular mechanisms in a model of ischemia–reperfusion (IR) in rats.

Methods

Twenty-four male Sprague–Dawley rats were divided into three groups: sham, IR, and IR + ATO. ATO was given by a single intraperitoneal injection (10 mg/kg) 30 min before reperfusion in the IR + ATO group. The IR group and sham group received saline vehicle via the intraperitoneal route.

Results

After 24 h of IR, serum creatinine levels were increased in the IR group compared with the sham group (p < 0.001). ATO treatment reduced the elevation of serum creatinine level by 18% (p < 0.05) and significantly increased the creatinine clearance rate (p < 0.001). Concentrations of advanced oxidation protein products and malondialdehyde were reduced in the ATO group, approaching levels observed in sham-group rats. ATO treatment alleviated pathological changes in renal tubular cells. Protein and mRNA levels of intercellular adhesion molecule-1 and monocyte chemotactic protein-1 were reduced significantly.

Conclusions

These data suggest that direct protection of injured kidneys by ATO was possible even though the drug was injected 30 min before reperfusion, and that ATO may reduce IR injury by anti-inflammatory effects and by reducing oxidation stress.
Immune response associated with Toll-like receptor 4 signaling pathway leads to steroid-induced femoral head osteonecrosis
Authors: Tian Lei , Wen Qi , Dang Xiaoqian , You Wulin , Fan Lihong , Wang Kunzheng
Published: January 2014

Background

Femoral head osteonecrosis is frequently observed in patients treated with excessive corticosteroids. The objective of the current study was to establish a rat model to investigate the disruption of immune response in steroid-induced femoral head osteonecrosis via Toll-like receptor 4 (TLR4) signaling pathway.

Methods

Male SD rats were divided into the treatment group (group A) and the model group (group B) consisting of 24 rats each, and were injected intramuscularly with 20 mg/kg methylprednisolone (MP) for 8 weeks, once a week. The rats in group A were injected intravenously with 7.5 mg/kg TAK242 before each MP administration. A control group (group N) consisted of 12 rats were received saline injection. All animals were sacrificed 8, 10 and 12 weeks from the first MP injection, respectively. Histopathological analysis was performed and the concentration of tartrate-resistant acid phosphatase (TRAP) in serum was tested. The signaling molecules including TLR4, MyD88, NF-κB p65 and MCP-1 were detected by immunohistochemistry, quantitative real-time PCR and Western blot.

Results

Femoral head osteonecrosis was observed in the model rats, and the concentration of TRAP and positive staining of all signaling molecules increased significantly in group B compared with that in group A and group N. Compare with the control group, the mRNA expressions and protein levels of all signaling molecules were enhanced significantly in group B, but no significant in group A.

Conclusions

Corticosteroids can induce femoral head osteonecrosis by disturbing the immune response via TLR4 signaling pathway. These findings suggest that the disruption of immune response play a role in the pathogenesis of osteonecrosis.
Standardizing therapeutic parameters of acupuncture for pain suppression in rats: preliminary study
Authors: Yeo Sujung , Lim Hyungtaeck , Choe Ilwhan , Kim Sung-Hoon , Lim Sabina
Published: January 2014

Background

Despite acupuncture’s wide and successful use, it is still considered as lacking scientifically rigorous evidence, especially with respect to its effectiveness. To address this problem, it is necessary to re-examine the practice of acupuncture using scientific methodology. The standardization of acupuncture practices may offer a solution. As a preliminary step towards the standardization of acupuncture stimulation in animal experiments, this study attempted to clarify the various therapeutic parameters that contribute to acupuncture’s efficacy.

Methods

This study identified specific acupoints, temporal point of needling, rotation of the needle, duration of acupuncture, and diameter of the needle as the parameters, through formalin test. In this test, acupuncture was performed on either the ST36 or LR2 point immediately after pain induction and 5 minutes after pain induction.

Results

The formalin test yielded no significant suppression of pain in the case of ST36 and LR2 acupuncture stimulation immediately following pain induction. When acupuncture was applied 5 minutes after pain induction, however, the ST36 stimulation resulted in a significant decrease in pain, while the LR2 stimulation produced no change. The duration of acupuncture, but not the diameter of the needle, was also significant. As for the rotation of the needle, there was no significant difference in the pain reduction achieved in the rotation and non-rotation groups.

Conclusions

We determined that specific acupoint, temporal point of needling, and duration of treatment are important factors in the inhibition of pain. These finding strongly suggest that in animal experiments, the application of a set of appropriate therapeutic parameters can significantly influence the outcome.
Cisplatin-induced epigenetic activation of miR-34a sensitizes bladder cancer cells to chemotherapy
Authors: Li Heng , Yu Gan , Shi Runlin , Lang Bin , Chen Xianguo , Xia Ding , Xiao Haibing , Guo Xiaolin , Guan Wei , Ye Zhangqun , Xiao Wei , Xu Hua
Published: January 2014

Background

Accumulating evidence suggests a tumor suppressive role for miR-34a in human carcinogenesis. However, its precise biological role remains largely elusive. This study aimed to reveal the association of the miR-34a expression and its modulation of sensitivity to cisplatin in muscle-invasive bladder cancer (MIBC).

Methods

miR-34a expression in MIBC cell lines and patient tissues was investigated using qPCR. The methylation analysis of miR-34a promoter region was performed by MassARRAY. Synthetic short single or double stranded RNA oligonucleotides and lentiviral vector were used to regulate miR-34a expression in MIBC cells to investigate its function in vitro and in vivo.

Results

miR-34a expression was frequently decreased in MIBC tissues and cell lines through promoter hypermethylation while it was epigenetically increased in MIBC cells following cisplatin treatment. Increased miR-34a expression significantly sensitized MIBC cells to cisplatin and inhibited the tumorigenicity and proliferation of cancer cells in vitro and in vivo. Furthermore, we identified CD44 as being targeted by miR-34a in MIBC cells following cisplatin treatment, and increased CD44 expression could efficiently reverse the effect of miR-34a on MIBC cell proliferation, colongenic potential and chemosensitivity.

Conclusions

Cisplatin-based chemotherapy induced demethylation of miR-34a promoter and increased miR-34a expression, which in turn sensitized MIBC cells to cisplatin and decreased the tumorigenicity and proliferation of cancer cells that by reducing the production of CD44.
Human aortic allograft: an excellent conduit choice for superior vena cava reconstruction
Authors: Spera Kristyn , Kesler Kenneth A , Syed Amjadullah , Boyd Jack H
Published: January 2014

Superior vena cava (SVC) reconstruction is occasionally required in the treatment of benign and malignant conditions. We report a patient with symptomatic SVC obstruction secondary to mediastinal fibrosis successfully reconstructed with an aortic allograft.
Biological effects of a new set 1,2,4-triazolo[1,5-a]quinazolines on heart rate and blood pressure
Authors: Al-Salahi Rashad , El-Tahir Kamal-Eldin , Alswaidan Ibrahim , Lolak Nabih , Hamidaddin Mohammed , Marzouk Mohamed
Published: January 2014

Background

Several quinazoline and triazole derivatives are reported to possess a wide-range of interesting pharmacological effects. Although various triazoloquinazoline subclasses having been synthesized and studied, the preparation of 1,2,4-triazolo[1,5-a]quinazolines as antihypertensive agent is still relatively unexplored. In continuation of our earlier research, we aimed at the synthesis and development of various potent antihypertensive 1,2,4-triazoloquinazoline derivatives.

Results

A new series of 1,2,4-triazolo[1,5-a]quinazoline derivatives have been synthesized. Their structures were mainly established by spectroscopic methods of analysis (IR, MS, 1H and 13C NMR). Their in vivo antihypertensive activity was evaluated by tail cuff method using Muromachi Blood Pressure Monitor (Model MK 2000) for rats and mice. Some of the tested compounds were found to exhibit valuable effects in terms of heart rate and blood pressure. According to the biological results, some of tested derivatives have abolished completely the tachycardia of the parent compounds and may be studied and modified as potential adrenoblockers and cardiac stimulant.

Conclusion

New series of fifteen 1,2,4-triazolo[1,5-a]quinazolines were synthesized by convenient methodology from four key molecules, whereby their structures were established by advanced spectroscopic analyses. Some lead compounds have abolished completely the tachycardia of the parent compounds, that may be examined as potent adrenoblockers and some other compounds seem to be a cardiac stimulant or may be modified to enhance their hypotensive activity.
Acute presentation of vasospastic angina induced by oral capecitabine: a case report
Authors: Golias Christos , Dimitriadis Georgios , Dimitriadis Dimokritos , Graidis Christos , Dimitrelos Ilias , Tsiakou Afroditi , Bitsis Theodosis , Charalabopoulos Konstantinos
Published: January 2014

Introduction

Oral capecitabine is an oral prodrug of 5-fluorouracil that has been integrated into the management of multiple cancer types because of the convenience of administration and its efficacy compared with 5-fluorouracil. Capecitabine mimics the pharmacokinetics of intravenous 5-fluorouracil. While cardiac events associated with the use of 5-fluorouracil are a well-known side effect, capecitabine-induced cardiotoxicity has only been rarely reported.

Case presentation

We present a case of a 46-year-old woman of Greek ethnicity who presented to our institution with an operated gastric sarcoma who experienced capecitabine-induced vasospastic angina. Primarily a clinical diagnosis of a possible acute coronary syndrome was proposed and the patient was admitted to the hospital for further investigation which was proved between normal limits. After a witnessed episode of angina, her prior history of capecitabine intake and an undertaken further imaging investigation we associated anginal symptoms and signs with vasospastic angina induced by capecitabine 36 hours prior to hospital admission.

Conclusion

Cardiologists should be aware of the potential cardiac hazards of capecitabine, especially in patients with cardiovascular risk factors. Due to the increasing usage of capecitabine during the last years, patients should be warned for the possibility of chest pain, particularly during the first few days of capecitabine treatment. Specifically, patients developing acute coronary syndrome should not be retreated with capecitabine. On the other hand, due to its promising antitumoral efficacy, its use should not be discouraged.
Determinants of the population growth of the West Nile virus mosquito vector Culex pipiens in a repeatedly affected area in Italy
Authors: Mulatti Paolo , Ferguson Heather M , Bonfanti Lebana , Montarsi Fabrizio , Capelli Gioia , Marangon Stefano
Published: January 2014

Background

The recent spread of West Nile Virus in temperate countries has raised concern. Predicting the likelihood of transmission is crucial to ascertain the threat to Public and Veterinary Health. However, accurate models of West Nile Virus (WNV) expansion in Europe may be hampered by limited understanding of the population dynamics of their primary mosquito vectors and their response to environmental changes.

Methods

We used data collected in north-eastern Italy (2009–2011) to analyze the determinants of the population growth rate of the primary WNV vectorCulex pipiens. A series of alternative growth models were fitted to longitudinal data on mosquito abundance to evaluate the strength of evidence for regulation by intrinsic density-dependent and/or extrinsic environmental factors. Model-averaging algorithms were then used to estimate the relative importance of intrinsic and extrinsic variables in describing the variations of per-capita growth rates.

Results

Results indicate a much greater contribution of density-dependence in regulating vector population growth rates than of any environmental factor on its own. Analysis of an average model ofCx. pipiensgrowth revealed that the most significant predictors of their population dynamics was the length of daylight, estimated population size and temperature conditions in the 15 day period prior to sampling. Other extrinsic variables (including measures of precipitation, number of rainy days, and humidity) had only a minor influence onCx. pipiensgrowth rates.

Conclusions

These results indicate the need to incorporate density dependence in combination with key environmental factors for robust prediction ofCx. pipienspopulation expansion and WNV transmission risk. We hypothesize that detailed analysis of the determinants of mosquito vector growth rate as conducted here can help identify when and where an increase in vector population size and associated WNV transmission risk should be expected.
Present and future potential of plant-derived products to control arthropods of veterinary and medical significance
Authors: George David R , Finn Robert D , Graham Kirsty M , Sparagano Olivier AE
Published: January 2014

The use of synthetic pesticides and repellents to target pests of veterinary and medical significance is becoming increasingly problematic. One alternative approach employs the bioactive attributes of plant-derived products (PDPs). These are particularly attractive on the grounds of low mammalian toxicity, short environmental persistence and complex chemistries that should limit development of pest resistance against them.

Several pesticides and repellents based on PDPs are already available, and in some cases widely utilised, in modern pest management. Many more have a long history of traditional use in poorer areas of the globe where access to synthetic pesticides is often limited. Preliminary studies support that PDPs could be more widely used to target numerous medical and veterinary pests, with modes of action often specific to invertebrates.

Though their current and future potential appears significant, development and deployment of PDPs to target veterinary and medical pests is not without issue. Variable efficacy is widely recognised as a restraint to PDPs for pest control. Identifying and developing natural bioactive PDP components in place of chemically less-stable raw or 'whole’ products seems to be the most popular solution to this problem. A limited residual activity, often due to photosensitivity or high volatility, is a further drawback in some cases (though potentially advantageous in others). Nevertheless, encapsulation technologies and other slow-release mechanisms offer strong potential to improve residual activity where needed.

The current review provides a summary of existing use and future potential of PDPs against ectoparasites of veterinary and medical significance. Four main types of PDP are considered (pyrethrum, neem, essential oils and plant extracts) for their pesticidal, growth regulating and repellent or deterrent properties. An overview of existing use and research for each is provided, with direction to more extensive reviews given in many sections. Sections to highlight potential issues, modes of action and emerging and future potential are also included.
Evaluation of the relationship between circulating omentin-1 concentrations and components of the metabolic syndrome in adults without type 2 diabetes or cardiovascular disease
Authors: Vu Anh , Sidhom Maha S , Bredbeck Brooke C , Kosmiski Lisa A , Aquilante Christina L
Published: January 2014

Background

Dysregulation of omentin-1, a beneficial adipokine, is thought to play a role in the development of type 2 diabetes and cardiovascular disease. The objective of this study was to evaluate the relationship between circulating omentin-1 concentrations and components of the metabolic syndrome in adults without type 2 diabetes or cardiovascular disease, and to determine if sex differences influenced the observed relationships.

Methods

Fasting blood samples were obtained from 93 adults, ages 30–60 years, without type 2 diabetes and/or cardiovascular disease. Participants were classified as having the metabolic syndrome according to American Heart Association/National Heart, Lung and Blood Institute criteria. Plasma omentin-1 concentrations were measured using a commercially-available enzyme-linked immunosorbent assay, and relationships between plasma omentin-1 and components of the metabolic syndrome were assessed in the entire study cohort, by metabolic syndrome status, and by sex.

Results

On average, participants were 48 ± 8 years of age, 50.5% were women, 54.8% were Caucasian, and 70% had the metabolic syndrome. Plasma omentin-1 concentrations did not differ significantly between individuals with versus without the metabolic syndrome (145.7 ± 70 versus 157.4 ± 79.3 ng/ml, p = 0.50). However, men with the metabolic syndrome had significantly lower omentin-1 levels than men without the metabolic syndrome (129.9 ± 66 versus 186.3 ± 84.3 ng/ml, p = 0.03). Plasma omentin-1 concentrations were significantly correlated with HDL cholesterol in the entire study cohort (r = 0.26; p = 0.01), which was primarily driven by a correlation in men (r = 0.451, p = 0.002) and participants with the metabolic syndrome (r = 0.36; p = 0.003). Plasma omentin-1 concentrations did not differ significantly between men and women; however men with the metabolic syndrome had 20% lower plasma omentin-1 levels than women with the metabolic syndrome (p = 0.06).

Conclusion

These data demonstrate that circulating omentin-1 levels are associated with HDL cholesterol, primarily in men and in the presence of the metabolic syndrome. In addition, sex appears to influence the relationship between plasma omentin-1 concentrations and components of the metabolic syndrome. Additional studies are needed to explore sexual dimorphism in circulating omentin-1 levels, and the role of omentin-1 in the metabolic syndrome.
Maternal Diabetes Leads to Unphysiological High Lipid Accumulation in Rabbit Preimplantation Embryos
Authors: Schindler Maria , Pendzialek Mareike , Navarrete Santos Alexander , Plösch Torsten , Seyring Stefanie , Gürke Jacqueline , Haucke Elisa , Knelangen Julia Miriam , Fischer Bernd , Santos Anne Navarrete
Published: January 2014

According to the “developmental origin of health and disease” hypothesis, the metabolic set points of glucose and lipid metabolism are determined prenatally. In the case of a diabetic pregnancy, the embryo is exposed to higher glucose and lipid concentrations as early as during preimplantation development. We used the rabbit to study the effect of maternal diabetes type 1 on lipid accumulation and expression of lipogenic markers in preimplantation blastocysts. Accompanied by elevated triglyceride and glucose levels in the maternal blood, embryos from diabetic rabbits showed a massive intracellular lipid accumulation and increased expression of fatty acid transporter 4, fatty acid–binding protein 4, perilipin/adipophilin, and maturation of sterol-regulated element binding protein. However, expression of fatty acid synthase, a key enzyme for de novo synthesis of fatty acids, was not altered in vivo. During a short time in vitro culture of rabbit blastocysts, the accumulation of lipid droplets and expression of lipogenic markers were directly correlated with increasing glucose concentration, indicating that hyperglycemia leads to increased lipogenesis in the preimplantation embryo. Our study shows the decisive effect of glucose as the determining factor for fatty acid metabolism and intracellular lipid accumulation in preimplantation embryos.
Proper Application of Antibodies for Immunohistochemical Detection: Antibody Crimes and How to Prevent Them
Authors: Ivell Richard , Teerds Katja , Hoffman Gloria E.
Published: January 2014

For several decades antibodies raised against specific proteins, peptides, or peptide epitopes have proven to be versatile and very powerful tools to demonstrate molecular identity in cells and tissues. New techniques of immunohistochemistry and immunofluorescence have improved both the optical resolution of such protein identification as well as its sensitivity, particularly through the use of amplification methodology. However, this improved sensitivity has also increased the risks of false-positive and false-negative staining and thereby raised the necessity for proper and adequate controls. In this review, the authors draw on many years of experience to illuminate many of the more common errors and problematic issues in immunohistochemistry, and how these may be avoided. A key factor in all of this is that techniques need to be properly documented and especially antibodies and procedures must be adequately described. Antibodies are a valuable and shared resource within the scientific community; it is essential therefore that mistakes involving antibodies and their controls are not perpetuated through inadequate reporting in the literature.
The endoplasmic reticulum exerts control over organelle streaming during cell expansion
Authors: Stefano Giovanni , Renna Luciana , Brandizzi Federica
Published: January 2014

Cytoplasmic streaming is critical for cell homeostasis and expansion but the precise driving forces are largely unknown. In plants partial loss of cytoplasmic streaming due to chemical and genetic ablation of myosins supports the existence of yet-unknown motors for organelle movement. Here we tested a role of the endoplasmic reticulum (ER) as propelling force for cytoplasmic streaming during cell expansion. Through quantitative live-cell analyses in wild-type cells and mutants with compromised ER structure and streaming, we demonstrate that cytoplasmic streaming undergoes profound changes during cell expansion and that it depends on motor forces co-exerted by the ER and the cytoskeleton.
The yeast Tsa1 peroxiredoxin protects against protein aggregate-induced oxidative stress
Authors: Weids Alan J. , Grant Chris M.
Published: January 2014

Peroxiredoxins are ubiquitous, thiol-specific proteins that have multiple functions in stress protection, including oxidative stress. Tsa1 is the major yeast peroxiredoxin and we show that it functions as a specific antioxidant to protect against oxidative stress caused by nascent protein misfolding and aggregation. Yeast mutants lacking TSA1 are sensitive to misfolding caused by exposure to the proline analogue azetidine-2-carboxylic acid (AZC). AZC promotes protein aggregation and its toxicity to a tsa1 mutant is caused by reactive oxygen species (ROS). Generation of [rhoo] cells lacking mitochondrial DNA rescues the tsa1 mutant AZC sensitivity indicating that mitochondria are the source of ROS. Inhibition of nascent protein synthesis with cycloheximide prevents AZC-induced protein aggregation and abrogates ROS generation confirming that aggregate formation causes ROS production. Protein aggregation is accompanied by mitochondrial fragmentation and we show that Tsa1 localizes to the sites of protein aggregation. Protein aggregates are formed adjacent to mitochondria and our data indicate that active mitochondria generate ROS. These data indicate a new role for peroxiredoxins in protecting against ROS, generated as a result of protein misfolding and aggregate formation.
Eco-mechanics of lamellar autotomy in larval damselflies
Authors: Gleason Jennifer E. , Fudge Douglas S. , Robinson Beren W.
Published: January 2014

In larval damselflies, the self-amputation (autotomy) of the caudal lamellae permits escape from predatory larval dragonflies. Lamellar joint size declines among populations with increasing risk of dragonfly predation, but the breaking force required for autotomy and the biomechanical factors that influence breaking force are unknown. If autotomy enhances survival in larval damselflies, then predation by larval dragonflies should select for joints that require less force to break. We test this adaptive hypothesis by evaluating whether breaking force is negatively related to local predation risk from larval dragonflies. We also test a cuticle structure hypothesis, which predicts that breaking force is positively related to joint size and to joint cuticle thickness because of a structural support relationship between joint and lamella. The peak force necessary for lamellar autotomy was assessed on individual larval Enallagma damselflies collected from populations that varied in risk of predation. Easier lamellar autotomy occurred in larvae from sites with higher predation risk because damselflies from fishless ponds (where predatory larval dragonflies are likely more abundant) had lower breaking forces than those from ponds with fish (where larval dragonfly predation is likely reduced). Furthermore, breaking force was a positive function of joint size and also of total cuticle cross-sectional area after controlling for joint size. This suggests that autotomy may evolve in larval damselflies under selection from small grasping predators such as larval dragonflies by favouring smaller joint size or reduced cuticle area of lamellar joints.