bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of mammalian target of rapamycin reduces epileptogenesis and blood–brain barrier leakage but not microglia activation
Authors: van Vliet Erwin A. , Forte Grazia , Holtman Linda , den Burger Jeroen C. G. , Sinjewel Arno , de Vries Helga E. , Aronica Eleonora , Gorter Jan A.
Published: May 2012

Purpose:  Previous studies have shown that inhibition of the mammalian target of rapamycin (mTOR) pathway with rapamycin prevents epileptogenesis after pharmacologically induced status epilepticus (SE) in rat models of temporal lobe epilepsy. Because rapamycin is also known for its immunosuppressant properties we hypothesized that one of the mechanisms by which it exerts this effect could be via suppression of brain inflammation, a process that has been suggested to play a major role in the development and progression of epilepsy.

Methods:  Rats were treated with rapamycin or vehicle once daily for 7 days (6 mg/kg/day, i.p.) starting 4 h after the induction of SE, which was evoked by electrical stimulation of the angular bundle. Hereafter rapamycin was administered every other day until rats were sacrificed, 6 weeks after SE. Video‐electroencephalography was used to monitor the occurrence of seizures. Neuronal death, synaptic reorganization, and microglia and astrocyte activation were assessed by immunohistologic staining. Fluorescein was administered to quantify blood–brain barrier leakage.

Key Findings:  Rapamycin treatment did not alter SE severity and duration compared to vehicle treatment rats. Rapamycin‐treated rats developed hardly (n = 9) or no (n = 3) seizures during the 6‐week treatment, whereas vehicle‐treated rats showed a progressive increase of seizures starting 1 week after SE (mean 8 ± 2 seizures per day during the sixth week). Cell loss and sprouting that normally occur after SE were prominent but on average significantly less in rapamycin‐treated rats versus vehicle‐treated rats. Nevertheless, various inflammation markers (CD11b/c and CD68) were dramatically upregulated and not significantly different between post‐SE groups. Of interest, blood–brain barrier leakage was barely detected in the rapamycin‐treated group, whereas it was prominent in the vehicle‐treated group.

Significance:  mTOR inhibition led to strong reduction of seizure development despite the presence of microglia activation, suggesting that effects of rapamycin on seizure development are not due to a control of inflammation. Whether the effects on blood–brain barrier leakage in rapamycin‐treated rats are a consequence of seizure suppressing properties of the drug, or contribute to a real antiepileptogenic effect still needs to be determined.
Targeted next generation sequencing as a diagnostic tool in epileptic disorders
Authors: Lemke Johannes R. , Riesch Erik , Scheurenbrand Tim , Schubach Max , Wilhelm Christian , Steiner Isabelle , Hansen Jörg , Courage Carolina , Gallati Sabina , Bürki Sarah , Strozzi Susi , Simonetti Barbara Goeggel , Grunt Sebastian , Steinlin Maja , Alber Michael , Wolff Markus , Klopstock Thomas , Prott Eva C. , Lorenz Rüdiger , Spaich Christiane , Rona Sabine , Lakshminarasimhan Maya , Kröll Judith , Dorn Thomas , Krämer Günter , Synofzik Matthis , Becker Felicitas , Weber Yvonne G. , Lerche Holger , Böhm Detlef , Biskup Saskia
Published: May 2012

Purpose:  Epilepsies have a highly heterogeneous background with a strong genetic contribution. The variety of unspecific and overlapping syndromic and nonsyndromic phenotypes often hampers a clear clinical diagnosis and prevents straightforward genetic testing. Knowing the genetic basis of a patient’s epilepsy can be valuable not only for diagnosis but also for guiding treatment and estimating recurrence risks.

Methods:  To overcome these diagnostic restrictions, we composed a panel of genes for Next Generation Sequencing containing the most relevant epilepsy genes and covering the most relevant epilepsy phenotypes known so far. With this method, 265 genes were analyzed per patient in a single step. We evaluated this panel on a pilot cohort of 33 index patients with concise epilepsy phenotypes or with a severe but unspecific seizure disorder covering both sporadic and familial cases.

Key Findings:  We identified presumed disease‐causing mutations in 16 of 33 patients comprising sequence alterations in frequently as well as in less commonly affected genes. The detected aberrations encompassed known and unknown point mutations (SCN1A p.R222X, p. E289V, p.379R, p.R393H; SCN2A p.V208E; STXBP1 p.R122X; KCNJ10 p.L68P, p.I129V; KCTD7 p.L108M; KCNQ3 p.P574S; ARHGEF9 p.R290H; SMS p.F58L; TPP1 p.Q278R, p.Q422H; MFSD8 p.T294K), a putative splice site mutation (SCN1A c.693A> p.T/P231P) and small deletions (SCN1A p.F1330Lfs3X [1 bp]; MFSD8 p.A138Dfs10X [7 bp]). All mutations have been confirmed by conventional Sanger sequencing and, where possible, validated by parental testing and segregation analysis. In three patients with either Dravet syndrome or myoclonic epilepsy, we detected SCN1A mutations (p.R222X, p.P231P, p.R393H), even though other laboratories had previously excluded aberrations of this gene by Sanger sequencing or high‐resolution melting analysis.

Significance:  We have developed a fast and cost‐efficient diagnostic screening method to analyze the genetic basis of epilepsies. We were able to detect mutations in patients with clear and with unspecific epilepsy phenotypes, to uncover the genetic basis of many so far unresolved cases with epilepsy including mutation detection in cases in which previous conventional methods yielded falsely negative results. Our approach thus proved to be a powerful diagnostic tool that may contribute to collecting information on both common and unknown epileptic disorders and in delineating associated phenotypes of less frequently mutated genes.
Using Systems Theory to Study Legal Pluralism: What Could Be Gained?
Authors: Nobles Richard , Schiff David
Published: May 2012

This article examines the ability of modern systems theory to provide a foundation for understanding the problematic notion of legal pluralism, and to the ability of scholars to apply that understanding to engage in the study of pluralistic legal orders. In particular, it develops the observations of systems theory of the relationship between state law and violence by adopting one of its linked ideas, that of structural coupling. It also considers the role played by translation when law is identified by reference to the application of the legal code: legal/illegal. The whole analysis is underpinned by systems theory's account of the differences between studying premodern and modern societies.
The Case for Intervening in Bankers’ Pay
Authors: THANASSOULIS JOHN
Published: May 2012

This paper studies the default risk of banks generated by investment and remuneration pressures. Competing banks prefer to pay their banking staff in bonuses and not in fixed wages as risk sharing on the remuneration bill is valuable. Competition for bankers generates a negative externality, driving up market levels of banker remuneration and hence rival banks’ default risk. Optimal financial regulation involves an appropriately structured limit on the proportion of the balance sheet used for bonuses. However, stringent bonus caps are value destroying, default risk enhancing, and suboptimal for regulators who control only a small number of banks.
Which CEO Characteristics and Abilities Matter?
Authors: KAPLAN STEVEN N. , KLEBANOV MARK M. , SORENSEN MORTEN
Published: May 2012

We exploit a unique data set to study individual characteristics of CEO candidates for companies involved in buyout and venture capital transactions and relate these characteristics to subsequent corporate performance. CEO candidates vary along two primary dimensions: one that captures general ability and another that contrasts communication and interpersonal skills with execution skills. We find that subsequent performance is positively related to general ability and execution skills. The findings expand our view of CEO characteristics and types relative to previous studies.
Differences between Men and Women in Opportunity Evaluation as a Function of Gender Stereotypes and Stereotype Activation
Authors: Gupta Vishal K. , Turban Daniel B. , Pareek Ashish
Published: May 2012

Opportunity evaluation represents a core aspect of the entrepreneurial process. Prior research suggests that evaluation of new opportunities is influenced by biases rooted in subjective beliefs, values, and assumptions. In the present study, we used stereotype activation theory to propose that respondent gender (men–women), content of stereotype (masculine–feminine), and the manner in which stereotype information is presented (subtle–blatant) interact to influence evaluations of a new business opportunity. We found that both masculine and feminine stereotype activation influenced men and women's evaluation of a business opportunity differently depending upon whether the stereotype was blatantly or subtly activated. Our results indicate that gender stereotype activation can both boost and impede men and women's subsequent actions on entrepreneurial tasks such as opportunity evaluation, depending on the content of the stereotype and the manner in which it is presented. Implications and directions for future research are discussed.
Entrepreneurship at the Periphery: Exploring Framework Conditions in Core and Peripheral Locations
Authors: Felzensztein Christian , Gimmon Eli , Aqueveque Claudio
Published: May 2012

This paper reports the findings of the first academic study in Latin America, and one of the few in any emerging economy, to explore entrepreneurial perceptions and activity in peripheral geographic locations. A survey of experts included 139 respondents from three peripheral regions and two core regions in Chile. A key finding is that those located at the periphery perceived critical entrepreneurial resources and access to markets less favorably than their counterparts at the core, but surprisingly, they perceived greater business opportunity in their area. A further survey of 2,200 respondents concerning actual entrepreneurial activities among the total adult population revealed no differences between peripheral and core regions. This study revives the debate about specific regional policies for fostering the growth of local business, and the entrepreneurial framework conditions required at the regional level in emerging economies.
Barista's Battle Scars
Authors: Jensen Susan M. , Seshadri Srivatsa , Carstenson Larry G.
Published: May 2012

This case tells the story of an entrepreneur couple who launched an upscale retail coffee business in a mid–sized college town in the Midwest. Barista's enjoyed immediate and overwhelming market acceptance and was even named “Entrepreneur of the Year,” yet had tremendous difficulty in obtaining expansion capital. The choice of legal advisor also proved to have enormous impact on the future viability of the business. Written from the perspective of the entrepreneurs, the case provides unique insight regarding the importance of cultivating the effective professional relationships needed for business success.
Failure to Deliver Therapy by a Riata Lead with Internal Wire Externalization and Normal Electrical Parameters During Routine Interrogation
Authors: SHAH PARTHIV , SINGH GURJIT , CHANDRA SHALABH , SCHUGER CLAUDIO D.
Published: May 2012

Failure to Deliver Therapy by a Riata Lead. We present a case of failure to deliver a shock by a St. Jude Medical defibrillator involving a Riata lead that was discovered incidentally while the device was attempting to deliver inappropriate therapy. Routine interrogation, including high voltage (HV) impedance, failed to reveal any abnormality. Failure to deliver therapy was confirmed during DFT testing, which revealed extremely low HV impedance only while attempting to deliver therapy. Fluoroscopy indicated moderate externalization of internal wires. This case highlights an under‐recognized issue with St. Jude Medical systems, namely the possibility that therapy may not be delivered despite the presence of normal electrical parameters during routine surveillance. (J Cardiovasc Electrophysiol, Vol. 24, pp. 94‐96, January 2013)
Association between obesity and periodontal disease in young adults: a population‐based birth cohort
Authors: Dickie de Castilhos Eduardo , Horta Bernardo Lessa , Gigante Denise Petrucci , Demarco Flávio Fernando , Peres Karen Glazer , Peres Marco Aurélio
Published: May 2012

Aim

To evaluate the association between obesity and periodontal disease and the mediating effect of oral hygiene, systemic inflammation and carbohydrate intake.

Material and methods

Subjects born in 1982 in Pelotas, Brazil (n = 5,914), have been followed for several times. Oral health was assessed in a representative sample of 720 individuals at 24 years. Obesity, waist circumference and number of episodes with obesity between 15 and 23 years of age were the main exposures. Mediating effect of oral hygiene, C‐reactive protein level and carbohydrate consumption was also assessed.

Results

Obese individuals were more likely to have ≥2 teeth with gingival bleeding. However, after adjusting for confounders, the association was not statistically significant [OR (obese × 2 or more teeth) 1.72 (95% CI: 0.95, 3.11)] and adjustment for potential mediators decreased the OR (OR = 1.38). The risk of presenting calculus in obese subjects was 10% higher [PR 1.10 (95% CI: 1.02, 1.18)]. The number of episodes of obesity between 15 and 23 years was associated with dental calculus. Periodontal pockets were not associated with obesity.

Conclusion

Systemic inflammation and oral hygiene may be mediating the association between obesity and gingivitis. Obesity was not associated with periodontal pockets in young adults in this cohort.
Expression of neuroserpin, a selective inhibitor of tissue‐type plasminogen activator in the human skin
Authors: Chéret Jérémy , Lebonvallet Nicolas , Misery Laurent , Le Gall‐Ianotto Christelle
Published: May 2012

Serine protease of the fibrinolytic system and their specific inhibitors, the serine protease inhibitors (SERPINs) are implicated in a number of physiological and pathological processes in skin. The main SERPIN is the plasminogen activator inhibitor‐1 (or PAI‐1), which is involved in wound healing and in pathogenesis of several diseases including skin fibrosis. Another member of SERPIN superfamily, the neuroserpin (NSP), is widely expressed in the central nervous system. It has been recently detected in different organs such as pancreas, heart, kidney and testis. In this study, we provided evidences for the presence of NSP in the skin, in 10 human skin samples (HSS) at mRNA level (RT‐PCR) and protein level (Western blot and immunohistochemistry). The immunohistochemistry analysis showed that this expression was located in dermis around blood vessels.
Melatonin prevents hemorrhagic shock‐induced liver injury in rats through an Akt‐dependent HO‐1 pathway
Authors: Hsu Jun‐Te , Kuo Chia‐Jung , Chen Tsung‐Hsing , Wang Frank , Lin Chun‐Jun , Yeh Ta‐Sen , Hwang Tsann‐Long , Jan Yi‐Yin
Published: May 2012

Abstract:  Although melatonin treatment following trauma‐hemorrhage or ischemic reperfusion prevents organs from dysfunction and injury, the precise mechanism remains unknown. This study tested whether melatonin prevents liver injury following trauma‐hemorrhage involved the protein kinase B (Akt)‐dependent heme oxygenase (HO)‐1 pathway. After a 5‐cm midline laparotomy, male rats underwent hemorrhagic shock (mean blood pressure approximately 40 mmHg for 90 min) followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle, melatonin (2 mg/kg), or melatonin plus phosphoinositide 3‐kinase (PI3K) inhibitor wortmannin (1 mg/kg). At 2 hr after trauma‐hemorrhage, the liver tissue myeloperoxidase activity, malondialdehyde, adenosine triphosphate, serum alanine aminotransferase, and aspartate aminotransferase levels were significantly increased compared with sham‐operated control. Trauma‐hemorrhage resulted in a significant decrease in the Akt activation in comparison with the shams (relative density, 0.526 ± 0.031 versus 1.012 ± 0.066). Administration of melatonin following trauma‐hemorrhage normalized liver Akt phosphorylation (0.993 ± 0.061), further increased mammalian target of rapamycin (mTOR) activation (5.263 ± 0.338 versus 2.556 ± 0.225) and HO‐1 expression (5.285 ± 0.325 versus 2.546 ± 0.262), and reduced cleaved caspase‐3 levels (2.155 ± 0.297 versus 5.166 ± 0.309). Coadministration of wortmannin abolished the melatonin‐mediated attenuation of the shock‐induced liver injury markers. Our results collectively suggest that melatonin prevents hemorrhagic shock‐induced liver injury in rats through an Akt‐dependent HO‐1 pathway.
Chewing number is related to incremental increases in body weight from 20 years of age in Japanese middle‐aged adults
Authors: Fukuda Hideki , Saito Toshiyuki , Mizuta Masato , Moromugi Shunji , Ishimatsu Takakazu , Nishikado Shinobu , Takagi Hiroshi , Konomi Yoshihiko
Published: May 2012

doi: 10.1111/j.1741‐2358.2012.00666.x

Chewing number is related to incremental increases in body weight from 20 years of age in Japanese middle‐aged adults

Background:  Eating habits are associated with both current obesity and incremental increases in body weight from young adulthood, but no study has focused on chewing number during meals among community residents.

Objective:  This study focused on the relationship between chewing number and incremental increases in body weight from 20 years of age.

Methods:  A total of 93 persons aged 35–61 years participated. The subjects were asked to set the device and record their chewing number during each meal on a particular day. They were also asked whether their body weight had increased by 10 kg or more since they were 20 years old.

Results:  The body weight of 28 subjects (30%) had increased more than 10 kg since the age of 20 years. Total chewing number showed a relationship with such body weight increases. The odds ratio of weight increments of more than 10 kg for the lowest tertile group was 4.6 [95% confidence interval (CI), 1.3–16.2] relative to the highest tertile group (Model 1). The odds ratio of weight increments for the lowest tertile group increased to 6.3 (95% CI, 1.6–25.4) in Model 2 and to 9.1 (95% CI, 1.7–49.8) in Model 3.

Conclusion:  Although this study was limited because it did not consider all risk factors, categorical chewing number was related independently to body weight increments of more than 10 kg from 20 years of age.
Functional tooth units and nutritional status of older people in care homes in Indonesia
Authors: Adiatman Melissa , Ueno Masayuki , Ohnuki Mari , Hakuta Chiyoko , Shinada Kayoko , Kawaguchi Yoko
Published: May 2012

Gerodontology 2012; doi: 10.1111/j.1741‐2358.2012.00673.x

Functional tooth units and nutritional status of older people in care homes in Indonesia

Objectives:  To investigate the relationship between functional tooth units (FTUs) and nutritional status.

Methods:  One hundred females (mean age: 72.4 ± 8.2 years) at four private care homes in Jakarta, Indonesia were interviewed and clinically examined. The oral examination included the assessment of teeth, prosthetic status, and number of FTUs. The total number of FTUs was further divided by tooth composition: natural tooth against natural tooth (NN‐FTUs), natural tooth against denture (ND‐FTUs), and denture against denture (DD‐FTUs). Nutritional status was evaluated using the body mass index (BMI) and the Mini Nutritional Assessment (MNA).

Results:  The mean numbers of teeth present, NN‐FTUs, ND‐FTUs, DD‐FTUs, and total FTUs were 13.1 ± 10.4, 1.7 ± 3.0, 1.2 ± 3.3, 0.4 ± 1.2 and 3.3 ± 4.4, respectively. The mean BMI and MNA scores were 24.8 ± 5.0 and 22.6 ± 2.8, respectively. Subjects with a normal BMI had a significantly higher total number of FTUs (3.6 ± 4.6) compared with underweight subjects (0.1 ± 0.3). Subjects with a normal MNA had a significantly higher number of NN‐FTU (2.6 ± 3.7) compared to those who were at risk or in a state of under‐nutrition (1.2 ± 2.4).

Conclusion:  This study revealed significant relationships between the number of FTUs and nutritional status. Keeping the posterior occlusion should be emphasized in order to maintain good nutritional status in older subjects.
Human HAD phosphatases: structure, mechanism, and roles in health and disease
Authors: Seifried Annegrit , Schultz Jörg , Gohla Antje
Published: May 2012

Phosphatases of the haloacid dehalogenase (HAD) superfamily of hydrolases are an ancient and very large class of enzymes that have evolved to dephosphorylate a wide range of low‐ and high molecular weight substrates with often exquisite specificities. HAD phosphatases constitute approximately one‐fifth of all human phosphatase catalytic subunits. While the overall sequence similarity between HAD phosphatases is generally very low, family members can be identified based on the presence of a characteristic Rossmann‐like fold and the active site sequence DxDx(V/T). HAD phosphatases employ an aspartate residue as a nucleophile in a magnesium‐dependent phosphoaspartyl transferase reaction. Although there is genetic evidence demonstrating a causal involvement of some HAD phosphatases in diseases such as cancer, cardiovascular, metabolic and neurological disorders, the physiological roles of many of these enzymes are still poorly understood. In this review, we discuss the structure and evolution of human HAD phosphatases, and summarize their known functions in health and disease.
Magnetic Spheres as Foreign Body into the Bladder
Authors: Graziottin Tulio M. , Soares Daniel de Freitas G. , Da Ros Carlos T. , Sogari Paulo R. , Telöken Cláudio , Laste Paulo Roberto
Published: May 2012

Introduction

A great variety of foreign bodies in the lower urinary tract have been described; many of them are self-inflicted by the patient with masturbatory purposes. Depending on the nature of the foreign body the diagnostic and management might be challenging.

Aims

We report a case of an unusual magnetic self-inserted foreign body into the bladder for autoerotism and briefly discuss the diagnostic and therapeutic implications in this challenging situation.

Methods

We describe all the steps we have used to adequately diagnose the problem, describe the foreign body and treatments for the patient. Related articles were found by utilizing the PubMed database and are summarized in this study.

Results

The management approach must be planned according to the nature of the foreign body and should minimize bladder and urethral trauma. However, most of cases can be managed endoscopically.

Conclusion

Removal of magnetic foreign body may be quite challenging, requiring high-level surgical skills and minimally invasive techniques resulting in fast recovery and low complication rate.
Tadalafil 5 mg Daily Treatment for Type 1 Diabetic Premenopausal Women Affected by Sexual Genital Arousal Disorder
Authors: Caruso Salvatore , Cicero Carla , Romano Mattea , Lo Presti Lucia , Ventura Betty , Malandrino Chiara
Published: May 2012

Introduction

Type 1 diabetic women may be affected by sexual dysfunction, mainly due to peripheral vascular disease.

Aim

To determine whether daily tadalafil 5 mg is effective in type 1 premenopausal women affected by sexual genital arousal disorder.

Method

Thirty-three volunteers were enrolled in a 12-week daily tadalafil 5 mg prospective study.

Main Outcome Measures

The efficacy of daily tadalafil 5 mg on sexual genital arousal (primary end point), and desire, orgasm, enjoyment and frequency of sexual activity, and genital pain (secondary end points) were assessed (i) subjectively by the Short Personal Experiences Questionnaire; and (ii) objectively by translabial color Doppler sonography of clitoral blood flow. Moreover, the Short Form-36 questionnaire was used to assess Quality of Life (QoL).

Results

Thirty-two women completed the study. Women reported a QoL improvement at the 12th week follow-up (P < 0.05). Tadalafil improved the experience of sexual genital arousal, and orgasm, sexual enjoyment, satisfaction by frequency of sexual activity, and frequency of sexual thoughts or fantasies (P < 0.05). Finally, dyspareunia decreased with respect to baseline (P < 0.001). After tadalafil administration, the mean peak systolic velocity increased and the mean diastolic velocity decreased from baseline (P < 0.001). Moreover, the mean resistance index and the mean pulsatility index were significantly higher compared with baseline values (P < 0.001).

Conclusions

Daily tadalafil 5 mg treatment seems to improve subjective sexual aspects and could be used to treat genital arousal disorder of premenopausal women with type 1 diabetes. The limits of the study were the small sample and the lack of a placebo control group.
Lung cancer stem cells: Tumor biology and clinical implications
Authors: NURWIDYA Fariz , MURAKAMI Akiko , TAKAHASHI Fumiyuki , TAKAHASHI Kazuhisa
Published: May 2012

The concept of cancer stem cells (CSC) has drawn great attention from researchers in both molecular and clinical fields as has brought a new perspective to the way we manage cancer. CSC have several characteristics that are shared by the properties of normal stem cells, such as differentiation, self‐renewal and homeostatic control. However, CSC have the capacity to both divide and expand the CSC pool and to differentiate into heterogeneous non‐tumorigenic cancer cells. Even more, CSC have an inherent high resistance to chemotherapeutic agents that leads to recurrence and poor long‐term survival, especially in lung cancer patients. CSC‐targeting agents are now undergoing in vitro and in vivo studies, some of which have provided promising results for further clinical studies setting. In this article we review the concept of CSC from the perspective of tumor biology, including the origin of CSC and its biomarkers. As lung cancer is the leading cause of cancer‐related deaths worldwide, we focus on the properties and clinical implications of lung CSC.
Innate phase behavior in the desert locust, Schistocerca gregaria
Authors: Guershon Moshe , Ayali Amir
Published: May 2012

Abstract  Detailed aspects of the transition from the solitarious to the gregarious phase in the framework of locust ecology are undoubtedly most important for understanding locust phase polyphenism. Nevertheless, due to obvious difficulties in studying the solitarious phase in nature, such information is limited and mostly available from research carried out under laboratory conditions. In the current study, we examined the dispersal patterns of newly hatched locust nymphs in a laboratory setup that simulated seminatural conditions. This was carried out with no previous manipulation of the nymphs other than controlling their parental density. We comparatively tested the spatial distribution of newly hatched nymphs on perches located at different ranges within an emergence arena, and the expected Poisson (random) distribution. Hatchlings were found to disperse among the perches in a pattern significantly different from that expected by random. Irrespective of their parents’ phase, the observed distributions of all nymphs were clearly clumped, similar or close to those expected for gregarious locusts. It seems that rather than emerging with a parentally derived and predetermined phase, hatchlings have an independent default or innate behavioral state, which reflects at least tolerance if not attraction to conspecifics. The typical phase behavior may later become dominant under the appropriate environmental conditions. These results imply novel perspectives on locust phase transformation, which contribute to our understanding of the formation of locust crowds under field conditions. These should be considered in any rationale for developing a preventative management strategy of locust populations.
Novel Cruzain Inhibitors for the Treatment of Chagas’ Disease
Authors: Rogers Kathleen E , Keränen Henrik , Durrant Jacob D. , Ratnam Joseline , Doak Allison , Arkin Michelle R. , McCammon J. Andrew
Published: May 2012

The protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas’ disease, affects millions of individuals and continues to be an important global health concern. The poor efficacy and unfavorable side effects of current treatments necessitate novel therapeutics. Cruzain, the major cysteine protease of T. cruzi, is one potential novel target. Recent advances in a class of vinyl sulfone inhibitors are encouraging; however, as most potential therapeutics fail in clinical trials and both disease progression and resistance call for combination therapy with several drugs, the identification of additional classes of inhibitory molecules is essential. Using an exhaustive virtual‐screening and experimental validation approach, we identify several additional small‐molecule cruzain inhibitors. Further optimization of these chemical scaffolds could lead to the development of novel drugs useful in the treatment of Chagas’ disease.
The hypothalamic–pituitary–adrenal axis and sex hormones in chronic stress and obesity: pathophysiological and clinical aspects
Authors: Pasquali Renato
Published: May 2012

Obesity, particularly the abdominal phenotype, has been ascribed to an individual maladaptation to chronic environmental stress exposure mediated by a dysregulation of related neuroendocrine axes. Alterations in the control and action of the hypothalamic–pituitary–adrenal axis play a major role in this context, with the participation of the sympathetic nervous system. The ability to adapt to chronic stress may differ according to sex, with specific pathophysiological events leading to the development of stress‐related chronic diseases. This seems to be influenced by the regulatory effects of sex hormones, particularly androgens. Stress may also disrupt the control of feeding, with some differences according to sex. Finally, the amount of experimental data in both animals and humans may help to shed more light on specific phenotypes of obesity, strictly related to the chronic exposure to stress. This challenge may potentially imply a different pathophysiological perspective and, possibly, a specific treatment.
Influence of Various Cooking Methods on the Concentrations of Volatile N‐Nitrosamines and Biogenic Amines in Dry‐Cured Sausages
Authors: Li Ling , Wang Peng , Xu Xinglian , Zhou Guanghong
Published: May 2012

Abstract:  N‐nitrosamines, biogenic amines, and residual nitrites are harmful substances and are often present in cured meats. The effects of different cooking methods (boiling, pan‐frying, deep‐frying, and microwave) were investigated on their contents in dry‐cured sausage. The various N‐nitrosamines were isolated by a steam distillation method and analyzed by gas chromatography mass spectrometry (GC‐MS). The biogenic amines were determined after extraction with perchloric acid as dansyl derivatives by high‐performance liquid chromatography (HPLC) method. The results showed that initial dry‐cured raw sausage contained 5.31 μg/kg of total N‐nitrosamines. Cooking by deep‐frying or pan‐frying resulted in products having the highest (P < 0.05) contents, compared with boiling or microwave treatments, which were not different from the raw. Although frying increased the content of N‐nitrosodimethylamine (NDMA), N‐nitrosodiethylamine (NDEA), and N‐nitrosopyrrolidine (NPYR), it decreased the contents of histamine and cadaverine. Boiling and microwave treatments decreased the total biogenic amines significantly (P < 0.05). Residual nitrite was significantly reduced by cooking treatments. The results suggest that boiling and microwave treatments were more suitable methods for cured meat.

Practical Application:  N‐nitrosamines and biogenic amines are considered potentially harmful substances to humans and often present in dry‐cured sausage. Different cooking methods may effect the content of these harmful substances. However, little information exists on the different cooking methods on dry‐cured meats.
Microencapsulation of Bifidobacterium bifidum F‐35 in Whey Protein‐Based Microcapsules by Transglutaminase‐Induced Gelation
Authors: Zou Qiang , Liu Xiaoming , Zhao Jianxin , Tian Fengwei , Zhang He‐ping , Zhang Hao , Chen Wei
Published: May 2012

Abstract:  Bifidobacterium bifidum F‐35 was microencapsulated into whey protein microcapsules (WPMs) by a transglutaminase (TGase)‐induced method after optimization of gelation conditions. The performance of these WPMs was compared with that produced by a spray drying method (WPMs‐A). WPMs produced by the TGase‐induced gelation method (WPMs‐B) had larger and denser structures in morphological examinations. Native gel and SDS‐PAGE analyses showed that most of the polymerization observed in WPMs‐B was due to stable covalent crosslinks catalyzed by TGase. The degradation properties of these WPMs were investigated in simulated gastric juice (SGJ) with or without pepsin. In the presence of pepsin, WPMs‐A degraded more quickly than did WPMs‐B. Finally, survival rates of the microencapsulated cells in both WPMs were significantly better than that of free cells and varied with the microencapsulation method. However, WPMs‐B produced by TGase‐induced gelation could provide better protection for microencapsulated cells in low pH conditions and during 1 mo of storage at 4 °C or at ambient temperature.
Update on the Pharmacologic Treatment of Hypertension in Pediatrics
Authors: Blowey Douglas L.
Published: May 2012

J Clin Hypertens (Greenwich). 2012; 14:383–387. ©2012 Wiley Periodicals, Inc.

The past decade of investigation into the pharmacologic treatment of hypertension in children has been rewarding. The studies have shown that blood pressure medications effectively reduce blood pressure in children with hypertension and that these agents are generally well tolerated with few treatment‐related adverse effects. While we have advanced our capacity to make rational therapeutic decisions, future efforts must be directed towards comparing the effectiveness of the different classes of antihypertensive agents and studies evaluating the impact of antihypertensive agents on outcome.
Neurocognitive Alterations in Hypertensive Children and Adolescents
Authors: Lande Marc B. , Kupferman Juan C. , Adams Heather R.
Published: May 2012

J Clin Hypertens (Greenwich). 2012; 14:353–359. ©2012 Wiley Periodicals, Inc.

Hypertensive adults demonstrate performance deficits on neuropsychological testing compared with scores of normotensive controls. This article reviews emerging preliminary evidence that children with hypertension also manifest neurocognitive differences when compared with normotensive controls. Database and single‐center studies suggest that children with hypertension manifest deficits on measures of neurocognition and have an increased prevalence of learning difficulties and that children with hypertension associated with obesity may be at increased risk for depression and anxiety. Studies suggesting blunted cerebrovascular reactivity in children with hypertension are also reviewed.
The Role of Uric Acid in the Pathogenesis of Hypertension in the Young
Authors: Feig Daniel I.
Published: May 2012

J Clin Hypertens (Greenwich). 2012; 14:346–352. ©2012 Wiley Periodicals, Inc.

Uric acid has been suspected to be a risk factor for hypertension since the 1870s. Numerous epidemiological studies demonstrate an association between uric acid and both incident and prevalent hypertension in diverse populations. Studies in elderly patients have had more variable results, raising the possibility that uric acid may be more significant to hypertension in the young. Animal models support a two‐phase mechanism for the development of hyperuricemic hypertension. Initially, uric acid induces vasoconstriction by activation of the renin‐angiotensin system and reduction of circulating nitric oxide, which can be reversed by lowering uric acid. Over time, uric acid uptake into vascular smooth muscle cells causes cellular proliferation and secondary arteriolosclerosis that impairs pressure natriuresis, causing sodium‐sensitive hypertension. Consistent with the animal model data, small clinical trials performed in adolescents with newly diagnosed essential hypertension demonstrate that at least in certain young patients, reduction of serum uric acid can mitigate blood pressure elevation. While more research is clearly necessary, the available data suggest that uric acid is likely causative in some cases of early‐onset hypertension.
Prehypertension in Adolescents: Risk and Progression
Authors: Redwine Karen M. , Daniels Stephen R.
Published: May 2012

J Clin Hypertens (Greenwich). 2012; 14:360–364. ©2012 Wiley Periodicals, Inc.

In 2004, the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents recommended a new designation of prehypertension for children with mildly elevated blood pressure (BP). This description was intended to help identify children most at risk for the development of persistent hypertension for whom targeted prevention programs would be most beneficial and was based largely on expert opinions and epidemiologic normal values. This review summarizes the knowledge that has been gained regarding the epidemiology and risk associated with prehypertension in adolescents since its inception and highlights future challenges in understanding and preventing the development of hypertensive disease in this population.
The dilemma of green business in tropical forests: how to protect what it cannot identify
Authors: Meijaard Erik , Sheil Douglas
Published: May 2012

Much tropical biodiversity resides in forests managed by timber, mining, and plantation companies. These companies can determine the local persistence of many species and have considerable implications for global conservation outcomes. Many companies are willing to invest in improved management as long as this does not undermine their business—indeed accessing green markets often makes commercial sense. Compliance with common standards of good commercial practice requires identification of all species of conservation significance which occur within their areas of management responsibility. But, as we demonstrate, it is impossible for companies to do this comprehensively. Such demands are often counterproductive in that they alienate those who might otherwise be willing to improve. Given the finite resources available for achieving conservation outcomes, we need to trade off data collection against other costs. To encourage adoption and implementation of conservation friendly practices requires incentives, not technical and financial obstacles. We challenge conservation biologists to reconsider the realities of good forest management, and provide pragmatic guidance for business compatible conservation. Until we engage more effectively with commercial interests, opportunities for improved conservation outcomes will be wasted.
Lowering environmental costs of oil‐palm expansion in Colombia
Authors: Garcia‐Ulloa John , Sloan Sean , Pacheco Pablo , Ghazoul Jaboury , Koh Lian Pin
Published: May 2012

Colombia is the fifth largest producer of palm oil in the world. The country's government and oil‐palm farmers association target a sixfold increase of crude palm‐oil production by 2020. We model the impacts of expanding oil‐palm agriculture in Colombia through a spatially explicit scenario analysis. We demonstrate that the impacts of oil‐palm expansion (e.g., deforestation, conversion of natural savannahs) would be minimized by establishing new plantations on pasture lands, given the low environmental value and economic utility, and the high agricultural potential of this land use. Impacts of oil‐palm expansion on beef and dairy production could be compensated by improving productivity of pasture lands elsewhere. However, the profitability of oil‐palm production in these areas might suffer over the long term due to high land purchase costs.
Incidence rate and causes of infection in Thai systemic sclerosis patients
Authors: Foocharoen Chingching , Siriphannon Yada , Mahakkanukrauh Ajanee , Suwannaroj Siraphop , Nanagara Ratanavadee
Published: May 2012

Background

Infection is a common cause of death in systemic sclerosis (SSc) but despite immunosuppressant therapy, there are few reports of opportunistic infection.

Objectives

To estimate the incidence of infection, to determine the etiologic organism, and to assess the risk factors for infection among Thai SSc patients.

Methods

A historical cohort analysis was conducted on patients over 15 years of age, diagnosed with SSc, who attended the Scleroderma Clinic at Srinagarind Hospital, Khon Kaen, Thailand, between January 1, 2005 and December 31, 2006.

Results

The medical records of 117 SSc patients were reviewed. The female‐to‐male ratio was 1.5 : 1.0. Of the total 310 person‐years under observation, 63 events of infection occurred. The incidence rate of infection was 20.3 per 100 person‐years (95% CI 15.6–26.0) and the incidence rate of major infection was 11.0 per 100 person‐years (95% CI 8.4–16.5). The mean age and mean duration of SSc at the time of infection was 50.1 ± 11.1 years (range, 25.2–76.6) and 12.9 ± 10.4 months (range, 0.5–34.6), respectively. Urinary tract infection was the most common infection (23.8%). Opportunistic infection was found in one case (esophageal candidiasis). Esophageal dysmotility was significantly related to major infection (odds ratio [OR] 3.22). There was a clinical association between aspiration pneumonia and esophageal dysmotility (OR 1.23), as well as non‐strongyloidiasis diarrhea and gastrointestinal involvement (OR 2.28). One person died due to severe bacterial aspiration pneumonia.

Conclusions

Infection is not uncommon among SSc patients; however, opportunistic infection is rare, despite immunosuppressant therapy. Esophageal dysmotility increases the risk of major infection, particularly of aspiration pneumonia.
Access to antiepileptic drug therapy in children in Camagüey Province, Cuba†
Authors: Arencibia Zeina Bárzaga , Leyva Alberto López , Peña Yordanka Mejías , Reyes Alba Rosa González , Nápolez Maurilys Acosta , Carbonell Perdomo Demetrio , Manzano Edita Fernández , Choonara Imti
Published: May 2012

Objective

To describe access to antiepileptic drug therapy and estimate the prevalence of epilepsy in children in Camagüey Province, Cuba.

Methods

All the community pharmacies in the province were visited and information collected about the number of children receiving antiepileptic drugs in 2009. Availability and cost of each antiepileptic drug were determined. The prevalence of epilepsy was estimated by determining the number of children receiving antiepileptic drugs.

Results

There were 923 children who received a total of 977 antiepileptic drugs in Camagüey Province. The estimated prevalence of epilepsy was 5.18 per thousand children which is lower than previously reported rates in other low and lower-middle income countries. Most of the children (871, 94%) received a single antiepileptic drug. Carbamazepine and valproate were the two most frequently prescribed antiepileptic drugs. Antiepileptic drugs were available from the local pharmacy on 76% of occasions. If the antiepileptic drug was not available from the local pharmacy, the parent had to travel to another pharmacy to obtain the medicine.

Conclusions

The estimated prevalence of epilepsy in children in Cuba is lower than that estimated in other lower-middle income countries. Access to drug therapy in children with epilepsy can be achieved in lower-middle income countries.
On the equations a2−2b6=cp and a2−2=cp
Authors: Chen Imin
Published: May 2012

We study the equation a2−2b6=cp and its specialization a2−2=cp, where p is a prime, using the modular method. In particular, we use a ℚ-curve defined over ${\mathbb Q}(\sqrt {2},\sqrt {3})$ for which the solution (a,b,c)=(±1,±1,−1) gives rise to a CM-form. This allows us to apply the modular method to resolve the equation a2−2b6=cp for p in certain congruence classes. For the specialization a2−2=cp, we use the multi-Frey technique of Siksek to obtain further refined results.
Cross characterization of ultrathin interlayers in HfO2 high-k stacks by angle resolved x-ray photoelectron spectroscopy, medium energy ion scattering, and grazing incidence extreme ultraviolet reflectometry
Authors: Banyay Matus , Juschkin Larissa , Bersch Eric , Franca Daniel , Liehr Michael , Diebold Alain
Published: May 2012

In order to miniaturize metal oxide semiconductor field effect transistors even further and improve their performance, channel lengths and gate dielectric thicknesses must be decreased. Traditionally deployed SiO2 dielectrics face the difficulty of excessive leakage current and must be replaced by alternative (high-k) materials with larger dielectric permitivitties and smaller equivalent oxide thicknesses. A current focus of the industry is studying thin films of HfO2 because they are a main candidate for the next generation of gate dielectrics. Measuring the depth profiles of the constituents of these layered systems is instructive in that it provides information about the thicknesses of the layers and the degree of intermixing between them. Here we demonstrate the use of a novel characterization technique, grazing incidence extreme ultraviolet reflectometry (GIXUVR), which utilizes short wavelength radiation from non-synchrotron sources to measure the depth profile of such thin-film structures. Depth profiles of samples from the same wafers were also measured using angle resolved x-ray photoelectron spectroscopy, medium energy ion scattering, and synchrotron GIXUVR. These measurements show the compatibility and complementarity of the results. The benefits of GIXUVR are the short measuring time (on the order of milliseconds to seconds), as well as high thickness, density, and material sensitivity due to a very efficient interaction of extreme ultraviolet light with matter.
FUKUSHIMA'S DECOMPOSITION FOR DIFFUSIONS ASSOCIATED WITH SEMI-DIRICHLET FORMS
Authors: MA LI , MA ZHI-MING , SUN WEI
Published: May 2012

Diffusion processes associated with semi-Dirichlet forms are studied in the paper. The main results are Fukushima's decomposition for the diffusions and a transformation formula for the corresponding martingale part of the decomposition. The results are applied to some concrete examples.
Photophysics and photochemistry of octaglucosylated zinc phthalocyanine derivatives
Authors: Iqbal Zafar , Ogunsipe Abimbola , Nyokong Tebello , Lyubimtsev Alexey , Hanack Michael , Ziegler Thomas
Published: May 2012

The ground state electronic absorption spectra, photophysics and photochemistry of amphiphilic octaglucosylated zinc phthalocyanines containing oxygen or sulfur bridges are presented. Triplet quantum yield values for the two dyes (in DMF and DMSO) vary between 0.71 and 0.84, while singlet quantum yield values lie between 0.63 and 0.75. Fluorescence lifetimes were determined experimentally by time correlated single photon counting and semi-empirically by fluorescence quenching techniques; and values from both methods were within the same range. Kinetic data were obtained for the quenching of the triplet state of the phthalocyanines by ground state molecular oxygen; the bimolecular collisional quenching rate constant range between 2.35 × 108 and 1.13 × 109 M-1.s-1. These values suggest that triplet states of the dyes are effectively quenched by ground molecular oxygen.
UNIFORM BENDING EFFECT ON ELECTRONIC PROPERTIES OF BORON NITRIDE NANORIBBONS: A COMPUTATIONAL INVESTIGATION
Authors: LIAO YUNLONG , CHEN ZHONGFANG
Published: May 2012

First-principles computations were performed to investigate the uniform bending effect on the electronic properties of armchair boron nitride nanoribbons (aBNNRs) with experimentally obtained width. For both bare and hydrogen-terminated aBNNRs, the band gaps only slightly depend on the uniform bending. The insensitivity of the band structures of BNNRs to the uniform bending makes them ideal materials when their wide band gap character is desired.