bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening for congenital cytomegalovirus infection using newborn urine samples collected on filter paper: feasibility and outcomes from a multicentre study
Authors: Koyano Shin , Inoue Naoki , Oka Akira , Moriuchi Hiroyuki , Asano Kimisato , Ito Yushi , Yamada Hideto , Yoshikawa Tetsushi , Suzutani Tatsuo ,   for the Japanese Congenital Cytomegalovirus Study Group
Published: July 2011

Background

As congenital cytomegalovirus (CMV) infection causes significant clinical consequences not only at birth but also later as neurological sequelae, it is critical to establish a strategy for screening congenitally infected newborns. Previous studies have identified an insufficient sensitivity in screening methods based on the use of dried blood spots (DBSs).

Objectives

To evaluate the feasibility of the authors' recently developed method for large-scale screening for congenital CMV infection and to identify risk factors for congenital infection.

Methods

More than 21 000 newborns were enrolled at 25 sites in six geographically separate areas of Japan. Urine was collected onto filter cards placed in the diapers, which were then analysed by quantitative PCR using the filter disc directly as a template. Clinical and physical findings of the newborns were extracted from their medical records. CMV strains from the cases and their siblings were genetically compared. Viral loads in DBSs obtained from some of the cases were compared with those in the urine filters.

Results

Congenital CMV infection was identified in 0.31% (95% CI 0.24% to 0.39%) of the newborns, and 30% of the cases (20/66) had typical clinical manifestations and/or showed abnormalities in brain images at birth. Although the positive predictive value of our screening was 94%, the lack of any comparison with a gold standard assay prevented calculation of the negative predictive value. Almost two-thirds of the cases had siblings, a significantly higher frequency than for uninfected newborns. Most of the cases (21/25) excreted CMV strains identical to those of their siblings. CMV DNA was undetectable in three out of 12 retrievable DBS specimens.

Conclusions

Implementation of an effective large-scale screening programme for congenital CMV infection is feasible. Siblings are the major risk factor for congenital CMV infection, which emphasises the need for education of mothers-to-be as well as vaccine development.
The European lactase persistence genotype determines the lactase persistence state and correlates with gastrointestinal symptoms in the Hispanic and Amerindian Chilean population: a case–control and population-based study
Authors: Morales Eugenia , Azocar Lorena , Maul Ximena , Perez Claudio , Chianale José , Miquel Juan Francisco
Published: July 2011

Background

The lactase persistent (LP) or lactase non-persistent (LNP) state in European adults is genetically determined by a single nucleotide polymorphism (SNP) located 13.9 kb upstream of the lactase (LCT) gene, known as LCT C>T−13910(rs4988235). The LNP condition leads to an inability to digest the milk sugar lactose leading to gastrointestinal symptoms and can affect nutrient and calcium intake in certain populations.

Objectives

The authors studied a group of 51 Chilean patients to assess whether this SNP influences the LP/LNP state in this population, and determined the prevalence of LCT C>T−13910genotypes in a representative sample of 216 Hispanics and 43 Amerindians with correlation to digestive symptoms.

Design

Case–control study done in Chilean patients with clinical suspicion of LNP that were assessed using clinical survey, hydrogen breath test (HBT) and SNP genotyping. The population sample of Hispanics and Amerindians was assessed by clinical survey and SNP genotyping.

Results

Of the 51 patients with clinical suspicion of LNP, 29 were HBT-positive. The CC genotype (LNP) was present in 89.7% of the patients with positive HBT and in only 4.7% of those with negative HBT. The prevalence of the CC genotype was 56.9% in the Hispanic population and 88.3% in Amerindians, and was associated with a higher self-reported clinical intolerance to ingestion of dairy products.

Conclusion

The LP/LNP state is determined by the LCT C>T−13910variant in Chileans. This variant predicts digestive symptoms associated with the ingestion of lactose and is a good tool for the diagnosis of primary adult hypolactasia. The LCT T−13910allele is rare in the Amerindian population and is suggestive of European ancestry in this contemporary population.
Life expectancy and disparity: an international comparison of life table data
Authors: Vaupel James W , Zhang Zhen , van Raalte Alyson A
Published: July 2011

Objectives

To determine the contribution of progress in averting premature deaths to the increase in life expectancy and the decline in lifespan variation.

Design

International comparison of national life table data from the Human Mortality Database.

Setting

40 developed countries and regions, 1840–2009.

Population

Men and women of all ages.

Main outcome measure

We use two summary measures of mortality: life expectancy and life disparity. Life disparity is a measure of how much lifespans differ among individuals. We define a death as premature if postponing it to a later age would decrease life disparity.

Results

In 89 of the 170 years from 1840 to 2009, the country with the highest male life expectancy also had the lowest male life disparity. This was true in 86 years for female life expectancy and disparity. In all years, the top several life expectancy leaders were also the top life disparity leaders. Although only 38% of deaths were premature, fully 84% of the increase in life expectancy resulted from averting premature deaths. The reduction in life disparity resulted from reductions in early-life disparity, that is, disparity caused by premature deaths; late-life disparity levels remained roughly constant.

Conclusions

The countries that have been the most successful in averting premature deaths have consistently been the life expectancy leaders. Greater longevity and greater equality of individuals' lifespans are not incompatible goals. Countries can achieve both by reducing premature deaths.
Early closure of temporary ileostomy—the EASY trial: protocol for a randomised controlled trial
Authors: Danielsen Anne Kjaergaard , Correa-Marinez Adiela , Angenete Eva , Skullmann Stefan , Haglind Eva , Rosenberg Jacob ,   SSORG (Scandinavian Outcomes Research Group)
Published: July 2011

Objective

The objective is to evaluate efficiency based on data on morbidity and mortality, health-related quality of life and healthcare-related costs after early reversal of temporary ileostomy after rectal resection for cancer compared with the standard procedure (late reversal).

Background

Reversal of a temporary ileostomy is generally associated with a low morbidity and mortality. However, ostomy reversal may cause complications requiring reoperation with subsequent major complications, in ranges from 0% to 7–9% and minor complications varying from 4–5% to 30%. Based on studies exploring and describing the time of closure in previous studies which are mostly of low quality, a recent review concluded that closing a temporary stoma within 2 weeks did not seem to be associated with an increase in morbidity and mortality.

Design and methods

Early closure of temporary ileostomy (EASY), a randomised controlled trial, is a prospective randomised controlled multicentre study which is performed within the framework of the Scandinavian Surgical Outcomes Research Group (http://www.ssorg.net/) and plans to include 200 patients from Danish and Swedish hospitals. The primary end-point of the study is the frequency of complications 0–12 months after surgery (the stoma creation operation). The secondary end-points of the study are (1) comparison of the total costs of the two groups at 6 and 12 months after surgery (stoma creation); (2) comparison of health-related quality of life in the two groups evaluated with the 36-item short-form and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CR29/CR30 at 3, 6 and 12 months after surgery (stoma creation); and (3) comparison of disease-specific quality of life in the two groups at 3, 6 and 12 months after surgery (stoma creation).

Discussion

The aim of the EASY trial is to evaluate the efficiency of early reversal of temporary ileostomy after surgery for rectal cancer versus late reversal. The EASY trial is expected to have a huge impact on patient safety as well as an improvement in patient-reported outcome.

Clinical trials identifier

NCT01287637.
Facet arthrography of a cervical synovial cyst
Authors: Tofuku Katsuhiro , Koga Hiroaki , Komiya Setsuro
Published: July 2011

A rare case is presented of a synovial cyst located at the level of C3–C4 that caused cervical myelopathy and that was preoperatively diagnosed by facet arthrography. A woman in her late seventies experienced muscle weakness and numbness in her right upper extremity and gait disturbance. MRI revealed an extradural lesion located dorsolaterally on the right side of the spinal cord at the level of C3–C4. CT facet arthrography revealed continuity of the extradural lesion with the right C3–C4 facet joint and infiltration of contrast medium into the lesion. Postoperatively, histological examination of the cyst showed fibrous tissue with calcium deposits and the presence of synovial lining. Preoperatively, cervical synovial cysts are often difficult to distinguish from other extradural lesions. In this case, facet arthrography allowed the preoperative determination of communication between the extradural lesion and the facet joint, leading to the diagnosis of a synovial cyst.
Do we know what foundation year doctors think about patient safety incident reporting? Development of a web based tool to assess attitude and knowledge
Authors: Robson Jean , de Wet Carl , McKay John , Bowie Paul
Published: July 2011

Background

Making healthcare safer is an international priority. Patient safety modules are now taught in medical schools, and methods to assess related student knowledge and attitudes have been developed. However, little is known about the attitudes and knowledge which foundation doctors are developing to patient safety and incident reporting in the healthcare workplace, since a specific assessment tool appears to be lacking.

Aims

To develop, content validate and pilot test an online questionnaire survey to elicit foundation doctors' knowledge and experience of patient safety and incident reporting, and assess related attitudes and behaviours.

Methods

Questionnaire content validity was facilitated through: a steering group; literature review; feedback from foundation year doctors and consultant staff; a modified Delphi group; and completion of a content validity index by experts. In 2010 a cross-sectional online survey of 110 foundation year 1 and 2 doctors was then undertaken in three Scottish NHS board areas, utilising the developed 25 item questionnaire.

Results

The questionnaire was validated, and piloted among 69 foundation year doctors who responded to the questionnaire. The pilot has provided valuable insights into trainee attitudes and experience. For example, 32 (48%) believed that most safety incidents were due to things that they could not do anything about; and 31 (43%) admitted to being involved in medication errors which were not formally reported.

Conclusions

The pilot study was successful in taking the first steps to developing a validated survey questionnaire for a key staff group, foundation year doctors, in a priority area. However, the findings raise concerns about trainee experience of and attitudes to reporting, and the frequency with which incidents go unreported.
Impact of tobacco advertisements on tobacco use among urban adolescents in India: results from a longitudinal study
Authors: Arora Monika , Gupta Vinay K , Nazar Gaurang P , Stigler Melissa H , Perry Cheryl L , Reddy K Srinath
Published: July 2011

Objectives

To examine the longitudinal relationship between exposure and receptivity to tobacco advertisements and progression towards tobacco use among adolescents in India.

Design and setting

A 2-year longitudinal group-randomised trial, Mobilizing Youth for Tobacco Related Initiatives (MYTRI), was undertaken from 2004 to 2006 in 32 schools in Delhi and Chennai. Among the control schools (n=16), mixed-effects regression models were used to assess the objectives.

Subjects

Students who were non-susceptible, never users of tobacco (n=2782) at baseline (2004) in the control schools of Project MYTRI, who progressed academically and were followed up at endline (2006).

Main outcome measures

Progression towards tobacco use (on tobacco uptake continuum).

Results

Bivariate results suggest that exposure to tobacco advertisements at baseline was associated in a dose-dependent manner with progression at endline. Students exposed at more than four places were 1.5 times (95% CI 1.12 to 1.94; p<0.05) more likely to progress towards tobacco use at endline versus those not exposed. Among boys, those exposed at more than four places were 1.7 times more likely to progress (95% CI 1.14 to 2.62; p<0.05). These significant results disappeared in multivariate analysis, when other psychosocial risk factors for tobacco use were controlled. In both bivariate and multivariate analyses, the risk of progression at endline was more than two times higher (95% CI 1.28 to 4.32; p<0.05) among boys who were highly receptive versus non-receptive boys. The same relationship did not hold among girls.

Conclusion

High receptivity to tobacco advertising predicts future progression to tobacco use among boys in India. Suggestive evidence exists of a causal relationship between tobacco marketing and adolescent tobacco use.
Sex hormone control of left ventricular structure/function: mechanistic insights using echocardiography, expression, and DNA methylation analyses in adult mice
Authors: Sebag Igal A. , Gillis Marc-Antoine , Calderone Angelino , Kasneci Amanda , Meilleur Melissa , Haddad Rami , Noiles William , Patel Bhavini , Chalifour Lorraine E.
Published: July 2011

Calcium flux into and out of the sarco(endo)plasmic reticulum is vitally important to cardiac function because the cycle of calcium entry and exit controls contraction and relaxation. Putative estrogen and androgen consensus binding sites near to a CpG island are present in the cardiac calsequestrin 2 (CSQ2) promoter. Cardiomyocytes express sex hormone receptors and respond to sex hormones. We hypothesized that sex hormones control CSQ2 expression in cardiomyocytes and so affect cardiac structure/function. Echocardiographic analysis of male and female C57bl6n mice identified thinner walled and lighter hearts in females and significant concentric remodeling after long-term gonadectomy. CSQ2 and sodium-calcium exchanger-1 (NCX1) expression was significantly increased in female compared with male hearts and decreased postovariectomy. NCX1, but not CSQ2, expression was increased postcastration. CSQ2 expression was reduced when H9c2 cells were cultured in hormone-deficient media; increased when estrogen receptor-α (ERα), estrogen receptor-β (ERβ), or androgen agonists were added; and increased in hearts from ERβ-deficient mice. CSQ2 expression was reduced in mice fed a diet low in the methyl donor folic acid and in cells treated with 5-azadeoxycytidine suggesting an involvement of DNA methylation. DNA methylation in CpG in the CSQ2 CpG island was significantly different in males and females and was additionally changed postgonadectomy. Expression of DNA methyltransferases 1, 3a, and 3b was unchanged. These studies strongly link sex hormone-directed changes in CSQ2 expression to DNA methylation with changed expression correlated with altered left ventricular structure and function.
Apelin-13 protects the heart against ischemia-reperfusion injury through inhibition of ER-dependent apoptotic pathways in a time-dependent fashion
Authors: Tao Jianping , Zhu Wei , Li Yapeng , Xin Ping , Li Jing , Liu Mingya , Li Jingbo , Redington Andrew N. , Wei Meng
Published: July 2011

Endoplasmic reticulum (ER) stress is activated during and contributes to ischemia-reperfusion (I/R) injury. Attenuation of ER stress-induced apoptosis protects the heart against I/R injury. Using apelin, a ligand used to activate the apelin APJ receptor, which is known to be cardioprotective, this study was designed to investigate 1) the time course of changes in I/R injury after ER stress; 2) whether apelin infusion protects the heart against I/R injury via modulation of ER stress-dependent apoptosis signaling pathways; and 3) how phosphatidylinositol 3-kinase (PI3K)/Akt, endothelial nitric oxide synthase (eNOS), AMP-activated protein kinase (AMPK), and ERK activation are involved in the protection offered by apelin treatment. The results showed that, using an in vivo rat I/R model induced by 30 min of ischemia followed by reperfusion, infarct size (IS) increased from 2 h of reperfusion (34.85 ± 2.14%) to 12 h of reperfusion (48.98 ± 3.35, P < 0.05), which was associated with an abrupt increase in ER stress-dependent apoptosis activation, as evidenced by increased CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, and JNK activation (CHOP: 2.49-fold increase, caspase-12: 2.09-fold increase, and JNK: 3.38-fold increase, P < 0.05, respectively). Administration of apelin at 1 μg/kg not only completely abolished the activation of ER stress-induced apoptosis signaling pathways at 2 h of reperfusion but also significantly attenuated time-related changes at 24 h of reperfusion. Using pharmacological inhibition, we also demonstrated that PI3K/Akt, AMPK, and ERK activation were involved in the protection against I/R injury via inhibition of ER stress-dependent apoptosis activation. In contrast, although eNOS activation played a role in decreasing IS at 2 h of reperfusion, it failed to modify either IS or ER stress-induced apoptosis signaling pathways at 24 h after reperfusion.
Acute and chronic angiotensin-(1–7) restores vasodilation and reduces oxidative stress in mesenteric arteries of salt-fed rats
Authors: Raffai Gábor , Durand Matthew J. , Lombard Julian H.
Published: July 2011

This study determined the effect of ANG-(1–7) on salt-induced suppression of endothelium-dependent vasodilatation in the mesenteric arteries of male Sprague-Dawley rats. Chronic intravenous infusion of ANG-(1–7), oral administration of the nonpeptide mas receptor agonist AVE-0991, and acute preincubation of the arteries with ANG-(1–7) and AVE-0991 all restored vasodilator responses to both ACh and histamine that were absent in the arteries of rats fed a high-salt (4% NaCl) diet. The protective effects of ANG-(1–7) and AVE-0991 were inhibited by acute or chronic administration of the mas receptor antagonist A-779, the ANG II type 2 (AT2) receptor blocker PD-123319, or N-nitro-l-arginine methyl ester, but not the ANG II type 1 receptor antagonist losartan. Preincubation with the antioxidant tempol or the nitric oxide (NO) donor diethylenetriamine NONOate and acute and chronic administration of the AT2 receptor agonist CGP-42112 mimicked the protective effect of ANG-(1–7) to restore vascular relaxation. Acute preincubation with ANG-(1–7) and chronic infusion of ANG-(1–7) ameliorated the elevated superoxide levels in rats fed a high-salt diet, but the expression of Cu/Zn SOD and Mn SOD enzyme proteins in the vessel wall was unaffected by ANG-(1–7) infusion. These results indicate that both acute and chronic systemic administration of ANG-(1–7) or AVE-0991 restore endothelium-dependent vascular relaxation in salt-fed Sprague-Dawley rats by reducing vascular oxidant stress and enhancing NO availability via mas and AT2 receptors. These findings suggest a therapeutic potential for mas/AT2 receptor activation in preventing the vascular oxidant stress and endothelial dysfunction associated with elevated dietary salt intake.
LEOPARD-type SHP2 mutant Gln510Glu attenuates cardiomyocyte differentiation and promotes cardiac hypertrophy via dysregulation of Akt/GSK-3β/β-catenin signaling
Authors: Ishida Hidekazu , Kogaki Shigetoyo , Narita Jun , Ichimori Hiroaki , Nawa Nobutoshi , Okada Yoko , Takahashi Kunihiko , Ozono Keiichi
Published: July 2011

LEOPARD syndrome (LS) is an autosomal dominant inherited multisystemic disorder. Most cases involve mutations in the PTPN11 gene, which encodes the protein tyrosine phosphatase Src homology 2-containing protein phosphatase 2 (SHP2). LS frequently causes severe hypertrophic cardiomyopathy (HCM), even from the fetal period. However, the molecular pathogenesis has not been clearly elucidated. Here, we analyzed the roles of the LS-type SHP2 mutant Gln510Glu (Q510E), which showed the most severe type of HCM in LS, in cardiomyocyte differentiation, and in morphological changes. We generated mutant P19CL6 cell lines, the most convenient cardiomyocyte differentiation model, which continuously expressed SHP2-Q510E, SHP2-D61N (Noonan-type mutant), wild-type SHP2, and green fluorescent protein (native SHP2 expression only). SHP2-Q510E mutant P19CL6 cells showed significant attenuation of myofibrillogenesis, with increased proliferative activity. Mature cardiomyocytes from the SHP2-Q510E mutant were significantly larger than those of controls and the other mutants. However, expression of cardiac-specific transcriptional factors (Gata4, Tbx5, and Nkx2.5) did not differ significantly between the LS-type SHP2-Q510E mutants and the other mutants and controls. Our results indicate that SHP2-Q510E mutants can differentiate into cardiac progenitors but are inhibited from undergoing terminal differentiation into mature cardiomyocytes. In contrast, Akt and glycogen synthase kinase (GSK)-3β phosphorylation were upregulated, and nuclear β-catenin at the late stage of differentiation was highly accumulated in SHP2-Q510E mutant P19CL6 cells. Supplementation with the phosphoinositide 3-kinase/Akt inhibitor LY-294002 during the late stage of differentiation was found to partially restore myofibrillogenesis while suppressing the increase in size of individual mature cardiomyocytes derived from the SHP2-Q510E mutants. Our findings suggest that dysregulation of the Akt/GSK-3β/β-catenin pathway can contribute to the pathogenesis of HCM in LS patients, not only through hypertrophic changes in individual cardiac cells but also via the expansion of cardiac progenitors.
EP3receptors mediate PGE2-induced hypothalamic paraventricular nucleus excitation and sympathetic activation
Authors: Zhang Zhi-Hua , Yu Yang , Wei Shun-Guang , Nakamura Yoshiko , Nakamura Kazuhiro , Felder Robert B.
Published: July 2011

Prostaglandin E2(PGE2), an important mediator of the inflammatory response, acts centrally to elicit sympathetic excitation. PGE2acts on at least four E-class prostanoid (EP) receptors known as EP1, EP2, EP3, and EP4. Since PGE2production within the brain is ubiquitous, the different functions of PGE2depend on the expression of these prostanoid receptors in specific brain areas. The type(s) and location(s) of the EP receptors that mediate sympathetic responses to central PGE2remain unknown. We examined this question using PGE2, the relatively selective EP receptor agonists misoprostol and sulprostone, and the available selective antagonists for EP1, EP3, and EP4. In urethane-anesthetized rats, intracerebroventricular (ICV) administration of PGE2, sulprostone or misoprostol increased renal sympathetic nerve activity, blood pressure, and heart rate. These responses were significantly reduced by ICV pretreatment with the EP3receptor antagonist; the EP1and EP4receptor antagonists had little or no effect. ICV PGE2or misoprostol increased the discharge of neurons in the hypothalamic paraventricular nucleus (PVN). ICV misoprostol increased the c-Fos immunoreactivity of PVN neurons, an effect that was substantially reduced by the EP3receptor antagonist. Real-time PCR detected EP3receptor mRNA in PVN, and immunohistochemical studies revealed sparsely distributed EP3receptors localized in GABAergic terminals and on a few PVN neurons. Direct bilateral PVN microinjections of PGE2or sulprostone elicited sympathoexcitatory responses that were significantly reduced by the EP3receptor antagonist. These data suggest that EP3receptors mediate the central excitatory effects of PGE2on PVN neurons and sympathetic discharge.
Improved pulse transit time estimation by system identification analysis of proximal and distal arterial waveforms
Authors: Xu Da , Ryan Kathy L. , Rickards Caroline A. , Zhang Guanqun , Convertino Victor A. , Mukkamala Ramakrishna
Published: July 2011

We investigated the system identification approach for potentially improved estimation of pulse transit time (PTT), a popular arterial stiffness marker. In this approach, proximal and distal arterial waveforms are measured and respectively regarded as the input and output of a system. Next, the system impulse response is identified from all samples of the measured input and output. Finally, the time delay of the impulse response is detected as the PTT estimate. Unlike conventional foot-to-foot detection techniques, this approach is designed to provide an artifact robust estimate of the true PTT in the absence of wave reflection. The approach is also applicable to arbitrary types of arterial waveforms. We specifically applied a parametric system identification technique to noninvasive impedance cardiography (ICG) and peripheral arterial blood pressure waveforms from 15 humans subjected to lower-body negative pressure. We assessed the technique through the correlation coefficient ( r) between its 1/PTT estimates and measured diastolic pressure (DP) per subject and the root mean squared error (RMSE) of the DP predicted from these estimates and measured DP. The technique achieved average r and RMSE values of 0.81 ± 0.16 and 4.3 ± 1.3 mmHg. For comparison, the corresponding values were 0.59 ± 0.37 ( P < 0.05) and 5.9 ± 2.5 ( P < 0.01) mmHg for the conventional technique applied to the same waveforms and 0.28 ± 0.40 ( P < 0.001) and 7.2 ± 1.8 ( P < 0.001) mmHg for the conventional technique with the ECG waveform substituted for the ICG waveform. These results demonstrate, perhaps for the first time, that the system identification approach can indeed improve PTT estimation.
Vasorelaxant and antiaggregatory actions of the nitroxyl donor isopropylamine NONOate are maintained in hypercholesterolemia
Authors: Bullen Michelle L. , Miller Alyson A. , Dharmarajah Janahan , Drummond Grant R. , Sobey Christopher G. , Kemp-Harper Barbara K.
Published: July 2011

Nitroxyl (HNO) displays pharmacological and therapeutic actions distinct from those of its redox sibling nitric oxide (NO∙). It remains unclear, however, whether the vasoprotective actions of HNO are preserved in disease. The ability of the HNO donor isopropylamine NONOate (IPA/NO) to induce vasorelaxation, its susceptibility to tolerance development, and antiaggregatory actions were compared with those of a clinically used NO∙ donor, glyceryl trinitrate (GTN), in hypercholesterolemic mice. The vasorelaxant and antiaggregatory properties of IPA/NO and GTN were examined in isolated carotid arteries and washed platelets, respectively, from male C57BL/6J mice [wild-type (WT)] maintained on either a normal diet (WT-ND) or high fat diet (WT-HFD; 7 wk) as well as apolipoprotein E-deficient mice maintained on a HFD (ApoE−/−-HFD; 7 wk). In WT-ND mice, IPA/NO (0.1–30 μmol/l) induced concentration-dependent vasorelaxation and inhibition of collagen (30 μg/ml)-stimulated platelet aggregation, which was predominantly soluble guanylyl cyclase/cGMP dependent. Compared with WT-HFD mice, ApoE−/−-HFD mice displayed an increase in total plasma cholesterol levels ( P < 0.001), vascular ( P < 0.05) and platelet ( P < 0.05) superoxide (O2·−) production, and reduced endogenous NO∙ bioavailability ( P < 0.001). Vasorelaxant responses to both IPA/NO and GTN were preserved in hypercholesterolemia, whereas vascular tolerance developed to GTN ( P < 0.001) but not to IPA/NO. The ability of IPA/NO (3 μmol/l) to inhibit platelet aggregation was preserved in hypercholesterolemia, whereas the actions of GTN (100 μmol/l) were abolished. In conclusion, the vasoprotective effects of IPA/NO were maintained in hypercholesterolemia and, thus, HNO donors may represent future novel treatments for vascular diseases.
ATP hydrolysis pathways and their contributions to pial arteriolar dilation in rats
Authors: Vetri Francesco , Xu Haoliang , Mao Lizhen , Paisansathan Chanannait , Pelligrino Dale A.
Published: July 2011

ATP is thought to be released to the extracellular compartment by neurons and astrocytes during neural activation. We examined whether ATP exerts its effect of promoting pial arteriolar dilation (PAD) directly or upon conversion (via ecto-nucleotidase action) to AMP and adenosine. Blockade of extracellular direct ATP to AMP conversion, with ARL-67156, significantly reduced sciatic nerve stimulation-evoked PADs by 68%. We then monitored PADs during suffusions of ATP, ADP, AMP, and adenosine in the presence and absence of the following: 1) the ecto-5′-nucleotidase inhibitor α,β-methylene adenosine 5′-diphosphate (AOPCP), 2) the A2 receptor blocker ZM 241385, 3) the ADP P2Y1 receptor antagonist MRS 2179, and 4) ARL-67156. Vasodilations induced by 1 and 10 μM, but not 100 μM, ATP were markedly attenuated by ZM 241385, AOPCP, and ARL-67156. Substantial loss of reactivity to 100 μM ATP required coapplications of ZM 241385 and MRS 2179. Dilations induced by ADP were blocked by MRS 2179 but were not affected by either ZM 241385 or AOPCP. AMP-elicited dilation was partially inhibited by AOPCP and completely abolished by ZM 241385. Collectively, these and previous results indicate that extracellular ATP-derived adenosine and AMP, via A2 receptors, play key roles in neural activation-evoked PAD. However, at high extracellular ATP levels, some conversion to ADP may occur and contribute to PAD through P2Y1 activation.
Caveolin-1 in cytokine-induced enhancement of intracellular Ca2+ in human airway smooth muscle
Authors: Sathish Venkatachalem , Abcejo Amard J. , VanOosten Sarah Kay , Thompson Michael A. , Prakash Y. S. , Pabelick Christina M.
Published: July 2011

Diseases such as asthma are characterized by airway hyperresponsiveness. Enhanced airway smooth muscle (ASM) intracellular Ca2+ ([Ca2+]i) response to agonist stimulation leading to increased airway constriction has been suggested to contribute to airway hyperresponsiveness. Caveolae are flask-shaped plasma membrane invaginations that express the scaffolding protein caveolin and contain multiple proteins important in [Ca2+]i signaling (e.g., agonist receptors, ion channels). We recently demonstrated that caveolae and caveolin-1 are important in [Ca2+]i regulation in human ASM. Proinflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-13 modulate [Ca2+]i in ASM. We hypothesized that cytokine upregulation of caveolar signaling in ASM contributes to enhanced agonist-induced [Ca2+]i in inflammation. Enzymatically dissociated human ASM cells were exposed to medium (control), 20 ng/ml TNF-α, or 50 ng/ml IL-13 for 24 h. Caveolae-enriched membrane fractions displayed substantial increase in caveolin-1 and -2 expressions by TNF-α and IL-13. Transfection with caveolin-1-mRed DNA substantially accelerated and increased plasma membrane caveolin-1 expression by TNF-α and to a lesser extent by IL-13. Caveolin-1 enhancement was inhibited by nuclear factor-κB and mitogen-activated protein kinase inhibitors. In fura 2-loaded ASM cells, [Ca2+]i responses to 1 μM ACh, 10 μM histamine, or 10 nM bradykinin were all exaggerated by TNF-α as well as IL-13 exposure. However, disruption of caveolae using caveolin-1 suppression via small-interfering RNA resulted in significant blunting of agonist-induced [Ca2+]i responses of vehicle and TNF-α-exposed cells. These functional data were correlated to the presence of TNFR1 receptor (but not the IL-4/IL-13 receptor) within caveolae. Overall, these results indicate that caveolin-1 plays an important role in airway inflammation by modulating the effect of specific cytokines on [Ca2+]i.
Role for PKCβ in enhanced endothelin-1-induced pulmonary vasoconstrictor reactivity following intermittent hypoxia
Authors: Snow Jessica B. , Gonzalez Bosc Laura V. , Kanagy Nancy L. , Walker Benjimen R. , Resta Thomas C.
Published: July 2011

Intermittent hypoxia (IH) resulting from sleep apnea causes both systemic and pulmonary hypertension. Enhanced endothelin-1 (ET-1)-induced vasoconstrictor reactivity is thought to play a central role in the systemic hypertensive response to IH. However, whether IH similarly increases pulmonary vasoreactivity and the signaling mechanisms involved are unknown. The objective of the present study was to test the hypothesis that IH augments ET-1-induced pulmonary vasoconstrictor reactivity through a PKCβ-dependent signaling pathway. Responses to ET-1 were assessed in endothelium-disrupted, pressurized pulmonary arteries (∼150 μm inner diameter) from eucapnic-IH [(E-IH) 3 min cycles, 5% O2-5% CO2/air flush, 7 h/day; 4 wk] and sham (air-cycled) rats. Arteries were loaded with fura-2 AM to monitor vascular smooth muscle (VSM) intracellular Ca2+concentration ([Ca2+]i). E-IH increased vasoconstrictor reactivity without altering Ca2+responses, suggestive of myofilament Ca2+sensitization. Consistent with our hypothesis, inhibitors of both PKCα/β (myr-PKC) and PKCβ (LY-333-531) selectively decreased vasoconstriction to ET-1 in arteries from E-IH rats and normalized responses between groups, whereas Rho kinase (fasudil) and PKCδ (rottlerin) inhibition were without effect. Although E-IH did not alter arterial PKCα/β mRNA or protein expression, E-IH increased basal PKCβI/II membrane localization and caused ET-1-induced translocation of these isoforms away from the membrane fraction. We conclude that E-IH augments pulmonary vasoconstrictor reactivity to ET-1 through a novel PKCβ-dependent mechanism that is independent of altered PKC expression. These findings provide new insights into signaling mechanisms that contribute to vasoconstriction in the hypertensive pulmonary circulation.
Arginine Vasopressin-Independent Mechanism of Impaired Water Excretion in a Patient with Sarcoidosis Complicated by Central Diabetes Insipidus and Glucocorticoid Deficiency
Authors: Yoshioka Katsunobu , Tanaka Nagaaki , Yamagami Keiko , Inoue Takeshi , Hosoi Masayuki
Published: July 2011

A 28-year-old man was admitted to our hospital because of reduced livido and increased fatigability. Four months before admission, he noticed polyuria, which was gradually relieved by admission. Magnetic resonance imaging revealed enhancing lesion centrally in the pituitary stalk. Biopsy from the skin revealed noncaseating granuloma composed of epithelioid cells, and a diagnosis of sarcoidosis was made. Although plasma arginine vasopressin (AVP) was undetectable after administration of hypertonic saline, urinary output was within normal range (1.5 to 2.2 L/day). The urine osmolality became above plasma levels during the hypertonic saline test. Hormonal provocative tests revealed partial glucocorticoid deficiency. Soon after the glucocorticoid therapy was begun, moderate polyuria (from 3.5–4.0 liters daily) occurred. At this time, plasma AVP was undetectable, and urine osmolality was consistently below plasma levels during the hypertonic saline test. In conclusion, we showed in human study that masked diabetes insipidus could be mediated by AVP-independent mechanisms.
A 41-Year-Old Man with Two Types of Metachronous Peptic Ulcer Complication due to Zollinger-Ellison Syndrome—Regression of Pancreatic Primary after Chemoembolization of Hepatic Metastases: A Case Report
Authors: Sarkeshikian Seyed Saeid , Ghadir Mohammad Reza
Published: July 2011

Introduction. Gastrinoma should be suspected when the peptic ulcer(s) is postbulbar, multiple, refractory, or recurrent, or ulcer is associated with nephrolithiasis, hypocalcaemia, or erosive esophagitis. The majority of gastrinomas are malignant.Case Presentation. The patient is a 41-year-old Iranian man who has been in good health until 36 months ago when duodenal perforation and two bouts of upper GI bleeding (GIB), each two months apart occurred. He also mentioned mild watery diarrhoea and decreased appetite. Serum gastrin level was elevated. Abdominal CT scan revealed pancreatic mass and three enhancing hepatic masses. CT-guided pancreatic biopsy revealed monotonous cells. Chemoembolization of hepatic metastases was done. New ct images 6 months later showed nearly total regressed hepatic and pancreatic lesions.Conclusion. Beside previously defined situations that take gastrinoma into account as the etiology of PUD, accumulation of PUD complications is highly suggestive of Zollinger-Ellisone syndrome (ZES). Regression of pancreatic primary after chemoembolization of hepatic metastases is unexplainable at the present time.
Bisphenyl-Polymer/Carbon-Fiber-Reinforced Composite Compared to Titanium Alloy Bone Implant
Authors: Petersen Richard C.
Published: July 2011

Aerospace/aeronautical thermoset bisphenyl-polymer/carbon-fiber-reinforced composites are considered as new advanced materials to replace metal bone implants. In addition to well-recognized nonpolar chemistry with related bisphenol-polymer estrogenic factors, carbon-fiber-reinforced composites can offer densities and electrical conductivity/resistivity properties close to bone with strengths much higher than metals on a per-weight basis.In vivobone-marrow tests with Sprague-Dawley rats revealed far-reaching significant osseoconductivity increases from bisphenyl-polymer/carbon-fiber composites when compared to state-of-the-art titanium-6-4 alloy controls. Midtibial percent bone area measured from the implant surface increased when comparing the titanium alloy to the polymer composite from 10.5% to 41.6% at 0.8 mm,P<10−4, and 19.3% to 77.7% at 0.1 mm,P<10−8. Carbon-fiber fragments planned to occur in the test designs, instead of producing an inflammation, stimulated bone formation and increased bone integration to the implant. In addition, low-thermal polymer processing allows incorporation of minerals and pharmaceuticals for future major tissue-engineering potential.
Abdominal Compartment Syndrome Caused by Massive Pyonephrosis in an Infant with Primary Obstructive Megaureter
Authors: Kavaguti Silvia K. , Mackevicius Barbara R. , de Andrade Murilo F. , Tucci Jr Silvio , Carlotti Ana P. C. P.
Published: July 2011

The authors report a case of abdominal compartment syndrome caused by massive pyonephrosis in an infant with primary obstructive megaureter successfully treated with emergency surgical decompression.
HPV16E6-Dependent c-Fos Expression Contributes to AP-1 Complex Formation in SiHa Cells
Authors: Liang Feixin , Kina Shinichiro , Takemoto Hiroyuki , Matayoshi Akira , Phonaphonh Thongsavanh , Sunagawa Nao , Arakaki Keiichi , Arasaki Akira , Kuang Hai , Sunakawa Hajime
Published: July 2011

To date, the major role of HPV16E6 in cancer has been considered to be its ability to inhibit the p53 tumor-suppressor protein, thereby thwarting p53-mediated cytotoxic responses to cellular stress signals. Here, we show that HPV16E6-dependent c-fos oncogenic protein expression contributes to AP-1 complex formation under oxidative stress in SiHa cells (HPV16-positive squamous cell carcinoma of the cervix). In addition, we examined the role of HPV16E6 in TGF-α-induced c-fos expression and found that the c-fos protein expression induced by TGF-αis HPV16E6 dependent. Thus, our results provide the first evidence that HPV16E6 contributes to AP-1 complex formation after both ligand-dependent and independent EGFR activation, suggesting a new therapeutic approach to the treatment of HPV-associated tumors.
Global Synchronization of Complex Networks with Discrete Time Delays on Time Scales
Authors: Cheng Quanxin , Cao Jinde
Published: July 2011

This paper studies the global synchronization problem for a class of complex networks with discrete time delays. By using the theory of calculus on time scales, the properties of Kronecker product, and Lyapunov method, some sufficient conditions are obtained to ensure the global synchronization of the complex networks with delays on time scales. These sufficient conditions are formulated in terms of linear matrix inequalities (LMIs). The main
contribution of the result is that the global synchronization problems with both discrete time and continuous time are unified
under the same framework.
Cytokines: The Future of Intranasal Vaccine Adjuvants
Authors: Thompson Afton L. , Staats Herman F.
Published: July 2011

Due to its potential as an effective, needle-free route of immunization for use with subunit vaccines, nasal immunization continues to be evaluated as a route of immunization in both research and clinical studies. However, as with other vaccination routes, subunit vaccines often require the addition of adjuvants to induce potent immune responses. Unfortunately, many commonly used experimental vaccine adjuvants, such as cholera toxin andE. coliheat-labile toxin, are too toxic for use in humans. Because new adjuvants are needed, cytokines have been evaluated for their ability to provide effective adjuvant activity when delivered by the nasal route in both animal models and in limited human studies. It is the purpose of this paper to discuss the potential of cytokines as nasal vaccine adjuvants.
Global Existence and Blowup Analysis to Single‐Species Bacillus System with Free Boundary
Authors: Ling Zhi , Lin Zhigui
Published: July 2011

This paper is concerned with a reaction‐diffusion equation which describes the dynamics of single bacillus population with free boundary. The local existence and uniqueness of the solution are first obtained by using the contraction mapping theorem. Then we exhibit an energy condition, involving the initial data,
under which the solution blows up in finite time. Finally we examine the long time behavior of global solutions;
the global fast solution and slow solution are given. Our results show that blowup occurs if the death rate is small and
the initial value is large enough. If the initial value is small the solution is global and fast, which decays at an exponential rate while there is a global slow solution provided that the death rate is small and the initial value is suitably large.
A Combined Methodology for Landslide Risk Mitigation in Basilicata Region by Using LIDAR Technique and Rockfall Simulation
Authors: Colangelo G. , Guariglia A.
Published: July 2011

Rockfalls represent a significant geohazards along the SS18 road of Basilicata Region, Italy. The management of these rockfall hazards and the mitigation of the risk require innovative approaches and technologies. This paper discusses a hazard assessment strategy and risk mitigation for rockfalls in a section of SS118, along the coast of Maratea, using LIDAR technique and spatial modelling. Historical rockfall records were used to calibrate the physical characteristics of the rockfall processes. The results of the simulations were used to define the intervention actions and engineering strategy for the mitigation of the phenomena. Within two months, 260 linear meters of high-energy rockfall barriers for impact energies up to 3000 kJ were installed. After that, according to road authority, the SS18 road was opened in a safe condition. The results represent a valid cognitive support to choose the most appropriate technical solution for topography strengthening and an example of good practice for the cooperation between innovative technologies and field emergency management.
Moving the Frontier of Quantum Control into the Soft X-Ray Spectrum
Authors: Aquila A. , Drescher M. , Laarmann T. , Barthelmeß M. , Chapman H. N. , Bajt S.
Published: July 2011

The femtosecond nature of X-ray free electron laser (FEL) pulses opens up exciting research possibilities in time-resolved studies including femtosecond photoemission and diffraction. The recent developments of seeding X-ray FELs extend their capabilities by creating stable, temporally coherent, and repeatable pulses. This in turn opens the possibility of spectral engineering soft X-ray pulses to use as a probe for the control of quantum dynamics. We propose a method for extending coherent control pulse-shaping techniques to the soft X-ray spectral range by using a reflective geometry 4f pulse shaper. This method is based on recent developments in asymmetrically cut multilayer optic technology and piezoelectric substrates.
Optimal Analysis Method for Dynamic Contrast-Enhanced Diffuse Optical Tomography
Authors: Ghijsen Michael , Lin Yuting , Hsing Mitchell , Nalcioglu Orhan , Gulsen Gultekin
Published: July 2011

Diffuse Optical Tomography (DOT) is an optical imaging modality that has various clinical applications. However, the spatial resolution and quantitative accuracy of DOT is poor due to strong photon scatting in biological tissue. Structurala prioriinformation from another high spatial resolution imaging modality such as Magnetic Resonance Imaging (MRI) has been demonstrated to significantly improve DOT accuracy. In addition, a contrast agent can be used to obtain differential absorption images of the lesion by using dynamic contrast enhanced DOT (DCE-DOT). This produces a relative absorption map that consists of subtracting a reconstructed baseline image from reconstructed images in which optical contrast is included. In this study, we investigated and compared different reconstruction methods and analysis approaches for regular endogenous DOT and DCE-DOT with and without MR anatomicala prioriinformation for arbitrarily-shaped objects. Our phantom and animal studies have shown that superior image quality and higher accuracy can be achieved using DCE-DOT together with MR structurala prioriinformation. Hence, implementation of a combined MRI-DOT system to image ICG enhancement can potentially be a promising tool for breast cancer imaging.
Viscoelastic Properties of Polypropylene Reinforced with Mica in and Transition Zones
Authors: Farzaneh S. , Tcharkhtchi A.
Published: July 2011

The viscoelastic properties of mica-reinforced polypropylene (PP) was studied in temperature range between −30°C and 120°C. WLF equation permits determining the free volume fraction in and transitions regions. It was shown that the value of this parameter is lower for transition, indicating that the free volume and thermal expansion of region is more than that of region. At a 40% loading level, it was shown that the storage and loss modulus of mica-filled PP increases dramatically (in comparison with the pure polypropylene). The relative modulus does not change significantly at glassy state but it increases for the temperature higher than . It was also shown that mica does not affect the glass transition temperature but results in an increase in transition.
Intrafamilial Genotyping ofHelicobacter pylorifrom Faecal DNA
Authors: McMillan M. , MacKay W. G. , Williams C. L. , Shepherd A. J. , Malcolm C. , Weaver L. T.
Published: July 2011

Helicobacter pyloriinfection, often acquired in early childhood, is a global cause of undernutrition, gastritis, peptic ulcer disease and gastric carcinoma. This study tested the feasibility of usingH. pylorished in the faeces as a source of DNA for non-invasive epidemiological studies.H. pyloriDNA was chemically recovered and isolated using a specific biotinylated oligonucleotide probe with magnetic capture from 28H. pyloripositive faecal samples obtained from children attending hospital for the investigation of suspectedH. pyloriinfection, together with close family members. Random amplification of polymorphic DNA (RAPD) was subsequently used to discriminate each isolate. 93% of stool samples selected were typeable. Parent, child and sibling samples were compared and similarities determined. Phylogenetic analysis showed thatH. pyloriDNA obtained from the faeces can be used to genotype individual strains, offering a means of studying intrafamilial transfer of this microorganism.