bluuebunny/crossref_metadata_2025 huggingface dataset:
Cord serum adiponectin is positively related to postnatal body mass index gain
Authors: Nakano Yuya , Itabashi Kazuo , Nagahara Keiko , Sakurai Motoichiro , Aizawa Madoka , Dobashi Kazushige , Mizuno Katsumi , Tanaka Daisuke
Published: November 2011

Background:  The roles of adiponectin and leptin in the early stages of life are poorly understood. We previously studied longitudinal changes in these adipocytokines from birth to 12 months of age. The aim of this investigation was to evaluate the correlation between cord serum adipocytokine levels and postnatal growth by 3 years of age.

Methods:  A questionnaire was sent to obtain the general physical measurements of 3‐year‐olds from 56 healthy newborn infants born at a gestational age of 35 weeks or more; 45 valid responses were obtained. The correlations between variables, including cord serum adipocytokine levels at birth and general physical measurements at 3 years, were investigated.

Results:  Body mass index (BMI) Z‐score gain from birth to 3 years was negatively correlated with birthweight SD scores (β=−0.395, P= 0.019) and gestational age (β=−0.557, P= 0.016), and positively correlated with cord serum adiponectin levels (β= 0.253, P= 0.043). BMI Z‐score gain from birth to 6 months was negatively correlated with only birthweight SD score (β=−0.442, P= 0.017). Cord serum leptin levels were not a significant predictor of BMI Z‐scores gain in our subjects. BMI Z‐scores at 6 months, 12 months, and 3 years of age were not related to cord serum adiponectin or leptin levels.

Conclusions:  Birthweight SD score, gestational age, and cord serum adiponectin levels are significant predictors of BMI Z‐score gain from birth to 3 years of age in Japanese infants.
Cost‐effectiveness of standard vs intensive antibiotic regimens for transrectal ultrasonography (TRUS)‐guided prostate biopsy prophylaxis
Authors: Adibi Mehrad , Pearle Margaret S. , Lotan Yair
Published: November 2011

Study Type – Diagnostic (cost effectiveness analysis)

Level of Evidence 3a

What's known on the subject? and What does the study add?

Multiple studies have shown an increase in the hospital admission rates due to infectious complications after transrectal ultrasonography (TRUS)‐guided prostate biopsy (TRUSBx), mostly related to a rise in the prevalence of fluoroquinolone‐resistant organisms. As a result, multiple series have advocated the use of more intensive prophylactic antibiotic regimens to augment the effect of the widely used fluoroquinolone prophylaxis for TRUSBx.

The present study compares the cost‐effectiveness fluoroquinolone prophylaxis to more intensive prophylactic antibiotic regimens, which is an important consideration for any antibiotic regimen used on a wide‐scale for TRUSBx prophylaxis.

OBJECTIVE

To compare the cost‐effectiveness of fluoroquinolones vs intensive antibiotic regimens for transrectal ultrasonography (TRUS)‐guided prostate biopsy (TRUSBx) prophylaxis.

PATIENTS AND METHODS

Risk of hospital admission for infectious complications after TRUSBx was determined from published data.

The average cost of hospital admission due to post‐biopsy infection was determined from patients admitted to our University hospital ≤1 week of TRUSBx.

A decision tree analysis was created to compare cost‐effectiveness of standard vs intensive antibiotic prophylactic regimens based on varying risk of infection, cost, and effectiveness of the intensive antibiotic regimen.

RESULTS

Baseline assumption included cost of TRUSBx ($559), admission rate (1%), average cost of admission ($5900) and cost of standard and intensive antibiotic regimens of $1 and $33, respectively.

Assuming a 50% risk reduction in admission rates with intensive antibiotics, the standard regimen was slightly less costly with average cost of $619 vs $622, but was associated with twice as many infections.

Sensitivity analyses found that a 1.1% risk of admission for quinolone‐resistant infections or a 54% risk reduction attributed to the more intensive antibiotic regimen will result in cost‐equivalence for the two regimens.

Three‐way sensitivity analyses showed that small increases in probability of admission using the standard antibiotics or greater risk reduction using the intensive regimen result in the intensive prophylactic regimen becoming substantially more cost‐effectiveness even at higher costs.

CONCLUSION

As the risk of admission for infectious complications due to TRUSBx increases, use of an intensive prophylactic antibiotic regimen becomes significantly more cost‐effective than current standard antibiotic prophylaxis.
SNAKES FROM STAVES? SCIENCE, SCRIPTURES, AND THE SUPERNATURAL IN MAURICE BUCAILLE
Authors: Bigliardi Stefano
Published: November 2011

Abstract The aim of this paper is to attain a philosophical evaluation of the ideas of the French author Maurice Bucaille. Bucaille formulated an influential discourse regarding the divinity of the Qur’an, which he tried to demonstrate through a comparison of some of its verses with what he defined as scientific data. With his works, which encompass a criticism of the Bible and a defense of creationism, Bucaille furthered the idea that Islam is in harmony with natural sciences, and ensured himself long‐lasting fame in the Muslim world. Such ideas have found numerous followers and the description of the “scientific miracles” of the Qur’an has turned into a popular genre. Several attempts have been made to criticize Bucaille about specific positions he holds. The thesis I develop here is that, even if Bucaille's work cannot be easily dismissed, a severe methodological shortcoming emerges through the analysis of the logic behind his claims regarding miraculous and supernatural events. Current attempts at defending the harmony between Islam and science should therefore credit Bucaille, but at the same time, be aware of the risk of inheriting his methodological flaws. In the first section, I briefly recall the works of Bucaille and his contribution to the debate on the harmony between Islam and science. In the second section, I reconstruct Bucaille's view of science and his analysis of the sacred scriptures. In the third section, I investigate how Bucaille characterizes the concept of supernatural. In the fourth section, I put forth a general evaluation of his reasoning.
INTRODUCTION TO “THE ENERGY TRANSITION: RELIGIOUS AND CULTURAL PERSPECTIVES”
Authors: Rasmussen Larry L. , Laurendeau Normand M. , Solomon Dan
Published: November 2011

Abstract Energy typically is discussed in terms of science, technology, economics, and politics. Little attention has been given to fundamental religious and ethical questions surrounding the upcoming transition to renewable energy. The essays in this thematic section seek to redress that deficiency. This introductory essay raises some key questions and summarizes various presentations on energy and religion, as these were held at the 2010 conference of the Institute on Religion in an Age of Science (IRAS). Some presentations described the energy landscape and provided data and perspectives needed for sound policy. Others raised ethical and religious considerations for energy decisions as the transition from nonrenewable to renewable sources is faced. Some posed the challenges of the energy transition to religion itself. Yet others offered examples of sustainable energy use and/or promising sources for meeting future needs sustainably. At the conclusion of the conference, presenters crafted a common “Statement on Energy and Climate Change” that includes a “Call to Action.” The “Energy Statement” follows as an appendix.
Multicentre prospective evaluation of implant–assisted mandibular bilateral distal extension removable partial dentures: Patient satisfaction
Authors: Wismeijer Daniel , Tawse‐Smith Andrew , Payne Alan G. T.
Published: November 2011

Objective

To compare the levels of patient satisfaction with either conventional mandibular bilateral distal extension partial dentures or those assisted by bilateral distal implants.

Materials and methods

Forty‐eight participants who were dissatisfied with their existing conventional mandibular distal extension dentures opposing complete maxillary dentures were selected for a multicentre prospective study in New Zealand, Colombia and the Netherlands. A control group of 12 participants in New Zealand received conventional mandibular partial dentures. Three test groups involving 36 participants in New Zealand (12), Colombia (12) and the Netherlands (12) received bilateral distal implants in the second molar regions. After conventional loading, the test group participants initially had healing caps placed on the distal implants providing support only, followed after approximately 6 months by ball abutments (retentive anchors) for support and retention. Patient outcomes were determined with questionnaires completed at specific stages of the study for up to 3 years.

Results

Visual analogue scale, Likert and oral health impact questionnaires before and after treatment indicated improved results. There were significantly improved parameters of overall satisfaction, stability, chewing and appearance after 3 years (P < 0.05). There were also improvements on stability, chewing and overall satisfaction. Speech also improved, but not significantly. Ball abutments (retentive anchors) on the distal implants, as opposed to healing caps improved patient satisfaction for stability, chewing and overall satisfaction. Changing to ball abutments (retentive anchors) revealed significant improvement by participant response when evaluating parameters of stability, chewing and overall satisfaction (P < 0.05).

Conclusion

Mandibular implant‐assisted removable partial dentures are a preferable treatment option for patients with complaints about their conventional distal extension partial dentures.
Marginal discrepancies of Ni/Cr crowns for a soft tissue‐level, trans‐mucosal implant system
Authors: Eliopoulos Dimitris , Torsello Ferruccio , Cordaro Luca
Published: November 2011

Objective

To examine the marginal fit of frameworks for implant‐supported single crowns built with or without the use of prefabricated plastic copings.

Methods

Sixty premolar sized metal crown frameworks for cemented implant restorations were prepared by two separate dental laboratories. Twenty were prepared with the use of original plastic copings for burn‐out (OPC), twenty without any prefabricated plastic coping (WPC), and finally twenty with modified plastic copings (MPC). Specimens were inspected at 100× magnification. Marginal discrepancies can emerge at the vertical level as marginal gaps (MG) or horizontal differences in the circumferential precision of the restorations (HEX). HEX and MG were recorded at 10 different points in each metal crown. The ANOVA test was performed to estimate if there were statistically significant differences between the two dental laboratories. ANOVA Test was also used between Groups OPC, WPC, and MPC to evaluate differences in the mean MG and HEX values. The Tukey's post hoc test was also performed to determine whether couples of data sets were different or not.

Results

No statistically significant differences regarding HEX and MG were found among the two dental laboratories. Significant differences were found among OPC, WPC, and MPC groups both for MG and HEX (P < 0.05). Tukey post hoc tests revealed that there were statistically significant differences (P‐value < 0.05) in all pairs of groups and for both dimensions measured. The OPC group showed horizontal and vertical over‐extension. The WPC group margins appeared vertically under‐extended but horizontally over‐extended. The WPC groups showed unpredictability of results in the vertical dimension. The MPC group margins demonstrated horizontal over‐extension and appeared vertically slightly under‐extended. The frameworks belonging to this group appeared the most precise in the vertical dimension.

Conclusions

Casting Ni/Cr alloys without the use of prefabricated plastic components leads to unpredictable precision in the vertical marginal discrepancies. The use of plastic copings results in more predictable but horizontally and vertical over‐extended margins when the snap‐on mechanism is not removed properly after the casting due to the hardness of the Ni/Cr alloys. The removal of the snap‐on mechanism after the wax‐up and before casting (MPC group) results in more uniform and smaller vertical marginal discrepancies.
Patterns of plant community assembly in invaded and non‐invaded communities along a natural environmental gradient
Authors: Santoro Riccardo , Jucker Tommaso , Carboni Marta , Acosta Alicia T.R.
Published: November 2011

Questions

Is the stress gradient hypothesis (SGH) effective in predicting patterns of community assembly in coastal dune plant communities along the sea–inland environmental gradient? Does the introduction of invasive plant species disrupt these patterns, leading to a collapse in community structure?

Location

Sandy coastal dunes of the Lazio region (Central Italy).

Methods

We randomly sampled coastal dune plant species in 2 m × 2 m plots (4 m2). Multivariate techniques were used to classify these plots and allowed identification of four plant communities along the sea–inland environmental gradient, three of which were invaded by Carpobrotus aff. acinaciformis (iceplant). For each community, we computed two different indices of co‐occurrence that take into account species abundance, and then used Monte Carlo permutations alongside appropriate null models to determine whether overlap in the use of space was greater (aggregated community structure) or smaller (segregated community structure) than what would be expected by chance alone.

Results

For the four non‐invaded communities, the analysis highlighted how community assemblage patterns were strongly tied to the sea–inland environmental gradient. In the two foredune communities, overlap in the use of space was greater than expected by chance, indicating an aggregated assemblage. In contrast, progressing along the zonation, assemblage patterns first shifted to random in the transition dune community and then became segregated in the fixed‐dune community. As for the three communities that were also found in an invaded state, the presence of iceplant was associated with a random structure in community assemblage.

Conclusions

Taken together, our results are consistent with the SGH, which predicts that along an environmental gradient, facilitation drives the assembly of plant communities where conditions are harsh, whereas competition is predominant where conditions are less severe. The comparison of the three invaded communities with their non‐invaded counterparts revealed how iceplant invasion has led to a shift to randomness in community structure, as has been documented for wildfires and other disturbances.
4‐Hydroxynonenal Induces Mitochondrial‐Mediated Apoptosis and Oxidative Stress in SH‐SY5Y Human Neuronal Cells
Authors: Abarikwu Sunny O. , Pant Aditya B. , Farombi Ebenezer O.
Published: November 2011

Abstract:  Excessive and sustained increases in oxidative stress and apoptosis have been implicated in the pathogenesis of many diseases. In this study, we demonstrated that 4‐hydroxynonenal (4‐HNE), a product of lipid peroxidation in a range of concentration (0.1–50 μM) showed cytotoxic effects on SH‐SY5Y cell culture at a concentration >5 μM at 4 hr of exposure. 4‐HNE dose dependently decreased cell viability and significantly promoted reactive oxygen species formation and enhanced oxidative stress as reflected in the increased level of lipid peroxidation and catalase activity and decreased glutathione peroxidase activity as well as glutathione levels. 4‐HNE‐induced oxidative stress was associated with increased transcriptional and translational expressions of Bax and p53 in SH‐SY5Y cells. Mitochondrial‐mediated apoptosis was confirmed by increased expression and activity of caspase‐3. Our data demonstrate that 4‐HNE induces neuronal cell death through abnormal expression of apoptotic markers (p53, Bax and caspase‐3). Oxidative stress may be involved in the initial priming of SH‐SY5Y cells to 4‐HNE‐induced cytotoxicity in vitro.
Treatment with fungicides influences phytochemical quality of blackcurrant juice
Authors: Nwankno A.J. , Gordon S.L. , Verrall S.R. , Brennan R.M. , Hancock R.D.
Published: November 2011

The impact of fungicide treatment on fungal infection and blackcurrant juice quality was examined in a series of field experiments over the course of 2 years. Fungicide treatment reduced the incidence of foliar disease and resulted in changes in the concentration of sugars, organic acids, polyphenols and anthocyanins in blackcurrant juice. Treatment with Signum®(containing pyraclostrobin, a strobilurin, and boscalid, a succinate dehydrogenase inhibitor) enhanced glucose, fructose and total sugar content in one treatment year but not in another. Treatment with Signum or Filan®(containing boscalid only) caused a reduction in the key organic acid citrate. Treatment with Signum or Platoon®(containing pyraclostrobin only) enhanced total polyphenol and anthocyanin content of juices. The data suggest a beneficial impact of fungicide treatment not only on disease control but also on juice phytochemistry.
Endovascular Treatment Strategies for Acute Ischemic Stroke
Authors: Ellis Jason A. , Youngerman Brett E. , Higashida Randall T. , Altschul Dorothea , Meyers Philip M.
Published: November 2011

The limitations of intravenous thrombolysis therapy have paved the way for the development of novel endovascular technologies for use in the setting of acute stroke. These technologies range from direct intraarterial thrombolysis to various thrombus disruption or retrieval devices to angioplasty and stenting. The tools in the armamentarium of the neuroendovascular interventionalist enable fast, effective revascularization to be offered to a wider population of patients that may otherwise have few therapeutic options available to them. In this paper, we review the current state-of-the-art in neuroendovascular intervention for acute ischemic stroke. Particular emphasis is placed on delineating the indications and outcomes for use of these various technologies.
Alternative Therapies for Stroke Treatment in Asia
Authors: Pandian Jeyaraj Durai , Liu Ming , Misbach Jusuf , Venketasubramanian N.
Published: November 2011

Patients seek alternative therapies for stroke in Asia due to dissatisfaction with poststroke recovery. Most alternative therapies are of unproven benefit in rehabilitation. Well-conducted trials are needed to better define the role of alternative therapies in the process of poststroke recovery; the CHInese Medicine Neuroaid Efficacy on Stroke recovery is ongoing. However, further studies, better health education and rehabilitation services and centers are also required.
Absence of Cerebral Microbleeds Predicts Reversion of Vascular ‘Cognitive Impairment No Dementia’ in Stroke
Authors: Tang Wai Kwong , Chen Yang-Kun , Lu Jin-Yan , Wong Adrian , Mok Vincent , Chu Winnie C. W. , Ungvari Gabor S. , Wong Ka Sing
Published: November 2011

Background

Cerebral microbleeds may contribute to cognitive deficits in stroke. Cognitive impairment that does not meet the criteria for dementia (cognitive impairment no dementia) is common in stroke, and patients with such impairment can revert to normal cognition.

Aims and hypothesis

This study examined the association between cerebral microbleeds and the reversion of cognitive impairment no dementia.

Method

A total of 328 Chinese patients with acute ischemic stroke admitted to the acute stroke unit of a university-affiliated regional hospital in Hong Kong participated in the study. All subjects were assessed for cognitive impairment no dementia with a neuropsychological test battery at three- and 15 months following the index stroke. Of the 180 patients with cognitive impairment no dementia at three-months poststroke, 143 (79·4%) attended the 15-month follow-up. Twenty-nine subjects had reverted from cognitive impairment no dementia to normal cognitive status (reverters), 98 were nonreverters and 16 had progressed to dementia.

Results

In univariate analysis, the reverters were found to be younger, less likely to have hypertension and cerebral microbleeds, and to have smaller white matter hyperintensity volumes. In multivariate analysis, the absence of cerebral microbleeds remained an independent predictor of reversion with an odds ratio of 4·3. Absence of deep cerebral microbleeds predicted the reversion of the language domain, whereas the absence of lobar cerebral microbleeds predicted the reversion of the visuomotor speed domain.

Conclusions

The results suggest that the absence of cerebral microbleeds may be associated with a higher likelihood of a reversible cognitive impairment in stroke patients. The mechanism of how this occurs is not well understood.
A Cluster Randomized Controlled Trial of a Structured Training Programme for Caregivers of Inpatients after Stroke (TRACS)
Authors: Forster Anne , Young John , Nixon Jane , Kalra Lalit , Smithard David , Patel Anita , Knapp Martin , Monaghan Josie , Breen Rachel , Anwar Shamaila , Farrin Amanda
Published: November 2011

Rationale

The majority of stroke patients are discharged home dependent on informal caregivers, usually family members, to provide assistance with activities of daily living, including bathing, dressing, and toileting. Many caregivers feel unprepared for this role, and this may have a detrimental effect on both the patient and caregiver.

Aims

To evaluate whether a structured, competency-based training programme for caregivers improves physical and psychological outcomes for patients and their caregivers after disabling stroke, and to determine if such a training programme is cost-effective.

Design

A cluster randomized controlled trial. The trial aims to recruit 25 patient and caregiver dyads from each of the 36 participating stroke rehabilitation units. Stroke units have been randomized to either the intervention or control group with randomization stratified by geographical region and quality of care. The intervention is the London Stroke Carer Training Course developed and evaluated in a previous single-centre study. The London Stroke Carer Training Course comprises a number of caregiver training sessions and competency assessment delivered while the patient is in the hospital and one follow-up session after discharge. The multidisciplinary teams in the units randomized to the intervention group have been trained to incorporate delivery of the London Stroke Carer Training Course into ward practice, while those randomized to the control group have continued to provide usual care according to national guidelines.

Study outcomes

The primary outcomes are extended activities of daily living for the patient and caregiver burden measured at six-months after recruitment. Secondary outcomes include mood and cost-effectiveness, with final follow-up at 12 months.
A Systematic Observational Study of a Juvenile Drug Court Judge
Authors: Salvatore Christopher , Hiller Matthew L. , Samuelson Benta , Henderson Jaime S. , White Elise
Published: November 2011

The shift of the juvenile justice system from its initial rehabilitative ideal toward a more punitive orientation highlights the need to systematically document key elements of the juvenile drug court model. In particular, it is important to clearly document the role of the juvenile court judge because he or she is considered vital to this program model. The current study used participant observation as well as confidential questionnaires on which youth shared their perceptions of the judge. Findings show the judge‐participant interactions typically were brief, varied by the participants' level of compliance with the program, and that sanctions were given twice as often as rewards. Youth perceived the judge to be fair, respectful, and concerned about their lives. Discussion focuses on the significant opportunity that juvenile drug court judges have for positively influencing the lives of drug‐involved youth.
Proton therapy for non–small cell lung cancer: Current evidence and future directions
Authors: Shirvani Shervin M. , Chang Joe Y.
Published: November 2011

Non–small cell lung cancer (NSCLC) is the leading cause of cancer‐related death worldwide. Radiation dose escalation can improve survival in NSCLC patients but is often limited by adverse effects. One promising radiotherapy modality is proton radiotherapy, which, because of its physical characteristics, delivers minimal exit dose beyond the target volume and thus results in better sparing of normal tissues than does photon radiotherapy. Passive‐scattering proton therapy and intensity‐modulated proton therapy have shown promise in the treatment of early‐stage and locally advanced non–small cell lung cancer. However, more studies are needed to optimize proton therapy, particularly intensity‐modulated proton therapy, to address motion and density changes and to guide appropriate patient selection.
The Cambrian Conundrum: Early Divergence and Later Ecological Success in the Early History of Animals
Authors: Erwin Douglas H. , Laflamme Marc , Tweedt Sarah M. , Sperling Erik A. , Pisani Davide , Peterson Kevin J.
Published: November 2011

Major animal clades evolved tens of millions of years before the widespread appearance of animal fossils.
Transplanted Hypothalamic Neurons Restore Leptin Signaling and Ameliorate Obesity in db/db Mice
Authors: Czupryn Artur , Zhou Yu-Dong , Chen Xi , McNay David , Anderson Matthew P. , Flier Jeffrey S. , Macklis Jeffrey D.
Published: November 2011

Neurons transplanted from healthy donor mice can repair brain circuitry and partially normalize metabolism in obese mice.
Phanerozoic Earth System Evolution and Marine Biodiversity
Authors: Hannisdal Bjarte , Peters Shanan E.
Published: November 2011

Environmental factors, more so than sampling biases, drive trends in biological evolution observed in the fossil record.
Discovery of an α-Amino C–H Arylation Reaction Using the Strategy of Accelerated Serendipity
Authors: McNally Andrew , Prier Christopher K. , MacMillan David W. C.
Published: November 2011

An unanticipated photocatalytic carbon-carbon bond-forming reaction emerged from screening many unusual reagent combinations.
Essential Role of the NH2-Terminal Region of Cdc24 Guanine Nucleotide Exchange Factor in Its Initial Polarized Localization in Saccharomyces cerevisiae
Authors: Fujimura-Kamada Konomi , Hirai Tomoe , Tanaka Kazuma
Published: November 2011

The cortical recruitment and accumulation of the small GTPase Cdc42 are crucial steps in the establishment of polarity, but this process remains obscure. Cdc24 is an upstream regulator of budding yeast Cdc42 that accelerates the exchange of GDP for GTP in Cdc42 via its Dbl homology (DH) domain. Here, we isolated five novel temperature-sensitive (ts)cdc24mutants, the green fluorescent protein (GFP)-fused proteins of which lose their polarized localization at the nonpermissive temperature. All amino acid substitutions in the mutants were mapped to the NH2-terminal region of Cdc24, including the calponin homology (CH) domain. These Cdc24-ts mutant proteins did not interact with Bem1 at the COOH-terminal PB1 domain, suggesting a lack of exposure of the PB1 domain in the mutant proteins. Thecdc24-tsmutants were also defective in polarization in the absence of Bem1. It was previously reported that a fusion protein containing Cdc24 and the p21-activated kinase (PAK)-like kinase Cla4 could bypass the requirement for Bem1 in polarity cue-independent budding (i.e., symmetry breaking). Cdc24-ts–Cla4 fusion proteins also showed ts localization at the polarity site. We propose that the NH2-terminal region unmasks the DH and PB1 domains, leading to the activation of Cdc42 and interaction with Bem1, respectively, to initiate cell polarization.
Activation of the Ras/Raf/MEK Pathway Facilitates Hepatitis C Virus Replication via Attenuation of the Interferon-JAK-STAT Pathway
Authors: Zhang Qi , Gong Rui , Qu Jing , Zhou Yijing , Liu Weiyong , Chen Mingzhou , Liu Yingle , Zhu Ying , Wu Jianguo
Published: November 2011

Hepatitis C virus (HCV) is a major cause of chronic liver diseases worldwide, often leading to the development of hepatocellular carcinoma (HCC). Constitutive activation of the Ras/Raf/MEK pathway is responsible for approximately 30% of cancers. Here we attempted to address the correlation between activation of this pathway and HCV replication. We showed that knockdown of Raf1 inhibits HCV replication, while activation of the Ras/Raf/MEK pathway by V12, a constitutively active form of Ras, stimulates HCV replication. We further demonstrated that this effect is regulated through attenuation of the interferon (IFN)-JAK-STAT pathway. Activation of the Ras/Raf/MEK pathway downregulates the expression of IFN-stimulated genes (ISGs), attenuates the phosphorylation of STAT1/2, and inhibits the expression of interferon (alpha, beta, and omega) receptors 1 and 2 (IFNAR1/2). Furthermore, we observed that HCV infection activates the Ras/Raf/MEK pathway. Thus, we propose that during HCV infection, the Ras/Raf/MEK pathway is activated, which in turn attenuates the IFN-JAK-STAT pathway, resulting in stimulation of HCV replication.
Inoculation of Swine with Foot-and-Mouth Disease SAP-Mutant Virus Induces Early Protection against Disease
Authors: Díaz-San Segundo Fayna , Weiss Marcelo , Pérez-Martín Eva , Dias Camila C. , Grubman Marvin J. , de los Santos Teresa
Published: November 2011

Foot-and-mouth disease virus (FMDV) leader proteinase (L
pro
) cleaves itself from the viral polyprotein and cleaves the translation initiation factor eIF4G. As a result, host cell translation is inhibited, affecting the host innate immune response. We have demonstrated that L
pro
is also associated with degradation of nuclear factor κB (NF-κB), a process that requires L
pro
nuclear localization. Additionally, we reported that disruption of a conserved protein domain within the L
pro
coding sequence, SAP mutation, prevented L
pro
nuclear retention and degradation of NF-κB, resulting in
in vitro
attenuation. Here we report that inoculation of swine with this SAP-mutant virus does not cause clinical signs of disease, viremia, or virus shedding even when inoculated at doses 100-fold higher than those required to cause disease with wild-type (WT) virus. Remarkably, SAP-mutant virus-inoculated animals developed a strong neutralizing antibody response and were completely protected against challenge with WT FMDV as early as 2 days postinoculation and for at least 21 days postinoculation. Early protection correlated with a distinct pattern in the serum levels of proinflammatory cytokines in comparison to the levels detected in animals inoculated with WT FMDV that developed disease. In addition, animals inoculated with the FMDV SAP mutant displayed a memory T cell response that resembled infection with WT virus. Our results suggest that L
pro
plays a pivotal role in modulating several pathways of the immune response. Furthermore, manipulation of the L
pro
coding region may serve as a viable strategy to derive live attenuated strains with potential for development as effective vaccines against foot-and-mouth disease.
Saffold Virus, a Novel Human Cardiovirus with Unknown Pathogenicity
Authors: Himeda Toshiki , Ohara Yoshiro
Published: November 2011

Although cardioviruses have been thought to mainly infect rodents, a novel human cardiovirus, designated Saffold virus (SAFV), was identified in 2007. SAFV is grouped with Theiler-like rat virus and Theiler's murine encephalomyelitis virus (TMEV) in the speciesTheilovirusof the genusCardiovirusof the familyPicornaviridae. Eight genotypes of SAFV have now been identified. SAFV has been isolated from nasal and stool specimens from infants presenting with respiratory and gastrointestinal symptoms as well as from children with nonpolio acute flaccid paralysis; however, the relationship of SAFV to this symptomatology remains unclear. Of note, the virus has also been isolated from the cerebrospinal fluid specimens of patients with aseptic meningitis. This finding is of interest since TMEV is known to cause a multiple sclerosis-like syndrome in mice. The involvement of SAFV in various diseases (e.g., respiratory illness, gastrointestinal illness, neurological diseases, and type I diabetes) is presently under investigation. In order to clarify the pathogenicity of SAFV, additional epidemiological studies are required. Furthermore, identification of the SAFV cellular receptor will help establish an animal model for SAFV infection and help clarify the pathogenesis of SAFV-related diseases. In addition, investigation of the tissue-specific expression of the receptor may facilitate development of a novel picornavirus vector, which could be a useful tool in gene therapy for humans. The study of viral factors involved in viral pathogenicity using a reverse genetics technique will also be important.
Stent retriever technology: concept, application and initial results
Authors: Rohde S , Bösel J , Hacke W , Bendszus M
Published: November 2011

Stent retrievers are increasingly used for flow restoration and thrombectomy in acute embolic stroke. First clinical results support the potential of these new devices, in particular the ability to rapidly restore flow and effectively retrieve clots from large intracranial arteries, with favorable clinical results in preliminary patient series. This article reviews the concept and technical aspects of this new technique of endovascular stroke treatment and summarizes the first clinical results.
Molecular mechanism of interleukin-2-induced mucosal homeostasis
Authors: Mishra Jayshree , Waters Christopher M. , Kumar Narendra
Published: November 2011

Sustained damage to the mucosal lining in patients with inflammatory bowel disease (IBD) facilitates translocation of intestinal microbes to submucosal immune cells leading to chronic inflammation. Previously, we demonstrated the role of Jak3 in IL-2-induced intestinal epithelial cell (IEC) migration, one of the early events during intestinal wound repair. In this study, we demonstrate that IL-2 also plays a role in IEC homeostasis through concentration-dependent regulation of IEC proliferation and cell death. At lower concentrations (≤50 U/ml), IL-2 promoted proliferation, while at higher concentrations (100 U/ml), it promoted apoptosis. Activation by IL-2 led to tyrosine phosphorylation-dependent interactions between Jak3 and p52ShcA only at lower concentrations. Phosphatase SHP1 dephosphorylated IL-2-induced phosphorylated p52ShcA. Higher concentrations of IL-2 decreased the phosphorylation of Jak3 and p52ShcA, disrupted their interactions, redistributed Jak3 to the nucleus, and induced apoptosis in IEC. IL-2 also induced dose-dependent upregulation of p52 shcA and downregulation of jak3-mRNA. Constitutive overexpression and mir-shRNA-mediated knockdown studies showed that expression of both Jak3 and p52ShcA were necessary for IL-2-induced proliferation of IEC. Doxycycline-regulated sh-RNA expression demonstrated that IL-2-induced downregulation of jak3-mRNA was responsible for higher IL-2-induced apoptosis in IEC. Collectively, these data demonstrate a novel mechanism of IL-2-induced mucosal homeostasis through posttranslational and transcriptional regulation of Jak3 and p52ShcA.
Estrogen prevents increased hepatic aquaporin-9 expression and glycerol uptake during starvation
Authors: Lebeck Janne , Gena Patrizia , O'Neill Heidi , Skowronski Mariusz T. , Lund Sten , Calamita Giuseppe , Praetorius Jeppe
Published: November 2011

In starvation, glycerol is released from adipose tissue and serves as an important precursor for hepatic gluconeogenesis. By unknown sex-specific mechanisms, women suppress the endogenous glucose production better than men and respond to metabolic stress with higher plasma glycerol levels. Hepatic glycerol uptake is facilitated by aquaporin-9 (AQP9), a broad-selectivity neutral solute channel, and represents an insulin-regulated step in supplying gluconeogenesis with glycerol. In the present study, hepatic AQP9 abundance was increased 2.6-fold in starved male rats as assessed by immunoblotting and immunohistochemistry. By contrast, starvation had no significant effect on hepatic AQP9 expression in female rats. Coordinately, plasma glycerol levels remained unchanged with starvation in male rats, whereas it was increased in female rats. The different responses to starvation were paralleled by higher glycerol permeability in basolateral hepatocyte membranes from starved male rats compared with starved females. Ovariectomy led to a starvation-response pattern identical to that observed in male rats with increased hepatic AQP9 expression and unchanged plasma glycerol levels. In cultured hepatocytes, 17β-estradiol and the selective estrogen receptor α-agonist, propyl pyrazole triol, caused a decrease in AQP9 expression. Our results support that a sex-specific regulation of the hepatic glycerol channel AQP9 during starvation contributes to the higher plasma glycerol levels observed in women during fasting and possibly results in a lower cytosolic availability of glycerol. Furthermore, the sexual dimorphism in the hepatic handling of glycerol during starvation might be explained by 17β-estradiol preventing the starvation-induced increase in hepatic AQP9 abundance.
Spontaneous fluctuations in the peripheral photoplethysmographic waveform: roles of arterial pressure and muscle sympathetic nerve activity
Authors: Chan Gregory S. H. , Fazalbhoy Azharuddin , Birznieks Ingvars , Macefield Vaughan G. , Middleton Paul M. , Lovell Nigel H.
Published: November 2011

Assessment of spontaneous slow waves in the peripheral blood volume using the photoplethysmogram (PPG) has shown potential clinical value, but the physiological correlates of these fluctuations have not been fully elucidated. This study addressed the contribution of arterial pressure and muscle sympathetic nerve activity (MSNA) in beat-to-beat PPG variability in resting humans under spontaneous breathing conditions. Peripheral PPG waveforms were measured from the fingertip, earlobe, and toe in young and healthy individuals ( n = 13), together with the arterial pressure waveform, electrocardiogram, respiration, and direct measurement of MSNA by microneurography. Cross-spectral coherence analysis revealed that among the PPG waveforms, low-frequency fluctuations (0.04–0.15 Hz) in the ear PPG had the highest coherence with arterial pressure (0.71 ± 0.15) and MSNA (0.44 ± 0.18, with a peak of 0.71 ± 0.16 at 0.10 ± 0.03 Hz). The normalized midfrequency powers (0.08–0.15 Hz), with an emphasis on the 0.1-Hz region, were positively correlated between MSNA and the ear PPG ( r = 0.77, P = 0.002). Finger and toe PPGs had lower coherence with arterial pressure (0.35 ± 0.10 and 0.30 ± 0.11, respectively) and MSNA (0.33 ± 0.10 and 0.26 ± 0.10, respectively) in the LF band but displayed higher coherence between themselves (0.54 ± 0.09) compared with the ear ( P < 0.001), which may suggest the dominance of regional vasomotor activities and a common sympathetic influence in the glabrous skin. These findings highlight the differential mechanisms governing PPG waveform fluctuations across different body sites. Spontaneous PPG variability in the ear includes a major contribution from arterial pressure and MSNA, which may provide a rationale for its clinical utility.
The maturational trajectories of NREM and REM sleep durations differ across adolescence on both school-night and extended sleep
Authors: Feinberg Irwin , Davis Nicole M. , de Bie Evan , Grimm Kevin J. , Campbell Ian G.
Published: November 2011

We recorded sleep electroencephalogram longitudinally across ages 9–18 yr in subjects sleeping at home. Recordings were made twice yearly on 4 consecutive nights: 2 nights with the subjects maintaining their ongoing school-night schedules, and 2 nights with time in bed extended to 12 h. As expected, school-night total sleep time declined with age. This decline was entirely produced by decreasing non-rapid eye movement (NREM) sleep. Rapid eye movement (REM) sleep durations increased slightly but significantly. NREM and REM sleep durations also exhibited different age trajectories when sleep was extended. Both durations exceeded those on school-night schedules. However, the elevated NREM duration did not change with age, whereas REM durations increased significantly. We interpret the adolescent decline in school-night NREM duration in relation to our hypothesis that NREM sleep reverses changes produced in plastic brain systems during waking. The “substrate” produced during waking declines across adolescence, because synaptic elimination decreases the intensity (metabolic rate) of waking brain activity. Declining substrate reduces both NREM intensity (i.e., delta power) and NREM duration. The absence of a decline in REM sleep duration on school-night sleep and its age-dependent increase in extended sleep pose new challenges to understanding its physiological role. Whatever their ultimate explanation, these robust findings demonstrate that the two physiological states of human sleep respond differently to the maturational brain changes of adolescence. Understanding these differences should shed new light on both brain development and the functions of sleep.
Acute renal venous obstruction is more detrimental to the kidney than arterial occlusion: implication for murine models of acute kidney injury
Authors: Li Xiang , Liu Manchang , Bedja Djahida , Thoburn Christopher , Gabrielson Kathleen , Racusen Lorraine , Rabb Hamid
Published: November 2011

In this study, we compared the traditional murine model with renal pedicle clamp with models that clamped the renal artery or vein alone as well as to a whole body ischemia-reperfusion injury (WBIRI) model. Male C57BL/6J mice underwent either clamping of the renal artery, vein, or both (whole pedicle) for 30 or 45 min followed by reperfusion, or 10 min of cardiac arrest followed by resuscitation up to 24 h. After 30 min of ischemia, the mice with renal vein clamping showed the mostly increased serum creatinine and the most severe renal tubule injury. After 45 min of ischemia, all mice with renal vasculature clamping had a comparable increase in serum creatinine but the renal tubule injury was most severe in renal artery-clamped mice. Renal arterial blood flow was most decreased in mice with a renal vein clamp compared with a renal artery or pedicle clamp. A 30-or 45-min renal ischemia time led to a significant increase in the protein level of interleukin-6, keratinocyte-derived chemokine (KC), and granular colony-stimulating factor in the ischemic kidney, but the KC was the highest in the renal pedicle-clamped kidney and the lowest in the renal vein-clamped kidney. Of note, 10 min of WBIRI led to kidney dysfunction and structural injury, although less than longer time clamping of isolated renal vasculature. Our data demonstrate important differences in ischemic AKI models. Understanding these differences is important in designing future experimental studies in mice as well as clinical trials in humans.
Basolateral P2X receptors mediate inhibition of NaCl transport in mouse medullary thick ascending limb (mTAL)
Authors: Marques Rita D. , de Bruijn Pauline I. A. , Sorensen Mads V. , Bleich Markus , Praetorius Helle A. , Leipziger Jens
Published: November 2011

Extracellular nucleotides regulate epithelial transport via luminal and basolateral P2 receptors. Renal epithelia express multiple P2 receptors, which mediate significant inhibition of solute absorption. Recently, we identified several P2 receptors in the medullary thick ascending limb (mTAL) including luminal and basolateral P2Y2receptors (Jensen ME, Odgaard E, Christensen MH, Praetorius HA, Leipziger J. J Am Soc Nephrol 18: 2062–2070, 2007). In addition, we found evidence for a basolateral P2X receptor. Here, we investigate the effect of basolateral ATP on NaCl absorption in isolated, perfused mouse mTALs using the electrical measurement of equivalent short-circuit current ( I′sc). Nonstimulated mTALs transported at a rate of 1,197 ± 104 μA/cm2( n = 10), which was completely blockable with luminal furosemide (100 μM). Basolateral ATP (100 μM) acutely (1 min) and reversibly reduced the absorptive I′sc. After 2 min, the reduction amounted to 24.4 ± 4.0% ( n = 10). The nonselective P2 receptor antagonist suramin blocked the effect. P2Y receptors were found not to be involved in this effect. The P2X receptor agonist 2-methylthio ATP mimicked the ATP effect, and the P2X receptor antagonist periodate-oxidized ATP blocked it. In P2X7−/−mice, the ATP effect remained unaltered. In contrast, in P2X4−/−mice the ATP-induced inhibition of transport was reduced. A comprehensive molecular search identified P2X4, P2X5, and P2X1receptor subunit mRNA in isolated mouse mTALs. These data define that basolateral ATP exerts a significant inhibition of Na+absorption in mouse mTAL. Pharmacological, molecular, and knockout mouse data identify a role for the P2X4receptor. We suggest that other P2X subunits like P2X5are part of the P2X receptor complex. These data provide the novel perspective that an ionotropic receptor and thus a nonselective cation channel causes transport inhibition in an intact renal epithelium.
Influence of rest and exercise at a simulated altitude of 4,000 m on appetite, energy intake, and plasma concentrations of acylated ghrelin and peptide YY
Authors: Wasse Lucy K. , Sunderland Caroline , King James A. , Batterham Rachel L. , Stensel David J.
Published: November 2011

The reason for high altitude anorexia is unclear but could involve alterations in the appetite hormones ghrelin and peptide YY (PYY). This study examined the effect of resting and exercising in hypoxia (12.7% O2; ∼4,000 m) on appetite, energy intake, and plasma concentrations of acylated ghrelin and PYY. Ten healthy males completed four, 7-h trials in an environmental chamber in a random order. The four trials were control-normoxia, control-hypoxia, exercise-normoxia, and exercise-hypoxia. During exercise trials, participants ran for 60 min at 70% of altitude-specific maximal oxygen consumption (V̇o2max) and then rested. Participants rested throughout control trials. A standardized meal was consumed at 2 h and an ad libitum buffet meal at 5.5 h. Area under the curve values for hunger (assessed using visual analog scales) tended to be lower during hypoxic trials than normoxic trials (repeated-measures ANOVA, P = 0.07). Ad libitum energy intake was lower ( P = 0.001) in hypoxia (5,291 ± 2,189 kJ) than normoxia (7,718 ± 2,356 kJ; means ± SD). Mean plasma acylated ghrelin concentrations were lower in hypoxia than normoxia (82 ± 66 vs. 100 ± 69 pg/ml; P = 0.005) while PYY concentrations tended to be higher in normoxia (32 ± 4 vs. 30 ± 3 pmol/l; P = 0.059). Exercise suppressed hunger and acylated ghrelin and increased PYY but did not influence ad libitum energy intake. These findings confirm that hypoxia suppresses hunger and food intake. Further research is required to determine if decreased concentrations of acylated ghrelin orchestrate this suppression.
Design Modifications in Electrospinning Setup for Advanced Applications
Authors: Sahay Rahul , Thavasi Velmurugan , Ramakrishna Seeram
Published: November 2011

The paper deals with the modification made to the general electrospinning setup. The emphasis is given to characterize the designs based on their applicability. Four basic categories are identified, namely, patterned fibers, fiber yarns, multicomponent, and deposition area of the fiber mat obtained. The mathematical modeling to better understand the physics behind the modification made to the general electrospinning setup is presented. Emphasis is given to critically analyse these categories on the basis of the applications served by them. Each of these categories is found to serve a specific poll of advanced application enabling the researchers to make a calculated choice for the design of the electrospinning setup for particular application.