bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacological protection of hearing loss in the mouse model of endolymphatic hydrops
Authors: Melki Sami J. , Heddon Chris M. , Frankel Jonathan K. , Levitt Alex H. , Momin Suhael R. , Alagramam Kumar N. , Megerian Cliff A.
Published: July 2010

Objectives/Hypothesis:

Excitotoxic and related inflammatory injury are implicated in the spiral ganglion degeneration seen with Meniere's disease and endolymphatic hydrops (ELH). Excitotoxicity is initiated with glutamate elevation and associated with downstream increases in reactive oxygen species resulting in inflammation‐mediated neuronal degeneration. This study tests the hypothesis that interruption of the initial and/or downstream aspects of excitotoxicity should provide hearing protection in ELH‐associated hearing loss.

Study Design:

This study tests whether riluzole, a glutamate release inhibitor, and dimethylsulfoxide (DMSO), an anti‐inflammatory and antioxidant solvent with favorable properties at the level of glutamate receptors, can protect against early‐stage hearing loss in a mouse model of ELH.

Methods:

ThePhexHyp‐Dukmouse spontaneously develops ELH and postnatal hearing loss. Starting at postnatal day 6 (P6), daily injections of riluzole + DMSO or just DMSO were administered. Untreated mutants served as controls. At P21, P25, and P30, hearing function was assessed by recording auditory brainstem responses. A cochlear function index was developed to assess global cochlear function at each time point.

Results:

Compared to no treatment, DMSO provided significant hearing protection (P< .05). The riluzole + DMSO also showed protection, but it was statistically indistinguishable from DMSO alone; a synergistic increase in protection with riluzole was not observed.

Conclusions:

This study demonstrates pharmacological hearing protection in an animal model of ELH. The results support the assertion that inflammatory (reactive oxygen species) injury, which is part of the excitotoxic pathway, contributes to the development of ELH‐associated hearing loss. Laryngoscope, 2010
Evaluation of intraoperative parathormone measurement for predicting successful surgery in patients undergoing subtotal/total parathyroidectomy due to secondary hyperparathyroidism
Authors: Kara Melih , Tellioglu Gurkan , Bugan Ugur , Krand Osman , Berber Ibrahim , Seymen Pinar , Eren Pinar Ata , Ozel Leyla , Titiz Izzet
Published: July 2010

Objectives/Background:

The aim of this study is to investigate the predictive value of intraoperative parathormone measurement addressing successful surgical resection in patients with secondary hyperparathyroidism.

Methods:

The study included 42 consecutive patients operated on between May 2006 and July 2008. Patients were grouped according to successful surgery (Group 1, n = 36) and persistent postoperative hyperparathyroidism (Group 2, n = 6). Serum phosphorus (P), total calcium (tCa), ionized calcium (iCa), intact parathormone (iPTH), and alkaline phosphatase (ALP) were drawn preoperatively and intraoperatively upon 15 minutes after completion of resection (iPTH15). The rate of decrease of pith detected by iPTH15 compared to preoperative values was calculated (iPTH%).

Results:

Preoperative P, tCa, iCa, iPTH, and ALP were comparable. Subtotal parathyroidectomy (sPx) (n = 27) and total parathyroidectomy with autotransplantation (tPx) (n = 15) were performed. Mean iPTH15 value, iPTH% rates were 145.9 ± 12.3 pg/mL, % 91.6 ± 0.7, and 522.5 ± 85.4 pg/mL, % 75.1 ± 2.0 (P = ,001) in Groups 1 and 2, respectively. Mean serum tCa and iCa at POD#1 in Group 1 were 7.6 ± 0.1 mg/dL, 0.910 ± 0.4 mmol/L, and Group 2 were 8.3 ± 0.3 mg/dL, 1.050 ± 0.4 mmol/L (P < .05), respectively. ALP levels were similar.

Conclusion:

iPTH15 value and iPTH% rate accurately predicts the completeness of resection in secondary hyperparathyroidism. The rate of decrease in serum iPTH detected intraoperatively compared to preoperative baseline levels exceeding 90% in sPx, 95% in tPx, accurately predicts the success of surgery. Postoperative normocalcemia without calcium replacement would raise a suspicion about completeness of surgical resection. Laryngoscope, 2010
Different biofilms, different disease? A clinical outcomes study
Authors: Foreman Andrew , Wormald Peter‐John
Published: July 2010

Objectives/Hypothesis:

A potential role for biofilms in Chronic Rhinosinusitis (CRS) has been proposed, and the adverse impact they have on disease severity and postoperative outcomes has also been well described. Recent advances have allowed the species within the biofilms of CRS patients to be clearly characterized. This study investigates whether different biofilm species have different disease outcomes.

Study Design:

Retrospective review.

Methods:

Twenty‐four patients with medically recalcitrant CRS undergoing Endoscopic Sinus Surgery (ESS), in whom we had previously characterized their biofilms using fluorescence in situ hybridization (FISH), were reviewed a median of 11 months after their surgery. They were evaluated for preoperative disease markers and evidence of on‐going disease in the postoperative period.

Results:

Thirty‐seven biofilms were identified in the 24 patients. Almost half had polymicrobial biofilms. The presence of polymicrobial, rather than single‐species biofilms adversely affected preoperative disease severity but did not alter postsurgical outcome. Patients with single organism Haemophilus influenzae biofilms presented with mild disease symptomatically and radiologically and achieved normal mucosa a short time after their surgery. Conversely, patients with Staphlococcus aureus in their biofilm makeup had more severe disease and a more complicated postoperative course. The effect of Pseudomonas aeruginosa and fungal biofilms is less clear.

Conclusions:

Different biofilm species are associated with different disease phenotypes. H. influenzae biofilms are typically found in patients with mild disease, whereas S. aureus is associated with a more severe, surgically recalcitrant pattern. Laryngoscope, 2010
Percutaneous injection laryngoplasty in the management of acute vocal fold paralysis
Authors: Damrose Edward J.
Published: July 2010

Objectives/Hypothesis:

To evaluate the clinical outcome of patients with acute vocal fold paralysis treated with bovine collagen via percutaneous injection laryngoplasty under simple topical anesthesia.

Study Design:

Retrospective case series.

Methods:

The charts of 38 consecutive patients with acute unilateral vocal fold paralysis who underwent percutaneous injection laryngoplasty under simple topical anesthesia were reviewed. Symptoms and laryngeal function were assessed pre‐ and postinjection using the Glottal Function Index (GFI), GRBAS Dysphonia Scale, Functional Outcome Swallowing Scale (FOSS), and maximum phonation time (MPT).

Results:

Mean GFI, GRBAS, FOSS, and MPT improved from 13.71 to 7.68, 7.24 to 3.95, 3.70 to 2.20, and 12.87 to 16.45, respectively (P ≤ .0001). There were no complications related to the procedure. In seven patients requiring tube feeding secondary to dysphagia and aspiration, injection was successful in restoring oral alimentation in only three patients, with the four failures occurring in patients with multiple cranial neuropathies.

Conclusions:

Percutaneous injection laryngoplasty is a viable option for immediate rehabilitation of acute vocal fold paralysis, and can be performed in the inpatient setting. With dysphagia and aspiration secondary to multiple cranial nerve palsies, medialization of the paralyzed cord alone may be insufficient to restore safe oral alimentation. Laryngoscope, 2010
Survival and cost-effectiveness analysis of competing strategies in the management of small hepatocellular carcinoma
Authors: Naugler Willscott E. , Sonnenberg Amnon
Published: July 2010

The aim of the present study is to compare the survival rates and cost-effectiveness of different treatment strategies for small (<2 cm) hepatocellular carcinoma (HCC). Markov chains are developed to model different management strategies for patients with compensated cirrhosis and small HCC. Probabilities of progression and survival and the likelihood of orthotopic liver transplantation are taken from the literature and incorporated into the models. As a starting population, 1000 patients are followed over a period of 10 years. Patients treated immediately with transarterial chemoembolization (TACE) or radiofrequency ablation (RFA) live as long as or longer than patients who are monitored expectantly with the intention of liver transplantation once the HCC has grown larger than 2 cm and a higher transplant priority score becomes available. With TACE, immediate treatment results in an average survival time of 4.269 years versus 4.324 years with the monitoring strategy. With RFA, immediate treatment results in an average survival time of 5.273 years versus 5.236 years with the monitoring strategy. In addition, the cost analysis shows that immediate treatment with either TACE or RFA is less expensive than monitoring. The better cost-effectiveness of immediate therapy versus the monitoring strategy remains robust and unaffected by variations of the assumptions built into the model. In conclusion, in patients with compensated cirrhosis and small HCC, a strategy of immediate treatment with either TACE or RFA prevails over a strategy of expectant monitoring with the intention of transplantation. Liver Transpl 16:1186–1194, 2010. © 2010 AASLD.
Patients on the waiting list for liver transplantation: Caregiver burden and stress
Authors: Miyazaki Eliane Tiemi , dos Santos Randolfo , Miyazaki Cristina M. , Domingos Neide M. , Felicio Hellen C. , Rocha Marcia F. , Arroyo Paulo C. , Duca William J. , Silva Renato F. , Silva Rita C. M. A.
Published: July 2010

Over the last few decades, informal caregivers of patients with chronic diseases have received more attention, and there is a growing volume of studies demonstrating high rates of burden, stress, and mental disorders in this group of individuals. The objective of this study was to evaluate the burden, stress, and psychosocial characteristics of informal caregivers of liver transplantation candidates. Participants were assessed by individual evaluations with the following instruments: a semistructured interview, the Caregiver Burden Scale, the Inventário de Sintomas de Stress para Adultos de Lipp, and the Beck Depression Inventory. The Mann-Whitney test was used for statistical analysis with a significance level of 0.05. The characteristics of the study group (n = 61) were similar to those of groups in other studies with respect to gender (82% were women), kinship (64% were spouses), and age (the mean age was 47.6 years). The main stressors identified by the participants were as follows: doubts about ways to react in a crisis or in emergency situations (42.6%), mood swings of the patient (29.5%), and care involving food and medications (27.9%). Approximately 25% of the caregivers reported that they felt unprepared to adequately perform their roles. Data analysis indicated a greater burden overall on caregivers when the patient's Model for End-Stage Liver Disease score was greater than or equal to 15 points (P = 0.041). Furthermore, caregivers of patients with alcoholic liver disease showed higher depression (P = 0.034) and overall burden scores (P = 0.031) versus caregivers of patients with liver disease due to other etiologies. In conclusion, the participants showed significantly high levels of burden, stress, and depression. Support measures and caregiver preparation should be implemented by health care providers. Liver Transpl 16:1164–1168, 2010. © 2010 AASLD.
Review of methods for measuring and comparing center performance after organ transplantation
Authors: Neuberger James , Madden Sue , Collett David
Published: July 2010

The assessment of outcomes after transplantation is important for several reasons: it provides patients with data so that they can make informed decisions about the benefits of transplantation and the success of the transplant unit; it informs commissioners that resources are allocated properly; and it provides clinicians reassurance that results are acceptable or, if they are not, provides early warning so that problems can be identified, corrections can be instituted early, and all interested parties can be reassured that scarce resources are used fairly. The need for greater transparency in reporting outcomes after liver transplantation and for comparisons both between and within centers has led to a number of approaches being adopted for monitoring center performance. We review some of the commonly used methods, highlight their strengths and weaknesses, and concentrate on methods that incorporate risk adjustment. Measuring and comparing outcomes after transplantation is complex, and there is no single approach that gives a complete picture. All those using analyses of outcomes must understand the merits and limitations of individual methods. When used properly, such methods are invaluable in ensuring that a scarce resource is used effectively, any adverse trend in outcomes is identified promptly and remedied, and best performers are identified; they thus allow the sharing of best practices. However, when they are used inappropriately, such measurements may lead to inappropriate conclusions, encourage risk-averse behavior, and discourage innovation. Liver Transpl 16:1119–1128, 2010. © 2010 AASLD.
Early-onset pneumonia after liver transplantation: Microbiological findings and therapeutic consequences
Authors: Weiss Emmanuel , Dahmani Souhayl , Bert Frederic , Janny Sylvie , Sommacale Daniel , Dondero Federica , Francoz Claire , Belghiti Jacques , Mantz Jean , Paugam-Burtz Catherine
Published: July 2010

Early-onset hospital-acquired pneumonia (E-HAP) is one of the leading causes of sepsis and mortality after liver transplantation (LT). The appropriate antimicrobial therapy is crucially important for surviving sepsis in this context. The aim of this study was to analyze microbiological findings, associated factors, and optimal antibiotic regimens for E-HAP after LT. Patients demonstrating E-HAP in a single-center cohort of 148 LT recipients were prospectively detected. The diagnosis of pneumonia relied on a combination of supportive clinical findings and a positive culture of a lower respiratory tract sample. E-HAP was considered present if pneumonia occurred within 6 days of intensive care unit (ICU) admission after LT. Twenty-three patients (15.5%) developed E-HAP, which were caused by 36 pathogens (61.1% were gram-negative bacilli, and 33.3% were classified as hospital-acquired). For patients who developed E-HAP, the duration of mechanical ventilation and the ICU stay were significantly longer. Despite a trend toward higher mortality at any time in the E-HAP group, there was no significant difference in mortality between patients with E-HAP and patients without E-HAP. Lactatemia, vasopressor requirements, Simplified Acute Physiology Score II (SAPS II) score on ICU admission, and mechanical ventilation lasting more than 48 hours after LT were associated with E-HAP. Combinations of broad-spectrum β-lactams and aminoglycosides were active against more than 91% of the encountered pathogens. However, antibiotic de-escalation was possible in more than one-third of cases after identification of the pathogens. In conclusion, E-HAP after LT is a severe condition that appears to be influenced by physiological derangements induced by the surgery, such as lactatemia, vasopressor requirements, and mechanical ventilation requirements, as well as the postoperative SAPS II score. At the time of treatment initiation, an antimicrobial regimen usually proposed for late-onset pneumonia should be followed. Liver Transpl 16:1178–1185, 2010. © 2010 AASLD.
Calculation of CLD Using Population Balance Equations of Generating Functions: Linear and Non‐Linear Ideal Controlled Radical Polymerization
Authors: Dias Rolando C. S. , Costa Mário Rui P. F. N.
Published: July 2010

Population balance equations in terms of generating functions (GF) are used to predict chain length distributions (CLD) of linear and non‐linear ideal controlled radical polymerization (CRP) systems. It is here shown that under simplified conditions analytical solutions for the CLD can be found and moreover the fundamental CLD derived by H. Tobita in 2006 is a limiting case of the more general solutions here presented. In order to deal with more complex CRP systems, solutions based upon the numerical inversion of GF are presented. These studies are also extended to the non‐linear CRP of vinyl/divinyl monomers where multimodal CLDs are predicted to occur.

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Early Stages of Growth of Plasma Polymer Coatings Deposited from Nitrogen‐ and Oxygen‐Containing Monomers
Authors: Vasilev Krasimir , Michelmore Andrew , Martinek Petr , Chan Joseph , Sah Vasu , Griesser Hans J. , Short Robert D.
Published: July 2010

Ultrathin functional coatings deposited by plasma polymerization have utility in nano‐ and microtechnologies, however, until now very little has been reported to validate the widely held view that these coatings can be deposited onto any type of substrate, without substrate influence. In order to ascertain the role of the substrate in the early stages of plasma growth we address the growth rate and chemistry of plasma polymer coatings from two nitrogen‐ and two oxygen‐containing monomers during the first stages of deposition onto gold and onto thiol MUA‐coated gold surfaces. SPR thickness measurements and XPS analyzes indicate the substrate must be taken into account when ultrathin plasma polymer coatings are used for surface modification and we speculate on why this should be so.

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Association of three different congenital malformations in a same pulmonary lobe in a 5‐year‐old girl
Authors: Carsin A. , Mely L. , Chrestian M.A. , Devred Ph. , de Lagausie P. , Guys J.M. , Dubus J.C.
Published: July 2010

We report the case of a 5‐year‐old girl with persistent chest X‐ray abnormalities following an episode of pneumonia who has a complex congenital pulmonary malformation comprising of a congenital pulmonary airway malformation, an intralobar sequestration and two bronchogenic cysts, all present within the same lobe. The observation suggests a common embryological origin of these malformations. Pediatr. Pulmonol. 2010; 45:832–835. © 2010 Wiley‐Liss, Inc.
Backbone cyclic insulin
Authors: Andersen Asser S. , Palmqvist Eva , Bang Susanne , Shaw Allan C. , Hubalek Frantisek , Ribel Ulla , Hoeg‐Jensen Thomas
Published: July 2010

Backbone cyclic insulin was designed and prepared by reverse proteolysis in partial organic solvent of a single‐chain precursor expressed in yeast. The precursor contains two loops to bridge the two chains of native insulin. The cyclisation method uses Achromobacter lyticus protease and should be generally applicable to proteins with C‐terminal lysine and proximal N‐terminal. The presence of the ring‐closing bond and the native insulin disulfide patterns were documented by LC–MS peptide maps. The cyclic insulin was shown to be inert towards degradation by CPY, but was somewhat labile towards chymotrypsin. Intravenous administration of the cyclic insulin to Wistar rats showed the compounds to be equipotent to HI despite much lower insulin receptor affinity. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.
Magnetic properties of rutile TiO2‐1/6 from first‐principles calculations
Authors: Han Guang‐bing , Hu Shu‐jun , Yan Shi‐shen , Kang Shi‐shou , Mei Liang‐mo
Published: July 2010

Based on first‐principles LDA + U calculations, the magnetic properties of undoped rutile TiO2 with high oxygen deficiency are theoretically investigated. Rather than a tunable parameter, the value of U is determined by constrained‐density‐functional calculations. The oxygen vacancies (Vo) can lead to a strong ferromagnetic coupling, which is mediated by the donor impurity state (F‐center) (mainly in the vicinity of Vo) and 90° cation–ation–cation superexchange interaction alternately in the large displacement direction of the Ti atom. This long‐range ferromagnetic mechanism in magnetic semiconductors was not yet reported previously. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The effect of fenugreek on the gene expression of arachidonic acid metabolizing enzymes
Authors: Varjas Timea , Nowrasteh Ghodratollah , Budán Ferenc , Horváth Gábor , Cseh József , Gyöngyi Zoltán , Makai Sándor , Ember István
Published: July 2010

The main bioactive compounds of Trigonella foenum graecum L. (fenugreek) seeds are protodioscin, trigoneoside, diosgenin and yamogenin, which have anticarcinogenic potency through inhibition of cell proliferation and inhibition of prostaglandin synthesis.

The effect of fenugreek on ALOX and COX genes was examined in AKR/J H‐2k mice exposed to dimethylbenz[α]anthracene (DMBA), a potent carcinogen. The expression pattern of these genes was determined by detecting the mRNA expression in various tissues (the lungs, liver, spleen and the kidneys) in four groups of mice. Two groups were fed with normal and two of them with fenugreek containing nutriment. Each group divided into DMBA treated and control groups. Mice were autopsied on day 7 after DMBA treatment for mRNA isolation. Fenugreek consumption itself did not change gene expression compared with the control group. DMBA could increase the expression of ALOX12, ALOX15, ALOX5 genes mainly in all organs. Fenugreek consumption was generally protective in each organ in a different manner. DMBA treatment increased COX2 gene expression, but fenugreek was protective in all tissues examined. In COX1 gene, the fenugreek diet could suppress the expression, except for spleen, independently from carcinogen exposure. Therefore by inhibiting the arachidonic acid metabolism fenugreek may prevent tumorigenesis. Copyright © 2010 John Wiley & Sons, Ltd.
Silymarin potentiates the antinociceptive effect of morphine in mice
Authors: Malekinejad Hassan , Taheri‐Broujerdi Maysam , Moradi Masumeh , Tabatabaie Seyed‐Hamed
Published: July 2010

Silymarin is a natural flavonoid found in the seeds of the milk thistle (Silybum marianum). Accumulating evidence indicates that silymarin exerts preventive/protective effects in animals and humans against many diseases. This study aimed to evaluate the antinociceptive effect of silymarin in the tail flick and writhing reaction assays. To understand the mechanism of the antinociceptive effect, the interaction of silymarin and morphine on acetic acid‐induced reaction was examined. Moreover, the effect of naloxone as a narcotic receptor antagonist on silymarin‐induced antinociception was studied. The antioxidant potency of silymarin was assessed by measuring the level of total thiol molecules in serum and the free radical scavenging activity. Silymarin lowered significantly (P< 0.05) the latency time in the tail flick test in a dose‐dependent fashion. In the writhing reaction assay, silymarin dose‐ and time‐dependently decreased the number of acetic acid‐induced contractions. Silymarin also enhanced the morphine produced antinociceptive effect, while pretreatment with naloxone resulted in antagonism of the silymarin‐induced antinociceptive effect, significantly (P< 0.05). Additionally, silymarin elevated the total thiol molecule level in the serum, which latter antioxidant property was confirmed by the concentration‐dependent radical scavenging activity. The data suggest that the silymarin antinociceptive effect may be attributed to its interaction with the opioid system and its antioxidant capacity. Copyright © 2010 John Wiley & Sons, Ltd.
Identification of cytochrome P450 (CYP) isoforms involved in the metabolism of corynoline, and assessment of its herb–drug interactions
Authors: Fang Zhong‐Ze , Zhang Yan‐Yan , Ge Guang‐Bo , Liang Si‐Cheng , Sun Dong‐Xue , Zhu Liang‐Liang , Dong Pei‐Pei , Cao Yun‐Feng , Yang Ling
Published: July 2010

Corynoline, an isoquinoline alkaloid isolated from the genusCorydalis, has been demonstrated to show multiple pharmacological effects including inhibition of acetylcholinesterase, inhibition of cell adhesion, fungitoxic and cytotoxic activity. The present study focused on its metabolism and metabolism‐based herb–drug interactions. After corynoline was incubated with human liver microsomes (HLMs) in the presence of NADPH, two metabolites (M‐1 and M‐2) were formed. Chemical inhibition experiments and assays with recombinant CYP isoforms showed that CYP2C9 was mainly involved in the formation of M‐1 and CYP3A4 mainly catalysed the production of M‐2. Among seven major CYP isoforms tested, corynoline showed strong inhibitory effects on the activities of CYP3A4 and CYP2C9, with an IC50of 3.3 ± 0.9 µmand 31.5 ± 0.5 µm, respectively. Kinetic analysis showed that inhibition of CYP3A4 by corynoline was best fit to a noncompetitive manner withKiof 3.2 µm, while inhibition of CYP2C9 by corynoline was best fit to a competitive manner withKiof 6.3 µm. Additionally, corynoline exhibited time‐dependent inhibition (TDI) toward CYP3A4. The inactivation kinetic parameters (KIandkinact) were calculated to be 6.8 µmand 0.07 min‐1, respectively. These data are of significance for the application of corynoline and corynoline‐containing herbs. Copyright © 2010 John Wiley & Sons, Ltd.
Improving performance and fostering accountability in the public sector through system dynamics modelling: From an ‘external’ to an ‘internal’ perspective
Authors: Bianchi Carmine
Published: July 2010

This paper aims to outline the benefits justifying a tailored approach to System Dynamics (SD) modelling in the public sector, to improve performance and foster decision makers' accountability. The need of combining an ‘internal’ with an ‘external’ perspective (in respect to decision makers) in developing SD models is claimed. Different levels of intervention (i.e. macro, micro and meso) are discussed. Two case studies are analysed. The first one demonstrates how a dynamic resource‐based view (DRBV) can support an analysis of the impact of back and front office units on a public sector organization's performance drivers. The second case shows how SD modelling based on a DRBV can also be applied to improve performance on a political level. Copyright © 2010 John Wiley & Sons, Ltd.
What can system dynamics learn from the public policy implementation literature?
Authors: Wheat I. David
Published: July 2010

More often than not, system dynamics model‐based public policy analysis is limited to testing parameter changes instead of designing and testing new stock‐and‐flow policy structures. That is problematic because improvements in behaviour require improvements in structure. This paper considers how the public policy implementation literature could improve the operational thinking skills required for designing policy structure for public sector models. A familiar model of a public health problem is used to illustrate the recommended approach. And an instructional training strategy is offered for teaching and learning to think operationally during the policy‐design stage of modelling. Copyright © 2010 John Wiley & Sons, Ltd.
A Small Synthetic Cripto Blocking Peptide Improves Neural Induction, Dopaminergic Differentiation, and Functional Integration of Mouse Embryonic Stem Cells in a Rat Model of Parkinson's Disease
Authors: Lonardo Enza , Parish Clare L. , Ponticelli Salvatore , Marasco Daniela , Ribeiro Diogo , Ruvo Menotti , De Falco Sandro , Arenas Ernest , Minchiotti Gabriella
Published: July 2010

Cripto is a glycosylphosphatidylinositol-anchored coreceptor that binds Nodal and the activin type I (ALK)-4 receptor, and is involved in cardiac differentiation of mouse embryonic stem cells (mESCs). Interestingly, genetic ablation of cripto results in increased neuralization and midbrain dopaminergic (DA) differentiation of mESCs, as well as improved DA cell replacement therapy (CRT) in a model of Parkinson's disease (PD). In this study, we developed a Cripto specific blocking tool that would mimic the deletion of cripto, but could be easily applied to embryonic stem cell (ESC) lines without the need of genetic manipulation. We thus screened a combinatorial peptide library and identified a tetrameric tripeptide, Cripto blocking peptide (BP), which prevents Cripto/ALK-4 receptor interaction and interferes with Cripto signaling. Cripto BP treatment favored neuroectoderm formation and promoted midbrain DA neuron differentiation of mESCs in vitro and in vivo. Remarkably, Cripto BP-treated ESCs, when transplanted into the striatum of PD rats, enhanced functional recovery and reduced tumor formation, mimicking the effect of genetic ablation of cripto. We therefore suggest that specific blockers such as Cripto BP may be used to improve the differentiation of ESC-derived DA neurons in vitro and their engraftment in vivo, bringing us closer towards an application of ESCs in CRT.
Inducible Gene and shRNA Expression in Resident Hematopoietic Stem Cells In Vivo
Authors: Laurenti Elisa , Barde Isabelle , Verp Sonia , Offner Sandra , Wilson Anne , Quenneville Simon , Wiznerowicz Maciej , MacDonald H. Robson , Trono Didier , Trumpp Andreas
Published: July 2010

Hematopoietic stem cells (HSC) are probably the best understood somatic stem cells and often serve as a paradigm for other stem cells. Nevertheless, most current techniques to genetically manipulate them in vivo are either constitutive and/or induced in settings of hematopoietic stress such as after irradiation. Here, we present a conditional expression system that allows for externally controllable transgenesis and knockdown in resident HSCs, based on a lentiviral vector containing a tet-O sequence and a transgenic mouse line expressing a doxycyclin-regulated tTR-KRAB repressor protein. HSCs harvested from tTR-KRAB mice are transduced with the lentiviral vector containing a cDNA (i.e., Green Fluorescent Protein (GFP)) and/or shRNA (i.e., p53) of interest and then transplanted into lethally irradiated recipients. While the vector is effectively repressed by tTR-KRAB during homing and engraftment, robust GFP/shp53 expression is induced on doxycyclin treatment in HSCs and their progeny. Doxycylin-controllable transcription is maintained on serial transplantation, indicating that repopulating HSCs are stably modified by this approach. In summary, this easy to implement conditional system provides inducible and reversible overexpression or knock down of genes in resident HSCs in vivo using a drug devoid of toxic or activating effects.
Human Embryonic Stem Cells as Models for Aneuploid Chromosomal Syndromes
Authors: Biancotti Juan-Carlos , Narwani Kavita , Buehler Nicole , Mandefro Berhan , Golan-Lev Tamar , Yanuka Ofra , Clark Amander , Hill David , Benvenisty Nissim , Lavon Neta
Published: July 2010

Syndromes caused by chromosomal aneuploidies are widely recognized genetic disorders in humans and often lead to spontaneous miscarriage. Preimplantation genetic screening is used to detect chromosomal aneuploidies in early embryos. Our aim was to derive aneuploid human embryonic stem cell (hESC) lines that may serve as models for human syndromes caused by aneuploidies. We have established 25 hESC lines from blastocysts diagnosed as aneuploid on day 3 of their in vitro development. The hESC lines exhibited morphology and expressed markers typical of hESCs. They demonstrated long-term proliferation capacity and pluripotent differentiation. Karyotype analysis revealed that two-third of the cell lines carry a normal euploid karyotype, while one-third remained aneuploid throughout the derivation, resulting in eight hESC lines carrying either trisomy 13 (Patau syndrome), 16, 17, 21 (Down syndrome), X (Triple X syndrome), or monosomy X (Turner syndrome). On the basis of the level of single nucleotide polymorphism heterozygosity in the aneuploid chromosomes, we determined whether the aneuploidy originated from meiotic or mitotic chromosomal nondisjunction. Gene expression profiles of the trisomic cell lines suggested that all three chromosomes are actively transcribed. Our analysis allowed us to determine which tissues are most affected by the presence of a third copy of either chromosome 13, 16, 17 or 21 and highlighted the effects of trisomies on embryonic development. The results presented here suggest that aneuploid embryos can serve as an alternative source for either normal euploid or aneuploid hESC lines, which represent an invaluable tool to study developmental aspects of chromosomal abnormalities in humans.
Loess
Authors: Gijbels Irène , Prosdocimi Ilaria
Published: July 2010

Linear least squares regression is among the most well known classical methods. This and other parametric least squares regression models do not perform well when the modeling is too restrictive to capture the nonlinear effect the covariates have on the response. Locally weighted least squares regression (loess) is a modern technique that combines much of the simplicity of the classical least squares method with the flexibility of nonlinear regression. The basic idea behind the method is to model a regression function only locally as having a specific form. This paper discusses the method in the univariate and multivariate case and robustifications of the technique, and provides illustrative examples. Copyright © 2010 John Wiley & Sons, Inc.

This article is categorized under:

Statistical and Graphical Methods of Data Analysis > Density Estimation
RNA in evolution
Authors: Lehman Niles
Published: July 2010

RNA has played a variety of roles in the evolutionary history of life on the Earth. While this molecule was once considered a poor cousin of the more influential polymers in the cell, namely DNA and proteins, a string of important discoveries over the last 50 years has revealed that RNA may in fact be the cornerstone of biological function. In particular, the finding that RNA can be catalytic, and thus possess both a genotype and a phenotype, has forced us to consider the possibility that life's origins began with RNA, and that the subsequent diversification of life is aptly described as a string of innovations by RNA to adapt to a changing environment. Some of these adaptations include riboswitches, ribonucleoproteins (RNPs), RNA editing, and RNA interference (RNAi). Although many of these functions may seem at first glance to be recent evolutionary developments, it may be the case that all of their catalytic activities trace their roots back to a primordial ‘RNA World’ some four billion years ago, and that RNA's diversity has a continuous thread that pervades life from its very origins. Copyright © 2010 John Wiley & Sons, Ltd.

This article is categorized under:

RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution

RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems

RNA-Based Catalysis > Miscellaneous RNA-Catalyzed Reactions
A micromechanically motivated higher‐order continuum formulation of linear thermal conduction
Authors: Temizer İ. , Wriggers P.
Published: July 2010

A higher‐order continuum theory of linearized thermal conduction is developed where a rigid heat conductor is modeled as a material of grade‐2 with a view towards capturing the thermal effects in BGK‐Burnett type formulations for microfluidic flows. The construction is based on a second‐order thermal homogenization framework which leads to the identification of a thermal dissipation potential that is a function of the higher‐order gradients of the temperature. The dissipation potential delivers the expressions for the higher‐order fluxes and forms the basis of a discussion regarding the satisfaction of the second law of thermodynamics. Further restrictions on the constitutive expressions arise from material symmetry considerations. Strong and weak formulations of the associated boundary value problem are derived based on an appropriate identification of the boundary conditions. The methodologies employed and the implications of the theory are reminiscent of similar approaches in linearized elasticity formulations and are compared with micromorphic and Cahn‐Hilliard type formulations.
The crack growth prediction in homogeneous materials and bimaterial systems
Authors: Mróz K.P. , Doliński K.
Published: July 2010

The new criterion determining the angle of crack propagation in mixed mode loading conditions is proposed. Both monotonic and cyclic loading are considered for homogeneous and bimaterial systems. For bimaterial it is assumed that either the crack does not touch or simply crosses the interface during its growth. The angle of the crack propagation corresponds with the direction where the ratio of the dissipation energy generated in the plastic processes to that generated in the decohesion processes reaches its smallest value. The criterion assumes also that the fracture crack propagation follows the direction for which the distortional component of the strain energy density, TD calculated along the line of the constant dilatation energy density TVC around the crack tip reaches its minimum value. The constant value of TVC is associated with the ultimate tensile stress σC. The criterion involves the T‐stress term that represents a constant stress parallel to the main crack orientation. A critical length of the radius of the decohesion zone determines the fracture condition. In the article a numerical method based on the singular integral technique involving the distribution of edge dislocations to represent the actual crack is proposed. The resulting singular integral equations with Cauchy‐type singularities are solved numerically. The method allows us to determine the stress intensity factors (SIFs) and T‐stress term at the tips of the propagating crack. The results show very good agreement with the numerical data found in the literature. The new equation to determine the fatigue crack growth rate is also proposed and used to trace the fatigue crack path in the homogeneous and bimaterial systems.
Enteric Fistulation After Renal Artery Reconstruction: A Systematic Literature Review
Authors: Bergqvist David , Björck Martin
Published: July 2010

A systematic literature review has revealed 14 cases of arterioenteric fistulation after renovascular reconstruction. Among the 14 patients, 9 had thrombotic occlusion of the reconstruction and 5 underwent nephrectomy, but neither procedure prevented fistulation. There was a dominance of right‐sided bypass reconstructions. All patients but one suffered from gastrointestinal bleeding; 3 died before operation and 5 had herald bleeds. Three died as a direct result of surgery. Various technical solutions were used, and the follow‐up time was clearly unsatisfactory; in only 2 patients was the follow‐up longer than 1 year. Arterioenteric fistulation is a serious complication, associated with a highmortality rate and a high incidence of kidney loss among survivors.
Specific Heat of Olive Oil to 356 MPa
Authors: Leu Bogdan M. , Yavaş Hasan , Kantor Innokenty , Prakapenka Vitali B.
Published: July 2010

We measured the velocity of sound in olive oil under pressure with the Brillouin light scattering technique. Using the values for the density and the thermal conductivity that have only recently been reported, we calculated the adiabatic compressibility and the isobaric specific heat up to 356 MPa and the thermal diffusivity up to 200 MPa. The specific heat displays a maximum at 124 MPa, suggesting a possible phase transition around this pressure. Apart from the theoretical and practical importance of these results for the food industry and beyond, this work shows that Brillouin light scattering and macroscopic methods are complementary and can be employed to measure thermophysical parameters of food liquids under pressure.
Flächeninanspruchnahme 2020 und das 30-ha-Ziel: Regionale Verteilungsschlüssel und Anpassungserfordernisse
Authors: Henger Ralph , Schröter-Schlaack Christoph , Ulrich Philip , Distelkamp Martin
Published: July 2010

The reduction of land development and the attainment of the national 30-ha-sustainability-target require all states, regions and municipalities in Germany to adjust. Up to now, however, regional targets for local jurisdictions have not been achieved. This paper presents a top-down mechanism by which a national target is subdivided according to the population and total area shares of each administrative unit. Distributional implications of this rule are analyzed on the level of states and regions. For this purpose, the derived sub-quantities are compared with the past and future land development rates. The future development of land consumption is estimated by the Panta Rhei Regio model, which projects growth rates of settlement and traffic areas until 2020. The results show that although land development will decline significantly in the next years, it will still clearly remain above the 30-ha-target level. As the simulation is modeled on county level the results also indicate the need to specify detailed quantity standards at regional level. A definition of subdivided targets for states, regions and municipalities offers the opportunity to improve the ongoing German debate on open space preservation and to initiate greater efforts on the way to a more efficient use of natural resource land.
Adolescents’ perceptions of parental practices: A cross‐national comparison of Canada, France, and Italy
Authors: Claes Michel , Perchec Cyrille , Miranda Dave , Benoit Amélie , Bariaud Françoise , Lanz Margherita , Marta Elena , Éric Lacourse
Published: July 2010

This study compares two dimensions of parenting—emotional bonding and control—as perceived by adolescents living in three countries: Canada (province of Québec), France, and Italy. A cross‐sectional sample was composed of 1256 adolescents who filled out a self‐report questionnaire. Multiple Correspondence Analyses provided a graphic synthesis of cross‐cultural results. Results indicate that parents are perceived as highly emotionally bonded, yet the perception of parental control produced two contrasting models. Canadian adolescents perceive less control and disciplinary actions from parents, and more tolerance. Conversely, Italian adolescents perceive more requirements and rules, and stricter disciplinary actions, while French adolescents’ perceptions fall between the two. Results also suggested a gradual decrease in the perception of parental control between the ages of 11 and 19 years across all three countries. This reduction in parental constraints is perceived earlier by Canadian adolescents and later by Italian adolescents.
Developmental Profiles of Preschool Children With Spastic Diplegic and Quadriplegic Cerebral Palsy
Authors: Lee Ya‐Chen , Wu Ching‐Yi , Liaw Mei‐Yun , Lin Keh‐Chung , Tu Ya‐Wen , Chen Chia‐Ling , Chen Chung‐Yao , Liu Wen‐Yu
Published: July 2010

Cerebral palsy (CP) is a disorder of movement and posture control with multiple impairments. The clinical manifestations of CP vary among children. The aim of this study was to compare the developmental profiles of preschool children with either of two types of CP: spastic diplegic (SD) CP and spastic quadriplegic (SQ) CP. Relationships between the children's various developmental functions were also investigated. We recruited 137 children with spastic CP, aged 1‐5 years (mean age = 3.7 ± 2.1 years), and we classified them into two groups: SD (n= 59) and SQ (n= 78). The comparison group comprised 18 children with typical development. Developmental functions were assessed in all the children, using the Chinese Child Development Inventory with the updated norms. This scale addressed eight functional domains: gross motor ability, fine motor ability, expressive language ability, concept comprehension ability, situation comprehension ability, self‐help ability, personal‐social skills, and general development. A development quotient (DQ) was determined for each domain as a percentage of the developmental age divided by the chronological age. The developmental profiles of the CP subtypes were found to differ. Children with SQ were found to have lower DQs than those with SD (p< 0.01). There was also a difference in the distribution of DQs between the SD and SQ groups, although the lowest DQ in both groups was for the gross motor domain. An uneven delay in the development of gross motor function was found in both groups of children with CP. Motor functions, including gross motor and fine motor functions, were significantly related to self‐help ability. Complex and significant correlations among developmental functions were also identified in children with CP. The findings in the present study may allow clinicians to anticipate the developmental profile of children with CP on the basis of whether they have the SD or SQ subtype. This, in turn, is likely to facilitate individual assessment, goal setting, and the planning of interventions in children with CP.
Repair of the Canine Vertebral Lamina With a Combination of Autologous Micromorselized Bone and Poly‐Lactic Acid Gel After a Total Laminectomy
Authors: Chuang Jin‐Peng , Chang Chih‐Peng , Shen Hung‐Tau , Kao Jiun , Yan Jing‐Lung
Published: July 2010

The complications of a total laminectomy can include epidural scar adhesion, secondary vertebral canal stenosis and lumbar instability. The aim of this study was to assess the ability of a combination of autologous micromorselized bone and polylactic acid (PLA) gel to stimulate bone repair within canine vertebral lamina defects, as well as to prevent peridural adhesion following a laminectomy. Twenty dogs underwent a L1, L3 and L5 laminectomy after a pre‐computed tomography examination. The 60 laminectomies were divided into 4 groups, and underwent the following treatments: Group A were treated with a combination of autologous micromorselized bone and PLA gel (n = 16); Group B were treated with micromorselized bone only (n = 16); Group C with PLA gel only (n = 14); and Group D were left untreated as they were the blank controls (n = 14). Vertebral laminae were harvested at 4th and 8th weeks, and examined by computed tomography and histological staining. Significant bone regeneration was observed at 4 and 8 weeks in Groups A and B, although the newly formed bone in the latter group was more irregular in shape. Spinal canal cross‐sectional areas in Group B decreased as compared with those in Group A(p < 0.05), and the degree of peridural adhesion in Groups A and C was significantly lower compared with Groups B and D (p < 0.05). These findings indicate that a combination of micromorselized bone and PLA gel may provide a better strategy for the treatment of spinal stenosis.
Outcome of Physical Therapy Intervention on Ventilator Weaning and Functional Status
Authors: Yang Pei‐Hsuan , Wang Chuan‐Sheng , Wang Yen‐Ching , Yang Chih‐Jen , Hung Jen‐Yu , Hwang Jhi‐Jhu , Wang Tung‐Heng , Chuang I‐Chun , Huang Ming‐Shyan
Published: July 2010

Our study aimed to understand the characteristics of ventilator dependence in patients at a respiratory care center and the potential effects of physical therapy on ventilator weaning and patients' functional status. Prospective data collection consisted of the following: (1) demographic data, including name, gender, age, diagnosis, the Acute Physiology and Chronic Health Evaluation as a severity of the disease, modified Glasgow Coma Scale, mobility at the time of admission, and days of hospitalization; (2) Rapid shallow breathing index (RSBI) as a predictive indicator of ventilator weaning, including indicators of ventilator weaning were collected from the respiratory flow sheet; and (3) Barthel index. Between July 1 and December 31, 2007, 126 patients were admitted to the respiratory care center, and those who required mechanical ventilation for more than 14 days were enrolled. Fifty‐five subjects received physical therapy. The RSBI in patients who received physical therapy was 75.7 ± 37.9 before therapy and 80.0 ± 48.5 afterwards, while the Barthel index increased from 0.8 ± 1.4 to 1.9 ± 2.5 (p < 0.05). The RSBI decreased as time of physical therapy lengthened, but not significantly (r = 0.12, p = 0.44). The success rate of ventilator weaning in patients receiving physical therapy intervention versus non‐physical therapy intervention was 58.2% and 40.9%, respectively. The results indicated that lengthening the physical therapy intervention time enhanced the ventilator weaning success rate while mobility was not affected (r = −0.11, p = 0.41). Physical therapy may be offered to ventilator‐dependent patients in line with their individual needs to improve or maintain basic mobility.