bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutagenesis as a Tool in Plant Genetics, Functional Genomics, and Breeding
Authors: Sikora Per , Chawade Aakash , Larsson Mikael , Olsson Johanna , Olsson Olof
Published: January 2012

Plant mutagenesis is rapidly coming of age in the aftermath of recent developments in high-resolution molecular and biochemical techniques. By combining the high variation of mutagenised populations with novel screening methods, traits that are almost impossible to identify by conventional breeding are now being developed and characterised at the molecular level. This paper provides a comprehensive overview of the various techniques and workflows available to researchers today in the field of molecular breeding, and how these tools complement the ones already used in traditional breeding. Both genetic (Targeting Induced Local Lesions in Genomes; TILLING) and phenotypic screens are evaluated. Finally, different ways of bridging the gap between genotype and phenotype are discussed.
The Bridge Helix of RNA Polymerase Acts as a Central Nanomechanical Switchboard for Coordinating Catalysis and Substrate Movement
Authors: Weinzierl Robert O. J.
Published: January 2012

The availability ofin vitroassembly systems to produce recombinant archaeal RNA polymerases (RNAPs) offers one of the most powerful experimental tools for investigating the still relatively poorly understood molecular mechanisms underlying RNAP function. Over the last few years, we pioneered new robot-based high-throughput mutagenesis approaches to study structure/function relationships within various domains surrounding the catalytic center. The Bridge Helix domain, which appears in numerous X-ray structures as a 35-amino-acid-long alpha helix, coordinates the concerted movement of several other domains during catalysis through kinking of two discrete molecular hinges. Mutations affecting these kinking mechanisms have a direct effect on the specific catalytic activity of RNAP and can in some instances more than double it. Molecular dynamics simulations have established themselves as exceptionally useful for providing additional insights and detailed models to explain the underlying structural motions.
An Unusual Case of Gastrointestinal Bleeding
Authors: Fiorino Kristin N. , Lestini Brian , Nichols Kim E. , Anupindi Sudha A. , Maqbool Asim
Published: January 2012

A 10-year-old boy presented with a 3-day history of worsening abdominal pain, fever, emesis and melena. Abdominal ultrasound revealed a right upper quadrant mass that was confirmed by computed tomography angiogram (CTA), which showed an 8 cm well-defined retroperitoneal vascular mass.123Iodine metaiodobenzylguanidine (123MIBG) scan indicated uptake only in the abdominal mass. Subsequent biopsy revealed a paraganglioma that was treated with chemotherapy. This case represents an unusual presentation of a paraganglioma associated with gastrointestinal (GI) bleeding and highlights the utility of CTA and123MIBG in evaluation and treatment.
Cervical Disc Herniation Causing Brown-Séquard's Syndrome: A Case Report and Literature Review
Authors: Rustagi Tarush , Badve Siddharth , Maniar Hemil , Parekh Aseem N.
Published: January 2012

Brown-Séquard's syndrome (BSS) is caused by hemisection or hemicompression of the cord leading to ipsilateral motor deficit and contralateral sensory loss. Cervical disc herniation has been reported to be a rare cause of Brown-Séquard's syndrome. We describe a rare case of multilevel cervical disc herniation presenting as BSS. The condition was confirmed by MRI scan. Cervical corpectomy, decompression, and fusion gave a satisfying result. Pertinent literature has been reviewed.
Inhibitory Effect of Polyphenol-Rich Fraction from the Bark ofAcacia mearnsiion Itching Associated with Allergic Dermatitis
Authors: Ikarashi Nobutomo , Sato Wataru , Toda Takahiro , Ishii Makoto , Ochiai Wataru , Sugiyama Kiyoshi
Published: January 2012

We examined the inhibitory effect of polyphenol-rich aqueous extract from the bark ofAcacia mearnsii(PrA) on itching associated with atopic dermatitis (AD). HR-1 mice were fed a normal diet, special diet (AD group), or special diet containing 3% PrA (PrA group) for 6 weeks. In the AD group, itching frequency and transepidermal water loss increased compared to the control group. In the PrA group, an improvement in atopic dermatitis symptoms was observed. Ceramide expression in the skin decreased in the AD group compared to the control group, but no decrease was observed in the PrA group. mRNA expression of ceramidase decreased in the PrA group compared to the AD group. The results of this study have revealed that PrA inhibits itching in atopic dermatitis by preventing the skin from drying. It is considered that the mechanism by which PrA prevents the skin from drying involves the inhibition of increased ceramidase expression associated with atopic dermatitis.
Efficient Method to Approximately Solve Retrial Systems with Impatience
Authors: Gimenez-Guzman Jose Manuel , Domenech-Benlloch M. Jose , Pla Vicent , Martinez-Bauset Jorge , Casares-Giner Vicente
Published: January 2012

We present a novel technique to solve multiserver retrial systems with impatience. Unfortunately these systems do not present an exact analytic solution, so it is mandatory to resort to approximate techniques. This novel technique does not rely on the numerical solution of the steady‐state Kolmogorov equations of the Continuous Time Markov Chain as it is common for this kind of systems but it considers the system in its Markov Decision Process setting. This technique, known as value extrapolation, truncates the infinite state space using a polynomial extrapolation method to approach the states outside the truncated state space. A numerical evaluation is carried out to evaluate this technique and to compare its performance with previous techniques. The obtained results show that value extrapolation greatly outperforms the previous approaches appeared in the literature not only in terms of accuracy but also in terms of computational cost.
Infinitely Many Homoclinic Orbits for 2nth‐Order Nonlinear Functional Difference Equations Involving thep‐Laplacian
Authors: He Xiaofei
Published: January 2012

By establishing a new proper variational framework and using the critical point
theory, we establish some new existence criteria to guarantee that the 2nth‐order nonlinear difference equation containing both advance and retardation with p‐Laplacian Δn(r(t − n)φp(Δnu(t − 1))) + q(t)φp(u(t)) = f(t, u(t + n), …, u(t), …, u(t − n)), n ∈ ℤ(3), t ∈ ℤ, has infinitely many homoclinic orbits, where φp(s) is p‐Laplacian operator;φp(s) = |s|p−2s(1 < p < ∞)r, q, f are nonperiodic in t. Our conditions on the potential are rather relaxed, and some existing results in the literature are improved.
Optimising Human Mesenchymal Stem Cell Numbers for Clinical Application: A Literature Review
Authors: Fossett E. , Khan W. S.
Published: January 2012

Adult mesenchymal stem cells (MSCs) are being investigated further for their use in stem cell therapies. However, as they are found in very low numbers in adult tissue, expansionin vitrois required to produce desired MSC numbers for clinical application. The need for effective cell-based therapies is increasing due to a rise in the ageing population, increasing the prevalence of musculoskeletal disorders. This review investigates how factors, age and gender of donor, as well as seeding density can affect MSC expansion. Age and gender of donor have received mixed results from studies, whereas seeding density studies have produced consistent results for numerous MSC sources, favouring lower seeding densities. Further research is required to reduce the risk of infection, loss of cell characterisation in cell culture, and making cell-based therapies more cost effective through creating rapid expansion of MSCs regardless of patient factors.
Mouthpart Morphology of Three Sympatric Native and Nonnative Gammaridean Species:Gammarus pulex,G. fossarum, andEchinogammarus berilloni(Crustacea: Amphipoda)
Authors: Mayer Gerd , Maas Andreas , Waloszek Dieter
Published: January 2012

In the last 20 years several nonnative amphipod species have immigrated inland waters of Germany and adjacent central European countries. Some of them have been very successful and could establish stabile populations. In some places, they have even replaced native or earlier established species. The gammaridEchinogammarus berillonioriginates from the Atlantic region of France and the north-western part of Spain and coexists in some central European waters with the nativeGammarus pulexandG. fossarum. Here, we describe and compare the mouthparts and other structures involved in food acquisition of these three sympatric gammaridean species. Our hypothesis was that differences in the mode of feeding of the three species could be the reason for their coexistence and that these differences would be expressed in differences in mouthpart morphology. The results of our SEM study demonstrate that there are indeed interspecific differences in details of the morphology of the feeding structures. This is especially true for the setation of antennae, maxillulae, gnathopods, and third uropods, which can be interpreted as adaptations to special modes of feeding. Generally, all three species are omnivorous, but specializations in details point to the possibility to use some food resources in a special effective way.
Unilateral NMR: a Noninvasive Tool for Monitoring In Situ the Effectiveness of Intervention to Reduce the Capillary Raise of Water in an Ancient Deteriorated Wall Painting
Authors: Di Tullio Valeria , Proietti Noemi , Gentile Gennaro , Giani Elisabetta , Poggi Domenico , Capitani Donatella
Published: January 2012

Portable unilateral NMR was used to quantitatively map in a fully noninvasive way the moisture distribution in an ancient deteriorated wall painting before and after an intervention to reduce the capillary raise of water through the wall. Maps obtained at a depth of 0.5 cm clearly showed the path of the capillary raise and indicated that, after the intervention, the moisture level was reduced. Maps obtained by measuring the first layers of the wall painting were affected by the critical environmental conditions of the second hypogeous level of St. Clement Basilica, Rome, and by the presence of salts efflorescence and encrustations on the surface of the wall painting. The morphology and the elemental composition of salts investigated by SEM-EDS indicated that efflorescences and encrustations were mostly constituted of gypsum and calcite. The presence of these salts is explained with the presence of high concentration of carbon dioxide and sulphur-rich particles due to pollution which, along with the high-moisture level and the extremely feeble air circulation, cause recarbonation and sulphation processes on the plaster surface.
From Rat to Human: Regulation of Renin-Angiotensin System Genes by Sry
Authors: Prokop Jeremy W. , Watanabe Ingrid Kazue Mizuno , Turner Monte E. , Underwood Adam C. , Martins Almir S. , Milsted Amy
Published: January 2012

The testis determining protein, Sry, has functions outside of testis determination. Multiple Sry loci are found on the Y-chromosome. Proteins from these loci have differential activity on promoters of renin-angiotensin system genes, possibly contributing to elevation of blood pressure. Variation at amino acid 76 accounts for the majority of differential effects by rat proteins Sry1 and Sry3. Human SRY regulated rat promoters in the same manner as rat Sry, elevatingAgt, Ren, andAcepromoter activity while downregulatingAce 2. Human SRY significantly regulated human promoters ofAGT, REN, ACE2, AT2,andMAScompared to control levels, elevatingAGTandRENpromoter activity while decreasingACE2, AT2,andMAS. While the effect of human SRY on individual genes is often modest, we show that many different genes participating in the renin-angiotensin system can be affected by SRY, apparently in coordinated fashion, to produce more Ang II and less Ang-(1–7).
Optimal Control of Gene Mutation in DNA Replication
Authors: Yu Juanyi , Li Jr-Shin , Tarn Tzyh-Jong
Published: January 2012

We propose a molecular-level control system view of the gene mutations in DNA replication from the finite field concept. By treating DNA sequences as state variables, chemical mutagens and radiation as control inputs, one cell cycle as a step increment, and the measurements of the resulting DNA sequence as outputs, we derive system equations for both deterministic and stochastic discrete-time, finite-state systems of different scales. Defining the cost function as a summation of the costs of applying mutagens and the off-trajectory penalty, we solve the deterministic and stochastic optimal control problems by dynamic programming algorithm. In addition, given that the system is completely controllable, we find that the global optimum of both base-to-base and codon-to-codon deterministic mutations can always be achieved within a finite number of steps.
Dynamic Magnetic Resonance Imaging Demonstrates the Integrity of Perineal Reconstruction following Cylindrical Abdominoperineal Excision with Reconstruction of the Pelvic Floor Using Porcine Collagen
Authors: Kavanagh D. O. , Imran H. , Almoudaris A. , Ziprin P. , Faiz O.
Published: January 2012

A 72-year-old female presented with a six-month history of increased frequency of defecation, rectal bleeding, and severe rectal pain. Digital rectal examination and endoscopy revealed a low rectal lesion lying anteriorly. This was confirmed histologically as adenocarcinoma. Radiological staging was consistent with a T3N2rectal tumour. Following long-course chemoradiotherapy repeat staging did not identify any metastatic disease. She underwent a laparoscopic cylindrical abdominoperineal excision withen blocresection of the coccyx and posterior wall of the vagina with a negative circumferential resection margin. The perineal defect was reconstructed with Permacol (biological implant, Covidien) mesh. She had no clinical evidence of a perineal hernia at serial followup. Dynamic MRI images of the pelvic floor obtained during valsalva at 10 months revealed an intact pelvic floor. A control case that had undergone a conventional abdominoperineal excision with primary perineal closure without clinical evidence of herniation was also imaged. This confirmed subclinical perineal herniation with significant downward migration of the bowel and bladder below the pubococcygeal line. We eagerly await further evidence supporting a role for dynamic MR imaging in assessing the integrity of a reconstructed pelvic floor following cylindrical abdominoperineal excision.
The Use of Interferon Gamma Release Assays in the Diagnosis of Active Tuberculosis
Authors: Vesenbeckh Silvan M. , Schönfeld Nicolas , Mauch Harald , Bergmann Thorsten , Wagner Sonja , Bauer Torsten T. , Rüssmann Holger
Published: January 2012

Interferon gamma release assays (IGRAs) arein vitroimmunologic diagnostic tests used to identifyMycobacterium tuberculosisinfection. They cannot differentiate between latent and active infections. The cutoff suggested by the manufacturer is 0.35 IU/mL for latent tuberculosis. As IGRA tests were recently approved for the differential diagnosis of active tuberculosis, we assessed the diagnostic accuracy of the latest generation IGRA for detection of active tuberculosis in a low-incidence area in Germany. Our consecutive case series includes 61 HIV negative,Mycobacterium tuberculosisculture positive patients, as well as 234 control patients. The retrospective analysis was performed over a period of two years. In 11/61 patients with active tuberculosis (18.0%) the test result was <0.35 IU/mL, resulting in a sensitivity of 0.82. We recommend establishing a new cut-off value for the differential diagnosis of active tuberculosis assessed by prospective clinical studies and in various regions with high and low prevalence of tuberculosis.
A Fast and Reliable Hybrid Data Delivery Protocol for Large-Scale Heterogeneous Sensor Networks
Authors: Kang Sanggil , Lim Yujin , Lopez Wilmarc , Hwang Hoyoung
Published: January 2012

We propose a hybrid data delivery method for the large-scale heterogeneous sensor networks, which is a fast and reliable delivery protocol for the aggregated data from the sinks to the GW. We develop a new multicriteria-ranking algorithm which determines multiple forwarders for each hop by ranking neighbor nodes. To rank the nodes, we compute the fitness value using features for each node such as the received signal strength, nodal delay, and hop distance. We determine the time of sending among forwarders using the waiting time assignment algorithm. In the experimental section, we show that our method outperforms conventional data delivery protocols in terms of data delivery ratio and end-to-end delay.
Right-Sided Pyriform Sinus Fistula: A Case Report and Review of the Literature
Authors: Cain Rachel B. , Kasznica Peter , Brundage William J.
Published: January 2012

Objectives. Pyriform sinus fistulae arise from disturbances in the development of the fetal third and fourth branchial pouches and are predominantly found on the left side. We report the rare case of a right-sided pyriform sinus fistula presenting as a lateral neck abscess.Study Design. Case report.Methods. A 24-year-old woman presented with a two-week history of right-sided neck abscess. A fluoroscopic sinogram revealed a fistulous tract extending from the abscess to the apex of the right pyriform sinus. It was determined that the fistula was likely a third or fourth branchial remnant, a rare right-sided finding. Chemocauterization of the fistulous tract with 40% trichloroacetic acid was used to successfully treat the patient.Results. Approximately 93–97% of branchial pouch anomalies are left sided. Treatment options include surgical excision and cauterization.Conclusions. Branchial cleft cyst and pyriform sinus fistula must be considered in the diagnosis of cervical abscess in either side of the neck.
Failure of Iniparib to Inhibit Poly(ADP-Ribose) Polymerase In Vitro
Authors: Patel Anand G. , De Lorenzo Silvana B. , Flatten Karen S. , Poirier Guy G. , Kaufmann Scott H.
Published: January 2012

Purpose: Poly(ADP-ribose) polymerase (PARP) inhibitors are undergoing extensive clinical testing for their single-agent activity in homologous recombination (HR)-deficient tumors and ability to enhance the action of certain DNA-damaging agents. Compared with other PARP inhibitors in development, iniparib (4-iodo-3-nitrobenzamide) is notable for its simple structure and the reported ability of its intracellular metabolite 4-iodo-3-nitrosobenzamide to covalently inhibit PARP1 under cell-free conditions. The present preclinical studies were conducted to compare the actions iniparib with the more extensively characterized PARP inhibitors olaparib and veliparib.

Experimental Design: The abilities of iniparib, olaparib, and veliparib to (i) selectively induce apoptosis or inhibit colony formation in HR-deficient cell lines, (ii) selectively sensitize HR-proficient cells to topoisomerase I poisons, and (iii) inhibit formation of poly(ADP-ribose) polymer (pADPr) in intact cells were compared.

Results: Consistent with earlier reports, olaparib and veliparib selectively induced apoptosis and inhibited colony formation in cells lacking BRCA2 or ATM. Moreover, like earlier generation PARP inhibitors, olaparib and veliparib sensitized cells to the topoisomerase I poisons camptothecin and topotecan. Finally, olaparib and veliparib inhibited formation of pADPr in intact cells. In contrast, iniparib exhibited little or no ability to selectively kill HR-deficient cells, sensitize cells to topoisomerase I poisons, or inhibit pADPr formation in situ. In further experiments, iniparib also failed to sensitize cells to cisplatin, gemcitabine, or paclitaxel.

Conclusions: While iniparib kills normal and neoplastic cells at high (>40 μmol/L) concentrations, its effects are unlikely to reflect PARP inhibition and should not be used to guide decisions about other PARP inhibitors. Clin Cancer Res; 18(6); 1655–62. ©2012 AACR.
Agonist-Independent Constitutive Activity of Angiotensin II Receptor Promotes Cardiac Remodeling in Mice
Authors: Yasuda Noritaka , Akazawa Hiroshi , Ito Kaoru , Shimizu Ippei , Kudo-Sakamoto Yoko , Yabumoto Chizuru , Yano Masamichi , Yamamoto Rie , Ozasa Yukako , Minamino Tohru , Naito Atsuhiko T. , Oka Toru , Shiojima Ichiro , Tamura Kouichi , Umemura Satoshi , Paradis Pierre , Nemer Mona , Komuro Issei
Published: January 2012

The angiotensin II (Ang II) type 1 (AT
1
) receptor mainly mediates the physiological and pathological actions of Ang II, but recent studies have suggested that AT
1
receptor inherently shows spontaneous constitutive activity even in the absence of Ang II in culture cells. To elucidate the role of Ang II–independent AT
1
receptor activation in the pathogenesis of cardiac remodeling, we generated transgenic mice overexpressing AT
1
receptor under the control of α-myosin heavy chain promoter in angiotensinogen-knockout background (AT
1
Tg-AgtKO mice). In AT
1
Tg-AgtKO hearts, redistributions of the Gα
q11
subunit into cytosol and phosphorylation of extracellular signal-regulated kinases were significantly increased, compared with angiotensinogen-knockout mice hearts, suggesting that the AT
1
receptor is constitutively activated independent of Ang II. As a consequence, AT
1
Tg-AgtKO mice showed spontaneous systolic dysfunction and chamber dilatation, accompanied by severe interstitial fibrosis. Progression of cardiac remodeling in AT
1
Tg-AgtKO mice was prevented by treatment with candesartan, an inverse agonist for the AT
1
receptor, but not by its derivative candesartan-7H, deficient of inverse agonism attributed to a lack of the carboxyl group at the benzimidazole ring. Our results demonstrate that constitutive activity of the AT
1
receptor under basal conditions contributes to the cardiac remodeling even in the absence of Ang II, when the AT
1
receptor is upregulated in the heart.
Analysis of Collaborative Communication for Linguistic Cues of Cognitive Load
Authors: Khawaja M. Asif , Chen Fang , Marcus Nadine
Published: January 2012

Objective:

Analyses of novel linguistic and grammatical features, extracted from transcribed speech of people working in a collaborative environment, were performed for cognitive load measurement.

Background:

Prior studies have attempted to assess users’ cognitive load with several measures, but most of them are intrusive and disrupt normal task flow. An effective measurement of people’s cognitive load can help improve their performance by deploying appropriate output and support strategies accordingly.

Methods:

The authors studied 33 members of bushfire management teams working collaboratively in computerized incident control rooms and involved in complex bushfire management tasks. The participants’ communication was analyzed for some novel linguistic features as potential indices of cognitive load, which included sentence length, use of agreement and disagreement phrases, and use of personal pronouns, including both singular and plural pronoun types.

Results:

Results showed users’ different linguistic and grammatical patterns with various cognitive load levels. Specifically, with high load, people spoke more and used longer sentences, used more words that indicated disagreement with other team members, and exhibited increased use of plural personal pronouns and decreased use of singular pronouns.

Conclusion:

The article provides encouraging evidence for the use of linguistic and grammatical analysis for measuring users’ cognitive load and proposes some novel features as cognitive load indices.

Application:

The proposed approach may be applied to many data-intense and safety-critical task scenarios, such as emergency management departments, for example, bushfire or traffic incident management centers; air traffic control rooms; and call centers, where speech is used as part of everyday tasks.
Can Vestibular‐Evoked Myogenic Potentials Help Differentiate Ménière Disease from Vestibular Migraine?
Authors: Zuniga M. Geraldine , Janky Kristen L. , Schubert Michael C. , Carey John P.
Published: January 2012

Objectives

To characterize both cervical and ocular vestibular‐evoked myogenic potential (cVEMP, oVEMP) responses to air‐conducted sound (ACS) and midline taps in Ménière disease (MD), vestibular migraine (VM), and controls, as well as to determine if cVEMP or oVEMP responses can differentiate MD from VM.

Study Design

Prospective cohort study.

Setting

Tertiary referral center.

Subjects and Methods

Unilateral definite MD patients (n = 20), VM patients (n = 21) by modified Neuhauser criteria, and age‐matched controls (n = 28). cVEMP testing used ACS (clicks), and oVEMP testing used ACS (clicks and 500‐Hz tone bursts) and midline tap stimuli (reflex hammer and Mini‐Shaker). Outcome parameters were cVEMP peak‐to‐peak amplitudes and oVEMP n10 amplitudes.

Results

Relative to controls, MD and VM groups both showed reduced click‐evoked cVEMP (P <. 001) and oVEMP (P <. 001) amplitudes. Only the MD group showed reduction in tone‐evoked amplitudes for oVEMP. Tone‐evoked oVEMPs differentiated MD from controls (P =. 001) and from VM (P =. 007). The oVEMPs in response to the reflex hammer and Mini‐Shaker midline taps showed no differences between groups (P >. 210).

Conclusions

Using these techniques, VM and MD behaved similarly on most of the VEMP test battery. A link in their pathophysiology may be responsible for these responses. The data suggest a difference in 500‐Hz tone burst–evoked oVEMP responses between MD and MV as a group. However, no VEMP test that was investigated segregated individuals with MD from those with VM.
Submandibular Space Abscess
Authors: Mohamadi Ardehali Mojtaba , Jafari Mehrdad , Bagheri Hagh Ali
Published: January 2012

Objective

In this study, the authors compare the external cervical approach with their new minimally invasive technique of intraoral drainage for submandibular space abscesses.

Study Design and Setting

In a randomized clinical trial, 40 patients with submandibular abscess entered the study in Amiralam Hospital of Tehran.

Subjects and Methods

Subjects were randomly divided in 2 groups of the classic external approach with skin incision in the submandibular area and the intraoral approach for abscess drainage. The data, including demographic details, need for a repeated surgery, days of postoperative hospitalization, scar formation, and possible complications, were recorded and analyzed.

Results

The patients required an average of 5.5 and 5.4 days of postoperative intravenous (IV) antibiotics in the intraoral and external approaches, respectively, and were discharged from the hospital 1 day after the cessation of the IV antibiotics. There was no significant difference between the 2 groups in terms of postoperative hospitalization and days of intravenous antibiotics administration. No patients had weakness in their marginal mandibular nerve or skin scarring postoperatively in the intraoral approach group.

Conclusion

This study reveals that submandibular abscess in selected cases can be successfully treated with an intraoral drainage approach, which is a better choice than the external technique in terms of better cosmetic outcome. Postoperative care in these patients is much easier because there is no need for daily irrigation and dressing of the wound. Also, there is possibly no risk for injury to surrounding nerves.
Electrocochleography during Cochlear Implantation for Hearing Preservation
Authors: Mandalà Marco , Colletti Liliana , Tonoli Giovanni , Colletti Vittorio
Published: January 2012

Objective

To determine whether intraoperative electrocochleography during cochlear implant surgery provides online feedback to modify surgical procedure, reduce trauma, and increase preservation of residual hearing.

Study Design

Prospective cohort study.

Setting

Tertiary referral center, Otolaryngology Department, University of Verona.

Subjects and Methods

Twenty‐seven adult patients undergoing cochlear implant surgery who had low‐ to mid‐frequency (0.25‐2 kHz) auditory thresholds measured preoperatively were enrolled. Fifteen subjects had compound action potentials measured to assess cochlear function during surgery. In those patients, surgery was modified according to electrocochleographic feedback. Twelve control subjects underwent cochlear implant surgery with blinded electrocochleographic monitoring.

Results

The average preoperative pure‐tone audiometry thresholds (0.25‐2 kHz) were 74.3 ± 10.2 and 81.5 ± 12.7 dB hearing level (HL) in the electrocochleographic feedback and control cohorts, respectively (P >. 05). Compound action potential recordings showed a mean maximum latency shift of 0.63 ± 0.36 ms and normalized amplitude deterioration of 59% ± 19% during surgery. All of these changes reverted to normal after electrode insertion in all but 1 subject in the electrocochleographic feedback group. The average shifts in postoperative pure‐tone average threshold (0.25‐2 kHz), evaluated before activation, were 8.7 ± 4.3 and 19.2 ± 11.4 dB HL in the electrocochleographic feedback and control cohorts, respectively (P =. 0051). Complete hearing preservation (loss of ≤10 dB) at 1 month before activation was achieved in 85% (11/13) of electrocochleographic feedback subjects and in 33% (4/12) of control patients (P =. 0154).

Conclusion

Monitoring cochlear function with electrocochleography gives real‐time feedback during surgery, providing objective data that might help in modifying the surgical technique in ways that can improve the rate of hearing preservation.
Genetic analyses of smoking initiation, persistence, quantity, and age-at-onset of regular cigarette use in Brazilian families: the Baependi Heart Study
Authors: Horimoto Andréa RVR , Oliveira Camila M , Giolo Suely R , Soler Júlia P , de Andrade Mariza , Krieger José E , Pereira Alexandre C
Published: January 2012

Background

The purpose of this study was to estimate the genetic influences on the initiation of cigarette smoking, the persistence, quantity and age-at-onset of regular cigarette use in Brazilian families.

Methods

The data set consisted of 1,694 individuals enrolled in the Baependi Heart Study. The heritability and the heterogeneity in genetic and environmental variance components by gender were estimated from variance components approaches, using the SOLAR (Sequential Oligogenic Linkage Analysis Routines) computer package. The mixed-effects Cox model was used for the genetic analysis of the age-at onset of regular cigarette use.

Results

The heritability estimates were high (> 50%) for smoking initiation and were intermediate, ranging from 23.4 to 31.9%, for smoking persistence and quantity. Significant evidence for heterogeneity in variance components by gender was observed for smoking initiation and age-at-onset of regular cigarette use. Genetic factors play an important role in the interindividual variation of these phenotypes in females, while in males there is a predominant environmental component, which could be explained by greater social influences in the initiation of tobacco use.

Conclusions

Significant heritabilities were observed in smoking phenotypes for both males and females from the Brazilian population. These data add to the literature and are concordant with the notion of significant biological determination in smoking behavior. Samples from the Baependi Heart Study may be valuable for the mapping of genetic loci that modulate this complex biological trait.
No effect of recumbency duration on the occurrence of post-lumbar puncture headache with a 22G cutting needle
Authors: Kim Sung R , Chae Hyun S , Yoon Mi J , Han Jung H , Cho Kwang J , Chung Sun J
Published: January 2012

Background

Supine recumbence has been widely performed to prevent post-lumbar puncture headache (PLPH). However, the optimal duration of supine recumbence is controversial. The aim of the study is to compare the occurrence of PLPH according to the duration of supine recumbence in patients with neurological disorders.

Methods

A non-equivalent control/experimental pre-/post-test study design was used. Seventy consecutive patients were prospectively enrolled between July 2007 and July 2008. Thirty-five patients underwent supine recumbence for four hours after lumbar puncture (Group 1) and 35 patients underwent supine recumbence for one hour (Group 2).

Results

The overall frequency of PLPH was 31.4%. The frequency of PLPH was not significantly different between the Group 1 (28.6%) and Group 2 (34.3%) (P = 0.607). In patients with PLPH, the median severity (P = 0.203) and median onset time of PLPH (P = 0.582) were not significantly different between the two groups. In a logistic regression analysis, the previous history of post-lumbar puncture headache was a significant risk factor for the occurrence of PLPH (OR = 11.250, 95% CI: 1.10-114.369, P = 0.041).

Conclusions

Our study suggests that short duration (one hour) of supine recumbence may be as efficient as long duration (four hours) of supine recumbence to prevent PLPH.
In vitro assessment of some sperm function following exposure to levonorgestrel in human fallopian tubes
Authors: Hermanny Alexia , Bahamondes M Valeria , Fazano Francisco , Marchi Nadia M , Ortiz Maria Elena , Genghini Maria Heloisa RR , Croxatto Horacio B , Bahamondes Luis
Published: January 2012

Background

The mechanism of action of levonorgestrel (LNG) as emergency contraception (EC) remains a subject of debate and its effect on sperm function has been only partially explained. The aim of this study was to assess whether LNG at a similar dose to those found in serum following oral intake for EC could affect spermatozoa when exposed to human fallopian tubes in vitro.

Methods

Fifteen mini-laparotomies were performed, the side on which ovulation occurred was recorded, and both tubes were removed and perfused with a suspension containing 1 × 10(6) motile spermatozoa, with or without LNG. Following 4-hour incubation, the tubes were sectioned to separate the isthmus and the ampulla. Each segment was flushed and the material was evaluated to quantify the number of motile sperm, the number of spermatozoa adhering to the oviductal epithelium and the acrosome reaction (AR) rate.

Results

The addition of LNG did not significantly alter the number of recovered motile spermatozoa either at the isthmus or at the ampulla, nor did it have any effect on the number of recovered spermatozoa adhered to the human tubal epithelium. Furthermore, LNG did not affect the AR rate. No significant differences were found even when the side on which ovulation occurred was taken into account.

Conclusions

In a similar dose to that observed in serum following oral intake for EC, LNG had no effect on the number of motile spermatozoa recovered from the human fallopian tubes in vitro, on their adhesion to the tubal epithelium, distribution or AR rate. The possible effect of LNG as EC on sperm function remains poorly understood.
Performance evaluation of the Pima™ point‐of‐care CD4 analyser using capillary blood sampling in field tests in South Africa
Authors: Glencross Deborah K , Coetzee Lindi M , Faal Mamsallah , Masango Martin , Stevens Wendy S , Venter WD Francois , Osih Regina
Published: January 2012

Background

Point‐of‐care CD4 testing can provide immediate CD4 reporting at HIV‐testing sites. This study evaluated performance of capillary blood sampling using the point‐of‐care Pima™ CD4 device in representative primary health care clinics doing HIV testing.

Methods

Prior to testing, prescribed capillary‐sampling and instrument training was undertaken by suppliers across all sites. Matching venous EDTA samples were drawn throughout for comparison to laboratory predicate methodology (PLG/CD4). In Phase I, Pima™ cartridges were pipette‐filled with EDTA venous blood in the laboratory (N = 100). In Phase II (N = 77), Pima™ CD4 with capillary sampling was performed by a single operator in a hospital‐based antenatal clinic. During subsequent field testing, Pima™ CD4 with capillary sampling was performed in primary health care clinics on HIV‐positive patients by multiple attending nursing personnel in a rural clinic (Phase‐IIIA, N = 96) and an inner‐city clinic (Phase‐IIIB, N = 139).

Results

Pima™ CD4 compared favourably to predicate/CD4 when cartridges were pipette‐filled with venous blood (bias ‐17.3 ± STDev = 36.7 cells/mm3; precision‐to‐predicate %CV < 6%). Decreased precision of Pima™ CD4 to predicate/CD4 (varying from 17.6 to 28.8%SIM CV; mean bias = 37.9 ± STDev = 179.5 cells/mm3) was noted during field testing in the hospital antenatal clinic. In the rural clinic field‐studies, unacceptable precision‐to‐predicate and positive bias was noted (mean 28.4%SIM CV; mean bias = +105.7 ± STDev = 225.4 cells/mm3). With additional proactive manufacturer support, reliable performance was noted in the subsequent inner‐city clinic field study where acceptable precision‐to‐predicate (11%SIM CV) and less bias of Pima™ to predicate was shown (BA bias ~11 ± STDev = 69 cells/mm3).

Conclusions

Variable precision of Pima™ to predicate CD4 across study sites was attributable to variable capillary sampling. Poor precision was noted in the outlying primary health care clinic where the system is most likely to be used. Stringent attention to capillary blood collection technique is therefore imperative if technologies like Pima™ are used with capillary sampling at the POC. Pima™ CD4 analysis with venous blood was shown to be reproducible, but testing at the point of care exposes operators to biohazard risk related to uncapping vacutainer samples and pipetting of blood, and is best placed in smaller laboratories using established principles of Good Clinical Laboratory Practice. The development of capillary sampling quality control methods that assure reliable CD4 counts at the point of care are awaited.
Polymersomes as nano-carriers to retain harmful recoil nuclides in alpha radionuclide therapy: a feasibility study
Authors: Thijssen L. , Schaart D. R. , de Vries D. , Morgenstern A. , Bruchertseifer F. , Denkova A. G.
Published: January 2012

Targeted alpha therapy has shown promising pre-clinical and clinical results in the fight against cancer. The use of in vivo generators, generating a highly cytotoxic cascade of alpha particles, is attracting increasing interest for clinical application. 225Ac is one of the nuclides that can serve as an in vivo generator. It is commercially available and provides four alpha particles with a total energy of 28 MeV per 225Ac decay. However, its alpha emitting daughter nuclides may escape from the target region due to recoil and cause unwanted toxicity in other parts of the body. In this paper, we investigate the feasibility of designing spherical, block-copolymer based nano-carriers (polymersomes) to retain the recoiling daughter nuclides. A Monte Carlo code, called NANVES, has been developed to simulate the range distributions of recoil atoms in different materials and to determine the optimum nano-carriers design. Recoil ranges in planar polystyrene films were determined experimentally and compared to simulations of the experiment, indicating that NANVES may provide accurate results. Simulations of various nano-carriers designs indicate that double-layered polymersomes with a diameter of 800 nm are capable of completely retaining the first daughter nuclide 221Fr, while the escape fraction of the third radioactive daughter 213Bi is reduced to 20% and the percentage of alpha particles emitted from escaped daughter products outside the nano-carriers is less than 10%.
Nuclear localization of parathyroid hormone-related peptide confers resistance to anoikis in prostate cancer cells
Authors: Park Serk In , McCauley Laurie K
Published: January 2012

Prostate cancer remains a leading cause of cancer-related death in men, largely attributable to distant metastases, most frequently to bones. Despite intensive investigations, molecular mechanisms underlying metastasis are not completely understood. Among prostate cancer-derived factors, parathyroid hormone-related peptide (PTHrP), first discovered as an etiologic factor for malignancy-induced hypercalcemia, regulates many cellular functions critical to tumor growth, angiogenesis, and metastasis. In this study, the role of PTHrP in tumor cell survival from detachment-induced apoptosis (i.e. anoikis) was investigated. Reduction ofPTHLH(encoding PTHrP) gene expression in human prostate cancer cells (PC-3) increased the percentage of apoptotic cells when cultured in suspension. Conversely, overexpression of PTHrP protected prostate cancer cells (Ace-1 and LNCaP, both typically expressing low or undetectable basal PTHrP) from anoikis. Overexpression of nuclear localization signal (NLS)-defective PTHrP failed to protect cells from anoikis, suggesting that PTHrP-dependent protection from anoikis is an intracrine event. A PCR-based apoptosis-related gene array showed that detachment increased expression of theTNFgene (encoding the proapoptotic protein tumor necrosis factor-α) fourfold greater in PTHrP-knockdown PC-3 cells than in control PC-3 cells. In parallel,TNFgene expression was significantly reduced in PTHrP-overexpressing LNCaP cells, but not in NLS-defective PTHrP overexpressing LNCaP cells, when compared with control LNCaP cells. Subsequently, in a prostate cancer skeletal metastasis mouse model, PTHrP-knockdown PC-3 cells resulted in significantly fewer metastatic lesions compared to control PC-3 cells, suggesting that PTHrP mediated antianoikis events in the bloodstream. In conclusion, nuclear localization of PTHrP confers prostate cancer cell resistance to anoikis, potentially contributing to prostate cancer metastasis.
Detecting Rare Variant Associations by Identity-by-Descent Mapping in Case-Control Studies
Authors: Browning Sharon R , Thompson Elizabeth A
Published: January 2012

Identity-by-descent (IBD) mapping tests whether cases share more segments of IBD around a putative causal variant than do controls. These segments of IBD can be accurately detected from genome-wide SNP data. We investigate the power of IBD mapping relative to that of SNP association testing for genome-wide case-control SNP data. Our focus is particularly on rare variants, as these tend to be more recent and hence more likely to have recent shared ancestry. We simulate data from both large and small populations and find that the relative performance of IBD mapping and SNP association testing depends on population demographic history and the strength of selection against causal variants. We also present an IBD mapping analysis of a type 1 diabetes data set. In those data we find that we can detect association only with the HLA region using IBD mapping. Overall, our results suggest that IBD mapping may have higher power than association analysis of SNP data when multiple rare causal variants are clustered within a gene. However, for outbred populations, very large sample sizes may be required for genome-wide significance unless the causal variants have strong effects.
Crossover Distribution and Frequency Are Regulated by him-5 in Caenorhabditis elegans
Authors: Meneely Philip M , McGovern Olivia L , Heinis Frazer I , Yanowitz Judith L
Published: January 2012

Mutations in the him-5 gene in Caenorhabditis elegans strongly reduce the frequency of crossovers on the X chromosome, with lesser effects on the autosomes. him-5 mutants also show a change in crossover distribution on both the X and autosomes. These phenotypes are accompanied by a delayed entry into pachytene and premature desynapsis of the X chromosome. The nondisjunction, progression defects and desynapsis can be rescued by an exogenous source of double strand breaks (DSBs), indicating that the role of HIM-5 is to promote the formation of meiotic DSBs. Molecular cloning of the gene shows that the inferred HIM-5 product is a highly basic protein of 252 amino acids with no clear orthologs in other species, including other Caenorhabditis species. Although him-5 mutants are defective in segregation of the X chromosome, HIM-5 protein localizes preferentially to the autosomes. The mutant phenotypes and localization of him-5 are similar but not identical to the results seen with xnd-1, although unlike xnd-1, him-5 has no apparent effect on the acetylation of histone H2A on lysine 5 (H2AacK5). The localization of HIM-5 to the autosomes depends on the activities of both xnd-1 and him-17 allowing us to begin to establish pathways for the control of crossover distribution and frequency.
Surrogate Genetics and Metabolic Profiling for Characterization of Human Disease Alleles
Authors: Mayfield Jacob A , Davies Meara W , Dimster-Denk Dago , Pleskac Nick , McCarthy Sean , Boydston Elizabeth A , Fink Logan , Lin Xin Xin , Narain Ankur S , Meighan Michael , Rine Jasper
Published: January 2012

Cystathionine-β-synthase (CBS) deficiency is a human genetic disease causing homocystinuria, thrombosis, mental retardation, and a suite of other devastating manifestations. Early detection coupled with dietary modification greatly reduces pathology, but the response to treatment differs with the allele of CBS. A better understanding of the relationship between allelic variants and protein function will improve both diagnosis and treatment. To this end, we tested the function of 84 CBS alleles previously sequenced from patients with homocystinuria by ortholog replacement in Saccharomyces cerevisiae. Within this clinically associated set, 15% of variant alleles were indistinguishable from the predominant CBS allele in function, suggesting enzymatic activity was retained. An additional 37% of the alleles were partially functional or could be rescued by cofactor supplementation in the growth medium. This large class included alleles rescued by elevated levels of the cofactor vitamin B6, but also alleles rescued by elevated heme, a second CBS cofactor. Measurement of the metabolite levels in CBS-substituted yeast grown with different B6 levels using LC–MS revealed changes in metabolism that propagated beyond the substrate and product of CBS. Production of the critical antioxidant glutathione through the CBS pathway was greatly decreased when CBS function was restricted through genetic, cofactor, or substrate restriction, a metabolic consequence with implications for treatment.
Randomized Trial of Oral Versus Sequential IV/Oral Antibiotic for Acute Pyelonephritis in Children
Authors: Bocquet Nathalie , Sergent Alaoui Aline , Jais Jean-Pierre , Gajdos Vincent , Guigonis Vincent , Lacour Bernard , Chéron Gérard
Published: January 2012

OBJECTIVE:

To confirm whether oral antibiotic treatment is as efficacious as sequential intravenous/oral antibiotic treatment in the prevention of renal scarring in children with acute pyelonephritis and scintigraphy-documented acute lesions.

METHODS:

In a prospective multicenter trial, children aged 1 to 36 months with their first case of acute pyelonephritis, a serum procalcitonin concentration ≥0.5 ng/mL, no known uropathy, and a normal ultrasound exam were randomized into 2 treatment groups. They received either oral cefixime for 10 days or intravenous ceftriaxone for 4 days followed by oral cefixime for 6 days. Patients with acute renal lesions detected on early dimercaptosuccinic acid scintigraphy underwent a follow-up scintigraphy 6 to 8 months later.

RESULTS:

The study included 171 infants and children. There were no significant differences between the 2 groups in any clinical characteristic. Initial scintigraphy results were abnormal for 119 children. Ninety-six children were measured for renal scarring at the follow-up scintigraphy (per protocol analysis population). The incidence of renal scarring was 30.8% in the oral treatment group and 27.3% for children who received the sequential treatment.

CONCLUSIONS:

Although this trial does not statistically demonstrate the noninferiority of oral treatment compared with the sequential treatment, our study confirmed the results of previously published reports and therefore supports the use of an oral antibiotic treatment of primary episodes of acute pyelonephritis in infants and young children.