bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of hyperbaric oxygen therapy on serological values of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF)
Authors: Jung Susanne , Wermker Kai , Poetschik Harald , Ziebura Thomas , Kleinheinz Johannes
Published: January 2011

Background

Hyperbaric oxygen (HBO) therapy is an effective adjunct treatment for ischemic disorders such as chronic infection or chronic wounds. It combines hyperoxic effects with the stimulating potential of post-therapeutic reactive hypoxia. As its crucial effects, stimulation of fibroblast growth, induction of collagen synthesis and the initiation of angiogenesis are discussed. Angiogenesis is a multistage process resulting in the growth of blood vessels. It includes degradation of extracellular matrix, proliferation and migration of different cell populations and finally formation of new vessel structures. This complex chain of procedures is orchestrated by different cytokines and growth factors. Crucial mediators of angiogenesis are basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF); theirin-vivofunction is still not fully understood.

Methods

Forty-three patients suffering from sudden sensorineural hearing loss or tinnitus were treated with HBO. The therapy included 10 sessions of 90 minutes each, one session a day. Serological levels of bFGF and VEGF were assessed by enzyme-linked immunosorbent assays performed according to the manufacturer's instructions on day 1, 2, 5 and 10 of HBO therapy and were compared to mean values of the control group, related to the patient's age and sex, and their development observed over the ten days of HBO.

Results

There was no sex- or age dependency of bFGF observed in the present study, whereas under HBO our results showed a significant mitigation of the bFGF concentration. In the present data, there was no connection between the VEGF concentration and the patients' ages. Women showed significantly higher levels of VEGF. There was no significant change of VEGF concentration or the VEGF/bFGF ratio during HBO. All scored results varied within the range of standard values as described in the current literature.

Conclusions

A significant effect of HBO on serum concentrations of bFGF and VEGF was not verified in the present study. Additional application of exogenous growth factors in conjunction with HBO was not obviously linked by a coherent cause-and-effect chain as far as wound healing is concerned.
Practices of entomophagy and entomotherapy by members of the Nyishi and Galo tribes, two ethnic groups of the state of Arunachal Pradesh (North-East India)
Authors: Chakravorty Jharna , Ghosh Sampat , Meyer-Rochow Victor Benno
Published: January 2011

We prepared a consolidated list of edible and therapeutic insects used in Arunachal Pradesh (N.E. India) by two tribal societies (i.e., the Nyishi of East Kameng and the Galo of West Siang). The list is based on thorough, semi-structured field-interviews with 20 informants of each tribal group. At least 81 species of local insects, belonging to 26 families and five orders of insects, namely Coleoptera (24 species), Orthoptera (17 species), Hemiptera (16 species), Hymenoptera (15 species) and Odonata (9 species), are being used as food among members of these two indigenous societies. However, Nyishi use overall more species of insects as food than Galo people do and consume mostly Coleoptera and Hemiptera; amongst the Galo, on the other hand, Odonata and Orthoptera dominate. The selection of the food insects amongst the Nyishi and Galo is dictated by traditional tribal beliefs as well as the taste and availability of the insects. Depending on the species, only particular or all developmental stages are consumed. Some food insects may be included in the local diet throughout the year, others only when seasonally available. Commonly specimens are being prepared for consumption by roasting, frying or boiling. Twelve species of insects are deemed therapeutically valuable by the locals and are being used by the tribes investigated to treat a variety of disorders in humans and domestic animals. Members of the Galo use a greater number of insect species for remedial purposes than the Nyishi. With the degradation of natural resources, rapid population growth, and increasing influence of 'westernization', the traditional wisdom of entomophagy and entomotherapy is at risk of being lost. There is thus an urgent need to record the role insects play as components of local diets and folk remedies and to assess insect biodiversity in the light of these uses.
A knowledge translation collaborative to improve the use of therapeutic hypothermia in post-cardiac arrest patients: protocol for a stepped wedge randomized trial
Authors: Dainty Katie N , Scales Damon C , Brooks Steve C , Needham Dale M , Dorian Paul , Ferguson Niall , Rubenfeld Gordon , Wax Randy , Zwarenstein Merrick , Thorpe Kevin , Morrison Laurie J
Published: January 2011

Background

Advances in resuscitation science have dramatically improved survival rates following cardiac arrest. However, about 60% of adults that regain spontaneous circulation die before leaving the hospital. Recently it has been shown that inducing hypothermia in cardiac arrest survivors immediately following their arrival in hospital can dramatically improve both overall survival and neurological outcomes. Despite the strong evidence for its efficacy and the apparent simplicity of this intervention, recent surveys show that therapeutic hypothermia is delivered inconsistently, incompletely, and often with delay.

Methods and design

This study will evaluate a multi-faceted knowledge translation strategy designed to increase the utilization rate of induced hypothermia in survivors of cardiac arrest across a network of 37 hospitals in Southwestern Ontario, Canada. The study is designed as a stepped wedge randomized trial lasting two years. Individual hospitals will be randomly assigned to four different wedges that will receive the active knowledge translation strategy according to a sequential rollout over a number of time periods. By the end of the study, all hospitals will have received the intervention. The primary aim is to measure the effectiveness of a multifaceted knowledge translation plan involving education, reminders, and audit-feedback for improving the use of induced hypothermia in survivors of cardiac arrest presenting to the emergency department. The primary outcome is the proportion of eligible OHCA patients that are cooled to a body temperature of 32 to 34°C within six hours of arrival in the hospital. Secondary outcomes will include process of care measures and clinical outcomes.

Discussion

Inducing hypothermia in cardiac arrest survivors immediately following their arrival to hospital has been shown to dramatically improve both overall survival and neurological outcomes. However, this lifesaving treatment is frequently not applied in practice. If this trial is positive, our results will have broad implications by showing that a knowledge translation strategy shared across a collaborative network of hospitals can increase the number of patients that receive this lifesaving intervention in a timely manner.

Trial Registration

ClinicalTrials.gov Trial Identifier: NCT00683683
The European Society of Human Reproduction and Embryology guideline for the diagnosis and treatment of endometriosis: an electronic guideline implementability appraisal
Authors: van Dijk Lotte JEW , Nelen Willianne LDM , D'Hooghe Thomas M , Dunselman Gerard AJ , Hermens Rosella PMG , Bergh Christina , Nygren Karl G , Simons Arnold HM , de Sutter Petra , Marshall Catherine , Burgers Jako S , Kremer Jan AM
Published: January 2011

Background

Clinical guidelines are intended to improve healthcare. However, even if guidelines are excellent, their implementation is not assured. In subfertility care, the European Society of Human Reproduction and Embryology (ESHRE) guidelines have been inventoried, and their methodological quality has been assessed. To improve the impact of the ESHRE guidelines and to improve European subfertility care, it is important to optimise the implementability of guidelines. We therefore investigated the implementation barriers of the ESHRE guideline with the best methodological quality and evaluated the used instrument for usability and feasibility.

Methods

We reviewed the ESHRE guideline for the diagnosis and treatment of endometriosis to assess its implementability. We used an electronic version of the guideline implementability appraisal (eGLIA) instrument. This eGLIA tool consists of 31 questions grouped into 10 dimensions. Seven items address the guideline as a whole, and 24 items assess the individual recommendations in the guideline. The eGLIA instrument identifies factors that influence the implementability of the guideline recommendations. These factors can be divided into facilitators that promote implementation and barriers that oppose implementation. A panel of 10 experts from three European countries appraised all 36 recommendations of the guideline. They discussed discrepancies in a teleconference and completed a questionnaire to evaluate the ease of use and overall utility of the eGLIA instrument.

Results

Two of the 36 guideline recommendations were straightforward to implement. Five recommendations were considered simply statements because they contained no actions. The remaining 29 recommendations were implementable with some adjustments. We found facilitators of the guideline implementability in the quality of decidability, presentation and formatting, apparent validity, and novelty or innovation of the recommendations. Vaguely defined actions, lack of facilities, immeasurable outcomes, and inflexibility within the recommendations formed barriers to implementation. The eGLIA instrument was generally useful and easy to use. However, assessment with the eGLIA instrument is very time-consuming.

Conclusions

The ESHRE guideline for the diagnosis and treatment of endometriosis could be improved to facilitate its implementation in daily practice. The eGLIA instrument is a helpful tool for identifying obstacles to implementation of a guideline. However, we recommend a concise version of this instrument.
5-HT receptors mediate lineage-dependent effects of serotonin on adult neurogenesis in Procambarus clarkii
Authors: Zhang Yi , Benton Jeanne L , Beltz Barbara S
Published: January 2011

Background

Serotonin (5-HT) is a potent regulator of adult neurogenesis in the crustacean brain, as in the vertebrate brain. However, there are relatively few data regarding the mechanisms of serotonin's action and which precursor cells are targeted. Therefore, we exploited the spatial separation of the neuronal precursor lineage that generates adult-born neurons in the crayfish (Procambarus clarkii) brain to determine which generation(s) is influenced by serotonin, and to identify and localize serotonin receptor subtypes underlying these effects.

Results

RT-PCR shows that mRNAs of serotonin receptors homologous to mammalian subtypes 1A and 2B are expressed in P. clarkii brain (referred to here as 5-HT1α and 5-HT2β). In situ hybridization with antisense riboprobes reveals strong expression of these mRNAs in several brain regions, including cell clusters 9 and 10 where adult-born neurons reside. Antibodies generated against the crustacean forms of these receptors do not bind to the primary neuronal precursors (stem cells) in the neurogenic niche or their daughters as they migrate, but do label these second-generation precursors as they approach the proliferation zones of cell clusters 9 and 10. Like serotonin, administration of the P. clarkii 5-HT1α-specific agonist quipazine maleate salt (QMS) increases the number of bromodeoxyuridine (BrdU)-labeled cells in cluster 10; the P. clarkii 5-HT2β-specific antagonist methiothepin mesylate salt (MMS) suppresses neurogenesis in this region. However, serotonin, QMS and MMS do not alter the rate of BrdU incorporation into niche precursors or their migratory daughters.

Conclusion

Our results demonstrate that the influences of serotonin on adult neurogenesis in the crayfish brain are confined to the late second-generation precursors and their descendants. Further, the distribution of 5-HT1α and 5-HT2β mRNAs and proteins indicate that these serotonergic effects are exerted directly on specific generations of neuronal precursors. Taken together, these results suggest that the influence of serotonin on adult neurogenesis in the crustacean brain is lineage dependent, and that 5-HT1α and 5-HT2β receptors underlie these effects.
Molecular analysis and intestinal expression of SAR1 genes and proteins in Anderson's disease (Chylomicron retention disease)
Authors: Georges Amandine , Bonneau Jessica , Bonnefont-Rousselot Dominique , Champigneulle Jacqueline , Rabès Jean P , Abifadel Marianne , Aparicio Thomas , Guenedet Jean C , Bruckert Eric , Boileau Catherine , Morali Alain , Varret Mathilde , Aggerbeck Lawrence P , Samson-Bouma Marie E
Published: January 2011

Background

Anderson's disease (AD) or chylomicron retention disease (CMRD) is a very rare hereditary lipid malabsorption syndrome. In order to discover novel mutations in the SAR1B gene and to evaluate the expression, as compared to healthy subjects, of the Sar1 gene and protein paralogues in the intestine, we investigated three previously undescribed individuals with the disease.

Methods

The SAR1B, SAR1A and PCSK9 genes were sequenced. The expression of the SAR1B and SAR1A genes in intestinal biopsies of both normal individuals and patients was measured by RTqPCR. Immunohistochemistry using antibodies to recombinant Sar1 protein was used to evaluate the expression and localization of the Sar1 paralogues in the duodenal biopsies.

Results

Two patients had a novel SAR1B mutation (p.Asp48ThrfsX17). The third patient, who had a previously described SAR1B mutation (p.Leu28ArgfsX7), also had a p.Leu21dup variant of the PCSK9 gene. The expression of the SAR1B gene in duodenal biopsies from an AD/CMRD patient was significantly decreased whereas the expression of the SAR1A gene was significantly increased, as compared to healthy individuals. The Sar1 proteins were present in decreased amounts in enterocytes in duodenal biopsies from the patients as compared to those from healthy subjects.

Conclusions

Although the proteins encoded by the SAR1A and SAR1B genes are 90% identical, the increased expression of the SAR1A gene in AD/CMRD does not appear to compensate for the lack of the SAR1B protein. The PCSK9 variant, although reported to be associated with low levels of cholesterol, does not appear to exert any additional effect in this patient. The results provide further insight into the tissue-specific nature of AD/CMRD.
Genome-wide analysis of Ollier disease: Is it all in the genes?
Authors: Pansuriya Twinkal C , Oosting Jan , Krenács Tibor , Taminiau Antonie HM , Verdegaal Suzan HM , Sangiorgi Luca , Sciot Raf , Hogendoorn Pancras CW , Szuhai Karoly , Bovée Judith VMG
Published: January 2011

Background

Ollier disease is a rare, non-hereditary disorder which is characterized by the presence of multiple enchondromas (ECs), benign cartilaginous neoplasms arising within the medulla of the bone, with an asymmetric distribution. The risk of malignant transformation towards central chondrosarcoma (CS) is increased up to 35%. The aetiology of Ollier disease is unknown.

Methods

We undertook genome-wide copy number and loss of heterozygosity (LOH) analysis using Affymetrix SNP 6.0 array on 37 tumours of 28 Ollier patients in combination with expression array using Illumina BeadArray v3.0 for 7 ECs of 6 patients.

Results

Non-recurrent EC specific copy number alterations were found at FAM86D, PRKG1 and ANKS1B. LOH with copy number loss of chromosome 6 was found in two ECs from two unrelated Ollier patients. One of these patients also had LOH at chromosome 3. However, no common genomic alterations were found for all ECs. Using an integration approach of SNP and expression array we identified loss as well as down regulation of POU5F1 and gain as well as up regulation of NIPBL. None of these candidate regions were affected in more than two Ollier patients suggesting these changes to be random secondary events in EC development. An increased number of genetic alterations and LOH were found in Ollier CS which mainly involves chromosomes 9p, 6q, 5q and 3p.

Conclusions

We present the first genome-wide analysis of the largest international series of Ollier ECs and CS reported so far and demonstrate that copy number alterations and LOH are rare and non-recurrent in Ollier ECs while secondary CS are genetically unstable. One could predict that instead small deletions, point mutations or epigenetic mechanisms play a role in the origin of ECs of Ollier disease.
Conformation dependent monoclonal antibodies distinguish different replicating strains or conformers of prefibrillar Aβ oligomers
Authors: Kayed Rakez , Canto Isabel , Breydo Leonid , Rasool Suhail , Lukacsovich Tamas , Wu Jessica , Albay Ricardo , Pensalfini Anna , Yeung Stephen , Head Elizabeth , Marsh J Lawrence , Glabe Charles
Published: January 2011

Background

Age-related neurodegenerative diseases share a number of important pathological features, such as accumulation of misfolded proteins as amyloid oligomers and fibrils. Recent evidence suggests that soluble amyloid oligomers and not the insoluble amyloid fibrils may represent the primary pathological species of protein aggregates.

Results

We have produced several monoclonal antibodies that specifically recognize prefibrillar oligomers and do not recognize amyloid fibrils, monomer or natively folded proteins. Like the polyclonal antisera, the individual monoclonals recognize generic epitopes that do not depend on a specific linear amino acid sequence, but they display distinct preferences for different subsets of prefibrillar oligomers. Immunological analysis of a number of different prefibrillar Aβ oligomer preparations show that structural polymorphisms exist in Aβ prefibrillar oligomers that can be distinguished on the basis of their reactivity with monoclonal antibodies. Western blot analysis demonstrates that the conformers defined by the monoclonal antibodies have distinct size distributions, indicating that oligomer structure varies with size. The different conformational types of Aβ prefibrillar oligomers can serve as they serve as templates for monomer addition, indicating that they seed the conversion of Aβ monomer into more prefibrillar oligomers of the same type.

Conclusions

These results indicate that distinct structural variants or conformers of prefibrillar Aβ oligomers exist that are capable of seeding their own replication. These conformers may be analogous to different strains of prions.
MyD88-adaptor protein acts as a preventive mechanism for memory deficits in a mouse model of Alzheimer's disease
Authors: Michaud Jean-Philippe , Richard Karine L , Rivest Serge
Published: January 2011

Background

Alzheimer's disease (AD) is an age-related neurodegenerative disorder associated with brain innate immune activation mainly mediated by microglia. These cells are known to be activated in the brain of AD patients and to produce inflammatory cytokines and neurotoxic molecules in response to Amyloid beta (Aβ). Activation of microglia can also promote Aβ clearance via Toll-like receptors (TLRs). Myeloid differentiation factor 88 (MyD88) is the adaptor molecule for most of these innate immune receptors, transducing the intracellular signal from TLRs to nucleus.

Results

Here, we report that more than 50% reduction in MyD88 expression in a mouse model of AD accelerated spatial learning and memory deficits. Brain of APPswe/PS1-MyD88+/- mice was characterized by a delay in accumulation of Aβ plaques and increased soluble levels of Aβ oligomers. Furthermore, inflammatory monocyte subset and brain IL-1β gene expression were significantly reduced in APPswe/PS1 mice with impaired MyD88 signaling.

Conclusions

These data indicate that activation of MyD88 intracellular signaling pathway, likely by TLRs, acts as a natural innate immune mechanism to restrict disease progression of APPswe/PS1 mice.
Preclinical study of dimebon on β-amyloid-mediated neuropathology in Alzheimer's disease
Authors: Wang Jun , Ferruzzi Mario G , Varghese Merina , Qian Xianjuan , Cheng Alice , Xie Mathew , Zhao Wei , Ho Lap , Pasinetti Giulio M
Published: January 2011

Background

Dimebon is a retired non-selective antihistamine drug currently being investigated as a therapeutic agent for the treatment of Alzheimer's disease (AD). Results from several completed clinical trials are mixed and contradictory. Proper interpretations of these clinical observations, as well as future development of dimebon in AD treatment are complicated by the lack of concrete information on the mechanisms by which dimebon might benefit AD.

Results

The present studies are designed specifically to assess whether dimebon might modulate β-amyloid (Aβ)-mediated responses which are central to the development and progression of AD dementia. We found that dimebon is bioavailable in the brains of mice following oral administration. AD mice chronically treated with dimebon exhibited a trend of improvement in spatial memory function without affecting the levels of total Aβ as well as soluble oligomeric Aβ in the brain. The same trend of behavior improvement is also seen in wild type animals chronically treated with dimebon.

Conclusion

Collectively, our preclinical studies using the TgCRND8 AD mouse model demonstrated that dimebon might have some beneficial effect in improving cognitive function independent of Alzheimer's disease-type Aβ-related mechanisms or global energy metabolism in the brain. Observations from our study and others suggesting dimebon might improve cognition in wild type mice and rats raises the possibility that dimebon might be able to benefit cognitive function in patients with other neurodegenerative disorders, such as Huntington's disease, or in the aging population. Additional studies will be necessary to clarify the mechanisms by which dimebon might directly or indirectly benefit cognitive function.
SAMMate: a GUI tool for processing short read alignments in SAM/BAM format
Authors: Xu Guorong , Deng Nan , Zhao Zhiyu , Judeh Thair , Flemington Erik , Zhu Dongxiao
Published: January 2011

Background

Next Generation Sequencing (NGS) technology generates tens of millions of short reads for each DNA/RNA sample. A key step in NGS data analysis is the short read alignment of the generated sequences to a reference genome. Although storing alignment information in the Sequence Alignment/Map (SAM) or Binary SAM (BAM) format is now standard, biomedical researchers still have difficulty accessing this information.

Results

We have developed a Graphical User Interface (GUI) software tool named SAMMate. SAMMate allows biomedical researchers to quickly process SAM/BAM files and is compatible with both single-end and paired-end sequencing technologies. SAMMate also automates some standard procedures in DNA-seq and RNA-seq data analysis. Using either standard or customized annotation files, SAMMate allows users to accurately calculate the short read coverage of genomic intervals. In particular, for RNA-seq data SAMMate can accurately calculate the gene expression abundance scores for customized genomic intervals using short reads originating from both exons and exon-exon junctions. Furthermore, SAMMate can quickly calculate a whole-genome signal map at base-wise resolution allowing researchers to solve an array of bioinformatics problems. Finally, SAMMate can export both a wiggle file for alignment visualization in the UCSC genome browser and an alignment statistics report. The biological impact of these features is demonstrated via several case studies that predict miRNA targets using short read alignment information files.

Conclusions

With just a few mouse clicks, SAMMate will provide biomedical researchers easy access to important alignment information stored in SAM/BAM files. Our software is constantly updated and will greatly facilitate the downstream analysis of NGS data. Both the source code and the GUI executable are freely available under the GNU General Public License at http://sammate.sourceforge.net.
WebGimm: An integrated web-based platform for cluster analysis, functional analysis, and interactive visualization of results
Authors: Joshi Vineet K , Freudenberg Johannes M , Hu Zhen , Medvedovic Mario
Published: January 2011

Cluster analysis methods have been extensively researched, but the adoption of new methods is often hindered by technical barriers in their implementation and use. WebGimm is a free cluster analysis web-service, and an open source general purpose clustering web-server infrastructure designed to facilitate easy deployment of integrated cluster analysis servers based on clustering and functional annotation algorithms implemented in R. Integrated functional analyses and interactive browsing of both, clustering structure and functional annotations provides a complete analytical environment for cluster analysis and interpretation of results. The Java Web Start client-based interface is modeled after the familiar cluster/treeview packages making its use intuitive to a wide array of biomedical researchers. For biomedical researchers, WebGimm provides an avenue to access state of the art clustering procedures. For Bioinformatics methods developers, WebGimm offers a convenient avenue to deploy their newly developed clustering methods. WebGimm server, software and manuals can be freely accessed at http://ClusterAnalysis.org/.
Stochastic simulations of the tetracycline operon
Authors: Biliouris Konstantinos , Daoutidis Prodromos , Kaznessis Yiannis N
Published: January 2011

Background

The tetracycline operon is a self-regulated system. It is found naturally in bacteria where it confers resistance to antibiotic tetracycline. Because of the performance of the molecular elements of the tetracycline operon, these elements are widely used as parts of synthetic gene networks where the protein production can be efficiently turned on and off in response to the presence or the absence of tetracycline. In this paper, we investigate the dynamics of the tetracycline operon. To this end, we develop a mathematical model guided by experimental findings. Our model consists of biochemical reactions that capture the biomolecular interactions of this intriguing system. Having in mind that small biological systems are subjects to stochasticity, we use a stochastic algorithm to simulate the tetracycline operon behavior. A sensitivity analysis of two critical parameters embodied this system is also performed providing a useful understanding of the function of this system.

Results

Simulations generate a timeline of biomolecular events that confer resistance to bacteria against tetracycline. We monitor the amounts of intracellular TetR2 and TetA proteins, the two important regulatory and resistance molecules, as a function of intrecellular tetracycline. We find that lack of one of the promoters of the tetracycline operon has no influence on the total behavior of this system inferring that this promoter is not essential for Escherichia coli. Sensitivity analysis with respect to the binding strength of tetracycline to repressor and of repressor to operators suggests that these two parameters play a predominant role in the behavior of the system. The results of the simulations agree well with experimental observations such as tight repression, fast gene expression, induction with tetracycline, and small intracellular TetR2 amounts.

Conclusions

Computer simulations of the tetracycline operon afford augmented insight into the interplay between its molecular components. They provide useful explanations of how the components and their interactions have evolved to best serve bacteria carrying this operon. Therefore, simulations may assist in designing novel gene network architectures consisting of tetracycline operon components.
An 82-year-old Caucasian man with a ductal prostate adenocarcinoma with unusual cystoscopic appearance: a case report
Authors: Sfoungaristos Stavros , Katafigiotis Ioannis S , Tyritzis Stavros I , Kavouras Adamantios , Kanatas Panagiotis , Petas Anastasios
Published: January 2011

Introduction

Ductal adenocarcinoma is a rare variety of the common acinar adenocarcinoma. It usually presents with refractory symptoms, and during cystoscopy, it is seen as an exophytic lesion at the area of the verumontanum.

Case presentation

An 82-year-old Caucasian man was diagnosed with ductal adenocarcinoma of the prostate after undergoing transurethral resection of the prostate for urinary retention. Immunohistochemistry confirmed the nature of the tumor. The patient was treated with triptorelin, 3.75 mg once/month, and bicalutamide, 50 mg 1 × 1. The serum prostate-specific antigen at three, six and 12 months after transurethral resection of the prostate was 0.1 ng/ml. The patient remains asymptomatic, and he entered a six-month follow-up protocol.

Conclusion

Ductal adenocarcinoma often involves the central ducts of the gland and may present as an exophytic papillary lesion in the prostatic urethra. This is why it usually presents with refractory symptoms. The outcome for men with prostatic ductal adenocarcinoma is, in most studies, worse than the outcome for men with prostatic acinar adenocarcinoma. Aggressive management is indicated, even with low-volume metastatic disease.
Congenital spinal tumor in a patient with encephalocele and hydrocephalus: a case report
Authors: Radmanesh Farid , Nejat Farideh , Mahjoub Fatemeh , El Khashab Mostafa
Published: January 2011

Introduction

Encephalocele is a rare congenital abnormality of the central nervous system, where brain tissue protrudes from a defect in the skull. Some anomalies are associated with encephalocele. However, the association of spinal teratoma and encephalocele has not been reported in the English literature.

Case presentation

We report the case of an Iranian girl with a history of encephalocele surgery, who, at the age of four years, developed an intramedullary spinal teratoma, and discuss the pathogenesis of this association.

Conclusion

To the best of our knowledge, this is the first report of an association between encephalocele and spinal teratoma.
Hyaluronidase recruits mesenchymal-like cells to the lung and ameliorates fibrosis
Authors: Bitencourt Claudia S , Pereira Priscilla AT , Ramos Simone G , Sampaio Suely V , Arantes Eliane C , Aronoff David M , Faccioli Lúcia H
Published: January 2011

Hyaluronidases (HYALs) comprise a group of enzymes that degrade hyaluronic acid (HA). In this report, we reveal that a single intranasal inoculation of HYAL induces an increase in mononuclear cells within the bronchoalveolar space demonstrating a mesenchymal-like phenotype, expressing stem cell antigen-1 (SCA-1), CD44 and CD73 but not CD34, CD45, CD3, CD4, CD8 or CD19. This influx of mesenchymal stem cell (MSC)-like cells was dependent on leukotriene production within the lung parenchyma. These findings prompted experiments demonstrating that HYAL treatment potently blocked bleomycin-induced lung injury and fibrosis while decreasing transforming growth factor (TGF)-β production and collagen deposition. These data suggest that HYAL is a novel and promising tool to use autologous MSC-like cells in the treatment of pulmonary fibrosis.
DNA methylation-mediated control of learning and memory
Authors: Yu Nam-Kyung , Baek Sung Hee , Kaang Bong-Kiun
Published: January 2011

Animals constantly receive and respond to external or internal stimuli, and these experiences are learned and memorized in their brains. In animals, this is a crucial feature for survival, by making it possible for them to adapt their behavioral patterns to the ever-changing environment. For this learning and memory process, nerve cells in the brain undergo enormous molecular and cellular changes, not only in the input-output-related local subcellular compartments but also in the central nucleus. Interestingly, the DNA methylation pattern, which is normally stable in a terminally differentiated cell and defines the cell type identity, is emerging as an important regulatory mechanism of behavioral plasticity. The elucidation of how this covalent modification of DNA, which is known to be the most stable epigenetic mark, contributes to the complex orchestration of animal behavior is a fascinating new research area. We will overview the current understanding of the mechanism of modifying the methyl code on DNA and its impact on learning and memory.
6-Nitro-2-(3-hydroxypropyl)-1H-benz[de]isoquinoline-1,3-dione, a potent antitumor agent, induces cell cycle arrest and apoptosis
Authors: Mukherjee Asama , Dutta Sushanta , Shanmugavel Muthiah , Mondhe Dilip M , Sharma Parduman R , Singh Shashank K , Saxena Ajit K , Sanyal Utpal
Published: January 2011

Background

Anticancer activities of several substituted naphthalimides (1H-benz[de]isoquinoline-1,3-diones) are well documented. Some of them have undergone Phase I-II clinical trials. Presently a series of ten N-(hydroxyalkyl) naphthalimides (compounds1a-j)were evaluated as antitumor agents.

Methods

Compounds1a-jwere initially screened in MOLT-4, HL-60 and U-937 human tumor cell lines and results were compared with established clinical drugs. Cytotoxicities of compounds1dand1iwere further evaluated in a battery of human tumor cell lines and in normal human peripheral blood mononuclear cells. Cell cycle analysis of compound1itreated MOLT-4 cells was studied by flow cytometry. Its apoptosis inducing effect was carried out in MOLT-4 and HL-60 cells by flow cytometry using annexin V-FITC/PI double staining method. The activities of caspase-3 and caspase-6 in MOLT-4 cells following incubation with compound1iwere measured at different time intervals. Morphology of the MOLT-4 cells after treatment with1iwas examined under light microscope and transmission electron microscope.3H-Thymidine and3H-uridine incorporation in S-180 cells in vitro following treatment with 8 μM concentration of compounds1dand1iwere studied.

Results

6-Nitro-2-(3-hydroxypropyl)-1H-benz[de]isoquinoline-1,3-dione (compound1i), has exhibited maximum activity as it induced significant cytotoxicity in 8 out of 13 cell lines employed. Interestingly it did not show any cytotoxicity against human PBMC (IC50value 273 μM). Cell cycle analysis of compound1itreated MOLT-4 cells demonstrated rise in sub-G1fraction and concomitant accumulation of cells in S and G2/M phases, indicating up-regulation of apoptosis along with mitotic arrest and/or delay in exit of daughter cells from mitotic cycle respectively. Its apoptosis inducing effect was confirmed in flow cytometric study in MOLT-4 and the action was mediated by activation of both caspase 3 and 6. Light and transmission electron microscopic studies corroborated its apoptosis inducing efficacy at a concentration of 10 μM in MOLT-4 cells. Its apoptosis induction was also observed in HL-60 cells to an extent much greater than well known apoptosis inducing agents as camptothecin and cis-platin at 10 μM concentration each. It significantly inhibited DNA and RNA synthesis in S-180.

Conclusions

In essence, compound1ishowed potential as an antitumor agent.
Quantitative analysis of residual protein contamination of podiatry instruments reprocessed through local and central decontamination units
Authors: Smith Gordon WG , Goldie Frank , Long Steven , Lappin David F , Ramage Gordon , Smith Andrew J
Published: January 2011

Background

The cleaning stage of the instrument decontamination process has come under increased scrutiny due to the increasing complexity of surgical instruments and the adverse affects of residual protein contamination on surgical instruments. Instruments used in the podiatry field have a complex surface topography and are exposed to a wide range of biological contamination. Currently, podiatry instruments are reprocessed locally within surgeries while national strategies are favouring a move toward reprocessing in central facilities. The aim of this study was to determine the efficacy of local and central reprocessing on podiatry instruments by measuring residual protein contamination of instruments reprocessed by both methods.

Methods

The residual protein of 189 instruments reprocessed centrally and 189 instruments reprocessed locally was determined using a fluorescent assay based on the reaction of proteins with o‐phthaldialdehyde/sodium 2‐mercaptoethanesulfonate.

Results

Residual protein was detected on 72% (n = 136) of instruments reprocessed centrally and 90% (n = 170) of instruments reprocessed locally. Significantly less protein (p < 0.001) was recovered from instruments reprocessed centrally (median 20.62 μg, range 0 ‐ 5705 μg) than local reprocessing (median 111.9 μg, range 0 ‐ 6344 μg).

Conclusions

Overall, the results show the superiority of central reprocessing for complex podiatry instruments when protein contamination is considered, though no significant difference was found in residual protein between local decontamination unit and central decontamination unit processes for Blacks files. Further research is needed to undertake qualitative identification of protein contamination to identify any cross contamination risks and a standard for acceptable residual protein contamination applicable to different instruments and specialities should be considered as a matter of urgency.
Squamous cell carcinoma of the tonsillar remnant - clinical presentation and oncological outcome
Authors: Skilbeck Christopher J , Jeannon Jean-Pierre , O'Connell Mary , Morgan Peter R , Simo Ricard
Published: January 2011

Background

Squamous cell carcinoma (SCC) of the tonsil is the most common malignant tumour of the oropharynx. Paediatric tonsillectomy is one of the most commonly performed procedures in Otorhinolaryngology. SCC of the tonsil remnant (SCCTR) in a previously tonsillectomised patient is rare.

Methods

Retrospective review of patients with SCCTR presenting to the Otorhinolaryngology, Head and Neck Unit January 2000 to December 2007.

Results

Two hundred and fifty patients with tonsil SCC were identified. Ten (4%) of these had previously undergone tonsillectomy in childhood. Nine patients underwent radical treatment including surgery, radiotherapy and in four cases concomitant chemotherapy. Eight patients are alive with no signs of recurrence with follow-up of a minimum of 24 months. One has been lost from follow-up.

Conclusions

Clinicians should be aware that SCC can arise from a tonsillar remnant. SCCTR has similar oncological outcomes as tonsillar tumours.
Body fluids and salt metabolism - Part II
Authors: Peruzzo Mattia , Milani Gregorio P , Garzoni Luca , Longoni Laura , Simonetti Giacomo D , Bettinelli Alberto , Fossali Emilio F , Bianchetti Mario G
Published: January 2011

There is a high frequency of diarrhea and vomiting in childhood. As a consequence the focus of the present review is to recognize the different body fluid compartments, to clinically assess the degree of dehydration, to know how the equilibrium between extracellular fluid and intracellular fluid is maintained, to calculate the effective blood osmolality and discuss both parenteral fluid maintenance and replacement.
In vivo microRNA-155 expression influences antigen-specific T cell-mediated immune responses generated by DNA vaccination
Authors: Mao Chih-Ping , He Liangmei , Tsai Ya-Chea , Peng Shiwen , Kang Tae Heung , Pang Xiaowu , Monie Archana , Hung Chien-Fu , Wu T-C
Published: January 2011

Background

MicroRNA (miRNA) molecules are potent mediators of post-transcriptional gene silencing that are emerging to be critical in the regulation of innate and adaptive immunity.

Results

Here we report that miR-155--an oncogenic miRNA with important function in the mammalian immune system--is induced in dendritic cells (DCs) upon maturation and potentially attenuates their ability to activate T cells. Biolistic epidermal transfection with DNA encoding miR-155 suppressed the induction of antigen-specific T cell-mediated immunity, whereas reduction of endogenous miR-155 by a partially complementary antisense sequence reversed this effect. Because DCs represent a significant component of epidermal tissue and are among the most potent of antigen-presenting cells, the inhibitory actions of miR-155 could be mediated through this subset of cells.

Conclusions

These results suggest that miR-155 may repress the expression of key molecules involved in lymph node migration, antigen presentation, or T cell activation in DCs, and thus forms part of a negative regulatory pathway that dampens the generation of T cell-mediated immune responses. Modulation of miR-155 expression in epidermis therefore represents a potentially promising form of gene therapy for the control of diseases ranging from autoimmunity to cancer and viral infection.
Joint and tendon subclinical involvement suggestive of gouty arthritis in asymptomatic hyperuricemia: an ultrasound controlled study
Authors: Pineda Carlos , Amezcua-Guerra Luis M , Solano Carla , Rodriguez-Henríquez Pedro , Hernández-Díaz Cristina , Vargas Angelica , Hofmann Fritz , Gutiérrez Marwin
Published: January 2011

Introduction

In this study, we aimed to investigate ultrasonographic (US) changes suggestive of gouty arthritis in the hyaline cartilage, joints and tendons from asymptomatic individuals with hyperuricemia.

Methods

We conducted a cross-sectional, controlled study including US examinations of the knees and first metatarsal-phalangeal joints (first MTPJs), as well as of the tendons and enthesis of the lower limbs. Differences were estimated by χ2 or unpaired t-tests as appropriate. Associations were calculated using the Spearman's correlation coefficient rank test.

Results

Fifty asymptomatic individuals with hyperuricemia and 52 normouricemic subjects were included. Hyperechoic enhancement of the superficial margin of the hyaline cartilage (double contour sign) was found in 25% of the first MTPJs from hyperuricemic individuals, in contrast to none in the control group (P < 0.0001). Similar results were found on the femoral cartilage (17% versus 0; P < 0.0001). Patellar enthesopathy (12% versus 2.9%; P = 0.01) and tophi (6% versus 0; P = 0.01) as well as Achilles enthesopathy (15% versus 1.9%; P = 0.0007) were more frequent in hyperuricemic than in normouricemic individuals. Intra-articular tophi were found in eight hyperuricemic individuals but in none of the normouricemic subjects (P = 0.003).

Conclusions

These data demonstrate that morphostructural changes suggestive of gouty arthritis induced by chronic hyperuricemia frequently occur in both intra- and extra-articular structures of clinically asymptomatic individuals.
Rare, evolutionarily unlikely missense substitutions in CHEK2contribute to breast cancer susceptibility: results from a breast cancer family registry case-control mutation-screening study
Authors: Le Calvez-Kelm Florence , Lesueur Fabienne , Damiola Francesca , Vallée Maxime , Voegele Catherine , Babikyan Davit , Durand Geoffroy , Forey Nathalie , McKay-Chopin Sandrine , Robinot Nivonirina , Nguyen-Dumont Tù , Thomas Alun , Byrnes Graham B ,   Breast Cancer Family Registry, Hopper John L , Southey Melissa C , Andrulis Irene L , John Esther M , Tavtigian Sean V
Published: January 2011

Introduction

Both protein-truncating variants and some missense substitutions in CHEK2 confer increased risk of breast cancer. However, no large-scale study has used full open reading frame mutation screening to assess the contribution of rare missense substitutions in CHEK2 to breast cancer risk. This absence has been due in part to a lack of validated statistical methods for summarizing risk attributable to large numbers of individually rare missense substitutions.

Methods

Previously, we adapted an in silico assessment of missense substitutions used for analysis of unclassified missense substitutions in BRCA1 and BRCA2 to the problem of assessing candidate genes using rare missense substitution data observed in case-control mutation-screening studies. The method involves stratifying rare missense substitutions observed in cases and/or controls into a series of grades ordered a priori from least to most likely to be evolutionarily deleterious, followed by a logistic regression test for trends to compare the frequency distributions of the graded missense substitutions in cases versus controls. Here we used this approach to analyze CHEK2 mutation-screening data from a population-based series of 1,303 female breast cancer patients and 1,109 unaffected female controls.

Results

We found evidence of risk associated with rare, evolutionarily unlikely CHEK2 missense substitutions. Additional findings were that (1) the risk estimate for the most severe grade of CHEK2 missense substitutions (denoted C65) is approximately equivalent to that of CHEK2 protein-truncating variants; (2) the population attributable fraction and the familial relative risk explained by the pool of rare missense substitutions were similar to those explained by the pool of protein-truncating variants; and (3) post hoc power calculations implied that scaling up case-control mutation screening to examine entire biochemical pathways would require roughly 2,000 cases and controls to achieve acceptable statistical power.

Conclusions

This study shows that CHEK2 harbors many rare sequence variants that confer increased risk of breast cancer and that a substantial proportion of these are missense substitutions. The study validates our analytic approach to rare missense substitutions and provides a method to combine data from protein-truncating variants and rare missense substitutions into a one degree of freedom per gene test.
Strategies of initiation and streamlining of antibiotic therapy in 41 French intensive care units
Authors: Montravers Philippe , Dupont Hervé , Gauzit Rémy , Veber Benoit , Bedos Jean-Pierre , Lepape Alain ,   CIAR (Club d'infectiologie en Anesthésie-Réanimation) Study Group
Published: January 2011

Introduction

Few studies have addressed the decision-making process of antibiotic therapy (AT) in intensive care unit (ICU) patients.

Methods

In a prospective observational study, all consecutive patients admitted over a one-month period (2004) to 41 French surgical (n = 22) or medical/medico-surgical ICUs (n = 19) in 29 teaching university and 12 non-teaching hospitals were screened daily for AT until ICU discharge. We assessed the modalities of initiating AT, reasons for changes and factors associated with in ICU mortality including a specific analysis of a new AT administered on suspicion of a new infection.

Results

A total of 1,043 patients (61% of the cohort) received antibiotics during their ICU stay. Thirty percent (509) of them received new AT mostly for suspected diagnosis of pneumonia (47%), bacteremia (24%), or intra-abdominal (21%) infections. New AT was prescribed on day shifts (45%) and out-of-hours (55%), mainly by a single senior physician (78%) or by a team decision (17%). This new AT was mainly started at the time of suspicion of infection (71%) and on the results of Gram-stained direct examination (21%). Susceptibility testing was performed in 261 (51%) patients with a new AT. This new AT was judged inappropriate in 58 of these 261 (22%) patients. In ICUs with written protocols for empiric AT (n = 25), new AT prescribed before the availability of culture results (P = 0.003) and out-of-hours (P = 0.04) was more frequently observed than in ICUs without protocols but the appropriateness of AT was not different. In multivariate analysis, the predictive factors of mortality for patients with new AT were absence of protocols for empiric AT (adjusted odds ratio (OR) = 1.64, 95% confidence interval (95%CI): 1.01 to 2.69), age ≥60 (OR = 1.97, 95% CI: 1.19 to 3.26), SAPS II score >38 (OR = 2.78, 95% CI: 1.60 to 4.84), rapidly fatal underlying diseases (OR = 2.91, 95% CI: 1.52 to 5.56), SOFA score ≥6 (OR = 4.48, 95% CI: 2.46 to 8.18).

Conclusions

More than 60% of patients received AT during their ICU stay. Half of them received new AT, frequently initiated out-of-hours. In ICUs with written protocols, empiric AT was initiated more rapidly at the time of suspicion of infection and out-of-hours. These results encourage the establishment of local recommendations for empiric AT.