Ultrastructure of the spermatozoon of Taeniarhynchus saginatus (syn. Taenia saginata) (Goeze, 1782) Weinland, 1858 (Cestoda, Taeniidae) an intestinal parasite of human. The mature Taeniarhynchus saginatus spermatozoon exhibits an apical cone of electron-dense material and one helicoidal crest-like body roughly 50 nm thick. The axoneme is of the 9 + "1" Trepaxonemata pattern. It is surrounded by a periaxonemal sheath of electron-dense material. The cytoplasm is electron lucent and divided into compartments by intracytoplasmic walls of electron-dense material in regions III and IV. The nucleus is an electron-dense cord 60-90 nm thick coiled in a spiral around the axoneme. It reaches the posterior extremity of the gamete where the axoneme is disorganized and is accompanied on all its posterior length by the nucleus. To our knowledge, such a posterior extremity has never been described before in a cyclophyllidean cestode.


A cysteine proteinase in the penetration glands of the cercariae of Cotylurus cornutus (Trematoda, Strigeidae). A cysteine proteinase from the penetration glands of Cotylurus cornutus cercariae was examined with histochemical and biochemical methods. The enzyme hydrolyzed gelatin, azocoll, azocasein, azoalbumin, N-blocked-L-arginine-4-methoxy-2-naphthylamide, and N-blocked-p-nitroanilide, but did not degrade elastin. The metal ion complexane ethylenediamine tetraacetate and the thiol-reducing compound dithioerythritol enhanced the proteinase activity, whereas the thiol-blocking compounds p-hydroxymercuribenzoate and N-ethylmaleimide (NEM) inhibited it. The enzyme was also sensitive to leupeptin but insensitive to soybean trypsin inhibitor. An electrophoretic separation of extract proteins from the cercariae under acidic, non-denaturing conditions and in the presence of 0.1% gelatin in a polyacrylamide gel revealed the presence of two distinct and three weak transparent bands in the gel resulting from a gelatinolytic activity at pH 6.8. The distinct bands apparently resulted from the activity of the glandular enzyme and lysosomal cathepsin B, whereas the weak ones presumably indicated these enzymes partially degraded in the course of the preparative procedure. No gelatinolysis occurred following treatment of an extract sample with 0.1 mM NEM.


Helminth parasites of freshwater fish in Chiapas, Mexico. An inventory based on previously published records and original data is presented for the helminth parasites reported in 54 fish species from 17 families from the state of Chiapas, southeast Mexico. This survey reports the presence of 43 helminth species in Chiapas for the first time. The actualized inventory of helminth parasites of freshwater fish from Chiapas contains 88 species from 67 genera and 40 helminth families. Trematodes and nematodes were the most abundant taxonomic groups. The helminth fauna in freshwater fishes from Chiapas consists of Central American species. All the helminth species recorded in Chiapas have also been collected from bodies of freshwater between the Isthmus of Tehuantepec and the Isthmus of Panama. This inventory shows that this fauna is quite similar to that from the neighboring basins of the lower Grijalva-Usumacinta system and the Yucatan Peninsula. The taxonomic composition and distribution data reported here for the helminth fauna of Chiapas' freshwater fish, contribute to a better understanding of this faunal component in Central America.


Molecular cloning of two novel mucin-like genes in the disease-susceptibility locus for diffuse panbronchiolitis. Diffuse panbronchiolitis (DPB) is a rare complex genetic disease affecting East Asians and is strongly associated with the class I human leukocyte antigens (HLA)-B54 in Japanese and HLA-A11 in Koreans. We recently showed that an HLA-associated major susceptibility gene for DPB is probably located within the 200 kb in the class I region 300 kb telomeric of the HLA-B locus on the chromosome 6p21.3. We cloned two novel mucin-like genes designated panbronchiolitis related mucin-like 1 and 2 (PBMUCL1 and PBMUCL2) in the candidate region, which form a mucin-like gene cluster together with two adjacent genes, MUC21 and DPCR1. PBMUCL1 gene expression was remarkably upregulated by polyinosine-polycytidylic acid [poly(I:C)] stimulation in normal human bronchial epithelial cells redifferentiated at the air-liquid interface. We found genetic polymorphisms in PBMUCL1 gene which were associated with DPB: the A-allele of the PBMUCL1 intron 2 single nucleotide polymorphism (SNP) was positively associated and variable numbers of tandem repeats (VNTR) polymorphism in exon 3 (1,890-base pair deletion) was negatively associated. Despite a strong association with HLA-B in the Japanese, the mucin-like gene PBMUCL1 is also one of the candidate genes of DPB susceptibility.


A novel survival multifactor dimensionality reduction method for detecting gene-gene interactions with application to bladder cancer prognosis. The widespread use of high-throughput methods of single nucleotide polymorphism (SNP) genotyping has created a number of computational and statistical challenges. The problem of identifying SNP-SNP interactions in case-control studies has been studied extensively, and a number of new techniques have been developed. Little progress has been made, however, in the analysis of SNP-SNP interactions in relation to time-to-event data, such as patient survival time or time to cancer relapse. We present an extension of the two class multifactor dimensionality reduction (MDR) algorithm that enables detection and characterization of epistatic SNP-SNP interactions in the context of survival analysis. The proposed Survival MDR (Surv-MDR) method handles survival data by modifying MDR's constructive induction algorithm to use the log-rank test. Surv-MDR replaces balanced accuracy with log-rank test statistics as the score to determine the best models. We simulated datasets with a survival outcome related to two loci in the absence of any marginal effects. We compared Surv-MDR with Cox-regression for their ability to identify the true predictive loci in these simulated data. We also used this simulation to construct the empirical distribution of Surv-MDR's testing score. We then applied Surv-MDR to genetic data from a population-based epidemiologic study to find prognostic markers of survival time following a bladder cancer diagnosis. We identified several two-loci SNP combinations that have strong associations with patients' survival outcome. Surv-MDR is capable of detecting interaction models with weak main effects. These epistatic models tend to be dropped by traditional Cox regression approaches to evaluating interactions. With improved efficiency to handle genome wide datasets, Surv-MDR will play an important role in a research strategy that embraces the complexity of the genotype-phenotype mapping relationship since epistatic interactions are an important component of the genetic basis of disease.


Genome-wide analysis of copy number variants in age-related macular degeneration. Age-related macular degeneration (AMD) is a complex genetic disease, with many loci demonstrating appreciable attributable disease risk. Despite significant progress toward understanding the genetic and environmental etiology of AMD, identification of additional risk factors is necessary to fully appreciate and treat AMD pathology. In this study, we investigated copy number variants (CNVs) as potential AMD risk variants in a cohort of 400 AMD patients and 500 AMD-free controls ascertained at the University of Iowa. We used three publicly available copy number programs to analyze signal intensity data from Affymetrix GeneChip SNP Microarrays. CNVs were ranked based on prevalence in the disease cohort and absence from the control group; high interest CNVs were subsequently confirmed by qPCR. While we did not observe a single-locus "risk CNV" that could account for a major fraction of AMD, we identified several rare and overlapping CNVs containing or flanking compelling candidate genes such as NPHP1 and EFEMP1. These and other candidate genes highlighted by this study deserve further scrutiny as sources of genetic risk for AMD.


Mechanisms for phenotypic variation in Lesch-Nyhan disease and its variants. Lesch-Nyhan disease is a neurogenetic disorder caused by mutation of the HPRT1 gene on the X chromosome. There is significant variation in the clinical phenotype, with more than 300 different known mutations. There are few studies that have addressed whether similar mutations result in similar phenotypes across different patients because hypoxanthine-guanine phosphoribosyltransferase (HGprt) deficiency is rare, and most mutations are unique or limited to individual families. However, recent studies have revealed multiple unrelated patients with similar mutations, providing an opportunity to examine genotype-phenotype correlations. We found significant variation among the clinical features of 10 patients from 8 unrelated families all carrying a mutation replacing guanine with adenine at base position 143 (c.143G>A) in the HPRT1 gene. This mutation results in replacement of arginine by histidine at amino acid position 48 (p.arg48his) in the HGprt enzyme. Biochemically, the enzyme exhibits reduced thermal integrity, a mechanism that may explain clinical variation. The literature reveals similar clinical variation among other patients with similar mutations, although the variation is relatively minor across the whole population of patients. Identifiable sources of clinical variation include known limitations of clinical ascertainment and mechanisms that affect residual enzyme activity and stability. These results are helpful for understanding genotype-phenotype correlations and discordance and likely are applicable to other neurogenetic disorders where similar variation occurs.


Effects of reduced saliva production on swallowing in patients with Sjogren's syndrome. This study aimed to further characterize the nature of swallowing dysfunction in patients with Sjogren's syndrome (SS). Subjects filled out a perception of swallow function form. Measures of stimulated salivary flow rate were also taken, and videofluoroscopic evaluation of swallowing was completed. The amount of saliva produced by patients with SS was significantly less than that produced by normal age-matched controls, and these patients perceived their swallowing to be impaired. Few statistically significant differences were found between the SS group and normal age-matched controls on temporal measures of swallowing, and 96% of swallows in the SS group were judged to be functional. There was no correlation between perception of swallowing and amount of saliva produced. No strong correlations were found between temporal measures of swallowing and salivary flow rate. Results indicated that patients with SS tend to perceive their swallowing to be worse than physiologic swallowing measures indicate. The decreased saliva production in these patients does not appear to be the cause of their perceived swallowing difficulty but may affect their sensory judgment of swallow function. Future studies will focus on how quality of saliva affects swallowing in these patients.


Hypochloremic metabolic alkalosis and failure to thrive: answer.


Hypochloremic metabolic alkalosis and failure to thrive: question.


Overexpression of SlGMEs leads to ascorbate accumulation with enhanced oxidative stress, cold, and salt tolerance in tomato. GDP-Mannose 3',5'-epimerase (GME; EC 5.1.3.18) catalyses the conversion of GDP-D-mannose to GDP-L-galactose, an important step in the ascorbic acid (AsA) biosynthesis pathway in higher plants. In this study, two members of the GME gene family were isolated from tomato (Solanum lycopersicum). Both SlGME genes encode 376 amino acids and share a 92% similarity with each other. Semi-quantitative RT-PCR indicated that SlGME1 was constantly expressed in various tissues, whereas SlGME2 was differentially expressed in different tissues. Transient expression of fused SlGME1-GFP (green fluorescent protein) and SlGME2-GFP in onion cells revealed the cytoplasmic localisation of the two proteins. Transgenic plants over-expressing SlGME1 and SlGME2 exhibited a significant increase in total ascorbic acid in leaves and red fruits compared with wild-type plants. They also showed enhanced stress tolerance based on less chlorophyll content loss and membrane-lipid peroxidation under methyl viologen (paraquat) stress, higher survival rate under cold stress, and significantly higher seed germination rate, fresh weight, and root length under salt stress. The present study demonstrates that the overexpression of two members of the GME gene family resulted in increased ascorbate accumulation in tomato and improved tolerance to abiotic stresses.


Contrast sensitivity in a harbor seal (Phoca vitulina). In this study, the contrast sensitivity function (CSF) of one harbor seal was determined behaviorally in a go-/no-go-experiment at an ambient light of 0.9 lx in air. Contrast sensitivity was assessed as the reciprocal value of the threshold contrast for spatial frequencies varying between 0.03 and 1.5 cycles/deg, which were displayed with contrast ranging from 0.02 to 1 on a TFT monitor with a mean luminance of 3.8 cd/m². The CSF of the harbor seal shows the general characteristics described for other species with a peak at an intermediate frequency, a low frequency roll-off and a high frequency cut-off towards the harbor seal's resolution limit determined in a previous study. The position of the CSF's peak lies at approximately 0.5 cycles/deg and adopts an absolute height of 40. These results compare well with the cat's CSF assessed at a comparable adaptation light which might reflect similarities in lifestyle and optics.


Spinal anesthesia in a child with Brachmann-de Lange (Cornelia de Lange) syndrome. Providing anesthesia to patients with Brachmann-de Lange syndrome (BdLS) may be challenging, mainly because of intubation difficulty, gastroesophageal reflux disease, and aspiration complications. The use of spinal anesthesia (SA) in this population has not been reported. We report the uneventful administration of awake SA to a 7-month-old girl with BdLS who was scheduled for rectal biopsy. The current literature is reviewed to discuss the indications for SA in those patients.


Assessment of insulin sensitivity (S I) and glucose effectiveness (S G) from a standardized hyperglucidic breakfast test in type 2 diabetics exhibiting various levels of insulin resistance. We investigated the measurement of insulin sensitivity (S I) with a standardized hyperglucidic breakfast (SHB) compared to minimal model analysis of an intravenous glucose tolerance test (S I-IVGTT) in 17 patients clinically referred as type 2 diabetics, not yet treated by insulin, and representing a wide range of body mass index and S I. To classify the patients, ten meal-tolerance test-based calculations of S I (MTT-S I) were compared to S I-IVGTT, and their reference values and distribution were measured on a separate sample of 200 control SHBs and 209 control IVGTTs. Eight MTT-SI indices exhibit significant correlations with S I-IVGTT: Mari's OGIS index, BIGTT-SI|0-30-120, BIGTT-SI|0-60-120, 1/G b I m, Caumo's oral minimal model (OMM), Sluiter's index "A" = 10(4)/(I p·G p), Matsuda's composite index given by the formula ISIcomp = 10(4)/(I b G b I m G m)(0.5), S I = 1/I b G b I m G m with r (2) ranging between 0,53 and 0,28. S I-IVGTT and S I-MTT exhibited in the lower range a very different (non-normal) pattern of distribution and thus the cutoff value for defining insulin resistance varied among indices. With such cutoffs, S I-MTT < 6.3 min(-1)/(μU/ml) 10(-4) with Caumo's OMM was the best predictor of insulin resistance defined as S I-IVGTT < 2 min(-1)/(μU/ml) 10(-4). Other indices, including OGIS and BIGTT, resulted in more misclassifications of patients. HOMA-IR and QUICKI were poor predictors. The formula [Formula: see text] satisfactorily predicts IVGTT-derived glucose effectiveness in type 2 diabetics. Thus, SHB appears suitable for the measurement of S I and S G in type 2 diabetics, and the OMM seems to provide the most accurate SHB-derived index in this population.


Glycation research in amino acids: a place to call home. This is an introduction to a collection of review articles by leading investigators in the field of protein glycation research, see following articles in this issue. With this we launch a section of this journal now established for presentation of research results, reviews and commentaries on protein glycation and related topics. Glycation is the spontaneous, non-enzymatic reaction of protein with saccharides and saccharide derivatives. Although studied in the modern scientific era for over 100 years, its importance in the biology, medicine, food and nutrition, pharmacology and toxicology, and technological processing remains intriguingly undisclosed. In this section of amino acids, research on glycation is a qualifier for publication. Glycation research now has a place to call home.


Synergic effect of α-tocopherol and naringenin in transglutaminase-induced differentiation of human prostate cancer cells. Prostate cancer is the second most common cancer in men worldwide. Its prevention and treatment remain a challenge to clinicians. Thus, there is an urgent need to discover novel, less toxic, and more effective therapies for patients. Many vitamins and related chemicals, including vitamin E, (tocopherols) have shown their anti-cancer activities as anti-oxidants, activators of transcription factors or factors influencing epigenetic events. Although laboratory tests including the use of animal models showed that this vitamin may have anticancer properties, whether it can effectively prevent the development and/or progression of prostate cancer in humans remains to be intensively studied. This review provides up-to-date information regarding the recent outcomes of laboratory, epidemiology and/or clinical trials on the effects of tocopherols on prostate cancer development, along with our last observations on a combined treatment of a prostate cancer cell line (PC-3) with two natural antineoplastic compounds, naringenin (NG) and α-tocopherol (α-TOC). We report the synergic effect of α-TOC and NG in transglutaminase-induced differentiation of human PC-3 prostate cancer cells. While our results are based on one histological class of tumor, the most significant implication of this observation is that establishes a new way in the screening for detecting new differentiative antineoplastic agents.


Theoretical study of hydrogen bond interactions of fluvastatin with ι-carrageenan and λ-carrageenan. The binding of the reductase inhibitor drug fluvastatin, hydroxy-3-methylglutaryl coenzyme A, with the hydrophilic ι- or λ-carrageenan polymers, serving as potential controllers of the drug's release rate, have been studied at the density functional level of theory with the B3LYP exchange correlation functional. Three low energy conformers of fluvastatin have been calculated. The vibrational spectroscopic properties calculated for the most stable conformer were in satisfactory agreement with the experimental data. A series of hydrogen bonded complexes of the most stable conformer of fluvastatin anion with low molecular weight models of the polymers have been fully optimized. In almost all, intermolecular H-bonds are formed between the sulfate groups of ι- or λ-carrageenan and fluvastatin's hydroxyls, resulting in a red shift of the fluvastatin's O - H stretching vibrations. Cooperative intramolecular H-bonds within fluvastatin or ι-, λ-carrageenan are also present. The BSSE and ZPE corrected interaction energies were estimated in the range 281-318 kJ mol⁻¹ for ι-carrageenan - fluvastatin and 145-200 kJ mol⁻¹ for λ-carrageenan - fluvastatin complexes. The electron density (ρ (bcp)) and Laplacian (∇²ρ (bcp)) properties at critical points of the intermolecular hydrogen bonds, estimated by AIM (atoms in molecules) calculations, have a low and positive character (∇²ρ(bcp) > 0), consistent with the electrostatic character of the hydrogen bonds. The structural and energetic data observed, as well as the extent of the red shift of the fluvastatin's O - H stretching vibrations upon complex formation and the properties of electron density show a stronger binding of fluvastatin to ι- than to λ-carrageenan.


Development of a simulation system in mandibular orthognathic surgery based on integrated three-dimensional data. Surgical simulation should reflect the 3D movement of dentition and the resultant movement of the osteotomized segments, which can influence surgical outcome. The present study was aimed at developing a new simulation system that enables virtual osteotomy of a given surgical situation and evaluation of the bony interference between the osteotomized segments of the mandible. The data of 3D computer tomography (CT) for maxillomandibular dental casts were integrated into the standard coordinates of a 3D cephalogram. To evaluate the accuracy of the system, measurement errors of the 3D CT virtual model from a dry skull were compared with the computer simulation system and a contact-type 3D digitizer. To examine the clinical accessibility, 15 mandibular prognathism patients with mild to severe asymmetry were evaluated with the simulation program. The average error of measurement in all directions was 1.31 mm. It was possible to simulate various osteotomy procedures by conversion of the 3D coordinates of the dental cast and CT data into the standard coordinate system of a 3D cephalogram. Using this simulation system, it was possible to prevent condylar torque or segment malpositioning by removing the bony interference visualized by a 3D virtual model. A new system, which enables the precise visualization of osteotomized segments and calculation of bony interference, was proposed in the present study. This new system provides an acceptable precision of treatment planning of orthognathic surgery, especially for facial asymmetry.


Diffuse swelling of the buccal mucosa and palate as first and only manifestation of an extranodal non-Hodgkin 'double-hit' lymphoma: report of a case. Most of the lymphomas arising in the oral cavity are of B-cell origin. Among these, diffuse large B-cell lymphomas are the most common. Diffuse large B-cell lymphomas may exhibit more than one chromosomal rearrangement and are then referred to as 'double-hit' or 'triple-hit' lymphomas. We present a case of an intraoral 'double-hit' lymphoma in a 76-year-old male who had been referred by an oral surgeon in private practice. Intraoral examination exhibited a firm, exophytic lesion in the region of the right hard palate and buccal mucosa with extension to the soft palate. Radiographic examination exhibited a massive thickening of the right sinus membrane, and arrosion of the lateral and basal cortical sinus walls in the right maxilla. After diagnosis of the lesion, the patient was treated with six cycles of chemotherapy. Lymphomas arising within the oral cavity account for less than 5% of all oral malignancies and typically affect the palatine tonsils and the palate. 'Double-hit' lymphomas are associated with older age, usually present with an advanced stage of disease, and show an aggressive clinical behaviour. They normally have a poor prognosis, even when treated with intensive chemotherapy regimens. Nevertheless, in the case presented, the patient was free of symptoms 1 year after initial diagnosis.


Feasibility of diagnosing influenza within 24 hours of symptom onset in children 1-3 years of age. Diagnosing influenza at an early stage of illness is important for the initiation of effective antiviral treatment. However, especially in young children, influenza often commences with an abrupt onset of fever, with full-blown respiratory symptoms developing only later. We determined the feasibility of diagnosing influenza in young children already during the first signs of the illness. During confirmed influenza activity, we obtained nasal swabs from children aged 1-3 years who presented as outpatients within 24 hours of the onset of fever (≥38.0°C). The specimens were tested for influenza viruses with viral culture, antigen detection, PCR, and a rapid point-of-care test (Actim Influenza A&B, Medix Biochemica, Finland). In addition, follow-up specimens were obtained from a proportion of children 3-7 days later. Influenza virus was detected already within 24 hours of symptom onset in 56 of 61 (92%; 95% CI 82-97%) children in whom influenza was eventually confirmed in the laboratory. A total of 158 rapid tests performed within 24 hours of symptom onset yielded a sensitivity of 90% (95% CI 74-98%) for influenza A viruses but only 25% (95% CI 3-61%) for influenza B viruses (P < 0.001), resulting in an overall sensitivity of 77% (95% CI 61-89%) and specificity of 99% (95% CI 95-100%) for all influenza viruses. In most young children, influenza can already be accurately diagnosed within 24 hours of symptom onset. The rapid point-of-care test used was sensitive and specific for diagnosing influenza A, but its sensitivity for influenza B was limited.


Identification of clinically relevant viridans group streptococci by phenotypic and genotypic analysis. Two phenotypic and three molecular methods were assessed for their ability to identify viridans group streptococci (VGS) to the species level. A panel of 23 clinical isolates, comprising strains isolated from infective endocarditis, blood cultures, pleural and peritoneal fluid, and 19 type/reference strains were analyzed. Identification was performed using two conventional phenotypic methods: API® rapid ID 32 Strep and the VITEK® 2 system, and genotypic analysis of the nucleotide sequence of the housekeeping gene sodA, restriction patterns generated by restriction fragment length polymorphism (RFLP) of the 16S rRNA gene and multilocus sequence analysis (MLSA) of seven housekeeping genes. The API® rapid ID 32 Strep accurately speciated 79% of the strains assessed, while the VITEK® 2 generated a successful identification for 55%, presenting limitations particularly with regard to species belonging to the mitis group. RFLP of the 16S rRNA gene correctly speciated 24% of the strains, having failed to allocate a species for 36% of the isolates examined. In contrast, sequence analysis of the sodA gene provided a correct identification for 95% of the strains assessed, while identification using the MLSA technique was unsuccessful due to practical limitations. The results generated herein indicate that no single methodology can be used to provide an accurate identification to the species level of all VGS, although nucleotide sequence analysis of the sodA gene proved to be useful in providing reliable speciation.


Six-month follow-up multicenter prospective study of 368 patients, phototypes III to V, on epilation efficacy using an 810-nm diode laser at low fluence. Laser hair removal is currently a popular cosmetic procedure. Traditional high-fluence laser treatment for hair elimination is associated with discomfort and adverse events and it is restricted to low phototype skins. A multicenter study of hair epilation with low fluences and high repetition pulse rate using an 810-nm diode laser was carried out on 368 patients (phototypes III to V) to test its efficacy in a 6-month follow-up after five treatments on the face and various body areas. Objective and subjective assessment as well as histologies show a high index of patient satisfaction due to high efficacy of hair elimination, also proved histologically by the damage observed at hair structure level. Results obtained a high degree of patient satisfaction and a low index of adverse events. Laser epilation was well accepted regarding discomfort and was also complication-free for dark and tanned skins. Treatment is easy to conduct and requires adapting the movement of the hand-piece to a constant speed in order to achieve high-energy deposit on tissue avoiding risks of burning.


Achilles paratendonitis as the initial manifestation of rheumatoid arthritis. We report a case of rheumatoid arthritis in which the earliest symptom was bilateral paratendonitis of the Achilles tendons, followed by paratendonitis of a finger extensor. A series of musculoskeletal ultrasonograms revealed a progression from paratendonitis of the extensor tendon to erosive synovitis of the adjacent metacarpophalangeal joint. High-resolution ultrasonography combined with power Doppler imaging seems to be a useful and convenient tool both for diagnosing paratendonitis early and for closely monitoring the progressing inflammation.


Dicoogle - an open source peer-to-peer PACS. Picture Archiving and Communication Systems (PACS) have been widely deployed in healthcare institutions, and they now constitute a normal commodity for practitioners. However, its installation, maintenance, and utilization are still a burden due to their heavy structures, typically supported by centralized computational solutions. In this paper, we present Dicoogle, a PACS archive supported by a document-based indexing system and by peer-to-peer (P2P) protocols. Replacing the traditional database storage (RDBMS) by a documental organization permits gathering and indexing data from file-based repositories, which allows searching the archive through free text queries. As a direct result of this strategy, more information can be extracted from medical imaging repositories, which clearly increases flexibility when compared with current query and retrieval DICOM services. The inclusion of P2P features allows PACS internetworking without the need for a central management framework. Moreover, Dicoogle is easy to install, manage, and use, and it maintains full interoperability with standard DICOM services.


How much money can be saved by applying intravenous antibiotics once instead of several times a day? The preparation, administration and monitoring of intravenous (IV) applications are time consuming and require human resources. We estimated the potential time and cost savings by replacing antibiotics given 3-4 times daily with antibiotics with similar spectrum and efficacy given once daily. The savings of indirect costs were estimated based on the antibiotic consumption data of a two-year period (i.e. 2007 and 2008), a nurse's mean workload per application and the average nurse's salary in Switzerland. The consumption of IV antibiotics in 2007 and 2008 at the University Hospital of Basel was 29.0 and 32.2 defined daily doses (DDD) per 100 patient days, respectively. Nurses spent an estimated 13,786 h on the application of the estimated 82,715 does of IV antibiotics. A total of 56,404 applications or nursing staff time costs of 338,436 Swiss Francs (CHF; 236,669 <euro>), equal to 16% of the overall costs spent on purchasing antibiotics in the year 2008, may have been saved by switching multiple-dose antibiotics to a hypothetical once-daily antibiotic. Including disposable materials, 21% or 456,884 CHF (319,499 <euro>) could be saved annually (purchase costs not taken into account). We found a potential cost saving of 21% of the purchase costs in a 750-bed institution. Hence, indirect costs should be included in the calculation of the total cost for the application of broad-spectrum IV antibiotics. Switching from a 3-4 times daily application to a once-daily antibiotic should be considered if a once-daily antibiotic is deemed equally effective and has a similar spectrum.


Hydroxamate siderophores of the ectomycorrhizal fungi Suillus granulatus and S. luteus. Despite indications that S. granulatus and S. luteus release iron-chelating compounds, the exact spectrum of ferric hydroxamates synthesized by these two Suillus species remained unclear. Hence the aim of this study was to identify all of the main siderophores produced by these two ectomycorrhizal fungal species under pure culture conditions. By means of HPLC and LC-MS analyses we show that S. granulatus releases cyclic and linear fusigen, ferrichrome, coprogen and triacetylfusarinine C into the nutrient medium, while S. luteus culture filtrates contain cyclic and linear fusigen, ferricrocin and coprogen. All of the different siderophores were identified on basis of reference compounds and their specific MS spectra which were recorded on a high resolution MS in positive electrospray ionisation mode. Initial HPLC separations were performed on a C-18 stationary phase, using an acidic eluent (0.1% formic acid in water and acetonitrile) in gradient mode. The potential of these two ectomycorrhizal fungal species to produce siderophores representing three different groups of hydroxamates is discussed in relation to its ecological significance.


A dynamic mechanical thermal analysis study of the viscoelastic properties and glass transition temperature behaviour of bioresorbable polymer matrix nanocomposites. The application of bioresorbable polymer nanocomposites in orthopaedics offer the potential to address several of the limitations associated with the use of metallic implants. Their enhanced biological performance has been demonstrated recently, but until now relatively little work has been reported on their mechanical properties. To this end, the viscoelastic properties and T(g) of bioresorbable polylactide-co-glycolide/α-tricalcium phosphate nanocomposites were investigated by dynamic mechanical thermal analysis. At room temperature of approximately 20°C, the storage moduli of the nanocomposites were generally higher than the storage modulus of the unfilled polymer due to the stiffening effect of the nano-particles. However at physiological temperature of approximately 37°C, the storage moduli of the nanocomposites decreased from 6.2 to 15.4% v/v nano-particle loadings. Similarly the T(g) of the nanocomposites also decreased from 6.2 to 15.4% v/v nano-particle loadings. These effects were thought to be due to weak interfacial bonding between the nano-particles and polymer matrix. The storage moduli at 37°C and T(g) increased from the minimum value when the particle loading was raised to 25.7 and 34.2% v/v loadings. SEM and particle size distribution histograms showed that at these loadings, there was a broad particle size distribution consisting of nano-particles and micro-particles and that some particle agglomeration was present. The consequent reduction in the interfacial area and the number of weak interfaces presumably accounts for the rise in the storage modulus at 37°C and the T(g).


Pitfalls of "hyper"-IgM syndrome: a new CD40 ligand mutation in the presence of low IgM levels. A case report and a critical review of the literature. Here, we report on a male infant with low serum IgG, IgA and IgM levels who suffered from Pneumocystis jirovecii and cytomegalovirus (CMV) pneumonia. The patient was tested to be HIV-negative. Absolute and relative numbers of lymphocyte subsets were normal, excluding the diagnosis of an X-linked agammaglobulinaemia (Bruton's disease). Despite the decreased serum IgM level, an X-linked hyper-IgM syndrome (X-HIGM) was considered. X-HIGM is a rare immunodeficiency usually characterised by recurrent severe opportunistic infections, low serum IgG and IgA, but normal or increased serum IgM. The syndrome is caused by mutations of the CD40 ligand (CD40L) gene. In our patient, CD40L mutation analysis proved a novel mutation at codon 257 associated with non-detectable expression of CD40L on the surface of activated T cells. A literature search revealed that approximately 6.4% of X-HIGM patients had been found to have low serum IgM levels. Our statistical analysis of the IgM levels as reported by different studies arouses suspicion that many patients with low IgM levels may not have undergone diagnostic procedures for X-HIGM. In summary, in this report and critical review of the literature, we described a new mutation of CD40L and highlighted the pitfalls of the diagnosis of X-HIGM.


Evaluating cell proliferation based on internal pore size and 3D scaffold architecture fabricated using solid freeform fabrication technology. The scaffold, as a medical component to regenerate tissues or organs in humans, plays an important role in tissue engineering. Recently, solid freeform fabrication (SFF) technology using computer-assisted methods was applied to address the problems of conventional fabrication methods in which the internal/outer architectures cannot be controlled. In this report, we propose suitable scaffolds for bone tissue regeneration considering the internal pore size and scaffold architecture. Poly(propylene fumarate) was used as the biodegradable photopolymer, and scaffolds were fabricated using microstereolithography (MSTL). We observed the relationship between the internal pores and architecture, and the proliferation of pre-osteoblast cells. To demonstrate the superiority of MSTL, we fabricated conventional and SFF scaffolds, and measured the cell proliferation rates for each. The results showed that cell proliferation on the MSTL scaffold was clearly superior and indicated that MSTL would be a good replacement for current conventional methods.


Endoglin suppresses human prostate cancer metastasis. Endoglin is a transmembrane receptor that suppresses human prostate cancer (PCa) cell invasion. Small molecule therapeutics now being tested in humans can activate endoglin signaling. It is not known whether endoglin can regulate metastatic behavior, PCa tumor growth, nor what signaling pathways are linked to these processes. This study sought to investigate the effect of endoglin on these parameters. We used a murine orthotopic model of human PCa metastasis, designed by us to measure effects at early steps in the metastatic cascade, and implanted PCa cells stably engineered to express differing levels of endoglin. We now extend this model to measure cancer cells circulating in the blood. Progressive endoglin loss led to progressive increases in the number of circulating PCa cells as well as to the formation of soft tissue metastases. Endoglin was known to suppress invasion by activating the Smad1 transcription factor. We now show that it selectively activates specific Smad1-responsive genes, including JUNB, STAT1, and SOX4. Increased tumor growth and increased Ki67 expression in tissue was seen only with complete endoglin loss. By showing that endoglin increased TGFβ-mediated suppression of cell growth in vitro and TGFβ-mediated signaling in tumor tissue, loss of this growth-suppressive pathway appears to be implicated at least in part for the increased size of endoglin-deficient tumors. Endoglin is shown for the first time to suppress cell movement out of primary tumor as well as the formation of distant metastasis. It is also shown to co-regulate tumor growth and metastatic behavior in human PCa.


Characterization of hybrid cells derived from spontaneous fusion events between breast epithelial cells exhibiting stem-like characteristics and breast cancer cells. Several data of the past years clearly indicated that the fusion of tumor cells and tumor cells or tumor cells and normal cells can give rise to hybrids cells exhibited novel properties such as an increased malignancy, drug resistance, or resistance to apoptosis. In the present study we characterized hybrid cells derived from spontaneous fusion events between the breast epithelial cell line M13SV1-EGFP-Neo and two breast cancer cell lines: HS578T-Hyg and MDA-MB-435-Hyg. Short-tandem-repeat analysis revealed an overlap of parental alleles in all hybrid cells indicating that hybrid cells originated from real cell fusion events. RealTime-PCR-array gene expression data provided evidence that each hybrid cell clone exhibited a unique gene expression pattern, resulting in a specific resistance of hybrid clones towards chemotherapeutic drugs, such as doxorubicin and paclitaxel, as well as a specific migratory behavior of hybrid clones towards EGF. For instance, M13MDA435-4 hybrids showed a marked resistance towards etoposide, doxorubicin and paclitaxel, whereas hybrid clones M13MDA-435-1 and -2 were only resistant towards etoposide. Likewise, all investigated M13MDA435 hybrids responded to EGF with an increased migratory activity, whereas the migration of parental MDA-MB-435-Hyg cells was blocked by EGF, suggesting that M13MDA435 hybrids may have acquired a new motility pathway. Similar findings have been obtained for M13HS hybrids. We conclude from our data that they further support the hypothesis that cell fusion could give rise to drug resistant and migratory active tumor (hybrid) cells in cancer.


Chronic beryllium disease: an updated model interaction between innate and acquired immunity. During the last decade, there have been concerted efforts to reduce beryllium (Be) exposure in the workplace and thereby reduce potential cases of this occupational lung disorder. Despite these efforts, it is estimated that there are at least one million Be-exposed individuals in the U.S. who are potentially at risk for developing chronic beryllium disease (CBD). Previously, we reviewed the current CBD literature and proposed that CBD represents a model interaction between innate and acquired immunity (Sawyer et al., Int Immunopharmacol 2:249-261, 2002). We closed this review with a section on "future directions" that identified key gaps in our understanding of the pathogenesis of CBD. In the intervening period, progress has been made to fill in some of these gaps, and the current review will provide an update on that progress. Based on recent findings, we provide a new hypothesis to explain how Be drives sustained chronic inflammation and granuloma formation in CBD leading to progressive compromised lung function in CBD patients. This paradigm has direct implications for our understanding of the development of an immune response to Be, but is also likely applicable to other immune-mediated lung diseases of known and unknown etiology.


Vesicular distribution of Secretory Pathway Ca²+-ATPase isoform 1 and a role in manganese detoxification in liver-derived polarized cells. Manganese is a trace element that is an essential co-factor in many enzymes critical to diverse biological pathways. However, excess Mn(2+) leads to neurotoxicity, with psychiatric and motor dysfunction resembling parkinsonism. The liver is the main organ for Mn(2+) detoxification by excretion into bile. Although many pathways of cellular Mn(2+) uptake have been established, efflux mechanisms remain essentially undefined. In this study, we evaluated a potential role in Mn(2+) detoxification by the Secretory Pathway Ca(2+), Mn(2+)-ATPase in rat liver and a liver-derived cell model WIF-B that polarizes to distinct bile canalicular and sinusoidal domains in culture. Of two known isoforms, only secretory pathway Ca(2+)-ATPase isoform 1 (SPCA1) was expressed in liver and WIF-B cells. As previously observed in non-polarized cells, SPCA1 showed overlapping distribution with TGN38, consistent with Golgi/TGN localization. However, a prominent novel localization of SPCA1 to an endosomal population close to, but not on the basolateral membrane was also observed. This was confirmed by fractionation of rat liver homogenates which revealed dual distribution of SPCA1 to the Golgi/TGN and a fraction that included the early endosomal marker, EEA1. We suggest that this novel pool of endosomes may serve to sequester Mn(2+) as it enters from the sinusoidal/basolateral domains. Isoform-specific partial knockdown of SPCA1 delayed cell growth and formation of canalicular domain by about 30% and diminished viability upon exposure to Mn(2+). Conversely, overexpression of SPCA1 in HEK 293T cells conferred tolerance to Mn(2+) toxicity. Taken together, our findings suggest a role for SPCA1 in Mn(2+) detoxification in liver.


Human B cell development and antibody production in humanized NOD/SCID/IL-2Rγ(null) (NSG) mice conditioned by busulfan. Busulfan treatment as a chemotherapeutic agent has been considered an alternative approach in xenograft model because it offers a simple, convenient, effective, and less toxic conditioning regimen. To investigate busulfan effects on the reconstitution of human immune cells and the generation of immune response to foreign antigens, we generated humanized NOD/SCID/IL-2Rγ(null) (NSG) mice conditioned either busulfan or total body irradiation (TBI) with hCD34(+) CB cells. Busulfan resulted in a high survival rate and effective reconstitution of human immune cells including B, T, macrophage, and dendritic cells in humanized NSG mice, compared to that of TBI. Moreover, the humanized NSG mice conditioned busulfan showed effective B cell development and thereby the high production of human antibody against immunized antigen. Humanized mice conditioned by busulfan provide a powerful and versatile tool for studying the entire process of human B-lymphocyte development and for producing specific human antibodies.


Binding of the general odorant binding protein of Bombyx mori BmorGOBP2 to the moth sex pheromone components. Insects use olfactory cues to locate hosts and mates. Pheromones and other semiochemicals are transported in the insect antenna by odorant-binding proteins (OBPs), which ferry the signals across the sensillum lymph to the olfactory receptors (ORs). In the silkworm, Bombyx mori (L.), two OBP subfamilies, the pheromone-binding proteins (PBPs) and the general odorant-binding proteins (GOBPs), are thought to be involved in both sensing and transporting the sex pheromone, bombykol [(10E,12Z)-hexadecadien-1-ol], and host volatiles, respectively. Quantitative examination of transcript levels showed that BmorPBP1 and BmorGOBP2 are expressed specifically at very high levels in the antennae, consistent with their involvement in olfaction. A partitioning binding assay, along with other established assays, showed that both BmorPBP1 and BmorGOBP2 bind to the main sex pheromone component, bombykol. BmorPBP1 also binds equally well to the other major pheromone component, bombykal [(10E,12Z)-hexadecadienal], whereas BmorGOBP2 discriminates between the two ligands. The pheromone analogs (10E,12Z)-hexadecadienyl acetate and (10E,12Z)-octadecadien-1-ol bind to both OBPs more strongly than does bombykol, suggesting that they could act as potential blockers of the response to sex pheromone by the male. These results are supported by further comparative studies of molecular docking, crystallographic structures, and EAG recording as a measure of biological response.


Combined impact of sexual risk behaviors for HIV seroconversion among women in Durban, South Africa: implications for prevention policy and planning. The objective of this study was to estimate the joint impact of demographic and sexual risk behaviors on HIV acquisition. A total of 2,523 HIV seronegative women were recruited through three community based studies in Durban, South Africa. Point and interval estimates of partial population attributable risk (PAR) were used to quantify the proportion of HIV seroconversions which can be prevented if a combination of risk factors is eliminated from a target population. More than 80% of the observed HIV acquisitions were attributed to five risk factors: lack of cohabitation, frequency of sex, sexually transmitted infections (STIs), incidence of pregnancy and not being employed/no income. Structural factors such as minimizing migratory patterns by ensuring cohabitation of partners, access to treatment of STIs, income generation and safe sex negotiation skills are likely to play an important role in future prevention strategies.


Soft drinks, sweetened beverages and risk of pancreatic cancer. Soft drinks usually contain sugar and caffeine that might influence pancreatic carcinogenesis. We considered the association between carbonated drink consumption and pancreatic cancer risk in an Italian case-control study conducted in 1991-2008 on 326 pancreatic cancer cases and 652 matched controls. We also combined the results from all the studies on soft drinks or sweetened beverages and pancreatic cancer published before June 2010, using a meta-analytic approach. In the case-control study, compared with non-drinkers, the multivariate odds ratio was 1.02 (95% confidence interval, CI, 0.72-1.44) for carbonated drink consumers and 0.89 (95% CI 0.53-1.50) for regular consumers (at least one drink/day). Besides our study, from the literature search, we identified 4 other case-control (1,919 cases) and 6 cohort studies (2,367 cases). The pooled relative risks (RR) for soft drink consumers vs. non-consumers were 0.97 (95% CI 0.81-1.16) for case-control, 1.05 (95% CI 0.94-1.17) for cohort, and 1.02 (95% CI 0.93-1.12) for all studies. The pooled RRs for heavy drinkers were 1.08 (95% CI 0.73-1.60) for case-control, 1.21 (95% CI 0.90-1.63) for cohort, and 1.16 (95% CI 0.93-1.45) for all studies. In conclusion, soft drink consumption is not materially related to pancreatic cancer risk.


Increased risk of adenomas in individuals with a family history of colorectal cancer: results of a meta-analysis. It is unclear to what extent the increased risk of colorectal cancer in individuals with a family history of colorectal cancer and no known genetic disorders is associated with a higher adenoma prevalence. Our aim is to estimate the relative difference in adenoma prevalence and its age-pattern in individuals with a family history of colorectal cancer compared to those without. We performed a literature search to identify colonoscopy studies reporting the adenoma prevalence by age. Using multilevel logistic regression, we examined how the adenoma prevalence by age differed between individuals with and without a family history of colorectal cancer. We excluded members of families with a known genetic disorder. Thirteen colonoscopy studies were identified. The adenoma prevalence was significantly higher in individuals with a family history than in those without (OR 1.7, 95% CI 1.4-3.5). The adenoma prevalence increased with age (OR per year of age 1.06, 95% CI 1.05-1.07). The age trend did not differ significantly between the two groups. Individuals with a family history of colorectal cancer have a considerably higher prevalence of adenomas compared to individuals without a family history. This is consistent with their increased risk of colorectal cancer.


Discussion of sexual risk behavior in HIV care is infrequent and appears ineffectual: a mixed methods study. Consensus guidelines in HIV care call for clinicians to provide a brief sexual risk behavioral intervention in each visit. Studies based on participant reports find this occurs infrequently, but studies based on direct observation of clinical encounters are lacking. We conducted a mixed method study that used audio recordings of 116 routine outpatient visits by 58 different patients with HIV, in five different practice sites. Transcripts of the visits were coded and analyzed using a quantitative system. In addition, we conducted a qualitative analysis of the dialogue segments in which sexual risk behaviors arose as a topic. Discussion of sexual risk behavior occurred in 10 visits, and was generally quite brief. Two visits featured substantial counseling about sexual risk reduction; two others included substantial discussion which was not evidently directed at the patient's changing behavior. Cues suggesting a need or opportunity for such discussion that physicians did not follow up on occurred in seven additional visits. Interactions about sexual risk had less patient engagement than interactions about other health behaviors. Physicians seldom provide sexual risk reduction counseling in HIV care, even where specific indications are present.


Triphenyltin induced growth inhibition and antioxidative responses in the green microalga Scenedesmus quadricauda. The toxicity of organotin compounds in the environment is closely related to their uptake by microorganisms and delivery through the food chain. The population at low trophic levels like microalgae plays an important role in this aspect. In this study, the toxic effects of triphenyltin (TPT) on Scenedesmus quadricauda were assessed at the population, cellular and subcellular levels. The alga was exposed to TPT of up to 64 μg l(-1) (nearly lethal concentration), but the algal growth was inhibited significantly when TPT was elevated to 8 μg l(-1). This growth inhibition was correlated to the presence of oxidative stress as evidenced by the accumulation of malondialdehyde (MDA) and confirmed by fluorescent probing of the intracellular reactive oxygen species (ROS) levels. The imbalanced activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) may lead to an accumulation of intracellular H(2)O(2), which can initiate an oxidative damage to cell components and cause growth inhibition and finally cell death. The detachment of plasma membrane from cell wall, the structural change of chloroplasts as well as the increased number and size of starch granules together with electron-dense deposits in chloroplasts were noticed through electron microscopic examination. It was suggested that mitochondria, chloroplasts and protoplasm might be the direct targets of TPT toxicity. This study confirmed that TPT poisoning on phytoplankton can happen at very low concentrations. There existed different defense mechanisms e.g., antioxidant enzyme activation, starch accumulation and possibly metal sequestration in algal species as the means to resist TPT toxicity.


Site-activated chelators derived from anti-Parkinson drug rasagiline as a potential safer and more effective approach to the treatment of Alzheimer's disease. chelators can modulate β-amyloid accumulation, protect against tau hyperphosphorylation, and block metal-related oxidative stress, and thereby hold considerable promise as effective anti-AD drugs. At present, a growing interest is focusing on increasing the efficacy and targeting of chelators through drug design. To this end, we have developed a new class of multifunctional prochelators from three FDA- approved drugs rasagiline, rivastigmine, and donepezil or tacrine. HLA20 A was designed by merging the important pharmacophores of rasagiline, rivastigmine, and donepezil into our newly developed multifunctional chelator HLA20. M30D was constructed using the key pharmacophoric moieties from rasagiline, rivastigmine, and tacrine. Experiments showed that both compounds possess potent anti-acetylcholinesterase (AChE) activity in vitro with weak inhibition of butyrylcholinesterase (BuChE), and without significant metal-binding activity. M30D was found also to be a highly potent MAO A inhibitor with moderate inhibition of MAO B in vitro. Both HLA20 and M30D can be activated by inhibition of AChE to release active chelators HLA20 and M30, respectively. HLA20 and M30 have been shown to be able to modulate amyloid precursor protein regulation and beta-amyloid reduction, suppress oxidative stress, and passivate excess metal ions (Fe, Cu, and Zn). Compared with the activated chelator HLA20 or M30, both HLA20A and M30D exhibited lower cytotoxicity in SH-SY5Y neuroblastoma cells, substantiating the prochelator strategy for minimizing toxicity associated with poor targeted chelators.


The correlation of mentoring and job satisfaction: a pilot study of mental health professionals. A pilot study examined the relationship between job satisfaction and perceived mentoring among 56 mental health supervisors and practitioners in a county mental health agency. Participants completed the Alleman Mentoring Activities Questionnaires and the Job Descriptive Index and Job in General Scale. Practitioners who perceived they were involved in mentoring relationships with supervisors were more satisfied with their jobs than those who perceived that they were not involved in mentoring relationships. The mentoring functions of sponsoring, assigning challenging tasks, and demonstrating trust predicted job satisfaction. Recommendations include incorporating mentoring functions in supervisory training to increase mental health professionals' job satisfaction.


Engaging religious experience in stroke rehabilitation. In this article, I respond to the problem of engaging with religious experience in health care environments. In particular, I illuminate the relational aspects of religious experience in the context of stroke rehabilitation by providing a commentary on data gathered from existing qualitative research and personal narratives in the acute and rehabilitation phases of stroke recovery. In so doing, I address the necessary balance of empathy and alterity in the art of resonant listening. I also provide some critical reflections on interdisciplinary approaches to engaging with religious experience with reference to a largely overlooked group of health care professionals-hospital chaplains.


Apparitions and possessions as boundary objects: an exploration into some tensions between mental health care and pastoral care. Apparitions and possessions can be taken as genuine spiritual events or as symptoms of psychopathology. We focus upon occasions when the two seemingly conflicting "interpretations" co-exist in order to explore these phenomena as kinds of boundary objects-polymorphous realities stable and graspable enough, yet belonging to different worlds at once. Related diagnostic knowledge is often uncertain and always incomplete. Yet it enables authoritative and effective professional interventions. We conclude by discussing the relevance of such a view for contemporary efforts to validate patients' spiritual experiences within mental health care.


Anti-inflammatory effects of chronic aspirin on brain arachidonic acid metabolites. Pro-inflammatory and anti-inflammatory mediators derived from arachidonic acid (AA) modulate peripheral inflammation and its resolution. Aspirin (ASA) is a unique non-steroidal anti-inflammatory drug, which switches AA metabolism from prostaglandin E₂ (PGE₂) and thromboxane B₂ (TXB₂) to lipoxin A₄ (LXA₄) and 15-epi-LXA₄. However, it is unknown whether chronic therapeutic doses of ASA are anti-inflammatory in the brain. We hypothesized that ASA would dampen increases in brain concentrations of AA metabolites in a rat model of neuroinflammation, produced by a 6-day intracerebroventricular infusion of bacterial lipopolysaccharide (LPS). In rats infused with LPS (0.5 ng/h) and given ASA-free water to drink, concentrations in high-energy microwaved brain of PGE₂, TXB₂ and leukotriene B₄ (LTB₄) were elevated. In rats infused with artificial cerebrospinal fluid, 6 weeks of treatment with a low (10 mg/kg/day) or high (100 mg/kg/day) ASA dose in drinking water decreased brain PGE₂, but increased LTB₄, LXA₄ and 15-epi-LXA₄ concentrations. Both doses attenuated the LPS effects on PGE₂, and TXB₂. The increments in LXA₄ and 15-epi-LXA₄ caused by high-dose ASA were significantly greater in LPS-infused rats. The ability of ASA to increase anti-inflammatory LXA₄ and 15-epi-LXA₄ and reduce pro-inflammatory PGE₂ and TXB₂ suggests considering aspirin further for treating clinical neuroinflammation.


Preparation, characterization and in vitro testing of poly(lactic-co-glycolic) acid/barium titanate nanoparticle composites for enhanced cellular proliferation. The recent advancements in tissue engineering and, more in general, in cell-based applications, has led to an ever increasing interest toward new materials for sustained cell proliferation and differentiation. Here, the preparation and the characterization of scaffolds based on poly(lactic-co-glycolic) acid / barium titanate nanoparticle composites are presented. In vitro testing on H9C2 cell line demonstrates how the presence of the nanoparticles positively affects both the proliferation and the differentiation of this muscle-like cell line. Finally, the possibility to obtain porous scaffold and, therefore, an actual 3D culture system, is introduced.


Kids' Life and Times: using an Internet survey to measure children's health-related quality of life. To examine the psychometric properties of an Internet version of a children and young person's quality of life measure originally designed as a paper questionnaire. Participants were 3,440 children aged 10 and 11 years in Northern Ireland who completed the KIDSCREEN-27 online as part of a general attitudinal survey. The questionnaire was animated using cartoon characters that are familiar to most children and the questions appeared on screen and were read aloud by actors. Exploratory principal component analysis of the online version of the questionnaire supported the existence of five components in line with the paper version. The items loaded on the components that would be expected based on previous findings with five domains--physical well-being, psychological well-being, autonomy and parents, social support and peers, and school environment. Internal consistency reliability of the five domains was measured using Cronbach's alpha, and the results suggested that the scale scores were reliable. The domain scores were similar to those reported in the literature for the paper version. These results suggest that the factor structure and internal consistency reliability scores of the KIDSCREEN-27 embedded within an online survey are comparable to those reported in the literature for the paper version.


The Generation R study: a candidate gene study and genome-wide association study (GWAS) on health-related quality of life (HRQOL) of mothers and young children. The aim of this paper is to describe the Generation R study as a template that enables candidate gene study and genome-wide association study regarding health-related quality of life (HRQOL) of mothers and their young children. Generation R is a population-based prospective cohort study from fetal life onwards in Rotterdam, The Netherlands. Children were born in 2002-2006. Blood from mothers and placenta cord blood were sampled. Mothers' HRQOL was measured 5 times during pregnancy and after birth using SF-12 and EQ-5D. Children's HRQOL was measured 5 times between age 1 and 5/6 years using Infant-Toddler Quality Of Life questionnaire (ITQOL), Health Status Classification System PreSchool (HSCS-PS) and Child Health Questionnaire Parent Form 28 items (CHQ-PF28), respectively. DNA is available for 8,055 mothers and 5,908 children. Genotyping of various candidate genes and a genome-wide association (GWA) scan (Illumina 610K) of child DNA were done. A template for gene-HRQOL analyses is provided. We start with candidate gene study on HRQOL of mothers and children. Gene-environment interaction and interaction with medical indicators of health status will be explored. Next, GWA study on HRQOL will be performed. Gaining insight into the determinants of HRQOL is essential to assisting efforts in health policy and clinical application to improve well-being and health. In the future, it might be possible to complement HRQOL assessments by examinations of genetic markers. Strengths and weaknesses of the Generation R study are discussed.


Carotid atheromatic plaque is commonly associated with hypopituitary men. Hypopituitarism increases the risks of many cardiovascular conditions and therefore, patients with this disease are more prone to cardiovascular disease. To our knowledge, there have been few studies on carotid artery plaque in male patients with hypopituitarism in assessing cardiovascular risks. The aim of this study was to specifically compare carotid artery plaque while examining other major cardiovascular risk factors between male patients with hypopituitarism and control subjects. Forty male patients aged 30-70 years with hypopituitarism and forty age, sex- matched control subjects were recruited at the Yonsei University Severance Hospital, Seoul, Korea. Carotid intima media thickness (IMT) and atheromatous plaque, anthropometry, lipid profile, and pituitary hormones were assessed. Atheromatous plaque in the carotid arteries was observed more frequently in patients with hypopituitarism than age- and sex-matched control subjects (59.5% vs. 2.5%, P<0.01) without differences of carotid IMTs. Patients with hypopituitarism also exhibited higher waist circumference, waist to hip ratio, total cholesterol and LDL cholesterol than control subjects. In subgroup analysis in male patients with hypopituitarism including GH deficiency, lower testosterone levels were associated with higher waist circumference (r=0.446, P=0.033). In conclusion, hypopituitary males exhibit an increased incidence of carotid artery plaque without differences of carotid IMTs, central obesity and higher total cholesterol level. Lower testosterone levels were associated with central obesity- a strong component of a metabolic syndrome, and unsubstituted testosterone deficiency might be an important cardiovascular risk factor in patients with hypopituitarism.


Glasgow Prognostic Score is a predictor of perioperative and long-term outcome in patients with only surgically treated esophageal cancer. Systemic inflammation (SI) plays a pivotal role in cancer. C-reactive protein (CRP) and albumin as parameters of SI form the Glasgow Prognostic Score (GPS). The purpose of the study was to evaluate the potential prognostic role of GPS in a homogeneous population of esophageal cancer (EC) patients undergoing only resection. GPS was evaluated on the basis of admission blood sample taken before surgery. Patients with a CRP < 10 mg/L and albumin > 35 g/L were allocated to GPS0 group. If only CRP was increased or albumin decreased patients were allocated to the GPS1 and patients in whom CRP was ≥10 mg/L and albumin level ≤35 g/L were classified as GPS2. GPS was correlated to clinicopathological parameters and clinical outcome. Increasing GPS significantly correlated with more aggressive tumor biology in terms of tumor size (P < 0.001), presence of regional (P = 0.01) and nonregional lymph node metastasis (P = 0.02), and higher tumor recurrence rate (P < 0.001). Furthermore, GPS was identified as an independent prognosticator of perioperative morbidity (odds ratio 1.9; P = 0.03). In addition, a gradual decrease in disease-free and overall survival was evident between the three GPS subgroups. Survival differences between the GPS groups remained apparent even after stratification of the study population to underlying tumor type and nodal status. GPS was identified as a strong prognosticator of tumor recurrence (hazard ratio 2.5; P < 0.001) and survival (hazard ratio 3.0; P < 0.001) in EC. GPS represents a strong prognosticator of perioperative morbidity and long-term outcome in resected EC patients without neoadjuvant or adjuvant treatment.


Single-incision transumbilical laparo-endoscopic gastric benign tumor resection. The authors report resection of a gastric benign tumor through single-incision laparoscopy, guided by peroperative gastroscopy. VIDEO: A 25-year-old man consulted after diagnosis of a 40 × 20 cm(2) endoluminal lesion of the gastric cardia. Preoperative work-up showed a stromal tumor with invasion of the muscular layer. The umbilical scar was incised and, after placement of a purse-string suture, an 11-mm nondisposable trocar was inserted for a 10-mm 30° angled scope. Curved and reusable instruments (Karl Storz-Endoskope, Tuttlingen, Germany) and straight ultrasonic shears (Ethicon Endosurgery, Cincinnati, OH, US) were inserted transumbilically. Peroperative gastroscopy located the lesion on the smaller gastric curvature, 1 cm from the gastroesophageal junction. A stitch was placed in the center of the lesion, and gastroscopic grasper helped in maintaining the limits of resection. Gastrostomy was closed using two converting absorbable running sutures. Because of the curves of the instruments there was no conflict between the instruments' tips inside the abdomen (Fig. 1a), or between the surgeon's hands outside the abdomen (Fig. 1b). Leak test with the gastroscope checked the integrity of the suture. The specimen was retrieved transumbilically in a plastic bag. Operative time was 150 min, and the umbilical incision was less than 15 mm. The patient was discharged after 5 days, and he is doing well 3 months postoperatively. Laparoscopic gastric resection can be safely performed through a single-access. Peroperative gastroscopy permits the limits of resection to be precisely determine, and use of curved and reusable instruments allows surgeon to achieve ergonomic conditions as in classic laparoscopy, without increasing the laparoscopic cost.


Balancing fertility and oncologic outcomes: can we have our cake and eat it too?


Phylogenetic analysis and inflow route of Tomato yellow leaf curl virus (TYLCV) and Bemisia tabaci in Korea. Tomato yellow leaf curl virus (TYLCV) is a member of the genus Begomovirus of the family Geminiviridae, members of which are characterized by closed circular single-stranded DNA genomes of 2.7-2.8 kb in length, and include viruses transmitted by the Bemisia tabaci whitefly. No reports of TYLCV in Korea are available prior to 2008, after which TYLCV spread rapidly to most regions of the southern Korean peninsula (Gyeongsang-Do, Jeolla-Do and Jeju-Do). Fifty full sequences of TYLCV were analyzed in this study, and the AC1, AV1, IR, and full sequences were analyzed via the muscle program and bayesian analysis. Phylogenetic analysis demonstrated that the Korea TYLCVs were divided into two subgroups. The TYLCV Korea 1 group (Masan) originated from TYLCV Japan (Miyazaki) and the TYLCV Korea 2 group (Jeju/Jeonju) from TYLCV Japan (Tosa/Haruno). A B. tabaci phylogenetic tree was constructed with 16S rRNA and mitochondria cytochrome oxidase I (MtCOI) sequences using the muscle program and MEGA 4.0 in the neighbor-joining algorithm. The sequence data of 16S rRNA revealed that Korea B. tabaci was closely aligned to B. tabaci isolated in Iran and Nigeria. The Q type of B. tabaci, which was originally identified as a viruliferous insect in 2008, was initially isolated in Korea as a non-viruliferous insect in 2005. Therefore, we suggest that two TYLCV Japan isolates were introduced to Korea via different routes, and then transmitted by native B. tabaci.


Inhibitory effects of ginger (Zingiber officinale Roscoe) essential oil on leukocyte migration in vivo and in vitro. Zingiber officinale Roscoe, popular name ginger, is grown naturally in many parts of the world, including Brazil. Ginger is used in pharmaceutical, cosmetic, and food and beverage industries and the essential oil has been used in folk medicine for manifold conditions including as an analgesic, anti-inflammatory, and antirheumatic. The purpose of this study was to investigate the effects of ginger (Zingiber officinale Roscoe) essential oil (GEO) in an in vitro chemotaxis assay and on leukocyte-endothelial interactions in vivo. GEO was analyzed by GC-MS and the main components identified were ar-curcumene (59%), β-myrcene (14%), 1,8-cineol (8%), citral (7.5%), and zingiberene (7.5%). Oral administration of GEO (200-500 mg/kg) reduced the rolling and leukocyte adherence after 2 h of carrageenan injection (100 μg) into the scrotal chamber. The number of leukocytes migrated to the perivascular tissue 4 h after the irritant stimulus was also diminished. GEO in all doses tested (10(-4), 10(-3), or 10(-2) μL/mL) caused a significant reduction of leukocyte chemotaxis (35.89 ± 4.33, 30.67 ± 0.70, and 35.85 ± 3.83%, respectively) toward casein stimuli. The data presented showed direct and systemic effects of GEO on leukocyte migration as an important mechanism of the anti-inflammatory action of ginger.


Quantitative analysis of neosalacinol and neokotalanol, another two potent α-glucosidase inhibitors from Salacia species, by LC-MS with ion pair chromatography. A quantitative analytical method for the highly polar sulfonium pseudo-sugar constituents neosalacinol (3) and neokotalanol (4), another two potent α-glucosidase inhibitors isolated from Ayurvedic traditional medicine Salacia species, was developed by employing an ion pair reagent upon chromatographic separation. The optimum conditions for separation and detection of these two constituents were achieved on an ODS column (3-µm particle size, 2.1-mm i.d. × 100 mm) with 5 mM undecafluorohexanoic acid-MeOH (99:1, v/v) as the mobile phase and using MS equipped with an electrospray ionization source. More than ten samples of Salacia from different origins were analyzed, and the results indicated that the assay was reproducible and precise and could be readily utilized for evaluation of α-glucosidase inhibitory activity of Salacia species. By combining this assay with the quantitative analytical method previously developed for salacinol (1) and kotalanol (2), a more precise and strict evaluation of α-glucosidase inhibitory activities of extracts from Salacia species (R = 0.959 for maltase and 0.795 for sucrase) was achieved.


On the role of arbitration of discordant double readings of screening mammography: experience from two Italian programmes. The authors sought to assess the role of arbitration by a third reader of discordant double readings to reduce the rate of recalls to diagnostic assessment. A consecutive series of 7,660 double readings of screening examinations were considered. Discordant recalls were arbitrated by an expert reader (negative/positive). Diagnostic assessment was performed irrespective of arbitration results, and its outcome was used as reference standard for the study purpose. Assuming that negative arbitration would deny recall, its impact was assessed in terms of reduced recall rate and reduced cancer detection rate. Cost analysis of introducing arbitration was performed according to these results. Recalls at double reading were 528 (6.8%), of which 230 (43.5%) were concordant and 298 (56.5%) were discordant. The latter underwent arbitration, which was negative in 216 (72.4%) and positive in 82 (27.6%) cases, respectively. Overall, 49 cancers were detected (6.39 ‰ screened, 9.2% recalled): 43 cancers were detected among concordant (5.6 ‰ screened, 18.6% concordant) and six among discordant recalls (0.7 ‰ screened, 2.0% discordant). Six cancers were observed among arbitrated cases: five (6%) in positive and one (4.6 ‰) in negative arbitrations. Negative arbitration would have spared 216 assessment procedures (2.8% absolute, 40.9% relative reduction of recall rate) while missing one cancer case (0.13 ‰ absolute, 2.0% relative reduction of cancer detection rate). Arbitration cost was 74 euro, whereas 216 spared assessment procedures would have cost 14,558.4-23,346 euro. Arbitration is a cost-effective procedure that could be employed as a first measure to counterbalance excess recall rate observed in a double-reading scenario.


The role of nasoenteric intubation in the MR study of patients with Crohn's disease: our experience and literature review. The aim of this study was to compare magnetic resonance (MR) enteroclysis with MR enterography to verify whether nasoenteric intubation in patients affected by Crohn's disease can provide supplementary information to that afforded by MR study of the small bowel. In a 12-month period, 40 patients (28 women and 12 men, mean age 35 years) affected by Crohn's disease underwent MR imaging. Distension of the small-bowel loops was obtained by administering polyethylene glycol: 15 patients were given the mixture by mouth (MR enterography), whereas the remaining 25 received it via nasoenteric intubation (MR enteroclysis). Our study protocol included morphological sequences taken before and after intravenous injection of contrast medium and real-time functional sequences. Accuracy criteria for the execution of the examinations were designed according to 11 bands. Complete distension of the small-bowel loops was obtained in the 25 patients who underwent MR enteroclysis, with the additional advantage of a suitable assessment of those segments involved in the pathological process. This was not the case for the 15 patients who underwent MR enterography, because both the jejunum and the small-bowel loops appeared partially collapsed. MR enteroclysis is the most effective technique for studying the small bowel in Crohn's disease, as it not only provides a suitable morphological assessment but also supplies functional information.


Role of echocardiography and cardiac MRI in depicting morphological and functional imaging findings useful for diagnosing hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy (HCM) is a hereditary disease characterised by primary hypertrophy of the left and/or right ventricle. The reference standard for imaging diagnosis is echocardiography. The aim of our study was to prospectively compare the diagnostic accuracy of echocardiography and cardiac magnetic resonance (MR) imaging in patients with HCM. Twenty-two consecutive patients with a known diagnosis of HCM were prospectively evaluated, with echocardiography and cardiac MR imaging performed within 2 weeks of each other (mean interval 7 days, range 2-14 days). Two experienced radiologists blinded to the previous clinical and imaging findings separately reviewed the images. The following parameters were calculated for both techniques: myocardial mass, wall thickness, end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), systolic anterior motion (SAM) of the mitral valve and degree of myocardial fibrosis (based on the ultrasonic reflectivity at echocardiography and degree of late enhancement at cardiac MR imaging). The statistical correlation was calculated with Student's t test, Spearman coefficient and Fisher's exact test. A value of p<0.05 was considered significant. The diagnosis of HCM was confirmed in all patients with both techniques, with absolute agreement in terms of the site of disease. The mean value of myocardial mass presented a statistically significant difference between the two techniques (114 g, p<0.001). In contrast, a nonsignificant difference between echocardiography and cardiac MR imaging was found for EDV (102 ml vs 111 ml; p=0.31), ESV (30 ml vs 38 ml; p=0.1), EF (74% vs 68%, p=0.5), SAM (p=0.1) and myocardial fibrosis (p=0.15). Cardiac MR imaging correlates well with echocardiography in defining the morphological and functional parameters useful for the imaging diagnosis of HCM and therefore, in selected cases (poor acoustic window, doubtful echocardiography findings), it may be a valid alternative to echocardiography.


Off-label use of intravascular iodinated organic and MR contrast media. This paper analyses off-label prescribing of the iodinated organic and magnetic resonance (MR) contrast media used in diagnostic imaging and evaluates the liability profiles and medicolegal issues associated with such use. The term off-label generally indicates the use of known drugs for which new scientific evidence suggests use in a manner and in clinical scenarios not explicitly addressed by the drug data sheet and is outside the indications for which the medication was approved. In addition, the term also indicates the use of drugs with a different route of administration and dosage from those indicated in the information leaflet. Intravascular contrast media used in diagnostic imaging are drugs in the complete sense of the term, even though they have unique characteristics which in many ways distinguish them from other pharmacological agents. The off-label use of contrast media in diagnostic imaging is a little-investigated field and most commonly, but not exclusively, applies to gadolinium-based contrast media used in MR angiography as well as cardiac and paediatric applications. In particular, the off-label use of contrast media mostly concerns deviations from the recommended dose. As contrast media are to all effects pharmaceutical agents, their off-label use can be considered admissible within the limitations laid down by the Italian law in force (Article 3 of Law 94/98) and its interpretation, i.e. the following criteria must be present: the lack of a valid diagnostic alternative; written informed consent by the patient; the presence of scientific publications validated at the international level; assumption of responsibility by the radiologist. The use of contrast media in modern image-guided medicine is essential. In cases in which the information contained in the information leaflet is modified and updated in any way whatsoever (indications, dosage, at others), specifically if restrictions are introduced in accordance with the law in force, the pharmaceutical industry must provide formal and timely notification to radiologists. On their part as prescribers and users of contrast media, radiologists must remain up to date regarding any changes in indications, dosage and route of administration. Lastly, we propose that the radiology report includes not only the type but also the dose of contrast medium used.


Editors' overview: topics in the responsible management of research data. Responsible data management is a multifaceted topic involving standards within the research community regarding research design and the sharing of data as well as the collection, selection, analysis and interpretation of data. Transparency in the manipulation of images is increasingly important in order to avoid misrepresentation of research findings, and research oversight is also critical in helping to assure the integrity of the research process. Intellectual property issues both unite and divide academe and industry in their approaches to data management. Central to the realization and promulgation of responsible data management is clear and careful communication of standards and expectations within the research community to trainees as well as among colleagues. These topics are examined and explored in depth in a special issue of Science and Engineering Ethics on responsible data management.


Dual-source CT coronary angiography: prospective versus retrospective acquisition technique. The aim of our work was to compare image quality and radiation dose in a group of patients who underwent cardiac dual-source computed tomography (DSCT) with prospective electrocardiographic (ECG) gating with those of a control group studied with retrospective gating. Sixty patients were randomly assigned to two groups of 30 individuals each. Patients with heart rates >70 bpm and body mass index (BMI) >30 kg/m(2) were excluded. Group A was examined with prospective ECG gating and group B with retrospective gating. The dose-length product (DLP) was recorded to calculate the radiation dose, whereas the effective dose was normalised to a standard 12-cm scan of the heart. Applying the best reconstruction interval, 98.6% of segments in the prospective group and 99.3% in the retrospective group were diagnostic. No significant difference (p>0.05) in image quality was observed between groups. Mean normalised radiation dose was 4.91 ± 0.4 mSv in the prospective-gating group and 14.62 mSv ± 4.36 in the retrospective-gating group (p<0.01). Coronary CT with prospective ECG gating, a standard feature on new scanners, allows for a significant reduction in radiation dose without causing any significant decrease in image quality or in the number of segments assessed. The prospective technique is thus recommended for patients with heart rates £70 bpm and BMI £30 kg/m(2).


Binding of heparin to metals.

Binding of heparin to metals. Heparin is a major prophylactic and treatment agent for thrombosis. Structurally, this anticoagulant is a polydisperse, highly negatively charged polysaccharide mixture that contains a variable density of sulfate group substituents per molecule. Previous study has shown that heparin molecules have a high affinity for a wide range of metal ions with varying oxidation states. However, reports in literature on binding of heparin to metals have investigated only a small sampling of heparin-metal ion interactions. Since interaction of heparin with fluid phase and cell surface macromolecules in vivo is dependent on the heparin structure when bound in a metal ion complex, a survey of the physical parameters for heparin binding to metals is imperative. Atomic absorption and spectrophotometry experiments were performed for metal quantification, and in this study, the relative values for affinity constants and number of binding sites for heparin binding to several alkaline, alkaline earth, main group, and transition metals in their most common oxidation states are reported. We found an overall trend for heparin-metal affinity to be Mn(2+) > Cu(2+) > Ca(2+) > Zn(2+) > Co(2+) > Na(+) > Mg(2+) > Fe(3+) > Ni(2+) > Al(3+)> Sr(2+), with the trend in N (b) being opposite compared with the K (a).


Postprandial lipemia detects the effect of soy protein on cardiovascular disease risk compared with the fasting lipid profile. Studies examining the effect of soy protein on cardiovascular disease (CVD) risk factors have not taken advantage of the postprandial state as an adjunct to the fasting lipid profile. The American Heart Association has acknowledged the efficacy of soy protein in reducing CVD risk factors to be limited. We hypothesized that the postprandial state would be more sensitive to any favorable changes associated with consuming soy protein compared with the fasting lipid profile. Furthermore, the presence of isoflavones in soy would enhance this effect. Thirty sedentary males aged 18-30 years were randomly assigned to milk protein (Milk), isoflavone-poor soy (Soy-), or isoflavone-rich soy (Soy+). Usual diets were supplemented with 25 g/day of protein for 28 days. Serum samples were collected before and after supplementation in a fasted state and postprandially at 30, 60, 120, 240, and 360 min after a high-fat, 1,000 kcal shake. Triacylglycerol (TAG), total cholesterol, non-esterified fatty acids, apolipoproteins B-100 and A-I and glucose concentrations were quantified. Fasting concentrations were not different after any protein supplementation. Postprandial TAG and TAG AUC increased after Soy-consumption supporting the postprandial state as a more sensitive indicator of soy ingestion effects on CVD risk factors compared with the fasting lipid profile. Furthermore, the absence of isoflavones in soy protein may have deleterious consequences on purported cardio-protective effects.


Increased ghrelin sensitivity and calorie consumption in subordinate monkeys is affected by short-term astressin B administration. Animals chronically exposed to stressors with access to diets high in fat and sugar consume and prefer these diets, a result consistent with the association between stress and comfort food ingestion in humans. As social subordination in rhesus monkeys provides an ethologically relevant translational model of psychosocial stress, we tested the hypothesis that differences in food intake between dominant and subordinate female monkeys are due to corticotropin-releasing hormone-(CRH) induced alteration in sensitivity to ghrelin, a potent orexigenic signal. We assessed food intake of animals given a choice between a low (LCD) and high calorie diet (HCD) in response to 4-day treatment with the CRH receptor antagonist, astressin B, and to an acute treatment of ghrelin. Ghrelin stimulated intake of LCD in subordinates but did not further increase consumption of HCD, whereas ghrelin decreased LCD consumption without affecting HCD intake in dominant females. Astressin B decreased cortisol levels and increased preference for and intake of the HCD in subordinates and decreased calorie intake and HCD preference in dominant animals. These results suggest that increased caloric intake by subordinates may, in part, be explained by a greater sensitivity to postprandial increases in ghrelin and that CRH receptor antagonism leading to a decrease in cortisol has mixed effects on food choice depending on an individual's stress background.


Barth syndrome: an X-linked cardiomyopathy with a novel mutation. The authors report a 6 yr old boy with Barth syndrome who presented with cardiomyopathy, neutropenia and hypotonia. Urine gas chromatography showed high level of 3-methylglutaconic acid. The DNA of both the patient and the mother showed a heterozygous 3 bp deletion in exon 8 of the tafazzin gene. This abnormality involves the deletion of the bases TGA starting at cDNA nucleotide 891 (c891_893delTGA), resulting in the absence of glutamic acid at codon 202 from a highly conserved area of the tafazzin protein, consistent with the diagnosis of Barth syndrome. This is the first case report of Barth syndrome in Arab population emphasizing the importance of detailed investigations in cases of hereditary cardiomyopathy.


Prostate cancer screening.

Prostate cancer screening. Prostate cancer is the most common cancer and the second leading cause of cancer-related deaths in American men. Although the use of the prostate-specific antigen (PSA) test for prostate cancer screening since the 1990s has led to increased early diagnoses, the most recent studies are in conflict about the risks and benefits of routine prostate cancer screening. Recently, evidence has emerged to support the use of the PSA test to lower mortality, but there is still concern that over-diagnosis may lead to over-treatment of cancers that would not significantly affect patients' health for several years. This article describes the results of important recent prostate cancer screening trials, the National Comprehensive Cancer Network and American Cancer Society screening guidelines, and discusses the implications for clinical practice.


C/EBPβ and CHOP participate in tanshinone IIA-induced differentiation and apoptosis of acute promyelocytic leukemia cells in vitro. Our studies indicated that Tanshinone IIA (TanIIA), which is widely applied in the treatment of cardiovascular diseases with a rare occurrence of side effects, could promote APL cell differentiation and apoptosis. We found TanIIA induced the differentiation of NB4 and MR2 cells with elevated C/EBPβ and CHOP. When C/EBPβ was overexpressed in NB4 cells, the level of CD11b in the transfected cells was significantly elevated. When we used CHOP siRNA to suppress CHOP expression in NB4 cells and then treated these cells with a high concentration of TanIIA, the differentiation and apoptosis of these cells were both significantly increased. These data demonstrate that C/EBPβ is critical for APL cell differentiation and apoptosis induced by TanIIA, and that CHOP acts as a negative regulator of C/EBPβ activity. Our study suggested that TanIIA is a promising drug for treating newly diagnosed and ATRA-resistant APL, and a high concentration of TanIIA associated with inhibition of CHOP, maybe a potentially promising therapy strategy.


Compartmentalization of the deep cerebellar nuclei based on afferent projections and aldolase C expression. The distribution of aldolase C (zebrin II)-positive and -negative Purkinje cells (PCs) can be used to define about 20 longitudinally extended compartments in the cerebellar cortex of the rat, which may correspond to certain aspects of cerebellar functional localization. An equivalent compartmental organization may exist in the deep cerebellar nuclei (DCN). This DCN compartmentalization is primarily represented by the afferent projection pattern in the DCN. PC projections and collateral nuclear projections of olivocerebellar climbing fiber axons have a relatively localized terminal arbor in the DCN. Projections of these axons make a closed olivo-cortico-nuclear circuit to connect a longitudinal stripe-shaped cortical compartment to a small subarea in the DCN, which can be defined as a DCN compartment. The actual DCN compartmentalization, which has been revealed by systematically mapping these projections, is quite different from the cortical compartmentalization. The stripe-shaped alternation of aldolase C-positive and -negative narrow longitudinal compartments in the cerebellar cortex is transformed to the separate clustering of positive and negative compartments in the caudoventral and rostrodorsal DCN, respectively. The distinctive projection of aldolase C-positive and -negative PCs to the caudoventral and rostrodorsal DCN underlies this transformation. Accordingly, the medial cerebellar nucleus is divided into the rostrodorsal aldolase C-negative and caudoventral aldolase C-positive parts. The anterior and posterior interposed nuclei generally correspond to the aldolase C-negative and -positive parts, respectively. DCN compartmentalization is important for understanding functional localization in the DCN since it is speculated that aldolase C-positive and -negative compartments are generally associated with somatosensory and other functions, respectively.


Controlling Ca2+-activated K+ channels with models of Ca2+ buffering in Purkinje cells. Intracellular Ca(2+) concentrations play a crucial role in the physiological interaction between Ca(2+) channels and Ca(2+)-activated K(+) channels. The commonly used model, a Ca(2+) pool with a short relaxation time, fails to simulate interactions occurring at multiple time scales. On the other hand, detailed computational models including various Ca(2+) buffers and pumps can result in large computational cost due to radial diffusion in large compartments, which may be undesirable when simulating morphologically detailed Purkinje cell models. We present a method using a compensating mechanism to replace radial diffusion and compared the dynamics of different Ca(2+) buffering models during generation of a dendritic Ca(2+) spike in a single compartment model of a PC dendritic segment with Ca(2+) channels of P- and T-type and Ca(2+)-activated K(+) channels of BK- and SK-type. The Ca(2+) dynamics models used are (1) a single Ca(2+) pool; (2) two Ca(2+) pools, respectively, for the fast and slow transients; (3) detailed Ca(2+) dynamics with buffers, pump, and diffusion; and (4) detailed Ca(2+) dynamics with buffers, pump, and diffusion compensation. Our results show that detailed Ca(2+) dynamics models have significantly better control over Ca(2+)-activated K(+) channels and lead to physiologically more realistic simulations of Ca(2+) spikes and bursting. Furthermore, the compensating mechanism largely eliminates the effect of removing diffusion from the model on Ca(2+) dynamics over multiple time scales.


Chemoinformatics and library design.

Chemoinformatics and library design. This chapter provides a brief overview of chemoinformatics and its applications to chemical library design. It is meant to be a quick starter and to serve as an invitation to readers for more in-depth exploration of the field. The topics covered in this chapter are chemical representation, chemical data and data mining, molecular descriptors, chemical space and dimension reduction, quantitative structure-activity relationship, similarity, diversity, and multiobjective optimization.


Polymorphisms in the 5'- and 3'-untranslated region of the VEGF gene and sporadic breast cancer risk and clinicopathologic characteristics. The wild and the variant alleles of the C936T and G634C vascular endothelial grow factor (VEGF) polymorphisms seem to be linked to higher angiogenic phenotype than the remaining alleles and may act on breast cancer (BC) origin. We investigated the influence of the VEGF C936T and G634C polymorphisms on the occurrence and clinicopathologic characteristics of sporadic breast cancer (SBC) in 235 patients and 235 controls. Peripheral blood samples of all individuals were analysed by the polymerase chain reaction for identification of genotypes and by enzyme-linked immunosorbent assay (ELISA) for quantification of serum VEGF levels. The variant 634CC genotype isolated (16.2% versus 10.7%, P  = 0.01) and in combination with the wild 936CC genotype (10.6% versus 5.5%, P  = 0.01) were more common in patients than in controls. The carriers of the respective genotypes were under a 2.20-fold and a 3.08-fold increased risks for the disease. Additionally, the frequency of the wild 936CC genotype was higher in patients with tumours of histological grade III compared to those with tumours of I+II histological grades (84.0% versus 64.7%, P  = 0.004) and in patients with positive oestrogen receptor tumours compared to those with tumours lacking oestrogen receptor expression (84.7% versus 73.9%, P  = 0.02). Similar serum values of VEGF were seen in patients and controls with the distinct genotypes of the VEGF. The data suggest that the VEGF wild 936CC and the variant 634CC genotypes constitute inherited determinants of SBC and SBC aggressiveness in Brazil, but are not significant predictors of circulating VEGF levels.


Historical overview of chemical library design. High-throughput chemistry (HTC) is approaching its 20-year anniversary. Since 1992, some 5,000 chemical libraries, prepared for the purpose of biological investigation and drug discovery, have been published in the scientific literature. This review highlights the key events in the history of HTC with emphasis on library design. A historical perspective on the design of screening, targeted, and optimization libraries and their application is presented. Design strategies pioneered in the 1990s remain viable in the twenty-first century.


Biological functions of microRNAs: a review. MicroRNAs (miRNAs) are a recently discovered family of endogenous, noncoding RNA molecules approximately 22 nt in length. miRNAs modulate gene expression post-transcriptionally by binding to complementary sequences in the coding or 3' untranslated region of target messenger RNAs (mRNAs). It is now clear that the biogenesis and function of miRNAs are related to the molecular mechanisms of various clinical diseases, and that they can potentially regulate every aspect of cellular activity, including differentiation and development, metabolism, proliferation, apoptotic cell death, viral infection and tumorgenesis. Here, we review recent advances in miRNA research, and discuss the diverse roles of miRNAs in disease.


A scalable approach to combinatorial library design. In this chapter, we describe an algorithm for the design of lead-generation libraries required in combinatorial drug discovery. This algorithm addresses simultaneously the two key criteria of diversity and representativeness of compounds in the resulting library and is computationally efficient when applied to a large class of lead-generation design problems. At the same time, additional constraints on experimental resources are also incorporated in the framework presented in this chapter. A computationally efficient scalable algorithm is developed, where the ability of the deterministic annealing algorithm to identify clusters is exploited to truncate computations over the entire dataset to computations over individual clusters. An analysis of this algorithm quantifies the trade-off between the error due to truncation and computational effort. Results applied on test datasets corroborate the analysis and show improvement by factors as large as ten or more depending on the datasets.