title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Increased QT variability in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. | Although sudden death (SD) accounts for numerous cases of premature mortality in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the risk factors responsible for this dramatic event remain unclear. We sought possible differences in the QT variability index (QTVI) -- a well-known index of temporal dispersion in myocardial repolarization strongly associated with the risk of SD -- between a group of patients with CADASIL and healthy controls. A total of 13 patients with CADASIL and 13 healthy volunteers underwent a 5-min electrocardiogram recording to calculate the QTVI. All the patients also underwent a clinical assessment, including functional status by Rankin score, and a magnetic resonance imaging (MRI) brain scan for quantitative analysis of T2-weighted (T2-W) and T1-weighted (T1-W) lesion volume (LV). Short-term QT-interval analysis showed significantly higher QTVI (P = 0.029) in patients than in controls. In patients, notwithstanding the limitations of the small sample size, QTVI also well correlated with T1-W LV (r = 0.747, P = 0.003) and T2-W LV (r = 0.731, P = 0.005). Because patients with CADASIL have increased temporal cardiac repolarization variability as assessed by QTVI, this mechanism could underlie these patients' risk of SD. Whether this easily assessed, non-invasive marker could be used to stratify the risk of malignant ventricular arrhythmias in patients with CADASIL and, possibly, to guide their therapeutic management warrants confirmation from larger prospective studies. | 18,803,652 |
Epilysin (MMP-28)--structure, expression and potential functions. | Epilysin (MMP-28) is the newest member of the matrix metalloproteinase (MMP) family of extracellular proteases. Together the MMPs can degrade almost all components of the extracellular matrix (ECM). MMPs also regulate cell behaviour by releasing growth factors and biologically active peptides from the ECM by modulating cell surface receptors and adhesion molecules and by regulating the activity of mediators of the inflammatory pathways. Epilysin differs from most other MMPs as it is expressed in a number of normal tissues, suggestive of functions in tissue homeostasis. The epilysin homologue in Xenopus laevis (XMMP-28) is expressed in neural tissues, where it cleaves the neural cell adhesion molecule. Enhanced expression of epilysin has been observed in basal keratinocytes during wound healing and in different forms of cancer. There are, however, also reports on the downregulation of epilysin in malignant cells. The roles of epilysin in cancer seem to vary based on tumor type and stage of the disease. Importantly, epilysin can induce stable epithelial to mesenchymal transition (EMT) when overexpressed in epithelial lung carcinoma cells. Transforming growth factor beta (TGF-beta) is a crucial mediator of this process, which was characterized by the loss of E-cadherin and increased cell migration and invasion. Current results suggest a plausible interaction between epilysin and TGF-beta also under physiological circumstances, where epilysin activity may not induce EMT but, instead, trigger less permanent changes in TGF-beta signalling and cell motility. | 18,803,661 |
Barriers to cross-fertilization between populations of a widely dispersed polychaete species are unlikely to have arisen through gametic compatibility arms-races. | Although there are theoretical reasons to suspect that gametic incompatibility may develop readily among populations of broadcast spawning marine invertebrates, there have been very few studies documenting geographic patterns of interpopulation incompatibility for any species. To address this we determined how successfully individuals of the intertidal serpulid polychaete, Galeolaria caespitosa, can cross-fertilize within and among populations from across temperate Australia. Fertilization assays revealed asymmetrical differences between very distantly located populations from different coasts, with near-complete incompatibility between eggs from Sydney with sperm from Adelaide, but the reverse cross (Adelaide eggs, Sydney sperm) was reasonably compatible. Although that pattern was congruent with a clear difference in Cytochrome B sequences between worms on the south and east coasts of Australia, we also detected some indication of interpopulation incompatibility within the genetic grouping on east coast, between two populations separated by only 220 km. We then assessed whether commonly proposed gametic compatibility arms-races could account for these patterns. Our results suggest reduced gametic compatibility may reduce a female's maximum fertilization potential, resulting in a cost to this potential mechanism for reducing polyspermy. Consequently, the apparently rapid development of reproductive barriers here seems unlikely to have been driven by arms-races involving sexual conflict over fertilization rate. | 18,803,690 |
Pathogenic missense MAPT mutations differentially modulate tau aggregation propensity at nucleation and extension steps. | Mutations in the MAPT gene encoding tau protein lead to neurofibrillary lesion formation, neurodegeneration, and cognitive decline associated with frontotemporal lobar degeneration. While some pathogenic mutations affect MAPT introns, resulting in abnormal splicing patterns, the majority occur in the tau coding sequence leading to single amino acid changes in tau primary structure. Depending on their location within the polypeptide chain, tau missense mutations have been reported to augment aggregation propensity. To determine the mechanisms underlying mutation-associated changes in aggregation behavior, the fibrillization of recombinant pathogenic mutants R5L, G272V, P301L, V337M, and R406W prepared in a full-length four-repeat human tau background was examined in vitro as a function of time and submicromolar tau concentrations using electron microscopy assay methods. Kinetic constants for nucleation and extension phases of aggregation were then estimated by direct measurement and mathematical simulation. Results indicated that the mutants differ from each other and from wild-type tau in their aggregation propensity. G272V and P301L mutations increased the rates of both filament nucleation and extension reactions, whereas R5L and V337M increased only the nucleation phase. R406W did not differ from wild-type in any kinetic parameter. The results show that missense mutations can directly promote tau filament formation at different stages of the aggregation pathway. | 18,803,694 |
Antioxidant effects of flavonoids used as food additives (purple corn color, enzymatically modified isoquercitrin, and isoquercitrin) on liver carcinogenesis in a rat medium-term bioassay. | To clarify the effects of purple corn color, enzymatically modified isoquercitrin (EMIQ), and isoquercitrin (IQ), registered as natural food additives in Japan, on liver carcinogenesis in vivo, a medium-term bioassay was employed. A total of 100 male F344 rats were divided into 5 groups; groups 1 to 4 were given a single intraperitoneal injection of diethylnitrosamine (200 mg/kg b.w.) on day 1. From weeks 2 to 8, they were administered basal diet purple corn color, EMIQ, or IQ as containing test chemicals at doses of 1.0% (groups 1 and 5), 0.1% (group 2), 0.01% (group 3), or 0% (group 4) (experiments 1, 4, and 5). All rats were subjected to two-thirds partial hepatectomy at week 3 and were sacrificed at week 8. Purple corn color exerted no significant modifying effects on GST-P positive foci, preneoplastic foci, development in the liver. However, serum of rats treated with purple corn color provided evidence of antioxidant power significantly by potential antioxidant (PAO) test in vivo (experiment 2). And microarray analyses showed purple corn color to induce RNA expression such as P450 (cytochrome) oxidoreductase, phosphatidylinositol 3-kinase, and phospholipase A2 (experiment 3). Higher doses of EMIQ or IQ with strong antioxidant power in vivo by PAO test treated groups were correlated with smaller numbers of GST-P positive foci, with Spearman's rank correlation coefficients of P= 0.002 and P= 0.049, respectively (experiments 4 and 5). Therefore, the tested food additives may be effective as antioxidants in vivo and have chemopreventive potential against liver preneoplastic lesion development. | 18,803,703 |
People with mental disabilities negotiating life in the risk society: a theoretical approach. | Risk assessment and risk management owing to the potential threat from people with serious mental disorders living in the local community have been given much attention in psychiatric and mental healthcare research. Research connected to risks associated with living in the community for people with mental disabilities has also been published. This paper focuses on the situation of people with mental health problems and disabilities from a quite different perspective. In the light of the societal change towards what has been named the 'risk society', the consequences for vulnerable groups, especially people with mental disabilities, are discussed. Furthermore, the purpose is to shed light on how structural factors, like the process of individualization and 'de-population' of societal institutions, are affecting the living conditions for people with mental disabilities - positively as well as negatively. The importance of trust in the risk society is highlighted, but also the important role that the local community might play in relation to people with mental disabilities. Finally, some potentialities and new roles that this development towards a risk society and increased individualization paradoxically can open up for people with mental disabilities are outlined. | 18,803,734 |
Seminal plasma proteins and sperm resistance to stress. | The role of seminal plasma (SP) in mammalian sperm function remains largely a matter of speculation as both inhibitory and stimulating effects have been found. Specific components of SP, particularly proteins, are adsorbed onto the surface of ejaculated sperm as they pass through the male and female reproductive tracts. These sperm coating components seem to have the important function of maintaining the stability of the membrane up to the process of capacitation (decapacitation factors). Therefore, they must be removed, modified or masked before the spermatozoa undergo the acrosome reaction, an essential process for successful fertilization. It is well known that low temperatures alter the function of spermatozoa. Cold shock results in the destabilization of sperm membranes and impairment of sperm function, and it is also well known that ram spermatozoa are more sensitive to cold-shock stress than those of other species. The addition of SP proteins to spermatozoa before and/or after cooling is able to minimize cryoinjury effects. The major proteins in ram SP which are able to protect and repair the cold-shock damage to sperm contain fibronectin-II domains. The significance of this domain and the role of these proteins in sperm capacitation and gamete interaction are discussed. | 18,803,753 |
Fate mapping in embryos of Neoceratodus forsteri reveals cranial neural crest participation in tooth development is conserved from lungfish to tetrapods. | Experimental evidence that the neural crest participates in tooth development in any osteichthyan fish has so far been lacking. Using vital dye cell-lineage tracking, we demonstrate that trigeminal stream neural crest cells contribute to the dental papilla of developing teeth in the Australian lungfish. Trigeminal neural crest cells labeled before migration have been traced during the earliest stages of tooth development. Neural crest cells from a single midbrain locus were relocated as ectomesenchyme in all developing teeth of the lungfish regardless of their topographical position in the dentition. These cells remain at the dental papilla interface and become cells committed to dentine production. Our findings provide the first cell-lineage evidence that cranial neural crest is fated to ectomesenchyme for tooth development and dentine production in the living sister-group to tetrapods. This shows that cranial neural crest contribution to teeth is conserved from this node on the tetrapod phylogeny. | 18,803,771 |
Application of individual increase in inbreeding to estimate realized effective sizes from real pedigrees. | The objective of this study was to test the performance of a recently proposed methodology for the estimation of realized effective size (N(e)) based on individual increase in inbreeding (DeltaF(i)) on several real pedigrees: (a) an experimental mice population; (b) a closed pedigree of fighting bulls; (c) the Spanish Purebred (SPB, Andalusian) horse pedigree; (d) the Carthusian strain of SPB pedigree; (e) the Spanish Arab horse pedigree; and (f) the Spanish Anglo-Arab horse pedigree. Several reference subpopulations were defined on the basis of generation length in order to consider only animals in the last generation, to assess the influence of the pedigree content on the estimates of N(e). The estimates of realized N(e) computed from DeltaF(i) (Ne) tended to be higher than those obtained from regression on equivalent generations. The new parameter Ne remained approximately stable when pedigree depth achieved about five equivalent generations. Estimates of take into account the genetic history of the populations, the size of their founder population, and the mating policy or bottlenecks caused by poor use of reproducing individuals. The usefulness of the realized N(e) computed from individual increase in inbreeding in real pedigrees is also discussed. | 18,803,785 |
Evolutionary origins of novel conchologic growth patterns in tropical American corbulid bivalves. | We conducted a combined sclerochronologic and phylogenetic analysis to document patterns and rates of shell accretion in several subclades of related corbulids, and to explore the evolutionary origins of novel conchologic developmental patterns. We found three disparate patterns of valve development in Neogene tropical American corbulid genera. These patterns include growth through primarily radial accretion along the sagittal plane, and two derivative patterns: one characterized by initial deposition of a thin shell followed by valve thickening with little increase in valve height, and another producing a well-defined nepioconch through a marked change in the primary growth direction. We conducted a species-level phylogenetic analysis of the taxa surveyed for growth patterns, focusing on the ([Bothrocorbula+Hexacorbula]+Caryocorbula) clade. The phylogenetic distribution of shell growth patterns suggests that this clade is characterized by derivative patterns of growth. Oxygen-isotope calibrated ontogenetic age estimates of species in the derived Bothrocorbula subclade further suggest that transitions from the ancestral radial (sagittal) growth pattern to a derived pattern of growth are a function of heterochrony (peramorphosis by acceleration). These findings are significant because they link previously observed patterns of morphological constraint with a specific evolutionary process, demonstrate how morphologic constraint and innovation can be interrelated, and serve as a model for understanding the evolution of morphologic diversity in the clade as a whole. Furthermore, this study highlights the utility of sclerochronologic records as an important component of evolutionary developmental research on organisms with accretionary skeletal growth. | 18,803,781 |
Malaria case-management under artemether-lumefantrine treatment policy in Uganda. | Case-management with artemether-lumefantrine (AL) is one of the key strategies to control malaria in many African countries. Yet, the reports on translation of AL implementation activities into clinical practice are scarce. Here the quality of AL case-management is reported from Uganda; approximately one year after AL replaced combination of chloroquine and sulphadoxine-pyrimethamine (CQ+SP) as recommended first line treatment for uncomplicated malaria. A cross-sectional survey, using a range of quality of care assessment tools, was undertaken at all government and private-not-for-profit facilities in four Ugandan districts. Main outcome measures were AL prescribing, dispensing and counseling practices in comparison with national guidelines, and factors influencing health workers decision to 1) treat for malaria, and 2) prescribe AL. 195 facilities, 232 health workers and 1,763 outpatient consultations were evaluated. Of 1,200 patients who needed treatment with AL according to guidelines, AL was prescribed for 60%, CQ+SP for 14%, quinine for 4%, CQ for 3%, other antimalarials for 3%, and 16% of patients had no antimalarial drug prescribed. AL was prescribed in the correct dose for 95% of patients. Only three out of seven AL counseling and dispensing tasks were performed for more than 50% of patients. Patients were more likely to be treated for malaria if they presented with main complaint of fever (OR = 5.22; 95% CI: 3.61-7.54) and if they were seen by supervised health workers (OR = 1.63; 95% CI: 1.06-2.50); however less likely if they were treated by more qualified health workers (OR = 0.61; 95% CI: 0.40-0.93) and presented with skin problem (OR = 0.29; 95% CI: 0.15-0.55). AL was more likely prescribed if the appropriate weight-specific AL pack was in stock (OR = 6.15; 95% CI: 3.43-11.05) and when CQ was absent (OR = 2.16; 95% CI: 1.09-4.28). Routine AL implementation activities were not associated with better performance. Although the use of AL was predominant over non-recommended therapies, the quality of AL case-management at the point of care is not yet optimal. There is an urgent need for innovative quality improvement interventions, which should be rigorously tested. Adequate availability of ACTs at the point of care will, however, ultimately determine the success of any performance interventions and ACT policy transitions. | 18,803,833 |
Posterior dislocation of the elbow associated with fracture of the radial head and olecranon, and with medial collateral ligament disruption: A case report. | Fracture dislocations of the elbow appear extremely complex. Identification of the basic injury patterns can facilitate management. A 38-year-old male motor-vehicle driver who fell on his right elbow after an accident was suffering from posterior dislocation of the elbow, without coronoid fracture, and with fracture of the radial head and olecranon, and medial collateral ligament disruption, which was not associated with any vascular or neural injury. Posterior dislocation of the elbow associated with fracture of the radial head and olecranon, and medial collateral ligament disruption may be a rare subgroup of elbow dislocation. We should pay more attention to medial collateral ligament injury with elbow dislocation. | 18,803,834 |
The metagenomics RAST server - a public resource for the automatic phylogenetic and functional analysis of metagenomes. | Random community genomes (metagenomes) are now commonly used to study microbes in different environments. Over the past few years, the major challenge associated with metagenomics shifted from generating to analyzing sequences. High-throughput, low-cost next-generation sequencing has provided access to metagenomics to a wide range of researchers. A high-throughput pipeline has been constructed to provide high-performance computing to all researchers interested in using metagenomics. The pipeline produces automated functional assignments of sequences in the metagenome by comparing both protein and nucleotide databases. Phylogenetic and functional summaries of the metagenomes are generated, and tools for comparative metagenomics are incorporated into the standard views. User access is controlled to ensure data privacy, but the collaborative environment underpinning the service provides a framework for sharing datasets between multiple users. In the metagenomics RAST, all users retain full control of their data, and everything is available for download in a variety of formats. The open-source metagenomics RAST service provides a new paradigm for the annotation and analysis of metagenomes. With built-in support for multiple data sources and a back end that houses abstract data types, the metagenomics RAST is stable, extensible, and freely available to all researchers. This service has removed one of the primary bottlenecks in metagenome sequence analysis - the availability of high-performance computing for annotating the data. http://metagenomics.nmpdr.org. | 18,803,844 |
Transcriptional regulation of mouse alpha A-crystallin gene in a 148kb Cryaa BAC and its derivates. | alphaA-crystallin is highly expressed in the embryonic, neonatal and adult mouse lens. Previously, we identified two novel distal control regions, DCR1 and DCR3. DCR1 was required for transgenic expression of enhanced green fluorescent protein, EGFP, in lens epithelium, whereas DCR3 was active during "late" stages of lens primary fiber cell differentiation. However, the onset of transgenic EGFP expression was delayed by 12-24 hours, compared to the expression of the endogenous Cryaa gene. Here, we used bacterial artificial chromosome (BAC) and standard transgenic approaches to examine temporal and spatial regulation of the mouse Cryaa gene. Two BAC transgenes, with EGFP insertions into the third coding exon of Cryaa gene, were created: the intact alphaA-crystallin 148 kb BAC (alphaA-BAC) and alphaA-BAC(DeltaDCR3), which lacks approximately 1.0 kb of genomic DNA including DCR3. Expression of EGFP in the majority of both BAC transgenics nearly recapitulated the endogenous expression pattern of the Cryaa gene in lens, but not outside of the lens. The number of cells expressing alphaA-crystallin in the lens pit was higher compared to the number of cells expressing EGFP. Next, we generated additional lines using a 15 kb fragment of alphaA-crystallin locus derived from alphaA-BAC(DeltaDCR3), 15 kb Cryaa/EGFP. A 15 kb region of Cryaa/EGFP supported the expression pattern of EGFP also in the lens pit. However, co-localization studies of alphaA-crystallin and EGFP indicated that the number of cells that showed transgenic expression was higher compared to cells expressing alphaA-crystallin in the lens pit. We conclude that a 148 kb alphaA-BAC likely contains all of the regulatory regions required for alphaA-crystallin expression in the lens, but not in retina, spleen and thymus. In addition, while the 15 kb Cryaa/EGFP region also supported the expression of EGFP in the lens pit, expression in regions such as the hindbrain, indicate that additional genomic regions may play modulatory functions in regulating extralenticular alphaA-crystallin expression. Finally, deletion of DCR3 in either alphaA-BAC(DeltaDCR3) or Cryaa (15 kb) transgenic mice result in EGFP expression patterns that are consistent with DCR's previously established role as a distal enhancer active in "late" primary lens fiber cells. | 18,803,847 |
Starting at the endophenotype: A role for alpha-CaMKII in schizophrenia? | Using an endophenotype-driven screen, a new study finds that α-calcium/calmodulin kinase II mutant mice exhibit a range of behavioral abnormalities related to schizophrenia. Perhaps most strikingly, this cluster of schizophrenia-related endophenotypes was associated with abnormal neurogenesis in the adult hippocampus, raising the possibility that disrupted adult neurogenesis lies at the core of this and other psychiatric disorders. | 18,803,858 |
Hfq regulates the expression of the thermostable direct hemolysin gene in Vibrio parahaemolyticus. | The hfq gene is conserved in a wide variety of bacteria and Hfq is involved in many cellular functions such as stress responses and the regulation of gene expression. It has also been reported that Hfq is involved in bacterial pathogenicity. However, it is not clear whether Hfq regulates virulence in Vibrio parahaemolyticus. To evaluate this, we investigated the effect of Hfq on the expression of virulence-associated genes including thermostable direct hemolysin (TDH), which is considered to be an important virulence factor in V. parahaemolyticus, using an hfq deletion mutant. The production of TDH in the hfq deletion mutant was much higher than in the parental strain. Quantification of tdh promoter activity and mRNA demonstrated that transcription of the tdh gene was up-regulated in the mutant strain. The hfq-complemented strain had a normal (parental) amount of tdh expression. The transcriptional activity of tdhA was particularly increased in the mutant strain. These results indicate that Hfq is closely associated with the expression level of the tdh gene. Interestingly, other genes involved in the pathogenicity of V. parahaemolyticus, such as VP1680, vopC, and vopT, were also up-regulated in the mutant strain. Hfq regulates the expression of virulence-associated factors such as TDH and may be involved in the pathogenicity of V. parahaemolyticus. | 18,803,872 |
Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres. | MicroRNAs (miRNAs), some of which function as oncogenes or tumor suppressor genes, are involved in carcinogenesis via regulating cell proliferation and/or cell death. MicroRNA miR-34 was recently found to be a direct target of p53, functioning downstream of the p53 pathway as a tumor suppressor. miR-34 targets Notch, HMGA2, and Bcl-2, genes involved in the self-renewal and survival of cancer stem cells. The role of miR-34 in gastric cancer has not been reported previously. In this study, we examined the effects of miR-34 restoration on p53-mutant human gastric cancer cells and potential target gene expression. Human gastric cancer cells were transfected with miR-34 mimics or infected with the lentiviral miR-34-MIF expression system, and validated by miR-34 reporter assay using Bcl-2 3'UTR reporter. Potential target gene expression was assessed by Western blot for proteins, and by quantitative real-time RT-PCR for mRNAs. The effects of miR-34 restoration were assessed by cell growth assay, cell cycle analysis, caspase-3 activation, and cytotoxicity assay, as well as by tumorsphere formation and growth. Human gastric cancer Kato III cells with miR-34 restoration reduced the expression of target genes Bcl-2, Notch, and HMGA2. Bcl-2 3'UTR reporter assay showed that the transfected miR-34s were functional and confirmed that Bcl-2 is a direct target of miR-34. Restoration of miR-34 chemosensitized Kato III cells with a high level of Bcl-2, but not MKN-45 cells with a low level of Bcl-2. miR-34 impaired cell growth, accumulated the cells in G1 phase, increased caspase-3 activation, and, more significantly, inhibited tumorsphere formation and growth. Our results demonstrate that in p53-deficient human gastric cancer cells, restoration of functional miR-34 inhibits cell growth and induces chemosensitization and apoptosis, indicating that miR-34 may restore p53 function. Restoration of miR-34 inhibits tumorsphere formation and growth, which is reported to be correlated to the self-renewal of cancer stem cells. The mechanism of miR-34-mediated suppression of self-renewal appears to be related to the direct modulation of downstream targets Bcl-2, Notch, and HMGA2, indicating that miR-34 may be involved in gastric cancer stem cell self-renewal/differentiation decision-making. Our study suggests that restoration of the tumor suppressor miR-34 may provide a novel molecular therapy for p53-mutant gastric cancer. | 18,803,879 |
Factor XIII deficiency in children--clinical presentation and outcome. | To determine the demographic features and clinical outcome of children with Factor XIII deficiency. Observational case series. The Aga Khan University Hospital, Karachi, from January 1996 to December 2006. Records of all hospitalized pediatric patients with discharge diagnosis of FXIII D, on the basis of factor XIII assay 5 mol/L urea test were retrospectively reviewed and abstracted on a pre-specified proforma. Demographic features, coagulation profile, family history and outcomes were noted. A total of 10 charts were reviewed. There were 5 boys and 5 girls. Almost all the children (9/10) were less than 5 years of age, out of whom 5 (50%) were infants, and 3 were neonates. Bruises and prolonged bleeding after trauma was the major presenting complaints in 80%, followed by prolonged bleeding from the umbilical stump in 2 patients. Nine patients had past history of prolonged umbilical bleeding. Two patients had history of FXIII D in siblings, while 2 had history of prolonged bleeding in other family members (cause unknown). Consanguinity was present in 80% of the families. Initial coagulation screen were normal in all patients. Two patients had intracranial hemorrhage, proved on neuro-imaging, were managed with plasma infusions and required craniotomy. The rest were managed conservatively with plasma transfusions. All were discharged alive in good clinical condition. Almost all were followed regularly in clinic with monthly cryoprecipitate transfusions. Although factor XIII deficiency is a rare genetic disorder in children with history of bruising, prolonged umbilical bleeding, family history of bleeding and consanguinity with normal initial coagulation screen (PT, APTT and platelets), FXIII D should be ruled out. | 18,803,895 |
Primary renal lymphoma. | A 62-year-old male patient presented with right flank pain and right renal mass on CT scan. Patient left against medical advice and had nephrectomy done elsewhere. Histopathology revealed a diffuse large cell B-cell lymphoma. Patient presented again, with disseminated disease and was started on chemotherapy. Although a rare disorder, missing primary renal lymphoma as one of the causes of renal mass can lead to disseminated disease and unnecessary nephrectomy, in spite of chemotherapy being standard management. | 18,803,901 |
Quantitative electroencephalography and attention-deficit/hyperactivity disorder: implications for clinical practice. | Although behavioral symptoms of inattention, impulsivity, and hyperactivity serve as a foundation for the accurate diagnosis of attention-deficit/hyperactivity disorder (ADHD), the low interrater reliability and specificity of behavioral rating scales and the absence of comprehensive screening for medical conditions that mimic ADHD have created a barrier to the effective treatment of ADHD. Recently published studies using quantitative electroencephalographic techniques have identified abnormal patterns of cortical activation through power spectral analysis, in event-related cortical potentials, and in slow cortical potentials that may serve as a basis for overcoming these barriers. This paper reviews the initial evidence indicating that power spectral analysis and event-related cortical potentials may be useful in differentiating ADHD from other psychiatric disorders, helping in medication selection, evaluating medication response, and improving the rate of treatment initiation and maintenance. Studies examining electroencephalogram biofeedback (neurotherapy) are reviewed using published efficacy guidelines. | 18,803,918 |
Parkinson disease: primacy of age as a risk factor for mitochondrial dysfunction. | In 1983, it was reported that certain drug users with a history of exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a contaminant of an illicitly produced meperidine analogue, developed an irreversible syndrome resembling idiopathic Parkinson disease (PD). Soon thereafter, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine's active metabolite, 1-methyl-4-phenylpyridine, was shown to be a complex I inhibitor. Activity of complex I (the point of entry for most electrons that traverse the mitochondrial electron transport chain) has been found to be impaired in the substantia nigra pars compacta and also in other brain tissues in PD patients. In 2006, high temporal and spatial resolution phosphorous functional magnetic resonance spectroscopy was used to demonstrate that, in 20 PD patients, mitochondrial dysfunction extended to the visual cortex. Epidemiologic studies have implicated a number of apparently disparate exogenous factors in the causation of PD. For example, exposure to certain pesticides and herbicides (many known to inhibit electron transport chain activity) increases PD risk. Parkinson disease risk can be doubled, tripled, or more in individuals with repeated head injuries. Over time, PD risk is almost doubled in men and women with prior type 2 diabetes mellitus. Nevertheless, despite evidence that certain exogenous and/or developmental factors play a role in causation of PD, their potential effect on PD incidence is greatly overshadowed by that of advancing age. In 1 prospective study, PD incidence rate in subjects at least 85 years old was about 14 times that observed in subjects aged 56 to 65 years. The dramatic effect of aging on PD risk may be explained in part by the fact that mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra pars compacta neurons. High levels of these mutations are associated with electron transport chain deficiency, a situation that favors increased oxidative damage, Lewy body formation, and apoptotic cell death. Systematic study of the effects of putative risk factors in animal models of parkinsonism may be expected to improve our understanding of PD's complex pathogenesis. | 18,803,967 |
Estimating the health benefits and costs associated with ezetimibe coadministered with statin therapy compared with higher dose statin monotherapy in patients with established cardiovascular disease: results of a Markov model for UK costs using data registries. | Ezetimibe has been reported to improve lipid control in patients with established cardiovascular disease (CVD). The aim of this study was to estimate the potential long-term impact on health status of prescribing ezetimibe in combination with statin therapy in patients with established CVD and evaluate its cost-effectiveness in a health economic model. A Markov model was used to compare ezetimibe and statin combination therapy with statin monotherapy. A published relationship linking changes in low-density lipoprotein cholesterol and cardiovascular events was used to estimate the cardiovascular events avoided through lipid-lowering therapies. The model was populated using results of extensive literature searches and a meta-analysis of clinical evidence. An adjustment was applied to model second-line lipid-lowering benefits. Conservative assumptions were used to extend the patient pathway beyond the clinical evidence. The analysis took the perspective of the UK Department of Health; therefore, only direct costs were included. Costs were calculated as year-2006 British pounds. For a cohort of 1,000 hypothetical male patients aged 55 years, ezetimibe coadministered with current statin therapy was estimated to prevent a mean of 43 nonfatal myocardial infarctions, 7 nonfatal strokes, and 26 cardiovascular deaths over a lifetime, compared with doubling the current statin dose. The events avoided would provide a mean of 134 additional quality-adjusted life-years (QALYs). With a mean incremental cost of pound 3,693,000, the lifetime discounted cost per QALY gained would be pound 27,475 (95% CI, pound 27,331- pound 27,620) and would rise to pound 32,000 for men aged 75 years. The results suggest that, in some instances, ezetimibe coadministration may be cost-effective compared with statin monotherapy, but there are several limitations with this model. The economic effects of ezetimibe must be revisited when long-term effectiveness and safety data become available. | 18,803,993 |
Cervical myelopathy: a case report of a "near-miss" complication to cervical manipulation. | Cases have been reported in which radiculopathy or myelopathy secondary to herniated disk has occurred after cervical manipulation. In each case, it is not possible to determine whether the neurologic symptoms and signs were directly caused by the manipulation or whether they developed as part of the natural history of the disorder. The purpose of this article is to report a case in which a patient with radiculopathy secondary to herniated disk was scheduled to receive manipulation but just before receiving this treatment developed acute myelopathy. A patient with arm pain and numbness was referred by a neurosurgeon for nonsurgical consult. He had a large C5-6 disk herniation with no signs or symptoms of myelopathy. He was determined to be a candidate for nonsurgical intervention, including manipulation. Manipulative treatment was planned for the second visit. Ten days after the initial visit, and before any manipulative treatment being rendered, the patient developed symptoms suggestive of myelopathy, which were later determined on examination to be related to acute myelopathy secondary to the disk herniation. Herniated disk in the cervical spine can progress to myelopathy as part of the natural history of this condition. Because of this, any interpretation of myelopathy that occurs after cervical manipulation, or any other procedure, must be made with caution. | 18,804,007 |
Attention deficit/hyperactivity disorder: a review and update. | Attention deficit/hyperactivity disorder (ADHD) is a prevalent, chronic, and pervasive childhood disorder characterized by developmentally inappropriate activity level, impulsivity, and inability to sustain attention and concentration. Core symptoms of the disorder are associated with impairment in multiple domains of functioning and often coexist with other psychiatric disorders, the most prevalent being oppositional defiant disorder, conduct disorder, depression, and anxiety disorders. Concerns have been expressed about the overdiagnosis of ADHD, an upsurge in prescription of stimulant medication, and wide variations in practice patterns related to diagnosis and treatment of children with ADHD among primary care providers. Clinical research and expert consensus guidelines over the past decade have increasingly clarified the most effective approaches to diagnosis and treatment of the disorder. Hence, the purpose of this article was to provide primary care providers with the most current, evidence-based information on the assessment and treatment of children with ADHD. | 18,804,015 |
Enteral feeding in neurologically impaired children with gastroesophageal reflux: Nissen fundoplication and gastrostomy tube placement versus percutaneous gastrojejunostomy. | Parents or caregivers of neurologically impaired children with gastroesophageal reflux who require enteral nutrition are often faced with the option of having their child undergo an antireflux surgery and placement of a gastrostomy tube or have a percutaneous gastrojejunostomy tube placed under fluoroscopic guidance. It is important that nurses have an understanding of these procedures and their associated risks and benefits as well as knowledge of the impact each might have on the daily life and care of these children to help support families during this decision-making process. | 18,804,022 |
Loss of a mycobacterial gene encoding a reductase leads to an altered cell wall containing beta-oxo-mycolic acid analogs and accumulation of ketones. | Mycolic acids are essential components of the mycobacterial cell wall. In this study, we show that a gene encoding a reductase involved in the final step of mycolic acid biosynthesis can be deleted in Mycobacterium smegmatis without affecting cell viability. Deletion of MSMEG4722 (ortholog of Mycobacterium tuberculosis Rv2509) altered culture characteristics and antibiotic sensitivity. The DeltaMSMEG4722 strain synthesized alpha-alkyl, beta-oxo intermediates of mycolic acids, which were found esterified to cell wall arabinogalactan. While the precursors could not be isolated directly due to their inherent instability during base treatment, their presence was established by prior reduction of the beta-oxo group by sodium borohydride. Interestingly, the mutant also accumulated unsaturated ketones, similar to tuberculenone from M. tuberculosis, which were shunt products derived from spontaneous decarboxylation of alpha-alkyl, beta-oxo fatty acid precursors of mycolic acids. | 18,804,030 |
Identification of chemical inhibitors to human tissue transglutaminase by screening existing drug libraries. | Human tissue transglutaminase (TGM2) is a calcium-dependent crosslinking enzyme involved in the posttranslational modification of intra- and extracellular proteins and implicated in several neurodegenerative diseases. To find specific inhibitors to TGM2, two structurally diverse chemical libraries (LOPAC and Prestwick) were screened. We found that ZM39923, a Janus kinase inhibitor, and its metabolite ZM449829 were the most potent inhibitors with IC(50) of 10 and 5 nM, respectively. In addition, two other inhibitors, including tyrphostin 47 and vitamin K(3), were found to have an IC(50) in the micromolar range. These agents used in part a thiol-dependent mechanism to inhibit TGM2, consistent with the activation of TGM2 by reduction of an intramolecular disulfide bond. These inhibitors were tested in a polyglutamine-expressing Drosophila model of neurodegeneration and found to improve survival. The TGM2 inhibitors we discovered may serve as valuable lead compounds for the development of orally active TGM2 inhibitors to treat human diseases. | 18,804,034 |
Cell-based therapies for osteonecrosis of the femoral head. | Osteonecrosis of the femoral head is a disabling condition and a known complication of hematopoietic cell transplants (HCT). It is characterized by empty lacunae in the osseous matrix and necrotic marrow elements. The most important risk factor in HCT recipients is steroid exposure, frequently in the context of graft-versus-host disease. Current treatment is surgical, and involves decompression of the affected area and the use of bone grafts or hip arthroplasty. Cellular-based therapies are now under investigation, and can be used in addition to, or instead of, invasive surgery. This review presents an overview of osteonecrosis with particular emphasis on HCT recipients and introduces the role of cell therapy, especially with mesenchymal stromal cells, as a promising new treatment. | 18,804,037 |
Posttransplant autoimmune hemolytic anemia and other autoimmune cytopenias are increased in very young infants undergoing unrelated donor umbilical cord blood transplantation. | Autoimmune cytopenias are a recognized complication of hematopoietic stem cell transplant (HSCT), and are considered to be a feature of chronic graft-versus-host disease (cGVHD). We report on a cohort of very young infants (< or =3 months of age) receiving HSCT from unrelated donor umbilical cord blood for genetic disorders who developed posttransplant autoimmune cytopenias at an increased rate compared to older aged controls. These infants received a conditioning regimen consisting of busulfan, cyclophosphamide, and antithymocyte globulin (ATG). All infants received HLA mismatched unrelated umbilical cord blood as graft source. GVHD prophylaxis was either cyclosporine + methylprednisolone (n = 16) or cyclosporine + mycophenolate mofetil (n = 3). Engraftment, acute GVHD (aGVHD) and cGVHD, survival, treatment-related mortality (TRM), and deaths were evaluated. Ten patients developed cGVHD manifesting as autoimmune cytopenias at a median 247 days posttransplant with a cumulative incidence of 44% (95% confidence interval [CI] 21%-68%) and 56% (95% CI 32%-80%) at 1 and 2 years, respectively. In 6 of 10 patients developing autoimmune cytopenias, cGVHD presented as autoimmune cytopenia de novo. The cytopenias observed included anemia (n = 4), thrombocytopenia (n = 1), anemia with thrombocytopenia (n = 3), and pancytopenia (n = 2). No graft factors were identified as being significant to development of cGVHD. All patients responded to treatment with methylprednisolone, azithioprine +/- rituximab. One patient required splenectomy. We hypothesize that posttransplant immunosuppression interferes with normal immune ontogeny creating immune dysregulation and graft directed cell destruction. Alternative strategies to prevent GVHD should be considered for this unique patient population. | 18,804,040 |
Persistence of human parvovirus B19 in multipotent mesenchymal stromal cells expressing the erythrocyte P antigen: implications for transplantation. | Multipotent mesenchymal stromal cells (MSCs) are used to improve the outcome of hematopoietic stem cell transplantation (HCST) and in regenerative medicine. MSCs may harbor persistent viruses that may compromise their clinical benefit, however. Retrospectively screened, 1 of 20 MSCs from healthy donors contained parvovirus B19 (B19) DNA. MSCs express the B19 receptor (P antigen/globoside) and a co-receptor (Ku 80) and can transmit B19 to bone marrow cells in vitro, suggesting that the virus can persist in the marrow stroma of healthy individuals. Two patients undergoing HSCT received the B19-positive MSCs as treatment for graft-versus-host disease; neither developed viremia nor symptomatic B19 infection. These findings demonstrate for the first time that persistent B19 in MSCs can infect hematopoietic stem cells and underscore the importance of monitoring B19 transmission by MSC products. | 18,804,048 |
Protein engineering on biphenyl dioxygenase for conferring activity to convert 7-hydroxyflavone and 5,7-dihydroxyflavone (chrysin). | A central part (amino-acid position 268-397 of 458 amino-acid residues) of the biphenyl dioxygenase large (alpha) subunit, BphA1, from Pseudomonas pseudoalcaligenes strain KF707 was exchanged with the corresponding part of BphA1 from another biphenyl-degrading bacterium, Pseudomonas putida strain KF715, to construct hybrid BphA1, BphA1 (715-707). When expressed in Escherichia coli together with the bphA2A3A4BC genes from strain KF707, this enzyme was shown to possess activity for degrading both 1-phenylnaphthalene and 2-phenylnaphthalene. Between central parts of BphA1 from strains KF707 and KF715, the difference of amino-acid residues resided only in position 324-325. An attempt was made to improve the substrate preference of BphA1 by applying random amino-acid substitutions at these positions to BphA1 (715-707). After screening the mutant library to bioconvert several flavonoids, BphA1 (1-22; T324A and I325L) and BphA1 (2-2; T324L and I325I) were selected. When expressed in E. coli together with bphA2A3A4B from strain KF707, both BphA1 (1-22) and BphA1 (2-2) bioconverted the refractory flavonoids, 7-hydroxyflavone and 5,7-dihydroxyflavone (chrysin), which were hardly converted by any unmodified and artificially-modified shuffled biphenyl dioxygeneses, into their vicinal diol forms, i.e., 2-(2,3-dihydroxyphenyl)-7-hydroxy-chromen-4-one and 2-(2,3-dihydroxyphenyl)-5,7-dihydroxy-chromen-4-one, respectively. In addition, trans-chalcone was converted into 3-(2,3-dihydroxyphenyl)-1-phenylpropan-1-one and further into 1,3-bis-(2,3-dihydroxyphenyl)-propan-1-one. The antioxidative activity of these generated compounds was markedly higher than that of the original substrates used. | 18,804,053 |
CoCl(2) inhibits neural differentiation of retinoic acid-treated embryoid bodies. | The effects of CoCl(2) on retinoic acid (RA)-treated embryoid bodies (EBs) were investigated. Four-day EBs were treated with 5x10(-6) M of RA for 4 d, then subjected to attached culturing for 7 d in the presence of CoCl(2) at 0, 20, and 100 microM. Differentiation into MAP2- and GFAP-immunopositive cells was inhibited by CoCl(2) in a dose-dependent manner. Next, RA-treated EBs were dissociated into single cells and cultured for 7 d at an initial cell density of 1x10(3)/cm(2). The number of cells increased in a CoCl(2)-dose dependent fashion. In cultures with 100 microM of CoCl(2), more than 90% of the cells were immunopositive for nestin and nestin-immunopositive cells formed clusters, while there were few cells immunopositive for MAP2 or GFAP. These results suggest that CoCl(2) inhibits neural differentiation of RA-treated EB cells and promotes the proliferation of nestin-immunopositive cells, i.e., embryonic stem (ES)-derived neural stem-like cells. | 18,804,056 |
Ischemic brain cell-derived conditioned medium protects astrocytes against ischemia through GDNF/ERK/NF-kB signaling pathway. | Conditioned medium (CM) collected from cultures of ischemic microglia, astrocytes, and neurons were protective to astrocytes under the in vitro ischemic condition (deprivation of oxygen, glucose and serum). Molecular and signaling pathway(s) responsible for the CMs protective activity were investigated. Results showed that CMs from the ischemic microglia (MCM), astrocytes (ACM) and neurons (NCM) contained glial cell line-derived neurotrophic factor (GDNF), which protects astrocytes against the in vitro ischemia. Expression of extra cellular signal-regulated kinase (ERK1/2) and nuclear factor-kappa B (NF-kB) by GDNF led to the inhibition of apoptosis of the ischemic astrocytes in a caspase 3-independent manner. However, CMs- and GDNF-mediated protection of the ischemic astrocytes was protein kinase B (Akt) independent. These results provided mechanistic data regarding how GDNF- and CMs-mediated protection of the ischemic astrocytes is taking place. These observations provide information for the use of GDNF and GDNF containing CMs in the control of cerebral ischemia. | 18,804,095 |
Inflammatory pathways in malaria infection: TLRs share the stage with other components of innate immunity. | Severe forms of malaria infection claim over 1 million lives annually. One aspect of severe malaria pathogenesis is an excessive or dysregulated inflammatory response to infection. With the characterization of Toll-like receptors (TLRs), which initiate inflammation upon detection of microbial products, involvement of TLRs in the host response to malaria has undergone intense investigation. While TLRs appear to mediate inflammation in malaria infection and may contribute to development of severe malaria, it is unlikely that they operate in isolation from other components of innate immunity. Here, we highlight recent findings implicating other innate immune mechanisms in the host inflammatory response to malaria, propose how they may integrate and synergize with TLR pathways, and discuss opportunities and challenges associated with anti-inflammatory adjunctive therapy for the treatment of severe malaria. | 18,804,125 |
Kalopanaxsaponin A induces apoptosis in human leukemia U937 cells through extracellular Ca2+ influx and caspase-8 dependent pathways. | In the present study, we investigated the effect of KPS-A on the apoptotic activity and the molecular mechanism of the action in human leukemia. Treatment with KPS-A significantly increased apoptotic DNA fragmentation in human histiocytic lymphoma U937 cells as shown by DAPI staining, flow cytometry, and agarose gel electrophoresis. In addition, stimulation of U937 cell with KPS-A induced a series of intracellular events: (1) the activations of caspase-8, caspase-9, and caspase-3; (2) the translocations of Bid and Bax proteins to mitochondria; (3) the loss of mitochondrial membrane potential; and (4) the increased release of cytochrome c to the cytosol. Pretreatment with a specific caspases-8, -9 or -3 inhibitor, neutralized the pro-apoptotic activity of KPS-A in U937 cells. We further demonstrated that KPS-A markedly induced an increase in intracellular Ca2+ level, which was reversed by EGTA, a general calcium chelator, but not by TMB-8 and dantrolene, intracellular Ca2+ release blockers. Moreover, KPS-A-induced DNA fragmentation and caspase activation were substantially reduced in the presence of EGTA. Taken together, these results suggest that KPS-A may play therapeutic role for leukemia via the potent apoptotic activity through Ca2+/caspases-8/MPT/caspases-9/caspases-3 signaling pathway. | 18,804,143 |
The septal area, site for the central regulation of penile erection during waking and rapid eye movement sleep in rats: a stimulation study. | The effects of electrical stimulation to the septum on penile erections in rats were examined to clarify the mechanisms for regulation of erectile responses during different states of vigilance. Penile responses were assessed by changes in pressure in the corpus spongiosum of penis (CSP) and electromyography (EMG) of the bulbospongiosus (BS) muscle. In anesthetized and un-anesthetized rats, stimulation in and around the septum induced three erectile patterns; 1) a Normal type response, which was indistinguishable from a spontaneous erection, characterized by a slow increase in CSP pressure with sharp CSP pressure peaks associated with BS muscle bursts, 2) Mixed type response, in which high frequency CSP pressure peaks were followed by a Normal type response, and 3) a Prolonged type response, evoked only in the anesthetized rat, consisting of a single sharp CSP peak followed by a slow increase in CSP pressure and a return to baseline with multiple subsequent events repeated for up to 960 s. In addition, a Micturition type response was also observed involving high frequency CSP pressure oscillations similar to the pressure pattern seen during spontaneous micturition. We found that erections were induced after stimulation to the lateral septum (LS), but not from the medial septum (MS). In anesthetized rats, a few responses were also obtained following stimulation of the horizontal limb of diagonal band (HDB). In un-anesthetized rats, responses were also induced from the HDB and the ventral limb of diagonal band (VDB) and the adjoining areas. The effective sites for eliciting erection during rapid eye movement (REM) sleep were located in the dorsal and intermediate parts of the LS, whereas the ventral part of the LS was the most effective site for eliciting erections during wakefulness. These results suggest a functional role for penile erection in the septum, and further suggest that subdivisions of the LS may have different roles in the regulation of penile erection during wakefulness and REM sleep. | 18,804,152 |
Rubratoxin B induces interleukin-6 secretion in mouse white adipose tissues and 3T3-L1 adipocytes. | Rubratoxin B is a mycotoxin that causes hepatic fatty changes. We examined whether white adipose tissue (WAT) contributes to rubratoxin B toxicity through effects on interleukin (IL)-6. Rubratoxin B was intraperitoneally injected into mice at 1.5mg/kg. Urinary albumin and macrophage inflammatory protein (MIP)-2 secretion were increased 24h after treatment with rubratoxin B. Rubratoxin B was previously reported to induce IL-6 secretion, although the secreting tissue was unknown. Here, rubratoxin B prominently augmented IL-6 transcription in epididymal WAT and to a lesser extent in perirenal WAT and liver. Rubratoxin B may thus exert its toxicity partly through IL-6 secretion from WATs. In contrast, MIP-2 gene expression increased only in liver. To examine the specific involvement of adipocytes, we used mouse 3T3-L1 cells, an in vitro differentiation model of adipocytes. Expression of IL-6 and MIP-2 mRNA in 3T3-L1 adipocytes after 24h of rubratoxin B treatment increased dose-dependently. Rubratoxin B also increased IL-6 and MIP-2 secretion from 3T3-L1 adipocytes. The increase in IL-6 secretion was markedly higher than the increase in IL-6 gene transcription, indicating that rubratoxin B-induced secretion of IL-6 from 3T3-L1 adipocytes is chiefly controlled post-transcriptionally. Rubratoxin B is thus the first mycotoxin known to exert its toxicity through effects on WATs. | 18,804,154 |
Tweaking biological switches through a better understanding of bistability behavior. | Many biological events are binary. The switch between mutually exclusive OFF to ON state in response to a stimulus is frequently mediated by a control circuit with a positive and/or a negative feedback. Such a system typically exhibits hysteresis with its switching ON and OFF stimulus levels dependent on the current state of the system. The system can be shown to be bistable both experimentally and mathematically. Work to synthesize such switches by combining natural or engineered components has begun to illustrate the potential of such control circuits in many areas of applications. | 18,804,166 |
Has nature already identified all useful antibacterial targets? | Novel antimicrobial targets are urgently needed to overcome rising antibiotic resistance of important human pathogens. However, evidence from previous antimicrobial screenings, in silico analysis, and experimental target evaluation suggests that the number of novel bacterial broad-spectrum targets might be severely limited. This is because of the poor conservation of genes among diverse bacterial pathogens, partial functional redundancy and nutrient-rich host environments. Remaining opportunities under these circumstances include the development of narrow-spectrum antibiotics against specific pathogens and the exploration of target combinations. | 18,804,175 |
Sequential effects within a short foreperiod context: evidence for the conditioning account of temporal preparation. | Responses to an imperative stimulus (IS) are especially fast when they are preceded by a warning signal (WS). When the interval between WS and IS (the foreperiod, FP) is variable, reaction time (RT) is not only influenced by the current FP but also by the FP of the preceding trial. These sequential effects have recently been proposed to originate from a trace conditioning process, in which the individuals learn the temporal WS-IS relationship in a trial-by-trial manner. Research has shown that trace conditioning is maximal when the temporal interval between the conditioned and unconditioned stimulus is between 0.25 and 0.60s. Consequently, one would predict that sequential effects occur especially within short FP contexts. However, this prediction is contradicted by Karlin [Karlin, L. (1959). Reaction time as a function of foreperiod duration and variability. Journal of Experimental Psychology, 58, 185-191] who did not observe the typical sequential effects with short FPs. To investigate temporal preparation for short FPs, three experiments were conducted, examining the sequential FP effect comparably for short and long FP-sets (Experiment 1), assessing the influence of catch trials (Experiment 2) and the case of a very dense FP-range (Experiment 3) on sequential FP effects. The results provide strong evidence for sequential effects within a short FP context and thus support the trace conditioning account of temporal preparation. | 18,804,193 |
New immunosuppressive approaches: oral administration of CD3-specific antibody to treat autoimmunity. | One of the major goals for the immunotherapy of autoimmune diseases is the induction of regulatory T cells that mediate immunologic tolerance. Parenteral administration of anti-CD3 monoclonal antibody is an approved therapy for transplantation in humans and is effective in autoimmune diabetes. We have found that oral administration of anti-CD3 monoclonal antibody is biologically active in the gut and suppresses experimental autoimmune encephalomyelitis both prior to disease induction and at the height of disease. Oral anti-CD3 antibody acts by inducing a unique type of regulatory T cell characterized by latency-associated peptide (LAP) on its cell surface that functions in vivo and in vitro via TGF-beta dependent mechanism. Orally delivered antibody would not have side effects including cytokine release syndromes, thus oral anti-CD3 antibody is clinically applicable for chronic therapy. These findings identify a novel and powerful immunologic approach that is widely applicable for the treatment of human autoimmune conditions. | 18,804,221 |
Diagnostic accuracy of an initial azoospermic reading compared with results of post-centrifugation semen analysis after vasectomy. | Semen analysis is a common laboratory procedure but few data are available to support recommendations as to whether centrifugation is necessary in the post-vasectomy context. We evaluated the accuracy of a pre-centrifugation determination of azoospermia compared with post-centrifugation results. We conducted a secondary analysis of data from 3,205 semen analyses performed during a randomized clinical trial of 2 vasectomy techniques--ligation and excision with fascial interposition vs ligation and excision without fascial interposition. We performed brief, initial microscopic examinations to categorize sperm numbers per high power field to decide whether centrifugation or dilution was needed before estimation of sperm concentration. For specimens initially categorized as azoospermic, we reviewed the post-centrifugation semen analysis results to estimate the accuracy of the initial finding. Of 2,104 samples categorized as azoospermic before centrifugation, post-centrifugation analysis demonstrated that all but 4 (99.8%) were azoospermic or had a sperm concentration of less than 100,000 sperm per ml. Four samples from 1 study site had counts between 104,000 and 315,000 sperm per ml. Of 1,610 apparently azoospermic samples obtained at 10 weeks or later after vasectomy there were 12 (0.7%) that had some motile sperm identified after centrifugation but the numbers of motile sperm were low (mean 1,124 motile sperm per ml, range 238 to 3,710). Microscopic examination of uncentrifuged specimens is a reliable method for identifying semen samples after vasectomy with more than 100,000 sperm per ml. | 18,804,227 |
Urinary symptoms before and after female urethral diverticulectomy--can we predict de novo stress urinary incontinence? | We assessed preoperative and postoperative urinary symptoms, and determined risk factors for de novo stress urinary incontinence after transvaginal urethral diverticulectomy. We reviewed the case records of 25 consecutive women who had transvaginal urethral diverticulectomy. Urinary symptoms were documented before and after surgery with a structured history and examination pro forma. Demographic, clinical and imaging parameters were reviewed to determine any association with preoperative and postoperative symptoms as well as possible risk factors for postoperative stress urinary incontinence. The most common presenting symptoms were urinary urgency and frequency (60%), and dyspareunia (56%). On physical examination the most common findings were a tender anterior vaginal wall mass (88%) and urethral discharge (40%). At a mean followup of 15.1 +/- 14.9 months (median 12) the rate of urgency-frequency symptoms and dyspareunia decreased significantly from 60% to 16% and from 56% to 8%, respectively. All the patients who had urge incontinence were cured of this symptom after the operation. De novo stress urinary incontinence developed in 4 patients (16%) postoperatively, and it was mild and only necessitated surgical treatment in 1 patient. A diverticulum larger than 30 mm and proximal urethral location were significant factors (p <0.05) for the development of de novo stress urinary incontinence. Irritative bladder symptoms are common in woman with urethral diverticulum and usually resolve after surgical excision. Stress urinary incontinence developed immediately after the operation, and had a significant association with a proximal urethral location and ultrasonically measured size greater than 30 mm. | 18,804,229 |
Coagulation dynamics of fractal flocs induced by enmeshment and electrostatic patch mechanisms. | The size and structure of flocs during floc formation were monitored for various coagulation mechanisms. Two distinctive mechanisms, namely, enmeshment and electrostatic patch, govern the dynamics of kaolin particles coagulation by polyaluminum chloride (PACl). They were investigated by small angle static light scattering (SASLS) and solid-state (27)Al NMR. In addition, a novel wet SEM (WSEM) was used in-situ to image the morphology of the aggregate in aqueous solution. Synthetic suspended particles were coagulated by two PACl products, a commercial product (PACl) and one laboratory product (PACl-E). The PACl-E contained more than 60% Al(13) while the PACl contained only 7% Al(13), with large percentage of colloidal Al. For coagulation by PACl at neutral pH and high dosage where the strong repulsion between particles occurs, the enmeshment ruled by reaction-limited aggregation (RLA) results in larger sweep flocs as well as higher fractal dimensional structure. For coagulation by PACl-E at alkaline pH and low dosage, the flocs were coagulated predominately by electrostatic patch with Al(13) aggregates. At such condition, it is likely that diffusion-limited aggregation (DLA) predominately rule PACl-E coagulation. The fractal dimension (D(s)) values of PACl and PACl-E flocs formed at enmeshment and electrostatic patch increased with dosage, respectively. When breakage of flocs occurs, the breakage rate of PACl-E flocs is slower than that of sweep flocs. By WSEM imaging, the adsorption of spherical Al precipitates onto the particles was observed to form sweep flocs with a rough and ragged contour, while the PACl-E flocs were formed with a smooth and glossy structure. | 18,804,257 |
Influence of liming on metal sequestration in lake sediments over recent decades. | Sediment profiles from five limed and six reference softwater lakes included in Swedish monitoring programmes were subjected to multi-element analysis to investigate the influence of lime treatment since 1977 on the sequestration of metals in lake sediments. We hypothesised that liming causes increased sedimentation of elements for which the mobility is primarily controlled by pH, e.g. Al, Cd, Co, Ni and Zn, whereas elements that are less influenced by pH fluctuations, e.g. Hg and Pb, are not affected by lime treatment. Further, we introduce a normalisation of metal concentrations with respect to Cu concentration in order to separate the effects of lime treatment from those related to temporal trends in airborne metal deposition or short-term variations in environmental conditions. This approach is shown to emphasise the effect of liming on the sediment accumulation of metals, thus separating it from other sources of variability. We found that liming causes increased sequestration of Al, As, Cd, Co, Fe, Mn, Ni and Zn, in the case of As and Co probably at least partly caused by an increased adsorption to Al, Fe and Mn oxyhydroxides. On the other hand, no influence of lime treatment could be demonstrated for Hg, Pb, Cr, V and P, despite an increase of pH by about two units. | 18,804,259 |
SPME-GCMS study of the natural attenuation of aviation diesel spilled on the perennial ice cover of Lake Fryxell, Antarctica. | In January 2003, a helicopter crashed on the 5 m thick perennial ice cover of Lake Fryxell (McMurdo Dry Valleys, East Antarctica), spilling approximately 730 l of aviation diesel fuel (JP5-AN8 mixture). The molecular composition of the initial fuel was analyzed by solid phase microextraction (SPME) gas chromatography-mass spectrometry (GC-MS), then compared to the composition of the contaminated ice, water, and sediments collected a year after the spill. Evaporation is the major agent of diesel weathering in meltpool waters and in the ice. This process is facilitated by the light non-aqueous phase liquid properties of the aviation diesel and by the net upward movement of the ice as a result of ablation. In contrast, in sediment-bearing ice, biodegradation by both alkane- and aromatic-degraders was the prominent attenuation mechanism. The composition of the diesel contaminant in the ice was also affected by the differential solubility of its constituents, some ice containing water-washed diesel and some ice containing exclusively relatively soluble low molecular weight aromatic hydrocarbons such as alkylbenzene and naphthalene homologues. The extent of evaporation, water washing and biodegradation between sites and at different depths in the ice are evaluated on the basis of molecular ratios and the results of JP5-AN8 diesel evaporation experiment at 4 degrees C. Immediate spread of the aviation diesel was enhanced where the presence of aeolian sediments induced formations of meltpools. However, in absence of melt pools, slow spreading of the diesel is possible through the porous ice and the ice cover aquifer. | 18,804,261 |
Production of transgenic recloned piglets harboring the human granulocyte-macrophage colony stimulating factor (hGM-CSF) gene from porcine fetal fibroblasts by nuclear transfer. | We used nuclear transfer (NT) to develop transgenic female pigs harboring goat beta-casein promoter/human granulocyte-macrophage colony stimulating factor (hGM-CSF). The expression of hGM-CSF was specific to the mammary gland, and the glycosylation-derived size heterogeneity corresponded to that of the native human protein. Although various cell types have been used to generate cloned animals, little is currently known about the potential use of fibroblasts derived from a cloned fetus as donor cells for nuclear transfer. The developmental potential of porcine cloned fetal fibroblasts transfected with hGM-CSF was evaluated in the present study. Cloned fetal fibroblasts were isolated from a recipient following the transplantation of NT embryos. The cells were transfected with both hGM-CSF and the neomycin resistance gene in order to be used as donor cells for NT. Reconstructed embryos were implanted into six sows during estrus; two of the recipient sows delivered seven healthy female piglets with the hGM-CSF gene (confirmed with PCR and fluorescent in situ hybridization) and microsatellite analysis confirmed that the clones were genetically identical to the donor cells. The expression of hGM-CSF was strong in the mammary glands of a transgenic pig that died a few days prior to parturition (110 d after AI). These results demonstrated that somatic cells derived from a cloned fetus can be used to produce recloned and transgenic pigs. | 18,804,273 |
Expansion of microvascular networks in vivo by phthalimide neovascular factor 1 (PNF1). | Phthalimide neovascular factor (PNF1, formerly SC-3-149) is a potent stimulator of proangiogenic signaling pathways in endothelial cells. In this study, we evaluated the in vivo effects of sustained PNF1 release to promote ingrowth and expansion of microvascular networks surrounding biomaterial implants. The dorsal skinfold window chamber was used to evaluate the structural remodeling response of the local microvasculature. PNF1 was released from poly(lactic-co-glycolic acid) (PLAGA) films, and a transport model was utilized to predict PNF1 penetration into the surrounding tissue. PNF1 significantly expanded microvascular networks within a 2mm radius from implants after 3 and 7 days by increasing microvessel length density and lumenal diameter of local arterioles and venules. Staining of histological sections with CD11b showed enhanced recruitment of circulating white blood cells, including monocytes, which are critical for the process of vessel enlargement through arteriogenesis. As PNF1 has been shown to modulate MT1-MMP, a facilitator of CCL2 dependent leukocyte transmigration, aspects of window chamber experiments were repeated in CCR2(-/-) (CCL2 receptor) mouse chimeras to more fully explore the critical nature of monocyte recruitment on the therapeutic benefits of PNF1 function in vivo. | 18,804,278 |
Effect of body mass index on shifts in ultrasound-based image-guided intensity-modulated radiation therapy for abdominal malignancies. | We investigated whether corrective shifts determined by daily ultrasound-based image-guidance correlate with body mass index (BMI) of patients treated with image-guided intensity-modulated radiation therapy (IG-IMRT) for abdominal malignancies. The utility of daily image-guidance, particularly for patients with BMI>25.0, is examined. Total 3162 ultrasound-directed shifts were performed in 86 patients. Direction and magnitude of shifts were correlated with pretreatment BMI. Bivariate statistical analysis and analysis of set-up correction data were performed using systematic and random error calculations. Total 2040 daily alignments were performed. Average 3D vector of set-up correction for all patients was 12.1mm/fraction. Directional and absolute shifts and 3D vector length were significantly different between BMI cohorts. 3D displacement averaged 4.9 mm/fraction and 6.8mm/fraction for BMI < or = 25.0 and BMI>25.0, respectively. Systematic error in all axes and 3D vector was significantly greater for BMI>25.0. Differences in random error were not statistically significant. Set-up corrections derived from daily ultrasound-based IG-IMRT of abdominal tumors correlated with BMI. Daily image-guidance may improve precision of IMRT delivery with benefits assessed for the entire population, particularly patients with increased habitus. Requisite PTV margins suggested in the absence of daily image-guidance are significantly greater in patients with BMI>25.0. | 18,804,301 |
Kinetics of transformation of 1,1,1-trichloroethane by Fe(II) in cement slurries. | This study examines the applicability of the iron-based degradative solidification/stabilization (DS/S-Fe(II)) process to 1,1,1-trichloroethane (1,1,1-TCA), which is one of common chlorinated aliphatic hydrocarbons (CAHs) of concern at contaminated sites. DS/S-Fe(II) combines contaminant degradation by Fe(II) and immobilization by the hydration reactions of Portland cement. The transformation of 1,1,1-TCA by Fe(II) in 10% Portland cement slurries was studied using a batch slurry reactor system. The effects of Fe(II) dose, pH, and initial concentration of 1,1,1-TCA on the kinetics of 1,1,1-TCA degradation were evaluated. Degradation of 1,1,1-TCA in cement slurries including Fe(II) was very rapid and could be described by a pseudo-first-order rate law. The half-lives for 1,1,1-TCA were measured between 0.4 and 5h when Fe(II) dose ranged from 4.9 to 39.2mM. The pseudo-first-order rate constant increased with pH to a maximum near pH 12.5. A saturation rate equation was able to predict degradation kinetics over a wide range of target organic concentrations and at higher Fe(II) doses. The major transformation product of 1,1,1-TCA in mixtures of Fe(II) and cement was 1,1-dichloroethane (1,1-DCA), which indicates that degradation occurred by a hydrogenolysis pathway. A small amount of ethane was observed. The conversion of 1,1,1-TCA to ethane was better described by a parallel reaction model than by a consecutive reaction model. | 18,804,328 |
Comparison of spine, carina, and tumor as registration landmarks for volumetric image-guided lung radiotherapy. | To assess the feasibility, reproducibility, and accuracy of volumetric lung image guidance using different thoracic landmarks for image registration. In 30 lung patients, four independent observers conducted automated and manual image registrations on Day 1 cone-beam computed tomography data sets using the spine, carina, and tumor (720 image registrations). The image registration was timed, and the couch displacements were recorded. The intraclass correlation was used to assess reproducibility, and the Bland-Altman analysis was used to compare the automatic and manual matching methods. Tumor coverage (accuracy) was assessed through grading the tumor position after image matching against the internal target volume and planning target volume. The image-guided process took an average of 1 min for all techniques, with the exception of manual tumor matching, which took 4 min. Reproducibility was greatest for automatic carina matching (intraclass correlation, 0.90-0.93) and lowest for manual tumor matching (intraclass correlation, 0.07-0.43) in the left-right, superoinferior, and anteroposterior directions, respectively. The Bland-Altman analysis showed no significant difference between the automatic and manual registration methods. The tumor was within the internal target volume 62% and 60% of the time and was outside the internal target volume, but within the planning target volume, 38% and 40% of the time after automatic spine and automatic carina matching, respectively. For advanced lung cancer, the spine or carina can be used equally for cone-beam computed tomography image registration without compromising target coverage. The carina was more reproducible than the spine, but additional analysis is required to confirm its validation as a tumor surrogate. Soft-tissue registration is unsuitable at present, given the limitations in contrast resolution and the high interobserver variability. | 18,804,335 |
Epidemiology of community-acquired pneumonia in older adults: a population-based study. | This study assessed incidence, aetiology, clinical outcomes and risk factors for community-acquired pneumonia (CAP) in older adults. This was a population-based cohort study that included 11,241 community-dwelling individuals aged 65 years or more, who were followed between 2002 and 2005 in the region of Tarragona, Spain. Primary endpoints were all-cause CAP (hospitalised and outpatient) and 30-day mortality after the diagnosis. All cases were radiographically proved and validated by checking clinical records. Incidence rate of overall CAP was 14 cases per 1000 person-years (10.5 and 3.5 for hospitalised and outpatient cases, respectively). Incidence was almost three-fold higher among immunocompromised patients (30.9 per 1000) than among immunocompetent subjects (11.6 per 1000). Maximum incidences were observed among patients with chronic lung disease and long-term corticosteroid therapy (46.5 and 40.1 cases per 1000 person-years, respectively). Overall 30-day case-fatality rate was 12.7% (2% in cases managed as outpatient and 15% in hospitalised patients). Among 358 patients with an aetiological work-up, a total of 142 pathogens were found (single pathogen in 121 cases and mixed pathogens in 10 cases). Streptococcus pneumoniae was the most common pathogen (49%), followed by Pseudomonas aeruginosa (15%), Chlamydia pneumoniae (9%) and Haemophilus influenzae (6%). In multivariable analysis, the variables most strongly associated with increasing risk of CAP were history of hospitalisation for CAP in the previous 2 years and presence of any chronic lung disease. CAP remains a major cause of morbidity and mortality in older adults. Incidence rates in this study largely doubled prior rates reported in Southern European regions. | 18,804,355 |
Unknown primary head and neck cancer treated with intensity-modulated radiation therapy: to what extent the volume should be irradiated. | To evaluate the efficacy and feasibility of irradiation with intensity-modulated radiotherapy (IMRT) technique in patients with head and neck carcinoma of unknown primary (HNCUP). Between February 2000 and November 2006, 22 consecutive patients diagnosed with HNCUP were treated with IMRT. Of these, four patients were excluded because two of them underwent IMRT only as a boost and the other two had distant metastasis at presentation and were treated palliatively. Of the remaining 18 patients eligible for analysis, 6 had definitive IMRT and 12 had postoperative IMRT (8 with neck dissection and 4 with excisional biopsy). One patient with abnormal lymph node found unexpectedly during carotid endarterectomy was treated to ipsilateral neck only. The target volumes for the other 17 patients include nasopharynx, oropharynx, retropharyngeal lymph nodes, and bilateral neck. In 1 patient who had extensive lymph node involvement, the hypopharynx and the larynx were defined as target. In all other patients the larynx including hypopharynx were defined as dose-limiting structures. The parotids, cervical esophagus, spinal cord, brain stem, optic nerves and the orbits are also outlined as dose-limiting structures. All patients completed their treatment without interruption and severe complications. With a median follow-up time of 25.5 months, 2 patients had persistent cervical lymphadenopathy and 2 had distant metastases. Another patient developed a lung cancer and a second pyriform sinus cancer 25 months after treatment. The 2-year overall survival, regional recurrence-free survival and distant metastases-free survival were 74.2%, 88.5%, and 88.2%, respectively. Six patients had prophylactic percutaneous endoscopic gastrostomy (PEG) tubes placed before radiation. Most had PEG tubes removed within 7 months after the completion of treatment. IMRT delivered to comprehensive bilateral neck and putative mucosal site (including nasopharynx, oropharynx, and retropharyngeal lymph nodes) appears to be effective for patients with HNCUP. Our preliminary results show that such approach does not compromise local-regional control. Further studies with more patients and longer follow-up are necessary to validate this approach. | 18,804,408 |
The capsaicin receptor participates in artificial sweetener aversion. | Artificial sweeteners such as saccharin, aspartame, acesulfame-K, and cyclamate produce at high concentrations an unpleasant after-taste that is generally attributed to bitter and metallic taste sensations. To identify receptors involved with the complex perception of the above compounds, preference tests were performed in wild-type mice and mice lacking the TRPV1 channel or the T1R3 receptor, the latter being necessary for the perception of sweet taste. The sweeteners, including cyclamate, displayed a biphasic response profile, with the T1R3 mediated component implicated in preference. At high concentrations imparting off-taste, omission of TRPV1 reduced aversion. In a heterologous expression system the Y511A point mutation in the vanilloid pocket of TRPV1 did not affect saccharin and aspartame responses but abolished cyclamate and acesulfame-K activities. The results rationalize artificial sweetener tastes and off-tastes by showing that at low concentrations, these molecules stimulate the gustatory system through the hedonically positive T1R3 pathway, and at higher concentrations, their aversion is partly mediated by TRPV1. | 18,804,451 |
TGF beta2-induced changes in LRP-1/T beta R-V and the impact on lysosomal A beta uptake and neurotoxicity. | Numerous studies suggest a central role for the low-density lipoprotein receptor-related protein/transforming growth factor beta receptor V in Alzheimer's Disease. We continue our investigation of a ligand for this receptor, transforming growth factor beta2, which is also implicated in Alzheimer Disease pathogenesis, but whose mechanism(s) remain elusive. Confocal imaging reveals that transforming growth factor beta2 rapidly targets amyloid beta peptide to the lysosomal compartment in cortical neurons and induces cell death. Low-density lipoprotein receptor-related protein/transforming growth factor beta receptor V is known as an endocytic receptor, delivering proteins to the lysosomal compartment for degradation. Transforming growth factor beta2 may alter this pathway resulting in increased uptake, intracellular accumulation and toxicity of amyloid beta peptide. RT-PCR and Western blot analysis of transforming growth factor beta2-treated cells demonstrate that transforming growth factor beta2 modestly increases the mRNA and protein levels of low-density lipoprotein receptor-related protein/transforming growth factor beta receptor V as well as increases the uptake activity. Furthermore, transforming growth factor beta2 alters the morphology and numbers of lysosomes in neurons. Lucifer Yellow and lysosomal hydrolase analysis show that transforming growth factor beta2 makes lysosomal membranes unstable and leaky and this effect is exacerbated with the addition of amyloid beta protein. Our data support a key role for low-density lipoprotein receptor-related protein/transforming growth factor beta receptor V in mediating transforming growth factor beta2 enhancement of amyloid beta peptide uptake and neurotoxicity. | 18,804,458 |
Wnt6 signaling regulates heart muscle development during organogenesis. | Mesodermal tissue with heart forming potential (cardiogenic mesoderm) is induced during gastrulation. This cardiogenic mesoderm later differentiates into heart muscle tissue (myocardium) and non-muscular heart tissue. Inhibition of Wnt/beta-catenin signaling is known to be required early for induction of cardiogenic mesoderm; however, the identity of the inhibiting Wnt signal itself is still elusive. We have identified Wnt6 in Xenopus as an endogenous Wnt signal, which is expressed in tissues close to and later inside the developing heart. Our loss-of-function experiments show that Wnt6 function is required in the embryo to prevent development of an abnormally large heart muscle. We find, however, that Wnt6 is not required as expected during gastrulation stages, but later during organogenesis stages just before cells of the cardiogenic mesoderm begin to differentiate into heart muscle (myocardium). Our gain-of-function experiments show that Wnt6 and also activated canonical Wnt/beta-catenin signaling are capable of restricting heart muscle development at these relatively late stages of development. This repressive role of Wnt signaling is mediated initially via repression of cardiogenic transcription factors, since reinstatement of GATA function can rescue expression of other cardiogenic transcription factors and downstream cardiomyogenic differentiation genes. | 18,804,460 |
Brief cross-linking of Fas/APO-1 (CD95) triggers engulfment of pre-apoptotic target cells. | Macrophage clearance of dying cells is of crucial importance to maintain tissue homeostasis. Here, we show that brief treatment (15min) of Jurkat T cells with agonistic anti-Fas antibodies or recombinant Fas ligand results in efficient phagocytosis by human monocyte-derived macrophages prior to the occurrence of common biomarkers of apoptosis. Similar findings were obtained when using primary human T cells. Macrophage engulfment of pre-apoptotic target cells was suppressed in the absence of serum. Moreover, pre-apoptotic cells secreted annexin I and administration of Boc1, a formyl peptide receptor/lipoxin receptor antagonist markedly attenuated their engulfment. Finally, pre-apoptotic Jurkat cells induced lower macrophage production of tumor necrosis factor-alpha and higher production of interleukin-10 in comparison to apoptotic target cells. | 18,804,468 |
Acoustic characteristics, early experience, and endocrine status interact to modulate female zebra finches' behavioral responses to songs. | Female songbirds use male songs as an important criterion for mate selection. Properties of male songs are thought to indicate the male's quality as a potential mate. Song preferences in female zebra finches are known to be influenced by two factors--early auditory experience and the acoustic characteristics of males' songs. Studies often investigate song preferences by priming females with estrogen. However, estrogenic influences on song preferences have not been studied. We investigated the relative influence of early auditory experience, acoustic features of songs, and estrogen availability on song responsiveness in female zebra finches. Juvenile female zebra finches were tutored for 10 days with 40 songs per day with one of three acoustically different song types--simple songs, long-bout songs or complex songs. A fourth group of females was untutored. Aside from this brief song exposure, females were raised and maintained without exposure to male songs. During adulthood, females' behavioral responses to the three song types were tested under three hormone conditions--untreated, estradiol-treated and 1,4,6-androstatriene-3,17-dione (ATD)-treated (to lower endogenous estrogen). Based on the results of our study, four conclusions can be drawn. First, song responsiveness in female zebra finches is strongly affected by minimal early acoustic experience. Second, inexperienced female zebra finches are inherently biased to respond more to complex songs over other song types Third, although female zebra finches are inherently biased to respond more to complex songs, early acoustic experience may either reinforce or weaken this inherent responsiveness to complex songs. Fourth, estrogen selectively accentuates song responsiveness in acoustically-experienced female zebra finches. | 18,804,474 |
Mixed allele malaria vaccines: host protection and within-host selection. | Malaria parasites are frequently polymorphic at the antigenic targets of many candidate vaccines, presumably as a consequence of selection pressure from protective immune responses. Conventional wisdom is therefore that vaccines directed against a single variant could select for non-target variants, rendering the vaccine useless. Many people have argued that a solution is to develop vaccines containing the products of more than one variant of the target. However, we are unaware of any evidence that multi-allele vaccines better protect hosts against parasites or morbidity. Moreover, selection of antigen-variants is not the only evolution that could occur in response to vaccination. Increased virulence could also be favored if more aggressive strains are less well controlled by vaccine-induced immunity. Virulence and antigenic identity have been confounded in all studies so far, and so we do not know formally from any animal or human studies whether vaccine failure has been due to evasion of protective responses by variants at target epitopes, or whether vaccines are just less good at protecting against more aggressive strains. Using the rodent malaria model Plasmodium chabaudi and recombinant apical membrane antigen-1 (AMA-1), we tested whether a bi-allelic vaccine afforded greater protection from parasite infection and morbidity than did vaccination with the component alleles alone. We also tested the effect of mono- and bi-allelic vaccination on within-host selection of mixed P. chabaudi infections, and whether parasite virulence mediates pathogen titres in immunized hosts. We found that vaccination with the bi-allelic AMA-1 formulation did not afford the host greater protection from parasite infection or morbidity than did mono-allelic AMA-1 immunization. Mono-allelic immunization increased the frequency of heterologous clones in mixed clone infections. There was no evidence that any type of immunization regime favored virulence. A single AMA-1 variant is a component of candidate malaria vaccines current in human trials; our results suggest that adding extra AMA-1 alleles to these vaccines would not confer clinical benefits, but that that mono-allelic vaccines could alter AMA-1 allele frequencies in natural populations. | 18,804,509 |
The role of amygdala during auditory verbal imagery of derogatory appraisals by others. | We tend to simulate or recall others' appraisals through auditory verbal imagery (AVI) process to react appropriately. In particular, the ability to imagine derogatory appraisals by others may be critically important for social survival. In this study, we investigated the neural correlates implicated in the processing of unpleasant emotion related to derogatory remark and its self-directedness during AVI process. Twenty-three right-handed healthy human subjects participated in our study. We asked each subject to imagine hearing one's own or another person's voice saying derogatory or non-derogatory neutral remarks during the scanning of functional magnetic imaging. A test of the interaction between derogatory emotion and its self-directedness revealed significant activation of the amygdala. Additionally, we observed decreased neural activity in the anterior cingulate cortex (ACC) during imagery of derogatory remarks compared to neutral remarks. Our findings indicate an important role of the amygdala in the processing of unpleasant emotion or self-relevance of information in the real world may also be expanded to the processing of self-directedness of unpleasant emotion in the imagined world, and thereby contribute to human higher social cognitive process. This study also suggests that deactivation of ACC may enable us to enact vivid affective responses, and thereby contribute to an effective simulation of social interaction. | 18,804,514 |
Hoodia gordonii: a natural appetite suppressant. | Several species of the stapeliads, a group of stem succulents belonging to the family Apocynaceae are reported on in the ethnopharmacology literature and many of the references relate to their use as food plants. The most important of these plants is Hoodia gordonii, which during the past decade has risen from an almost forgotten spiny, desert plant to an important commercial appetite-suppressant herbal. The aim of this review is to summarize the botany, ethnopharmacology and phytochemistry of Hoodia gordonii. Journal articles and books were used to collect information on Hoodia gordonii and related species. Many books and articles documented the use of stapeliad species as food plants and earlier references refer to the use Hoodia species as a thirst quencher. However, prior to the publication of the patent application, only a single reference referring to the use of Hoodia pilifera as appetite suppressant was found. The structures of several steroid glycosides isolated from Hoodia gordonii are summarized. Hoodia gordonii illustrates how a combination of ethnobotany and scientific research can lead to a commercial product which can greatly benefit the indigenous people. | 18,804,523 |
Molecular signatures associated with transformation and progression to breast cancer in the isogenic MCF10 model. | Comparative microarray analyses provided insight into understanding transcript changes during cancer progression; however, a reproducible signature underlying breast carcinogenesis has yet to be little available. We utilized gene expression profiling to define molecular signatures associated with transformation and cancer progression in a series of isogenic human breast cancer cell lines including a normal, benign, noninvasive and invasive carcinoma. Clustering analysis revealed four distinct expression patterns based on upregulation or downregulation patterns. These profiles proved quite useful for describing breast cancer tumorigenesis and invasiveness. Downregulation of TNFSF7, S100A4, S100A7, S100A8, and S100A9 (calcium-binding protein family), and upregulation of kallikrein-5 and thrombospondin-1 were associated with transformation and progression of breast cancer cells. Importantly, downregulation of the genes was reversed by treatment with silencing inhibitors, implying the potential roles of epigenetic inactivation in breast carcinogenesis. Exogenous expressions of S100A8 and S100A9 inhibit growth in benign and noninvasive carcinoma cells, suggesting their negative role in cell proliferation. The data presented here may facilitate the identification and functional analyses of prognostic biomarkers for breast cancer. | 18,804,527 |
Long-term global and regional brain volume changes following severe traumatic brain injury: a longitudinal study with clinical correlates. | Traumatic brain injury (TBI) results in neurodegenerative changes that progress for months, perhaps even years post-injury. However, there is little information on the spatial distribution and the clinical significance of this late atrophy. In 24 patients who had sustained severe TBI we acquired 3D T1-weighted MRIs about 8 weeks and 12 months post-injury. For comparison, 14 healthy controls with similar distribution of age, gender and education were scanned with a similar time interval. For each subject, longitudinal atrophy was estimated using SIENA, and atrophy occurring before the first scan time point using SIENAX. Regional distribution of atrophy was evaluated using tensor-based morphometry (TBM). At the first scan time point, brain parenchymal volume was reduced by mean 8.4% in patients as compared to controls. During the scan interval, patients exhibited continued atrophy with percent brain volume change (%BVC) ranging between -0.6% and -9.4% (mean -4.0%). %BVC correlated significantly with injury severity, functional status at both scans, and with 1-year outcome. Moreover, %BVC improved prediction of long-term functional status over and above what could be predicted using functional status at approximately 8 weeks. In patients as compared to controls, TBM (permutation test, FDR 0.05) revealed a large coherent cluster of significant atrophy in the brain stem and cerebellar peduncles extending bilaterally through the thalamus, internal and external capsules, putamen, inferior and superior longitudinal fasciculus, corpus callosum and corona radiata. This indicates that the long-term atrophy is attributable to consequences of traumatic axonal injury. Despite progressive atrophy, remarkable clinical improvement occurred in most patients. | 18,804,539 |
Neural substrates of reward magnitude, probability, and risk during a wheel of fortune decision-making task. | Economic decision-making involves the weighting of magnitude and probability of potential gains/losses. While previous work has examined the neural systems involved in decision-making, there is a need to understand how the parameters associated with decision-making (e.g., magnitude of expected reward, probability of expected reward and risk) modulate activation within these neural systems. In the current fMRI study, we modified the monetary wheel of fortune (WOF) task [Ernst, M., Nelson, E.E., McClure, E.B., Monk, C.S., Munson, S., Eshel, N., et al. (2004). Choice selection and reward anticipation: an fMRI study. Neuropsychologia 42(12), 1585-1597.] to examine in 25 healthy young adults the neural responses to selections of different reward magnitudes, probabilities, or risks. Selection of high, relative to low, reward magnitude increased activity in insula, amygdala, middle and posterior cingulate cortex, and basal ganglia. Selection of low-probability, as opposed to high-probability reward, increased activity in anterior cingulate cortex, as did selection of risky, relative to safe reward. In summary, decision-making that did not involve conflict, as in the magnitude contrast, recruited structures known to support the coding of reward values, and those that integrate motivational and perceptual information for behavioral responses. In contrast, decision-making under conflict, as in the probability and risk contrasts, engaged the dorsal anterior cingulate cortex whose role in conflict monitoring is well established. However, decision-making under conflict failed to activate the structures that track reward values per se. Thus, the presence of conflict in decision-making seemed to significantly alter the pattern of neural responses to simple rewards. In addition, this paradigm further clarifies the functional specialization of the cingulate cortex in processes of decision-making. | 18,804,540 |
Tissue engineering for bone defect healing: an update on a multi-component approach. | The need for an interdisciplinary approach in order to establish new therapeutic strategies for the therapy of bone defects has been acknowledged by the scientific community for many years. This awareness makes itself felt when looking at the multitude of approaches--ranging from cell-based to scaffold-based strategies and also including the use of osteogenic growth factors and genetic engineering--that are currently being combined to assess their potential to develop effective concepts for the treatment of extensive loss of osseous tissue. With a strong focus on the preclinical research in this field, the goal of this review is to give an update on the multi-component approaches that are currently being investigated in tissue engineering of bone. | 18,804,579 |
Improved microfluidic chip-based sequential-injection trapped-droplet array liquid-liquid extraction system for determination of aluminium. | An improved microfluidic chip-based sequential-injection trapped-droplet array liquid-liquid extraction system with chemiluminescence (CL) detection was developed in this work. Two recess arrays were fabricated on both sides of the extraction channel to produce droplet arrays of organic extractant. A chip integrated monolithic probe was fabricated at the inlet of the extraction channel on the glass chip instead of the capillary probe connected to the microchannel, in order to improve the system stability and reliability. A slotted-vial array system coupled with the monolithic probe was used to sequentially introduce sample and different solvents and reagents into the extraction channel for extraction and CL detection. The performance of the system was demonstrated in the determination of Al(3+) using Al(3+)-dihydroxyazobenzene (DHAB) and tributyl phosphate (TBP) extraction system. The operation conditions, including extraction time, concentration and flow rate of the CL reagents, were optimized. Within one analysis cycle of 12 min, an enrichment factor of 85 was obtained in the extraction stage with a sample consumption of 1.8 microL. The consumption of CL reagent, bis(2-carbopentyloxy-3,5,6-trichlorophenyl)oxalate (CPPO), was 120 nL/cycle. The detection limit of the system for Al(3+) was 1.6x10(-6)mol/L with a precision of 4.5% (R.S.D., n=6). | 18,804,631 |
Comparison of microwave-assisted digestion procedures for total trace element content determination in calcareous soils. | The aim of the study was to determine total trace (Cd, Co, Cr, Cu, Mn, Pb and Zn) and major (Al and Fe) element concentrations in calcareous soils using microwave-assisted digestion procedures. The literature showing lack of consensus regarding digestion procedures and unsatisfying recoveries for calcareous materials, four procedures using various acid combinations (HCl, HNO(3), H(2)O(2), HF) and volumes were tested using a certified reference material (CRM 141R) and natural calcareous soil samples. Digests were analysed by inductively coupled plasma-atomic emission spectrometry (ICP-AES). Repeatability (R.S.D. <5%) and recoveries (82-116%) showed that the procedures were precise and accurate for most elements. Five calcareous soil samples from a Champagne vineyard plot were, then, subjected to these procedures. In calcareous materials, the presence of HF resulted in Al being severely underestimated (recovery <5%) and Co overestimated (recovery >124%) due to complex formation or spectrochemical interferences, respectively. As digestion was not significantly influenced by the addition of H(2)O(2), the procedure corresponding to Aqua regia (HCl-HNO(3)) appeared as the best compromise and was selected for further multielemental environmental studies on calcareous materials, even if the absence of HF could lead to incomplete digestion of accessory silicate minerals. Results for a vineyard plot showed that the soils were contaminated (3.65 mg kg(-1) Cd, 67 mg kg(-1) Cr, 278 mg kg(-1) Cu, 143 mg kg(-1) Pb and 400 mg kg(-1) Zn) as a consequence of urban waste and copper-treatment applications. | 18,804,634 |
Renal conservation of folates role of folate transport proteins. | Folates play vital roles in one-carbon metabolism that produces the early substrates necessary for nucleotide synthesis and salvage. Folates are essential vitamins in that humans cannot synthesize them and are totally dependent on the diet to obtain them. As water-soluble vitamins, they would be easily filtered by the kidney and lost to the tubular fluid but for a highly efficient renal conservation mechanism. This renal "folate trap" is made up of alpha-folate receptors and reduced folate carriers. The locations of these transporters are such that they direct folate transport from the apical/luminal sides of kidney cells to the basolateral/plasma sides. In addition, other transporters such as organic anion transporters and multidrug resistance proteins are also found in kidney cells and play a role in renal elimination of folate analogues such as antifolate cancer chemotherapy drugs. This chapter discusses how these transporter activities manifest themselves in folate and antifolate pharmacokinetics. It also discusses effects of alcohol on renal reabsorption of folates. | 18,804,695 |
Structure and function of the reduced folate carrier a paradigm of a major facilitator superfamily mammalian nutrient transporter. | Folates are essential for life and folate deficiency contributes to a host of health problems including cardiovascular disease, fetal abnormalities, neurological disorders, and cancer. Antifolates, represented by methotrexate, continue to occupy a unique niche among the modern day pharmacopoeia for cancer along with other pathological conditions. This article focuses on the biology of the membrane transport system termed the "reduced folate carrier" or RFC with a particular emphasis on RFC structure and function. The ubiquitously expressed RFC is the major transporter for folates in mammalian cells and tissues. Loss of RFC expression or function portends potentially profound physiological or developmental consequences. For chemotherapeutic antifolates used for cancer, loss of RFC expression or synthesis of mutant RFC protein with impaired function results in antifolate resistance due to incomplete inhibition of cellular enzyme targets and low levels of substrate for polyglutamate synthesis. The functional properties for RFC were first documented nearly 40 years ago in murine leukemia cells. Since 1994, when RFC was first cloned, tremendous advances in the molecular biology of RFC and biochemical approaches for studying the structure of polytopic membrane proteins have led to an increasingly detailed picture of the molecular structure of the carrier, including its membrane topology, its N-glycosylation, identification of functionally and structurally important domains and amino acids, and helix packing associations. Although no crystal structure for RFC is yet available, biochemical and molecular studies, combined with homology modeling, based on homologous bacterial major facilitator superfamily transporters such as LacY, now permit the development of experimentally testable hypotheses designed to establish RFC structure and mechanism. | 18,804,694 |
Statins, low-density lipoprotein cholesterol, and risk of cancer. | We sought to assess whether statin-mediated reductions in low-density lipoprotein cholesterol (LDL-C) are associated with an increased risk of cancer. We recently reported an inverse association between on-treatment LDL-C levels and incident cancer in statin-treated patients enrolled in large randomized controlled trials, raising concern that LDL-C lowering by statins may increase cancer risk. However, meta-analyses suggest a neutral overall effect of statins on incident cancer. A systematic literature search identified 15 eligible randomized controlled trials of statins with >or=1,000 person-years of follow-up that provided on-treatment LDL-C levels and rates of incident cancers (19 statin and 14 control arms, 437,017 person-years cumulative follow-up, and 5,752 incident cancers). In the statin arms, meta-regression analysis demonstrated an inverse association between on-treatment LDL-C and incident cancer, with an excess of 2.2 (95% confidence interval: 0.7 to 3.6) cancers per 1,000 person-years for every 10 mg/dl decrement in on-treatment LDL-C (p=0.006). The corresponding difference among control arms was 1.2 (95% confidence interval: -0.2 to 2.7, p=0.09). Compared with the control arms, the statin regression line was significantly shifted leftward, such that similar rates of incident cancer were associated with lower on-treatment LDL-C (p<0.05). Meta-regression demonstrated that statins lack an effect on cancer risk across all levels of on-treatment LDL-C. There is an inverse association between on-treatment LDL-C and incident cancer. However, statins, despite producing marked reductions in LDL-C, are not associated with an increased risk of cancer. | 18,804,740 |
In search of the best method to predict acute coronary syndrome using only the electrocardiogram from the emergency department. | The aim of this study was to compare different methods to predict acute coronary syndrome (ACS) using only data from a single electrocardiogram (ECG) in the emergency department (ED). We compared the ACS prediction abilities of classical ECG criteria, human expert ECG interpretation, a logistic regression model and an artificial neural network ensemble (ANN). The ED ECG and discharge diagnoses were retrieved for 861 patient visits to the ED for chest pain. Cross-validation was used to estimate the generalization performance of the logistic regression and the ANN model. The logistic regression model had the overall best performance in predicting ACS with an area under the receiver operating characteristic curve of 0.88. The sensitivities of logistic regression, ANN, expert physicians, and classical ECG criteria were 95%, 95%, 82%, and 75%, respectively, and the specificities were 54%, 44%, 63%, and 69%. Our logistic regression model was the best overall method to predict ACS, followed by our ANN. Decision support models have the potential to improve even experienced ECG readers' ability to predict ACS in the ED. | 18,804,783 |
Disrupting the interaction between HOX and PBX causes necrotic and apoptotic cell death in the renal cancer lines CaKi-2 and 769-P. | The HOX genes are a family of homeodomain containing transcription factors that determine embryonic tissue identity and also have regulatory and oncogenic roles in adult cells. We quantified the expression of HOX genes in normal kidney tissue, primary tumors and derived cell lines, and examined their role in renal cancer cell survival. Quantitative polymerase chain reaction was used to evaluate HOX gene expression in cells and tissues. HOX gene function was disrupted using a peptide that blocks the interaction between HOX proteins and their PBX cofactor. Apoptosis was assessed by annexin/propidium iodide staining and direct measurement of caspase activity. Primary renal tumors and derived cell lines showed abnormal HOX gene expression. Furthermore, blocking HOX activity by targeting the interaction between HOX and its cofactor PBX caused apoptotic and necrotic cell death in the renal cancer cell lines CaKi-2 and 769-P, while sparing normal adult kidney cells. Our findings suggest that the HOX/PBX dimer is a potential therapeutic target in renal cancer. | 18,804,814 |
Contamination by polybrominated diphenyl ethers of sediments from the Lake Maggiore basin (Italy and Switzerland). | Polybrominated diphenyl ethers (PBDEs) are characterized by chemical properties and toxicological profiles similar to other POPs (persistent organic pollutants) included in the EU Priority Pollutant List (2455/01/CE). However, limited data have been available for these compounds thus far for Italian freshwater abiotic matrices. Lake Maggiore basin, a heavily industrialized and densely populated area, was selected for studying PBDE contamination in Italy. PBDEs and OCs (organochlorine compounds) in the basin were quantified by analysing both sediment cores collected in 2005 from the lake and grab samples from the main tributaries and the emissary. Fourteen PBDEs, from tri-BDE to hepta-BDE congeners and BDE209, were compared with some organochlorine POPs (PCBs and DDTs) characterizing Lake Maggiore basin contamination. Analyses of tri-to hepta-BDEs, PCBs and DDTs were undertaken by GC-MS/MS, while BDE-209 was analysed by GC/ECD. Results showed a dominant presence of BDE-209 (>95% of SigmaBDE) and limited amounts of BDE-47, BDE-99, BDE-100, BDE-153 and BDE-154. Lake core profiles highlighted a decreasing trend in PCB concentrations starting from the year 2000, while PBDEs showed greater concentrations after the beginning of the 1990s (up to 30 ng g(-1)d.w.). Among the tributaries, the Bardello and Boesio rivers were the most PBDE-contaminated (up to 290 ng g(-1)d.w.). | 18,804,840 |
Mechanical properties of experimental dental composites containing a combination of mesoporous and nonporous spherical silica as fillers. | Mesoporous fillers have been investigated for use in dental composites because of their potential for creating micromechanical filler/resin matrix interphase bonding. Such a micromechanical bonding could eliminate the need for the silane treatment of fillers for interfacial chemical bonding that is prone to hydrolysis in the oral environment. In the case of micromechanical bonding, dental polymer chains are threaded mechanically (like a "necklace") through nanosized channels in the fillers. A combination of mesoporous silica, which was synthesized using the non-surfactant templating method, and nonporous spherical silica (500nm) was used to prepare experimental dental composites. The porous silica used in this study contained interconnected pores and channels as opposed to porous fillers containing surface pores. The compressive strength, compressive modulus, flexural modulus, and flexural strength of these composites were evaluated. The results showed that composites containing a combination of mesoporous and nonporous fillers have better mechanical properties than the composites having either of these fillers alone. The results showed that a combination of mesoporous and nonporous materials can be used to prepare stronger dental materials that may resist hydrolysis and wear. | 18,804,855 |
Electrolytic deposition of lithium into calcium phosphate coatings. | Lithium ions stimulate the Wnt signaling pathway and the authors previously demonstrated that lithium enhances the proliferation of tissue cultured human mesenchymal stem cells. The aim of this study was to prepare and characterize a calcium phosphate/lithium coating by means of electrolytic deposition. It was hypothesized that the hybrid coatings would enhance the proliferation of MG63 osteoblast-like cells in vitro. Calcium phosphate coatings were electrolytically deposited in electrolytes containing 0, 0.5 and 5g/L lithium chloride, respectively. They were characterized by scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. The coating thickness, lithium content and release profile were also measured. The cell attachment and cell-doubling index of MG63 cells on these coatings were determined through a Cell Counting Kit-8. Lithium inhibited calcium phosphate deposition in a dose-dependent manner. Both crystallinity and thickness of the coatings were reduced with increasing lithium concentration in the electrolyte. The incorporation of lithium was 2.2 and 5.5microg/mg, respectively. The hybrid coatings demonstrated a burst lithium release within half an hour upon immersion into simulated physiological solution. Both attachment and early proliferation of MG63 cells on these hybrid coatings were enhanced. These results suggest that lithium can be effectively incorporated into calcium phosphate coatings. The incorporation of lithium interferes with calcium phosphate deposition; however, it enhances the biocompatibility of the coatings. | 18,804,857 |
Strontium modified biocements with zero order release kinetics. | Strontium-substituted beta-TCP with the general formula Ca((3-x))Sr(x)(PO(4))(2) (0<x<1) was synthesized by calcination of powder mixtures with the appropriate stoichiometry and reacted with acidic monocalcium phosphate monohydrate (MCPM) to form a cementitious matrix of secondary calcium phosphates. The use of Sr-substituted beta-TCP as a reactant not only induced strontium substitution in the setting products but surprisingly it also favoured the formation of monetite (CaHPO(4)) as setting product, whereas Sr-free cements set to brushite (CaHPO(4).2H(2)O). Release experiments under dynamic conditions for up to 15 days revealed the release of Sr(2+) ions at dose ranges of 12-30 ppm with zero order release kinetic. Cement cytocompatibility was investigated by culturing human osteoblast cell line hFOB1.19 on cement surfaces whereas Sr-containing cements were as good as Sr-free cements in providing a template for cell growth and function. | 18,804,862 |
Brominated flame retardants and organochlorines in the European environment using great tit eggs as a biomonitoring tool. | Large-scale studies are essential to assess the emission patterns and spatial distribution of organohalogenated pollutants (OHPs) in the environment. Bird eggs have several advantages compared to other environmental media which have previously been used to map the distribution of OHPs. In this study, large-scale geographical variation in the occurrence of OHPs, such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and organochlorine pesticides (OCPs), was investigated throughout Europe using eggs of a terrestrial residential passerine species, the great tit (Parus major). Great tit eggs from 22 sampling sites, involving urban, rural and remote areas, in 14 European countries were collected and analysed (5-8 eggs per sampling site). The environmentally most important congeners/compounds of the analysed pollutants were detectable in all sampling locations. For PCBs, PBDEs and OCPs, no clear geographical contamination pattern was found. Sum PCB levels ranged from 143 ng/g lipid weight (lw) to 3660 ng/g lw. As expected, PCB concentrations were significantly higher in the sampled urban compared to the remote locations. However, the urban locations did not show significantly higher concentrations compared to the rural locations. Sum PBDEs ranged from 4.0 ng/g lw to 136 ng/g lw. PBDEs were significantly higher in the urbanized sampling locations compared to the other locations. The significant, positive correlation between PCB and PBDE concentrations suggests similar spatial exposure and/or mechanisms of accumulation. Significantly higher levels of OCPs (sum OCPs ranging from 191 ng/g lw to 7830 ng/g lw) were detected in rural sampling locations. Contamination profiles of PCBs, PBDEs and OCPs differed also among the sampling locations, which may be due to local usage and contamination sources. The higher variance among sampling locations for the PCBs and OCPs, suggests that local contamination sources are more important for the PCBs and OCPs compared to the PBDEs. To our knowledge, this is the first study in which bird eggs were used as a monitoring tool for OHPs on such a large geographical scale. | 18,804,864 |
Excision repair cross-complementation group 1 (ERCC1) in platinum-based treatment of non-small cell lung cancer with special emphasis on carboplatin: a review of current literature. | Patients diagnosed with advanced non-small cell lung cancer have a dismal prognosis and are often relative resistant to chemotherapy. A need for markers has emerged based on tumour biology in order to predict which patients will respond to treatment. Excision repair cross-complementation group 1 (ERCC1) has shown potential as a predictive marker in patients with NSCLC treated with cisplatin-based chemotherapy. Carboplatin has gained widespread use in the treatment of advanced NSCLC and its mechanisms of action are likely similar to that of cisplatin. A literature review on ERCC1 was conducted as predictor in NSCLC patients receiving platinum-based treatment with emphasis on carboplatin. English language publications from January 1996 to February 2008 were eligible and data on methodology and outcome were recorded. Eight preclinical articles, 25 clinical articles and 1 clinical abstract were identified. Laboratory methods were mainly RT-PCR (reverse transcriptase polymerase chain reaction) or immunohistochemistry (IHC) for expression of ERCC1. Preclinical studies pointed towards similar mechanisms of chemotherapy-resistance among platinum compounds. A statistically significant benefit in outcome was found among NSCLC patients, who received adjuvant treatment, and had low-ERCC1 expression. Advanced NSCLC patients treated with cisplatin showed improved response rates (RR) but no difference in other endpoints. Studies on advanced NSCLC patients treated with carboplatin were sparse, heterogeneous and small thus reporting varying results. The literature on advanced NSCLC patients treated with carboplatin or cisplatin are dominated by small and heterogeneous patient populations and yielded different results. No firm conclusions can be drawn on carboplatin based on the current literature. Research on the development of a reliable methodology is warranted followed by validation in large, prospective, randomized trials as ERCC1 may possibly play an important role as tumour marker in tailored chemotherapy for NSCLC. | 18,804,893 |
Reverse flow flap use in upper extremity burn contractures. | Upper extremity contractures still happen and constitute one of the most trying challenges in burn patients. This series comprised of 4 radial forearm flaps, 14 dorsoulnar artery flaps, and 4 medial arm flaps, all of which were used in a reverse pattern for upper extremity postburn contractures. The reverse flow radial forearm flap (RRFF) was chosen for reconstruction of extensive palmar contractures after burn. The reverse flow dorsoulnar flap (RDUF) was used particularly for reconstruction of the hypothenar aspect of the hand which requires moderate size tissue transfer. The reverse medial arm flap (RMAF) was used for elbow contractures after burn. In the first RMAF, venous congestion occurred and was finaly resolved with minimal flap loss, which was managed with STSG later. In the following 3 cases the flap was supercharged with anastomosis of the brachial vein into the antebrachial vein. Both RRFF and RDUF may provide a smooth and efficient solution. However, RMAF has a significant venous problem, which may result in flap loss, therefore, this flap should not be considered as a first option in the elbow area. | 18,804,917 |
Immediate endovascular repair for acute traumatic injuries of the thoracic aorta: a multicenter analysis of 28 cases. | Endovascular repair of injured thoracic aorta offers a new minimal invasive therapeutic option that could be beneficial in the urgent management of polytrauma patients. The aim of this study was to assess our multicenter experience of immediate endovascular repair for acute traumatic injuries of the thoracic aorta. Between April 2002 and October 2007, all patients treated for an acute traumatic injury of the thoracic aorta, in a less than 12-hour delay, by endovascular repair, were reviewed retrospectively in three Parisian trauma centers. Collected data included age, sex, associated comorbidities, and traumatic lesions to determine the Traumatic Injury Severity Score (TRISS), the type of aortic lesion assessed by computed tomography (CT)-scan and transesophageal ultrasonography, technical aspects of endovascular repair, length of hospital stay, and postoperative mortality. Patients were regularly followed by clinical examination, chest radiographs, and thoracic CT-scan. Twenty-eight patients (20 males, mean age 45 +/- 18.8 years) were treated in a median delay of 5 hours (range 2 to 10 hours) after initial trauma. They all experienced severe traumatic injuries with a mean predictive mortality of 55.6% +/- 33.1% according to TRISS. Aortic lesions were associated with aortic parietal hematoma (71%), hemomediastinum (86%), and hemothorax (68%). All endovascular procedures were technically successful through femoral (n = 24) or iliac access (n = 4), in a mean operating time of 94 +/- 35.8 minutes. Proximal sealing of the endografts required the coverage of the origin of the left subclavian artery in 13 cases and of the left common carotid in one case. The median of hospital stay was 27 days (range 9 to 127 days), with an overall hospital mortality of 17.9% (n = 5). All deaths were unrelated to the aortic rupture or the stent placement, and no intervention-related morbidity or mortality was recorded during a median follow-up of 24 months (range 5 to 73 months). Endovascular stent grafting allows an immediate efficient repair for acute traumatic injuries of the thoracic aorta. This early management is, however, associated with a high in-hospital mortality, related to the severe concomitant injuries of such unselected multitrauma patients. | 18,804,937 |
Concurrent splenic peliosis and vascular Ehlers-Danlos syndrome. | This case report describes concurrent splenic peliosis and vascular Ehlers-Danlos syndrome (EDS) in a 59-year-old male patient. After splenic rupture due to peliosis, the complicated postoperative period hinted at the possibility of vascular EDS. This diagnosis was confirmed by genetic testing, which revealed a novel point mutation in the COL3A1 gene, c.2545G-->C, leading to a codon encoding for arginine instead of glycine (p.Gly849Arg). In addition, a histological diagnosis of splenic peliosis could be established. | 18,804,950 |
Leiomyoma of the greater saphenous vein: a case report and review of the literature. | Greater saphenous vein tumors are exceedingly rare, whether benign or malignant. Leiomyoma is one of the benign vascular tumors that can present as a localized mass; however, the diagnosis cannot be made clinically. Multiple radiologic imagings are usually required, as well as histological examination, to make a definitive diagnosis. This tumor is treated by wide excision along with a normal portion of the vessel, and the recurrence rate is very low. We describe the case of a patient with great saphenous vein leiomyoma. | 18,804,951 |
Changes in glucose metabolism due to aging and gender-related differences in the healthy human brain. | Using [(18)F]fluoro-deoxy-glucose-PET, we studied relative metabolic changes due to age- and gender-related differences in the brain of 126 healthy subjects from their twenties to seventies. We used a data-extraction technique, the three-dimensional stereotactic surface projections (3D-SSP) method, to measure metabolic changes with fewer effects of regional anatomic variances. Simple regression analysis revealed significant age-related increases in relative metabolic values in the parahippocampal and amygdala regions in both sexes in their twenties to forties, and significant age-related decreases in both sexes in their fifties to seventies. Relative values in the frontal lobe showed significant age-related decreases in both sexes in their twenties to forties, but these effects were not seen in subjects in their fifties to seventies. Significant gender differences in correlation coefficients of relative values with age were shown in the parahippocampal, primary sensorimotor, temporal, thalamus and vermis regions in subjects in their 20s to 40s, but disappeared in subjects in their twenties to forties, but were not apparent in subjects in their fifties to seventies except in the vermis. Males in their twenties to sixties and females in their fifties showed significant laterality in relative values in the temporal lobes. Our study demonstrated age- and gender-related differences in glucose metabolism in healthy subjects. | 18,804,967 |
Association of genetic profiles to Crohn's disease by linear combinations of single nucleotide polymorphisms. | A large number of single nucleotide polymorphisms (SNPs) are supposed to be involved in onset, differentiation and development of complex diseases. Univariate analysis is limited in studying complex traits since does not take into account gene-gene interaction, and the correlation of multiple SNPs with a specific phenotype. Moreover it might underestimate gene variants with weaker genetic contribution. Therefore more sophisticated techniques should be adopted when investigating the role of a panel of genetic markers in disease predisposition. In this paper we describe a general method to simultaneously investigate the association between SNPs profile and Crohn's disease (CD), by evaluating the susceptibility or protective role of single or groups of markers. As an association measure we adopted a weighted linear combination of SNPs in which suitable weighting vectors belonged to predefined and over-complete vocabularies of vectors (frames), or were determined by the data. The proposed method found a weighted linear combination of SNPs statistically associated to CD (p=3.81 x 10(-10)) describing the role of the markers in the pathology. In particular, MCP1-A2518G gave the major contribution as protective locus, similarly to TNF-alpha-C857T, DLG5 rs124869, PTPN22 C1858T variants. The NF kappaB -94ATTG variants was found to be irrelevant for CD. For the remaining markers, a susceptibility role was attributed also confirming that markers on CARD15 gene, in particular G908R and L1007fsinsC, are involved with CD to the same extent as FcGIIIA G559T and TNF-alpha-G308A. Moreover, an odds ratio of 3.99(p<1.0 x 10(-4)) was assigned to this combination which is greater than the best odds ratio found in the single SNP analysis. Our methodology allowed to statistically measure the association of a panel of SNPs with a specific phenotype. Therefore this approach could be suitable for a population screening program with simultaneous evaluation of a large set of gene polymorphism. | 18,804,983 |
Altered monocyte CD44 expression in peripheral arterial disease is corrected by fish oil supplementation. | CD44 and its splice variants can be expressed on all leukocytes, conferring adhesive properties and enhancing cellular recruitment to the endothelium during inflammation. CD44 expression is increased in inflammatory conditions such as rheumatoid arthritis and CD44 variant 3 (CD44v3) expression may be associated with inflammation. We have examined CD44 and CD44v3 expression on peripheral blood monocytes from patients with peripheral arterial disease (PAD) and healthy controls. We have also examined the effect of fish oil supplementation on these markers. CD44 and CD44v3 were assessed at baseline and following dietary supplementation with fish oil for 12 weeks in both PAD and control groups. Monocytes from PAD patients had higher CD44 expression than those from controls (median intensity fluorescence (MIF): 480+/-278 vs 336+/-251 (mean+/-SD); p<0.001). Following 12 weeks' dietary supplementation with fish oil, CD44 expression was reduced in PAD patients (MIF: 480+/-278 vs 427+/-262; p=0.05) but not in controls (336+/-251 vs 355+/-280; ns). Monocyte CD44v3 expression was lower in cultured monocytes from PAD patients compared to those from controls (0.15+/-0.15 vs 0.22+/-0.14 OD units; p<0.02). This was increased in the PAD group following fish oil supplementation (0.15+/-0.14 to 0.27+/-0.23 OD units; p<0.001). Monocyte CD44 and CD44v3 expression are altered in arterial disease but are returned towards levels seen in control subjects by dietary fish oil supplementation. | 18,804,988 |
A new amperometric nanostructured sensor for the analytical determination of hydrogen peroxide. | A new amperometric, nanostructured sensor for the analytical determination of hydrogen peroxide is proposed. This sensor was constructed by immobilizing silver nanoparticles in a polyvinyl alcohol (PVA) film on a platinum electrode, which was performed by direct drop-casting silver nanoparticles that were capped in a PVA colloidal suspension. UV-vis spectroscopy, X-ray diffraction and transmission electron microscopy were used to give a complete characterization of the nanostructured film. Cyclic voltammetry experiments yielded evidence that silver nanoparticles facilitate hydrogen peroxide reduction, showing excellent catalytic activity. Moreover, the cronoamperometric response of modified sensors was dependent on nanoparticle lifetime. Experiments were performed, using freshly prepared solutions, after 4 and 8 days. Results concerning the quantitative analysis of hydrogen peroxide, in terms of detection limit, linear range, sensitivity and standard deviation (STD), are discussed for each tested sensor type. Utilization of two different linear ranges (40 microM to 6mM and 1.25 microM to 1.0mM) enabled the assessment of concentration intervals having up to three orders of magnitude. Moreover, the electrode made using a 4-day-old solution showed the maximal sensitivity of 128 nA microM(-1)(4090 nA microM(-1)cm(-2)), yielding a limit of detection of 1 microuM and STD of 2.5 microAmM(-1). All of these analytical parameters make the constructed sensors suitable for peroxide determination in aqueous solution. | 18,804,993 |
Do earthworms affect dynamics of functional response and genetic structure of microbial community in a lab-scale composting system? | Two laboratory-scale systems were set up (i) composting (without earthworms) and (ii) vermicomposting (with earthworms) and were monitored for 60 days after pre-composting. The physico-chemical parameters (pH, C/N, organic matter, NH(4)(+)-N and ash content) showed similar evolution in both systems except a higher NH(4)(+)-N in the initial vermicomposts. However, principle component analysis (PCA) of enzymatic activities and community level physiological profiles revealed differences in the functional response of microbial communities in compost and vermicompost during maturation. Dehydrogenase activity and bacterial counts indicated a steady decrease in biological activity and population during composting, whereas vermicomposting exhibited higher activity on day 30 and a reduction in bacterial counts on day 10. PCA of denatured gradient gel electrophoresis (DGGE) profiles showed divergent dynamics of bacterial communities in two processes. These results indicated differences in the functional response and genetic structure of microbial community in composts and vermicomposts despite similar changes in their physico-chemical parameters. | 18,805,002 |
Fluorescent polycyclic ligands for nitric oxide synthase (NOS) inhibition. | In recent years polycyclic compounds have been shown to exhibit pharmacological profiles of importance in the symptomatic and proposed curative treatment of neurodegenerative diseases (e.g., Parkinson's and Alzheimer's disease). These structures also show modification and improvement of the pharmacokinetic and pharmacodynamic properties of drugs in current use. Nitric oxide (NO) is a molecular messenger involved in a number of physiological processes in mammals. It is synthesised by nitric oxide synthase (NOS) from L-arginine and its overproduction could lead to a number of neurological disorders. The aim of this study was to synthesise a series of novel indazole, indole and other fluorescent derivatives conjugated to polycyclic structures for evaluation in NOS assays. NOS is a target system where fluorescent techniques and fluorescently labelled NOS inhibitors can be used for detecting the biophysical properties of enzyme-ligand interactions and thus facilitate development of novel inhibitors of neurodegeneration. This could lead to a greater insight into the neuroprotective mechanism and a possible cure/treatment for neurodegenerative diseases. A series of compounds incorporating polycyclic structures such as 3-hydroxy-4-aza-8-oxoheptacyclo[9.4.1.0.(2,10)0.(3,14)0.(4,9)0.(9,13)0(12,15)]tetradecane and amantadine as well as suitable fluorescent moieties were selected for synthesis. In the biological evaluation the oxyhaemoglobin (oxyHb) assay was employed to determine the activity of the novel compounds at an enzymatic level of NOS. IC(50) values of the novel fluorescent compounds were compared to that of aminoguanidine (AG) and 7-nitroindazole (7-NI), two known NOS inhibitors, and showed moderate to high affinity (IC(50) values ranging from 7.73 microM to 0.291 microM) for the NOS enzyme. | 18,805,011 |
Biomechanical analysis of axial distraction mobilization of the glenohumeral joint--a cadaver study. | The axial distraction mobilization techniques are frequently employed for treating patients with joint hypomobility. However, there is a lack of basic biomechanical studies and description of this procedure. The purpose of this study was to analyze humeral head displacement while performing an axial distraction mobilization of the glenohumeral joint. Twelve experienced orthopedic physical therapists participated. Distraction mobilization techniques were performed in three different positions of glenohumeral abduction on a fresh cadaveric specimen. Outcome measures were displacements of the humeral head center during distraction mobilization. Result indicated that displacement of the humeral head was largest in the resting position (27.38 mm) followed by the neutral (22.01 mm) and the end range position (9.34 mm). There were significant differences for both the displacement of the humeral head (p<0.002) and the distraction forces used (p<0.015) among the three joint positions. Greater gain in mobility was obtained in distraction at the end range position. In conclusion, during distraction mobilization, the force applied by the therapist and displacement of the humeral head depends on the joint position tested. Our results also provide rationales for choosing end range distraction mobilization for improving joint mobility. | 18,805,038 |
Expression of growth differentiation factor 15 is positively correlated with histopathological malignant grade and in vitro cell proliferation in oral squamous cell carcinoma. | Previously, we established an in vitro cellular carcinogenesis model of oral squamous cell carcinoma (OSCC) and expression microarray analysis showed that the gene encoding growth differentiation factor 15 (GDF15) was significantly upregulated in this model. In this study, we confirmed that expression of GDF15 was increased both at mRNA and protein levels in a panel of OSCC lines and clinical samples from primary OSCC patients. We also observed that expression of GDF15 was positively correlated with the malignancy of the disease: a higher level of GDF15 expression indicates a higher malignant grade of OSCC. Treatment of OSCC cell line (Tca3118) with siRNA against GDF15 significantly inhibited cellular proliferation and colony formation. Based on these observations, we conclude that GDF15 is a positive gene of OSCC development and progression and GDF15 can be used as an additional marker for histopathologic evaluation of OSCC differentiation. | 18,805,046 |
A SEC-HPLC-ICP MS hyphenated technique for identification of sulfur-containing arsenic metabolites in biological samples. | The present study describes the synthesis and characterization of thioarsenicals using electro-spray ionization-MS and time of flight-MS. Separation of thioarsenicals was found to be better by size-exclusion column compared to anion exchange column coupled with HPLC-inductively coupled argon plasma mass spectrometer (ICP MS). Although four thioarsenicals were confirmed as dimethylthioarsinous acid (m/z=138), methylmonothioarsonous acid (m/z=122), dimethyldithioarsinic acid (m/z=170) and methyltrithioarsonic acid (m/z=188), it is noted that HPLC-ICP MS alone were not sufficient for their identification. Also, none of them was stable with time. This is the first report detailing the synthesis and identification of methyltrithioarsonic acid. Both dimethyldithioarsinic acid and dimethylthioarsinous acid were detected in human nail samples while dimethyldithioarsinic acid was found in urine samples. So, the above technique could be applicable to the identification of sulfur-containing biomolecules in the biological samples. | 18,805,071 |
Lasker-Koshland Award to 21st century microbe master. | The 2008 Lasker-Koshland Award will be presented to Stanley Falkow, one of the legendary figures in the history of microbiology research. Falkow's many contributions remade the way we think about bacterial pathogens, antibiotic resistance, and infectious disease. | 18,805,081 |
Regulation of neurogenesis by interkinetic nuclear migration through an apical-basal notch gradient. | The different cell types in the central nervous system develop from a common pool of progenitor cells. The nuclei of progenitors move between the apical and basal surfaces of the neuroepithelium in phase with their cell cycle, a process termed interkinetic nuclear migration (INM). In the retina of zebrafish mikre oko (mok) mutants, in which the motor protein Dynactin-1 is disrupted, interkinetic nuclei migrate more rapidly and deeply to the basal side and more slowly to the apical side. We found that Notch signaling is predominantly activated on the apical side in both mutants and wild-type. Mutant progenitors are, thus, less exposed to Notch and exit the cell cycle prematurely. This leads to an overproduction of early-born retinal ganglion cells (RGCs) at the expense of later-born interneurons and glia. Our data indicate that the function of INM is to balance the exposure of progenitor nuclei to neurogenic versus proliferative signals. | 18,805,097 |
Comparative outcome of bidirectional Glenn shunt in patients with pulmonary vascular resistance > or = 3.5 woods units versus < 3.5 woods units. | Moderate to severe pulmonary hypertension is considered to be an absolute contraindication to the performance of bidirectional Glenn (BDG) shunting. However, BDG shunting has been performed in young children with pulmonary hypertension associated with unrestricted pulmonary blood flow. In this study, the medical records of patients who underwent BDG starting from October 2000 to March 2004 were reviewed. Patients were divided into 2 groups on the basis of indexed pulmonary vascular resistance (PVRI) measured in room air: a high-risk group (n = 12) with PVRI > or = 3.5 Woods units (WU)/m(2) and a low-risk group (n = 28) with PVRI <3.5 WU/m(2) in room air. The 2 groups were comparable with respect to age, weight, ventricular morphology, pulmonary arterial anatomy, and atrioventricular valve function. Mean pulmonary arterial pressure and PVRI were significantly higher in the high-risk group compared with the low-risk group (39.2 +/- 20.7 vs 15.1 +/- 6.25 mm Hg, p <0.002, and 6.0 +/- 2.5 vs 1.6 +/- 0.82 WU/m(2), p <0.0005, respectively). The ratio of pulmonary flow to systemic flow was 1.45 +/- 0.76 in the high-risk group and 1.24 +/- 1.2 in the low-risk group. In the high-risk group, mean PVRI decreased to 2.0 +/- 1.0 WU/m(2) on 100% oxygen (p <0.0005). A contraindication to Glenn shunting was PVRI >3.5 WU/m(2) on 100% oxygen. Hospital mortality was 17% (2 of 12) in the high-risk group and 4% (1 of 28) in the low-risk group. Of 10 survivors in the high-risk group, 1 had undergone a Kawashima procedure, 7 had undergone Fontan procedures (with 1 death), and 2 were awaiting the completion of Fontan procedures as of this writing. In conclusion, these preliminary data suggest that in young children with increased pulmonary flow, BDG shunting can be safely performed, despite the apparent elevation of pulmonary arterial pressure to inoperable levels, provided PVRI decreases to < or = 3.5 WU/m(2) on 100% oxygen. | 18,805,120 |
Defining optimal research study design for cardiovascular imaging using computed tomography angiography as a model. | Patients, physicians, and payers are facing a significant increase in cardiovascular (CV) imaging use, resulting in skyrocketing societal costs, without clear improvement in patient outcomes. The need for studies evaluating the effects of CV imaging that assess appropriate end points is critical to address continued concerns over the lack of well-designed clinical studies. Thus, the investigators propose a framework, using computed tomographic angiography as a model, that should be considered in the optimal design of future imaging research and would potentially provide payers with data to make appropriate reimbursement decisions. The inclusion of risk stratification, randomization, multiple-site participation, and multigeography site enrollment are key elements in the construction of such studies. Meaningful end points with regard to operating characteristics, downstream testing, CV event rates, outcomes, and costs are essential to appropriately evaluate any new imaging technology. Only once better level evidence is formed to support CV imaging can the central issues of quality and appropriateness of CV imaging truly be evaluated. If the CV community does not embrace this type of scientific evaluation of CV imaging modalities and fails to adequately identify the value in these techniques, it may ultimately lose the ability to use them to provide optimal care to its patients. | 18,805,127 |
Endobronchial ultrasound-guided fine-needle aspiration of mediastinal lymph nodes: a single institution's early learning curve. | The gold standard for mediastinal lymph node evaluation is mediastinoscopy, which is invasive and allows access to only a limited number of mediastinal lymph node (MLN) stations (1, 2, 3, 4, and 7). Endobronchial ultrasound-guided fine-needle aspiration (EBUS-FNA) is emerging as a useful, less invasive technique that offers access to a wider range of MLN stations (2, 3, 4, 7, 10, and 11). We report our initial experience with this procedure. Using our prospectively maintained database, we performed a single-institution retrospective chart review. Our study group consisted of all patients at the University of Minnesota who underwent EBUS-FNA for evaluation of mediastinal lymphadenopathy or for thoracic malignancy staging from September 1, 2006, through December 15, 2007. To assess our learning curve, we plotted the cumulative sensitivity (%) and accuracy (%) of our EBUS-FNA results as a function of the number of procedures we performed. During the study period, 100 patients underwent EBUS, 92 with FNA. Of these, 56 patients (34 women, 22 men; mean age, 60.4 +/- 13.7 years) met our inclusion criteria. We found no complications. After our first 10 procedures, the sensitivity of our EBUS-FNA results was 96.2%; accuracy was 97.8% (rates comparable with other large series in the literature). We conclude that the learning curve for EBUS-FNA for thoracic surgeons is about 10 procedures. | 18,805,141 |
Clinical application of direct bronchial ultrasound to visualize and determine endobronchial tumor margins for surgical resection. | We describe the first experience of direct bronchial (epi-bronchial) ultrasound to visualize and determine the endobronchial tumor margins for surgical resection. An ultrasound probe was applied onto the membranous portion of the right main bronchus directly over a pedunculated tumor. The tumor was visualized due to the water content, with a total loss of signal (air-tumor interface) at the tumor edge. A sterile marker was used to outline the air-tumor interface. Traditionally, surgical technique involves palpation of the tumor with an incision to inspect the endobronchial lumen determining the position of the pedicle, thus estimating the amount of airway to resect. Using direct bronchial ultrasound, the right main palpated margin was 0.5-cm proximal to the ultrasound margin, which correctly identified the tumor margin. The upper lobe palpated margin was 1 cm proximal to the ultrasound margin, which correctly identified the tumor margin. In the intermediate bronchus, the palpated and ultrasound margin were the same and correct. By using the air-tumor interface, epi-bronchial ultrasound scanning can accurately demarcate the base of endobronchial tumors for surgical resection and reconstruction. | 18,805,189 |
Veno-venous extracorporeal membrane oxygenation in surgery for bronchial repair. | Single-lung ventilation using a double-lumen endobronchial tube is often performed for surgical procedures involving the thorax. Tracheobronchial rupture during use of an endobronchial tube is an uncommon and serious complication. We present the case of a patient undergoing a right pneumonectomy who experienced a bronchial rupture due to a double-lumen endobronchial tube. Institution of veno-venous extracorporeal membrane oxygenation allowed removal of the endobronchial tube, and the repair was successfully performed. We hope that this information can provide further insight into the management of such a complication. | 18,805,192 |
Early aortic bioprosthetic valve deterioration in an octogenarian. | We experienced extremely early aortic bioprosthetic valve deterioration with leaflet calcification and stiffening 2 1/2 years after aortic valve replacement in a female octogenarian. We could not identify the possible reason for this devastating complication; however, daily calcium supplement consumption may play a role of acceleration of calcium deposition in the leaflets of implanted bioprosthetic heart valves. | 18,805,202 |
Cone beam tomographic imaging anatomy of the maxillofacial region. | Multiplanar imaging is a fairly new concept in diagnostic imaging available with a number of contemporary imaging modalities such as CT, MR imaging, diagnostic ultrasound, and others. This modality allows reconstruction of images in different planes (flat or curved) from a volume of data that was acquired previously. This concept makes the diagnostic process more interactive, and proper use may increase diagnostic potential. At the same time, the complexity of the anatomical structures on the maxillofacial region may make it harder for these images to be interpreted. This article reviews the anatomy of maxillofacial structures in planar imaging, and more specifically cone-beam CT images. | 18,805,226 |
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