title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Evaluation of cis-regulatory function in zebrafish. | As increasing numbers of vertebrate genomes are sequenced, comparative genomics offers tremendous promise to unveil mechanisms of transcriptional gene regulation on a large scale. However, the challenge of analysing immense amounts of sequence data and relating primary sequence to function is daunting. Several teleost species occupy crucial niches in the world of comparative genomics, as experimental model organisms of wide utility and living roadmaps of molecular evolution. Extant species have evolved after a teleost-specific genome duplication, and offer the opportunity to examine the evolution of thousands of duplicate gene pairs. Transgenesis in zebrafish is being increasingly employed to functionally examine non-coding sequences, from fish and mammals. Here, we discuss current approaches to the study of gene regulation in teleosts, and the promise of future research. | 18,820,318 |
Sarcina-like bacteria associated with bloat in young lambs and calves. | Sarcina species are fastidious Gram-positive anaerobic bacteria that occur in cubical packets of eight or more cells. In 2006 to 2007, they were associated with cases of acute abomasal bloat in young lambs and calves. Two incidents were in lambs aged three to six weeks that were found dead, with one or two cases in each of a group of 15 and 100 lambs. Three incidents were recorded in small groups of calves up to 10 days of age, two cases in each incident, with the calves found dead or dying after a short illness characterised by bloat. Their gross lesions included emphysema and oedema of the abomasal wall, mucosal hyperaemia and haemorrhage, and rupture of the abomasum. Histological lesions included abomasitis with congestion, haemorrhage, emphysema and oedema. Bacteria characteristic of Sarcina species were observed in sections associated with the superficial mucosa of these cases, but the bacteria were not detected in cultures. | 18,820,327 |
Using music in leisure to enhance social relationships with patients with complex disabilities. | Acquired and complex disabilities stemming from severe brain damage and neurological illness usually affect communication, cognitive, physical or sensory abilities in any combination. Improved understanding of the care needs of people with complex disabilities has addressed many functional aspects of care. However, relatives and carers can be left at a loss knowing how to provide or share in meaningful activities with someone who can no longer communicate or respond to their environment. As a result, the individual with complex needs can become increasingly isolated from their previous support network. Based on theoretical foundations for music as instinctive in human beings, this paper offers practical recommendations for the creative use of music for people with complex physical and sensory needs which prevent active participation in previous leisure pursuits. Recommendations are made for relatives and carers to manage the environment of an individual who has limited capacity to control their environment or make choices about leisure activities. Particular emphasis is given to activities which can be shared between a facilitator and the patient, thereby enhancing social relationships. | 18,820,394 |
Tailoring leisure to suit a wider audience through creative event planning with a multi-sensory approach. | Caregiving for long-term conditions is increasingly focused on holistic "person centred" care [9,34], with leisure and recreation providing an important and essential part of maintaining quality of life. This article documents examples of large leisure events and creative projects. These were adapted for, and considered to be suitable and supportive of, the needs of adults with complex and profound disability as a result of neurological damage or disease. The ways in which events have been tailored by the Recreation and Leisure Service, incorporating sensory elements with the view to increased accessibility and enjoyment for participants, are highlighted in this article. The ultimate challenge faced was programming events to suit more than 170 people aged over 18 who each have particular preferences, varied interests and abilities including the most profound physical and cognitive impairments. These developments and changes in format have encouraged essential input from participants themselves and their families and carers, whilst involving the wider community; volunteers, external charitable groups and professional organisations. | 18,820,400 |
Axon regeneration after spinal cord injury: insight from genetically modified mouse models. | The use of genetically modified mice to study axon regeneration after spinal cord injury has served as a useful in vivo model for both loss-of-function and gain-of-function analysis of candidate proteins. This review discusses the impact of genetically modified mice on axon regeneration after spinal cord injury in the context of axon growth inhibition by myelin, the glial scar, and chemorepellent molecules. We also discuss the use of mice which transgenically express fluorescent proteins in specific axons for increasing our understanding of how spinal cord axons behave after injury. | 18,820,409 |
History of ergonomics and occupational therapy. | Ergonomics is commonly known as "the scientific study of human work" [14, p. 3] and "the application of scientific information concerning human beings to the design of objects, systems, and environments" (p. 4). The American Occupational Therapy Association defines occupational therapy as "skilled treatment that helps individuals achieve independence in all facets of their lives. It gives people the 'skills for the job of living' necessary for independent and satisfying lives [1]." Both professions share common backgrounds. Occupational therapy has been involved in health care and ergonomics is looking for its place in the health care field. | 18,820,415 |
New advances in stem cell biology: A perspective from gametogenesis. | Regeneration of adult tissues relies on a small population of adult stem cells located in a specialized microenvironment. The adult stem cells divide continuously to produce new stem cells, as well as differentiated daughter cells to replenish lost cells due to damage or aging. The molecular mechanisms controlling their ability to divide, self-renew and differentiate remain largely undiscovered. The Drosophila reproductive systems have proven to be excellent models to understand the basic mechanisms regulating stem cell function. This report summarizes some of the recent advances in this field that were presented at the 49(th) Drosophila Research Conference held in San Diego in April 2008. | 18,820,451 |
The design and implementation of a multidisciplinary global health residency track at the Mount Sinai School of Medicine. | The Mount Sinai Global Health Center established a new multidisciplinary Global Health Residency Track (GHRT) in 2006. The goal of the GHRT is to provide participants with a foundation in global health issues and population-based health care, a chance to develop basic research and public health skills in the field, and guidance for career development. The authors describe how the GHRT was created, present its structure, and discuss their experience implementing this new program. Other selected global health residency training programs are also reviewed. The Mount Sinai GHRT is a two-year program that comprises a didactic curriculum, with participants required to take selected classes in the Master of Public Health Program of the Mount Sinai School of Medicine of New York University, and "field experience," which consists of a public health project that is implemented during a two-month elective period during the second year. Core competencies include (1) epidemiology and research skills, (2) health disparities, human rights, and cultural competency, (3) needs assessment and project development, (4) tropical medicine and infectious disease, and (5) reproductive, maternal, and child health. Nine residents were selected from four Mount Sinai residency programs to participate in the GHRT in its first year, and, during the winter of 2007, senior residents conducted public health projects in the Dominican Republic, India, Kenya, and East Harlem. All components of the track performed well in evaluations. An outcomes survey is ongoing to track career choices among graduates and to identify barriers to continuing involvement in global health. | 18,820,521 |
Antivirals and influenza: frequency of resistance. | Antivirals are effective in prophylaxis and therapy for influenza and are likely to be active against a new pandemic variant. They can be divided into the M2 inhibitors, adamantane and rimantadine, and the neuraminidase inhibitors (NAIs), zanamivir and oseltamivir. The former are limited in activity to type A viruses, whereas the latter are also active against type B viruses. Both classes of drugs appear similarly efficacious in prophylaxis at approximately 70-90%. However, use of M2 inhibitors (adamantanes) in therapy is limited by side effects, more common with amantadine, and also by production of antiviral resistance and lack of demonstrated prevention of complications. The NAIs prevent both types of seasonal influenza, shorten duration of illness, and reduce complications. As such, their use for seasonal influenza treatment has been increasing. They are active against A(H5N1) but oseltamivir has been most extensively stockpiled because the infection in humans may be disseminated. Resistance does emerge, but not at the same frequency as with the M2 inhibitors. Resistant viruses also appear less fit and thus less able to spread. However, as use increases, resistance needs to be carefully monitored. | 18,820,569 |
Mitochondrial tRNAThr G15927A mutation may modulate the phenotypic manifestation of ototoxic 12S rRNA A1555G mutation in four Chinese families. | To investigate the role of mitochondrial modifiers in the development of deafness associated with 12S rRNA A1555G mutation. Four Chinese families with nonsyndromic and aminoglycoside-induced deafness were studied by clinical and genetic evaluation, molecular and biochemical analyses of mitochondrial DNA (mtDNA). These families exhibited high penetrance and expressivity of hearing impairment. Penetrances of hearing loss in WZD31, WZD32, WZD33, and WZD34 pedigrees ranged from 50 to 67% and from 39 to 50%, respectively, when aminoglycoside-induced hearing loss was included or excluded. Matrilineal relatives in these families developed hearing loss at the average of 14, 13, 16, and 15 years of age, respectively, when aminoglycoside-induced deafness was excluded. Mutational analysis of entire mtDNA in these families showed the homoplasmic A1555G mutation and distinct sets of variants belonging to haplogroup B5b1. Of these, the tRNA G15927A mutation locates at the fourth base in the anticodon stem (conventional position 42) of tRNA. A guanine (G42) at this position of tRNA is highly conserved from bacteria to human mitochondria. The lower levels and altered electrophoretic mobility of tRNA were observed in cells carrying A1555G and G15927A mutations or only G15927A mutation but not cells carrying only A1555G mutation. The abolished base pairing (28C-42G) of this tRNA by the G15927A mutation caused a failure in tRNA metabolism, worsening the mitochondrial dysfunctions altered by the A1555G mutation. The G15927A mutation has a potential modifier role in increasing the penetrance and expressivity of the deafness-associated 12S rRNA A1555G mutation in those Chinese pedigrees. | 18,820,594 |
Connexin 43 hemichannels contribute to the propagation of apoptotic cell death in a rat C6 glioma cell model. | Gap junctions (GJs) have been demonstrated to communicate cell death signals from apoptotic to healthy cells, thereby spatially extending apoptosis. Before being incorporated into GJs, hemichannels (hemi-GJs) are normally closed but recent evidence suggests that they can be opened by various messengers and conditions, thereby forming a pore through which molecules can enter or leave the cell potentially leading to cell death. The aim of this study was to determine the contribution of GJs and hemichannels in the communication of apoptosis toward surrounding cells. We induced apoptosis in C6 glioma cells stably transfected with connexin (Cx)43, with cytochrome C (cytC) using in situ electroporation and found that healthy surrounding cells underwent apoptotic transformation. Work with various cell death markers, wild-type (WT) and Cx43-expressing cells, inhibitors of GJs and/or hemichannels, and Cx43 gene silencing showed that GJs contribute to the spread of apoptosis in a zone next to where apoptosis was triggered whereas hemichannels also promoted cell death beyond this area. Buffering cytoplasmic Ca(2+) changes inhibited the spread of apoptosis in both cases. We conclude that Cx43 hemichannels, in concert with their GJ counterparts, play a role in communicating cytC-induced apoptotic cell death messages. | 18,820,645 |
Case-control study of subconjunctival triamcinolone acetonide injection vs intravenous methylprednisolone pulse in the treatment of endothelial corneal allograft rejection. | To assess the safety and effectiveness of treating corneal endothelial rejection with a subconjunctival injection of 20 mg triamcinolone acetonide in combination with topical application of 1% prednisolone acetate, as compared to treatment with an intravenous pulse of 500 mg methylprednisolone in combination with topical application of 1% prednisolone acetate. A case-controlled study including a literature review was performed. Patients who presented with an initial episode of corneal endothelial rejection were treated with subconjunctival injection of 20 mg triamcinolone in combination with topically applied 1% prednisolone and were retrospectively matched for age and diagnosis to patients who received a single intravenous injection of 500 mg methylprednisolone in combination with topical 1% prednisolone. Patients were analysed regarding reversion of the rejection episode, intraocular pressure, and visual acuity after 1 year. Overall, the triamcinolone group had a better outcome regarding reversion of corneal transplant rejection (P=0.025), with 15 of 16 patients in the triamcinolone group having clear grafts, compared to only 10 of 16 patients in the methylprednisolone group. Intraocular pressure (IOP) was increased in both groups at day 30 (P=0.002), although there was no statistically significant difference in IOP between the groups (P=0.433). Visual acuity improved in both groups after 1 year (P=0.049), although slightly more improvement was observed in the triamcinolone group (P=0.002). The results observed in this case-controlled study suggest that the use of subconjunctival triamcinolone acetonide may benefit patients with corneal transplant rejection. | 18,820,657 |
Primary retroperitoneal myxoid/round cell liposarcoma is a nonexisting disease: an immunohistochemical and molecular biological analysis. | Almost all primary retroperitoneal liposarcomas can be classified as well-/dedifferentiated liposarcoma. Rarely, however, primary retroperitoneal liposarcoma is classified as myxoid/round cell liposarcoma, based on the presence of myxoid areas and vascular crow's feet pattern, which has resulted in a debate on the classification of liposarcoma in the retroperitoneum. Genetically, myxoid/round cell liposarcoma and well-/dedifferentiated liposarcoma are different diseases. Myxoid/round cell liposarcoma is characterized by a translocation causing FUS-CHOP or EWSR1-CHOP fusion, whereas well-/dedifferentiated liposarcoma is characterized by an amplification of the 12q13-15 region, including MDM2 and CDK4 genes. As myxoid/round cell liposarcoma is highly radio- and chemosensitive, differentiation between subtypes is important to optimize treatment. We studied whether primary retroperitoneal liposarcomas diagnosed as myxoid/round cell liposarcoma represent molecularly true myxoid/round cell liposarcoma or are histopathological mimics and represent well-/dedifferentiated liposarcoma. Primary retroperitoneal myxoid/round cell liposarcoma (n=16) were compared to primary extremity myxoid/round cell liposarcoma (n=20). Histopathological and immunohistochemical features were studied. Amplification status of the 12q13-15 region was studied using a multiplex ligation-dependent probe amplification analysis, and FUS-CHOP or EWS-CHOP translocations were studied using RT-PCR. In primary retroperitoneal myxoid/round cell liposarcoma, MDM2 and CDK4 staining was both positive in 12 of 15 cases. In primary extremity myxoid/round cell liposarcoma, MDM2 was negative in 18/20 and CDK4 was negative in all cases. Multiplex ligation-dependent probe amplification showed the amplification of 12q13-15 region in 16/16 primary retroperitoneal myxoid/round cell liposarcomas and in 1/20 primary extremity myxoid/round cell liposarcomas. Translocation was present in all (18/18) primary extremity myxoid/round cell liposarcomas, but absent in all primary retroperitoneal myxoid/round cell liposarcomas. On the basis of immunohistochemical and molecular characteristics, apparent primary retroperitoneal myxoid/round cell liposarcoma can be recognized as well-/dedifferentiated liposarcoma with morphological features mimicking myxoid/round cell liposarcoma. In these cases, treatment should probably be specifically designed as for well-/dedifferentiated liposarcoma. Moreover, finding of myxoid/round cell liposarcoma translocations in a retroperitoneal localization is highly suggestive of metastasis and should prompt search for a primary localization outside the retroperitoneum. | 18,820,664 |
Digestive histopathological presentation of IPEX syndrome. | Immunodysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX) syndrome is a well recognized and particularly severe form of autoimmune enteropathy. It has an X-linked recessive transmission, and is caused by mutations in the FOXP3 gene. We studied the intestinal morphological changes characterizing IPEX syndrome in a series of 12 children with a molecularly confirmed diagnosis. Histological examination of duodenal, gastric and colonic biopsies were retrospectively reviewed and compared by two independent experienced pathologists. In parallel, the presence of circulating anti-enterocyte antibodies was analysed using an indirect immunofluorescence technique and a quantitative radioligand assay against the 75-kDa autoantigen. The morphology of the inflammatory gut lesions could be categorized into three different entities, namely graft-vs-host disease-like changes (9/12 patients), a coeliac disease-like pattern (2/12) and an enteropathy with a complete depletion of goblet cells (1/12). Our results do not suggest any phenotype-genotype correlation. Circulating antibodies were detected in all 12 patients, with an anti-brush border pattern (11/12) and anti-goblet cell antibodies (1/12), as well as by a radioligand assay. The histological presentation of autoimmune enteropathy is rather variable. However, a graft-vs-host disease-like pattern associated with positive anti-enterocyte antibodies is the most frequent intestinal presentation of IPEX syndrome, and constitutes a very valuable tool for pathologists to suspect this diagnosis. | 18,820,676 |
Comprehensive mass-spectrometry-based proteome quantification of haploid versus diploid yeast. | Mass spectrometry is a powerful technology for the analysis of large numbers of endogenous proteins. However, the analytical challenges associated with comprehensive identification and relative quantification of cellular proteomes have so far appeared to be insurmountable. Here, using advances in computational proteomics, instrument performance and sample preparation strategies, we compare protein levels of essentially all endogenous proteins in haploid yeast cells to their diploid counterparts. Our analysis spans more than four orders of magnitude in protein abundance with no discrimination against membrane or low level regulatory proteins. Stable-isotope labelling by amino acids in cell culture (SILAC) quantification was very accurate across the proteome, as demonstrated by one-to-one ratios of most yeast proteins. Key members of the pheromone pathway were specific to haploid yeast but others were unaltered, suggesting an efficient control mechanism of the mating response. Several retrotransposon-associated proteins were specific to haploid yeast. Gene ontology analysis pinpointed a significant change for cell wall components in agreement with geometrical considerations: diploid cells have twice the volume but not twice the surface area of haploid cells. Transcriptome levels agreed poorly with proteome changes overall. However, after filtering out low confidence microarray measurements, messenger RNA changes and SILAC ratios correlated very well for pheromone pathway components. Systems-wide, precise quantification directly at the protein level opens up new perspectives in post-genomics and systems biology. | 18,820,680 |
Triggering the succinate receptor GPR91 on dendritic cells enhances immunity. | Succinate acts as an extracellular mediator signaling through the G protein-coupled receptor GPR91. Here we show that dendritic cells had high expression of GPR91. In these cells, succinate triggered intracellular calcium mobilization, induced migratory responses and acted in synergy with Toll-like receptor ligands for the production of proinflammatory cytokines. Succinate also enhanced antigen-specific activation of human and mouse helper T cells. GPR91-deficient mice had less migration of Langerhans cells to draining lymph nodes and impaired tetanus toxoid-specific recall T cell responses. Furthermore, GPR91-deficient allografts elicited weaker transplant rejection than did the corresponding grafts from wild-type mice. Our results suggest that the succinate receptor GPR91 is involved in sensing immunological danger, which establishes a link between immunity and a metabolite of cellular respiration. | 18,820,681 |
Priming for T helper type 2 differentiation by interleukin 2-mediated induction of interleukin 4 receptor alpha-chain expression. | T helper type 2 (T(H)2) cells are essential for humoral immunity and host defense. Interleukin 4 (IL-4) drives T(H)2 differentiation and IL-2 augments the accessibility of Il4 chromatin. Here we demonstrate that IL-2, by inducing binding of STAT5 to the Il4ra locus, which encodes IL-4 receptor alpha-chain (IL-4Ralpha), was essential for inducing and maintaining IL-4Ralpha expression. Although IL-4 induced IL-4Ralpha expression, T cell receptor-induced IL-4Ralpha expression was normal in Il4(-/-) cells but was much lower in Il2(-/-) cells. Notably, forced IL-4Ralpha expression restored the T(H)2 differentiation of Il2(-/-) cells. Moreover, genome-wide mapping by chromatin immunoprecipitation coupled with sequencing showed broad interaction of the transcription factors STAT5A and STAT5B with genes associated with T(H)2 differentiation. Our results identify a previously unappreciated function for IL-2 in 'priming' T cells for T(H)2 differentiation and in maintaining the expression of Il4ra and other genes in T(H)2-committed cells. | 18,820,682 |
Forebrain steroid levels fluctuate rapidly during social interactions. | Neurosteroids are powerful modulators of brain function and behavior, yet their dynamics in the brain have remained elusive. Using in vivo microdialysis in male zebra finches, we found that local estradiol levels increased rapidly in the forebrain during social interactions with females. Furthermore, when males were exposed to other males' songs, local estradiol levels also increased and testosterone levels dropped in a cortical/pallial auditory region that is analogous to mammalian auditory cortex. We also found that local estradiol and testosterone levels were differentially regulated in this same region by the conventional neurotransmitters glutamate and GABA, respectively. This study provides direct evidence that forebrain steroid levels are acutely and differentially regulated during social behavior in a region-specific manner and in a rapid time course similar to that of traditional neuromodulators. | 18,820,691 |
Origin of correlated activity between parasol retinal ganglion cells. | Cells throughout the CNS have synchronous activity patterns; that is, a cell's probability of generating an action potential depends both on its firing rate and on the occurrence of action potentials in surrounding cells. The mechanisms producing synchronous or correlated activity are poorly understood despite its prevalence and potential effect on neural coding. We found that neighboring parasol ganglion cells in primate retina received strongly correlated synaptic input in the absence of modulated light stimuli. This correlated variability appeared to arise through the same circuits that provide uncorrelated synaptic input. In addition, ON, but not OFF, parasol cells were coupled electrically. Correlated variability in synaptic input, however, dominated correlations in the parasol spike outputs and shared variability in the timing of action potentials generated by neighboring cells. These results provide a mechanistic picture of how correlated activity is produced in a population of neurons that are critical for visual perception. | 18,820,692 |
Mirror-image representation of action in the anterior parietal cortex. | Mimicking hand actions made by someone facing us (that is, allocentric viewpoint) is typically performed with the opposite hand. Using functional magnetic resonance imaging (fMRI), we found a similar mirror-image representation of others' actions in the human anterior parietal cortex. Viewing egocentric-based actions elicited greater fMRI activation in the contralteral hemisphere (as in, self action), whereas observation of action seen from an allocentric viewpoint generated greater activation in the ipsilateral hemisphere. This mirror-like mapping occurs without active imitation, providing further evidence for an automatic action-simulation system in the parietal cortex. | 18,820,694 |
Questioning the role of rebound firing in the cerebellum. | A key component of recent theories on cerebellar function is rebound firing in neurons of the deep cerebellar nuclei (DCN). Despite the robustness of this phenomenon in vitro, in vivo studies have provided little evidence for its prevalence. We found that intact mouse or rat DCN neurons rarely showed rebound firing under physiological conditions in vitro or in vivo. These observations necessitate a critical re-evaluation of recent cerebellar models. | 18,820,695 |
Control of rice grain-filling and yield by a gene with a potential signature of domestication. | Grain-filling, an important trait that contributes greatly to grain weight, is regulated by quantitative trait loci and is associated with crop domestication syndrome. However, the genes and underlying molecular mechanisms controlling crop grain-filling remain elusive. Here we report the isolation and functional analysis of the rice GIF1 (GRAIN INCOMPLETE FILLING 1) gene that encodes a cell-wall invertase required for carbon partitioning during early grain-filling. The cultivated GIF1 gene shows a restricted expression pattern during grain-filling compared to the wild rice allele, probably a result of accumulated mutations in the gene's regulatory sequence through domestication. Fine mapping with introgression lines revealed that the wild rice GIF1 is responsible for grain weight reduction. Ectopic expression of the cultivated GIF1 gene with the 35S or rice Waxy promoter resulted in smaller grains, whereas overexpression of GIF1 driven by its native promoter increased grain production. These findings, together with the domestication signature that we identified by comparing nucleotide diversity of the GIF1 loci between cultivated and wild rice, strongly suggest that GIF1 is a potential domestication gene and that such a domestication-selected gene can be used for further crop improvement. | 18,820,698 |
Wnt-beta-catenin signaling in the pathogenesis of osteoarthritis. | Osteoarthritis (OA) is a progressively degenerative joint condition that is influenced by various metabolic and structural factors. The canonical Wnt-frizzled-beta-catenin pathway has been implicated in the pathogenesis of OA. Products of the Wnt, frizzled, secreted frizzled-related protein (sFRP), Dickkopf and LDL-receptor-related protein gene families have crucial roles in the development and maintenance of bone, cartilage and joints. Increased levels of beta-catenin have been observed in degenerative cartilage, suggesting that a diminished capacity to limit Wnt signaling might contribute to cartilage loss. Polymorphisms in genes involved in Wnt signaling-particularly in the gene encoding sFRP-3-are associated with an increased susceptibility to the development of OA. At least one of these polymorphisms in the gene encoding sFPR-3 is associated with a reduced ability to limit beta-catenin signaling. In addition, the canonical Wnt signaling pathway is influenced by local factors, including alterations in glycosaminoglycan sulfation, cartilage matrix content, transforming growth factor beta and vitamin D. A higher circulating level of the Wnt inhibitor Dickkopf-1, for instance, is associated with slowed progression of hip OA. Hence, the sum of local and systemic factors contributes to the outcome of the Wnt-frizzled pathways. Further investigation is needed to fully define the role of Wnt signaling in OA. | 18,820,702 |
Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium. | Mesenchymal stem cells have been shown to mediate immunomodulatory effects. They have been used in patients with steroid-refractory acute GVHD (aGVHD), but their relevance as a therapeutic agent targeting aGVHD has still to be defined. In this case series, we report 13 patients with steroid-refractory aGVHD who received BM-derived MSC expanded in platelet lysate-containing medium from unrelated HLA disparate donors. MSC were characterized by their morphological, phenotypical and functional properties. All tested preparations suppressed the proliferation of in vitro activated CD4+ T cells. MSC were transfused at a median dosage of 0.9 x 10(6)/kg (range 0.6-1.1). The median number of MSC applications was 2 (range 1-5). Only two patients (15%) responded and did not require any further escalation of immunosuppressive therapy. Eleven patients received additional salvage immunosuppressive therapy concomitant to further MSC transfusions, and after 28 days, five of them (45%) showed a response. Four patients (31%) are alive after a median follow-up of 257 days, including one patient who initially responded to MSC treatment. In our patient cohort, response to MSC transfusion was lower than in the series reported earlier. However, our experience supports the potential efficacy of MSC in the treatment of steroid-refractory aGVHD. | 18,820,709 |
GVHD after chemotherapy conditioning in allogeneic transplanted mice. | GVHD is a major complication in allogeneic SCT. Available GVHD models are mainly based on radiotherapy-conditioning and/or immune deficient mice. GVHD models based on chemotherapy-based regimens remain poorly studied, despite 50% of all transplantations being chemotherapy based. Our aim was to develop a GVHD model using chemotherapy as conditioning. Female BALB/c (H-2Kd) were conditioned with BU-CY and transplanted with 2 x 10(7) BM and 3 x 10(7) spleen cells from either C57BL/6 (H-2 Kb) mice (allogeneic setting) or from male BALB/c to serve as a control group for regimen-related toxicity and engraftment. GVHD manifestations and histopathological changes were evaluated. Chimerism and donor T cells presence in skin, intestine and liver were studied using FACS-, FISH analysis and immunohistochemistry. Allogeneic transplanted mice developed lethal GVHD starting from day+7 with both histological and clinical signs. Donor T cells accumulated in recipient skin and intestine with GVHD progression. BM-failure, apoptosis and T-lymphocyte infiltration into target organs were significantly higher in allogeneic when compared with the syngeneic group. No toxicity or GVHD signs were observed in the syngeneic setting. We report a mouse model of GVHD using BU-CY conditioning that represents the most common myeloablative-conditioning regimen in clinical SCT. This model can be utilized to study the role of conditioning on mechanisms underlying GVHD. | 18,820,712 |
Arp2/3 branched actin network mediates filopodia-like bundles formation in vitro. | During cellular migration, regulated actin assembly takes place at the cell leading edge, with continuous disassembly deeper in the cell interior. Actin polymerization at the plasma membrane results in the extension of cellular protrusions in the form of lamellipodia and filopodia. To understand how cells regulate the transformation of lamellipodia into filopodia, and to determine the major factors that control their transition, we studied actin self-assembly in the presence of Arp2/3 complex, WASp-VCA and fascin, the major proteins participating in the assembly of lamellipodia and filopodia. We show that in the early stages of actin polymerization fascin is passive while Arp2/3 mediates the formation of dense and highly branched aster-like networks of actin. Once filaments in the periphery of an aster get long enough, fascin becomes active, linking the filaments into bundles which emanate radially from the aster's surface, resulting in the formation of star-like structures. We show that the number of bundles nucleated per star, as well as their thickness and length, is controlled by the initial concentration of Arp2/3 complex ([Arp2/3]). Specifically, we tested several values of [Arp2/3] and found that for given initial concentrations of actin and fascin, the number of bundles per star, as well as their length and thickness are larger when [Arp2/3] is lower. Our experimental findings can be interpreted and explained using a theoretical scheme which combines Kinetic Monte Carlo simulations for aster growth, with a simple mechanistic model for bundles' formation and growth. According to this model, bundles emerge from the aster's (sparsely branched) surface layer. Bundles begin to form when the bending energy associated with bringing two filaments into contact is compensated by the energetic gain resulting from their fascin linking energy. As time evolves the initially thin and short bundles elongate, thus reducing their bending energy and allowing them to further associate and create thicker bundles, until all actin monomers are consumed. This process is essentially irreversible on the time scale of actin polymerization. Two structural parameters, L, which is proportional to the length of filament tips at the aster periphery and b, the spacing between their origins, dictate the onset of bundling; both depending on [Arp2/3]. Cells may use a similar mechanism to regulate filopodia formation along the cell leading edge. Such a mechanism may allow cells to have control over the localization of filopodia by recruiting specific proteins that regulate filaments length (e.g., Dia2) to specific sites along lamellipodia. | 18,820,726 |
Anti-plasmodium activity of angiotensin II and related synthetic peptides. | Plasmodium species are the causative agents of malaria, the most devastating insect-borne parasite of human populations. Finding and developing new drugs for malaria treatment and prevention is the goal of much research. Angiotensins I and II (ang I and ang II) and six synthetic related peptides designated Vaniceres 1-6 (VC1-VC6) were assayed in vivo and in vitro for their effects on the development of the avian parasite, Plasmodium gallinaceum. Ang II and VC5 injected into the thoraces of the insects reduced mean intensities of infection in the mosquito salivary glands by 88% and 76%, respectively. Although the mechanism(s) of action is not completely understood, we have demonstrated that these peptides disrupt selectively the P.gallinaceum cell membrane. Additionally, incubation in vitro of sporozoites with VC5 reduced the infectivity of the parasites to their vertebrate host. VC5 has no observable agonist effects on vertebrates, and this makes it a promising drug for malaria prevention and chemotherapy. | 18,820,728 |
Hyaluronidase of bloodsucking insects and its enhancing effect on leishmania infection in mice. | Salivary hyaluronidases have been described in a few bloodsucking arthropods. However, very little is known about the presence of this enzyme in various bloodsucking insects and no data are available on its effect on transmitted microorganisms. Here, we studied hyaluronidase activity in thirteen bloodsucking insects belonging to four different orders. In addition, we assessed the effect of hyaluronidase coinoculation on the outcome of Leishmania major infection in BALB/c mice. High hyaluronidase activity was detected in several Diptera tested, namely deer fly Chrysops viduatus, blackflies Odagmia ornata and Eusimilium latipes, mosquito Culex quinquefasciatus, biting midge Culicoides kibunensis and sand fly Phlebotomus papatasi. Lower activity was detected in cat flea Ctenocephalides felis. No activity was found in kissing bug Rhodnius prolixus, mosquitoes Anopheles stephensi and Aedes aegypti, tse-tse fly Glossina fuscipes, stable fly Stomoxys calcitrans and human louse Pediculus humanus. Hyaluronidases of different insects vary substantially in their molecular weight, the structure of the molecule and the sensitivity to reducing conditions or sodium dodecyl sulphate. Hyaluronidase exacerbates skin lesions caused by Leishmania major; more severe lesions developed in mice where L. major promastigotes were coinjected with hyaluronidase. High hyaluronidase activities seem to be essential for insects with pool-feeding mode, where they facilitate the enlargement of the feeding lesion and serve as a spreading factor for other pharmacologically active compounds present in saliva. As this enzyme is present in all Phlebotomus and Lutzomyia species studied to date, it seems to be one of the factors responsible for enhancing activity present in sand fly saliva. We propose that salivary hyaluronidase may facilitate the spread of other vector-borne microorganisms, especially those transmitted by insects with high hyaluronidase activity, namely blackflies (Simuliidae), biting midges (Ceratopogonidae) and horse flies (Tabanidae). | 18,820,742 |
Changes in types of muscle fibers induced by transcutaneous electrical stimulation of the diaphragm of rats. | The objective of the present study was to assess the effect of transcutaneous electrical diaphragmatic stimulation (TEDS) on different types of diaphragm muscle fibers. Male Wistar rats (8-12 weeks old) were divided into 2 experimental groups (N = 8 in each group): 1) control, 2) animals submitted to TEDS [frequency = 50 Hz; T(ON)/T(OFF) (contraction/relaxation time) = 2/2 s; pulse duration = 0.4 ms, intensity = 5 mA with a 1 mA increase every 3 min for 20 min] for 7 days. After completing this treatment period, the I, IIA, IIB, and IID diaphragm muscle fibers were identified using the mATPase technique. Statistical analysis consisted of the normality, homoscedasticity and t-tests (P < 0.05). There was a 19.6% (P < 0.05) reduction in the number of type I fibers and a 49.7% increase (P < 0.05) in type IID fibers in the TEDS group compared with the control group. An important result of the present study was that electrical stimulation with surface electrodes was efficient in altering the distribution of fibers in diaphragm muscle. This therapeutic resource could be used in the treatment of respiratory muscle alterations. | 18,820,771 |
Training-related changes in the R-R interval at the onset of passive movements in humans. | The aim of the present study was to determine whether training-related alterations in muscle mechanoreflex activation affect cardiac vagal withdrawal at the onset of exercise. Eighteen male volunteers divided into 9 controls (26 +/- 1.9 years) and 9 racket players (25 +/- 1.9 years) performed 10 s of voluntary and passive movement characterized by the wrist flexion of their dominant and non-dominant limbs. The respiratory cycle was divided into four phases and the phase 4 R-R interval was measured before and immediately following the initiation of either voluntary or passive movement. At the onset of voluntary exercise, the decrease in R-R interval was similar between dominant and non-dominant forearms in both controls (166 +/- 20 vs 180 +/- 34 ms, respectively; P > 0.05) and racket players (202 +/- 29 vs 201 +/- 31 ms, respectively; P > 0.05). Following passive movement, the non-dominant forearm of racket players elicited greater changes than the dominant forearm (129 +/- 30 vs 77 +/- 17 ms; P < 0.05), as well as both the dominant (54 +/- 20 ms; P < 0.05) and non-dominant (59 +/- 14 ms; P < 0.05) forearms of control subjects. In contrast, changes in R-R interval elicited by the racket players' dominant forearm were similar to that observed in the control group, indicating that changes in R-R interval at the onset of passive exercise were not attenuated in the dominant forearm of racket players. In summary, cardiac vagal withdrawal induced by muscle mechanoreflex stimulation is well-maintained, despite long-term exposure to training. | 18,820,774 |
The use and midium-term evaluation of decellularized allograft cusp in the surgical treatment of the tetralogy of fallot. | To describe the technique of implantation and to show the echocardiographic follow-up of the decellularized cusps allografts used in patients with tetralogy of fallot. Fifteen patients underwent this implantation between March 2005 and August 2007 and they were clinically followed-up. An echocardiogram was performed to evaluate the morphofunctional result of the allografts. The mean follow-up was 12.7 months (1-25 months). The echocardiography results showed that pulmonary insufficiency was mild in nine (60%) patients, moderate in three (20%) patients, and severe in three (20%) patients. The results also showed that the systolic right ventricle function was normal in 13 (86.7%) and that there was mild dysfunction in two (13.3%). Eleven (73.4%) patients did not present any gradient in the right ventricular outflow tract and four (26.6%) presented mild stenosis. The mobility of the cusps were normal in all cases and there was no thickness larger than 1.5 mm. There was no calcification; 14 patients (93.3%) presented Z score between -1 and 0,7 and one patient presented dilated pulmonary annulus with a Z score of + 2.5. In midium-term follow-up, the decellularized allograft seemed to be a good option for right ventricle outflow tract enlargement in patients underwent tetralogy of Fallot. | 18,820,782 |
Heparin quality control in the Brazilian market: implications in the cardiovascular surgery. | The change in the heparin solution trade mark in Brazil that had been commonly used in cardiac surgery has shown increased number in the coagulopathy, re-exploration and other side effects in our Institution and others. All four different heparin solutions available in the Brazilian market were studied in the Connective Tissue Lab, HUCFF, UFRJ and compared to the Liquemine (out of the market) and the international control solution. All samples were evaluated by magnetic nuclear resonance as well as their anticoagulant effectiveness. There were significant differences among them regarding the anticoagulant activity. It was also observed contamination with other dermatan sulfate, samples chemically degraded and with significant change in the molecular weight. Among the studied samples, none of them can offer security in cardiac surgeries on pump. None of them has demonstrated similar quality to Liquemine, which is not available in the Brazilian market. | 18,820,778 |
High-frequency ultrasonic waves cause endothelial dysfunction on canine epicardial coronary arteries. | Application of ultrasound energy by an endarterectomy probe can facilitate the removal of atheromatous plaque, but the effect of this procedure on surrounding vessel structure and function is still a matter of experimental investigations. To determine whether ultrasound energy impairs the production of nitric oxide or damages vascular smooth muscle function, isolated canine epicardial coronary artery segments were exposed to either high (25 W) or low (0-10 W) ultrasonic energy outputs, for 15 seconds, using an endarterectomy device prototype. After exposure, segments of epicardial coronary artery were studied in organ chambers. The following drugs were used: adenosine diphosphate (ADP), acetylcholine (Ach) and sodium fluoride (NaF) to study endothelium-dependent relaxation and sodium nitroprusside (SNP) and isoproterenol to evaluate endothelium-independent relaxation. Application of high ultrasonic energy power impaired endothelium-dependent relaxation to ADP (10(-9)-10(-4) M), Ach (10(-9)-10(-4) M) and NaF (0.5-9.5 mM) in epicardial coronary arteries. However, low ultrasound energy output at the tip of the probe did not alter the endothelium-dependent relaxation (either maximal relaxation or EC50) to the same agonists. Vascular smooth muscle relaxation to isoproterenol (10(-9)-10(-5) M) or SNP (10(-9)-10(-6) M) was unaltered following exposure to either low or high ultrasonic energy outputs. These experiments currently prove that ultrasonic energy changes endothelial function of epicardial coronary arteries at high power. However, ultrasound does not alter the ability of vascular smooth muscle of canine epicardial coronary arteries to relax. | 18,820,781 |
Alternate HMQC experiments for recording HN and HC-correlation spectra in proteins at high throughput. | Alternate implementations of the SOFAST-HMQC experiment are described. In these alternate SOFAST-HMQC experiments (ALSOFAST-HMQC) excitation of the magnetization of interest is achieved by non-selective rf pulses while preserving the equilibrium polarization of passive spins. This alternate excitation scheme also allows the incorporation of a novel sensitivity enhancement protocol which has been most recently developed by Brutscher and coworkers and which permits simultaneous detection of both the x- and y-components of the indirectly detected t(1)-interferograms without the need to introduce additional rf pulses and delays. We show that the ALSOFAST HC-HMQC experiment, which implements an alternate means of frequency selection, enables the detection of methyl resonances with large secondary proton chemical shifts. This is achieved by selecting coherences of interest via a frequency selective carbon inversion pulse. Detailed comparisons between SOFAST- and the presented ALSOFAST-HMQC experiment reveals a considerable degree of mutual complementarity. | 18,820,839 |
Incidence and predictability of amiodarone-induced thyrotoxicosis and hypothyroidism. | To determine the incidence and predictability of amiodarone-induced thyrotoxicosis (AIT) and hypothyroidism (AIH) in patients with cardiomyopathy. A total of 72 patients (mean age 69 +/- 11 years) living in an area previously endemic for thyroid disease but with currently sufficient iodine intake were enrolled in this prospective study. All participants were treated with amiodarone for the first time. The course of thyroid function in patients with normal thyroid morphology and in those with goiter was monitored over a median follow-up period of eight months in 71 (98.6%) patients. Of 72 participants, 18 (25.0%) had a morphologically normal thyroid gland as evidenced by sonography. The prevalence of thyroid dysfunction before initiation of amiodarone was 37.6% (27 of 72) with almost equal distribution between hypothyroidism and hyperthyroidism (14 and 13 patients). After treatment with amiodarone, thyroid dysfunction was diagnosed in 56.8% (25 of 44) of the patients without preexisting dysfunction. Of these 25 patients, nine (36%) developed either subclinical or overt AIH and 16 (64.0%) developed either subclinical or overt AIT. Although 61.1% (44 of 72) had normal thyroid function before initiation of amiodarone, this number decreased to 26.7% (19 of 71, P < 0.001) after treatment. Factors such as (99m)Tc-pertechnetate scan uptake, thyroid autoimmunity, age, thyroid autonomy or abnormal thyroid morphology were not significantly associated with the development of thyroid dysfunction. Prevalence of thyroid dysfunction was high in elderly patients treated with amiodarone. Cases of AIT and AIH occurred in patients with and without preexisting thyroid disorders. Because of the high incidence of amiodarone-induced thyroid dysfunction, regular testing of thyroid function is mandatory during and following amiodarone treatment. | 18,820,854 |
Evaluation of pain experienced during breast ductal endoscopy. | Ductal endoscopy is valuable for the differential diagnosis of bloody nipple discharge; however, the pain associated with this procedure has not been evaluated. This study aims to assess the pain experienced by patients during ductal endoscopy. We studied a consecutive series of women who underwent ductal endoscopy, to investigate the cause of bloody nipple discharge. The procedure was performed using standard local anesthesia (lidocaine 1% 10 ml without epinephrine, involving nipple block and periaureolar administration). Patients were asked to score the level of pain with a visual analog scale, 1, 4, 7, 12, 17, 22, 27, and 32 min after the procedure, and describe their overall and maximum pain. This series comprised 20 women aged from 27 to 68 years old. The overall pain (mean +/- SE) score was equal to 5.8 +/-0.3, and the maximum pain score was 8.3 +/- 0.2. The peak of pain corresponded with when the dilator was inserted through the sphincter. The group in which the dilator was inserted after 4 min experienced more intense maximum and overall pain after 7, 12, 17 and 22 min. Pain is an important factor in ductal endoscopy, and peaks relatively early. A standard, baseline local lidocaine dose of greater than 10 ml may be necessary at the beginning of the procedure. Late insertion of the dilator seems to be an indicator of the force of the procedure. | 18,820,862 |
Clinical spectrum of internal hernia: a surgical emergency. | To define the indicators of bowel ischemia caused by congenital or acquired internal hernia, based on our 10-year experience in one center. We reviewed the medical records, imaging studies, and operative findings of 20 patients who underwent surgery for an internal hernia at our medical center between 1995 and 2005. The clinical characteristics and related indicators of the patients with, and those without bowel ischemia were compared and analyzed statistically. The subtypes of congenital internal hernia (CIH) included transmesenteric (n = 6, 60%), paraduodenal (n = 2, 20%), and pericecal (n = 2, 20%) hernia. The abdominal surgical procedures preceding acquired internal hernia (AIH) were Roux-en-Y anastomosis (n = 6, 60%) and appendectomy (n = 3, 30%). Transmesenteric hernia was the most prevalent type of CIH in children. Abdominal rebound tenderness, advanced leukocytosis (>18 000/mm(3)), or a high level of manual band form (>6%) were the positive predictive factors for bowel ischemia, whereas a history of chronic intermittent abdominal pain was a negative indicator. No recurrence was noted during the 10-year study period. The overall mortality rate was 20%, attributable to enteral bacteria sepsis in all cases. Internal hernia is a rare but lethal condition. Early diagnosis and prompt surgical intervention provide the only chance of a successful outcome. | 18,820,864 |
Expression of the endocannabinoid system in the bi-potential HEL cell line: commitment to the megakaryoblastic lineage by 2-arachidonoylglycerol. | The role of the endocannabinoid system in haematopoietic cells is not completely understood. We investigated whether human erythroleukemia (HEL) cells were able to bind, metabolise and transport the main endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG). We also investigated whether AEA or 2-AG could modulate HEL differentiation. Although able to internalise both endocannabinoids, HEL cells had the machinery to metabolise 2-AG only, since they were devoid of the enzymes needed to synthesise and degrade AEA. Nonetheless, the intracellular transport of exogenous AEA might be required to activate the vanilloid receptors, with yet unknown implications for vascular biology. On the contrary, 2-AG appeared to play a role in lineage determination. Indeed, 2-AG itself drove HEL cells towards megakaryocytic differentiation, as it enhanced expression of beta3 integrin subunit, a megakaryocyte/platelet surface antigen, and glycoprotein VI, a late marker of megakaryocytes; in parallel, it reduced the amount of messenger RNA encoding for glycophorin A, a marker of erythroid phenotype. All these effects were mediated by activation of CB(2) cannabinoid receptors that triggered an extracellular signal-regulated kinase-dependent signalling cascade. In addition, classical inducers of megakaryocyte differentiation reduced 2-AG synthesis (although they did not affect the binding efficiency of CB(2) receptors), suggesting that levels of this endocannabinoid may be critical for committing HEL cells towards the megakaryocytic lineage. | 18,820,887 |
Does the SLC40A1 gene modify HFE-related haemochromatosis phenotypes? | Most hereditary haemochromatosis patients are homozygous for the C282Y mutation of the HFE gene. However, the phenotypic expression and clinical aggressiveness of the disease differs considerably from patient to patient. The main objective of this work was to study the role of variants in the SLC40A1 gene in the severity of iron overload and his clinical consequences in 100 Spanish probands homozygous for the C282Y mutation of the HFE gene. We performed automated sequencing of the coding regions, including intron-exon junctions of the SLC40A1 gene. We studied the association between polymorphisms in the SLC40A1 gene and median values of iron removed, taking into account statistical corrections for multiple comparisons. No pathogenic mutations in the SLC40A1 were detected. Five known single nucleotide polymorphisms (SNPs) were identified, and two of them were associated with phenotypic characteristics. IVS1-24 C>G was associated with the amount of iron removed and presence of liver disease: Of the 83 patients finally studied for this SNP, the amount of iron removed was above the median in 36 of 56 (64.3%) for C/C, in nine of 23(39.1%) for C/G and in zero of four (0%) for G/G patients (P=0.01). Liver damage was observed in 34 of 56 patients (60.7%) for C/C, in eight of 23 (34.8%) for C/G and in zero of four (0%) for G/G (P=0.01). Both associations remained significant at multivariate analysis (P=0.011 and P=0.023, respectively). IVS1-24 C>G on the ferroportin gene seems to be a genetic modifier for clinical aggressiveness of HFE1 haemochromatosis. | 18,820,912 |
[Classification of prosthetic loosening and determination of wear particles]. | Nowaday, loosening of orthopaedic implants implies important medical and socioeconomic problems. Implant loosening is caused by implant infections as well as aseptic loosening, due to particle disease and mechanical alterations. Clinically we divide the implant infection into early and late infections. Morphologically it is possible to reliably detect the infection by quantification of neutrophil granulocytes. Additionally molecular methods are suitable to detect micro-organisms which are responsible for the prosthetic joint infection including their resistance to antibiotics. Particle disease may be reproducibly classified by the detection of different types of wear particles, particularly polyethylene, metal, ceramic and cement. The aetiology of the indeterminate type of the periprosthetic membrane is obscure, but may be associated with osteopathies. This classification of the periprosthetic membrane morphology provides clinically significant information concerning clinical management of implant loosening. | 18,820,921 |
Autoimmune lymphoproliferative syndrome-like syndrome presented as lupus-like syndrome with mycobacterial joint infection evolved into the lymphoma. | The autoimmune lymphoproliferative syndrome (ALPS) and ALPS-like syndrome are variable clinical conditions characterized by lymphoproliferative disease, autoimmune cytopenias and susceptibility to malignancy. A 59-year-old woman was admitted to the hospital for intractable generalized pain and stiffness with multiple swollen joints for 2 weeks. A low-grade fever, intermittent hypotension and confusion were associated with the pain. The evaluation revealed multiple joint bony erosions with effusion and a ruptured Baker's cyst and positive AFB testing on the joint biopsy of the right wrist. In addition, there were a macular skin rash with telangiectasia and perivascular lymphocyte infiltration, a cytopenia without abnormal cells, a hepatosplenomegaly, a pericardial thickness with effusion and pleural effusion. The patient was treated with anti-mycobacterial drugs, NSAIDs and glucocorticoids for 10 months. But with the symptoms worsening, the patient developed cervical lymph node enlargements and was diagnosed as a diffuse large B cell lymphoma with hemophagocytosis on biopsy. | 18,820,932 |
MAGE-A1 expression is associated with good prognosis in neuroblastoma tumors. | Neuroblastoma is an embryonal tumor of neuroectodermal cells. Patients with metastatic neuroblastoma have a poor survival rate, which has led to numerous efforts to develop prognostic markers. Cancer/testis-specific antigens MAGE-A1 and MAGE-A3 genes were proposed as minimal residual disease (MRD) markers in neuroblastoma, but its usefulness for this purpose is rather limited. We studied 47 primary neuroblastoma tumors. RNA was extracted and cDNA was prepared by reverse transcription. Detection of the MAGE-A1 expression was done by hybridization of the RT-PCR products. We used methylation-specific-PCR to perform the epigenetic studies. We studied the MAGE-A1 and MAGE-A3 expressions, and the MAGE-A1 expression showed significant association with tumor stage, absence of bone marrow infiltration and survival. A multivariate analysis enabled us to conclude that the MAGE-A1 expression represents a new independent predictive factor, which is independent of N-Myc amplification (P value = 0.000), age at diagnosis (P value = 0.002) or tumoral stage (P value = 0.024). Considering the epigenetic regulation of MAGE-A1, we analyzed its methylation profile, and found a significant association with its expression in tumor cells. Moreover, we found tumors that failed to show the MAGE-A1 expression despite the hypomethylated sequence, and corresponded to advanced neuroblastoma that might share another mechanism involved in MAGE-A1 silencing. Given the association described between genome-wide hypomethylation and microsatellite instability, we determined the MSI status of tumor samples, finding a significant correlation with the MAGE-A1 expression and, more specifically, with the hypomethylated status of this gene only in female patients. We conclude that the MAGE-A1 expression is associated with good prognosis in neuroblastoma. | 18,820,946 |
Arthroscopic hemitrapeziectomy for first carpometacarpal arthritis: results at 7-year follow-up. | The purpose of this study was to determine the outcome of arthroscopic hemitrapeziectomy combined with thermal capsular plication and temporary K-wire fixation in patients with painful thumb basal joint due to either osteoarthritis or posttraumatic arthritis. There were 18 thumbs that were evaluated in this retrospective study of arthroscopic hemitrapeziectomy of the distal trapezium in addition to a pancapsular thermal shrinkage at an average of 7.6-year follow-up. No patient has required further surgery. A subjective improvement in pain, pinch activities, strength, and range of motion (ROM) was noted in all patients, and no patient had further surgery on their thumb. On exam, no patient had a first carpal-metacarpal grind or laxity. Total ROM of the thumb axis decreased by 20%, but all patients could oppose to the fifth finger. Grip strength remained unchanged, key pinch improved from 8 to 11 lbs, and tip pinch improved from 4 to 5 lbs. Radiographs showed a metacarpal subsidence of 1.8 mm (0-4 mm). Four complications were noted: two cases of dorsal radial nerve neuritis, one rupture of the flexor pollicis longus, and one prolonged hematoma. Results demonstrate that arthroscopic hemitrapeziectomy and capsular shrinkage for first carpometacarpal arthritis is an effective technique that provides high patient satisfaction, a functional pain-free thumb, and a reliable rate of return to activity. | 18,820,976 |
Single-blinded randomized trial of mechanical bowel preparation for colon surgery with primary intraperitoneal anastomosis. | We report the final analysis of a prospective single-blinded randomized trial designed to investigate whether omission of preoperative mechanical bowel preparation increases the rate of surgical-site infection and anastomotic failure after elective colon surgery with intraperitoneal anastomosis by a single surgeon. Patients scheduled to undergo an elective colon or proximal rectal resection with a primary anastomosis by a single surgeon were randomized to receive either oral polyethylene glycol (Group A) or no mechanical bowel preparation (Group B). Patients were followed by an independent surgeon. One hundred and forty nine patients were enrolled. Three patients (2%) were preoperatively excluded because of active immunosuppression and 13 (9%) were excluded from the final analysis. Of the remaining 129 patients, 65 were assigned to Group A and 64 to Group B. Thirty patients (23.2%) developed wound infection, (Group A = 24.6% and Group B = 17.2%; NS). There were three cases of intra-abdominal sepsis a (Group A 4.6%). The anastomotic failure rate was 5.4% (n = 7), four patients in Group A (6.2%) vs. three patients in Group B (4.7%) (NS). When SSI and anastomotic failure were combined, the complication rate in Group A was 35.4% vs. 21.9% for Group B. The NNH was 7.4. Our final analysis shows that a single surgeon will not have a higher rate of either surgical-site infection or anastomotic failure if he/she routinely omits preoperative mechanical bowel preparation. | 18,820,977 |
Carotid artery stenting: findings based on 8 years' experience. | Carotid artery stenting (CAS) may be an alternative to surgical endarterectomy not only in high-risk patients. Few data are available regarding the long-term clinical efficacy of CAS with the use of cerebral protection devices and the incidence of restenosis. Our experience demonstrates that if certain requirements are fulfilled, CAS can be considered a safe and effective treatment with high short-and long-term success rates. In the past 8 years, we treated 1,003 patients (1,096 arteries) affected by internal carotid artery stenosis, 93 with bilateral stenosis. Of these, 567 (51.74%) were symptomatic and 529 (48.26%) asymptomatic lesions. The preprocedural evaluation was performed with Doppler ultrasound (US), magnetic resonance (MR) angiography/computed tomography (CT) angiography and a neurological evaluation. Antiplatelet therapy was administered before and after the procedure. Technical success was achieved in 1,092 cases (99.6%), and a cerebral protection device was successfully used in 1,019 procedures (92.9%). The 30-day transient ischaemic attack (TIA)/stroke/death rate was 2.16%: death (0.18%) major stroke (0.45%) and minor stroke/TIA (1.53%). During a follow-up up to 8 years, restenoses occurred in 39 cases (3.57%), of which 28 were post-CAS (2.57%) and 11 post-CAS performed for restenosis after carotid endarterectomy (1%). Only five symptomatic restenoses>80% were treated with a repeated endovascular procedure. A retrospective analysis of our experience suggests that CAS is a safe and effective procedure with better results than endarterectomy. In up to 8 years of follow-up, CAS seems to be effective in preventing stroke, with a low restenosis rate. | 18,820,992 |
Anion binding mediated precipitation of a peptibody. | Understand the underlying mechanism governing the salt-induced precipitation of a basic (pI = 8.8) protein, Peptibody A (PbA), in acidic solutions. The rate, extent, and reversibility of PbA precipitation was monitored over 4-weeks as a function of pH (3.7-5.0), salt concentration (0-400 mM), and ion identity using a series of monovalent, Hofmeister anions (F(-), Cl(-), Br(-), I(-), ClO(4) (-), SCN(-)) and cations (Li+, Na+, K+, Rb+, Cs+). The effects of salt on conformational stability and reduced valence were determined using Fourier-transform infrared spectroscopy, circular dichroism, and capillary electrophoresis/analytical ultracentrifugation. PbA precipitation occurred upon salt addition and could be modulated with solution pH, salt identity & concentration. The precipitation was sensitive to anions, but not cations, and increased with anion size. A reverse Hofmeister effect (SCN(-) approximately ClO(4) (-)>I(-)>Cl(-)>Br(-)>F(-)) was observed with "salting-in" anions being the more effective precipitants. An increase in the precipitation rate below pH 4.3 indicated that protonation of aspartyl and glutamyl side-chains was also important for precipitation. The reversibility of precipitation was excellent (100%) at 4 degrees C but decreased upon storage at 25 degrees C and 37 degrees C; the loss in reversibility correlated with an increase in intermolecular beta-sheet content of the precipitate. Salts, employed as buffering, tonicifying, and viscosity modifying agents, may adversely affect the solubility of basic proteins formulated under acidic conditions. | 18,820,999 |
Knowledge about breastfeeding among a group of primary care physicians and residents in Puerto Rico. | Physicians have an essential role in promoting, protecting, and supporting breastfeeding as the ideal method of infant feeding. They are in an important position to promote breastfeeding but report difficulty in advising mothers with lactation problems. The purpose of this study is to assess knowledge about breastfeeding among primary care physicians and residents and identify potential barriers to its promotion. One hundred seventy-seven residents and physicians answered an anonymous questionnaire. The participants recognized breastfeeding benefits but 26% did not encourage exclusive breastfeeding. Mastitis, breast abscess, and the use of medications by the mother were considered contraindications to breastfeeding. Temporary breastfeeding discontinuation and bilirubin levels measurement were the preferred recommendations for the jaundiced infant. Most physicians received training in breastfeeding benefits although they report fair knowledge in myths, techniques, and contraindications. Physicians demonstrated to recognize breastfeeding benefits, but formal education is needed to eliminate barriers to breastfeeding promotion and support. | 18,821,003 |
The 76-gene signature defines high-risk patients that benefit from adjuvant tamoxifen therapy. | To assess the benefit from adjuvant systemic tamoxifen therapy in breast cancer risk groups identified by the previously established prognostic 76-gene signature. In 300 lymph node-negative (LNN), estrogen receptor-positive (ER+) breast cancer patients (136 treated with adjuvant tamoxifen, 164 having received no systemic adjuvant therapy), distant metastasis-free survival (DMFS) as a function of the 76-gene signature was determined in a multicenter fashion. In 136 tamoxifen-treated patients, the 76-gene signature identified a group of patients with a poor prognosis [hazard ratio (HR), 4.62; P = 0.0248]. These patients showed a 12.3% absolute benefit of tamoxifen in 10-year DMFS (HR, 0.52; P = 0.0318) compared with untreated high-risk patients. This represented a 71% increase in relative benefit compared with the 7.2% absolute benefit observed for all 300 patients without using the gene signature. In the low-risk group there was no significant 10-year DMFS benefit of tamoxifen. The 76-gene signature defines high-risk patients who benefit from adjuvant tamoxifen therapy. Although we did not study the value of chemotherapy in this study, low-risk patients identified by the 76-gene signature have a prognosis good enough that chemotherapy would be difficult to justify. The prognosis of these patients is sufficiently good, in fact, that a disease-free benefit for tamoxifen therapy is difficult to prove, though benefits in terms of loco-regional relapse and a reduction in risk for contralateral breast cancer might justify hormonal therapy in these patients. | 18,821,012 |
Fabrication of protein chips based on 3-aminopropyltriethoxysilane as a monolayer. | Although 3-aminopropyltriethoxysilane (APTES) is widely adopted as a monolayer in biosensors, experimental silanization takes at least 1 h at high temperature. Therefore, the feasibility of the silanization with APTES in a short reaction time and at room temperature was investigated. The surface modification of glass slides using a self-assembled monolayer of APTES with a concentration of 10% was studied by immobilizing FITC. APTES was successfully immobilized on the glass slide. The effect of reaction temperature and time of silanization were investigated. Various silanization conditions of APTES were examined by contact angle measurement and fluorescence microscopy. The surface of glass patterns with a gold thin film as background was characterized by determining the fluorescent intensities following the immobilization of fluorescein isothiocyanate (FITC), protein A-FITC, antimouse IgG-FITC and sheep anti-bovine albumin-FITC. The normalized fluorescent intensity indicated that a short period (4 min) of silanization at 25 degrees C suffices to form an APTES thin film by the immobilization of protein A on a glass surface. Such a condition does not require microheaters and temperature sensors in a microfluidic system, which will significantly reduce the manufacturing process, cost, and reaction time in the future. | 18,821,014 |
Effect of actuation sequence on flow rates of peristaltic micropumps with PZT actuators. | Many biomedical applications require the administration of drugs at a precise and preferably programmable rate. The flow rate generated by the peristaltic micropumps used in such applications depends on the actuation sequence. Accordingly, the current study performs an analytical and experimental investigation to determine the correlation between the dynamic response of the diaphragms in the micropump and the actuation sequence. A simple analytical model of a peristaltic micropump is established to analyze the shift in the resonant frequency of the diaphragms caused by the viscous damping effect. The analytical results show that this damping effect increases as the oscillation frequency of the diaphragm increases. A peristaltic micropump with three piezoelectric actuators is fabricated on a silicon substrate and is actuated using 2-, 3-, 4- and 6-phase actuation sequences via a driving system comprising a microprocessor and a phase controller. A series of experiments is conducted using de-ionized water as the working fluid to determine the diaphragm displacement and the flow rates induced by each of the different actuation sequences under phase frequencies ranging from 50 Hz to 1 MHz. The results show that the damping effect of actuation sequences influences diaphragm resonant frequency, which in turn affects the profiles of flow rates. | 18,821,016 |
Adrenal changes associated with adrenarche. | The mechanisms causing the rise in adrenal androgen production during the course of adrenarche remain to be defined. However, the increase in steroid release is clearly associated with a series of intra-adrenal changes in the expression of steroidogenic enzymes needed for dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) production, as well as an expansion of the adrenal zona reticularis (ZR). We and others have defined the adrenal expression pattern of key steroidogenic enzymes during adrenarche. As adrenarche proceeds, the expanding ZR expresses greater levels of cytochrome b5 (CYB5) and steroid sulfotransferase (SULT2A1) than the adjacent fasciculata. In contrast, the growing ZR is deficient in 3beta-hydroxysteroid dehydrogenase type 2 (HSD3B2). The resulting profile of steroidogenic enzymes lends itself to the production of adrenal androgens and appears to track the progression of adrenarche. This article reviews the intra-adrenal changes of the adrenal cortex associated with adrenarche. | 18,821,019 |
Circulating fatty acids and prostate cancer risk in a nested case-control study: the Multiethnic Cohort. | Dietary fat, including specific fatty acids, has been proposed to contribute to prostate cancer pathogenesis, but findings from the studies based on biomarkers have been conflicting. We examined the association between erythrocyte membrane fatty acid composition and prostate cancer risk in a nested case-control study within a multiethnic cohort of African Americans, Native Hawaiians, Japanese Americans, Latinos, and Whites. Analyses included 376 cases and 729 matched controls. Conditional logistic regression was used to estimate the odds ratios and 95% confidence intervals with adjustment for multiple covariates. No significant association was found for saturated, mono- and polyunsaturated fatty acid, or for specific n-3 and n-6 fatty acids, even when the analysis was limited to advanced or high grade prostate cancer. In ethnic specific analyses, there was a positive association with palmitic acid in Japanese Americans that was significantly different from the null results in other groups. There was also an increased risk with n-3 fatty acids and the ratio of n-3/n-6 fatty acids in Whites. Although there was a suggestion of ethnic specific associations with some fatty acids, our overall findings do not support a role for fatty acids in prostate carcinogenesis. | 18,821,021 |
Monitoring of the physical parameters and evaluation of the chemical composition of river and groundwater in Calabar (Southeastern Nigeria). | A 12-month study was carried to assess the seasonal and tidal effects on the physical parameters of river and groundwater, which constitute the major potable water sources in Calabar (Nigeria). The study also included an evaluation of the chemical composition of the different water bodies and their relationship. The results show that there was a significant seasonal effect on dissolved oxygen (DO) and nitrate in groundwater on one hand, and on temperature, redox potential (Eh), and DO in river water on the other. Also, a significant tidal influence exists on DO in both river-and groundwater. Comparison between groundwater and river water show statistically significant difference in EC, TDS, Eh, DO, Na, Cl and NO(3). The significant differences in EC, TDS, Na and Cl are due to tidal flushing. The difference in Eh is due to geology of the area while, NO(3) is as a result of anthropogenic pollution. The concentrations of ions in the river and groundwater for the different seasons and tidal cycles show an inverse relationship, while the river water is generally more concentrated than the groundwater. Using a binary mixing model, estimates show that the degree of mixing of river water and groundwater is low, with values of between 1.93% and 2.76% respectively, in the western and eastern parts of the study area. The study concludes that tidal flushing, anthropogenic effects and oxygen supply during recharge contribute to the shaping of water chemistry in the area. | 18,821,024 |
Production of Prnp-/- goats by gene targeting in adult fibroblasts. | Homozygous mice devoid of functional Prnp are resistant to scrapie and prion propagation, but heterozygous mice for Prnp disruption still suffer from prion disease and prion deposition. We have previously generated heterozygous cloned goats with one allele of Prnp functional disruption. To obtain goats with both alleles of Prnp be disrupted which would be resistant to scrapie completely, a second-round gene targeting was applied to disrupt the wild type allele of Prnp in the heterozygous goats. By second-round gene targeting, we successfully disrupted the wild type allele of Prnp in primary Prnp (+/-) goat skin fibroblasts and obtained a Prnp (-/-) cell line without Prnp expression. This is the first report on successful targeting modification in primary adult somatic cells of animals. These cells were used as nuclear donors for somatic cell cloning to produce Prnp (-/-) goats. A total of 57 morulae or blastocytes developed from the reconstructed embryos were transferred to 31 recipients, which produced 7 pregnancies at day 35. At 73 days of gestation, we obtained one cloned fetus with Prnp (-/-) genotype. Our research not only indicated that multiple genetic modifications could be accomplished by multi-round gene targeting in primary somatic cells, but also provided strong evidence that gene targeting in adult cells other than fetal cells could be applied to introduce precise genetic modifications in animals without destroying the embryos. | 18,821,027 |
Suicide and alcohol-related mortality in Hungary in the last two decades. | Suicide and alcohol-related mortality are often linked to each other in recent times, especially in the unfavourable mortality trends detected in Russia. Recent study has aimed to investigate suicide and alcohol-related mortality in Hungary between 1986 and 2005. This paper is based on the concept of social anomie and expects to find more favourable trends for both causes of death among those who were less exposed to unfavourable economic and social trends in the last two decades. In a cross-sectional design sex, age- and education-specific mortality rates were calculated. We found falling suicide rates in all socio-demographic groups, except well-educated middle aged men. Suicide has fallen more among women than men, more among the elderly than the young and more among the more educated than the less educated. Alcohol-related mortality has risen by 5-10 %, and its occurrence in different socio-demographic groups was found to be changing entirely proportionally. Developments in suicide mortality are generally in accordance with the hypothesis based on the concept of social anomie while those of alcohol-related mortality showed no relation with this concept. | 18,821,056 |
Daidzein-metabolizing phenotypes in relation to mammographic breast density among premenopausal women in the United States. | Mammographic breast density is an established marker of breast cancer risk, and is hormonally sensitive. Studies suggest that production of the daidzein metabolites equol and O-Desmethylangolensin (ODMA) may be associated with hormones and hormonally mediated factors, but few studies have assessed relationships between the capacity to produce these metabolites and breast density. To evaluate the relationship between equol- and ODMA-producer phenotypes and breast density in premenopausal women in the United States. Two hundred and three women attended a clinic visit and 200 provided a urine sample following a 3 day soy challenge. Samples were analyzed for isoflavones by GC-MS to determine daidzein-metabolizing phenotypes. Percent density on recent (<14 month prior to their clinic visit) mammograms was assessed by one reader using a computer-assisted method. Multiple regression analysis was used to assess relationships between the production of equol and ODMA and breast density. Results 55(27.5%) and 182(91%) women were classed as equol- and ODMA-producers (>87.5 ng/ml urine), respectively. In unadjusted and adjusted analyses, there were no differences in breast density between producers and non-producers of either equol or ODMA (P > 0.05). In this population of low-soy consuming premenopausal women, there were no associations between daidzein-metabolizing phenotypes and breast density, suggesting that these phenotypes per se do not influence premenopausal breast density. | 18,821,061 |
Risk-adapted management for patients with clinical stage I non-seminomatous germ cell tumour of the testis. | Testis cancer is the most common cancer in young men and its incidence continues to rise. Even if prognosis is considered as good, a group with bad prognosis still remains. We aimed to evaluate whether two courses of chemotherapy after orchiectomy in patients with clinical stage I, non-seminomatous germ cell testicular tumour at high risk of relapse, will spare patients additional chemotherapy or surgery. High-risk patients had one or more of the following: preorchiectomy alpha-fetoprotein level of 80 ng/dl, 80% embryonal cell carcinoma or greater, vessel invasion in the primary tumour and tumour stage pT2 or greater. Low-risk patients had none of these factors or had 50% teratoma or more without vessel invasion. High-risk patients were offered two 21-day courses of outpatient chemotherapy consisting cisplatin, etoposide and bleomycin (BEP). Low-risk patients were observed. Of the 108 patients, we classified 71 as high risk and 37 as low risk of relapse. All of the high-risk patients received two courses of BEP chemotherapy. Low-risk patients were kept on close-up. The median follow-up was 26 months (range 10-60). Of the 71 patients in high-risk group, 3 relapsed with viable cancer and required additional chemotherapy and 1 patient with normal biomarkers and a late-appearing mass underwent retroperitoneal lympadenectomy for mature teratoma. All 4 relapsed patients were in high-risk group and presently they are free of disease. None of the 37 patients at low risk of recurrences developed relapse. We recommend two courses of adjuvant chemotherapy after postorchiectomy for high-risk patients with stage I non-seminomatous germ cell tumour of the testis. Adjuvant chemotherapy for these patients results in a low relapse and morbidity, wich compares favourably with the results of surveillance or RPLND. This well-tolerated approach may spare patients additional surgery or protracted chemotherapy, reduce the cost and eliminate the compliance problems associated with intensive follow up of high-risk patients. | 18,821,067 |
NK and NKT cell dynamics after rituximab therapy for systemic lupus erythematosus and rheumatoid arthritis. | Biomarkers of clinical response to rituximab (RTX) therapy and early predictors of outcome are still under investigation. We report a flow cytometric immunophenotyping analysis from peripheral blood leukocyte subpopulations of two patients with systemic lupus erythematosus (SLE) associated thrombocytopenia and one patient with rheumatoid arthritis (RA), before and after 6 weeks of treatment with RTX. Our results show a reduced population of CD19(+) expressing cells (B cells) after RTX treatment in all three patients. Increased frequency of peripheral regulatory CD4(+)CD25(high) T cell subset and the CD3(-)CD16(-)CD56(bright) NK cell subset after RTX therapy were also observed in all patients, the latter being more pronounced in the SLE patient with sustained clinical response. In addition, an increased population of NKT cell subsets was observed in the patients with clinical response. This is the first evaluation of NK and NKT cells as biomarkers of clinical response after rituximab therapy in rheumatic diseases. | 18,821,073 |
Movement disorder emergencies. | Movement disorder emergencies include any movement disorder which evolves over hours to days, in which failure to appropriately diagnose and manage can result in patient morbidity or mortality. It is crucial that doctors recognize these emergencies with accuracy and speed by obtaining the proper history and by being familiar with the phenomenology of frequently encountered movements. These disorders will be discussed based on the most common associated involuntary movement, either parkinsonism, dystonia, chorea, tics or myoclonus, and, when available, review the workup and treatment options based on the current literature. | 18,821,080 |
Integrating research into practice: a challenge for local authority occupational therapy. | The aim of this qualitative study was to identify and analyse the experiences of Swedish local health authority occupational therapists with regard to their participation in, and the implementation of, research. Data were collected from three focus-group interviews, with five different occupational therapists in each. The interviews were taped and transcribed and thereafter analysed using broad coding. One core category-"feeling professionally competent"-emerged, comprising three subcategories: "perceiving congruence between research and practice", "having the necessary skills", and "making a contribution". Feeling professionally competent embraces the occupational therapists' definition and delimitation of their professional domain and the obligations related to this. It also embraces the perception of having the skills necessary for participating in research projects and implementing research findings in a scientific manner. The implementation of research was not only perceived as contributing to the knowledge base of the profession, but personal gains could also be made. The knowledge gained from this study can help in the development of strategies to promote the integration of research in local authority occupational therapy practice. This is necessary; otherwise the occupational therapy provided will be based on the knowledge and perceptions of individual professionals, rather than on state-of-the-art knowledge gained through research. | 18,821,136 |
Metabolic syndrome and multiple organ damage in essential hypertension. | We investigated the prevalence of the metabolic syndrome (MS) in hypertensive patients categorized according to the number of markers of organ damage (OD) in order to assess the value of a systematic search for cardiac and extra-cardiac OD in the MS setting. A total of 3119 untreated and treated essential hypertensives included in the Evaluation of Target Organ Damage in Hypertension (ETODH), an observational registry of hypertension-related OD, were considered for this analysis. All patients underwent extensive investigation for left ventricular hypertrophy (LVH) or LV concentric remodeling (cardiac OD), carotid plaques and/or intima-media thickening (vascular OD) and microalbuminuria (MA) and/or increased serum creatinine (renal OD). Subjects were classified as: positive for none (group 0), one (group I), two (group II) or three markers (group III) of OD. MS prevalence rates progressively rose across the groups stratified according to the OD score, reaching a 2.3-fold increase in group III compared with their MS counterparts in group 0. The distribution of subjects with and without the MS across the groups was 15% vs 29% (group 0), 32% vs 38% (group I), 39% vs 26% (group II) and 14% vs 7% (group III), respectively. Thus, subjects having two or three markers of OD were 53% among those with MS and 33% (p<0.01) among those without it. Our findings indicate a strong association between the MS and OD by showing that a clustering of two or three markers of OD is the prevalent cardiovascular phenotype in MS hypertensives referred to a specialist center and call for a systematic evaluation of cardiac and extracardiac OD in this setting. | 18,821,143 |
Evaluation of the role of peroxisome proliferator-activated receptor alpha (PPARalpha) in mouse liver tumor induction by trichloroethylene and metabolites. | Trichloroethylene (TCE) is an industrial solvent and a widespread environmental contaminant. Induction of liver cancer in mice by TCE is thought to be mediated by two metabolites, dichloroacetate (DCA) and trichloroacetate (TCA), both of which are themselves mouse liver carcinogens. TCE, TCA, and DCA are relatively weak peroxisome proliferators (PP), a group of rodent hepatocarcinogens that activate a nuclear receptor, PP-activated receptor alpha (PPARalpha. The objective of this review is to assess the weight of evidence (WOE) that PPARalpha is or is not mechanistically involved in mouse liver tumor induction by TCE and metabolites. Based on similarities of TCE and TCA to typical PP, including dose-response characteristics showing PPARalpha-dependent responses coincident with liver tumor induction and abolishment of TCE and TCA effects in PPARalpha-null mice, the WOE supports the hypothesis that PPARalpha plays a dominant role in TCE- and TCA-induced hepatocarcinogenesis. Data indicates that the MOA for DCA tumor induction is PPARalpha-independent. Uncertainties remain regarding the genesis of the TCE-induced tumors. In contrast to the TCA-induced tumors, which have molecular features similar to those induced by typical PP, there is evidence, albeit weak, that TCE tumors arise by a mode of action (MOA) different from that of TCA tumors, based largely on dissimilarities in molecular markers found in TCE versus TCA-induced tumors. In summary, the WOE indicates that TCA-induced liver tumors arise by a PPARalpha-dependent MOA. Although the TCE MOA is likely dominated by a PPARalpha-dependent contribution from TCA, the contribution of a PPARalpha-independent MOA from DCA cannot be ruled out. | 18,821,149 |
Preparation and evaluation of fast-disintegrating effervescent tablets of glibenclamide. | Fast-dissolving effervescent tablets (FETs) were prepared by the modification of nonreactive liquid-based wet granulation technique. Effervescent systems are not stable in the presence of trace amount of moisture, and elimination or inactivation of free water is the key to stability apart from manufacturing in controlled humidity environment. Our main objective of the project was to develop FETs of glibenclamide based on highly plastic granules that can be compressed at low pressure to form fast-melting pharmaceutical tablets. In this study, we have screened various acid and carbonate sources for the effervescent system. Citric acid was coated with plastic materials such as polyethylene glycol (PEG), which provide a physical barrier to the reaction. The inherent hygroscopic nature of PEG could decrease the affinity for moisture of effervescent mixtures and can provide a stabilizing effect. Sodium bicarbonate was blended with sugar alcohol like mannitol, which would give a protective coating. PEG 1000 melts at body temperature (approximately 37 degrees C) and thereby does not delay the reaction between the acid source and base. The present formulation using citric acid-sodium bicarbonate and citric acid-sodium glycine carbonate tablet with PEG and mannitol was found to have better reaction properties and reaction stability than does the standard citric acid-sodium bicarbonate tablet. FETs of glibenclamide might aid in dissolution due to increase in microenvironmental pH around the granules and saliva. Sensory study on disintegration time and mouth feel attributes ranked the present formulation based on grittiness, chalkiness, and overall preference as best. | 18,821,151 |
Occupational therapy, professional development, and ethics. | The aim of this article is to reflect on and contribute to developing occupational therapy as a profession. The author proposes an ethical interpretation of health and helping professions in general and occupational therapy in particular. According to this ethical interpretation, the essential function and mission of classical health and helping professions are defined by certain ethical values: the basic elements of a good human life. The author argues that the central concepts of occupational therapy, activity and participation, can plausibly be understood in this light. However, this seems to imply a rather substantial conception of well-being which the author tries to spell out. In addition, the basic principles of biomedical ethics are specified in the context of occupational therapy according to an ethical interpretation. In conclusion, four advantages of the ethical interpretation are highlighted: it adds precision and content to ethical principles and guidelines; it contributes to building up and preserving a shared professional identity; it puts emphasis on a client-centred perspective on professional work; and it provides a constructive framework for inter-professional cooperation. | 18,821,177 |
Evidence-based research and practice in clinical neuropsychology. | While a definition for evidence-based clinical neuropsychological practice (EBCNP) has yet to emerge, it is likely to integrate the same core features as evidence-based medicine; namely, best research evidence, clinical expertise, and individual patient needs. Given the nascent stage of EBCNP, suggestions are made to advance evidence-based approaches in both research and practice. The common elements are: recognition that clinical outcomes are recorded at the level of the individual; and to be useful, outcomes research must be presented in a way that can be directly applied on a case-by-case basis. Tracking the outcomes of our clinical services in an evidence-based manner that is publicly verifiable will demonstrate the value of neuropsychological services to our patients, our referral sources, and ultimately to payers. | 18,821,179 |
Longitudinal changes in memory and executive functioning are associated with longitudinal change in instrumental activities of daily living in older adults. | Impaired everyday function is a diagnostic criterion for dementia, and a determinant of healthcare utilization and caregiver burden. Although many previous studies have demonstrated a cross-sectional relationship between cognition (particularly executive functions and memory) and everyday function in older adults, very little is known about longitudinal relationships between these domains. This study examined the association between longitudinal change in episodic memory (MEM) and executive functioning (EXEC) and change in everyday function. Participants were a cognitively heterogeneous group of 100 elderly persons including those with normal cognition, as well as those with mild cognitive impairment and dementia. They were followed for an average of 5 years. Random effects modeling showed that change in both MEM and EXEC were independently associated with rate of change in informant-rated instrumental activities of daily living (IADLs), even after controlling for age, education, and gender. Findings indicate that declines in MEM and EXEC over time make unique and independent contributions to declines in older adults' ability to function in daily life. | 18,821,181 |
Women's experiences of increasing subjective well-being in CFS/ME through leisure-based arts and crafts activities: a qualitative study. | To understand the meanings of art-making among a group of women living with the occupational constraints and stigma of CFS/ME. The study explored their initial motives for art-making, and then examined how art-making had subsequently influenced their subjective well-being. Ten women with CFS/ME were interviewed; three provided lengthy written accounts to the interview questions. Illness had resulted in devastating occupational and role loss. Participants took many years to make positive lifestyle changes. Art-making was typically discovered once participants had accepted the long-term nature of CFS/ME, accommodated to illness, and reprioritized occupations. Several factors then attracted participants specifically to art-making. It was perceived as manageable within the constraints of ill-health. Participants also tended to be familiar with craft skills; had family members interested in arts and crafts, and some desired a means to express grief and loss. Once established as a leisure activity, art-making increased subjective well-being mainly through providing increased satisfaction in daily life, positive self-image, hope, and contact with the outside world. Participants recommended provision of occupational/recreational counselling earlier in the illness trajectory. Creative art-making occurred as part of a broader acceptance and adjustment process to CFS/ME, and allowed some psychological escape from a circumscribed lifeworld. | 18,821,193 |
Threshold of pain in chronic magnetic field- (50 Hz, 17.9 microT) exposed rats: effect of sucrose ingestion. | Both magnetic field (MF) exposure and sucrose ingestion produce opioid mediated analgesia, independently. This article addresses the query whether or not sucrose ingestion potentiates the analgesia of MF exposure. The pain threshold, as reflected by withdrawal of tail (thresholds of tail flick, TF), vocalization during stimulus (VD), and vocalization after stimulus (VA) were determined in 7 sessions at 0, 5, 10, 15, 30, 45, and 60 min, respectively (control rats). After an interval of 24 h the rats were provided with sucrose solution and were allowed to ingest it for 10 min. The pain thresholds were determined (Control sucrose-fed rats). The rats then received exposure to magnetic field (50 Hz, 17.9 microT) for 7 d (8 h/d) (MF-exposed rats) and the effect of sucrose ingestion was repeated (MF-Sucrose-fed rats). The basal threshold of pain did not vary in between the control and MF-exposed rats. Pain threshold during sessions II-VII did not vary in control rats but it increased in MF rats. Moreover, the pain thresholds were elevated in MF rats as compared to control rats. Sucrose-ingestion elevated the threshold of TF in controls but not in MF-exposed rats; while the thresholds of VA and VD were elevated more in control than MF rats. The results suggest that the MF exposure (50 Hz, 17.9 microT, 8 h/d) for 7 d did not affect the basal thresholds of pain, increased stress induced analgesia, and attenuated the sucrose ingestion-induced analgesia. | 18,821,201 |
Effects of extremely low-frequency-pulsed electromagnetic field on different-derived osteoblast-like cells. | The aim of this study is to investigate the effects of extremely low-frequency pulsed electromagnetic field (PEMF) on osteoblast-like cells. PEMF with a magnetic flux density of 1.55 mT at 48 Hz was employed to stimulate the MC3T3-E1 cell and the primary osteoblast cell derived from 2-day-old Sprague Dawley (SD) rat calvaria for different time. MTS method was applied to analyze cell proliferation and flow cytometry to detect cell cycle. The intracellular alkaline phosphatase (ALP) activity was measured by colorimetry. Our results demonstrated that PEMF of 1.55 mT at 48 Hz did not affect cell number of MC3T3-E1 cell, whereas the cell percentage of S and G(2)M phase decreased significantly. Although the cell number of the primary osteoblast cell did not alter by MTS assay after being exposed to PEMF for 24 h continuously, the cell percentage of S and G(2)M phase increased significantly. When culture time extended to 48 h, the cell number increased greatly and the cell percentage of S and G(2)M phase decreased significantly despite of the exposure type. After the primary osteoblast cell was exposed to PEMF for 24 h continuously, the ALP activity decreased significantly, whereas it increased significantly when being exposed to PEMF for 48 h continuously. From the results we concluded that PEMF of 1.55 mT at 48 Hz did not affect proliferation and differentiation of MC3T3-E1 cell, but it promoted proliferation, inhibited differentiation at proliferation stage, and promoted differentiation at differentiation stage of primary osteoblast cells. | 18,821,205 |
A simple image analysis algorithm for evaluation of extended filaments length based on the enhanced digitized image. | An automated image analysis procedure was developed to determine extended filaments length and floc area to evaluate settling characteristics of activated sludge. Digitized image obtained by Gram staining granted the first step of algorithm, segmentation, to be extremely clear and simple. The image analysis work could become more accurate and less time consuming one to be required only 1 minute of operation time per image. Filamentous bulking phenomenon of the biological sludge was induced in a laboratory-scale bioreactor system under an extreme operational condition, and the non-bulking and filamentous bulking sludge samples captured were examined with image analysis as well as traditional settling test. There existed a linear relationship between DSVI (Diluted Sludge Volume Index) and the extended filaments length. Similar results were also obtained with the extended filaments per floc area. The arithmetic mean extended filaments length showed an excellent linearity with the DSVI. It is believed that the image analysis algorithm developed in this study can be utilized for estimation of the extended filaments length and for evaluation of the settling characteristics of activated sludge effectively. | 18,821,233 |
Extraction of nonylphenol and nonylphenol ethoxylates from sewage sludge using the pressurized fluid extraction method and the supercritical fluid extraction method. | To establish endocrine disruptor (ED) monitoring and control methods for wastewater treatment plants, it is necessary to clarify the fate of EDs in each process of a sludge treatment system. However, the ED analysis method for sewage sludge containing large quantities of organic matters has not been established. So, a highly reliable analytical method that accurately measures EDs in sewage sludge must be developed. This paper reports on the results of applying the Pressurized Fluid Extraction (PFE) method and the Supercritical Fluid Extraction (SFE) method to the extraction of nonylphenol (NP) and nonylphenol ethoxylate (NPnEO) existence of which has often been confirmed in past surveys. To clarify the quantity of EDs in sludge specimens and the fate of EDs in the sludge treatment process, appropriate analytical methods should be developed. In this study, the PFE method and the SFE method were tested to extract NP and NPnEO from sewage sludge specimens. The findings indicate that the extraction from dried sludge by the PFE method can extract a larger quantity of NP and NPnEO in a shorter time than the widely used heating reflux method. Regarding the extraction by the SFE method, conditions for extraction of NP and NPnEO at a higher rate than the heating reflux method were not found. | 18,821,236 |
Chemical sludge conditioning in combination with different conventional and alternative dewatering devices: chamber filter press, decanter and Bucher press. | The Kemicond process for sludge conditioning consists of chemical treatment with sulphuric acid and hydrogen peroxide at a pH-value of approximately 4 followed by a dewatering unit. It is shown that chemical treatment can improve the dewaterability of ferruginous digested sludge. It is concluded that the Fenton process as well as the oxidation of organics and the formation of iron hydroxo complexes are important reaction mechanisms. Furthermore, the organic matter changes through the acidic oxidative process. With the improvement in dewaterability, it is possible to achieve an increase in TS concentration, which affects a reduction of the sludge volume. Cost savings for sludge disposal can amortize the additional investment and operational costs for chemical treatment. | 18,821,238 |
Synthesis and immunosuppressive activity evaluation of substituted N-imidazolidin-2-ones and N-tetrahydropyrimidin-2(1H)-ones. | Seventeen compounds with either an imidazolin-2-one or a tetrahydropyrimidin-2(1H)-one scaffold were synthesized and evaluated for their immunosuppressive activity in a concanavallin A (ConA)-stimulated mouse splenocytes proliferation test. Three of these molecules exerted a significant activity at 90 microM. All the compounds of the tetrahydropyrimidin-2(1H)-one series have turned out to be inactive showing the crucial role of the imidazolidin-2-one scaffold in the induction of an immunosuppressive activity. | 18,821,255 |
Pathological gambling, delusional parasitosis and adipsia as a post-haemorrhagic syndrome: a case report. | The authors describe the case of a 70-year-old male who developed a peculiar syndrome characterized by pathological gambling (PG), delusional parasitosis and adipsia with mild frontal symptoms. Onset of the syndrome followed a cerebral haematoma involving hypothalamic and bilateral ventromedial prefrontal areas. The potential manifestation of PG following a lesion in the above areas may contribute towards furthering the understanding of pathological conditions underlying this disorder. | 18,821,269 |
Multiple parietal operculum subdivisions in humans: tactile activation maps. | We focused the present analysis on blood-oxygen-level-dependent responses evoked in four architectonic subdivisions of human posterior parietal operculum (PO) during two groups of tasks involving either vibrotactile stimulation or rubbing different surfaces against the right index finger pad. Activity localized in previously defined parietal opercular subdivisions, OP 1-4, was co-registered to a standard cortical surface-based atlas. Four vibrotactile stimulation tasks involved attention to the parameters of paired vibrations: (1) detect rare target trials when vibration frequencies matched; (2) select the presentation order of the vibration with a higher frequency or (3) longer duration; and (4) divide attention between frequency and duration before selecting stimulus order. Surface stimulation tasks involved various discriminations of different surfaces: (1) smooth surfaces required no discrimination; (2) paired horizontal gratings required determination of the direction of roughness change; (3) paired shapes entailed identifying matched and unmatched shapes; (4) raised letters involved letter recognition. The results showed activity in multiple somatosensory subdivisions bilaterally in human PO that are plausibly homologues of somatosensory areas previously described in animals. All tasks activated OP 1, but in vibrotactile tasks foci were more restricted compared to moving surface tasks. Greater spatial extents of activity especially in OP 1 and 4 when surfaces rubbed the finger pad did not support previously reported somatotopy of the second finger representation in "S2". The varied activity distributions across OP subdivisions may reflect low-level perceptual and/or cognitive processing differences between tasks. | 18,821,280 |
Increased prevalence of erectile dysfunction (ED): results of the second epidemiological study on sexual activity and prevalence of ED in Thai males. | The aim of this study is to investigate changes in sexual activity and the prevalence of erectile dysfunction (ED) in Thai males. In addition, the treatment-seeking behaviour of Thai patients suffering from ED is also investigated. In a cross sectional study using a standardized questionnaire with a multi-stage stratified random sampling, 2,269 men aged 40-70 were interviewed. The questionnaire was designed to investigate the effects of socioeconomic factors, medical conditions and unhealthy lifestyles on the development of ED. Furthermore, the questionnaire was designed to characterize the treatment-seeking behaviour of Thai patients suffering from ED. Compared to the first report dated the year 2000, the prevalence of ED has increased from 37.5% to 42.18%. In terms of socioeconomic factors, the highest prevalence of ED was observed among unemployed men (78.51%). Prostatism and/or prostatitis (Odd ratios (OR) = 2.02) and long histories of smoking (more than 30 years, OR = 2.36) were identified as statistically significant risk factors for ED, with p-values of <0.001. It is important to notice that 38.78% of the ED patients wanted to discuss their problem with spouses or partners. Three quarters of the ED patients (74.54%) preferred oral medication as therapy. The epidemiology of ED in Thailand is changing. An increased prevalence of ED does require further epidemiological studies on a regular basis in order to better understand the etiology of ED and look for measures (such as education) to counter the disease. | 18,821,288 |
Noninvasive cardiac imaging: implications for risk assessment in adolescents and young adults. | Noninvasive imaging of cardiovascular end organ injury has now been applied to adolescents and young adults to better understand the early natural history of chronic heart disease. Echocardiography, assessment of endothelial function, and subclinical atherosclerosis imaging using carotid intima-media thickness measures and coronary calcium identified on computed tomography scanning have all been applied at young ages to demonstrate adverse effects of cardiovascular risk factors. Intervention trials using these techniques as end points may improve understanding of the natural history of acquired cardiovascular disease. | 18,821,334 |
Diagnosed eating disorders in the U.S. Military: a nine year review. | The objective of this study was to determine the incidence of three types of eating disorders (ED); anorexia nervosa (AN), bulimia nervosa (BN) and eating disorder not otherwise specified (EDNOS), diagnosed in the U.S. Military. Diagnosed cases of ED were obtained from the Defense Medical Epidemiology Database for all Service Members (SM) from 1998-2006. The percentage per year of SM with an ED diagnosis was .30%. Eating disorders were diagnosed significantly more in 2006 (.41%) compared to 1998 (.23%) (p < .001). Females were diagnosed significantly more than males (p < .001). The majority of AN cases (66%) were in the Marines. This is the first known study to investigate the incidence of ED in SM using medical record data. Service Members diagnosed with ED have increased. Females, specifically White females, have higher incidence of ED. The reported incidence of diagnosed ED in SM was lower compared to previous research. | 18,821,361 |
Water disinfection and hygiene behaviour in an urban slum in Kenya: impact on childhood diarrhoea and influence of beliefs. | In this research project, we studied factors that presumably affect the incidence of diarrhoea among young children in urban slums in developing countries: consumption of safe drinks, hygiene behaviour, cleanliness of household surroundings and the quality of raw water. Beliefs concerning the causes of diarrhoea were also related to health-improving behaviour, namely the application of the water-treatment method SODIS (solar water disinfection) and hygiene behaviour. We conducted a survey in a shanty town in Nairobi, Kenya. Field workers interviewed 500 households. Analysis with regression models revealed that two out of the four postulated factors were significant: children have a lower risk of contracting diarrhoea when they consume high percentages of safe drinks and live in households with good hygiene. As regards beliefs, we found that biomedical knowledge of children's diarrhoea as well as the perceived social norm for treating water was associated with the use of SODIS and good hygiene. | 18,821,373 |
Characterization of cells expressing RNA polymerase II tagged with green fluorescent protein: effect of ionizing irradiation on RNA synthesis. | To isolate and to characterize cells expressing RNA polymerase II tagged with green fluorescent protein for analyses of the effects of ionizing radiation on transcription in living cells. We introduced an alpha-amanitin-resistant mutation into a vector encoding the largest subunit of RNA polymerase II tagged with green fluorescent protein (GFP-pol). Cell lines stably expressing functional GFP-pol were isolated under selection with alpha-amanitin from a Chinese hamster cell line, CHO-K1, and a radiation-sensitive mutant CHO cell line, XR-1. We tested the functionality of the fusion protein in vivo by determining RNA synthesis activity by incorporation of nucleoside analogues. Both CHO-K1 and XR-1 cells expressing GFP-pol had properties similar to those of their respective parental cell lines, indicating that GFP-pol is functional. These stable lines might prove useful for analyses of the roles of transcription after ionizing radiation. | 18,821,392 |
Influence of zoo visitor presence on the behavior of captive Indian gaur (Bos gaurus gaurus) in a zoological park. | Visitors to zoos can be a source of potential disturbance and stress to some captive, nonhuman animals in the wild. To determine the influence of visitor presence on captive bison (Bos gaurus gaurus), the study analyzed the behavior of 4 individuals at the Arignar Anna Zoological Park, India. The study often observed the behavior of the animals on visitor-present days and on days when visitors were absent. In the presence of zoo visitors, the bison showed a higher level of intragroup aggression and moving behavior. In contrast, the bison rested more when no visitors were present. The results revealed that the presence of zoo visitors significantly influenced the behavior of captive bison and thereby may have affected their welfare. | 18,821,404 |
High psychiatric symptom severity is a moderator of substance abuse treatment outcomes among women in single vs. mixed gender group treatment. | This exploratory study examined psychiatric symptom severity as a moderator of outcomes among women receiving either the Women's Recovery Group (WRG), a new manualized group treatment for substance use disorders combining single-gender group composition and women-focused content, or Group Drug Counseling (GDC), an empirically supported mixed-gender group treatment. We used a mixed model analysis of variance. We found a significant 3-way interaction effect of treatment condition, time, and baseline Brief Symptom Inventory scores as well as Beck Depression Inventory scores. Single-gender group treatment may confer added benefit for women with substance abuse and high psychiatric symptom severity than mixed-gender treatment. | 18,821,452 |
History of physical or sexual abuse and participation in 12-step self-help groups. | Although 12-step groups are an important resource for managing substance use problems, their efficacy for patients with a physical or sexual abuse history is unknown. In the present study, patients with a history of physical or sexual (n = 122) or no (n = 143) abuse were interviewed at entry to outpatient substance use treatment at the Veterans Administration. After adjusting for baseline substance use, physical or sexual abuse was associated with more attendance at and involvement in 12-step groups. Participation in 12-step groups predicted abstinence at one year, regardless of abuse history. Limitations and implications are discussed. | 18,821,455 |
Advances in immunotherapy of castration-resistant prostate cancer: bisphosphonates, phosphoantigens and more. | Medical progress has prolonged life expectancy in patients with castration-resistant prostate cancer; however, the lack of effective therapies has fuelled an intensive search for novel modalities, including immunotherapy. Human gammadelta T-cells can be activated by endogenous pyrophosphates (phosphoantigens), or by agents that provoke their accumulation. Among the latter, aminobisphosphonates are well-established in the clinic. In this review, the possibility that the intentional activation of gammadelta T-cells in vivo by phosphoantigens, or aminobisphosphonates and interleukin-2, may represent a promising target for the design of novel and highly innovative immunotherapy in patients with prostate cancer is discussed. | 18,821,471 |
[Antiepileptic drugs - fast versus slow titration and discontinuation]. | The indication and management of an appropriate therapy with antiepileptic drugs (AEDs) requires an individualized diagnostic evaluation considering the clinical situation. Based on the current scientific data the therapeutic options and special aspects of the available AEDs are discussed with emphasis on the possibility of rapid initiation (therapeutic loading doses on day 1) or need of slow uptitration over several days or weeks in the context of different clinical situations. A sudden discontinuation or withdrawal of AEDs is only justified due to life-threatening side effects or for diagnostic purposes in the context of a presurgical workup. The debate on the appropriate time for a slow AED discontinuation (over a few weeks or several months) is still ongoing. | 18,821,523 |
Origin of diastereocontrol in the oxy-Michael reactions of delta-lactol anions: a computational and experimental study. | The diastereoselectivity in the alkylation and Michael addition of "naked" 6-substituted delta-lactolates has been studied by density functional (B3LYP) calculations with ab initio (MP2) energy refinements. The resulting proposed model for the origins of stereocontrol in this reaction has been tested by experiment. The reactions lead to a high cis diastereoselectivity across the THP ring due to the preference for both the alkoxide and the 6-substituent to sit equatorial in the alkylation transition structure. In the oxy-Michael addition of these lactolates to beta-substituted nitroolefins, we propose that the high diastereoselectivity beta- to the nitro group is a result of a combination of steric, stereoelectronic and solvation factors. | 18,821,546 |
Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations. | Attention deficit hyperactivity disorder (ADHD) is a complex condition with environmental and genetic etiologies. Up to this point, research has identified genetic associations with candidate genes from known biological pathways. In order to identify novel ADHD susceptibility genes, 600,000 SNPs were genotyped in 958 ADHD proband-parent trios. After applying data cleaning procedures we examined 429,981 autosomal SNPs in 909 family trios. We generated six quantitative phenotypes from 18 ADHD symptoms to be used in genome-wide association analyses. With the PBAT screening algorithm, we identified 2 SNPs, rs6565113 and rs552655 that met the criteria for significance within a specified phenotype. These SNPs are located in intronic regions of genes CDH13 and GFOD1, respectively. CDH13 has been implicated previously in substance use disorders. We also evaluated the association of SNPs from a list of 37 ADHD candidate genes that was specified a priori. These findings, along with association P-values with a magnitude less than 10(-5), are discussed in this manuscript. Seventeen of these candidate genes had association P-values lower then 0.01: SLC6A1, SLC9A9, HES1, ADRB2, HTR1E, DDC, ADRA1A, DBH, DRD2, BDNF, TPH2, HTR2A, SLC6A2, PER1, CHRNA4, SNAP25, and COMT. Among the candidate genes, SLC9A9 had the strongest overall associations with 58 association test P-values lower than 0.01 and multiple association P-values at a magnitude of 10(-5) in this gene. In sum, these findings identify novel genetic associations at viable ADHD candidate genes and provide confirmatory evidence for associations at previous candidate genes. Replication of these results is necessary in order to confirm the proposed genetic variants for ADHD. | 18,821,565 |
Comparison of rehabilitation results in deaf patients with and without genetically related hearing loss. | The introduction of prognostic tools to evaluate rehabilitation progress in cochlear implant patients (CI patients) is of great importance. The authors attempted to verify whether the identified 35delG mutation in the GJB2 gene can serve as a valuable indicator for rehabilitation progress of CI patients. A group of 51 subjects was studied. Molecular analysis was based on the identification of 35delG in GJB2. Logopedic assessment was performed with a non-verbal test of seven sounds, evaluating detection, discrimination and identification of the sounds during the first, third and sixth months after implantation. Results indicated that patients with GJB2-related deafness (DFNB1)s achieve better results in rehabilitation, but only at the early stages of rehabilitation. Prolonged rehabilitation equalised differences, which, subsequently, excluded this marker as an indicator for rehabilitation evaluation. | 18,821,568 |
Isolation and characterization of porcine adult muscle-derived progenitor cells. | Here, we report the isolation of progenitor cells from pig skeletal muscle tissue fragments. Muscle progenitor cells were stimulated to migrate from protease-digested tissue fragments and cultured in the presence of 5 ng/ml basic fibroblast growth factor. The cells showed a sustained long-term expansion capacity (>120 population doublings) while maintaining a normal karyotype. The proliferating progenitor cells expressed PAX3, DESMIN, SMOOTH MUSCLE ACTIN, VIMENTIN, CD31, NANOG and THY-1, while MYF5 and OCT3/4 were only expressed in the lower or higher cell passages. Myogenic differentiation of porcine progenitor cells was induced in a coculture system with murine C2C12 myoblasts resulting in the formation of myotubes. Further, the cells showed adipogenic and osteogenic lineage commitment when exposed to specific differentiation conditions. These observations were determined by Von Kossa and Oil-Red-O staining and confirmed by quantitative RT-PCR analysis. In conclusion, the porcine muscle-derived progenitor cells possess long-term expansion capacity and a multilineage differentiation capacity. | 18,821,573 |
A questionnaire based review of long-term follow-up programs for survivors of childhood cancer in Canada. | Major advances have been made in the treatment of childhood cancer; however, survivors of childhood cancer are at increased risk for morbidity and mortality. There is little literature regarding available long-term follow-up programs for survivors of childhood cancer. In March 2007, 16 surveys were sent to pediatric hematology/oncology programs across Canada to determine what programs were available for survivors of childhood cancer, and the nature of such programs. Of 15 participating centers, 13 (87%) have multi-disciplinary programs for the long-term follow-up of pediatric cancer survivors. Research databases were documented in 9/15 (60%) of centers to document late effects. Dedicated programs for adult survivors of childhood cancer were established in 8/15 (53%) of centers. Access to subspecialty care for survivors was rated as quite good. Concerns were raised by many participants about patients being lost to follow-up. Respondents indicated that primary care physicians appear to be under-represented within dedicated long-term follow-up programs. Long-term follow-up programs for survivors of childhood cancer are available in 87% of Canadian pediatric oncology centers. While programs reported good access to care for childhood survivors, many adult survivors of childhood cancer have more limited timely access to services and patients are often lost to follow-up. New models of care incorporating primary care physicians are necessary due to growing numbers of survivors. | 18,821,577 |
Aberrant methylation of EphA7 in human prostate cancer and its relation to clinicopathologic features. | EphA7 is a member of Eph/ephrins family and play diverse roles in carcinogenesis. The aim of our study was to investigate functional and structural alterations of EphA7 in prostate cancer and determine if those findings correlate with the clinicopathologic features of prostate cancer. Forty-eight prostate carcinomas, 31 benign prostate hyperplasias, 5 normal prostate tissues and 3 prostate cell lines (LNCaP, DU145 and PC-3) were examined with quantitative RT-PCR, methylation-specific PCR and immunohistochemistry. Downregulation or loss of EphA7 mRNA expression was detected in 23 of 48 (47.9%) prostate carcinomas, and 2 of 31 (6.5%) hyperplasias. Methylation of the EphA7 promoter region was present in 20 of 48 (41.7%) of carcinomas and 6 of 31 (19.3%) hyperplasias, respectively. Immunostaining analysis showed EphA7 protein was absent in 10 of 30 (33.3%) carcinoma samples available and 8 of them (80.0%) exhibited hypermethylation. The frequency of EphA7 methylation was higher in cancer patients with higher Gleason score. Treatment of DU145 cells harboring methylation with 5-aza-2'-deoxycytidine reactivated expression of EphA7. Ectopic expression of EphA7 in DU145 cells did not suppress cell growth but inhibited colony formation. Our study provides evidence that epigenetic inactivation of EphA7 may be involved in prostate carcinogenesis. | 18,821,581 |
Dynamic perfusion MRI: capability for evaluation of disease severity and progression of pulmonary arterial hypertension in patients with connective tissue disease. | To prospectively evaluate the capability of dynamic perfusion MRI for assessment of disease severity and progression to pulmonary arterial hypertension (PAH) in connective tissue disease (CTD) patients. In all, 18 gender- and age-matched CTD patients without and with PAH and nine healthy volunteers underwent dynamic perfusion MRI, Doppler echocardiography, and pulmonary function test. Disease severity of CTD was assessed in terms of diffusing capacity for carbon monoxide (%DL(CO)) and estimated systolic pulmonary arterial pressure (sPAP), and progression of PAH in terms of pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR). From calculated pulmonary perfusion parameter maps, means of pulmonary blood flow (mPBF), pulmonary blood volume (mPBV), and mean transit time (mMTT) were determined as averages of all region of interest (ROI) measurements. To determine disease severity in CTD, all parameters were statistically correlated with sPAP and %DL(CO). To determine progression to PAH, all parameters were statistically correlated with mPAP and PVR. All pulmonary perfusion parameters correlated significantly with sPAP and % DL(CO) (P < 0.05). mPBF and mPBV correlated significantly with mPAP and moderately with PVR (P < 0.05). Dynamic perfusion MRI can be used for assessment of disease severity and progression of PAH in CTD patients. | 18,821,609 |
Reproducible MRI measurement of adipose tissue volumes in genetic and dietary rodent obesity models. | To develop ratio MRI [lipid/(lipid+water)] methods for assessing lipid depots and compare measurement variability with biological differences among lean controls (spontaneously hypertensive rats [SHRs]), dietary obese rats (SHR-DOs), and genetic/dietary obese rats (SHROBs). Images with and without chemical shift-selective (CHESS) water suppression were processed using a semiautomatic method that accounts for relaxometry, chemical shift, receive coil sensitivity, and partial volume. Partial volume correction improved results by 10% to 15%. Over six operators, volume variation was reduced to 1.9 mL from 30.6 mL for single-image-analysis with intensity inhomogeneity. For three acquisitions on the same animal, volume reproducibility was <1%. SHROBs had six times more visceral and eight times more subcutaneous adipose tissue than SHRs. SHR-DOs had enlarged visceral depots (three times larger than those in SHRs). SHROBs had significantly more subcutaneous adipose tissue, indicating a strong genetic component to this fat depot. Liver ratios in SHR-DO and SHROB were higher than in SHR, indicating elevated fat content. Among SHROBs, evidence suggested a phenotype SHROB* having elevated liver ratios and visceral adipose tissue volumes. Effects of diet and genetics on obesity were significantly larger than variations due to image acquisition and analysis, indicating that these methods can be used to assess accumulation/depletion of lipid depots in animal models of obesity. | 18,821,617 |
Magnetic resonance imaging and spectroscopy for monitoring liver steatosis. | To compare noninvasive MRI and magnetic resonance spectroscopy (MRS) methods with liver biopsy to quantify liver fat content. Quantification of liver fat was compared by liver biopsy, proton MRS, and MRI using in-phase/out-of-phase (IP/OP) and plus/minus fat saturation (+/-FS) techniques. The reproducibility of each MR measure was also determined. An additional group of overweight patients with steatosis underwent hepatic MRI and MRS before and after a six-month weight-loss program. A close correlation was demonstrated between histological assessment of steatosis and measurement of intrahepatocellular lipid (IHCL) by MRS (r(s) = 0.928, P < 0.0001) and MRI (IP/OP r(s) = 0.942, P < 0.0001; FS r(s) = 0.935, P < 0.0001). Following weight reduction, four of five patients with >5% weight loss had a decrease in IHCL of >or=50%. These findings suggest that standard MRI protocols provide a rapid, safe, and quantitative assessment of hepatic steatosis. This is important because MRS is not available on all clinical MRI systems. This will enable noninvasive monitoring of the effects of interventions such as weight loss or pharmacotherapy in patients with fatty liver diseases. | 18,821,619 |
Evaluation of motion correction effect and image quality with the periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) (BLADE) and parallel imaging acquisition technique in the upper abdomen. | To evaluate motion correction effect and image quality in the upper abdomen with the periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) (BLADE) and parallel imaging acquisition technique. A total of 50 consecutive patients underwent abdominal MR imaging. Fat-saturated T2-weighted turbo spin-echo sequences were obtained by respiratory triggering. The subjects were examined with three different conditions of echo train length (ETL), blade width, and percent k-space coverage in the same scanning time: 19/30/100%, 30/30/100%, and 30/52/175%, which were designated as L/C(1), L/C(2), and L/C(3), respectively. The parallel imaging acquisition technique was used to either reduce ETL from 30 to 19 in L/C(1) or increase k-space coverage from 100% to 175% in L/C(3) compared with L/C(2). Motion and streak artifacts, and overall image quality were evaluated visually by two radiologists, independently. Motion and streak artifacts were mostly reduced in L/C(3) condition. The L/C(3) image also gave the best overall image quality compared with other conditions (P < 0.001). The inter-rater reliability for each evaluation agreed well. In upper abdominal BLADE MRI, it was possible to reduce image artifacts and obtain better image quality by increasing the k-space coverage with parallel imaging in the same scanning time. | 18,821,630 |
Signal features of the atherosclerotic plaque at 3.0 Tesla versus 1.5 Tesla: impact on automatic classification. | To investigate the impact of different field strengths on determining plaque composition with an automatic classifier. We applied a previously developed automatic classifier-the morphology enhanced probabilistic plaque segmentation (MEPPS) algorithm-to images from 20 subjects scanned at both 1.5 Tesla (T) and 3T. Average areas per slice of lipid-rich core, intraplaque hemorrhage, calcification, and fibrous tissue were recorded for each subject and field strength. All measurements showed close agreement at the two field strengths, with correlation coefficients of 0.91, 0.93, 0.95, and 0.93, respectively. None of these measurements showed a statistically significant difference between field strengths in the average area per slice by a paired t-test, although calcification tended to be measured larger at 3T (P = 0.09). Automated classification results using an identical algorithm at 1.5T and 3T produced highly similar results, suggesting that with this acquisition protocol, 3T signal characteristics of the atherosclerotic plaque are sufficiently similar to 1.5T characteristics for MEPPS to provide equivalent performance. | 18,821,634 |
Biocatalytic polyester acrylation--process optimization and enzyme stability. | An OH-functional polyester has been acrylated via transesterification of ethyl acrylate, catalyzed by Candida antarctica lipase B (CalB) in two different preparations: Novozym 435 and immobilized on Accurel MP1000. The batch process resulted in incomplete acrylation as well as severe degradation of the polyester. A high degree of acrylation was achieved by optimization through the application of low pressure (15 kPa), continuous inflow of ethyl acrylate and continuous distillation to evaporate the by-product, ethanol. The enzyme preparations displayed good stability with half-lives of 180 and 324 h for Novozym 435 and CalB/MP1000, respectively. This translates into product yields of 3600 and 6200 times the weight of the catalyst, indicating that the enzyme will have a marginal impact on the total process cost. | 18,821,636 |
An efficient and scalable process for helper-dependent adenoviral vector production using polyethylenimine-adenofection. | Safety requirements for adenoviral gene therapy protocols have led to the development of the third generation of vectors commonly called helper-dependent adenoviral vectors (HDVs). HDVs have demonstrated a high therapeutic potential; however, the poor efficiency and reliability of the actual production process hampers further large-scale clinical evaluation of this new vector. The current HDV production methods involve a preliminary rescue step through transfection of adherent cell cultures by an HDV plasmid followed by a helper adenovirus (HV) infection. Amplification by serial co-infection of complementary cells allows an increase in the HDV titer. Using a HEK293 FLP/frt cell system in suspension culture, an alternative protocol to the current transfection/infection procedure was evaluated. In this work, the adenofection uses the HDV plasmid linked to the HV with the help of polyethylenimine (PEI) and has shown to outperform standard protocols by producing higher HDV yield. The influence of complex composition on the HDV production was examined by a statistical design. The optimized adenofection and amplification conditions were successively performed to generate HDV at the 3 L bioreactor scale. Following only two serial co-infection passages, up to 1.44 x 10(8) HDV infectious units/mL of culture were generated, which corresponded to 26% of the total particles produced. This production strategy, realized in cell suspension culture, reduced process duration and therefore the probability of vector recombination by introducing a cost-effective transfection protocol, ensuring production of high-quality vector stock. | 18,821,637 |
Induction of osteoclast-associated receptor, a key osteoclast costimulation molecule, in rheumatoid arthritis. | Osteoclast-associated receptor (OSCAR) is a newly identified osteoclast-specific receptor and is of key importance in the process of osteoclast costimulation. This study was undertaken to define the role of costimulation in osteoclast differentiation during inflammatory arthritis. OSCAR expression was assessed in the synovium and peripheral blood monocytes of patients with rheumatoid arthritis (RA), and associations with disease activity were assessed. Serum levels of OSCAR were determined by enzyme-linked immunosorbent assay. In vitro osteoclast assays were performed to characterize the role of OSCAR in human osteoclastogenesis. Cytokine regulation of OSCAR was investigated by reverse transcriptase-polymerase chain reaction. OSCAR was expressed by osteoclasts at the erosion front and by mononuclear cells around synovial microvessels. Flow cytometry revealed enhanced expression of OSCAR in peripheral blood monocytes of RA patients as compared with healthy controls. OSCAR expression was correlated with disease activity and acute-phase reactant concentrations. Serum levels of soluble OSCAR were lower in RA patients than in healthy controls. Monocytes with high OSCAR expression exhibited an enhanced potential to differentiate into osteoclasts. Tumor necrosis factor alpha was identified as the main inducer of OSCAR expression in monocytes. These data suggest that the osteoclast costimulation pathway is activated in RA. OSCAR is induced in monocytes of RA patients, facilitating their differentiation into osteoclasts and bone resorption. | 18,821,671 |
Vascular endothelial growth factor is highly expressed in muscle tissue of patients with polymyositis and patients with dermatomyositis. | To investigate the expression of vascular endothelial growth factor (VEGF) in muscle biopsy specimens and serum from patients with polymyositis and patients with dermatomyositis compared with that in healthy control subjects. Muscle biopsy specimens from 33 patients with polymyositis or dermatomyositis and 15 healthy control subjects and serum samples from 56 patients and 56 healthy control subjects were analyzed. Patients were categorized into 3 groups, depending on disease duration and the presence or absence of inflammatory infiltrates. The expression of VEGF and the vessel marker CD31 in muscle was analyzed by immunohistochemistry, the expression of VEGF messenger RNA (mRNA) was analyzed by in situ hybridization, and serum levels of VEGF were determined by enzyme-linked immunosorbent assay. Patients with polymyositis or dermatomyositis in the early or chronic phase without inflammatory infiltrates had a decreased total number of capillaries compared with healthy individuals. In patients with early disease without inflammatory infiltrates, the number of VEGF-expressing muscle fibers was increased compared with that in control subjects, whereas VEGF expression was unchanged in the chronic phase of disease. In patients with established disease with inflammatory infiltrates, total VEGF expression was high compared with that in healthy control subjects. In healthy control subjects, VEGF was expressed in endothelial cells and in occasional muscle fibers. VEGF mRNA was expressed in muscle fibers in both healthy individuals and patients. The level of serum VEGF was significantly increased in patients compared with control subjects. Our observations support a role of VEGF in the early phases of polymyositis and dermatomyositis. A reduced number of capillaries could lead to induction of VEGF expression in muscle fibers. Furthermore, differences in molecular expression during certain phases of disease may help in the development of specific therapeutic algorithms in the treatment of myositis. | 18,821,695 |
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